Journal articles on the topic '811/.54'

811 Background: Little knowledge is available for postsurgical changes in cognitive and physical functions that may be useful for considering indication for surgery in elderly patients with gastric cancer. We therefore conducted a prospective study aimed to determine the influence of gastrectomy on these patients. Methods: We recruited patients older than 75 years for whom gastrectomy for gastric cancer had been planned, and assessed their cognitive and physical functions, daily activities, episodes of depression, confusion, and delirium before surgery (baseline), upon discharge, and at 6 months after surgery (POM 6). Results: Among 54 elderly patients registered between February 2017 and February 2020. There were no significant decreases in MMSE scores between baseline and at POM 6, nor were there significant differences in physical function and indicators of depression and confusion between these time points. As many as 20% of patients were found to have the functional decline on the basic activities of daily living scores (BADL) after surgery compared with the baseline. The only variable significantly associated with a functional decline in BADL was postoperative complications. Conclusions: Postoperative cognitive functions did not significantly decline when compared with the baseline scores, although postoperative BADL scores of patients who experienced postoperative complications were significantly lower than those who did not.

Pulmonary surfactant protein B (SP-B) is required for normal surfactant function and for survival at birth. To further study SP-B gene expression, we sequenced genomic clones and examined promoter activity of SP-B DNA fragments by transient transfection. A plasmid construct containing human SP-B fragment -1039/+431 linked to chloramphenicol acetyltransferase (CAT) reporter gene was readily expressed in H441 cells, which are derived from a human lung adenocarcinoma, but was < 4% as active in Hep G2, HeLa, and Calu 6 cell lines. SP-B promoter activity in H441 cells was orientation dependent and increased by linked Rous sarcoma virus (RSV) enhancer and was stronger than for thymidine kinase (tk) and RSV promoters. Deletional mapping of the 5' flanking region with exonuclease III suggested nonspecific negative (-811/-1039)- and positive (-453/-641)-control regions and a cell-specific enhancer region at -208 to -54. When a fragment from -403 to -35 base pairs (bp) was placed upstream or downstream of tkCAT, in either orientation, expression in H441 cells but not other cell lines was increased 4- to 28-fold relative to tkCAT. Deletional analysis of the 3' terminus indicated a requirement for at least 7 bp 3' of the transcription start site. Promoter activity was strongly inhibited in a dose-dependent fashion by phorbol ester, with responsiveness mapped to bp -208/-54, but was not responsive to glucocorticoid.(ABSTRACT TRUNCATED AT 250 WORDS)

496 Background: HCC patients (pts) with Child Pugh B (CPB) cirrhosis have poor prognosis and limited treatment (Tx) options. Nivolumab demonstrated durable responses and acceptable safety in Child Pugh A (CPA) HCC in the CheckMate-040 trial with rates of hepatotoxicity similar to non-HCC populations. The safety and efficacy of nivolumab has not been established in pts with CPB cirrhosis. Methods: Design: Retrospective case series with IRB approval. Key eligibility: HCC with CPB cirrhosis; treated with nivolumab as standard Tx; enrolled in the UCSF Hepatobiliary Tissue Bank and Registry. Study endpoints: Safety during nivolumab Tx including all-cause grade(Gr) ≥ 3 adverse events (AE), serious AE (SAE), any grade immune-related (ir)AE, and systemic steroid (SS) requirement; clinical outcomes including time on Tx (TOT) with nivolumab and overall survival (OS). Results: Thirteen pts were included: male 77%; Asian 38%, white 54%; median age 66 (range: 26-86); HCV Ab+ 31%, HBsAg+ 23%; BCLC B/C 31%/69%; median Child-Pugh score 8; median prior systemic Tx 1 (range: 0-6); prior sorafenib 69%, median duration on prior sorafenib 137 days (range 10-341). The Table depicts safety outcomes on nivolumab. Median TOT on nivolumab: 44 days (95% CI: 32, 98) (range: 17-811+). Median OS from start of nivolumab: 119 days (95% CI: 40, 247) (range: 40-811+). Best response of at least stable disease occurred in 3/13 (23%) of patients, including prolonged stable disease (SD) for 6+ months and complete response (CR) for 24+ months on nivolumab (1 pt each). Conclusions: CPB HCC pts treated with nivolumab experienced high rates of all-cause Gr ≥ 3 AE and SAE and short OS, similar to prior studies in CPB HCC. Rates of irAE attributed to nivolumab were similar to rates reported in CheckMate-040 CPA population, without unexpected AE. A subset of pts experienced prolonged stable disease and CR. Nivolumab warrants further study in CPB HCC.[Table: see text]

210 Background: Neoadjuvant chemoradiation (NT) has become the standard for patients with locally advanced esophageal cancer. Thirty percent of patients who undergo esophagectomy will develop atrial fibrillation (AF). NT may contribute to patients developing AF and this may be a surrogate for anastomotic dehiscence (AD). Methods: We queried a prospective esophageal database to identify patients who underwent esophagectomy with or without NT. Demographics and post-operative complications were all compared with fisher exact test and considered significant at p<0.05. Results: We identified 811 patients who underwent esophagectomy with a mean age of 68 +/- 12 years. Five-hundred and fifteen (63.5%) were treated with NT and 296 (36.5%) were not. Eighty-nine (11%) of patients developed AF, 59 (11.5%) in the NT group, and 30 (10.1%) in the non NT group. There was no significant differences noted in the incidence of AF in those that were treated with NT and those that were not (p=0.64). A total of 54 (6.7%) patients were identified as having AD, 27 (5.2%) in the NT cohort and 27 (9.1%) in the non NT cohort. The NT group had lower incidence of AD compared to their non NT counterparts (p=0.04). Of the 54 patients who experienced AD, 6 (11%) had concomitant AF, and 48 (89%) did not and the remaining 83 patients who developed AF did not develop AD (p=1). Conclusions: NT prior to esophagectomy does not increase patient’s risk for developing postoperative AF. Moreover, the presence of AF in the post esophagectomy patient, did not serve as a surrogate for identifying AD.

Abstract Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, &gt; 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.

Introduction. It is uncertain whether starting screening at 45 years old would improve colorectal cancer prevention and currently available studies in adults younger than 50 years old are limited. Aim. To evaluate the adenoma detection rate at different age intervals. Materials and methods. Colonoscopies performed on adult outpatients were analyzed. Adenoma detection was recorded in the total population and in patients with screening indication. First, patients were divided into two groups: 50 years or older (group A) and younger than 50 years (group B). Then, we analyzed the different age segments: up to 44 years (group 1) 45 to 49 (group 2), 50 to 54 (group 3), and 55 or older (group 4). Results. A total of 5090 patients were included, 2877 with indication for screening. Patients were divided as follows: 3883 in group A, 1207 in group B, 811 in group 1, 396 in group 2, 749 in group 3 and 3134 in group 4. In the total population, adenoma detection was 20.5%: 23.5% in group A, 10.5% in group B (p = 0.000); 8.3% in group 1, 14.8% ingroup 2, 18.1% in group 3, and 24.8% in group 4 (group 1vs. group 2: p = 0.001, group 2 vs. group 3: p = 0.189, andgroup 3 vs. group 4: p = 0.000). In the screening population,adenoma detection was 20.5%: 21.4% in group A, 14.8%in group B (p = 0.004); 13.1% in group 1, 17.0% in group2, 16.1% in group 3, and 22.8% in group 4 (group 1 vs.group 2: p = 0.31; group 2 vs. group 3: p = 0.81; and group3 vs. group 4: p = 0.001). Conclusion. Adenoma detectionis not different between 45 to 49 and 50 to 54 years of age,and is lower below 45 years of age, which suggests startingcolorectal cancer screening at this age.

Bacillus licheniformis is a soil bacterium with many industrial applications. In addition to enzymes, platform chemicals, antibiotics and phytohormones, the species produces exopolysaccharides (EPSs) of various biological activities. This study revealed that Bulgarian isolate B. licheniformis 24 produced EPSs consisting of galactose, glucose and mannose with substrate-dependent ratio. From glucose, B. licheniformis 24 secreted EPS1, consisting of 54% galactose, 39% glucose and 7% mannose. From fructose, the strain formed EPS2, containing 51% glucose, 30% mannose and 19% galactose. Batch cultivation in flasks yielded 2.2–2.6 g/L EPS1 and 1.90–2.11 g/L EPS2. Four to five times higher yields of EPS were obtained from both substrates during batch and fed-batch processes in a fermenter at 37.8 °C, pH 6.2 and aeration 3.68 vvm. The batch process with 200 g/L of starting substrates received 9.64 g/L EPS1 and 6.29 g/L EPS2, reaching maximum values at the 33rd and 24th h, respectively. Fed-batch fermentation resulted in the highest yields, 12.61 g/L EPS1 and 7.03 g/L EPS2. In all processes, EPSs were produced only in the exponential growth phase. Both EPSs exhibited antioxidant activity, but EPS2 was much more potent in this regard, reaching 811 μM Vitamin C Equivalent Antioxidant Capacity (versus 135 μM for EPS1). EPS1 displayed antibacterial activity against a non-O1 strain of Vibrio cholerae.

Summary: аssessment of the prevalence of type 2 diabetes mellitus (DM2) in the adult population of Tskhinval, Republic of South Ossetia. Material and methods. The outpatient records of 811 patients registered with the endocrinologist of the municipal polyclinic with a diagnosis of DM2 were analyzed. The study took into account outpatient records of 478 women and 333 men. To obtain a representative sample, patients (aged 38 to 93 years) were stratified by age, gender, and body mass index. The level of glycemia and the year of occurrence in the initial setting of DM2 were also taken into account. Results. The average age at the diagnosis of DM2 in women was higher than in men (62 and 57 years, respectively). The prevalence of DM2 in relation to gender was higher in women than in men (59 and 41%). At the age of 51–58 years, the largest number of newly detected cases of DM2 was observed. Conclusions. The prevalence of DM2 among the population of Tskhinval is 4.4%. Given the data from the NATION study that only 54% of cases of DM2 are diagnosed, the number of patients with DM2 in Tskhinval may be about 2.5 thousand people (about 8.1% of the urban population). The obtained data should form the basis of the service for medical examination of the population, prevention and treatment of DM2 in the Republic of South Ossetia

Diabetic nephropathy is a major cause of end-stage renal disease worldwide. The current studies were performed to determine the later stages of the progression of renal disease in type II diabetic mice (BKS; db/db). Methodology was developed for determining glomerular filtration rate (GFR) in conscious, chronically instrumented mice using continuous intravenous infusion of FITC-labeled inulin to achieve a steady-state plasma inulin concentration. Obese diabetic mice exhibited increased GFR compared with control mice. GFR averaged 0.313 ± 0.018 and 0.278 ± 0.007 ml/min in 18-wk-old obese diabetic ( n = 11) and control ( n = 13) mice, respectively ( P < 0.05). In 28-wk-old obese diabetic ( n = 10) and control ( n = 15) mice, GFR averaged 0.348 ± 0.030 and 0.279 ± 0.009 ml/min, respectively ( P < 0.05). GFR expressed per gram BW was significantly reduced in 18- and 28-wk-old obese diabetic compared with control mice (5.9 ± 0.3 vs. 9.0 ± 0.3; 6.6 ± 0.6 vs. 7.8 ± 0.3 μl·min−1·g body wt−1), respectively ( P < 0.05). However, older nonobese type II diabetic mice had significantly reduced GFR (0.179 ± 0.023 ml/min; n = 6) and elevated urinary albumin excretion (811 ± 127 μg/day) compared with obese diabetic and control mice (514 ± 54, 171 ± 18 μg/day), which are consistent with the advanced stages of renal disease. These studies suggest that hyperfiltration contributes to the progression of renal disease in type II diabetic mice.

Background There has been increasing attention on assessing rates of sexting in adolescents and of the potential negative effects of the behaviour. Our aim was to assess rates and correlates of sexting in Australian students in years10, 11 and 12. Methods: The current study was part of The Fifth National Survey of Australian Secondary Students and Sexual Health and reports on responses of 2114 students (811 male, 1303 female). Sexting was assessed using six items: sending a sexually explicit written text message; receiving a sexually explicit text message; sending a sexually explicit nude or nearly nude photo or video of themselves; sending a sexually explicit nude or nearly nude photo or video of someone else; receiving a sexually explicit nude or nearly nude photo or video of someone else; and using a social media site for sexual reasons. Results: Approximately half of the students had received (54%, 1139/2097) or sent (43%, 904/2107) a sexually explicit written text message. Sexually explicit images had been received by 42% (880/2098) of students, one in four students had sent a sexually explicit image of themselves (26%, 545/2102) and one in 10 had sent a sexually explicit image of someone else (9%, 180/2095). Finally, 22% (454/2103) of students had used social media for sexual reasons. Sexting was associated with several correlates. Conclusions: Sexting was relatively common in this sample of year 10, 11 and 12 Australian students, particularly among older students, those who are sexually active, and those who use recreational substances.

Aim and research question: The aim of this study is to test Macswan’s ((1999). A minimalist approach to intrasentential code switching. New York, NY: Garland; (2000). The architecture of the bilingual language faculty: Evidence from intrasentential code-switching. Bilingualism: Language and Cognition, 3, 37–54; (2005). Codeswitching and generative grammar: A critique of the MLF model and some remarks on “modified minimalism”. Bilingualism: Language and Cognition, 8, 1–22.) PF Disjunction Theorem (PFDT), which was proposed based on Chomsky’s ((1995). The minimalist program. Cambridge, MA: MIT Press.) minimalist programme, to answer the following question: Is code-switching (CS) behaviour governed by CS-specific grammar or an innate mechanism that produces monolingual and bilingual utterances in our language faculty? Methodology: A quantitative approach was adopted to test the PFDT with the Southern Min/Mandarin CS data. Data and analysis: 811 lexical items extracted from 343 bilingual clauses in my Southern Min/Mandarin CS corpus, and almost no violation against this model (i.e., a word-internal switch) was found, except one example that was regarded as the informant’s slip of tongue. Findings/conclusions: The results of this study confirm the prediction of the PFDT that phonological systems cannot be mixed within a word. Originality: Although the morphosyntactic structures and in some cases the pronunciations of morphemes are identical, tonal differences of these two languages still prohibit word-internal switches. Significance/implications: This study thus supports the PFDT and argues that CS behaviour is governed by a single innate mechanism that governs both monolingual and bilingual language production and that the so-called CS-specific grammar/mechanism is not necessary.

Abstract A climatology of precipitation features (or objects) from the Great Britain and Ireland radar-derived precipitation mosaic from 2006 to 2015 is constructed, with features defined as contiguous areas of nonzero precipitation rates. Over the 10 years, there are 54 811 747 nonunique precipitating features over 100 km2 in area, with a median precipitation feature area of 249 km2, median major axis length of 29.2 km, median aspect ratio of 2.0:1, median feature mean precipitation rate of 0.49 mm h−1, and median feature maximum precipitation rate of 2.4 mm h−1. Small-scale precipitating systems are most common, but larger systems exceeding 10 000 km2 contribute close to 70% of the annual precipitation across the study region. Precipitation feature characteristics are sensitive to changes in annual and diurnal environment, with feature intensities peaking during the afternoon in summer and the largest precipitation features occurring during winter. Precipitation intensities less than 5 mm h−1 comprise 97.3% of all precipitation occurrences and contribute 83.6% of the total precipitation over land. Banded precipitation features (defined as precipitation features with aspect ratio at least 3:1 and major axis length at least 100 km) comprise 3% of all precipitation features by occurrence, but contribute 23.7% of the total precipitation. Mesoscale banded features (defined as banded precipitation features with major axis length at least 100 km and total area not exceeding 10 000 km2) and mesoscale convective banded features (defined as banded precipitation features with at least 100 km2 of precipitation rates exceeding 10 mm h−1) are most prevalent in southwestern England, with mesoscale convective banded features contributing up to 2% of precipitation.

