Artículos de revistas sobre el tema "823.912 f"

Abstract. In this paper, we present observations of equatorial spread F (ESF) irregularities made using a newly installed 18MHz radar located at Trivandrum. We characterize the morphology and the spectral parameters of the 8.3-m ESF irregularities which are found to be remarkably different from that observed so extensively at the 3-m scale size. We also present statistical results of the irregularities in the form of percentage occurrence of the echoes and spectral parameters (SNR, Doppler velocity, Spectral width). The Doppler spectra are narrower, less structured and less variable in time as compared to those observed for 3-m scale size. We have never observed the ESF irregularity velocities to be supersonic here unlike those at Jicamarca, and the velocities are found to be within ±200ms–1. The spectral widths are found to be less than 150ms–1. Hence, the velocities and spectral width both are smaller than those reported for 3-m scale size. The velocities and spectral widths are further found to be much smaller than those of the American sector. These observations are compared with those reported elsewhere and discussed in the light of present understanding on the ESF irregularities at different wavelengths. Key words. Ionoshphere (equatorial ionosphere, plasma waves and instabilities; ionospheric irregularities)

Abstract We present a near-infrared transmission spectrum of the long-period (P = 542 days), temperate (T eq = 294 K) giant planet HIP 41378 f obtained with the Wide-Field Camera 3 instrument aboard the Hubble Space Telescope (HST). With a measured mass of 12 ± 3 M ⊕ and a radius of 9.2 ± 0.1 R ⊕, HIP 41378 f has an extremely low bulk density (0.09 ± 0.02 g cm−3). We measure the transit depth with a median precision of 84 ppm in 30 spectrophotometric channels with uniformly sized widths of 0.018 μm. Within this level of precision, the spectrum shows no evidence of absorption from gaseous molecular features between 1.1 and 1.7 μm. Comparing the observed transmission spectrum to a suite of 1D radiative-convective-thermochemical-equilibrium forward models, we rule out clear, low-metallicity atmospheres and find that the data prefer high-metallicity atmospheres or models with an additional opacity source, such as high-altitude hazes and/or circumplanetary rings. We explore the ringed scenario for HIP 41378 f further by jointly fitting the K2 and HST light curves to constrain the properties of putative rings. We also assess the possibility of distinguishing between hazy, ringed, and high-metallicity scenarios at longer wavelengths with the James Webb Space Telescope. HIP 41378 f provides a rare opportunity to probe the atmospheric composition of a cool giant planet spanning the gap in temperature, orbital separation, and stellar irradiation between the solar system giants, directly imaged planets, and the highly irradiated hot Jupiters traditionally studied via transit spectroscopy.

To determine the prevalence of cervical Chlamydia trachomatis genotypes in Iran for the first time and their association with three clinical symptoms/signs, i.e. abnormal vaginal discharge, lower abdominal pain (LAP) and swab-induced bleeding, and patient age, 620 cervical specimens were obtained from women with symptomatic genital infection referred to gynaecological clinics and 108 C. trachomatis-positive specimens were genotyped by direct omp1 gene PCR-RFLP analysis. Eight genotypes were identified. The most prevalent genotype was E (31.5 %), followed by F (23.1 %), D/Da (13 %), K (9.2 %), I (8.3 %), G (7.5 %), H (5.5 %) and J (1.9 %). For analysing the association of C. trachomatis genotypes with symptoms/signs and age, P-values were separately evaluated for genogroups and genotypes. The analysis of genogroups showed that women infected with genogroup F/G manifested the symptom of LAP significantly more often than those infected with the other genogroups (P=0.02), while the analysis of genotypes revealed that women infected with genotype F reported LAP slightly more often than women infected with the other genotypes (P=0.08). No significant correlation between genogroups and age was found; however, genotype E was somewhat less prevalent among women aged 25–34 years than among other age groups (P=0.08).

Abstract Background: An evaluation of SENTiFIT® 270 (Sentinel Diagnostics, Italy; Sysmex, Spain) analyser for the quantitation of faecal haemoglobin (f-Hb) was performed. Methods: The analytical imprecision, linearity, carry over and f-Hb stability were determined. Evaluation of the diagnostic accuracy was performed on 487 patients. Results: Within-run and between-run imprecision ranged 1.7%–5.1% and 3.8%–6.2%, respectively. Linearity studies revealed a mean recovery of 101.1% (standard deviation, 6.7%) for all dilutions. No carry over was detected below 7650 μg Hb/g faeces. Decay of f-Hb in refrigerated samples ranged 0.2%–0.5% per day. f-Hb in patients with advanced colorectal neoplasia (ACRN) (colorectal cancer [CRC] plus advanced adenoma [AA]) were significantly higher than from those with a normal colonoscopy. Sensitivity for ACRN at f-Hb cutoffs from 10 to 60 μg Hb/g faeces ranged from 28.9% (95% confidence interval [CI], 21.7%–37.2%) to 46.5% (95% CI, 38.1%–55%), the specificity ranged from 85% (95% CI, 82.3%–87.3%) to 93.2% (95% CI, 91.2%–94.8%), positive predictive values for detecting CRC and AA ranged from 11.6% (95% CI, 7.6%–17.2%) to 20.6% (95% CI, 13.3%–30.3%) and from 34.7% (95% CI, 28.1%–42%) to 42.3% (95% CI, 32.4%–52.7%), respectively, and the negative predictive value for ACRN ranged from 90.2% (95% CI, 87.9%–92.2%) to 88.4% (95% CI, 86%–90.4%). Using two samples per patient sensitivity increased with a slight decrease in specificity. Conclusions: The analytical and clinical performances of SENTiFIT assay demonstrate a specific and accurate test for detecting ACRN in symptomatic patients and those undergoing surveillance.

Abstract Storage roots of 10 sweet potato clones [Ipomoea batatas (L.) Lam.] were screened for resistance to Fusarium solani (Sacc.) Mart, emend. Snyd. and Hans. Clones were inoculated after 0, 6, and 36 days of postharvest storage and incubated in sterile moist chambers for 23 days. Resistance was evaluated by measuring volume of rotted tissue in each clone at the end of the incubation period. Clones tested (in increasing order of average rot volume over three screenings) were: NC 910, NC 925, NC 928, ‘NC Porto Rico 198’, ‘Centennial’, NC 825, NC 835, NC 818, W 125, and ‘Jewel’. Differences among clones for mean rot volume were highly significant within each storage period, and mean rot volumes generally increased in all clones as the length of the preinoculation storage period increased. The average rot volume of roots of resistant clones NC Porto Rico 198, NC 928, NC 910 and NC 925 was 19% that of ‘Jewel’ roots. Correlations between rot volume and postharvest quality factors in comparably stored healthy roots of the same genotypes were too low to be useful selection indices for F. solani resistance.

Abstract Formulated biological insecticides were evaluated for toxicity to lepidopterous pests of cotton in the laboratory. Bioassays were conducted by applying insecticides to cotton terminals (‘STV 213’) held in water pics using a laboratory spray table. The spray table was calibrated to deliver 6 gal/acre at 2 mph with 30 psi at one TX6 nozzle. Each treatment consisted of 3 replicates of 15 terminals/replicate. Controls were treated with water only. Laboratory strains of each insect were reared on artificial diet and each species was tested separately. The average weight of insects tested in mg was: TB, 6.5 ± 1.4; BW, 9.2 ± 2.7; BA, 6.9 ± 1.6; SL, 8.3 ± 1.8. One larva was placed on each terminal 30 min after spraying and held under ventilated cups at 85°F and 55-60% RH. Mortality was determined 72 h after treatment. Mortality was corrected for control mortality by Abbott‘s formula. Data were transformed to arcsin J for analysis; actual percent mortalities are shown.

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment as the first or an alternative option to biologic disease- modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi). The similarity in retention of TNFi and TOFA was previously reported separately by the Ontario Best Practices Research Initiative (OBRI) and the Quebec cohort RHUMADATA®.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TNFi compared to TOFA, using pooled data from both these registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA or TNFi between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Time to discontinuation was assessed using adjusted Kaplan-Meier (KM) survival and Cox regression models. To deal with confounding by indication, we estimated propensity scores for covariates with a standard difference greater than 0.1. Models were then adjusted using stratification and inverse probability of treatment weight (IPTW) methods. Multiple imputation (Imputation by Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Results:A total of 1318 patients initiated TNFi (n=825) or TOFA (n=493) with mean (SD) disease duration of 8.9 (9.3) and 13.0 (10.1) years, respectively. In the TNFi group, 78.8% were female and mean age (SD) at treatment initiation was 57.6 (12.6) years. In the TOFA group, 84.6% were female and mean (SD) age at treatment initiation was 59.5 (11.5) years. The TNFi group was less likely to have prior biologic use (33.9%) than the TOFA group (66.9%). At treatment initiation, the mean (SD) CDAI was significantly (p<0.05) lower in the TNFi group [20.0 (11.7)] compared to the TOFA group [22.1(12.4)]. Physical function measured by HAQ-DI was also significantly lower (p<0.05) in the TNFi compared to the TOFA group (1.2 vs.1.3).Over a mean follow-up of 23.2 months, discontinuation was reported in 309 (37.5%) and 182 (36.9%) of all TNFi and TOFA patients, respectively. After adjusting for propensity score deciles across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 0.96, 95% CI: 0.78-1.18; p=0.69). The results were similar for two propensity adjustment methods. Figure 1 shows IPTW adjusted KM survival curves comparing discontinuation rates in patients treated with TNFi and TOFA.Figure 1.Note: Propensity Score Weighted (IPTW) Survival Curves was performed using one imputed datasetConclusion:In this pooled real -world data study, we found that TNFi and TOFA retention is similar in patients with RA. In the next step we will analysis the data for specific reasons of dicontinutaion. We will also repeat analysis comparing discontinuation in the first users versus those after one or more biologic failure.Disclosure of Interests:Mohammad Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata® is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: None declared, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm. Speaker Honoraria Agreements: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis. Consulting Agreements/Advisory Board Membership: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Claire Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Aurora, Bristol-Meyers Squibb, Celgene, Hospira, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB.Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Tujuan penelitian adalah untuk mengetahui Pengaruh Minat Konsumen dan Spesifikasi Produk Terhadap Keputusan Pembelian Produk Pada PT. Cahaya prima Lestari Abadi di Medan, jenis penelitian kuantitatif dengan mengunakan data sekunder, teknik analisis data yang digunakan adalah dengan regresi linier berganda. Hasil penelitian menunjukkan berdasarkan uji t, variabel minat konsumen berpengaruh positif dan signifikan terhadap keputusan pembelian dengan nilai thitung sebesar 2,124 > ttabel 1,994 dengan tingkat signifikansi 0,037. Variabel spesifikasi produk secara parsial berpengaruh positif dan signifikan terhadap keputusan pembelian dengan nilai thitung 7,49 > ttabel 1,994 dengan tingkat signifikansi sebesar 0,000. Berdasarkan uji F, variabel independen yaitu minat konsumen dan spesifikasi produk secara bersama-sama mempengaruhi variabel dependen yaitu keputusan pembelian dengan nilai fhitung 377.324 > ftabel 3,13 dengan tingkat signifikansi 0,000. Nilai R square (R2) dalam penelitian ini diperoleh sebesar 0.917 atau 91,7%. Hal ini berarti bahwa variabel dependen keputusan pembelian dapat dijelaskan oleh variabel Independen minat konsumen dan spesifikasi produk sebesar 91,2% sedangkan sisanya yaitu sebesar 8,3% dijelaskan oleh variabel lain di luar variabel penelitian yang digunakan.

Background: Each year more than 200,000 new cancer cases are expected in children & adolescents aged 0-14 years at global level. Although the long term survival rates have been improved to 85% in high income countries, it is still lower than this LMICs with a wide range around the world. Pediatric registries are critical for planning for pediatric cancer care. This study summarizes the update of pediatric cancer registry in Turkey. Aim: To analyze the pediatric cancer distribution through Turkish Pediatric Cancer Registry for the years of 2009-2017. Method: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association established a Web based cancer registry in Turkey in 2002. The registry information for 2002-2008 was presented earlier. This study, now, is presents the distribution of pediatric cancers for the years of 2009-2017. International Childhood Classification System was used in classification. Basic demographic findings, ICD-O-3 morphology & topography codes were recorded for each cases. This is an update of the Turkish Pediatric Cancer Registry. Results: During the 9 years from 2009 to 2017, 14,769 pediatric cancer cases were recorded. For all cases, median age was 6.7 years (0-17 M/F 8318/6443, 3 hermaphrodite 5 unknown). Age distribution was 0-4 yrs, 40.8%; 5-9 yrs, 24.5%; 10-14 yrs, 23.3%; 15-19 yrs, 11.4%. The distribution of tumor types were [number of cases, percentage of total, median age years, M/F]: leukemia (4114, 27.9%, 5.5, 2366/1748); lymphoma and other RES tumors (2823, 19.1%, 9.6, 1904/914, 1 hermaphrodite 4 unknown); CNS [brain & spinal] (1950, 13.2%, 7.1, 1072/828); sympathetic system (1166, 7.9%, 2.4, 609/557); retinoblastoma (351, 2.4%, 1.4, 197/154); renal (736, 5.0%, 3.3, 345/391); liver (242, 1.6%, 1.8, 132/110); malignant bone (965, 6.5%, 12.6, 527/438); soft tissue sarcomas (991, 6.7%, 7.4, 580/411); germ cell (911, 6.2%, 8.2, 331/577, 2 hermaphrodite, 1 unknown); carcinoma and other malignant epithelial (436, 3.0%, 13.6, 212/224); other/nonspecific malignant (84, 0.6%, 7.1, 43/41) tumors. Five year survival rate was found as 67.8%. Conclusion: Registry provides the essential information for planning the pediatric cancer care. This registry became a critical source for health care professionals in Turkey since beginning. Survival rates for children increased to 67.8% based on this study. This is compatible with the survival rates from other upper middle income countries. This data also allows the comparison of the national data with the national and international studies. Investment on the pediatric cancer registry is one of the first steps of investments on pediatric cancer care.

Research objective. To define methodological approaches to pedagogical control of dynamics of motor and functional readiness of girls aged 15-16.Research methods. To solve the tasks set, the study used the following methods: analysis of scientific and methodological literature, pedagogical testing and methods of mathematical statistics of data reduction. The testing program consisted of the commonly known tests: jumping with “increases f weight” (number of jumps in the given corridor), evaluation of time parameters of movement (error in re-creating the duration of five-second running in place), evaluation of perception of strength movement parameters (the error in re-creating the efforts is 0.5 of the maximum), shuttle run 4×9 m (s), bending and unbending of arms from the lying position (times), bending and unbending of arms in suspension (times), bent suspension (s), standing long jump (cm).Research results. The girls aged 15 show statistically significantly better readiness by the results of the tests: No. 1 “Jumping with ‘increases of weight’, times”, No. 3 “Bending and unbending of arms from the lying position, times”, No. 5 “Bent suspension, s”, and by the indicators of functional tests (p < 0.05).The most informative indicators for the routine control of the motor readiness of girls aged 15 are the following tests: “Bending and unbending of arms from the lying position” (,951), Ghencea test (,929), “Standing long jump (cm)” (,930), “Shuttle run 4×9 m, s” (,911).The most informative indicators for the routine control of the motor readiness of girls aged 16 are the following tests: Ghencea test (,945), “Bending and unbending of arms in suspension” (,883), “Bending and unbending of arms from the lying position” (,823).

Prior to the experiment two groups of 10 sheep were fed to either gain (group F) or lose (group T) weight. At the beginning of the experiment group F sheep weighed on average 57.7 kg fleece-free liveweight (W) and had a total body fat (TBF) content of 154 kg, while group T sheep weighed 42.6 kg and had a TBF content of 9.7 kg. During the experiment all sheep were given a urea-treated rice straw-based diet ad libitum for 56 days with an intra-ruminal infusion of urea and sodium sulfate. Measurements were made of feed intake and digestibility and of the amounts and composition of digesta in the reticula-rumen (ReRu) and flowing through the abomasum.Group T sheep consumed more feed (dry matter intake 1 170 v. 1040 g day-1, 24.9 v. 19.1 g kg W-1) and spent more time chewing (16.5 v. 14.1 h day-1) than group F sheep. There were no differences in the digestibility of dietary constituents.Associated with the greater feed intakes by group T sheep were increased amounts of total digesta (8.59 v 7.67 kg) and of dry matter (DM) (1040 v. 960 g), organic matter (OM) (820 v. 750 g) and neutral detergent fibre (NDF) (690 v. 620 g) in the ReRu. Flows of total digesta (22.45 v. 18.64 kg day-1), DM (910 v. 800 g day-1), OM (600 v. 510 g day-1) and NDF (330 v. 270 g day-1) through the abomasum were also greater in group T sheep. However, there were no differences between treatments in the proportion of digestion which occurred in the ReRu, in the fractional digestion rate of NDF in the ReRu or in the fractional passage rate of NDF from the ReRu.Group T sheep generally maintained weight (-4 g day-1) throughout the experiment and their TBF only declined from 9.7 to 9.1 kg. In contrast, group F sheep lost weight at 74 g day-1 and TBF declined from 15.8 to 14.1 kg.It is concluded that removal of limitations of essential nutrients enabled sheep in poor condition to consume more of this straw-based diet than those in good condition.