Abstract de Lima, TR and Silva, DAS. Handgrip strength is not associated with high blood pressure and does not have good discriminatory power for high blood pressure in adolescents. J Strength Cond Res 37(1): 46–54, 2023—Muscle strength measured by handgrip strength (HGS) was inversely and independently associated with high blood pressure (HBP). In addition, HGS has been used as a valuable indicator for monitoring pediatric health. This study aimed to investigate the association between HGS indexes and HBP, verify the discriminatory capacity of HGS to identify HBP in adolescents, and propose cut-points for HGS to be used in the early identification of HBP if good discriminatory power is identified between the variables. This was a cross-sectional study comprising 811 adolescents (male: 48.9%; age: 16.4 ± 1.3 years) from southern Brazil. Blood pressure was measured by the oscillometric method. Handgrip strength was assessed by a hand dynamometer and 3 different approaches were adopted: (a) HGS in kilogram-force, (b) normalized HGS (HGS/body mass), and (c) allometric HGS (HGS/body mass−0.67). Binary logistic regression was used to verify the association between HGS indexes and HBP, and the receiver operating characteristic (ROC) was used to determine the possible use of HGS as a diagnostic tool for HBP. Handgrip strength indexes were not associated with HBP (p > 0.05), and ROC analyses showed a nonsignificant discriminating accuracy for most of the HGS indexes analyzed (p > 0.05) in identifying HBP in boys and girls. The area under curve (AUC) values ranged from 0.499 (95% CI [0.403–0.596] for allometric HGS among overweight or obese boys) to 0.595 (95% CI [0.546–0.643] for HGS among boys). Handgrip strength was not associated with HBP, and its use in the screening of HBP in adolescents is not recommended.

Abstract Background More than a century of research on the neurobiological underpinnings of the Major Psychoses (Schizophrenia SZ, Bipolar Disorder BD, Major Depressive Disorder, Schizoaffective Disorder SZA) has been unable to identify diagnostic “markers”. An alternative approach is to study dimensional psychopathological syndromes that cut across categorical diagnoses. Brain imaging studies on the correlates of syndromes are thus far restricted to one diagnosis, however it is unclear, whether structural brain correlates of syndromes are the same across diagnoses. Previously, we have identified 7 syndromes in n=811 patients suffering from major psychoses, applying a confirmatory factor analysis, including depressed mood, negative symptoms, delusions, formal thought disorders, hallucinations, mania and increased appetite. The aim of the current study was to identify gray matter volume correlates of these syndromes across the major psychoses. Methods We tested the association of the above 7 psychopathological factors with whole brain GMV (voxel-based morphometry) in a sample of n=713 patients meeting DSM-IV criteria for MDD (n=550), BD (n=79), SZ (n=51) and SZA (n=33) (www.for2107.de). T1 weighted brain images were acquired at a 3-Tesla MRI. Images were pre-processed as implemented in the Cat12 (SPM12) toolbox. We performed multiple regression analyses for each factor separately and used the family wise error correction (FWE) to correct for multiple comparisons. Additionally, we tested if local VBM associations were driven by one diagnosis extracting the beta-volumes of the clusters and then comparing the subgroups using ANCOVA. Results The delusion factor was negatively correlated with gray matter volume in the left inferior temporal gyrus/fusiform gyrus (k=138 voxels, x/y/z=-48/-58/-15, t=5.23, p&lt;.05 FWE peak level) and the left amygdala/hippocampus (k=23 voxels, x/y/z=-15/-12/-12, t=4.84, p&lt;.05 FWE peak level). The hallucinatory syndrome was negatively correlated with volume in the right thalamus proper (k=54 voxels, x/y/z=8/-4/-2, t=4.9, p&lt;.05 FWE peak level). Extraction of the beta-volumes revealed no effect of diagnosis (delusions (F (3,708) p=.54; hallucinations (F (3,708) p=.542). Discussion Volume changes underlying psychopathological syndromes are independent of diagnosis. We could confirm previous results from much smaller studies which have restricted themselves to single diagnoses or case control designs. Our findings open a new avenue for neurobiological research of the major psychoses, using syndrome based, dimensional approaches rather than DSM or ICD diagnoses.

Abstract Immunoglobulin G antibody response, measured as sample-to-positive (S/P) ratio, to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) has been proposed as an indicator trait for improved reproductive performance in PRRSV-infected purebred sows and PRRSV-vaccinated crossbred gilts. In this study, we investigated the genetic correlations (rg) of S/P ratio following a PRRSV outbreak and PRRSV-vaccination with performance in non-exposed and PRRSV-exposed sows. PRRSV outbreak phase was defined based on previously described methodologies after the detection of typical clinical signs of PRRSV infection. 541 Landrace sows had S/P ratio measured at ~54 days after the beginning of the PRRSV outbreak (S/Poutbreak), and 906 Landrace x Large White naïve F1 gilts had S/P ratio measured at ~50 days after vaccination with a commercial modified live PRRSV vaccine (S/PVx). 711 and 428 Landrace sows had reproductive performance recorded before and during the PRRSV outbreak, respectively. 811 vaccinated F1 animals had farrowing performance for up to 3 parities. All animals were genotyped for ~28K SNPs. The estimate of rg of S/Poutbreakwith S/PVx was high (rg±SE = 0.72±0.18). Estimates of rg of S/Poutbreak with reproductive performance in F1 sows were low to moderate, ranging from 0.05±0.23 (number stillborn) to 0.30±0.20 (total number born). Estimates of rg of S/PVxwith reproductive performance in non-infected purebred sows were moderate and favorable with number born alive (0.50±0.23), but low (0 to -0.11±0.23) with litter mortality traits. Estimates of rg of S/PVx were moderate and negative (-0.47±0.18) with the number of mummies in PRRSV-infected purebred sows and low with other traits (-0.29±0.18 for total number born to 0.05±0.18 for number stillborn). These results indicate that selection for antibody response following a PRRSV outbreak collected in purebred sows and to PRRSV vaccination collected in commercial crossbred gilts may increase litter size of non-infected and PRRSV-exposed purebred and commercial crossbred sows.

A novel genus-specific PCR for mycobacteria with simple identification to the species level by restriction fragment length polymorphism (RFLP) was established using the 16S-23S ribosomal RNA gene (rDNA) spacer as a target. Panspecificity of primers was demonstrated on the genus level by testing 811 bacterial strains (122 species in 37 genera from 286 reference strains and 525 clinical isolates). All mycobacterial isolates (678 strains among 48 defined species and 5 indeterminate taxons) were amplified by the new primers. Among nonmycobacterial isolates, only Gordonia terrae was amplified. The RFLP scheme devised involves estimation of variable PCR product sizes together with HaeIII and CfoI restriction analysis. It yielded 58 HaeIII patterns, of which 49 (84%) were unique on the species level. Hence,HaeIII digestion together with CfoI results was sufficient for correct identification of 39 of 54 mycobacterial taxons and one of three or four of seven RFLP genotypes found inMycobacterium intracellulare and Mycobacterium kansasii, respectively. Following a clearly laid out diagnostic algorithm, the remaining unidentified organisms fell into five clusters of closely related species (i.e., the Mycobacterium aviumcomplex or Mycobacterium chelonae-Mycobacterium abscessus) that were successfully separated using additional enzymes (TaqI, MspI, DdeI, orAvaII). Thus, next to slowly growing mycobacteria, all rapidly growing species studied, including M. abscessus,M. chelonae, Mycobacterium farcinogenes,Mycobacterium fortuitum, Mycobacterium peregrinum, and Mycobacterium senegalense (with a very high 16S rDNA sequence similarity) were correctly identified. A high intraspecies sequence stability and the good discriminative power of patterns indicate that this method is very suitable for rapid and cost-effective identification of a wide variety of mycobacterial species without the need for sequencing. Phylogenetically, spacer sequence data stand in good agreement with 16S rDNA sequencing results, as was shown by including strains with unsettled taxonomy. Since this approach recognized significant subspecific genotypes while identification of a broad spectrum of mycobacteria rested on identification of one specific RFLP pattern within a species, this method can be used by both reference (or research) and routine laboratories.

AbstractIntroduction:In July 2013, a train carrying 72 cars of crude oil derailed in the town of Lac-Mégantic (Eastern Townships, Quebec, Canada). This disaster provoked a major conflagration, explosions, 47 deaths, the destruction of 44 buildings, the evacuation of one-third of the local population, and an unparalleled oil spill. Notwithstanding the environmental impact, many citizens of this town and in surrounding areas have suffered and continue to suffer substantial losses as a direct consequence of this catastrophe.Problem:To tailor public health interventions and to meet the psychosocial needs of the community, the Public Health Department of Eastern Townships has undertaken repeated surveys to monitor health and well-being over time. This study focuses on negative psychosocial outcomes one and two years after the tragedy.Methods:Two cross-sectional surveys (2014 and 2015) were conducted among large random samples of adults in Lac-Mégantic and surrounding areas (2014: n = 811; 2015: n = 800), and elsewhere in the region (2014: n = 7,926; 2015: n = 800). A wide range of psychosocial outcomes was assessed (ie, daily stress, main source of stress, sense of insecurity, psychological distress, excessive drinking, anxiety or mood disorders, psychosocial services use, anxiolytic drug use, gambling habits, and posttraumatic stress symptoms [PSS]). Exposure to the tragedy was assessed using residential location (ie, six-digit postal code) and intensity of exposure (ie, intense, moderate, or low exposure; from nine items capturing human, material, or subjective losses). Relationships between such exposures and adverse psychosocial outcomes were examined using chi-squares and t-tests. Distribution of outcomes was also examined over time.Results:One year after the disaster, an important proportion of participants reported human, material, and subjective losses (64%, 23%, and 54%, respectively), whereas 17% of people experienced intense exposure. Participants from Lac-Mégantic, particularly those intensely exposed, were much more likely to report psychological distress, depressive episode, anxiety disorders, and anxiolytic drug use, relative to less-exposed ones. In 2015, 67% of the Lac-Mégantic participants (76% of intensely exposed) reported moderate to severe PSS. Surprisingly, the use of psychosocial services in Lac-Mégantic declined by 41% from 2014 to 2015.Conclusion:The psychosocial burden in the aftermath of the Lac-Mégantic tragedy is substantial and persistent. Public health organizations responding to large-scaling disasters should monitor long-term psychosocial consequences and advocate for community-based psychosocial support in order to help citizens in their recovery process.

Abstract Background. Different types of BCR-ABL fusion mRNAs can be found in pts with CML due to different genomic breakpoints and alternative splicing. The two major forms join ABL exon 2 with exons 13 or 14 of BCR, resulting in two main transcripts, b2a2 and b3a2, respectively, that codify for a p210 protein present in the majority of CML patients. b3a2 is more frequent in newly diagnosed patients than the b2a2 transcript, and occasionally both transcripts may be present. The clinical significance of the specific transcript among CML pts treated with imatinib has not been clearly established, and some have suggested that b2a2 may be associated with better outcome. (Blood2006108: Abstract 4780) Genet.Mol. Res.4(4): 803–811 (2005)Journal of Clinical Oncology, 2007 Vol 25, No 18S (June 20 Supplement), 2007: 7043. Purpose: To determine if there is a difference in outcome after imatinib therapy in CML pts according to their BCR-ABL transcript. Methods: We analyzed 480 pts with CP CML treated with imatinib, 251 receiving imatinib as frontline therapy and 229 after interferon (IFN) failure. Molecular response was evaluated using RT PCR every 3 months (mo). Results: The median follow-up was 62 mo (range 1–92 mo) Median age was 51 years (range 15–84). Overall, 187 of 480 (39%) pts expressed b2a2, 234 (49%) b3a2, 55 (11%) expressed both, and 4 (1%) expressed e1a2. The rates of major and complete cytogenetic response were similar for pts with b3a2 and b2a2, both in the newly diagnosed and the post-IFN failure: CCyR 91% for b3a2 and 89% for b2a2 in frontline, and 72% and 78%, respectively in the post-IFN failure group. However, among 433 pts evaluable for molecular response, transcript levels were significantly lower at 3, 6 and 12 months from start of therapy for pts with b3a2 compared to those with b2a2 (Table 1). Table 1. Median BCR-ABL transcript levels over time by transcript type 3 months 6 months 9 months overall b2a2 1.8284 0.318 0.186 0.0464 b3a2 0.5175 0.0553 0.0352 0.0033 p-value 0.001 &lt;0.001 &lt;0.001 &lt;0.001 This resulted in a significantly higher probability of achieving a major molecular remission (MMR) and complete molecular remission (CMR; ie, undetectable transcript levels) for pts with the b3a2 transcript (Table 2). Table 2 Molecular Response in patients Post IFN failure and patients newly treated Transcript No.* MMR** (%) P value CMR*** (%) P value *Number of evaluable patients. Dx=Diagnosis New Dx b2a2 106 63 59 26 25 New Dx b3a2 115 88 77 0.008 54 47 0.002 Post IFN b2a2 62 21 34 10 16 Post IFN b3a2 97 61 63 0.001 41 42 0.001 There was a trend for an improved transformation-free survival for pts with b3a2 compared to those with b2a2 (4-yr rates 98% vs 93%, respectively, p=0.08) and event-free survival (94% vs 87%, p=0.37). Although fewer pts co-expressed both transcript types, they behaved like the pts with b3a2. Conclusion: Pts with the b3a2 transcript have a better molecular response to imatinib that those with b2a2. This prognostic factor should be considered when evaluating response to therapy.