В работе методами растровой электронной микроскопии и ультрамягкойрентгеновской эмиссионной спектроскопии были проведены исследования особенностейформирования многослойных структур пористого кремния и установлено влияние изменения плотности тока при электрохимическом травлении монокристаллических пластин кремния на фазовый состав поверхностных слоев сформированной пористой структуры. ЛИТЕРАТУРА1. Moshnikov V., Gracheva I., Lenshin A., Spivak Yu. Porous silicon with embedded metal oxides for gassensing applications // Journal of Non-Crystalline Solids, 2012 v. 358(3), pp. 590–595. DOI: https://doi.org/10.1016/j.jnoncrysol.2011.10.0172. Pacholski C. Photonic crystal sensors based on porous silicon // Sensors, 2013, v. 13(4), pp. 4694–4713.DOI: https://doi.org/10.3390/s1304046943. Harraz F. Porous silicon chemical sensors and biosensors: A review // Sensors and Actuators B, 2014,v. 202, pp. 897–912. DOI: https://doi.org/10.1016/j.snb.2014.06.0484. 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SummaryEvaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects ≥5 years of age with baseline FVIII:C ≤2%, and ≥150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHFPFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemor rhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18.Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.

Abstract Objectives To assess the acute effect of adequate water consumption on copeptin, a marker of arginine vasopressin, in low drinkers. Methods Six healthy (5 males, 1 female) low drinkers (age 43 ± 7 y, BMI 30.5 ± 3) were recruited based on self-reported daily water consumption ≤1.5 L·day−1 in males or 1.0 L·day−1 in females (854 ± 432 mL·d−1) and 24-h urine osmolality ≥800 mmol·kg−1 (968 ± 114 mmol·kg−1). Participants completed two counterbalanced crossover 11-h protocols. They were provided either the Institute of Medicine's recommended amount of water excluding food (males: 3 L, females: 2 L, HWI) or an amount representing the bottom quartile of water consumption observed in the National Health and Nutrition Examination Survey (males: 0.5 L, females: 0.4 L, LWI). Food was provided to participants and standardized to body weight (100 kJ·Kg−1) using a consistent ratio of macronutrients. Blood samples were collected at hours 700, 800, 900, 1200, 1300, 1400, 1600, 1700, and 1800. Results There was a significant main effect of water intake on plasma osmolality (F = 11.838, P = 0.018) with greater values in LWI at 1200 (HWI: 287 ± 3, LWI: 291 ± 3; P = 0.013), 1400 (HWI: 287 ± 4, LWI: 291 ± 5; P = 0.049), and 1700 (HWI: 287 ± 2, LWI: 292 ± 4; P = 0.004). There was also a significant main effect of water intake on copeptin (F = 9.848, P = 0.026) with higher values in LWI at 0800 (HWI: 6.1 ± 2.3, LWI: 8.7 ± 3.7; P = 0.016), 0900 (HWI: 5.3 ± 2.4, LWI: 9.2 ± 4.5; P = 0.013), 1200 (HWI: 4.2 ± 1.9, LWI: 7.8 ± 4.6; P = 0.021), 1400 (HWI: 4.3 ± 1.8, LWI: 8.3 ± 4.7; P = 0.033), 1600 (HWI: 4.7 ± 2.5, LWI: 7.6 ± 4.5; P = 0.049), and 1800 (HWI: 4.4 ± 2.5, LWI: 7.8 ± 5.2; P = 0.048). Water intake did not influence change in plasma volume (P = 0.214). Conclusions Copeptin was suppressed in response to acute increases in water consumption via suppression of plasma osmolality. Copeptin may serve as a sensitive marker for changes in total water intake. Funding Sources This study was supported by Arizona State University College of Health Solutions.

10067 Background: In childhood cancers cure rates increased up to 80% in the developed countries. On the other hand cure rates goes down 10-20% percent in countries with low resource settings. Reliable pediatric cancer data is essential for all countries. We established a nationwide pediatric cancer registry. Methods: Turkish Pediatric Oncology & Pediatric Hematology Society established a web-based database for the registry of all pediatric cancers. 11898 cases were registered between 2002-2008 from 65 centers. Various demographic data & survival endpoints were recorded & analyzed. Diseases were grouped according to the International Classification of Childhood Cancer. Results: In all 11898 cases, median age was 6 years (M/F= 6786/5112=1.32). Distribution in age groups were: 0-4 years, 42.5%; 5-9 years, 27.2%; 10-14 years, 23.4%; 15-19 years, 6.8%; >19 years, 0.1%. Only 3.8% of cases were diagnosed with clinical+radiological, the rest with histopathological data Distribution of cases in disease groups were [median age in yrs, M/F]: Leukemias (n=3777) 31.7% [5.5, 2137/1640=.31]; Lymphomas (n=2040) 17.1% [8.3, 1405/635=2.21]; CNS tumors (n=1588) 13.3% [6.9, 913/675=1.3 ]; Sympathetic tumors (n=889) 7.5% [2.1, 453/436=1.03]; Retinoblastoma (n=371) 3.1% [2, 181/190=0.95]; Renal tumors (n=655) 5.5% [3, 333/322=1.03]; Hepatic (n=166) 1.4% [1.8, 101/65=1.5]; Bone tumors (n=717) 6% [12.2, 407/310=1.3]; Soft tissue tumors (n=773) 6.5% [6.5, 442/331=1.3]; Germ cell tumors (n=531) 4.5% [5, 210/321=0.6 ]; Carcinomas and other malignant epithelial tumors (n=323) 2.7% [12, 164/159=1.03]; Others/unspecified malignant tumors (n=68) 0.6% [4.5, 40/28=1.4]. Five-year overall survival in all cases was 65%. Conclusions: This registry provides a critical information about the distribution of childhood cancer since this is the only nationwide pediatric cancer registry in Turkey. With the recent trends in non-communicable diseases at global level, registry data will be very helpful for national cancer control plans, which will also be used to compare at national and international level. This will also be a good example for many other countries with similar resources to do such projects.

8512 Background: The combination of platinum doublet chemotherapy with sotorasib may improve anti-tumor activity and overcome therapeutic resistance in KRASG12C-mutated advanced non-small cell lung cancer (NSCLC). We report updated efficacy and safety of sotorasib plus carboplatin and pemetrexed from the international CodeBreaK 101 phase 1b trial (NCT04185883). Methods: Patients (Pts) with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg QD plus carboplatin AUC 5 IV Q3W and pemetrexed 500 mg/m2 IV Q3W for up to 4 cycles followed by sotorasib plus pemetrexed maintenance until disease progression/unacceptable toxicity. Data were analyzed by prior therapy in the locally advanced/metastatic setting (1L and 2L+). Primary endpoints were safety/tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) according to RECIST v1.1 per investigator, and overall survival (OS). Results: As of December 1, 2023, 58 pts (median age, 65.5 yrs; 45% male; ECOG status 0/1, 38%/62%) were treated with sotorasib plus carboplatin and pemetrexed; 37 (64%) pts in the 1L and 21 (36%) in the 2L+ setting. In 2L+, 18/21 (86%) pts had received prior anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 54 (93%) pts; grade 3–4 in 30 (52%) pts and fatal in 1 (2%) (Table). In 1L, ORR was 65% (95% CI, 46.5–80.3), DCR was 100%, median DOR was 9.1 mo (95% CI, 4.4–12.5), and median PFS was 10.8 mo (95% CI, 5.4–NE; median follow-up [f/u], 9.2 mo). Median PFS was 11.9 mo (95% CI, 5.3–NE) in the PD-L1 <1% subgroup (n=19). For 2L+, ORR was 42% (95% CI, 20.3–66.5), DCR was 84%, median DOR was NE, and median PFS was 8.3 mo (95% CI, 4.1–NE; median f/u, 4.4 mo). OS data remained immature. Conclusions: Sotorasib plus platinum doublet chemotherapy conferred robust and durable responses with a manageable safety profile in CodeBreaK 101, supporting evaluation of this regimen in the ongoing CodeBreaK 202 phase 3 trial in treatment naïve, PD-L1 negative, KRAS G12C-mutated advanced NSCLC (NCT05920356). Clinical trial information: NCT04185883 . [Table: see text]

A study of Synodontis punctifer (family: Mochokidae) of Taabo Lake was conducted from October 2015 to September 2016. This was carried out so as to evaluate its quantity (biomass) caught by fishing and also its morphological characteristics. The fish were caught using gillnets at 4 sites of the lake and different measurements were made. The fishing effort was 23 to 11 fishermen / day in Taabo city, 17 to 11 fishermen / day in Courandjourou, 13 to 5 fishermen / day in Ahondo, and 8 to 3 fishermen / day in Taabo village. The catch per unit effort (CPUE) ranged from 17.7 to 3.7 g / fisherman / day, 9.2 to 1.2 g / fisherman / day, 8.3 to 0.7 g / fisherman /day, 8 to 1g / fisherman / day at Ahondo, Courandjourou, Taabo city and Taabo village, respectively. The overall annual production was estimated at 2199.3 kg, i.e. 817 kg (40%) at Ahondo, 788.3 kg (35%) at Courandjourou, 462.5 kg (20%) at Taabo, and 131.5 kg (5%) in Taabo village. The overall sex ratio (1: 1.33) was in favor of females. Individuals have negative allometric growth at all sites with values ranging from 1.72 to 2.89. The condition factor does not vary significantly between different categories of individuals (ANOVA, F = 2.79, p ˃ 0.05). A significant difference was observed between the average sizes of the individuals of the different sites (test, p˂0,05). The large size specimens were captured at Ahondo, mean (avg = 15.38 ± 1.68 cm FL). In Courandjourou, the sizes were intermediate (avg = 13.63 ± 1.64 cm LF). Smalls sizes have been observed in Taabo city (mean= 12.37 ± 1.24 cm FL) and Taabo village (mean= 15.58 ± 1.58 cm FL).

Abstract Aim The aim of this study was to determine the frequency and distribution of third-molar agenesis in orthodontic patients from the East Anatolian Region of Turkey. Methods and Materials Our data were obtained from the panoramic radiographs of the 2,579 patients 12 to 16 years of age in the Department of Orthodontics at the Atatürk University in Erzurum, Turkey. Subjects with congenital deformities, such as a cleft palate, were excluded from the study. Statistical analysis was performed using SPSS software and a chi-squared test. Results Of the 2,579 subjects, 1,964 (76.2 percent) had all four third-molar teeth, 238 (9.2 percent) had three, 214 (8.3 percent) had two, 66 (2.6 percent) had one third molar, and 97 (3.8 percent) had agenesis of all third-molar teeth. There was no significant difference in agenesis of third-molar teeth between the right and left sides and no gender predilection was noted. However, significantly more third-molar teeth were found to be missing from the maxilla compared to the mandible, with a ratio of approximately 1.5:1. Conclusion According to our results, the absence of one third molar is the most frequently detected pattern in the East Anatolian population. Additionally, the absence of third molars is more frequent in the maxilla than the mandible. Clinical Significance To date no information about third-molar agenesis in the East Anatolian population from Turkey is documented. This is believed to be the first known study on this subject in this population. Citation Kazanci F, Celikoglu M, Miloglu O, Oktay H. Third-Molar Agenesis among Patients from the East Anatolian Region of Turkey. J Contemp Dent Pract [Internet]. 2010 July; 11(4):033-040. Available from: http://www.thejcdp. com/journal/view/volume11-issue4-kazanci

Abstract Abstract 5183 Carriers of α°-thalassemia (α-thalassemia trait) show microcytosis, hypochromia, and normal percentages of HbA2 and HbF. Carriers of α + -thalassemia (α-thalassemia silent carrier) have either a silent hematologic phenotype or present with a moderate thalassemia-like hematologic picture. Homozygosity for α + -thalassemia results in an α°-thalassemia (α-thalassemia trait) hematologic phenotype. Diagnostic of Alfa Thalassemia Heterozygous: Classic testing for α-thalassemia includes: hematologic testing of red blood cell indices, peripheral blood smear, supravital stain to detect RBC inclusion bodies, and qualitative and quantitative hemoglobin analysis. HBA1, the gene encoding α1-globin, and HBA2, the gene encoding α2-globin, are the two genes most commonly associated with α-thalassemia. Molecular genetic testing of HBA1 and HBA2 detects deletions in about 90% and point mutations in about 10% of affected individuals. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV, @RSF, @MAF, @LHD% and many morphological parameters for RBC and Reticulocytes calles Cell Population Data. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Alfa Thalassemia Heterozygous. Patient and Methods: We have collected 48 patients with Alfa Thalassemia Heterozygous All of them were confirmed by red cell morphology, Hgb Electroforesis, cromatography in liquid phase in human whole blood for the determination of Hemoglobin A2, F, A1c, and identification of abnormal hemoglobins and DNA analysis (DNA Analysis by GAP-PCR). We have compared these patients with a control group (184 individuals) and with other anemias (see Table 1). Results: Using ROC analysis, the best parameters differentiating the Alfa Thalassemia Heterozygous from the normals were: MCV (AUC 0. 963), @RSF (AUC 0. 936), @MSCV (AUC 0. 912), RDW (AUC 0. 848), @MAF(AUC 0. 845), @LHD(AUC 0. 829). Using ROC analysis, the best parameters differentiating the Alfa Thalassemia Heterozygous from other anemias (excluding normals) were: RDW (AUC 0. 885), @MAF(AUC 0. 857), @MCNRET (AUC 0. 832). Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Ferrokin: Research Funding; Apopharma: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Abstract A novel, stable human immunodeficiency virus type 1 (HIV-1) vector packaging system, STAR, was tested for its ability to transduce human cord blood CD34+ progenitor cells assayed both in vitro and after transplantation to NOD/SCID mice. Vectors pseudotyped with three different gammaretrovirus envelopes were used; the amphotropic MLV envelope (MLV-A), a modified gibbon ape leukemia virus envelope (GALV+) and a modified feline endogenous virus RD114 envelope (RDpro). Titration of vectors harvested from the stable packaging cells gave the following results: MLV-A: 1–3x106 inf.u/ml, GALV+: 1x106 inf.u/ml and RDpro: 3–10x106 inf.u/ml CB CD34+ cells were transduced on Retronectin® preloaded with vector either in fresh medium (PL alone) or in vector containing medium (PL+VCM). Gene transfer to freshly thawed CD34+ in the absence of cytokines was very low. Addition of cytokines (CK; SCF, TPO and FL) increased gene transfer efficiency significantly and this was further augmented if the cells were prestimulated for 24 hours wit the same cytokines. Concentration of the vectors (15-fold) by low-speed ultracentrifugation increased gene transfer to CD34+ cells in vitro even further. More than 90% of cells were transduced with a single exposure to the RDpro vector as determined by GFP expression using flow cytometry. The two other pseudotypes transduced approximately 70% of the cells under the same conditions. Detailed in vitro transduction data is shown in table as percentage GFP positive cells: RDpro MLV-A GALV+ PL alone PL+VCM PL alone PL+VCM PL alone PL+VCM No CK 9.2±2 0.9±0.8 12.5±3.5 6.6±0.1 0.9±0.4 1.4±0.5 With CK 22.4±8.3 3.3±5.3 18.2±3.8 10.8±3.8 4.8±1.7 16.7±9.0 CK prestim f 24 hours 57.6±14.9 35.3±32.1 45.4±14.9 36.3±14.8 3.4±1.7 19.5±12.2 Concentrated vector CK prestim f 24 h 93.4±3.3 93.3±3.7 73.3±7.6 40.3±20.4 66.1±7.5 77.8±10.9 Transplantation of CD34+ cells prestimulated for 24 hours and then transduced with a single hit of concentrated vector to irradiated NOD/SCID mice revealed that the RDpro vector transduced 55.1% of NOD/SCID repopulating human cells which was significantly higher than the MLV-A (12.6%) or GALV+ (25.1%) pseudotyped vectors. Thus, the STAR packaging system, especially with the modified RD114 envelope, appears to be a new valuable tool for the genetic modification of primitive human progenitor cells.