Introduction The kidney is an important target organ in plasma cell dyscrasias, subjected to various mechanisms of injury such as tubular obstruction, hypercalcemia, and pre-existing disease. Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) is of concern as treatment-related toxicity (for instance infections and mucositis) is known to increase with renal impairment (RI). However, even severe MM-induced RI may recover with anti-myeloma treatment. We set out to compare three induction regimens in patients (pts) with transplant-eligible NDMM in terms of renal recovery and toxicity, MM response and associated adverse events (AEs). Pts from two prospective trials (NCT00833560, NCT01685814) were analyzed, provided post-induction (PInd) restaging data was available. They received three 3-week induction cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD); btz, lenalidomide (len), and dex (VRD); or three 4-week cycles with len, adriamycin, and dex (RAD). All pts had to have measurable disease, an estimated glomerular filtration rate (eGFR) of >30 ml/min and to be up to 60 (VCD) and 65 years (yrs) of age, respectively. VCD consisted of intravenous (IV) btz 1.3 mg/m² on day (D) 1, 4, 8, 11; IV cyclophosphamide 900 mg/m2D1; dex 20 mg D 1+2, 4+5, 8+9, 11+12. VRD of subcutaneous (SQ) btz 1.3 mg/m² D 1, 4, 8, 11; len 25 mg, D1-14; dex 20 mg D 1+2, 4+5, 8+9, 11+12; and RAD of len 25 mg D1-21; IV adriamycin 9 mg/m² D1-4; dex 40 mg D 1-4 + 17-20. MethodsThis is a secondary analysis of a phase 2 and a phase 3 study. We hypothesized MM disease response (and in turn, renal recovery) would be best with VRD. GFR was estimated by the MDRD IV or CKD-Epi formulas. The increase (and decrease, respectively) of renal function expressed by "GFRpost induction- GFRscreening" was tested for significance (p<.05) by an averaging process. In addition to absolute values, we performed slope analysis of changes in eGFR over time. ResultsThe safety set included 883 patients, 811 of whom received three induction cycles plus restaging and were eligible. 395 patients had received VCD; 214 VRD; and 202 RAD, with similar median ages of 54, 56 and 55 yrs, respectively. Baseline body mass index, heart rate and systolic/diastolic blood pressure were well balanced between groups. Proportion of ISS III pts was around 15% with all regimens. 8.1% of VCD pts, 12.6% of VRD and 10.9% of RAD pts all had baseline eGFR <50 ml/min (group I). eGFR rates of > 50 ml/min and ≤ 70 ml/min (group II) were observed in 11.6 % of VCD pts, 29.9% of VRD and 25.2 % of RAD pts, respectively. 78.2% of VCD pts, 56.1% of VRD and 63.9% of RAD pts had a baseline eGFR of > 70 ml/min (group III; p<.0001, chi-square-test). Evaluating MM PInd response by IMWG and EBMT criteria, 85.1% of VCD pts, 91.1% of VRD pts and 90.6% of RAD pts all achieved >PR (p=.0387). In the whole cohort, proportion of patients in eGFR group I had decreased from 10.0 to 3.0% (p<.001). The respective values were 1.8% post VCD, 5.6% post VRD and 2.5% post RAD (p<.0001). A downgrade of at least one GFR group occurred in 1.8% after VCD, 8.4% after VRD and 6.4% after RAD, respectively (distribution of group changes: p=.0030). In eGFR slope analysis (baseline vs PInd), median value was +3.8 mL/min(/1.73m²)/month in VCD pts, +0.7 mL/min(/1.73m²)/month in VRD and +2.1 mL/min(/1.73m²)/month in RAD patients (p=.0714). Next, we used three categories for incremental slope changes: < 0 ml/min(/1.73m²)/month; ≥ 0 ml/min(/1.73m²)/month and ≤ +2 ml/min(/1.73m²)/month; and > +2 ml/min(/1.73m²)/month, respectively. 25.7% of VCD, 29.4% of VRD and 23.3% of RAD pts fell into the <0 ml/min(/1.73m²)/month categories. An incremental change of >+2 ml/min was achieved by 55.2% of VCD vs 42.1% of VRD treated pts, respectively (Figure 1; p<.0001). ConclusionsIn our cohort of 811 NDMM pts, 10 % presented with <50 ml/min baseline eGFR. This proportion decreased significantly to 3.0% PInd. The different MM response across induction protocols was obviously not reflected by a concordant rate of renal recovery. Significantly more VCD vs VRD-treated patients achieved a positive eGFR slope of > +2 ml/min(/1.73m²)/month. It is tempting to speculate that either the difference between SQ and IV btz, differential effects of len and cyclophosphamide on kidney function or non-MM related factors account for these unexpected and discordant renal and MM responses. Kidney-specific AEs, urine protein studies and comorbidities will be presented. Disclosures Mügge: Celgene: Research Funding; Celgene, Janssen: Honoraria. Schreder:Janssen, Celgene: Consultancy, Honoraria. Schaefer-Eckart:Pfizer, Janssen, Celgene: Honoraria. Metzler:Bristol-Myers Squibb, Celgene: Consultancy, Honoraria. Hertenstein:RS Media: Research Funding. Maschmeyer:Gilead, Janssen Cilag, Astra Zeneca; BMS, Merk-Serono: Honoraria. Salwender:Janssen Cilag: Consultancy, Honoraria, Other: Travel grants; Celgene: Honoraria, Other: Travel grants; AMGEN: Honoraria, Other: Travel grants; Sanofi: Honoraria, Other: Travel grants; Bristol-Myers Squibb: Honoraria, Other: Travel grants; Takeda: Honoraria, Other: Travel grants; Oncopeptides: Honoraria, Other: Travel Grants. von Lilienfeld-Toal:Celgene, Oncopeptides: Consultancy, Honoraria. Straka:Celgene, Janssen, AMGEN: Consultancy, Research Funding, Speakers Bureau. Knop:Janssen, AMGEN, Bristol-Myers Squibb, Celgene: Consultancy, Honoraria. OffLabel Disclosure: Lenalidomide, adriamycin, dexamethsone in newly diagnosed multiple myeloma

Background:Type 2 diabetes mellitus (T2DM) and arthritis are considered two separate conditions. However, inflammation and metabolic changes play a major role in diabetes co-morbidity (1). The pathogenesis of the joint pain and stiffness in diabetes patients is not fully understood. Diabetic osteoarthropathy (neuropathic arthropathy) considers a quite rare condition (0.1–0.4% of diabetic patients), involving destructive, lytic joint changes (2). Interestingly, over 52% of diabetic patients have joint diseases, compare to only 27% without diabetes; and people with arthritis have over 60%higher risk of diabetes development (3).Objectives:The purpose of the study was to determine the association between the lesions of low extremity arteries (LEA) and the prevalence of arthritis (joint pain and stiffness) among patients with type 2 diabetes.Methods:This is the pilot analysis of the musculoskeletal data obtained from the prospective cohort study of patients with diabetes complications 2013-2016 (179 consecutive T2DM pts undergoing transfemoral amputation (TFA) due to gangrene of lower limb (4,5), and 199 patients experienced balloon angioplasty (BA) of the LEA (without gangrenes). The computer tomography angiography was performed, along with clinical, laboratory and instrumental examination. Functional class of joint lesions (hip, knee or foot) was obtained based on self-service and (un)professional activity.Results:All observed patients had diabetic neuropathy. The affected extremity in all the patients undergoing TFA had critical arterial ischemia along with foot gangrene, knee/hip pain, stiffness and rigidity. The second extremity also had stenoses of popliteal, anterior or posterior tibial arteries and the severity of stenoses was positively correlated with the severity of muscle and joints pain (r=0.771, p<0.001).Among 199 patients without gangrene of lower limb, BA was done on superficial femoral artery 46 (23.1%) patients, popliteal in 44 (22.1%), posterior tibial 54 (27.1%), arterial tibial 41 (20.6), and peroneal artery 14 (7%). At least 1 large and 1 small joint was affected per person. The correlation between the prevalence of joint pain/stiffness and peripheral artery stenosis of the same lower extremity in patients without gangrene was significant r=0.632, indicating a large positive relationship (approximately 39.9% of the total variance). A linear regression analysis was conducted to evaluate the association between the severity of artery lesions and the severity of joint functional class,F(1, 198) = 57.82,p<0.001,t= 7.91,p< 0.001. The 95% confidence interval for the slope was 0.71 to 1.29, which did not include the value of zero.Conclusion:The results show that the more severe the peripheral artery stenosis was the more prevalent join lesions are and worsen the function class. However, more studies are needed.References:[1]Shalaeva E.V. et al. Impact of purulent complications and sepsis on cardiovascular system in patients with type 2 diabetes. Critical Care 2014, 18(Suppl 2):P6; doi:10.1186/cc14009[2]Kim R.P., et al. Musculoskeletal Complications of Diabetes Mellitus. Clinical Diabetes. 2001, 19 (3) 132-135; DOI: 10.2337/diaclin.19.3.132[3]Piva S.R., Susko A.M. et al. Links between Osteoarthritis and Diabetes:Implications for Management from a Physical Activity Perspective.[4]Shalaeva E.V., Saner H, et al. Coronary artery calcium score and coronary computed tomographic angiography for major perioperative cardiovascular complications in symptomatic diabetic patients undergoing trans-femoral amputation. International Journal of Cardiology 221 (2016) 806–811.http://dx.doi.org/10.1016/j.ijcard.2016.06.165Disclosure of Interests:None declared

The experience of 811 bronchoscopies (100%) was analysed in patients on artificial lung ventilation. The position of the intubation tube in the trachea during the procedure was assessed. In 78 cases (9,618%) there was an incorrect position of the intubation tube requiring correction. In 35 cases (4,316%), the intubation tube was displaced to the right main bronchus and as result, the left lung was not ventilated. In the remaining cases, various ways of the incorrect position of the intubation tube above the tracheal bifurcation carina were noted. As a recommendation, endoscopic criteria of the correct position of the intubation tube are suggested. For timely diagnostics and correction of such disturbances, it is recommended to perform obligatory bronchoscopic monitoring.

BackgroundNumerous cytokines that influence disease activity in psoriatic arthritis (PsA) are modulators of the Janus Kinases/Signal Transducers and Activators of Transcription (JAK/STAT) pathway. The JAK1/STAT1/STAT3/STAT5 network can drive the expansion of Th17 and regulatory T cells via proinflammatory cytokines in PsA joints,[1], [2] while hyperphosphorylation of STAT3 in immune cells has previously been shown to promote PsA pathogenesis through the Interleukin (IL)-23/IL-17/IL-22 axis.[3] Therefore, the phosphorylation status of STAT molecules in leucocytes of PsA patients may indicate active disease and could potentially guide treatment with JAK inhibitors.ObjectivesTo analyse phosphorylated STAT (pSTAT) levels of circulating leucocyte subsets in PsA patients with active and inactive diseaseMethodsWhole blood was drawn on consecutive PsA patients fulfilling the CASPAR criteria[4] to perform flow cytometry analysis using the BD FACSLyric platform. Disease activity was assessed using the Disease activity for psoriasis arthritis (DAPSA) score.[5] All steps from storage of drawn blood to cell fixation were performed at 4°C to prevent auto-activation of leucocytes. The geometric mean fluorescence intensities (gMFI) of pSTATs in granulocytes, monocytes, B cells and CD4+/- naïve/memory T cells were compared between patients with moderate to high (MoDA/HDA) and remission to low disease activity (REM/LDA). Correlation analysis between gMFIs and DAPSA scores were performed.ResultsForty-two patients (female ratio: 0.48) with established PsA (median ± standard deviation, age: 56 ± 12.54 years, disease duration: 8.50 ± 7.10 years) were included in this study. Twenty-one percent of patients were in MoDA/HDA, while the remaining 79% were in REM/LDA. Patients in MoDA/HDA showed significantly higher pSTAT3 levels in CD4+ naïve (gMFI median ± standard deviation: 284.5 ± 79.9 vs 238 ± 92.9, p = 0.011), CD4- naïve (297 ± 107.5 vs 238 ± 98.4, p = 0.04), CD4+ memory (227 ± 62.9 vs 190.5 ± 72.2, p = 0.009) and CD4- memory T cells (209 ± 66.8 vs 167.0 ± 64.9, p = 0.036). On the other hand, PsA patients in remission or low disease activity displayed higher pSTAT1 levels in granulocytes (2509 ± 1887 vs 1330.5 ± 784.1, p = 0.040) and monocytes (255 ± 230 vs 144 ± 62.5, p = 0.049). Positive correlations were found between DAPSA scores and pSTAT3 in CD4+ naïve and memory T cells (Spearman’s correlation coefficient rho (ρ) = 0.5, p = 0.0012 and ρ = 0.47, p = 0.0025 resp.) whereas pSTAT1 in granulocytes and monocytes were negatively correlated with the DAPSA scores (ρ = -0.45, p = 0.0074 and ρ = -0.34, p = 0.05).ConclusionDifferential phosphorylation of STAT3 and STAT1 molecules in circulating leucocyte subsets indicates PsA disease activity. Further studies to examine the value of STAT phosphorylation patterns guiding JAK inhibitor therapy are underway.References[1]U. Fiocco et al., “Ex vivo signaling protein mapping in T lymphocytes in the psoriatic arthritis joints,” J. Rheumatol., vol. 93, pp. 48–52, 2015, doi: 10.3899/jrheum.150636.[2]S. K. Raychaudhuri, C. Abria, and S. P. Raychaudhuri, “Regulatory role of the JAK STAT kinase signalling system on the IL-23/IL-17 cytokine axis in psoriatic arthritis,” Ann. Rheum. Dis., vol. 76, no. 10, pp. e36–e36, 2017.[3]E. Calautti, L. Avalle, and V. Poli, “Psoriasis: A STAT3-centric view,” International Journal of Molecular Sciences, vol. 19, no. 1. MDPI AG, Jan. 06, 2018, doi: 10.3390/ijms19010171.[4]W. Taylor, D. Gladman, P. Helliwell, A. Marchesoni, P. Mease, and H. Mielants, “Classification criteria for psoriatic arthritis: Development of new criteria from a large international study,” Arthritis Rheum., vol. 54, no. 8, pp. 2665–2673, 2006, doi: 10.1002/art.21972.[5]M. M. Schoels, D. Aletaha, F. Alasti, and J. S. Smolen, “Disease activity in psoriatic arthritis (PsA): Defining remission and treatment success using the DAPSA score,” Ann. Rheum. Dis., vol. 75, no. 5, pp. 811–818, 2016, doi: 10.1136/annrheumdis-2015-207507.Disclosure of InterestsBarbara Dreo: None declared, Daniel Ruben Pietsch: None declared, Rusmir Husic Speakers bureau: MSD, Lilly und Abbvie, Angelika Lackner: None declared, Johannes Fessler: None declared, Janine Rupp: None declared, Anirudh Subramanian Muralikrishnan: None declared, Jens Thiel Speakers bureau: GSK, BMS, AbbVie, Novartis, Consultant of: GSK, Novartis, Grant/research support from: BMS, Martin Stradner Speakers bureau: Eli Lilly, Pfizer, MSD, BMS, AbbVie, Janssen, Consultant of: Eli Lilly, AbbVie, Janssen, Philipp Bosch Grant/research support from: Pfizer

Background: ITP is an acquired autoimmune disease characterized by transient or persistent thrombocytopenia. ITP substantially impairs pts' quality of life (QoL), including daily activities, social interactions, work and emotional wellbeing, with fatigue being the most common symptom reported by pts. Corticosteroids are the standard first-line treatment for ITP, while thrombopoietin receptor agonists (TPO-RAs), rituximab and fostamatinib are recommended for later lines; however, these treatments have limited sustained efficacy and may be associated with short- and long-term side effects that impact QoL. Aim: To assess pt and physician (MD) perceptions of current ITP treatment and treatment goals using data from I-WISh 2.0. Methods: I-WISh 2.0 was developed using findings from I-WISh 1.0 and surveyed 1018 pts with ITP aged &gt;18 years and 431 MDs who managed ≥3 pts with ITP. I-WISh 2.0 was conducted from February to July 2022 in 15 countries. The surveys, developed by a steering committee (supported by Novartis) comprising expert ITP MDs and pt advocates, included questionnaires about prescribed ITP treatments, their impact on QoL and treatment satisfaction and goals. Results: Of 1018 pts (median age: 46 years), 67% were female and 48% reported ≥1 comorbidity. 97% (956/987) of pts had received ≥1 treatment for ITP and 12% (126/1018) had a splenectomy; 80% (811/1018) were receiving ITP treatment at survey completion and median time on most recent treatment was 30 weeks (n=608). Corticosteroids and TPO-RAs were the most common first- and second-line treatments prescribed by MDs, respectively (Figure 1); MDs estimated that 15% of their pts have opted against receiving ITP treatment (n=431). 73% of MDs (313/431) considered their pts' perception of medications when making treatment decisions. Pts reported a significant burden due to their current ITP medication: 34% (202/597) experienced daily disruption, 37% (214/576) were bothered by needing to plan meals, and 22% (204/939) had difficulty keeping up with daily medications. 19% (172/897) of pts were dissatisfied with their treatment's platelet level control, and 18% (155/843) disagreed that their medication effectively controlled their symptoms. Pts worried about their treatment's short- (48%; 400/833) and long-term (62%; 527/844) side effects. 38% (162/431) of MDs were neutral toward current ITP treatment options and 9% (37/431) were dissatisfied. Of the 37 dissatisfied MDs, limited options (68%), inability to achieve deep/stable remission (54%), lack of efficacy (43%) and inability to reach treatment goals (43%) were the most common reasons. 32% (327/1016) and 13% (127/1016) of pts believed they were not or did not know if they were in sustained remission, respectively. A treatment offering a sustained remission or cure for ITP was an important goal for 82% (823/1007) of pts. Of treatment goals mentioned in their top 3, the most common were healthy blood counts (56%), improving QoL (44%) and increasing energy levels (43%) for pts (n=1018), and reducing spontaneous bleeds (79%), healthy blood counts (60%) and improving QoL (52%) for MDs (n=431). Limiting time on treatment would substantially affect the treatment preference of 66% (668/1009) of pts. 38% (294/775) of pts did not want to take their ITP treatment for the foreseeable future; however, 67% (680/1013) were concerned about relapse if they stopped. Immunosuppression due to ITP treatment worried 414/787 (53%) pts, with 679/1007 (67%) considering it important when discussing treatment decisions. MDs considered corticosteroids and other immunosuppressants to have the most negative impact on fatigue (Figure 2), yet only 12% (52/431) strongly agreed they aimed to limit immunosuppressive effects. Conclusions: Pts with ITP are dissatisfied with current treatment options because of a perceived lack of efficacy, the burden of short- and long-term side effects, and the need for daily, life-long administration. Additionally, some commonly prescribed treatments for ITP are associated with fatigue. Pts and MDs would like new ITP treatments to offer a sustained period of remission or cure, and pts wish to be able to discontinue them without fear of relapse. There is an unmet need for well-tolerated therapies with disease-modifying potential that can safely achieve these goals.

Background: Conventional precision medicine for cancer targets specific gene mutations, but single agent inhibitors rarely result in remission or improve survival in acute leukemia. Current functional screening strategies assay individual drugs, thus missing potential synergistic combinations. We therefore developed a multi-omic approach that integrates mutation data, gene expression data (transcriptome), and in vitro drug sensitivity (functional) data to select drugs including drug combinations for individual patients. Herein we report results of the clinical trial testing this concept [NCT02551718]. This study contributed to validation of 44 genes identified for which expression correlates with drug sensitivity (Lee S-I et al. Nat Commun 2018). Patients and Methods: Eligible patients failed at least 2 prior regimens, or if adverse risk, one multi-drug intensive regimen, had ECOG PS 0-3 and at least 1 million blasts in blood, marrow, tissue or fluid for analysis. The original enrollment was 25 patients to establish feasibility, and the study was later expanded to provide an option for refractory patients. Samples were obtained from the 54 consented patients (44 AML, 8 ALL, 2 acute leukemias of ambiguous lineage). Median age is 58 (range 23-82) and 31.5% of patients had an antecedent hematologic disorder. Of the AML patients (n=44), 7 were favorable, 13 intermediate, and 24 adverse risk (ELN 2017). Patients had a median of 3 prior treatments (range 1-6); 39 patients (72%) had relapsed after prior complete remission (CR) with median duration of 6 months (m) (range: 0-52 m), and 20 had relapsed after allogeneic transplant, 8 within the first 100 days, and 3 never achieved a CR after transplant. Enriched blasts were assayed in a custom CLIA-approved high throughput sensitivity (HTS) screen with 153 drugs and combinations, both conventional and targeted inhibitors, both FDA approved and investigational. Results were obtained within a mean of 5.2 (range 4-7) days. Mutation testing was performed by Invivoscribe using MyAML® targeted NGS panel. Clinical outcomes examined were peripheral blast reduction, response and survival. Results: Twenty-nine patients (53.7%; 25 AML, 2 ALL, 2 acute leukemias of ambiguous lineage) received therapy based on the HTS and mutation analysis. The remaining patients did not receive protocol treatment for a variety of reasons, including insufficient marrow blasts for testing, opting for palliative care, returning to their local area, denial by insurance , lack of access to investigational drugs, or medical complications making them ineligible. Of the 22 patients who had circulating peripheral blasts, 21 (95%) had a reduction, including 7 eradication, of circulating peripheral blasts following therapy. The median number of assay-directed regimens patients received was 2 (range 1-10, mean 2.5). Therapies administered are shown in the Table. Mutation testing on 47 patients revealed that 32 samples (68%) harbored mutations for which an approved or investigational targeted inhibitor could be considered (Figure 1). Figure 2 shows the heatmaps for individual patient mutations and drug sensitivity. Median survival following initiation of protocol therapy was 70 days (range 19-811). Of these often heavily pre-treated patients, 2 achieved CR, 1 CRi, and 6 had partial remissions (PRs), overall response rate (ORR) 31%. It was not always possible to obtain the top drugs if the use was off label or they were investigational, so drugs were selected that were lower in the ranked list of IC50s. When we observed 1-3 log reduction in IC50s for a combination compared to the single agents, the combination regimen would be recommended. For the 9 patients who received intensive combination regimens, there were 1 CR and 2 PRs, (ORR 33%), and for the 13 who received low intensity regimens, there was 1 CR, 1 CRi and 1 PR (ORR 23%). Enrolled allogeneic transplant recipients who received study treatment had a median survival of 476 days post-transplant compared to 340 days for those who did not receive assay guided therapy. Conclusions: This study demonstrates the feasibility of simultaneous collection of genomics, gene expression, and functional drug sensitivity data with the intent to guide choice of therapy. Responses were observed after study guided treatment. Future trials will incorporate new algorithms based on the correlative analyses obtained by this study to optimize treatment choices. Disclosures Becker: The France Foundation: Honoraria; Accordant Health Services/Caremark: Consultancy; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding. Oehler:NCCN: Consultancy. Blau:All4Cure: Equity Ownership. Hammer:Glycomimetics: Consultancy. Cassaday:Kite/Gilead: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests. Scott:Agios: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Walter:Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; Seattle Genetics: Research Funding; Race Oncology: Consultancy; Pfizer: Consultancy, Research Funding; New Link Genetics: Consultancy; Boston Biomedical: Consultancy; Boehringer Ingelheim: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy. Gardner:Abbvie: Speakers Bureau. Carson:Invivoscribe, Inc: Employment. Patay:Invivoscribe, Inc: Employment. OffLabel Disclosure: Bortezomib is approved for multiple myeloma. Cladribine is approved for hairy cell leukemia. Etoposide is approved for small cell lung and testicular cancer. Sorafenib is approved for hepatocellular and renal cell carcinoma, thyroid cancer. Romidepsin is approved for T cell lymphoma. Decitabine is approved for myelodysplastic syndrome. Gemcitabine is approved for non small cell lung cancer and ovarian cancer. Vinblastine is approved for breast cancer, choriocarcinoma, Hodgkin lymphoma, Kaposi sarcoma, mycosis fungoides, NHL, and testicular cancer. Trametinib is approved for melanoma, anaplastic thyroid and non small cell lung cancer. Omacetaxine is approved for CML.

Child Distance Learning (CDL) during the pandemic has led to an optimal development of children and effective teaching and learning processes in kindergartens. To overcome this, teachers need to apply a teaching approach in accordance with the principles of kindergarten education. In addition, teachers' self-efficacy of their ability to teach is also important for developing children's skills. This study aims to describe the teaching approach and the efficacy of kindergarten teachers during the CDL process and to identify the relationship between the two. The research method used is quantitative through document analysis as a source of data findings. A total of 116 Public Kindergarten (PK) teachers in DKI Jakarta participated in filling out the Classroom Management Scale and Teachers' Sense of Efficacy Scale online. All data were processed using descriptive statistics and correlation. Furthermore, there is a document analysis carried out on the Daily / Weekly Learning Program Design in PK Jakarta. The findings identified that the teaching approach of kindergarten teachers during CDL included only two principles of kindergarten education, namely thematic teaching and developing life skills. Furthermore, PK teachers in the Jakarta area showed low self-efficacy during CDL. The teaching approach and self-efficacy were caused by teachers' unpreparedness in facing challenges during CDL. In addition, other findings indicate that there is a relationship between teaching approaches and teacher self-efficacy. Another CDL model Interventions to increase teacher self-efficacy and the extent to which the relationship between the two variables can be studied further in future studies. Keywords: Early Childhood, Distance Learning, Teaching Approach, Teacher Self-Efficacy References: Agustin, M., & Wahyudin, U. (2011). Penilaian perkembangan anak usia dini. Refika Aditama. Agustin, M., Puspita, R. D., Nurinten, D., & Nafiqoh, H. (2020). Tipikal Kendala Guru PAUD dalam Mengajar pada Masa Pandemi Covid 19 dan Implikasinya. Jurnal Obsesi: Jurnal Pendidikan Anak Usia Dini, 5(1), 334. https://doi.org/10.31004/obsesi.v5i1.598 Ayu, N. (2015). Pengelolaan Kurikulum 2013 Di Tk Negeri Pembina Semarang. Program Sarjana Universitas Negeri Semarang. Bullock, A., Coplan, R. J., & Bosacki, S. (2015). Exploring links between early childhood educators’ psychological characteristics and classroom management self-efficacy beliefs. Canadian Journal of Behavioural Science, 47(2), 175–183. https://doi.org/10.1037/a0038547 Cheung, S. K., Fong, R. W. tsz, Leung, S. K. Y., & Ling, E. K. wei. (2019). The Roles of Hong Kong Preservice Early Childhood Teachers’ Creativity and Zest in Their Self-efficacy in Creating Child-centered Learning Environments. Early Education and Development, 30(6), 788–799. https://doi.org/10.1080/10409289.2019.1586224 Choi, J., Lee, J., & Kim, B. 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Background: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL). Most patients with MCL relapse after first-line immunochemotherapy, with poor responses to salvage therapy. Chimeric antigen receptor (CAR) T cell therapy has shown clinical efficacy in patients with relapsed/refractory (R/R) NHL. We report the results of the dose-finding and dose-expansion parts of the ongoing phase 1 TRANSCEND NHL 001 study (NCT02631044) in patients with R/R MCL (MCL cohort) who received lisocabtagene maraleucel (liso-cel), an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. Methods: Eligible patients had confirmed MCL (cyclin D1 expression, t[11;14]) with R/R disease after ≥1 prior line of therapy. After lymphodepleting chemotherapy, patients received liso-cel infusion at 1 of 2 dose levels (DLs): DL1 (50 × 106 CAR+ T cells) or DL2 (100 × 106 CAR+ T cells). Bridging therapy was allowed between leukapheresis and initiation of lymphodepleting chemotherapy. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival, overall survival, and pharmacokinetics (PK). Results: At data cutoff, 41 patients had undergone leukapheresis and 32 had received liso-cel (DL1, n = 6; DL2, n = 26). Among the 32 patients who received liso-cel, the median (range) age was 67 (36‒80) years and 27 patients (84%) were male. Twelve patients (37.5%) had blastoid morphology, 23 (72%) had documented Ki67 ≥30%, 7 (22%) had a TP53 mutation, and 11 (34%) had a complex karyotype. Patients had a median (range) sum of the product of perpendicular diameters before lymphodepleting chemotherapy of 28.7 (0-209.6) cm2 and median lactate dehydrogenase of 251.5 (117-811) U/L. Patients had received a median (range) of 3 (1-7) prior systemic therapies, and most (72%) were refractory to their last prior therapy. Of 28 patients (87.5%) who had received a prior Bruton tyrosine kinase inhibitor, 11 (34%) were refractory to the therapy. Seventeen patients (53%) received bridging therapy. Eighteen patients (56%) had serious treatment-emergent adverse events (TEAEs), and 27 (84%) had grade ≥3 TEAEs, primarily neutropenia (41%), anemia (34%), and thrombocytopenia (31%). Grade ≥3 thrombocytopenia was more frequent at DL2 (n = 9/26 [35%]) than at DL1 (n = 1/6 [17%]). Prolonged grade ≥3 cytopenias (present at study Day 29) occurred in 11 patients (34%). Sixteen patients (50%; DL1, n = 2/6 [33%]; DL2, n = 14/26 [54%]) had cytokine release syndrome (CRS), including 1 grade 4 event at DL2. There were no grade 3 or 5 CRS events. Median (range) time to CRS onset and resolution was 6 (2‒10) days and 4 (2‒9) days, respectively. Nine patients (28%) had neurological events (NEs), all at DL2, including 3 grade 3 NEs. No grade 4 or 5 NEs were reported. Median (range) time to NE onset and resolution was 8 (2‒25) days and 3 (1‒51) days, respectively. Ten patients (31%) received tocilizumab and/or corticosteroids for treatment of CRS and/or NEs. Grade 5 TEAEs occurred in 2 patients (at DL2): one patient with high tumor burden had tumor lysis syndrome and 1 patient had cryptococcal meningoencephalitis. DL2 was selected for dose expansion. Of 32 patients, 27 responded to liso-cel (ORR, 84%: DL1, n = 4/6 [67%]; DL2, n = 23/26 [88%]), and 19 (59%) achieved a CR (DL1, n = 2/6 [33%]; DL2, n = 17/26 [65%]). Among the 12 patients with blastoid morphology, 9 patients had a response (ORR, 75%), including 7 (58%) who achieved a CR. Overall, the median (range) time to first CR was 1 (1-6) month. At data cutoff, 20 (74%) of 27 responders were censored with an ongoing response or had completed the study. Median (range) follow-up duration was 10.9 (1.2-24.8) months for DL1 and 3.1 (0.4-23.0) months for DL2. Preliminary PK analysis indicated that median maximum expansion was higher among patients at DL2 than at DL1. Conclusions: In this phase 1 study of patients with R/R MCL, treatment with liso-cel was associated with a low incidence of grade ≥3 CRS and NEs, late onset of CRS/NEs, and promising clinical activity. Dose confirmation is ongoing at DL2 in the MCL cohort. Disclosures Palomba: Pharmacyclics: Honoraria; Juno: Honoraria; Celgene: Honoraria; Merck: Honoraria; Novartis: Honoraria; Regeneron: Research Funding; Juno: Research Funding; Genentech: Research Funding. Gordon:Zylem Biosciences: Patents & Royalties: Patents, No Royalties. Siddiqi:Juno: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BeiGene: Other: DMC member; Juno Therapeutics, Pharmacyclics LLC, an AbbVie Company, AstraZeneca, Celgene, Kite Pharma, and BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company, Seattle Genetics, Janssen, and AstraZeneca: Speakers Bureau; Pharmacyclics LLC, an AbbVie Company, Juno Therapeutics, KITE Pharma, AstraZeneca, TG Therapeutics, Celgene, Oncternal, and BeiGene: Research Funding; AstraZeneca: Other: Travel/accommodations/expenses; Astrazenca: Membership on an entity's Board of Directors or advisory committees; PCYC: Membership on an entity's Board of Directors or advisory committees. Abramson:Celgene: Honoraria, Other: Scientific Advisory Board; Juno Therapeutics: Other: Scientific Advisory Board; AbbVie: Other: Scientific Advisory Board; EMD Serono: Other: Scientific Advisory Board; Genentech/Roche: Other: Scientific Advisory Board; Janssen: Other: Scientific Advisory Board; Karyopharm: Other: Scientific Advisory Board; Gilead: Other: Scientific Advisory Board; Verastem: Other: Scientific Advisory Board; Bayer: Other: Scientific Advisory Board; Merck: Other; KIte Pharma: Other; Novartis: Other; Amgen: Other; Seattle Genetics: Other; Allogene: Other; Morphosys: Other; C4 Therapeutics: Other; BeiGene: Other; AstraZeneca: Honoraria; Incyte: Honoraria. Kamdar:Seattle Genetics: Speakers Bureau; Karyopharm: Consultancy; BMS: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy. Lunning:Acrotech: Consultancy; ADC Therapeutics: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; Curis: Research Funding; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; TG Therapeutics: Research Funding; Verastem: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria. Maloney:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Patents are pending, but not issued, licensed, no royalties, no licensees., Research Funding; Bioline Rx: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Andreadis:Genentech: Other: Spouse Employee (salary and stock); Novartis: Research Funding; Celgene/Juno: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead/Kite: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Astellas: Other: Advisor; Seattle Genetics: Other: Advisor; Karyopharm: Other: Advisor; Incyte: Other. Arnason:Regeneron: Consultancy; Juno: Consultancy. Ghosh:Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; Karyopharm: Consultancy; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Kite/Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Roche/Genentech: Research Funding; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Celgene/Bristol-Myers Squibb: Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau. Mehta:Innate Pharmaceuticals: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Gelgene/BMS: Research Funding; Oncotartis: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Parmaceuticals/BMS: Research Funding; fortyseven Inc/Gilead: Research Funding; Takeda: Research Funding; Roche-Genentech: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Affimed: Research Funding. Farazi:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Garcia:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb Company: Current equity holder in publicly-traded company. Dehner:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Ogasawara:Bristol-Myers Squibb: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Gao:Bristol-Myers Squibb: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current Employment. Wang:Juno: Consultancy, Research Funding; Acerta Pharma: Research Funding; Loxo Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; OncLive: Honoraria; Molecular Templates: Research Funding; Verastem: Research Funding; Dava Oncology: Honoraria; Guidepoint Global: Consultancy; Pulse Biosciences: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; BioInvent: Research Funding; VelosBio: Research Funding.