Abstract Introduction There is increasing awareness of the importance of sleep for health and wellness in children, and the impact technology has on sleep. However, many children are not getting the necessary sleep for optimal school functioning. The purpose of this project is to describe cellphone access, placement at night, and bedtime in 8–9-year-olds attending an elementary school in a rural area. Methods TigerCHAT is a school-based health education outreach program for children K-6th grades. It focuses on 45-minute sessions addressing various health topics, including sleep. Data are collected after IRB approval. In fall of 2022, nursing students led small groups of students in a sleep educational module during their gym period. Before education began, 50 3rd- grade students filled in a questionnaire regarding phone usage (do they have one, location during bedtime, bedtime and wake time). Results Frequencies, percentages, and ANOVA were run on the data to describe sleep and phone placement during the nighttime. Children ages 8-9 years (n = 50, 49% female, 51% male, 91.2% White, 8.4% Black, 46.4% classified as economically disadvantaged, 41% receive free or reduced lunch). Over half reported having a cellphone (n=31, 62% yes; n=19, 38% no). Of those with a cellphone, eleven (22%) reported having it under or by pillow, 11 (22%) reported having it on the bedside table, and 9 (18%) reported it not in their room at night. There was no significant difference in bedtime between those with a phone or without (F=.696, p=.402,) or where cellphone was located (in vs outside room) (F=1.55, p=.277). Children self-reported an average bedtime of 9:12pm (range 7:30pm-1am), and an average wake time of 5:15am (range 4:30am-6:30am), with an average total sleep time of 8.3 hours (range 4-10 hours). Conclusion The majority of students in this sample reported having access to a cellphone, and also reported having the cellphone close to them at night. While there was no significant difference in bedtime based on location or having a phone in this sample, it is still an important aspect of the sleep environment. Future studies should examine the significance of nighttime cellphone placement for school age and adolescent populations. Support (if any)

Abstract Abstract 4028 Poster Board III-964 CDAII, the most frequent type of congenital dyserythropoietic anemia family, is an autosomal recessive disease characterized by ineffective erythropoiesis, peripheral hemolysis, erythroblasts' morphological abnormalities and hypoglycosylation of some RBC membrane proteins. Recent studies indicated that CDAII is not a distinct glycosylation disorder but caused by a defect disturbing Golgi processing in erythroblasts. Linkage analysis located the CDAII gene in a 5 cM region on chromosome 20 and several candidate genes have been excluded. We recently investigated the cytoplasmic proteome of human red blood cells (RBCs) using a combinatorial peptide ligand library as a capturing agent to amplify the signal of low- and very-low abundance proteins: 1578 proteins, most of them unexpected, were identified allowing a deep exploration of the RBC pathways (Roux-Dalvai, Mol Cell Proteomics, 2008). In this study we used a proteomic-genomic approach to identify the candidate gene for CDAII by matching the data on the cytoplasmic proteome of human RBC with the chromosomic localization of CDAN2 locus. The analysis of RBCs cytoplasmic proteome allowed us to identify 17 proteins codified by genes located in the chromosomic region between 20p11.23 and 20q11.23: SNX5, SEC23B, DTD1, NAT5, GINS1, BCL2L1, MAPRE1, CHMP4B, EIF2S2, AHCY, ACSS2, GSS, EIF6, CPNE1, EPB41L1, RPRD1B(C20orf77), TGM2. Most of them were excluded because found to be associated to other diseases, already excluded in CDAII by previous works, or because not related by function to CDAII. Among the remaining proteins we focus on SEC23B for its possible role in the endoplasmic reticulum-to Golgi trafficking and its localisation on 20p11, the region with the highest LOD-score in CDAII after the recent mapping of the markers on the current contigs (Denecke et al, Biochim Biophys Acta, 2009). The 20 exons and intronic flanking regions of SEC23B gene were analysed by direct sequencing in 16 CDA II patients from 13 families; 13 different mutations were detected among the 28 mutated alleles identified: 6 of them were missense, 2 frameshift, 1 splicing and 4 stop codon. All the missense mutations affected highly conserved aminoacids, and were not found in 100 normal alleles examined. Two of them (c.40C>T and c.325G>A) were detected in various unrelated patients. Despite all exons and flanking intronic regions were sequenced, one patient failed to show mutations and two cases displayed only one mutation, suggesting the possibility that a second gene could be involved in CDAII. Patients' data are summarised on the table (*,° = members of the same family). SEC23B is a member of the SEC23/SEC24 family, a component of COPII coat protein complex which is involved in protein trafficking through membrane vesicles. Very recently it has been shown that knockdown of Zebrafish SEC23B leads to aberrant erythrocyte development (Schwarz et al, Nat Genet, 2009). Even if the exact function of human SEC23B is not completely clarified, abnormalities in this gene are likely to disturb ER-to Golgi trafficking affecting different glycosylation pathways, and ultimately accounting for the cellular phenotype observed in CDA II. Case Sex Origin Hb g/dL Retics 10e9/L Band3 hypoglyc Mutations Exons Effects 1 F N Italy 9.7 160 Yes c.40 C>T/c.428 A>CG 2/5 Arg 14 Trp/Frameshift 2 F C Italy 11.4 44 Yes c. 1821 delT/? 16/? Frameshift/? 3 F Bolivia 9.9 61 Yes c.568 C>T/c.1808 C>T 5/16 Arg 190 STOP/Ser 603 Leu 4 M Rumania 9.8 102 Yes c.40 C>T/c.1660 C>T 2/14 Arg 14 Trp/Arg 554 STOP 5 M S Italy 10.4 nd Yes c.325 G>A/c.325 G>A 4/4 Glu 109 Lys/Glu 109 Lys 6 F C Italy 8.3 103 Yes c.40 C>T/Ivs6 +1g>a 2/Ivs6 Arg 14 Trp/Splicing 7 M C Italy 9.7 100 Yes c.1489C>T/c. 2101 C>T 13/18 Arg 497 Cys/Arg 701 Cys 8° F N Italy 9.2 121 Yes c.325 G>A/c.325 G>A 4/4 Glu 109 Lys/Glu 109 Lys 9° M N Italy 11.3 115 Yes c.325 G>A/c.325 G>A 4/4 Glu 109 Lys/Glu 109 Lys 10° F N Italy 11.7 63 Yes c.325 G>A/c.325 G>A 4/4 Glu 109 Lys/Glu 109 Lys 11 F N Italy 11.6 104 Yes c.40 C>T/c.1043 A>C 2/9 Arg 14 Trp/Asp 348 Ala 12* M S Italy 11.9 90 Yes c.40 C>T/c.649 C>T 2/6 Arg 14 Trp/Arg 217 STOP 13* F S Italy 7.8 61 Yes c.40 C>T/ c.649 C>T 2/6 Arg 14 Trp/Arg 217 STOP 14 F N Italy 9.5 105 Yes c.325 G>A/c.325 G>A 4/4 Glu 109 Lys/Glu 109 Lys 15 M N Italy 10.4 236 Yes c.367 C>T/? 5/? Arg 123 STOP/? 16 F S Italy 10.7 87 Yes ?/? ?/? ?/? Disclosures: No relevant conflicts of interest to declare.

Abstract Background We previously reported (Styczynski et al, Blood, 2012) that hematopoietic stem cells (HSC) collection from bone marrow (BM) or peripheral blood (PB) in pediatric sibling donors is safe, however there is a risk of mild, short-term early side effects. No data are available so far on follow-up in children donating HSC. Objective To analyze donor safety and side effects related to HSC collection from BM or PB in pediatric sibling donors after 1-year. Donors 171 children: 90 male (M), 81 female (F), median age 9.2 (range: 0.7-17.3) yrs, including 45 children’s weight <20 kg, 64 between 20-40 kg, 82 weight >40 kg; 31 donors were <4 yrs, 40 at 4-8 yrs, 100 at age >8 yrs. There were 25 PB donors 9 (PBD) (18 M, 7 F; median age 11.0, range: 1.3-17.3 yrs ) and 146 BM donors (BMD) (72 M, 74 F; median age 8.3, range: 0.7-17.3 yrs). Methods Data from 14 participating EBMT Centers were registered on specific forms, sent to the PDWP office and statistically analyzed. Results During follow-up local pain was reported by 16/161 (9.9%) donors at catheter site (n=1) or collection site in 16 (14/137 BM; 2/24 PB, ns). 14 (8.1%) donors complained for pain persistence for 1-6 months (1mo-5, 2mo-5, 3mo-2, 5mo-1, 6mo-1). Late vomiting was observed in 7/163 (4.3%) (BMD only), and hematuria in 1 donor. Fever episodes were observed in 21/164 (12.8%) (21/140 BMD, p=0.045), lower respiratory tract infection in 3/164 (1.8%) (1/140 BMD, 2/25 PBD, p=0.056), upper respiratory tract infection in 21/171 (12.3%) (21/146 BM, p=0.046) and urinary tract infection in 5/171 (2.9%) (5/146 BMD, ns). No other infections (including gastroenterocolitis or hepatitis) were reported. Anemia was diagnosed in 6/164 (3.6%) (6/140 BMD, ns). At 1 year follow-up iron was supplemented in 24/164 (14.6%) (22/140 BMD, 2/24 PBD, ns) and folinic acid in 2/163 (1.2%) (BMD only). No other hematological problems (including thrombotic events) were reported. One donor was diagnosed for chronic disease (0.6%) (asthma), 4 (2.4%) had another hospital stay: physiotherapy (n=1), circumcision (n=1), plastic surgery due to an accident (n=1), and donation for MSC (n=1). Assessment of profile of psychological status consisted of a six item questionnaire. At 1-year follow-up, donors felt helpful in 132/154 (85.7%) cases (BMD 109/130, PBD 23/24, ns); happy in 117/149 (78.5%) cases (BMD 93/125, PBD 24/24, p=0.011); proud in 113/147 (76.8%) cases (BMD 91/124, PBD 22/23, p=0.039); depressed in 11/147 (7.5%) cases (BMD 11/124, PBD 0/23, ns) and responsible for recipient in 97/145 (66.9%) cases (BMD 83/122, PBD 14/23, ns). Willingness for subsequent HSC donation was reported by 113/147 (76.8%) children (BMD 94/125, PBD 19/22, ns). Conclusions At one-year follow-up after BM or PB HSC collection in pediatric sibling donors no major side effects were reported, however there is a risk of mild side effects. A donor registry should document and evaluate the course of minors who donate hematopoietic stem cells to better define possible risk factors of BM or PBSC harvest. Disclosures: Dreger: Riemser Pharma : Consultancy, Honoraria, Research Funding.

7169 Background: Erlotinib is an orally available, reversible inhibitor of the EGFR tyrosine kinase with a proven survival advantage for patients with locally advanced or metastatic NSCLC who have failed one prior chemotherapy regimen. Preliminary data suggest that never smokers respond particularly well, as assessed by both response and survival. Method: This is a phase IIIb, multicenter, open-label trial of erlotinib in patients with advanced NSCLC who have progressed following standard chemotherapy treatment. The trial allowed patients access to erlotinib therapy prior to FDA approval; patients could remain on study up to 9 months following approval. The co-primary objectives were best ORR (as assessed by investigator) and OS associated with erlotinib therapy in this group, and in patient subsets defined by tobacco history. Secondary objectives include evaluating safety; characterization of OS and RR in sub-populations, including histology, sex, ethnicity; duration of time on treatment. Patients and Treatment: Between August and November 2004, 229 patients were enrolled and treated. Erlotinib was given at the standard dose of 150mg once daily. Demographics are as follows: M/F% 60/40; median age 68 (27–90); ECOG PS% 0/1/2/3 25/44/23/7; squamous histology 34%, adenocarcinoma 45%; >1 prior regimen 47%; prior platinum 83%; never smoked 9%. Results: At the time of the final analysis (August 2005), 60% of subjects had died; data are therefore mature. Among the 229 treated subjects, the best ORR was 8.3% (CI: 5.2% - 12.4%). The ORR in never-smokers, previous smokers and current smokers was 28.6% (CI: 13.2% - 50.6%), 6.0% (CI: 3.0% - 10.4%) and 7.3% (CI: 2.0% - 19.0%), respectively. Median overall survival for all patients was 6.3 months (CI: 4.7 - 8.0). Median survival was 5.2 (CI: 4.2 - 7.3) and 6.3 months (CI: 3.6 - 9.2) in previous smokers and current smokers, respectively; and was not reached in never-smokers. Median duration of treatment was 10.6 weeks. One ILD-like event was reported (0.4%). Conclusions: No unexpected safety signals were seen. The observed ORR and survival data are consistent with the findings from the pivotal phase III randomized trial. [Table: see text]