La investigación –cuantitativa, descriptiva, correlacional y transversal– pretendió conocer si las dimensiones del liderazgo directivo –transformacional, transaccional y laissez-faire– predicen significativamente el desempeño docente, de acuerdo con la percepción de 105 docentes de un grupo de nueve colegios privados salvadoreños, quienes respondieron (a) el Cuestionario Multifactorial (MQL), de 45 ítems, y (b) el Cuestionario de Autoevaluación Docente, para medir la variable desempeño docente, de 20 ítems. Se utilizó el análisis de regresión múltiple. De las tres dimensiones del liderazgo del director, el liderazgo transaccional mostró una correlación positiva con el desempeño docente. La predicción es significativa para todas las dimensiones del desempeño docente, excepto emocionalidad. Los docentes que laboran en colegios cuyos directores están en función por más de siete años mostraron un desempeño significativamente mejor en las dimensiones de capacidad pedagógica y emocionalidad. A la vez, demostraron una percepción del liderazgo transformacional más baja en términos de motivación por inspiración. Referencias Aguilar Ludeña, E. H. (2018). Liderazgo directivo y el desempeño docente en la institución educativa 1278, La Molina (Tesis de maestría). Universidad Nacional de Educación Enrique Guzmán y Valle, Perú. Alonso Ayala, O., Ávila Sánchez, M. y Sánchez López, M. (2016). Desempeño del profesional de enfermería en la atención a los pacientes con afecciones traumatológicas y ortopédicas. Revista Cubana de Tecnología de la Salud, 7(4), 30-35. Alzate Sánchez, A. y López Cortés, M. C. (2014). 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Rapid urbanization rates impact significantly on the nature of Land Cover patterns of the environment, which has been evident in the depletion of vegetal reserves and in general modifying the human climatic systems (Henderson, et al., 2017; Kumar, Masago, Mishra, & Fukushi, 2018; Luo and Lau, 2017). This study explores remote sensing classification technique and other auxiliary data to determine LULCC for a period of 50 years (1967-2016). The LULCC types identified were quantitatively evaluated using the change detection approach from results of maximum likelihood classification algorithm in GIS. Accuracy assessment results were evaluated and found to be between 56 to 98 percent of the LULC classification. The change detection analysis revealed change in the LULC types in Minna from 1976 to 2016. Built-up area increases from 74.82ha in 1976 to 116.58ha in 2016. Farmlands increased from 2.23 ha to 46.45ha and bared surface increases from 120.00ha to 161.31ha between 1976 to 2016 resulting to decline in vegetation, water body, and wetlands. The Decade of rapid urbanization was found to coincide with the period of increased Public Private Partnership Agreement (PPPA). Increase in farmlands was due to the adoption of urban agriculture which has influence on food security and the environmental sustainability. The observed increase in built up areas, farmlands and bare surfaces has substantially led to reduction in vegetation and water bodies. The oscillatory nature of water bodies LULCC which was not particularly consistent with the rates of urbanization also suggests that beyond the urbanization process, other factors may influence the LULCC of water bodies in urban settlements. Keywords: Minna, Niger State, Remote Sensing, Land Surface Characteristics References Akinrinmade, A., Ibrahim, K., & Abdurrahman, A. (2012). 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Настоящая работа является первым общим описанием на русском языке двух некрополей Кампокиаро (Кампобассо, Италия) – Виченне и Морионе, датируемых последней третью VII в. – началом VIII в. Культурное содержание некрополей показывает прочные связи с населением центральноазиатского происхождения. Важнейшим признаком некрополей являются захоронения с конем, соответствующие евразийскому кочевому погребальному обряду. Автор поддержал выводы европейских исследователей о том, что с большой долей вероятности некрополи оставлены булгарами дукса–гаштальда Алзеко, зафиксированными Павлом Диаконом в VIII в. на территориях Бояно, Сепино и Изернии. Аналогии некрополей Кампокиаро с погребениями Аварского каганата показывают присутствие в аварском обществе булгар со схожим погребальным обрядом. Из тысяч погребений с конем, оставленных аварским населением, булгарам могла принадлежать большая часть. Авары и булгары составляли основу и правящую верхушку каганата. 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ABSTRACTWe have investigated the electromigration resistance of Al-Si/Ti multilayer interconnects. For comparison Al-Si and Al-Si/Ti/Al-Si films were also prepared. The linewidths ranged between 1.6 and 5, um. A temperature-ramp resistance analysis was applied at direct wafer level, to detect electrically transport of material and derive the electromigration kinetic parameters in test vehicles with different geometries.

Abstract Vast amounts of transcriptomic data reside in public repositories, but effective reuse remains challenging. Issues include unstructured dataset metadata, inconsistent data processing and quality control, and inconsistent probe–gene mappings across microarray technologies. Thus, extensive curation and data reprocessing are necessary prior to any reuse. The Gemma bioinformatics system was created to help address these issues. Gemma consists of a database of curated transcriptomic datasets, analytical software, a web interface and web services. Here we present an update on Gemma’s holdings, data processing and analysis pipelines, our curation guidelines, and software features. As of June 2020, Gemma contains 10 811 manually curated datasets (primarily human, mouse and rat), over 395 000 samples and hundreds of curated transcriptomic platforms (both microarray and RNA sequencing). Dataset topics were represented with 10 215 distinct terms from 12 ontologies, for a total of 54 316 topic annotations (mean topics/dataset = 5.2). While Gemma has broad coverage of conditions and tissues, it captures a large majority of available brain-related datasets, accounting for 34% of its holdings. Users can access the curated data and differential expression analyses through the Gemma website, RESTful service and an R package. Database URL: https://gemma.msl.ubc.ca/home.html

Study Design: Retrospective cohort. Objective: The objective of this study was to assess the effectiveness of the O-arm as an intraoperative imaging tool by comparing accuracy of pedicle screw placement to freehand technique. Methods: The study comprised a total of 1161 screws placed within the cervical (n = 187) thoracic (n = 657), or lumbar (n = 317) spinal level. A pedicle breach was determined by any measurable displacement of the screw outside of the pedicle cortex in any plane on postoperative images. Each pedicle screw was subsequently classified by its placement relative to the targeted pedicle. Statistical analysis was then performed to determine the frequency and type of pedicle screw mispositioning that occurred using the O-arm versus freehand technique. Results: A total of 155 cases (O-arm 84, freehand 71) involved the placement of 454 pedicle screws in the O-arm group and 707 pedicle screws in the freehand group. A pedicle breach occurred in 89 (12.6%) screws in the freehand group and 55 (12.1%) in the O-arm group ( P = .811). Spinal level operated upon did not influence pedicle screw accuracy between groups ( P > .05). Three screws required revision surgery between the 2 groups (O-arm 1, freehand 2, P > .05). The most frequent breach type was a lateral pedicle breach (O-arm 22/454, 4.8%; freehand 54/707, 7.6%), without a significant difference between groups ( P > .05). Conclusions: The use of the O-arm coupled with navigation does not assure improved transpedicular screw placement accuracy when compared with the freehand technique.

Background: Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published ‘protocol papers’ for contemporary randomised controlled trials. Methods: A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively. Results: Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%–51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term ‘audit’ to describe ‘monitoring’. Discussion: Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.

Abstract Background We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS). Patients and Methods Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P &lt; .2) if limited number of events. Results Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 in the total population, 111 (24.0%) were treated in first-line; 129 (28.8%) were BRAFV600E-mutated and 153 (32.8%) RAS-mutated. Median follow-up was 20.9 months. In adjusted analysis of the whole population (PFS/OS events = 186/133), no associations with PFS and OS were observed for BRAFV600E-mutated (PFS HR= 1.20, P = .372; OS HR = 1.06, P = .811) and RAS-mutated patients (PFS HR = 0.93, P = .712, OS HR = 0.75, P = .202). In adjusted analysis in the Lynch/sporadic status-assigned population (n = 242; PFS/OS events = 80/54), LS-liked patients had an improved PFS compared to sporadic cases (HR = 0.49, P = .036). The adjusted HR for OS was 0.56 with no significance (P = .143). No adjustment on BRAFV600E mutation was done due to collinearity. Conclusion In this cohort, RAS/BRAFV600E mutations were not associated with survival while LS conferred an improved PFS.

Background: Estimating the number of people using illicit drugs and alcohol is necessary for informing health policy and programming. However, it is often challenging to reliably estimate the size of these marginalized populations through direct methods. In this study, we estimated the population size of these groups using the indirect Network Scale-Up (NSU) method in Iran from 2015 to 2016. Methods: Using a self-administered questionnaire, we asked 15,124 individuals (54% male) about the number of people they know who used different types of drugs at least once in the past 12 months. Prevalence estimates were reported per 100,000 population. The uncertainty level (UL) was calculated using the bootstrap method. Results: The average age of the respondents was 33 years old, and 35.1% of them were unmarried. The most common drugs and their prevalence were as follows: opium (2,534 [95% UL: 2467-2598]), hashish (849 [95% UL: 811-886]), stimulants (methamphetamine, ecstasy pills, cocaine, and Ritalin) (842 [95% UL: 802-879]), heroin/crack (578 [95% UL: 550-607]), and drug injection (459 [95% UL: 438-484]). Additionally, we estimated the prevalence of alcohol use as 2,797 (95% UL: 2731-2861). On average, substance use was 5.23 times more prevalent among men than women. Opium use was more prevalent among individuals aged > 50 years old. Moreover, alcohol use was more prevalent among participants between 18 and 30 years old (5164 per 100,000 population). Conclusion: Although opium continues to be the most prevalent illicit drug in Iran, the patterns of illicit drug use are heterogeneous among different age groups, genders, and provinces. Age-gender specific and culturally appropriate interventions are warranted to meet the needs of people in different subgroups.

PURPOSE For postmenopausal patients with breast cancer, previous subgroup analyses have shown a modest benefit from adjuvant bisphosphonate treatment. However, the efficacy of oral nitrogen-containing bisphosphonates such as ibandronate is unclear in this setting. TEAM-IIB investigates adjuvant ibandronate in postmenopausal women with estrogen receptor–positive (ER+) breast cancer. METHODS TEAM-IIB is a randomized, open-label, multicenter phase III study. Postmenopausal women with stage I-III ER+ breast cancer and an indication for adjuvant endocrine therapy (ET) were randomly assigned 1:1 to 5 years of ET with or without oral ibandronate 50 mg once daily for 3 years. Major ineligibility criteria were bilateral breast cancer, active gastroesophageal problems, and health conditions that might interfere with study treatment. Primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population. RESULTS Between February 1, 2007, and May 27, 2014, 1,116 patients were enrolled, 565 to ET with ibandronate (ibandronate arm) and 551 to ET alone (control arm). Median follow-up was 8.5 years. DFS was not significantly different between the ibandronate and control arms (HR 0.97; 95% CI, 0.76 to 1.24; log-rank P = .811). Three years after random assignment, DFS was 94% in the ibandronate arm and 91% in the control arm. Five years after random assignment, this was 89% and 86%, respectively. In the ibandronate arm, 97/565 (17%) of patients stopped ibandronate early because of adverse events. Significantly more patients experienced GI issues, mainly dyspepsia, in the ibandronate arm than in the control arm (89 [16%] and 54 [10%], respectively; P < .003). Eleven patients in the ibandronate arm developed osteonecrosis of the jaw. CONCLUSION In postmenopausal women with ER+ breast cancer, adjuvant ibandronate 50 mg once daily does not improve DFS and should not be recommended as part of standard treatment regimens.

Abstract Antibody response, measured as sample-to-positive (S/P) ratio, to porcine reproductive and respiratory syndrome virus (PRRSV) following a PRRSV-outbreak (S/POutbreak) in a purebred nucleus and following a PRRSV-vaccination (S/PVx) in commercial crossbred herds have been proposed as genetic indicator traits for improved reproductive performance in PRRSV-infected purebred and PRRSV-vaccinated crossbred sows, respectively. In this study, we investigated the genetic relationships of S/POutbreak and S/PVx with performance at the commercial (vaccinated crossbred sows) and nucleus level (non-infected and PRRSV-infected purebred sows), respectively, and tested the effect of previously identified SNP for these indicator traits. Antibody response was measured on 541 Landrace sows ~54 d after the start of a PRRSV outbreak, and on 906 F1 (Landrace × Large White) gilts ~50 d after vaccination with a commercial PRRSV vaccine. Reproductive performance was recorded for 711 and 428 Landrace sows before and during the PRRSV outbreak, respectively, and for 811 vaccinated F1 animals. The estimate of the genetic correlation (rg) of S/POutbreak with S/PVx was 0.72 ± 0.18. The estimates of rg of S/POutbreak with reproductive performance in vaccinated crossbred sows were low to moderate, ranging from 0.05 ± 0.23 to 0.30 ± 0.20. The estimate of rg of S/PVx with reproductive performance in non-infected purebred sows was moderate and favorable with number born alive (0.50 ± 0.23) but low (0 ± 0.23 to −0.11 ± 0.23) with piglet mortality traits. The estimates of rg of S/PVx were moderate and negative (−0.38 ± 0.21) with number of mummies in PRRSV-infected purebred sows and low with other traits (−0.30 ± 0.18 to 0.05 ± 0.18). Several significant associations (P0 &gt; 0.90) of previously reported SNP for S/P ratio (ASGA0032063 and H3GA0020505) were identified for S/P ratio and performance in non-infected purebred and PRRSV-exposed purebred and crossbred sows. Genomic regions harboring the major histocompatibility complex class II region significantly contributed to the genetic correlation of antibody response to PRRSV with most of the traits analyzed. These results indicate that selection for antibody response in purebred sows following a PRRSV outbreak in the nucleus and for antibody response to PRRSV vaccination measured in commercial crossbred sows are expected to increase litter size in purebred and commercial sows.