BackgroundFibrotic changes of the internal organs, such as lungs, heart, kidneys, and gastrointestinal tract, characterize the clinical course of both limited (lcSSc) and diffuse cutaneous SSc (dcSSc), potentially leading to organ dysfunction. However, liver involvement is less defined.ObjectivesIn a cross-sectional study we investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidence of liver diseases due to heavy alcohol consumption, viral infection, drug.MethodsA total of 65 SSc patients were recruited, satisfied the 2013 ACR)/ (EULAR) classification. In addition to the clinical and laboratory data, modified Rodnan skin score (mRSS), and activity index, video-capillaroscopy, echocardiography, and lung function were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis and liver steatosis with CAP values ≥ 248 dB/m were considered consistent with mild steatosis (S1), ≥268 dB/m with moderate steatosis (S2) and ≥280 dB/m with severe steatosis (s3)ResultsThe median age of patients (60 women) was 50.5 years (range 20-80) and the median disease duration was 5.5 years (range 1-10). The median LS value was 4.65 kPa (range 3.1-8.3); the median CAP value was 220.5 (164-327). By Spearman Rank Correlation LS value vs age has a p value 0.02 (CI 95% 0.290.64), vs corticosteroid use has a p value 0.0032 (CI95% 0.179-0.731). On the contrary Cap value vs age has a p value 0.026 (CI 95% 0.04-0.64). Forty-six (70.8%) patients had no fibrosis (F=0); 17 (26%) had a LS value from 5.2 and 7.4; 3 patient (4.6%) LS>7.4 (F3) significant liver fibrosis. Eight patients (12.3%) had mild liver steatosis (CAP value was ≥ 248 dB/m) and 6 patient (9.2%) had moderate steatosis (S2) (CAP value ≥268 dB/m)ConclusionIn our studythe prevalence of significant liver fibrosis was relatively low (4.6%). Long-term corticosteroid therapy was associated with increased liver stiffness on Fibroscan. Thelow number of patients is a limitation of the study, we await the data relating to a more representative population.Reference[1]Maria Lorena et al;. J. Clin. Med. 2022Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Introduction: Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b on B-cell non-Hodgkin lymphoma. In the randomized cohort of GO29365, a Phase [Ph] Ib/II study (NCT02257567; data cut-off: April 30, 2018), Pola plus bendamustine and rituximab (Pola+BR) improved progression-free survival (PFS) and overall survival (OS) compared with BR alone in patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The study met its primary endpoint, with an independent review committee (IRC)-assessed complete response (CR) rate of 40.0% with Pola+BR vs 17.5% with BR. These results led to regulatory approvals of Pola+BR for the treatment of pts with R/R DLBCL. The study was later amended to include a single-arm Ph II extension (Ext) cohort of additional pts who received Pola+BR. Here, we report updated results from the GO29365 study, including the Ph Ib safety run-in cohort, Ph II randomized arms, and previously unpublished results from the Ext cohort. Methods: This open-label study enrolled pts with R/R DLBCL (aged ≥18 years, stem cell transplant [SCT]-ineligible, ECOG performance status of 0-2). Pts with Grade [Gr] &gt;1 peripheral neuropathy [PN] were excluded. In the initial study, Pola+BR was investigated in DLBCL in a Ph Ib safety run-in cohort (Pola+BR; N=6) and Ph II randomized arms (Pola+BR vs BR; N=80); full methods were previously described (Sehn et al. J Clin Oncol 2020). Pts in the Ext cohort received Pola+BR with the same dosing regimen (Pola 1.8mg/kg IV with each cycle of BR). The primary endpoint was IRC-assessed CR at primary response assessment [PRA] by PET-CT (modified Lugano criteria). Secondary endpoints included objective response rate (ORR), best objective response (BOR), OS, PFS, duration of response (DOR), and safety. Results: As of January 2, 2020, median follow-up for pts treated with Pola+BR was 56.1 mo in the safety run-in cohort (N=6), 42.9 mo in the randomized arm (N=40), and 9.7 mo for the Ext cohort (N=106). Baseline characteristics (Table 1) were largely similar between the randomized Pola+BR arm and the Ext cohort. Updated survival data from the randomized cohort (Pola+BR vs BR) showed the median IRC-assessed PFS (95% confidence interval [CI]) was 9.2 (6.0-13.0) vs 3.7 (2.1-4.5) mo (hazard ratio [HR] 0.4; 95% CI: 0.2-0.7); median OS (95% CI) was 12.4 (9.0-32.0) vs 4.7 (3.7-8.3) mo (HR 0.4; 95% CI: 0.2-0.7), respectively (Figure). In the Pola+BR arm, 6 pts (15%) had an IRC-assessed DOR of &gt;24 mo (range: 26.6-38.6 mo) at last follow-up; 5 pts received no new treatment, 1 pt underwent an allogeneic SCT. In the Ext cohort (N=106), the primary endpoint of IRC-assessed PET-CR at PRA was 39.6% (n=42; 95% CI: 30.3-49.6) (Table 2), consistent with that observed in the randomized Pola+BR arm (16/40; 40.0%). The BOR rate was 56.6% and best CR rate was 52.8%. The median (95% CI) IRC-assessed PFS and OS were 6.1 (5.1-8.0) and 11.0 (8.3-14.2) mo, respectively; however, OS was not fully mature. An exploratory subgroup analysis of all Pola+BR-treated pts (N=152) showed differences in median (m) PFS and OS between: pts who were primary refractory (n=97) vs non-primary refractory (n=55) (mPFS: 4.8 vs 12.6 mo; mOS: 7.8 vs 32 mo); pts who were refractory to last treatment (n=116) vs pts who were not (n=36) (mPFS: 5.3 vs 14.2 mo; mOS: 9.1 mo vs not reached); and pts who had received 1 (n=50) vs ≥2 (n=102) prior lines of therapy (mPFS: 10.4 vs 6 mo; mOS: 14 vs 9.5 mo). There were no new safety signals with Pola+BR. A safety analysis of all pts who received Pola+BR in the safety run-in, randomized and Ext cohorts (N=151) showed that 121 (80.1%) pts had Gr 3-4 adverse events (AEs), 84 (55.6%) had serious AEs, most commonly infections, febrile neutropenia, and pyrexia, and 18 (11.9%) had Gr 5 AEs, which were primarily infections. PN events of any grade were reported in 46 (30.5%) pts; 3 pts experienced Gr 3 PN, 2 of which were reported as muscular weakness. Secondary malignancies were reported in 4 (2.6%) pts. Conclusions: With additional follow-up for the randomized arms, the significant improvement in PFS and OS seen with Pola+BR vs BR persisted. The Ext cohort of additional pts who received Pola+BR (N=106) shows overall consistent efficacy with the randomized Pola+BR arm. No new safety signals were identified with Pola+BR. These data further strengthen the evidence that Pola+BR is an effective treatment for R/R DLBCL. An updated clinical cut-off date providing more mature data will be presented. Disclosures Sehn: Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria. Hertzberg:Bristol Myers Squibb: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Opat:CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding; AstraZenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Herrera:Immune Design: Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Assouline:AbbVie: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Research Funding; Pfizer: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; BeiGene: Consultancy, Honoraria, Research Funding. Flowers:Cancer Prevention and Research Institute of Texas: Research Funding; Eastern Cooperative Oncology Group: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Bayer: Consultancy; V Foundation: Research Funding; Kite: Research Funding; National Cancer Institute: Research Funding; BeiGene: Consultancy; Spectrum: Consultancy; Acerta: Research Funding; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; AbbVie: Consultancy, Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Burroughs Wellcome Fund: Research Funding. Kim:Takeda: Consultancy; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; Novartis: Consultancy; AstraZeneca: Consultancy. McMillan:Celgene: Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel expenses, Speakers Bureau. Ozcan:Janssen: Other: Travel support, Research Funding; Abdi Ibrahim: Other; Sanofi: Other; Jazz Pharmaceuticals: Other; Amgen: Honoraria, Other: Travel support; Bristol Myers Squibb: Other: Travel support; F. Hoffmann-La Roche Ltd: Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Celgene: Research Funding; Bayer: Research Funding; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Archigen Biotech: Research Funding. Salles:Karyopharm: Consultancy; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Genmab: Consultancy; Autolus: Consultancy; Debiopharm: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Other; Novartis: Consultancy, Honoraria, Other; Epizyme: Consultancy; Bristol Myers Squibb: Consultancy, Other. Musick:Roche/Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Hirata:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Chang:F. Hoffmann-La Roche: Current Employment, Current equity holder in private company. Ku:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Matasar:Rocket Medical: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Merck: Consultancy; Juno Therapeutics: Consultancy; Immunovaccine Technologies: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; IGM Biosciences: Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Teva: Consultancy.

Методами поляризационных и импедансных измерений изучено анодное поведение Mn5Si3-электрода в растворах (0.5–3.0) М NaОН в области от E коррозии до E выделения кислорода включительно. Сделан вывод, что поверхность силицида марганца в щелочном электролите обогащена металлическим компонентом сплава и продуктами его окисления. Установлены кинетические закономерности анодного поведения Mn5Si3, выяснены механизмы растворения и пассивации силицида, определены кинетические параметры реакции выделения кислорода. ЛИТЕРАТУРА Samsonov G. V., Dvorina L. A., Rud' B. M. Silitsidy [Silicides]. Moscow, Metallurgiya Publ., 1979, 272 p. (in Russ.) Agladze G. R., Kveselava V. M., Koiava N. Sh. V sb.: Elektrokhimiya margantsa [In: Manganese Electrochemistry], Tbilisi, AN GSSR Publ., 1978, vol. 7, pp. 118–126. (in Russ.) Shein A. B., Zubova E. N. Protection of Metals, 2005, vol. 41, no. 3, pp. 234–242. https://doi.org/10.1007/s11124-005-0034-z Nikolaichuk P. A., Shalyapina T. I., Tyurin A. G. Vestnik YuUrGU, 2010, no. 31, pp. 72–80. (in Russ.) Okuneva T. G., Panteleeva V. V., Shein A. B. Condensed Matter and Interphases, 2016, vol. 18, no. 3, pp. 383–393. URL: http://www.kcmf.vsu.ru/resources/t_18_3_2016_009.pdf (in Russ.) Polkovnikov S., Panteleeva V. V., Shein A. B. Vestnik Permskogo universiteta. Khimiya, 2017, vol. 7, no. 3, pp. 250–259. (in Russ.) Sukhotin A. M., Osipenkova I. G. Zhurnal prikladnoi khimii, 1978, vol. 51, no. 4, pp. 830–832. (in Russ.) Agladze R. I., Domanskaya G. M. V sb.: Elektrokhimiya margantsa, Tbilisi, AN GSSR Publ., 1957, vol. 1, pp. 503–514. (in Russ.) Agladze I., Domanskaya G.M. Zhurnal prikladnoi khimii, 1951, vol. 24, no. 9, pp. 917–514. (in Russ.) Petriashvili L. D. V sb.: Elektrokhimiya margantsa [In: Manganese Electrochemistry], Tbilisi, AN GSSR Publ., 1978, vol. 7, pp. 127–137. (in Russ.) Poirbaix M. Atlas of Electrochemical Equilibria in Aqueous solutions. Oxford, Perqamon Press, 1966, p. 664. Sukhotin A. M. Spravochnik po elektrokhimii [Handbook of Electrochemistry]. Leningrad, Khimiya Publ., 1981, 488 p. (in Russ.) Remi G. Kurs neorganicheskoi khimii [Course of Inorganic Chemistry]. Moscow, Mir Publ., 1972, 824 p. (in Russ.) Myamlin V. A., Pleskov Yu. V. Elektrokhimiya poluprovodnikov [Electrochemistry of Semiconductors]. Moscow, Nauka Publ., 1965, 338 p. (in Russ.) Gel'd P. V., Sidorenko F. A. Silitsidy perekhodnykh metallov chetvertogo perioda [Transition Metal Silicides of the Fourth Period]. Moscow, Metallurgiya Publ., 1981, 632 p. (in Russ.) Keddam M., Lizee J.-F., Pallotta C., Takenouti H. Electrochem. Soc., 1984, vol. 131, no. 9, p. 2016. https://doi.org/10.1149/1.2116010 Hepel M., Tomkiewicz M. Electrochem. Soc., 1985, vol. 132, no. 1, p. 32. https://doi.org/10.1149/1.2113786 Rabinovich V. A., Khavin Z. Ya. Kratkii khimicheskii spravochnik [Brief Chemical Hand Book]. Leningrad, Khimiya, Publ., 1978, 392 p. (in Russ.) Polkovnikov I. S., Shaidullina A. R., Panteleeva V. V., Shein A. B. Vestnik Permskogo universiteta. Khimiya, 2018, vol. 8, no. 3, pp. 325–341. DOI: 17072/2223-1838-2018-3-325-341 (in Russ.) Odynets L. L., Orlov V. M. Anodnye oksidnye plenki [Anodic Oxide Films]. Leningrad, Nauka Publ., 1990, 200 p. (in Russ.) Popov Yu. A. Teoriya vzaimodeistviya metallov i splavov s korrozionno-aktivnoi sredoi [Theory of Interaction of Metals and Alloys with a Corrosive-active Medium]. Moscow, Nauka Publ, 1995, 200 p. (in Russ.)

Abstract Background: Despite the existence of well-established clinical prognostic indices for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the 2 most common subtypes of NHL, significant heterogeneity in survival remains even within prognostic groups. SES has not previously been evaluated as a prognostic factor for NHL, particularly using an unselected patient population. We therefore used the large multiethnic CCR to examine NHL survival according to histology, race/ethnicity and neighborhood SES. Methods: NHL pts were identified from the CCR for the period 1988–97 using standardized ICD-0-3 classifications (morphology codes 9690–99 for FL & 9680–84 for DLBCL). Patients with evidence of HIV/AIDS were excluded. Neighborhood SES was assigned based on the address of residence at diagnosis, according to 1990 US Census Bureau census block group (each block contains about 1500 residents), and is based upon principal components of 7 indicator variables of SES (education level, proportion with blue collar job, proportion unemployed, median household income, proportion below 200% of poverty line, median rent & median home value). Using this index, we assigned each patient into an SES quintile (SES-1 lowest, SES-5 highest) based on the statewide distribution of neighborhood SES. We computed 5-year relative survival ± standard error (SE) with SEER*Stat software using customized race and SES-specific life tables based on US Census Bureau estimates for California residents. Results: Unselected DLBCL pts [n=13,604; comprising 73% non-Hispanic White (W), 4% Black (B), 14% Hispanic (H), 8% Asian/Pacific Islander (A)] & FL pts (n=7372; 82% W, 3% B, 11% H, 4% A) were identified. The overall 5 yr relative survival for DLBCL was 45.5% (SE 0.5) and for FL was 71.1% (SE 0.6); females had a better survival than males for DLBCL [F 48.3% (SE 0.7) vs. M 42.3% (SE 0.6)] but not for FL. Lower SES was associated with inferior survival for both DLBCL & FL (Table 1). Within SES groups there were not significant racial/ethnic differences in survival. However, in DLBCL, B (34%) and H (33%) pts were proportionally more likely to be in SES-1 than W (9%) or A pts (15%), and less likely to be in SES-5 (9% B, 10% H) than W (27%) or A (22%) pts. Similarly, in FL, B (39%) & H (26%) pts were also more likely than W (8%) & A (10%) pts to be in SES-1 and less likely to be in SES-5 (W-29%, A-32%, B-10%, H-11%). Conclusion: SES predicts survival in DLBCL and FL. Race/ethnicity differences in SES distribution are apparent in NHL patients, but when stratified by SES, race/ethnicity does not appear to predict for significant differences in NHL survival. 5 Year Relative Survival in DLBCL & FL by SES & Race SES-1 (%) SE (%) n SES-5 (%) SE (%) n W-non-Hispanic White; A-Asian/Pacific Islander; B-Black; H-Hispanic DLBCL 40.6 1.3 1905 49.4 1.0 3192 W 38.4 1.9 915 49.4 1.1 2701 A 44.0 4.2 168 48.2 3.5 244 B 45.0 4.2 185 54.3 7.3 51 H 41.6 2.1 637 48.9 4.0 196 FL 66.4 2.1 823 76.6 1.2 1959 W 66.3 2.7 502 77.1 1.2 1753 A 65.4 10.0 30 72.0 5.0 93 B 69.1 6.5 85 76.1 10.0 22 H 65.9 3.8 206 71.8 5.4 91

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The chemical vapour deposition method is widely used to synthesise high quality graphene with a large surface area. However, the cooling process leads to the formations of ripples and wrinkles in the graphene structure. When a self-adhered wrinkle achieves the maximum height, it then folds onto the surface and leads to a collapsed wrinkle. The presence of such deformations often affects the properties of graphene. In this article, we describe a novel mathematical model to understand the formation and geometry of these wrinkles. The stability of these wrinkles is examined based on variational derivations for the energy of each structure. The model provides detailed explanations for the geometry of these wrinkles which would help in tuning their properties. References J. Aljedani, M. J. Chen, and B. J. Cox. Variational model for collapsed graphene wrinkles. Appl. Phys. A 127.11, 886 (2021), pp. 1–13. doi: 10.1007/s00339-021-05000-y A. A. Balandin, S. Ghosh, W. Bao, I. Calizo, D. Teweldebrhan, F. Miao, and C. N. Lau. Superior thermal conductivity of single-layer graphene. Nano Lett. 8.3 (2008), pp. 902–907. doi: 10.1021/nl0731872 S. Chen, Q. Li, Q. Zhang, Y. Qu, H. Ji, R. S. Ruoff, and W. Cai. Thermal conductivity measurements of suspended graphene with and without wrinkles by micro-Raman mapping. Nanotech. 23.36, 365701 (2012). doi: 10.1088/0957-4484/23/36/365701 on p. C85). B. J. Cox, T. Dyer, and N. Thamwattana. A variational model for conformation of graphene wrinkles formed on a shrinking solid metal substrate. Mat. Res. Express 7.8, 085001 (2020). doi: 10.1088/2053-1591/abaa8f A. K. Geim. Graphene: Status and prospects. Science 324.5934 (2009), pp. 1530–1534. doi: 10.1126/science.1158877 on p. C85). K. Kostarelos and K. S. Novoselov. Graphene devices for life. Nature Nanotech. 9 (2014), pp. 744–745. doi: 10.1038/nnano.2014.224 F. Long, P. Yasaei, R. Sanoj, W. Yao, P. Král, A. Salehi-Khojin, and R. Shahbazian-Yassar. Characteristic work function variations of graphene line defects. ACS Appl. Mat. Inter. 8.28 (2016), pp. 18360–18366. doi: 10.1021/acsami.6b04853 R. Muñoz and C. Gómez-Aleixandre. Review of CVD synthesis of graphene. Chem. Vapor Dep. 19.10–12 (2013), pp. 297–322. doi: 10.1002/cvde.201300051 L. Spanu, S. Sorella, and G. Galli. Nature and strength of interlayer binding in graphite. Phys. Rev. Lett. 103.19, 196401 (2009). doi: 10.1103/PhysRevLett.103.196401 T. Verhagen, B. Pacakova, M. Bousa, U. Hübner, M. Kalbac, J. Vejpravova, and O. Frank. Superlattice in collapsed graphene wrinkles. Sci. Rep. 9.1, 9972 (2019). doi: 10.1038/s41598-019-46372-9 C. Wang, Y. Liu, L. Li, and H. Tan. Anisotropic thermal conductivity of graphene wrinkles. Nanoscale 6.11 (2014), pp. 5703–5707. doi: 10.1039/C4NR00423J W. Wang, S. Yang, and A. Wang. Observation of the unexpected morphology of graphene wrinkle on copper substrate. Sci. Rep. 7.1 (2017), pp. 1–6. doi: 10.1038/s41598-017-08159-8 Y. Wang, R. Yang, Z. Shi, L. Zhang, D. Shi, E. Wang, and G. Zhang. Super-elastic graphene ripples for flexible strain sensors. ACS Nano 5.5 (2011), pp. 3645–3650. doi: 10.1021/nn103523t Y. Wei, B. Wang, J. Wu, R. Yang, and M. L. Dunn. Bending rigidity and Gaussian bending stiffness of single-layered graphene. Nano Lett. 13.1 (2013), pp. 26–30. doi: 10.1021/nl303168w Z. Xu and M. J. Buehler. Interface structure and mechanics between graphene and metal substrates: A first-principles study. J. Phys.: Cond. Mat. 22.48, 485301 (2010). doi: 10.1088/0953-8984/22/48/485301 Y. Zhang, N. Wei, J. Zhao, Y. Gong, and T. Rabczuk. Quasi-analytical solution for the stable system of the multi-layer folded graphene wrinkles. J. Appl. Phys. 114.6, 063511 (2013). doi: 10.1063/1.4817768 W. Zhu, T. Low, V. Perebeinos, A. A. Bol, Y. Zhu, H. Yan, J. Tersoff, and P. Avouris. Structure and electronic transport in graphene wrinkles. Nano Lett. 12.7 (2012), pp. 3431–3436. doi: 10.1021/nl300563h

BackgroundThe aim of the Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) is to examine the disease course of patients with systemic lupus erythematosus (SLE) in relation to their type I interferon gene signature (IFNGS) status.1 IFNGS has been associated with SLE disease activity.2ObjectivesTo identify associations between IFNGS status and patient-reported outcomes (PROs) among patients receiving clinical care while enrolled in SPOCS.MethodsThis noninterventional, international, prospective, observational cohort study included adult patients (≥18 years) with moderate to severe SLE receiving standard therapy. Short Form 36 Health Survey version 2 (SF-36; 0–100), Lupus Quality of Life (LupusQoL; 0–100) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; 0–52) were assessed at baseline, 6 months, and 12 months. Higher scores indicate better outcomes. Analyses were stratified by high or low IFNGS status (4-gene test) at baseline.ResultsOf 827 patients, mean (standard deviation [SD]) age was 45.1 (14.0) years, 771 (93%) were female, 525 (63%) were IFNGS high, and 219 (26%) were IFNGS low. IFNGS-high patients were younger than IFNGS-low (mean [SD] 43.0 [13.7] vs 50.7 [12.9] years), had fewer comorbidities (83% vs 91%) and similar baseline disease activity (mean [SD]: SLE Disease Activity Index 2000, 9.8 [4.3] vs 9.2 [5.2]; Physician’s Global Assessment, both 1.5 [0.6]). At baseline, there were some differences in PROs between IFNGS-high and -low patients. At Month 12, changes in most domains did not meet the minimal clinically important difference (MCID). Slight improvement was observed only in selected domains in the IFNGS-high group. This group was younger and had fewer comorbidities at baseline. (Table 1, Figure 1).Table 1.PRO Scores at Baseline and Month 12 by IFNGS StatusBaselineMonth 12Change From BaselineMCID (≥)PROTotal (n=810)IFNGS HighIFNGS Low (n=219)Total (n=431)IFNGS HighIFNGS Low (n=147)TotalIFNGS HighIFNGS Low(n=525)(n=279)SF-36Physical Component Summary37.4 (10.5)38.3 (10.5)+35.2 (10.6)139.8 (10.8)41.7 (10.4)+35.7 (10.8)2.3 (7.6)3.0 (8.1)*0.6 (6.4)2.5Mental Component Summary43.2 (11.6)43.6 (11.7)42.7 (11.6)44.9 (11.2)45.9 (10.6)43.4 (11.5)0.9 (9.2)1.4 (9.6)-0.3 (8.4)2.5LupusQoLPhysical health56.4 (27.4)58.1 (27.0)+52.1 (27.7)60.5 (26.9)65.0 (25.3)+52.5 (27.7)2.6 (18.1)5.0 (19.2)*-1.4 (16.4)3.4Pain54.3 (30.3)55.7 (29.8)50.2 (30.8)61.4 (28.5)66.0 (26.5)+52.6 (29.1)5.4 (23.8)8.1 (25.2)0.7 (21.3)8.5Planning61.4 (32.2)63.7 (31.8)+57.0 (32.2)66.3 (29.6)70.8 (27.8)+58.5 (30.8)2.9 (24.4)4.2 (24.7)-1.0 (22.9)6.5Intimate relationships58.0 (34.8)61.2 (34.1)+50.9 (34.8)59.8 (33.9)65.6 (32.3)+50.6 (34.7)-0.6 (24.5)-0.7 (25.9)-0.8 (22.3)9.2Burden to others50.7 (32.6)50.7 (32.6)50.4 (33.5)56.4 (30.7)59.7 (29.5)51.8 (31.7)3.1 (25.4)5.6 (26.0)*0.1 (23.9)5.3Emotional health66.3 (25.6)66.1 (26.0)67.8 (24.8)71.1 (24.7)72.9 (23.8)69.2 (24.7)1.8 (19.4)3.1 (20.3)-0.5 (18.1)3.4Body image62.6 (29.4)61.0 (30.1)66.4 (28.3)68.2 (27.6)70.3 (27.4)65.1 (27.0)2.0 (23.9)*4.1 (24.3)*-0.4 (22.1)1.1Fatigue48.6 (27.8)49.9 (27.6)45.5 (28.2)53.7 (26.9)57.4 (26.2)+46.9 (25.7)2.1 (19.3)3.5 (20.0)-0.9 (18.7)3.9FACIT-F25.8 (13.4)26.9 (13.4)+23.4 (12.9)28.7 (13.2)31.1 (12.7)+24.6 (12.9)2.3 (9.6)3.2 (10.2)0.6 (8.5)4.0Data are mean (SD). Asterisks (*) indicate changes from baseline ≥ MCID. +Comparison between high and low IFNGS status by Mann-Whitney U test (nominal p-value<0.01).Data for n are patients per subgroup and do not reflect responses per PRO assessment.ConclusionIn this cohort study, patients with moderate to severe SLE had poor health status, health-related quality of life, and fatigue. A clinically meaningful change was not met in most PROs, suggesting patients continue to have a high need for improved treatment options.References[1]Hammond ER. BMJ Open 2020;10:e036563.[2]Dall’era MC. Ann Rheum Dis 2005;64:1692–7.AcknowledgementsWriting assistance by Shelley Harris, PhD (Fishawack). This study was sponsored by AstraZeneca.Disclosure of InterestsMartin Aringer Speakers bureau: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, HEXAL, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, UCB, Consultant of: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, GSK, Pfizer, Roche, Sanofi, Laurent Arnaud Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Christine Peschken Consultant of: AstraZeneca, GSK, Grant/research support from: AstraZeneca, Richard Furie Speakers bureau: AstraZeneca, Genentech, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: GSK, Novartis, Paid instructor for: AstraZeneca, Biogen, Eli Lilly, Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, Servier, Grant/research support from: Abbvie, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, Caroline Seo Shareholder of: AstraZeneca, Employee of: AstraZeneca, Eleni Rapsomaniki Employee of: AstraZeneca, Jonatan Hedberg Shareholder of: AstraZeneca, Employee of: AstraZeneca, Jacob Knagenhjelm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Tina Grünfeld Eén Shareholder of: AstraZeneca, Employee of: AstraZeneca, Barnabas Desta Shareholder of: AstraZeneca, Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca, Alessandro Sorrentino Shareholder of: Galapagov, Abbott Laboratories, Gilead Sciences, Moderna, Employee of: Janssen, Sanofi, AstraZeneca, Heide Stirnadel-Farrant Shareholder of: AstraZeneca, GSK, Employee of: AstraZeneca

[1] Hawkey CR, Yap T, Pereira J, Moore DA, Davidson RN, Pasvol G, et al. Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis. Clinical infectious diseases. 2005;40(9):1368-71. [2] Breton G. Syndrome inflammatoire de reconstitution immune (IRIS) associé à la tuberculose. Journal des Anti-infectieux. 2012;14(4):180-5. [3] Cheng V, Ho P, Lee R, Chan K, Woo P, Lau S, et al. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. European Journal of Clinical Microbiology and Infectious Diseases. 2002;21(11):803-9. [4] Al-Majed S. Study of paradoxical response to chemotherapy in tuberculous pleural effusion. Respiratory medicine. 1996;90(4):211-4. [5] Campbell I, Dyson A. Lymph node tuberculosis: a comparison of various methods of treatment. Tubercle. 1977;58(4):171-9. [6] Memish Z, Mah M, Mahmood SA, Bannatyne R, Khan M. Clinico‐diagnostic experience with tuberculous lymphadenitis in Saudi Arabia. Clinical microbiology and infection. 2000;6(3):137-41. [7] Choremis C, Padiatellis C, ZOU MLD, Yannakos D. Transitory exacerbation of fever and roentgenographic findings during treatment of tuberculosis in children. American review of tuberculosis. 1955;72(4):527. [8] Orlovic D, Smego J. Paradoxical tuberculous reactions in HIV-infected patients. The International Journal of Tuberculosis and Lung Disease. 2001;5(4):370-5. [9] Park I-S, Son D, Lee C, Park JE, Lee J-S, Cheong M-H, et al. Severe paradoxical reaction requiring tracheostomy in a human immunodeficiency virus (HIV)-negative patient with cervical lymph node tuberculosis. Yonsei medical journal. 2008;49(5):853-6. [10] Martinez V, Bricaire F. Réactions paradoxales. La Presse Médicale. 2006;35(1):1753-6. [11] Narita M, Ashkin D, Hollender ES, Pitchenik AE. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. American journal of respiratory and critical care medicine. 1998;158(1):157-61. [12] Vidal CG, Garau J. Systemic steroid treatment of paradoxical upgrading reaction in patients with lymph node tuberculosis. Clinical infectious diseases. 2005;41(6):915-6. [13] Rakotoarivelo R, Vandenhende M-A, Michaux C, Morlat P, Bonnet F. Réactions paradoxales sous traitement antituberculeux chez des personnes non infectées par le VIH: quatre nouvelles observations et revue de la littérature. La Revue de médecine interne. 2013;34(4):202-8. [14] Cheng V, Yam W, Woo P, Lau S, Hung I, Wong S, et al. Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients. European Journal of Clinical Microbiology and Infectious Diseases. 2003;22(10):597-602. [15] Rao GP, Nadh BR, Hemaratnan A, Srinivas T, Reddy PK. Paradoxical progression of tuberculous lesions during chemotherapy of central nervous system tuberculosis: report of four cases. Journal of neurosurgery. 1995;83(2):359-62. [16] Fontanilla J-M, Barnes A, Von Reyn CF. Current diagnosis and management of peripheral tuberculous lymphadenitis. Clinical Infectious Diseases. 2011;53(6):555-62. [17] Guinchard A-C, Pasche P. Lymphadénite tuberculeuse cervicale et réaction paradoxale: diagnostic et traitement. ORL. 2012;356(34):1860-5. [18] Colebunders R, John L, Huyst V, Kambugu A, Scano F, Lynen L. Syndrome inflammatoire de reconstitution immunitaire de la tuberculose dans les pays à ressources limitées. Int J Tuberc Lung Dis. 2006;10(9):946-53. [19] Malone J, Paparello S, Rickman L, Wagner K, Monahan B, Oldfield E. Intracranial tuberculoma developing during therapy for tuberculous meningitis. Western Journal of Medicine. 1990;152(2):188. [20] Valdez LM, Schwab P, Okhuysen PC, Rakita RM. Paradoxical subcutaneous tuberculous abscess. Clinical infectious diseases. 1997;24(4):734-. [21] Bouchez B, Arnott G, Colover J. Paradoxical expansion of intracranial tuberculomas during chemotherapy. The Lancet. 1984;324(8400):470-1. [22] [Recommendations of the French Language Pneumology Society for tuberculosis management in France: consensus conference. Nice, France, 23 January 2004]. Revue des maladies respiratoires. 2004;21(3 Pt 2):S3-104. [23] Rabar D, Issartel B, Petiot P, Boibieux A, Chidiac C, Peyramond D. Tuberculomes et méningoradiculite tuberculeuse d’évolution paradoxale sous traitement. La Presse Médicale. 2005;34(1):32-4. [24] Chambers S, Record C, Hendrickse W, Rudge P, Smith H. Paradoxical expansion of intracranial tuberculomas during chemotherapy. The Lancet. 1984;324(8396):181-4. [25] Safdar A, Brown AE, Kraus DH, Malkin M. Paradoxical reaction syndrome complicating aural infection due to Mycobacterium tuberculosis during therapy. Clinical infectious diseases. 2000;30(3):625-7. [26] Hejazi N, Hassler W. Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report. Infection. 1997;25(4):233-9.

During a survey conducted in October 2013 in tomato greenhouses in Diano Marina (Imola Province, northwest Italy), in a single greenhouse, unusual disease symptoms were observed in four out 1,400 (~0.3%) of tomato plants cv. Ingrid, grafted on ‘Beaufort’ rootstock. Symptoms including shortened apical internodes associated with tiny, deformed, and brittle chlorotic leaves, while ripe fruits appeared reduced in size and pale red. Samples of leaves from the four plants were collected and examined using commercial antisera (Bioreba AG, Reinach, Switzerland) by double antibody sandwich (DAS)-ELISA against Tomato spotted wilt virus, Cucumber mosaic virus, Alfalfa mosaic virus, Tomato/Tobacco mosaic viruses, and by indirect plate trapped antigen (PTA)-ELISA against potyviruses (potygroup test). None of the tested viruses were detected in the four leaf samples. In addition, PCR tests for begomoviruses and phytoplasmas were also negative. In a host range study, the original symptoms, consisting mainly of stunting and chlorosis, were reproduced within ~10 days in tomato seedlings (Momor line), mechanically inoculated at two true leaves stage with sap extract obtained from the four symptomatic tomato plants, whereas no symptoms were observed in Chenopodium amaranticolor, C. quinoa, Nicotiana tabacum (cv. Xanthi nc), N. glutinosa, or Phaseolus vulgaris (cv. Borlotto rosso). Total RNAs extracted with the RNeasy Plant Mini Kit (Qiagen, Hilden, Germany) from symptomatic samples were tested in RT-PCR using pospiviroids generic primers PSTVd-32/33 (1), designed to amplify the whole genome of Potato spindle tuber viroid (PSTVd), Tomato apical stunt viroid (TASVd), and Columnea latent viroid (CLVd), and CEVd-FW/RE primers, designed to amplify the whole genome of Citrus exocortis viroid (CEVd) and TASVd (3). Each of the four samples yielded amplicons of the same size (364 bp) with both primer combinations. The identity of the viroid was then determined by sequencing, on both strands, amplicons obtained from the four symptomatic plants at MWG (Ebersberg, Germany). Sequences obtained were identical, showing the highest nucleotide identity (99.7%) with the TASVd isolate Sj1 (AM777161), identified in Germany on Solanum jasminoides. The sequence was deposited in GenBank (Accession No. HG916812) and the field isolate named To1-IT. Two other cases of pospiviroid infection in tomato in Italy have been reported so far and the viroid species detected were PSTVd (2) and CLVd (4), respectively. To our knowledge, this is the first report of TASVd infecting tomato in Italy. The origin of this infection is still unclear, although based on the biological properties and sequence similarity, the To1-IT isolate probably originated from an ornamental species, most likely S. jasminoides, as recently reported for other tomato TASVd isolates, according to their biological and genetic features (5). References: (1) F. Di Serio. J. Plant Pathol. 89:297, 2007. (2) B. Navarro et al. J. Plant Pathol. 91:723, 2009. (3) N. Önelge. Turk. J. Agric. For. 21:419, 1997. (4) G. Parrella et al. Acta Hortic. 914:149, 2011. (5) J. Th. J. Verhoeven et al. Eur. J. Plant Pathol. 133:803, 2012.