Abstract Background Dysglycaemia is associated with cardiovascular disease even below the diagnostic diabetes threshold. Atrial fibrillation (AF) has been found to be associated with the metabolic syndrome and life-style changes after AF have been found to reduce recurrence of AF. Purpose We explored the association glucose and risk of first event of AF, HF and combined event. Methods Subject with fasting glucose in the AMORIS cohort, obtained 1985–1996 at routine occupational health check-ups or primary care in the Stockholm area were included. Subjects with prevalent AF, HF, ischemic heart disease, revascularization and cerebrovascular disease were excluded. Glucose levels were categorised as low (<3.9 mmol/L), normal (3.9–6.0mmol/L), impaired (IFG; 6.1–6.9 mmol/L) and diabetes (≥7.0 mmol/L or a diabetes diagnosis) according to WHO definition in 2006. First events of AF, HF or a combined event was identified until December 2011 by linkage to national registries. Information on co-morbidities was obtained from the National Patient Register. Hazard ratios (HR and 95% CI) by glucose group for AF and heart failure were calculated using Cox proportional hazards with attained age as timescale and adjusting for gender, total cholesterol and triglycerides. The change in AF risk by increasing glucose level was described by using splines (Figure). Results 243 665 subjects with mean age 48.3 at index date, 54% male were included. During a mean follow-up time of 19.1 years and 4,7 million person years, 23 522 events of AF, 21 411 events of HF and 35 131 combined events occurred. The proportion with IFG and diabetes were 3.2% and 3.3% respectively. In the diabetes group about half were diagnosed prevalent cases (1.5%). Glucose was continuously associated with developement of AF (Table and Figure) and even more of HF (Table). Events (n) and HR by glucose category Atrial fibrillation Heart failure Combined event Event HR [95% CI] Event HR [95% CI] Event HR [95% CI] Low 405 0.97 [0.88–1.08] 326 0.97 [0.87–1.08] 598 1.00 [0.92–1.09] Normal 20 663 1.00 17 811 1.00 30 159 1.00 IFG 1185 1.20 [1.13–1.28] 1319 1.43 [1.35–1.51] 1901 1.30 [1.24–1.36] Diabetes 1269 1.28 [1.20–1.35] 1955 2.19 [2.08–2.29] 2473 1.73 [1.66–1.81] Events (n) of AF, HF and combined and HR (95% CI) by fasting glucose category. HR for AF by glucose level spline graph Conclusion Dysglycaemia, including glucose levels below the diabetes threshold, is continuously associated with future risk of both AF and HF. These data are important considering the large population with undetected dysglycaemia at risk for AF and HF where preventive measures including life-style changes could be of importance even before the onset of overt diabetes. Acknowledgement/Funding Swedish Heart and Lung foundation

ImportanceThe COVID-19 pandemic reportedly increased behavioral health needs and impacted treatment access.ObjectiveTo assess changes in incident prescriptions dispensed for medications commonly used to treat depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and opioid use disorder (OUD), before and during the COVID-19 pandemic.Design, Setting, and ParticipantsThis was a cross-sectional study using comprehensive, population-level, nationally projected data from IQVIA National Prescription Audit on incident prescriptions (prescriptions dispensed to patients with no prior dispensing from the same drug class in the previous 12 months) dispensed for antidepressants, benzodiazepines, Schedule II (C-II) stimulants, nonstimulant medications for ADHD, and buprenorphine-containing medication for OUD (MOUD), from US outpatient pharmacies. Data were analyzed from April 2018 to March 2022.ExposureIncident prescriptions by drug class (by prescriber specialty, patient age, and sex) and drug.Main Outcomes and MeasuresInterrupted time-series analysis to compare changes in trends in the monthly incident prescriptions dispensed by drug class and percentage changes in aggregate incident prescriptions dispensed between April 2018 and March 2022.ResultsIncident prescriptions dispensed for the 5 drug classes changed from 51 500 321 before the COVID-19 pandemic to 54 000 169 during the pandemic. The largest unadjusted percentage increase in incident prescriptions by prescriber specialty was among nurse practitioners across all drug classes ranging from 7% (from 1 811 376 to 1 944 852; benzodiazepines) to 78% (from 157 578 to 280 925; buprenorphine MOUD), whereas for patient age and sex, the largest increases were within C-II stimulants and nonstimulant ADHD drugs among patients aged 20 to 39 years (30% [from 1 887 017 to 2 455 706] and 81% [from 255 053 to 461 017], respectively) and female patients (25% [from 2 352 095 to 2 942 604] and 59% [from 395 678 to 630 678], respectively). Trends for C-II stimulants and nonstimulant ADHD drugs (slope change: 4007 prescriptions per month; 95% CI, 1592-6422 and 1120 prescriptions per month; 95% CI, 706-1533, respectively) significantly changed during the pandemic, exceeding prepandemic trends after an initial drop at the onset of the pandemic (level changes: −50 044 prescriptions; 95% CI, −80 202 to −19 886 and −12 876 prescriptions; 95% CI, −17 756 to −7996, respectively). Although buprenorphine MOUD dropped significantly (level change: −2915 prescriptions; 95% CI, −5513 to −318), trends did not significantly change for buprenorphine MOUD, antidepressants, or benzodiazepines.Conclusions and RelevanceIncident use of many behavioral health medications remained relatively stable during the COVID-19 pandemic in the US, whereas ADHD medications, notably C-II stimulants, sharply increased. Additional research is needed to differentiate increases due to unmet need vs overprescribing, highlighting the need for further ADHD guideline development to define treatment appropriateness.

Abstract Background Delirium is an independent predictor of mortality in patients admitted with community-acquired pneumonia (Pieralli, 2014), but significance and incidence in Covid-19 infection has not been established. The Nightingale Hospital Exeter (NHE) as a multidisciplinary team model, managed 242 patients with Covid-19 from November 2020 to February 2021. This study identifies the delirium incidence, outcome, premorbid function and demographics of this cohort. Methods Electronic records were retrospectively reviewed for keywords ‘Delirium’, ‘Hyperactive’, ‘Hypoactive’, ‘Confused’ and ‘Muddled’. Patients were categorised as Hyperactive, Hypoactive or Confused/non-specified. Prior functional support (independent, package of care, residential or nursing care) and presence of pre-established neurological conditions (including dementia) were noted. Results 242 patients were included, average age 84 years (range 59–102). Of these patients, 130 (54%) developed delirium (29 (22%) hyperactive, 37 (28%) hypoactive, 2 (1%) mixed and 62 (48%) ‘confused’/non-specified). Of those with delirium, 56 (43%) were previously living independently and 51 (39%) were living at home with a package of care. 60 (46%) of those diagnosed had no pre-existing neurological condition, 32% had underlying dementia. There were 37 deaths at NHE (mortality 15%), 73% of these patients had delirium during their admission compared to 50% of those who survived. Conclusions Over half this cohort developed delirium, a high proportion of whom had been living independently prior to admission with no pre-existing neurological condition, emphasising how common delirium is in patients with Covid-19. In a comparable cohort with pneumonia (mean age 82 years, range 65–99) 25% developed delirium, and it was an independent predictor of in-hospital mortality (Pieralli, 2014). The fact that 73% of all patients who died developed delirium suggests it may have important prognostic implications, and both this and the high incidence indicate further work is required to fully understand how to prevent and manage delirium in Covid-19.

Cremer, Annette C. / Martin Mulsow (Hrsg.), Objekte als Quellen der historischen Kulturwissenschaften. Stand und Perspektiven der Forschung (Ding, Materialität, Geschichte, 2), Köln / Weimar / Wien 2017, Böhlau, 352 S. / Abb., € 50,00. (Alexander Georg Durben, Münster) Pfister, Ulrich (Hrsg.), Kulturen des Entscheidens. Narrative – Praktiken – Ressourcen (Kulturen des Entscheidens, 1), Göttingen 2019, Vandenhoeck &amp; Ruprecht, 409 S. / Abb., € 70,00. (Wolfgang Reinhard, Freiburg i. Br.) Krischer, André (Hrsg.), Verräter. Geschichte eines Deutungsmusters, Wien / Köln / Weimar 2019, Böhlau, 353 S. / Abb., € 39,00. (Wolfgang Reinhard, Freiburg i. Br.) Baumbach, Hendrik / Horst Carl (Hrsg.), Landfrieden – epochenübergreifend. Neue Perspektiven der Landfriedensforschung auf Verfassung, Recht, Konflikt (Zeitschrift für Historische Forschung, Beiheft 54), Berlin 2018, Duncker &amp; Humblot, 280 S., € 69,90. (Fabian Schulze, Ulm / Augsburg) Ertl, Thomas (Hrsg.), Erzwungene Exile. 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This issue of M/C Journal is devoted to all things cute – Internet animals and stuffed toys, cartoon characters and branded bears. In what follows our nine contributors scrutinise a diverse range of media objects, discussing everything from the economics of Grumpy Cat and the aesthetics of Furbys to Reddit’s intellectual property dramas and the ethics of kitten memes. The articles range across diverse sites, from China to Canada, and equally diverse disciplines, including cultural studies, evolutionary economics, media anthropology, film studies and socio-legal studies. But they share a common aim of tracing out the connections between degraded media forms and wider questions of culture, identity, economy and power. Our contributors tell riveting stories about these connections, inviting us to see the most familiar visual culture in a new way. We are not the first to take cute media seriously as a site of cultural politics, and as an industry in its own right. Cultural theory has a long, antagonistic relationship with the kitsch and the disposable. From the Frankfurt School’s withering critique of cultural commodification to revisionist feminist accounts that emphasise the importance of the everyday, critics have been conducting sporadic incursions into this space for the better part of a century. The rise of cultural studies, a discipline committed to analysing “the scrap of ordinary or banal existence” (Morris and Frow xviii), has naturally provided a convincing intellectual rationale for such research, and has inspired an impressive array of studies on such things as Victorian-era postcards (Milne), Disney films (Forgacs), Hallmark cards (West, Jaffe) and stock photography (Frosh). A parallel strand of literary theory considers the diverse registers of aesthetic experience that characterize cute content (Brown, Harris). Sianne Ngai has written elegantly on this topic, noting that “while the avant-garde is conventionally imagined as sharp and pointy, as hard- or cutting-edge, cute objects have no edge to speak of, usually being soft, round, and deeply associated with the infantile and the feminine” (814). Other scholars trace the historical evolution of cute aesthetics and commodities. Cultural historians have documented the emergence of consumer markets for children and how these have shaped what we think of as cute (Cross). Others have considered the history of domestic animal imagery and its symptomatic relationship with social anxieties around Darwinism, animal rights, and pet keeping (Morse and Danahay, Ritvo). And of course, Japanese popular culture – with its distinctive mobilization of cute aesthetics – has attracted its own rich literature in anthropology and area studies (Allison, Kinsella). The current issue of M/C Journal extends these lines of research while also pushing the conversation in some new directions. Specifically, we are interested in the collision between cute aesthetics, understood as a persistent strand of mass culture, and contemporary digital media. What might the existing tradition of “cute theory” mean in an Internet economy where user-generated content sites and social media have massively expanded the semiotic space of “cute” – and the commercial possibilities this entails? As the heir to a specific mode of degraded populism, the Internet cat video may be to the present what the sitcom, the paperback novel, or the Madonna video was to an earlier moment of cultural analysis. Millions of people worldwide start their days with kittens on Roombas. Global animal brands, such as Maru and Grumpy Cat, are appearing, along with new talent agencies for celebrity pets. Online portal I Can Haz Cheezburger has received millions of dollars in venture capital funding, becoming a diversified media business (and then a dotcom bubble). YouTube channels, Twitter hashtags and blog rolls form an infrastructure across which a vast amount of cute-themed user-generated content, as well as an increasing amount of commercially produced and branded material, now circulates. All this reminds us of the oft-quoted truism that the Internet is “made of kittens”, and that it’s “kittens all the way down”. Digitization of cute culture leads to some unusual tweaks in the taste hierarchies explored in the aforementioned scholarship. Cute content now functions variously as an affective transaction, a form of fandom, and as a subcultural discourse. In some corners of the Internet it is also being re-imagined as something contemporary, self-reflexive and flecked with irony. The example of 4Chan and LOLcats, a jocular, masculinist remix of the feminized genre of pet photography, is particularly striking here. How might the topic of cute look if we moving away from the old dialectics of mass culture critique vs. defense and instead foreground some of these more counter-intuitive aspects, taking seriously the enormous scale and vibrancy of the various “cute” content production systems – from children’s television to greeting cards to CuteOverload.com – and their structural integration into current media, marketing and lifestyle industries? Several articles in this issue adopt this approach, investigating the undergirding economic and regulatory structures of cute culture. Jason Potts provides a novel economic explanation for why there are so many animals on the Internet, using a little-known economic theory (the Alchian-Allen theorem) to explain the abundance of cat videos on YouTube. James Meese explores the complex copyright politics of pet images on Reddit, showing how this online community – which is the original source of much of the Internet’s animal gifs, jpegs and videos – has developed its own procedures for regulating animal image “piracy”. These articles imaginatively connect the soft stuff of cute content with the hard stuff of intellectual property and supply-and-demand dynamics. Another line of questioning investigates the political and bio-political work involved in everyday investments in cute culture. Seen from this perspective, cute is an affect that connects ground-level consumer subjectivity with various economic and political projects. Carolyn Stevens’ essay offers an absorbing analysis of the Japanese cute character Rilakkuma (“Relaxed Bear”), a wildly popular cartoon bear that is typically depicted lying on the couch and eating sweets. She explores what this representation means in the context of a stagnant Japanese economy, when the idea of idleness is taking on a new shade of meaning due to rising under-employment and precarity. Sharalyn Sanders considers a fascinating recent case of cute-powered activism in Canada, when animal rights activists used a multimedia stunt – a cat, Tuxedo Stan, running for mayor of Halifax, Canada – to highlight the unfortunate situation of stray and feral felines in the municipality. Sanders offers a rich analysis of this unusual political campaign and the moral questions it provokes. Elaine Laforteza considers another fascinating collision of the cute and the political: the case of Lil’ Bub, an American cat with a rare genetic condition that results in a perpetually kitten-like facial expression. During 2011 Lil’ Bub became an online phenomenon of the first order. Laforteza uses this event, and the controversies that brewed around it, as an entry point for a fascinating discussion of the “cute-ification” of disability. These case studies remind us once more of the political stakes of representation and viral communication, topics taken up by other contributors in their articles. Radha O’Meara’s “Do Cats Know They Rule YouTube? How Cat Videos Disguise Surveillance as Unselfconscious Play” provides a wide-ranging textual analysis of pet videos, focusing on the subtle narrative structures and viewer positioning that are so central to the pleasures of this genre. O’Meara explains how the “cute” experience is linked to the frisson of surveillance, and escape from surveillance. She also explains the aesthetic differences that distinguish online dog videos from cat videos, showing how particular ideas about animals are hardwired into the apparently spontaneous form of amateur content production. Gabriele de Seta investigates the linguistics of cute in his nuanced examination of how a new word – meng – entered popular discourse amongst Mandarin Chinese Internet users. de Seta draws our attention to the specificities of cute as a concept, and how the very notion of cuteness undergoes a series of translations and reconfigurations as it travels across cultures and contexts. As the term meng supplants existing Mandarin terms for cute such as ke’ai, debates around how the new word should be used are common. De Seta shows us how deploying these specific linguistic terms for cuteness involve a range of linguistic and aesthetic judgments. In short, what exactly is cute and in what context? Other contributors offer much-needed cultural analyses of the relationship between cute aesthetics, celebrity and user-generated culture. Catherine Caudwell looks at the once-popular Furby toy brand its treatment in online fan fiction. She notes that these forms of online creative practice offer a range of “imaginative and speculative” critiques of cuteness. Caudwell – like de Seta – reminds us that “cuteness is an unstable aesthetic that is culturally contingent and very much tied to behaviour”, an affect that can encompass friendliness, helplessness, monstrosity and strangeness. Jonathon Hutchinson’s article explores “petworking”, the phenomenon of social media-enabled celebrity pets (and pet owners). Using the famous example of Boo, a “highly networked” celebrity Pomeranian, Hutchinson offers a careful account of how cute is constructed, with intermediaries (owners and, in some cases, agents) negotiating a series of careful interactions between pet fans and the pet itself. Hutchinson argues if we wish to understand the popularity of cute content, the “strategic efforts” of these intermediaries must be taken into account. Each of our contributors has a unique story to tell about the aesthetics of commodity culture. The objects they analyse may be cute and furry, but the critical arguments offered here have very sharp teeth. We hope you enjoy the issue.Acknowledgments Thanks to Axel Bruns at M/C Journal for his support, to our hard-working peer reviewers for their insightful and valuable comments, and to the Swinburne Institute for Social Research for the small grant that made this issue possible. ReferencesAllison, Anne. “Cuteness as Japan’s Millenial Product.” Pikachu’s Global Adventure: The Rise and Fall of Pokemon. Ed. Joseph Tobin. Durham: Duke University Press, 2004. 34-48. Brown, Laura. Homeless Dogs and Melancholy Apes: Humans and Other Animals in the Modern Literary Imagination. Ithaca: Cornell University Press, 2010. Cross, Gary. The Cute and the Cool: Wondrous Innocence and Modern American Children's Culture. Oxford: Oxford University Press, 2004. Forgacs, David. "Disney Animation and the Business of Childhood." Screen 33.4 (1992): 361-374. Frosh, Paul. "Inside the Image Factory: Stock Photography and Cultural Production." Media, Culture & Society 23.5 (2001): 625-646. Harris, Daniel. Cute, Quaint, Hungry and Romantic: The Aesthetics of Consumerism. New York: Basic Books, 2000. Jaffe, Alexandra. "Packaged Sentiments: The Social Meanings of Greeting Cards." Journal of Material Culture 4.2 (1999): 115-141. Kinsella, Sharon. “Cuties in Japan” Women, Media and Consumption in Japan. Ed. Lise Skov and Brian Moeran. Honolulu: University of Hawaii Press, 1995. 220 - 54. Frow, John, and Meaghan Morris, eds. Australian Cultural Studies: A Reader. Chicago: University of Illinois Press, 1993. Milne, Esther. Letters, Postcards, Email: Technologies of Presence. New York: Routledge, 2012. Morse, Deborah and Martin Danahay, eds. Victorian Animal Dreams: Representations of Animals in Victorian Literature and Culture. Aldershot: Ashgate Publishing. 2007. Ngai, Sianne. "The Cuteness of the Avant‐Garde." Critical Inquiry 31.4 (2005): 811-847. Ritvo, Harriet. The Animal Estate: The English and Other Creatures in the Victorian Age. Cambridge: Harvard University Press, 1987. West, Emily. "When You Care Enough to Defend the Very Best: How the Greeting Card Industry Manages Cultural Criticism." Media, Culture & Society 29.2 (2007): 241-261.