BackgroundNovel treatment options are needed for pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Upadacitinib (UPA) is an oral, selective Janus kinase (JAK) inhibitor with a positive benefit-risk profile in adult patients with moderate-to-severe active rheumatoid arthritis.[1,2]ObjectivesTo evaluate the safety and efficacy of UPA in pediatric patients with pcJIA.MethodsThis open-label, 3-part, phase 1 trial (NCT03725007) enrolled pediatric patients aged 2 to < 18 years with pcJIA and ≥ 5 active joints at 31 sites across North America, Europe, and Asia. UPA was dosed as a twice-daily oral solution or once-daily tablet based on body weight. Part 1 evaluated multiple ascending doses of UPA for 7 days. Parts 2 and 3 evaluated long-term safety and efficacy of UPA for up to 156 weeks. This interim analysis (cutoff date of 22 September 2022) evaluated all available safety data in parts 1, 2, and 3; efficacy was evaluated in parts 1 and 2 through week 12. Efficacy endpoints included the JIA American College of Rheumatology (JIA ACR) 30, 50, and 70 response; the Childhood Health Assessment Questionnaire (C-HAQ); and the 27-point Juvenile Arthritis Disease Activity Score based on C-reactive Protein (JADAS-27 [CRP]).ResultsA total of 57 pediatric patients (78.9% female) with mean (SD) age of 9.5 (4.4) years and mean (SD) weight of 38.1 (20.4) kg received UPA; of these, 51 patients were treated in parts 1 and 2. In part 1, 8 (15.7%) of 51 patients reported adverse events (AEs) through 7 days; no patients reported serious AEs or AEs leading to treatment discontinuation. At a mean (median) duration of exposure of 514.9 (412.0) days, 52 (91.2%) of 57 patients reported AEs that were predominately mild to moderate in severity (Table 1). The most common treatment-emergent AEs were COVID-19 infection (n = 23/57, 40.4%), upper respiratory tract infection (n = 23/57, 40.4%), nasopharyngitis (n = 13/57, 22.8%), gastroenteritis (n = 10/57, 17.5%), pyrexia (n = 10/57, 17.5%), abdominal pain (n = 9/57, 15.8%), and nausea (n = 8/57, 14.0%). The most common AEs of special interest included elevated creatine phosphokinase levels (n = 6/57, 10.5%), hepatic disorder (n = 3/57, 5.3%), and neutropenia (n = 2/57, 3.5%); all were nonserious events. Six (31.6%) of 19 patients in the group aged 12 to <18 years reported serious AEs and 2 (10.5%) reported AEs leading to treatment discontinuation. A high proportion of patients across all age groups achieved JIA ACR30, 50, and 70 response at week 12 (Figure 1). Improvement from baseline to week 12 in C-HAQ and JADAS-27 [CRP] scores was observed across all age groups.ConclusionIn pediatric patients with pcJIA, UPA was well tolerated and associated with improvements in disease activity and physical function at week 12.References[1] Burmester GR, et al.Lancet.2018;391:2503-12.[2] Smolen JS, et al.Lancet.2019;393:2303-11.Table 1.Interim Analysis of Safety of Upadacitinib up to 156 Weeks(All Patients Treated in Parts 1, 2, and 3)TEAEAge 2 to <6 years n = 14Age 6 to <12 years n = 24Age 12 to <18 years n = 19Total N = 57Patients with TEAE (%)Any AE11 (78.6)22 (91.7)19 (100)52 (91.2)Any serious AE006 (31.6)6 (10.5)AE leading to discontinuation of study drug002 (10.5)2 (3.5)Deaths0000AEs of special interestSerious infections001 (5.3)a1 (1.8)aOpportunistic infection001 (5.3)b1 (1.8)bHepatic disorder02 (8.3)c1 (5.3)c3 (5.3)cAnemia1 (7.1)001 (1.8)Neutropenia02 (8.3)02 (3.5)Lymphopenia001 (5.3)1 (1.8)Elevated creatine phosphokinase03 (12.5)3 (15.8)6 (10.5)TEAE, treatment-emergent adverse event.aUpper respiratory tract infection.bCandida oesophagitis infection.c1 hepatosplenomegaly event, 2 high AST events, and 2 high ALT events.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approving the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. All authors agreed to submit this abstract to the EULAR 2023 Congress. Medical writing support was provided by Michael Dyle, PhD, of JB Ashtin, and funded by AbbVie.Disclosure of InterestsHermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, and Pfizer, Consultant of: AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cerocor, Eli Lilly, EMD Serono, Idorsia, Janssen, GlaxoSmithKline, F Hoffmann-La Roche, Merck, Novartis, R-Pharm, and Sanofi, Gerd Horneff Grant/research support from: AbbVie, Bayer, Chugai, GlaxoSmithKline, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi, Ivan Foeldvari Consultant of: Eli Lilly, Hexal, Medac, Novartis, and Pfizer, Jordi Anton Consultant of: AbbVie, Alexion, Amgen, Gebro, GSK Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, and Lilly, Grant/research support from: AbbVie, Alexion, Amgen, Gebro, GSK Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, and Lilly, Mohamed-Eslam Mohamed Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Yuli Qian Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Kristina Unnebrink Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Shuai Hao Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Heidi Camp Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Nasser Khan Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Anna Shmagel Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie.

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BackgroundOlokizumab (OKZ) is an interleukin-6-inhibitor for treatment of rheumatoid arthritis (RA). In these analyses we present patient reported outcomes (PROs) reported by TNF-IR patients with moderate to severely active RA receiving OKZ or placebo in a phase 3 randomized controlled trial (RCT) (ClinicalTrials.gov number, NCT02760433).ObjectivesTo assess the effect of OKZ treatment compared with placebo in patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), fatigue (FACIT-F) and health related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores) at 12 weeks.Methods368 patients were randomized 2:2:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg q4w, or placebo, plus MTX. PROs were assessed at baseline, weeks 12 (primary endpoint) and 24. At week 16, all patients receiving placebo were switched to either OKZ dose. Between groups differences in least-squares mean (LSM) changes from baseline were analyzed, p < 0.05 considered significant; nominal p-values for PROs not in the hierarchy.ResultsBaseline demographics and disease characteristics were comparable between groups. At week 12, treatment with OKZ q2w compared with placebo resulted in significantly greater LSM changes from baseline in Pain, HAQ-DI, FACIT-F, SF-36 PCS, MCS and 4 domains; with OKZ q4w in PtGA, Pain, SF-36 MCS and 4 domains (Table 1, Figure 1). Improvements reported at week 12 in PROs continued or increased with both doses of OKZ until week 24. Post hoc analyses demonstrated that a higher proportion of patients receiving OKZ reported improvements ≥minimum clinically important differences vs placebo (p<0.05) in FACIT-F, SF-36 PCS and MCS scores, indicating that these changes translated into clinically meaningful benefits on an individual patient basis. Numbers needed to treat to gain these benefits in fatigue and physical function ranged from 9.2 - 15.4 with OKZ q2w vs 10.5 - 13.3 with OKZ q4w, respectively.Table 1.Mean baseline values and LSM changes from baseline to week 12 for PROsBaseline, mean (standard deviation)12 weeks LSM changes (standard error)OKZ q2w, N=138OKZ q4w, N=161Placebo, N=69OKZ q2w, N=138OKZ q4w, N=161Placebo, N=69PtGA-VAS (mm)64.8 (20.5)68.1 (19.1)72.1 (18.5)-24.9 (2.1)-25.0(1.9)*-16.9 (2.9)Pain-VAS (mm)67.2 (19.5)69.3 (19. 1)69.6 (21.9)-28.2 (2.2)**-27.5(2.0)**-15.0 (3.0)HAQ-DI†1.79 (0.53)1.78 (0.56)1.78 (0.64)-0.49 (0.05)*-0.39(0.04)-0.32(0.07)SF-36 PCS score31.4 (6.8)30.6 (7.2)30.6 (5.9)6.9 (0.7)**5.7 (0.6)3.9 (0.9)SF-36 MCS score44.3 (12.6)44.5 (11.1)45.1 (10.2)4.1 (0.8)*3.4 (0.8)*0.5 (1.1)Physical functioning29.9 (7.9)29.8 (8.5)29.6 (8.4)6.1 (0.8)5.2 (0.7)3.7 (1.1)Role physical32.8 (6.9)33.1 (7.4)33.7 (6.8)6.0 (0.7)5.0 (0.7)*3.3 (1.0)Bodily pain34.5 (6.9)33.2 (6.0)33.0 (6.6)8.5 (0.7)***7.8 (0.7)***3.7 (1.0)General health38.3 (8.3)36.5 (8.6)36.9 (8.5)4.7 (0.7)*3.3 (0.6)2.1 (1.0)Vitality40.8 (10.1)40.7 (9.5)41.1 (8.1)5.7 (0.8)6.0 (0.7)*3.0 (1.1)Social functioning38.8 (9.9)38.7 (9.8)39.6 (9.3)6.7 (0.8)***3.6 (0.8)*0.2 (1.2)Role emotional39.1 (12.5)39.1 (11.2)38.9 (11.1)4.3 (0.9)*3.4 (0.8)1.0 (1.2)Mental health41.4 (11.6)41.4 (10.5)42.2 (10.3)4.4 (0.8)4.6 (0.8)1.9 (1.1)FACIT-Fatigue27.0 (10.2)26.6 (10.6)27.3 (9.9)7.8 (0.9)*6.8 (0.8)4.6 (1.2)Footnotes: NRI for Missing data.†, secondary endpoint; *p≤0.05, **p<0.01, ***p<0.001 vs placebo;Figure 1.SF-36 domain changes from baseline to week 12. *p≤0.05, **p<0.01, ***p<0.001 for OKZ q2w vs placebo; *p≤0.05, **p<0.01, ***p<0.001 for OKZ q4w vs placebo; AGNorms, age- and gender-matched normative values; BL, baseline.ConclusionTreatment with OKZ over 12 weeks resulted in statistically significant improvements in PROs vs placebo reported by TNF-IR RA patients. Benefits were more frequently reported by patients receiving OKZ q2w than q4w in this phase 3 RCT of limited size in treatment experienced patients.AcknowledgementsR-Pharm funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship.Disclosure of InterestsVibeke Strand Consultant of: Abbvie, Amgen, Arena, AstraZeneca, Bayer, BMS, Boehringer, Ingelheim, Chemocentryx, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Inmedix, Janssen, Kiniksa, Lilly, Novartis, Pfizer, Regeneron, Rheos, R-Pharm, Samsung, Sandoz, Sanofi, Scipher, Servier, Setpoint, Sorrento, Spherix, UCB, Ernest Choy Consultant of: Abbvie, Amgen, Bristol Myer Squibbs, Chugai Pharma, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, RPharm, Roche, Sanofi, and UCB., Grant/research support from: Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi and UCB, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Tatiana Lisitsyna: None declared, Alexander Lila Consultant of: Abbvie, Amgen, Bayer, Biotechnos, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, RPharm, Roche, Sanofi, Stada, Viatris and UCB, Grant/research support from: Novartis, Pfizer, Sofia Kuzkina Employee of: R-Pharm, Mikhail Samsonov Employee of: R-Pharm, Eugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer

The rust fungus Phragmidium tuberculatum Jul. Müll. is a common pathogen on Rosa spp., on which all life cycle stages are formed. Symptoms occur in spring and may include distorted stems, yellow spots on the upper leaf surface, and a bright orange spore mass formed on the abaxial leaf surface. In late summer, sori become speckled with black as fascicles of teliospores develop. The current known distribution of P. tuberculatum is mostly limited to Europe with some occurrence in Asia and into Australasia (2). There is some documented occurrence in North America (Alaska, Connecticut, and Canada [2]), where most rose rust disease is attributed to P. mucronatum (Pers.) Schltdl. This study used a combination of molecular and morphological analyses on newly collected material from across North America (California: BPI877978, PURN7783; Oregon: BPI877980; Massachusetts: BPI877977; and Quebec: BPI877979) and herbarium material from South and Central America (Honduras: BPI864186; and Argentina: BPI843677; both previously identified as P. mucronatum) to document a much broader distribution of P. tuberculatum. Collectively, teliospores from these collections are 4 to 6 celled, dark to black-brown, warted, elongated to cylindrical, 64.7 to 92.4 μm in length by 23.1 to 39.3 μm in width (average 77.6 × 30.0 μm) (30 teliospores from 2 leaves), with 2 to 3 pores/cell and a pronounced hyaline apiculus 4.6 to 18.5 μm long (average 8.3 μm). P. tuberculatum is similar morphologically to P. mucronatum, but sensu Gäumann (3) differs in having wider (30 to 36 μm) and longer (65 to 110 μm) teliospores with an average of 6 to 8 cells/spore. However, the two are easily distinguished by DNA analyses (4). The 28S sequences were amplified using the protocols described in Aime (1) and compared phylogenetically to 28S sequences available in the GenBank database for P. tuberculatum, P. mucronatum, and other Phragmidium spp. (4). In a maximum likelihood analysis, all isolates formed a 99% bootstrap supported clade with P. tuberculatum sequences from Germany, and shared 100% sequence identity with JF907675 P. tuberculatum. In contrast, comparison with HQ421646 P. mucronatum produced only 92% identity (e.g., 836/911 bp for PURN7783). This information indicates that P. tuberculatum is likely to be widespread in the Americas but simply misidentified as P. mucronatum, as was found to be the case for the two herbarium specimens sampled. Detailed examination of historical herbarium material may help to pinpoint how long the fungus has been present and the current extent of its distribution. The rose rust fungus is not considered to be a problem economically, but its spread within North America may be an indicator of commercial practices that serve as a vector for other diseases on ornamental plants. Voucher specimens have been deposited in the U.S. National Fungus Collections (BPI) and Arthur Fungarium (PUR); voucher sequences are deposited in GenBank (Accession Nos. KJ841917 to 23). References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) J. F. Arthur. Manual of the rusts in United States and Canada. Purdue Research Foundation, 1934. (3) E. Gäumann. Die Rostpilze Mitteleuropas mit besonderer Berücksichtigung der Schweiz. Büchler, Bern, 1959. (4) C. M. Ritz et al. Mycol. Res. 109:603, 2005.