In this issue of our journal, there are three articles reporting on tuberculosis, a disease which has historically been a big problem in our country – much longer than the current COVID-19 pandemic.It cannot be denied that COVID-19 is a big problem right now and should indeed be a priority. As of October 24, 2020,the DOH reports that there have been 367,819 cases of COVID-19 from the time it began monitoring the numbers some nearly nine months ago.1The effect of COVID-19 goes beyond these number of cases, as many of them have already died.However, against this alarming situation, even more concern lurks underneath. Just 10 days previously, the WHO released its 2020 Global Tuberculosis Report.2Among other things, prominent mention in the 2020 Report is the threat that theCOVID-19 pandemic can reverse the gains made in TB control over recent years in many countries, including the Philippines.In 2019, prior to the COVID-19 pandemic, the Philippines is reported to rank fourth in terms of the number of TB cases,contributing 6% of the total global burden of TB.3 Computing this on a per capita basis paints an even darker picture: the Philippines has 554 TB cases per 100,000 population, exceeded worldwide only by Lesotho, a small country in Southern Africa with a population of just around 2% that of the Philippines.4Identifying new TB cases is a key strategy in TB control. It is an important step in identifying and initiating treatmentfor those who need it. However, gaps in estimated incidence and notifications have long been a problem in the Philippines.2,3And with the COVID-19 pandemic, this has now become bigger. The 2020 WHO Report says that there has been a dropof 50 to 75% in the monthly notifications for the April to June period compared to January 2020 in the Philippines. Sucha trend – reported in other countries as well – is attributed to under-reporting of new TB cases during this COVID-19pandemic.5-13 The sudden drop over a few months cannot be due to any sudden improvement of TB control but more to the challenges that the pandemic has had on the TB control programs. In many TB high burden but low-income countries like the Philippines, reallocation of human, financial and other resources from TB to the COVID-19 response is happening. For example, GeneXpert™ machines are being diverted for use in COVID-19 testing.14 Staff in national TB programs as well as healthcare frontliners are being assigned to COVID-19 related duties. Similar to other countries, community lockdowns, patient concerns on getting infected, lack of public transportation, and loss of jobs and its attendant financial consequences, among others, are also serious considerations limiting access to TB diagnosis and treatment in the Philippines.15Any benefit from social distancing and wearing of face masks to reduce TB transmission are likely outweighed by health service disruption.16 As is the case with other patient co-morbidities, the interaction between COVID-19 and tuberculosis have also been looked into. However, current data do not allow any meaningful conclusions.14,17 Because of similarities in presentation symptoms such as fever, cough and difficulty of breathing, the recognition of tuberculosis may also be confused with COVID-19.18,19All of these are predicted to further worsen TB incidence due to increased transmission and along with greater diseaseseverity will have a larger negative effect on GDP per capita, undernutrition and catastrophic costs to families.2According to the model presented in the 2020 Global TB Report, assuming a more conservative 50% decrease in case detection over a six-month period could result in 700,000 excess deaths due to TB, globally.2The economic burden of additional cases has also been estimated for other countries and is quite substantial.20In an article published in this issue of our journal, drug resistance is identified as the biggest risk for unsuccessfultreatment outcomes in patients with tuberculosis.21 There are already increasing RR/MDR TB cases in the country based on the results of the 2016 National TB Prevalence Survey and other data.2,4,22 Previous unsuccessful treatment continues to be a big driver in the development of this drug resistance; and unsurprisingly, we now see that drug resistance in turn further drives even more unsuccessful TB treatment.In the latest WHO country profile report, RR/MDR TB incidence is estimated at 3.8% overall; but shoots up to 28%in previously treated cases.23 Most importantly, success of treatment was reported in only 58% of RR/MDR TB cases started on second-line drugs. As MDR-TB becomes more prevalent, and person-to-person transmission becomes more common, we may soon end up with MDR-TB as a major initial presentation of TB in our country. This is definitely undesirable as treatment of MDR-TB requires significantly more financial resources compared to DS-TB and can further strain the already limited resources allocated for TB control in our country. With the big challenges we face with the COVID-19 pandemic and the resulting effect it presents to ongoing TB control,it is reasonable to fear that we will have more unsuccessful treatment of TB in the country. Even as this potentially increases the number of TB cases in general, the even greater threat of further increasing MDR-TB should make us even more concerned.We cannot afford to lose focus and momentum in our efforts to control TB. Others have in fact stated that the currentpandemic may actually be a good opportunity to evaluate and if needed, to revise some of the programs we have in TBcontrol.24,25 The WHO has also made some recommendations which we can hopefully follow as we maintain our vigilance on TB control during this pandemic.26The 2020 WHO Global Tuberculosis Report highlights many of the gains we have made in the Philippines. Hopefully,this COVID-19 pandemic will not push it back. Joven Q. Tanchuco, MD, MHAEditor-in-ChiefActa Medica Philippina REFERENCES1. COVID 19 Case Tracker. DOH COVID 19. Case Bulletin # 224[Internet]. [cited 2020 Oct 25]. Available from: https://www.doh.gov.ph/covid-19/case-tracker2. Global tuberculosis report 2020. Geneva: World Health Organization.License: CC BY-NC-SA 3.0 IGO [Internet]. 2020 [cited 2020 Oct25]. Available from: https://www.who.int/tb/publications/global_report/en/3. Global tuberculosis report 2019. Geneva: World Health Organization;License: CC BY-NC-SA 3.0 IGO.4. Tanchuco JQ. Risk factors, molecular mechanisms and testing of drugresistance in Mycobacterium tuberculosis: Focus on the Philippines.Philipp J Intern Med. 2020; 58(3):72-105.5. Jain VK, Iyengar KP, Samy DA, Vaishya R. Tuberculosis in the eraof COVID-19 in India. Diabetes Metab Syndr. 2020 Sep-Oct;14(5):1439-43. doi: 10.1016/j.dsx.2020.07.034.6. Amimo F, Lambert B, Magit A. What does the COVID-19 pandemicmean for HIV, tuberculosis, and malaria control? Trop Med Health.2020; 48:32. https://doi.org/10.1186/s41182-020-00219-67. Ong CWM, Migliori GB, Raviglione M, Mac Gregor-Skinner G,Sotgiu G, Alffenaar J, et al. Epidemic and pandemic viral infections:impact on tuberculosis and the lung. Eur Respir J. 2020; 56(4):2001727.https://doi.org/10.1183/13993003.01727-20208. Fei H, Yinyin X, Hui C, Ni W, Xin D, Wei C, et al. The impact ofthe COVID-19 epidemic on tuberculosis control in China. The LancetRegional Health – Western Pacific. 2020; 3:100032 https://doi.org/10.1016/j.lanwpc.2020.1000329. Komiya K, Yamasue M, Takahashi O, Hiramatsu K, Kadota J, KatoS. The COVID-19 pandemic and the true incidence of Tuberculosisin Japan. J Infect. 2020; 81(3):e24–e25. https://doi.org/10.1016/j.jinf.2020.07.00410. Togun T, Kampmann B, Stoker NG, Lipman M. Anticipating theimpact of the COVID-19 pandemic on TB patients and TB controlprogrammes. Ann Clin Microbiol Antimicrob. 2020; 19(1):21.https://doi.org/10.1186/s12941-020-00363-111. Ribeiro VST, Telles JP, Tuon FF. Concerns about COVID-19 andtuberculosis in Brazil: Social and public health impacts. EnfermInfecc Microbiol Clin. 2020; S0213-005X(20)30278-0. https://doi.org/10.1016/j.eimc.2020.08.01312. Alene KA, Wangdi K, Clements ACA. Impact of the COVID-19Pandemic on Tuberculosis Control: An Overview. Trop Med InfectDis. 2020; 5(3):123. https://doi.org/10.3390/tropicalmed503012313. Magro P, Formenti B, Marchese V, Gulletta M, Tomasoni LR, CaligarisS, et al. Impact of the SARS-CoV-2 epidemic on tuberculosis treatmentoutcome in Northern Italy. Eur Respir J. 2020; 56(4):2002665.https://doi.org/10.1183/13993003.02665-202014. Karim QA, Karim SSA. COVID-19 affects HIV and tuberculosiscare. Science. 2020; 369(6502):366–8. doi: 10.1126/science.abd1072.With the big challenges we face with the COVID-19 pandemic and the resulting effect it presents to ongoing TB control,it is reasonable to fear that we will have more unsuccessful treatment of TB in the country. Even as this potentially increases thenumber of TB cases in general, the even greater threat of further increasing MDR-TB should make us even more concerned.We cannot afford to lose focus and momentum in our efforts to control TB. Others have in fact stated that the currentpandemic may actually be a good opportunity to evaluate and if needed, to revise some of the programs we have in TBcontrol.24,25 The WHO has also made some recommendations which we can hopefully follow as we maintain our vigilanceon TB control during this pandemic.26The 2020 WHO Global Tuberculosis Report highlights many of the gains we have made in the Philippines. Hopefully,this COVID-19 pandemic will not push it back.15. Adepoju P. Tuberculosis and HIV responses threatened byCOVID-19. Lancet HIV. 2020; 7(5):e319-e320. doi: 10.1016/S2352-3018(20)30109-0.16. McQuaid CF, McCreesh N, Read JM, Sumner T, Houben RMGJ,White RG, et al. The potential impact of COVID-19-relateddisruption on tuberculosis burden. Eur Respir J. 2020; 56(2):2001718.https://doi.org/10.1183/13993003.01718-202017. Crisan-Dabija R, Grigorescu C, Pavel CA, Artene B, Popa IV,Cernomaz A, et al. Tuberculosis and COVID-19: Lessons from thepast viral outbreaks and possible future outcomes. Can Respir J. 2020;2020:1401053. doi: 10.1155/2020/1401053.18. Bandyopadhyay A, Palepu S, Bandyopadhyay K, Handu S. COVID-19and tuberculosis co-infection: a neglected paradigm. MonaldiArch Chest Dis. 2020; 90(3). doi: 10.4081/monaldi.2020.143719. Wingfield T, Cuevas LE, MacPherson P, Millington KA, Squire SB.Tackling two pandemics: a plea on World Tuberculosis Day. LancetRespir Med. 2020; 8(6):536-8 https://doi.org/10.1016/S2213-2600(20)30151-X20. Reid MJA, Silva S, Arinaminpathy N, Goosby E. Building atuberculosis-free world while responding to the COVID-19 pandemic.Lancet. 2020; 396(10259):1312-3. https://doi.org/10.1016/S0140-6736(20)32138-321. Macatangay IOD, Liao SAS, Dadural JJA, Gagui FJS, Galas AJA, SanAntonio RDFA, et al. Factors Associated with Treatment Outcomeof Patients with Pulmonary Tuberculosis in the Philippines, 2015 to2016. Acta Med Philipp. 2020; 54(5):604-1122. DOH. National Tuberculosis Prevalence Survey 2016 Philippines[Internet]. 2018 [cited 2020 Oct 25]. Available from: http://www.ntp.doh.gov.ph/downloads/publications/Philippines_2016%20National%20TB%20Prevalence%20Survey_March2018.pdf23. WHO. 2020 Global Tuberculosis Report [Internet]. [cited 2020Oct 25]. Available from: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&lan=%22EN%22&iso2=%22PH%2224. Keene C, Mohr-Holland E, Cassidy T, Scott V, Nelson A, Furin J, et al.How COVID-19 could benefit tuberculosis and HIV services in SouthAfrica. Lancet Respir Med. 2020; 8(9):844–6. https://doi.org/10.1016/S2213-2600(20)30311-825. Manyazewal T, Woldeamanuel Y, Blumberg HM, Fekadu A,Marconi VC. The fight to end tuberculosis must not be forgotten inthe COVID-19 outbreak. Nat Med. 2020; 26(6):811–2. https://doi.org/10.1038/s41591-020-0917-126. WHO. Updated WHO Information Note: Ensuring the continuityof TB services during the COVID-19 pandemic [Internet]. 2020[cited 2020 Oct 25]. Available from: https://www.who.int/docs/default-source/documents/tuberculosis/infonote-tb-covid-19.pdf?sfvrsn=b5985459_18