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Abstract Differences in baseline features and follow-up among patients with chronic myeloid leukemia (CML) according to age at diagnosis have been recently reported in cohorts from clinical controlled trials (Castagnetti F et al, 2015). To evaluate this issue in a real-life setting, we revised 207 consecutive CML patients treated at our Institution with imatinib frontline from 6/2002 to 6/2013, dividing them in young adults (>20 <45 years) (YA), middle-aged adults (≥45 <65 years) (MA) and elderly (≥65 years) (EL). The main features at baseline of the whole cohort and of the 3 age groups are reported in the Table. Table.ALLYAMAELpN° of patients207617274M/F108/8930/3140/3238/360.752Median WBC (x 109/l)IQR66.1 (32.7 - 119.0)109.8 (65.9 - 148.0)59.5 (31.3 - 126.6)40.1 (26.5 - 81.4)<0.001Median Hb (g/dl)(IQR)12.5 (11.0 - 13.5)11.7 (9.8 - 12.7)12.7 (11.0 - 14.2)12.8 (11.3 - 13.7)0.002Median PLT (x 109/l)IQR414 (275 - 616)445 (291 - 597)378 (262 - 546)457 (271 - 732)0.287Spleen enlargement (>5cm) N° (%)17 (8.3)11 (18.3)4 (5.6)2 (2.7)0.003Sokal score (N°)Low/Int/High89/93/2047/9/338/27/54/57/12<0.001Comorbidities ≥ 2, N° (%)77 (37.2)5 (8.1)26 (36.1)46 (62.1)<0.001 The rates of complete cytogenetic response (CCyR) were similar (86.4% in YA, 95.5% in MA and 91.0% in EL, p=0.227) while the rate of major molecular response was higher in the MA group (89.7% vs 63.8% in YA and 75.8% in EL, p=0.001). The number of events (permanent discontinuation due to toxicity, primary or secondary resistance, any death for CML related or unrelated causes) was lower in the MA group [8 (11.1%) vs 21 (34.4%) in YA and 28 (37.8%) in EL, p=0.001]: no difference was observed in the rate of evolution to blastic phase [3 (4.9%) in YA, 1 (1.4%) in MA and 2 (2.7%) in EL, p=0.478]. The number of deaths was higher in the EL group [12 (16.2%) vs 2 (3.2%) in YA and 0 in MA, p<0.001]: it is worth of note, however, that 11/12 deaths in the EL group were not related to CML progression. The 4-year event-free survival (EFS) for the whole cohort was 73.5% (95%CI 67.0 - 80.0): the 4-year EFS in the MA group [92.0% (95%CI 85.1 - 98.9)] was significantly higher than in YA group [67.3% (95%CI 55.1 - 79.5)] and in EL group [61.1% (95%CI 49.5 - 73.7)] (p=0.001). The 4-year overall survival (OS) for the whole cohort was 94.4% (95%CI 90.9 - 97.9): the 4-year OS in the EL group [72.4.% (95%CI 56.9 - 87.9)] was significantly lower than in YA group [96.3% (95%CI 91.2 - 100)] and in MA group (100%) (p<0.001). In conclusion, age at diagnosis influences significantly the course of CML patients treated with imatinib: the MA group has the best follow-up with an excellent OS and EFS, while the relatively lower OS and EFS in the EL group are clearly related to the incidence of unrelated deaths like in the general aged population. A possible explanation of the counterintuitive worse course of YA group is the delayed diagnosis in these patients (higher WBC counts, lower Hb levels, higher rate of spleen enlargement > 5 cm) compared to aged patients, who have often concomitant diseases and make routinely blood analyses: however, a more aggressive biology of CML in YA could not be excluded and warrants further investigations. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: There is a lack of evidence or consensus on the optimum frequency and duration of mammographic surveillance and follow-up for breast cancer patients aged 50 years and older at diagnosis. Mammo-50 will provide clinicians with valuable, risk-adjusted information to guide their future practice and is due to report December 2023. Quality of life (QoL) was assessed in a sub-study of the main trial. Methods: A multi-centre, randomised controlled, phase III trial of annual mammography versus 2-yearly for conservation surgery and 3-yearly for mastectomy patients with an observational cohort to explore reasons for non-participation. The trial randomised 5235 women between April 2014 and September 2018 and a further 915 registered in the cohort; 90% of women agreed to participate in the QoL sub-study. QoL questionnaires were completed at trial entry (3 years post-surgery) and then annually for up to 10 years. The distress thermometer was used as a patient reported measure of distress and concerns throughout the trial. The trial team contacted the patient’s clinical care team informing them of the reasons causing patients’ high levels of distress. Results: A total of 4521 (74%) women completed the distress thermometer at baseline. Of these, 289 (6.4%) reported high levels of distress (score 8-10), 825 (18.2%) medium levels of distress (score 5-7), 2033 (45.0%) low levels of distress (1-4) and 1374 (30.4%) reported no distress. Levels of distress were similar across clinical characteristics including surgery type, disease type and ER status, but differed for hormone therapy use (p=0.004). Women who had stopped hormone therapy tended to have higher levels of distress than those who had never had hormone therapy or for whom hormone therapy was ongoing. The most common reasons for causing high levels of distress (score, 8-10) in the 289 patients were sleep problems and/or nightmares (135 (47%)), fatigue, exhaustion or extreme tiredness (132 (46%)), worry, fear or anxiety (111 (38%)), hot flushes (94 (33%)), pain (89 (31%)), memory or concentration (84 (29%)) and sadness or depression (84 (29%)) of patients. Conclusions: Within the Mammo-50 trial, 6.4% of women reported high levels of distress upon trial entry. A quarter of women reported high/medium levels of distress with sleep, fatigue, worry, hot flushes, memory and sadness/depression being the main concerns. Levels of distress were highest in those women who had stopped hormone therapy. These results have been fed back to the UK NCRI breast cancer symptom management group whose remit it is to identify and provide guidelines for supporting women with unmet needs. Acknowledgement and disclaimer: This study is funded by the NIHR HTA programme (project ref. 11/25/03). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Citation Format: Amy F. Campbell, Andrea Marshall, Janet A. Dunn, Peter K. Donnelly, Andy J. Evans, Nada I. Elbeltagi, David A. Cameron, Riccardo A. Audisio, Lesley Turner, Eila Watson, Sophie J. Gasson, Annie M. Young, Alastair M. Thompson, Mammo-50 Trial Management Group. Mammo-50: Mammographic surveillance in early breast cancer patients aged over 50 years – patient reported outcomes 3 years post diagnosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-04.

Abstract Background The Cancer Genome Atlas Research Network (TCGA) published a hallmark sequencing study on molecular mutations in 200 fully characterized adult de novo AML (NEJM 2013). According to their data AML harbor in average 13 mutations in the coding region of the genome of which 5 are in genes known to be recurrently mutated in AML. Further, detailed data on co-occurrence and mutual exclusiveness of molecular mutations was presented. However, given the heterogeneity of AML a cohort of 200 AML might not be fully representative. Aims 1. Compare the published mutation frequency to our cohort 2. Evaluate, whether the mutation frequencies vary with age. 3. Determine the number of additional mutations in genetically defined AML subgroups 4. Analyze the co-occurrence of molecular mutations. Patients and Methods 1,291 adult de novo AML (700 m/591 f; median: 68 yrs; 18-100 yrs) were analyzed for mutations by different PCR assays and next-generation sequencing including the 11 most frequently mutated genes reported by TCGA (FLT3-ITD/-TKD, NPM1, DNMT3A, IDH1, IDH2, TET2, RUNX1, TP53, NRAS, CEPBA, WT1) and also ASXL1, KRAS, MLL-PTD (that had been found at lower frequencies by TCGA), and CBL. Cytogenetics was performed in all cases. Results Mutations were found in NPM1: n=410/1,189 (34.5%), DNMT3A: n=105/340 (30.9%), TET2: n=104/349 (29.8%), FLT3-ITD: n=305/1,231 (24.8%), RUNX1: n=201/1,045 (19.2%), IDH2: n=154/938 (16.4%), ASXL1: n=157/1,000 (15.7%), TP53: n=97/743 (13.1%), NRAS: n=101/842 (12.0%), IDH1: n=93/1,053 (8.8%), FLT3-TKD: n=94/1,132 (8.3%), MLL-PTD: 98/1,181 (8.3%), CEPBA: n=84/1,105 (7.6%) (double-mut: n=38; single-mut: n=46), KRAS: n=38/552 (6.9%), WT1: n=58/918 (6.3%), and CBL: 8/352 (2.3%). These mutation frequencies are comparable to those reported by TCGA. Only ASXL1 mutations were less frequently observed by TCGA (2.5%). The following mutations were more frequent in pts <60 yrs: FLT3-ITD (P=0.003), NPM1mut and WT1mut (P<0.001 for both). In contrast, ASXL1, RUNX1 (P<0.001, each) and TET2mut (P=0.005) were more frequent in pts ≥60yrs. A total of 802 pts were investigated for at least 9 markers (ASXL1, FLT3-ITD, FLT3-TKD, CEBPA, MLL-PTD, IDH1, IDH2, NPM1, RUNX1): The median number of molecular mutations was 2 (range, 0-5; mean±SD, 1.6±0.9). The lowest number of additional mutations was observed in pts with RUNX1-RUNX1T1 (0.3±0.6) and reciprocal MLL rearrangements (mean±SD, 0.4±0.6) followed by CBFB-MYH11 (0.6±0.8), NPM1 (0.9±0.7), CEPBAmut (0.9±1.0), and MLL-PTD (1.2±0.7). In concordance with TCGA results, a significant coincidence of ASXL1mut with IDH2mut and RUNX1mut was found. A total of 335 pts was screened for FLT3-ITD, DNMT3Amut, and NPM1mut in parallel and there was a high coincidence: 27/335 (8.1%) with all 3 mutations and further 63 (18.8%) with 2 out of 3; all combinations P<0.001, each). Beyond the observations within the TCGA study, we found additional positive correlations such as IDH1mut to DNMT3A (P=0.004) and as well to NPM1mut (P=<0.001), and FLT3-ITD to MLL-PTD (P=0.010) as well as to WT1mut (p=0.001). Furthermore, according to the TCGA data, the following mutations were mutually exclusive: TP53mut to NPM1mut and to FLT3-ITD (P<0.001, each), and in addition RUNX1mut to NPM1mut (P<0.001). However, we could not confirm the mutual exclusiveness of RUNX1mut and FLT3-ITD as 21.0% of RUNX1mut AML also showed FLT3-ITD. Beyond the TCGA data, we found the following mutations to show significant negative correlations: MLL translocations were significantly negatively correlated with FLT3-ITD, NPM1, DNMT3A, IDH2, and RUNX1mut, as well were RUNX1-RUNX1T1 rearrangements with FLT3-ITD, NPM1, and IDH2mut, and CBFB-MYH11 rearrangements with FLT3-ITD and NPM1mut. Conclusions 1) Investigation of a large cohort of de novo AML largely confirmed the mutation frequencies of the TCGA data, but revealed a higher frequency of ASXL1mut. 2) In addition, we depicted new patterns of positive and negative correlations of genetic alterations. 3) This further emphasizes the variety of pathways of leukemogenesis in de novo AML requiring additional analyses to delineate the prognostic impact of different marker combinations and their impact on treatment decisions. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Bacher:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Background:Gouty arthritis is a common, potentially disabling and increasingly prevalent disease [1]. The main goals of treatment are to treat acute arthritis, decrease uric acid (UA) levels and prevent occurrence of further attacks. According to 2016 updated EULAR evidence-based recommendations for the management of gout, the most common and efficient options include prescription of colchicine (up to 6 mg during the first day) and intra-articular injections of glucocorticoids (GC) [2]. First option often causes diarrhea, the latter is extremely traumatic and painful in this group of patients.Objectives:The aim of this study was to determine the efficacy of sustainability of anti-inflammatory effect of combination of low dose colchicine with sporadic intramuscular injections of betamethasone in the treatment of acute gouty arthritis.Methods:41 treatment naïve patients with acute gouty arthritis (27 male /65,9 %/, 14 female /34,1 %/, mean age 55,9 ± 13,7 years, mean disease duration 5,9 ± 4,4 years) were recruited in the study. On the first visit all the patients were prescribed 1.5 mg of colchicine per day and 2 intramuscular injections of betamethasone preparation (7mg-1ml) with an interval of 4 days. On the second visit (30thday) daily dose of colchicine was decreased to 1.0 mg, urate-lowering therapy (ULT) was begun. 21 patients (51,2%) received febuxostat 80 mg/day, 20 patients (48,8%) – allopurinol 100-150 mg/day.Routine investigation included accurate collection of disease history, objective examination with determining the disease activity (Gout Activity Score /GAS/) and visual analogue scale (VAS patient), CBC, CRP, measurement of serum UA and creatinine level, urinalysis and other examinations [4]. GAS, VAS, CRP and uric acid were measured 3 times: at baseline, on 30thand 60thday of follow-up period.Results:Investigation had shown the following results at baseline: sUA1- 9,2 ± 1,5 mg/dl, CRP1- 24,3 ± 21,5 mg/L, VAS1- 8,3 ± 1,3 cm, GAS16,3 ± 0,7. All enrolled patients completed 60 days of treatment. Preparations were well tolerated, no serious adverse events occurred: mild dyspepsia was observed in 4 (9,8%) patients, mild hypertension – in 7 (17,1%), 10 (24,4%) patients had transient diarrhea. Only in 14 out of 41 patients (34,1 %) there was a necessity to add NSAIDs to the main scheme of treatment.On the second visit (30thday) all investigated measures with exception for UA (sUA2- 8,8 ± 1,9 mg/dl, p>0.05) had shown significantly lower results: CRP2- 4,9±3,5 mg/dl, VAS2– 4,2±1,2 cm, GAS2- 4,9 ± 0,7 (p<0.001).On the third visit (60thday) the following results were obtained: sUA3- 4,7 ± 1,3 mg/dl, CRP3- 3,5±2,0 mg/L, VAS3- 3,3±2,1 cm, GAS3- 3,7±0,9. All the measures were significantly lower than at baseline (p<0,001).During all the follow-up period recurrent attacks of arthritis were observed in 6 patients (14,6%), particularly, only 2 patients experienced arthritis after the prescription of ULT.Conclusion:Low dose colchicine in combination with sporadic (1-2) intramuscular injections of betamethasone can present as an efficient, non-traumatic, safe and cost-effective option for the treatment of acute gouty arthritis. Moreover, according to results of our study, anti-inflammatory effect was stable even after the prescription of ULT.References:[1]Kuo C-F, Grainge MJ, Zhang W, et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015;11:649–62. doi:10.1038/nrrheum.2015.91[2]Richette P, et al. 2016 updated EULAR evidence-based recommendations for the management of gout Ann Rheum Dis 2017;76:29–42. doi:10.1136/annrheumdis-2016-209707[3]Scirè, Carlo A et al. “Development and First Validation of a Disease Activity Score for Gout.” Arthritis care & research vol. 68,10 (2016): 1530-7. doi:10.1002/acr.22844Disclosure of Interests: :None declared

Abstract Background: Pregnancy after breast cancer (BC) is of substantial importance for many young women at diagnosis and during follow-up. BC treatment including standard endocrine therapy (ET) (5-10 years) may reduce ovarian reserve and the chances of subsequent successful pregnancy, given conception is contraindicated during ET. A temporary interruption of ET to attempt and carry a pregnancy in this population has never been prospectively studied. Methods: POSITIVE is a single-arm, prospective, investigator-initiated, international trial evaluating the safety and pregnancy outcomes of interrupting ET for young women with early-stage hormone-receptor-positive (HR+) BC who desire pregnancy. The primary objective is to assess the risk of BC relapse associated with ET interruption for ~2 years to achieve pregnancy. Women ≤42 years with stage I-III HR+ BC who received adjuvant ET (SERM alone, GnRH analogue plus SERM or AI) for 18 to 30 months and wished to interrupt ET to attempt pregnancy were eligible. The primary endpoint is breast cancer free interval (BCFI) defined as the time from enrollment to the first BC event (local, regional, distant recurrence or a new invasive contralateral BC). Planned sample size was 500 patients. Three interim analyses of BCFI were reviewed by the Data Safety Monitoring Committee (DSMC) to assure a 95% chance of stopping the trial early if the annual BCFI event rate exceeded 4%; with primary analysis triggered after 1600 patient years of follow-up (pyfu) and no more than 46 BCFI events defined as the safety threshold. The DSMC recommended continuing the study following each interim analysis. We now report the primary results. Results: From 12/2014 to 12/2019, 518 women were enrolled. At enrollment, the median age of participants was 37 years (27-43 years); 75.0% were nulliparous, 93.4% had stage I/II disease, 66.3% node-negative. Median time from BC diagnosis to enrollment was 29 months (IQR: 25-32). Tamoxifen alone was the most prescribed ET (41.7%), followed by tamoxifen+ovarian function suppression (35.7%). 62.0% of participants had received neo/adjuvant chemotherapy. At a median follow-up of 41 months (1638 pyfu), 44 participants had experienced a BCFI event, not exceeding the pre-specified safety threshold of 46 events. The 3-year BCFI failure percent was 8.9% (95% CI: 6.3 to 11.6%), similar to the 9.2% (95% CI: 7.6 to 10.8%) calculated in the comparative external control cohort from the SOFT/TEXT trials (Sun et al, Breast 2020). Of 497 women followed for pregnancy status, 368 (74.0%) had at least one pregnancy, 317 (63.8%) had at least one live birth, with a total of 365 babies born. Based on competing risk analysis, 76.3% of patients resumed ET (half within 26 months), 8.3% had BCFI event/death before ET resumption, and 15.4% had not resumed ET yet. Conclusions: The POSITIVE trial demonstrates that for young women with early HR+ BC desiring pregnancy, temporary interruption of ET to attempt pregnancy does not confer a greater short-term risk of recurrence than that observed in a modern historical control group that did not interrupt ET. Most participants have had a live birth. Further follow-up is planned to confirm long-term safety. These results should be considered in counselling BC patients desiring future pregnancy. Citation Format: Ann Partridge, Olivia Pagani, Samuel M. Niman, Monica Ruggeri, Fedro Alessandro A. Peccatori, Hatem A. Azim, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Saetersdal, Judith Kroep, Audrey Mailliez, Ellen Warner, Virginia F. Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice Walshe, Manuel Ruiz Borrego, Halle Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Karen L. Smith, Teresa Ferreiro Vilarino, Karin Ribi, Kathryn Ruddy, Sarra El-Abed, Martine Piccart, Larissa A. Korde, Aron Goldhirsch, Richard D. Gelber. Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer: Primary Results from the POSITIVE Trial (IBCSG 48-14/BIG 8-13) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-09.