IntroductionAustralia is at a particular point in its history where there is a noticeable diaspora of artists and creative practitioners away from the major capitals of Sydney and Melbourne (in particular), driven in no small part by ballooning house prices of the last eight years. This has meant big changes for some regional spaces, and in turn, for the face of Australian cultural life. Regional cultural precincts are forming with tourist flows, funding attention and cultural economies. Likewise, there appears to be growing consciousness in the ‘art centres’ of Melbourne and Sydney of interesting and relevant activities outside their limits. This research draws on my experience as an art practitioner, curator and social researcher in one such region (Castlemaine in Central Victoria), and particularly from a recent interview series I have conducted in collaboration with art space in that region, Wide Open Road Art. In this, 23 regional and city-based artists were asked about the social, economic and local conditions that can and have supported their art practices. Drawing from these conversations and Bourdieu’s ideas around cultural production, the article suggests that authentic, diverse, interesting and disruptive creative practices in Australian cultural life involve the increasingly pressing need for security while existing outside the modern imperative of high consumption; of finding alternative ways to live well while entering into the shared space of cultural production. Indeed, it is argued that often it is the capacity to defy key economic paradigms, for example of ‘rational (economic) self-interest’, that allows creative life to flourish (Bourdieu Field; Ley “Artists”). While regional spaces present new opportunities for this, there are pitfalls and nuances worth exploring.Changes in Regional AustraliaAustralia has long been an urbanising nation. Since Federation our cities have increased from a third to now constituting two-thirds of the country’s total population (Gray and Lawrence 6; ABS), making us one of the most urbanised countries in the world. Indeed, as machines replaced manual labour on farms; as Australia’s manufacturing industry began its decline; and as young people in particular left the country for city universities (Gray and Lawrence), the post-war industrial-economic boom drove this widespread demographic and economic shift. In the 1980s closures of regional town facilities like banks, schools and hospitals propelled widespread belief that regional Australia was in crisis and would be increasingly difficult to sustain (Rentschler, Bridson, and Evans; Gray and Lawrence 2; Barr et al.; ABS). However, the late 1990s and early 21st century saw a turnaround that has been referred to by some as the rise of the ‘sea change’. That is, widespread renewed interest and idealisation of not just coastal areas but anywhere outside the city (Murphy). It was a simultaneous pursuit of “a small ‘a’ alternative lifestyle” and escape from rising living costs in urban areas, especially for the unemployed, single parents and those with disabilities (Murphy). This renewed interest has been sustained. The latest wave, or series of waves, have coincided with the post-GFC house price spike, of cheap credit and lenient lending designed to stimulate the economy. This initiative in part led to Sydney and Melbourne median dwelling prices rising by up to 114% in eight years (Scutt 2017), which alone had a huge influence on who was able to afford to live in city areas and who was not. Rapid population increases and diminished social networks and familial support are also considered drivers that sent a wave of people (a million since 2011) towards the outer fringes of the cities and to ‘commuter belt’ country towns (Docherty; Murphy). While the underprivileged are clearly most disadvantaged in what has actually been a global development process (see Jayne on this, and on the city as a consumer itself), artists and creatives are also a unique category who haven’t fared well with hyper-urbanisation (Ley “Artists”). Despite the class privilege that often accompanies such a career choice, the economic disadvantage art professions often involve has seen a diaspora of artists moving to regional areas, particularly those in the hinterlands around and train lines to major centres. We see the recent ‘rise of a regional bohemia’ (Regional Australia Institute): towns like Toowoomba, Byron Bay, Surf Coast, Gold Coast-Tweed, Kangaroo Valley, Wollongong, Warburton, Bendigo, Tooyday, New Norfolk, and countless more being re-identified as arts towns and precincts. In Australia in 2016–17, 1 in 6 professional artists, and 1 in 4 visual artists, were living in a regional town (Throsby and Petetskaya). Creative arts in regional Australia makes up a quarter of the nation’s creative output and is a $2.8 billion industry; and our regions particularly draw in creative practitioners in their prime productive years (aged 24 to 44) (Regional Australia Institute).WORA Conservation SeriesIn 2018 artist and curator Helen Mathwin and myself received a local shire grant to record a conversation series with 23 artists who were based in the Central Goldfields region of Victoria as well as further afield, but who had a connection to the regional arts space we run, WideOpenRoadArt (WORA). In videoed, in-depth, approximately hour-long, semi-structured interviews conducted throughout 2018, we spoke to artists (16 women and 7 men) about the relocation phenomenon we were witnessing in our own growing arts town. Most were interviewed in WORA’s roving art float, but we seized any ad hoc opportunity we had to have genuine discussions with people. Focal points were around sustainability of practice and the social conditions that supported artists’ professional pursuits. This included accessing an arts community, circles of cultural production, and the ‘art centre’; the capacity to exhibit; but also, social factors such as affordable housing and the ability to live on a low-income while having dependants; and so on. The conversations were rich with lived experiences and insights on these issues.Financial ImperativesIn line with the discussion above, the most prominent factor we noticed in the interviews was the inescapable importance of being able to live cheaply. The consistent message that all of the interviewees, both regional- and city-based, conveyed was that a career in art-making required an important independence from the need to earn a substantial income. One interviewee commented: “I do run my art as a business, I have an ABN […] it makes a healthy loss! I don’t think I’ve ever made a profit […].” Another put it: “now that I’m in [this] town and I have a house and stuff I do feel like there is maybe a bit more security around those daily things that will hopefully give me space to [make artworks].”Much has been said on the pervasive inability to monetise art careers, notably Bourdieu’s observations that art exists on an interdependent field of cultural capital, determining for itself an autonomous conception of value separate to economics (Bourdieu, Field 39). This is somewhat similar to the idea of art as a sacred phenomenon irreducible to dollar terms (Abbing 38; see also Benjamin’s “aura”; “The Work of Art”). Art’s difficult relationship with commodification is part of its heroism that Benjamin described (Benjamin Charles Baudelaire 79), its potential to sanctify mainstream society by staying separate to the lowly aspirations of commerce (Ley “Artists” 2529). However, it is understood, artists still need to attain professional education and capacities, yet they remain at the bottom of the income ladder not only professionally, but in the case of visual artists, they remain at the bottom of the creative income hierarchies as well. Further to this, within visual arts, only a tiny proportion achieve financially backed success (Menger 277). “Artistic labour markets are characterised by high risk of failure, excess supply of recruits, low artistic income level, skewed income distribution and multiple jobholding” (Mangset, Torvik Heian, Kleppe, and Løyland; Menger). Mangset et al. point to ideas that have long surrounded the “charismatic artist myth,” of a quasi-metaphysical calling to be an artist that can lead one to overlook the profession’s vast pitfalls in terms of economic sustainability. One interviewee described it as follows: “From a very young age I wanted to be an artist […] so there’s never been a time that I’ve thought that’s not what I’m doing.” A 1% rule seems widely acknowledged in how the profession manages the financial winners against those who miss out; the tiny proportion of megastar artists versus a vast struggling remainder.As even successful artists often dip below the poverty line between paid engagements, housing costs can make the difference between being able to live in an area and not (Turnbull and Whitford). One artist described:[the reason we moved here from Melbourne] was financial, yes definitely. We wouldn’t have been able to purchase a property […] in Melbourne, we would not have been able to live in place that we wanted to live, and to do what we wanted to do […]. It was never an option for us to get a big mortgage.Another said:It partly came about as a financial practicality to move out here. My partner […] wanted to be in the bush, but I was resistant at first, we were in Melbourne but we just couldn’t afford Melbourne in the end, we had an apartment, we had a studio. My partner was a cabinet maker then. You know, just every month all our money went to rent and we just couldn’t manage anymore. So we thought, well maybe if we come out to the bush […] It was just by a happy accident that we found a property […] that we could afford, that was off-grid so it cut the bills down for us [...] that had a little studio and already had a little cottage on there that we could rent that out to get money.For a prominent artist we spoke to this issue was starkly reflected. Despite large exhibitions at some of the highest profile galleries in regional Victoria, the commissions offered for these shows were so insubstantial that the artist and their family had to take on staggering sums of personal debt to execute the ambitious and critically acclaimed shows. Another very successful artist we interviewed who had shown widely at ‘A-list’ international arts institutions and received several substantial grants, spoke of their dismay and pessimism at the idea of financial survival. For all artists we spoke to, pursuing their arts practice was in constant tension with economic imperatives, and their lives had all been shaped by the need to make shrewd decisions to continue practising. There were two artists out of the 23 we interviewed who considered their artwork able to provide full-time income, although this still relied on living costs remaining extremely low. “We are very lucky to have bought a very cheap property [in the country] that I can [also] have my workshop on, so I’m not paying for two properties in Melbourne […] So that certainly takes a fair bit of pressure off financially.” Their co-interviewee described this as “pretty luxurious!” Notably, the two who thought they could live off their art practices were both men, mid-career, whose works were large, spectacular festival items, which alongside the artists’ skill and hard work was also a factor in the type of remuneration received.Decongested LivingBeyond more affordable real estate and rental spaces, life outside our cities offers other benefits that have particular relevance to creative practitioners. Opera and festival director Lindy Hume described her move to the NSW South Coast in terms of space to think and be creative. “The abundance of time, space and silence makes living in places like [Hume’s town] ideal for creating new work” (Brown). And certainly, this was a theme that arose frequently in our interviews. Many of our regionally based artists were in part choosing the de-pressurised space of non-metro areas, and also seeking an embedded, daily connection to nature for themselves, their art-making process and their families. In one interview this was described as “dreamtime”. “Some of my more creative moments are out walking in the forest with the dog, that sort of semi-daydreamy thing where your mind is taken away by the place you’re in.”Creative HubsAll of our regional interviewees mentioned the value of the local community, as a general exchange, social support and like-minded connection, but also specifically of an arts community. Whether a tree change by choice or a more reactive move, the diaspora of artists, among others, has led to a type of rural renaissance in certain popular areas. Creative hubs located around the country, often in close proximity to the urban centres, are creating tremendous opportunities to network with other talented people doing interesting things, living in close proximity and often open to cross-fertilisation. One said: “[Castlemaine] is the best place in Australia, it has this insane cultural richness in a tiny town, you can’t go out and not meet people on the street […] For someone who has not had community in their life that is so gorgeous.” Another said:[Being an artist here] is kind of easy! Lots of people around to connect—with […] other artists but also creatively minded people [...] So it means you can just bump into someone from down the street and have an amazing conversation in five minutes about some amazing thing! […] There’s a concentration here that works.With these hubs, regional spaces are entering into a new relevance in the sphere of cultural production. They are generating unique and interesting local creative scenes for people to live amongst or visit, and generating strong local arts economies, tourist economies, and funding opportunities (Rentschler, Bridson, and Evans). Victoria in particular has burgeoned, with tourist flows to its regions increasing 13 per cent in 5 years and generating tourism worth $10 billion (Tourism Victoria). Victoria’s Greater Bendigo is Australia’s most popularly searched tourist destination on Trip Advisor, with tourism increasing 52% in 10 years (Boland). Simultaneously, funding flows have increased to regional zones, as governments seek to promote development outside Australia’s urban centres and are confident in the arts as a key strategy in boosting health, economies and overall wellbeing (see Rentschler, Bridson, and Evans; see also the 2018 Regional Centre for Culture initiative, Boland). The regions are also an increasingly relevant participant in national cultural life (Turnbull and Whitford; Mitchell; Simpson; Woodhead). Opportunities for an openness to productive exchange between regional and metropolitan sites appear to be growing, with regional festivals and art events gaining importance and unique attributes in the consciousness of the arts ‘centre’ (see for example Fairley; Simpson; Farrelly; Woodhead).Difficulties of Regional LocationDespite this, our interviews still brought to light the difficulties and barriers experienced living as a regional artist. For some, living in regional Victoria was an accepted set-back in their ambitions, something to be concealed and counteracted with education in reputable metropolitan art schools or city-based jobs. For others there was difficulty accessing a sympathetic arts community—although arts towns had vibrant cultures, certain types of creativity were preferred (often craft-based and more community-oriented). Practitioners who were active in maintaining their links to a metropolitan art scene voiced more difficulty in fitting in and successfully exhibiting their (often more conceptual or boundary-pushing) work in regional locations.The Gentrification ProblemThe other increasingly obvious issue in the revivification of some non-metropolitan areas is that they can and are already showing signs of being victims of their own success. That is, some regional arts precincts are attracting so many new residents that they are ceasing to be the low-cost, hospitable environments for artists they once were. Geographer David Ley has given attention to this particular pattern of gentrification that trails behind artists (Ley “Artists”). Ley draws from Florida’s ideas of late capitalism’s ascendency of creativity over the brute utilitarianism of the industrial era. This has got to the point that artists and creative professionals have an increasing capacity to shape and generate value in areas of life that were previous overlooked, especially with built environments (2529). Now more than ever, there is the “urbane middle-class” pursuing ‘the swirling milieu of artists, bohemians and immigrants” (Florida) as they create new, desirable landscapes with the “refuse of society” (Benjamin Charles Baudelaire 79; Ley New Middle Class). With Australia’s historic shifts in affordability in our major cities, this pattern that Ley identified in urban built environments can be seen across our states and regions as well.But with gentrification comes increased costs of living, as housing, shops and infrastructure all alter for an affluent consumer-resident. This diminishes what Bourdieu describes as “the suspension and removal of economic necessity” fundamental to the avant-garde (Bourdieu Distinction 54). That is to say, its relief from heavy pressure to materially survive is arguably critical to the reflexive, imaginative, and truly new offerings that art can provide. And as argued earlier, there seems an inbuilt economic irrationality in artmaking as a vocation—of dedicating one’s energy, time and resources to a pursuit that is notoriously impoverishing. But this irrationality may at the same time be critical to setting forth new ideas, perspectives, reflections and disruptions of taken-for-granted social assumptions, and why art is so indispensable in the first place (Bourdieu Field 39; Ley New Middle Class 2531; Weber on irrationality and the Enlightenment Project; also Adorno’s the ‘primitive’ in art). Australia’s cities, like those of most developed nations, increasingly demand we busy ourselves with the high-consumption of modern life that makes certain activities that sit outside this almost impossible. As gentrification unfolds from the metropolis to the regions, Australia faces a new level of far-reaching social inequality that has real consequences for who is able to participate in art-making, where these people can live, and ultimately what kind of diversity of ideas and voices participate in the generation of our national cultural life. ConclusionThe revival of some of Australia’s more popular regional towns has brought new life to some regional areas, particularly in reshaping their identities as cultural hubs worth experiencing, living amongst or supporting their development. Our interviews brought to life the significant benefits artists have experienced in relocating to country towns, whether by choice or necessity, as well as some setbacks. It was clear that economics played a major role in the demographic shift that took place in the area being examined; more specifically, that the general reorientation of social life towards consumption activities are having dramatic spatial consequences that we are currently seeing transform our major centres. The ability of art and creative practices to breathe new life into forgotten and devalued ideas and spaces is a foundational attribute but one that also creates a gentrification problem. 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Rib Fractures are a common injury in trauma patients and affect 10% of all injured patients who require admission to the hospital. Currently, there is no consensus on the most efficacious treatment for rib fractures with the debate comparing non-surgical versus surgical management. Medical management of rib fractures often requires admission to the intensive care unit with a focus on pain control to allow good pulmonary hygiene. Pain control involved a multimodal approach with current techniques including epidural anesthesia and paravertebral blocks. Although many patients recover with medical management alone, some patients may benefit from surgical stabilization of rib fractures as a means of augmenting pain control. Flail chest is the most evidence-based indication for surgical stabilization of rib fractures SSRF with many studies showing decreased days on mechanical ventilation, risk of pneumonia, intensive care unit length of stay, and hospital length of stay. Additionally, in patients with non-flail chest and ventilator dependent respiratory failure, surgical stabilization of rib fractures may provide an advantage over medical management for pain control. There are relatively few contraindications and complications associated with surgical stabilization of rib fractures. Therefore, with proper patient selection, surgical stabilization of rib fractures can improve outcomes in patients with rib fractures. Medical management with or without surgical intervention requires a multidisciplinary approach to prevent adverse clinical outcomes. Keywords: Surgical stabilization of rib fractures, rib plating, rib fracture, flail chest, non-flail chest Article Details How to Cite RAFFA, Taylor et al. Surgical Stabilization of Rib Fractures: A Review of the Indications, Technique, and Outcomes. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4694>. 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