Abstract Abstract 3796 Background: In 2008 the WHO classification combined the former categories RCMD (refractory cytopenia with multilineage dysplasia) and RCMD-RS (with ring sideroblasts ≥15%) thus not separating according to ring sideroblasts anymore in MDS with multilineage dysplasia, while the category refractory anemia with ring sideroblasts (RARS) was maintained separately. One aim of this study was to evaluate whether or not a separation with respect to ring sideroblasts is reasonable. Study Design: To investigate the clinical impact and genetic background of these MDS subtypes, we studied outcomes, cytogenetics, and molecular genetics in 1082 de novo MDS pts (153 RARS, 606 RCMD, 323 RCMD with ring sideroblasts ≥15% termed “RCMD-RS“): 703 m/379 f; median age, 73.1 yrs; 21.0–90.4 yrs. Cytogenetic risk groups were defined according to the International Prognostic Scoring System (IPSS; Greenberg et al., 1997). Results: Sex ratio (male preponderance in all subtypes; male/female ratio 1.9 in the whole cohort) did not differ significantly between the 3 MDS subgroups. Mean age (RARS: 71.8; RCMD: 70.1; RCMD-RS: 72.6 yrs) reached significant difference between RARS vs RCMD (p=0.020) and between RCMD vs RCMD-RS (p=0.004). Mean WBC count differed between all subgroups (RARS: 6.1; RCMD: 4.4; RCMD-RS: 5.3×10(9)/l; RARS vs RCMD p<0.001; RARS vs RCMD-RS p=0.039; RCMD vs RCMD-RS p<0.001) whereas mean platelet count (RARS: 232; RCMD: 144; RCMD-RS: 218 × 10(9)/l) and Hb level (RARS: 96; RCMD: 105; RCMD-RS: 98 g/l) differed between RARS vs RCMD and RCMD vs RCMD-RS (all p-values <0.001). IPSS categories were available in 854/1082 pts as follows: 514 pts (60.2%) low-risk, 312 (36.5%) intermediate-1, and only 28 (3.3%) intermediate-2 risk (no pt was assigned to high risk IPSS). Cytogenetics was available in all 1082 pts: The majority (918/1082; 84.4%) had good karyotypes (KTs) according to IPSS mainly due to high rates of normal KTs (821/1082, 75.9%); 112 pts had intermediate (10.4%); and only 52 (4.8%) had poor KTs. In detail, good KTs were equally distributed in RARS: 123/153; 80.4%; in RCMD: 530/606; 87.5%; and in RCMD-RS: 265/323; 82.0%. 3-yr overall survival (OS) rates did not differ significantly between the three MDS subtypes (RARS: 78.1%; RCMD: 86.7%; RCMD-RS: 80.6%). Also when entities with ≥15% ring sideroblasts (RARS + RCMD-RS) were compared to RCMD (<15% ring sideroblasts), 3-yr OS rate was similar (80.0% vs 86.7%; n.s.). Further, multilineage dysplasia per se did not impact on 3-yr OS rate (RCMD + RCMD-RS: 83.8% vs 78.1% in RARS; n.s.). In contrast, 3-year OS rate was better in good KTs compared to intermediate or poor KTs (91.4% vs 60.0% vs 29.3%; p<0.001) in the total cohort. Also in the different MDS subtypes, good karyotypes showed better 3-year OS rate than intermediate/poor karyotypes (p-values for comparison of cytogenetic risk groups: RARS: p<0.001; RCMD: p=0.032; RCMD-RS: p=0.007). In subcohorts genes were analysed and were found to be mutated only with low frequencies: RUNX1 mut: 14/213 (6.6%), NRAS mut: 1/283 (0.4%), MLL -PTD: 4/294 (1.4%), FLT3 -ITD: 0/285. This underlines the low risk profile of the cohort. In univariable analysis, good + intermediate vs poor KTs (p<0.001), aberrant vs normal KT (p<0.001), age (p=0.080), and Hb level (both continuous; p=0.007) had a significant impact on OS, while WBC count, platelets, and percentage of ring sideroblasts (all as continuous variables) were not significant. In multivariable analysis, IPSS cytogenetic risk groups (p=0.005) and Hb (p=0.008) only remained significant. Conclusions: As investigated here in 1082 pts, RARS, RCMD, and RCMD-RS all show high rates of good karyotypes as defined by IPSS and show similar clinical outcomes which clearly supports to skip the RCMD-RS category as done by the WHO in 2008. The karyotype and Hb level were the only independent prognostically relevant parameters in multivariable analysis. However, >80% of patients show a good risk cytogenetic profile making prognostication according to karyotype relevant only in a small subset of patients. To overcome this shortcoming only an increasing panel of new molecular markers in MDS can pave future investigations which presently becomes available by the advanced sequencing techniques. After diagnosed by morphology and cytogenetics especially molecular genetic information may therefore guide treatment in the near future for this low risk subgroup of MDS patients as investigated here. Disclosures: Kern: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Alpermann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

В данной работе продемонстрирована возможность применения ИК-микроспектроскопии для многомерной визуализации и анализа интеграции с нативными твердыми тканями зуба человека нового поколения биомиметических материалов, воспроизводящих минералорганический комплекс эмали и дентина.На основе ИК-картирования интенсивности конкретной функциональной молекулярной группы с использованием синхротронного излучения найдены и визуализированы характеристические особенности биомиметического переходного слоя в межфазной области эмаль/стоматологический материал и определено расположение функциональных групп, отвечающих процессам интеграции биомиметического композита REFERENCES Rohr N., Fischer J. Tooth surface treatment strategies for adhesive cementation // The Journal of Advanced Prosthodontics, 2017, v. 9(2), pp. 85–92. https://doi.org/10.4047/jap.2017.9.2.85 Pereira C. N. de B., Daleprane B., Miranda G. L. P. de, Magalhães C. S. de, Moreira A. N. 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En las últimas décadas las referencias al Análisis de Redes han ganado protagonismo entre los historiadores. Hemos asistido a una auténtica proliferación de artículos, monográficos y proyectos de investigación en los que el estudio de las interconexiones en sociedades del pasado ocupa un papel central. Desafortunadamente, en algunos de estos trabajos la conceptualización y la cuantificación han estado ausentes. El presente artículo pretende explorar el potencial del Análisis de Redes como herramienta metodológica aplicable a la disciplina histórica en sus distintos campos de investigación. Pretendemos hacer una apuesta clara por la integración de esta herramienta, superando la retórica de las palabras, pero también de la imagen. Para ello, incorporamos una panorámica de las principales aportaciones al Análisis de Redes en la historiografía. Además, analizamos sus elementos fundamentales y describimos su uso con ejemplos de publicaciones recientes, explorando los retos que se plantean de cara al futuro. Palabras Claves: Análisis de Redes, Metodología, Métricas, VisualizaciónTopónimos: Latinoamérica, EuropaPeriodo: Neolítico-Siglo XX ABSTRACTDuring recent decades, historians have referred with increasing frequency to network analysis. We have witnessed a veritable proliferation of papers, monographs and research projects in which the study of interconnections among individuals from past societies plays a central role. Unfortunately, conceptualization and quantifications have been absent from most of these works. This paper aims to explore the potential of network analysis as a methodological tool applied to history. The objective is to integrate this tool into the historian’s work, transcending the rhetoric of words and images. To this end, I first present the main contributions of network analysis to historiography, together with a description of its main elements, using examples from recent academic works. The paper also explores the challenges facing future research. Keywords: Network Analysis, Methodology, Metrics, VisualizationPlace names: Latin America, EuropePeriod: Neolithic- 20th Century REFERENCIASAhnert, R., Ahnert, S., Coleman. C. N. y Weingart, S. B. (2020), The Network Turn. Changing Perspectives in the Humanities, Cambridge, University Press.Batagelj, V. Mrvar, A. (2001), “A subquadratic triad census algorithm for large sparse networks with small maximum degree”, Social Networks, 23, pp. 237-243.Bernabeu Aubán, J., Lozano, S y Pardo-Gordó, S. (2017), “Iberian Neolithic Networks: The Rise and Fall of the Cardial World”, Frontiers in Digital Humanities (4).Bertrand, M., Guzzi-Heeb, S. y Lemercier, C. (2011), “Introducción: ¿en qué punto se encuentra el análisis de redes en Historia?”, REDES. 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Бинарные и сложные халькогениды с тетрадимитоподобной слоистой структурой представляют большой практический интерес как топологические изоляторы, термоэлектрические и оптоэлектронные материалы. Их фундаментальные термодинамические функции в совокупности с фазовыми диаграммами важны для разработки и оптимизации методов синтеза и выращивания кристаллов. В работе представлены результаты термодинамического исследования исходных соединений и твердых растворов системы Bi2Se3-Bi2Te3 методом электродвижущих сил (ЭДС). Различные модификации этого метода широко применяются для исследования бинарных и сложных халькогенидов металлов. Исследования проводили измерением ЭДС концентрационных цепей типа:(–) Bi (тв.) | ионная жидкость + Bi3+ | Bi в сплаве (тв.) (+) в интервале температур 300-450 K.В качестве правых электродов были использованы предварительно синтезированные равновесные сплавы Bi2Se3–хTex (х = 0; 0.6; 1.2; 1.8; 2.0; 2.4; 3.0) с 0.5 ат. % избытком теллура. В качестве электролита использовали ионную жидкость (формиат морфолина) с добавлением BiCl3.Полученные экспериментальные данные обработаны с помощью компьютерной программы «Microsoft Office Excel 2003» методом наименьших квадратов и получены линейные уравнения типа E = a + bT. Из полученных уравнений температурных зависимостей ЭДС рассчитаны относительные парциальные молярные функции висмута в сплавах. На основании диаграммы твердофазных равновесий системы Bi–Se–Te были определены уравнения потенциалобразующих реакций, с использованием которых вычислены стандартные термодинамические функцииобразования и стандартные энтропии соединений Bi2Se3, Bi2Te3 и твердых растворов Bi2Se3–xTex вышеуказанных составов. Также вычислены термодинамические функции образования твердых растворов Bi2Se3–xTex из исходных бинарных соединений. 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La historiografía sobre fortificaciones medievales en el ámbito medieval cristiano es tan amplia como dispersa. Abundan los estudios de carácter local abordados con metodologías y desde disciplinas diversas, empezando por los clásicos trabajos de Historia del Arte e Historia de la Arquitectura, y, por supuesto, los de contenido estrictamente histórico, planteados desde el estudio de las fuentes escritas y, más recientemente, desde la Arqueología. Faltan, no obstante, estudios de conjunto y aunque se ha abordado el tema de la conceptualización y clasificación tipológica de estas fortalezas, creemos que sigue siendo una asignatura pendiente en el ámbito de la castellología. El presente trabajo pretende pues abordar la problemática sobre la definición y límites del castillo medieval, para pasar después a plantear una clasificación tipológica y funcional de los castillos cristianos peninsulares, para lo cual tendremos en cuenta no sólo la producción historiográfica reciente, sino también nuestras propias investigaciones de base fundamentalmente arqueológica. Palabras clave: Castellología, castillo feudal, tipología castral, reinos cristianos peninsulares, poliorcéticaTopónimos: Península IbéricaPeríodo: siglos VIII-XV ABSTRACTHistoriography on the subject of medieval fortifications in the medieval Christian area is as wide as it is disperse. There is an abundance of local studies undertaken employing different methodologies, starting with the History of Art, the History of Architecture and, of course, those of strictly historical content, based on the study of written sources and, more recently, on Archaeology. However, there is a lack of comprehensive studies and, although the problem of the conceptualisation and typological classification of these fortresses has been addressed, I believe that this continues to be an unresolved issue in the field of castellology. This article aims to address the problem of the definition and limits of the medieval castle, and then propose a typological and functional classification of peninsular Christian castles, taking into account not only recent historiographical production but also my own archaeological research. Keywords: castellology, feudal castle, castral typology, peninsular Christian kingdoms, polyorceticPlace names: Iberian PeninsulaPeriod: 8th-15th centuries REFERENCIASAcién Almansa, M. (2002), “De nuevo sobre la fortificación del emirato” en Mil anos de Fortificações na Península Ibérica e no Magreb (500-1500). Actas do simpósio internacional sobre castelos, Lisboa, pp. 59-75.Almedia, C. A. F. de (1991), “Castelos e cercas medievais. 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ABSTRACT The stability of Islamic finance has made many researchers interested in discussing Islamic finance. Sukuk is included in one of the widely published areas of Islamic finance, making it a topic of discussion in several scholarly forums. This study used the Scopus database, where there were 2,128 articles related to sukuk in the Scopus web in 2011-2021, but only 108 articles were included in the criteria and used as a research sample using bibliometric methods and SLR to obtain results related to publication activities, popular topics, research trends, and recommendations for research directions related to sukuk. In the bibliometric analysis method with the help of biblioshiny applications and SLR analysis by reviewing each article and grouping research topics. The results showed that sukuk related publication articles were spread in several countries that were not restricted. Malaysia is the country with the most publications related to sukuk, and most often conducts research collaborations in both Multiple Country Collaboration (MPC) and Single Country Collaboration (SCP). The results of SLR analysis have four themes that are most discussed in research related to sukuk, so researchers provide recommendations for further research directions that can be used by researchers in the future, such as adding research using qualitative methods or discussing the impact of sukuk performance in real terms not only from secondary data. Keywords: Bibliometric, Islamic Bond, Sukuk, Systematic Literature Review (SLR). ABSTRAK Stabilnya Keuangan Islami menjadikan banyak peneliti yang tertarik membahas Keuangan Islami. Sukuk termasuk dalam salah satu sektor Keuangan Islami yang banyak diterbitkan sehingga menjadikan sukuk sebagai topik bahasan diskusi dalam beberapa forum ilmiah. Penelitian ini menggunakan database scopus dimana terdapat 2.128 artikel terkait sukuk pada tahun 2011-2021 dalam web scopus, akan tetapi hanya 108 artikel yang masuk dalam kriteria dan dijadikan sampel penelitian dengan menggunakan metode bibliometrik dan SLR untuk mendapatkan hasil terkait aktivitas publikasi, tema popular, tren penelitian dan rekomendasi arah penelitian terkait sukuk. Pada metode bibliometrik analisis menggunakan bantuan aplikasi biblioshiny dan analisis SLR dengan melakukan review setiap artikel dan mengelompokkan tema penelitian. Hasil penelitian menunjukkan artikel publikasi terkait sukuk tersebar di beberapa negara yang tidak dibatasi. Malaysia merupakan negara dengan publikasi terbanyak terkait sukuk dan paling sering melakukan kolaborasi penelitian baik secara Multiple Country Collaboration (MPC) dan Single Country Collaboration (SCP). Hasil analisis SLR terdapat empat tema yang paling banyak dibahas dalam penelitian terkait sukuk, sehingga peneliti memberikan rekomendasi arah penelitian selanjutnya yang dapat digunakan oleh peneliti selanjutnya dengan menambah penelitian menggunakan metode kualitatif atau membahas dampak kinerja sukuk secara real bukan hanya dari data sekunder. Kata Kunci: Bibliometric, Islamic Bond, Sukuk, Systematic Literature Review (SLR). REFFERENCES Ahmad, A. U. F., Muneeza, A., Farooq, M. O., & Hasan, R. (2018). Post-default sukuk restructuring: an appraisal of shari’ah issues. In Hassan, M.K. and Rashid, M. (Ed.) Management of Islamic Finance: Principle, Practice, and Performance (pp. 113–128). Bingley: Emerald Publishing Limited Al Fathan, R., & Arundina, T. (2019). Finance-growth nexus: Islamic finance development in Indonesia. International Journal of Islamic and Middle Eastern Finance and Management, 12(5), 698–711. doi:10.1108/IMEFM-09-2018-0285 Al Madani, H., Alotaibi, K. 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e4444019This article presents the results of an investigation into contributions of the analysis of authentic classroom situations to the professional development of the beginner teacher who teaches statistics, constituting a discussion about the formative processes of this professional. To achieve this, we considered the reflections that took place in three episodes of a mathematics teacher training that was part of a specialization course, carried out in the West Zone of Rio de Janeiro, Brazil. In these three episodes, the teachers analyzed video recordings from an 8th grade class of a basic school, in the City School Network of Rio de Janeiro, addressing statistical representations. They also examined the content related to the task proposed to the students, the didactic potential of the task, and the students’ answers. A qualitative analysis of interpretative nature of the audio transcriptions of the teachers’ discussions in the episodes was carried out, as well as an analysis of the reports they produced based on a script prepared by the trainer. The results show that the analysis of the tasks and students’ responses and the analysis of the videos provided a learning experience about the teaching of statistics, namely regarding the teacher actions according to the reasoning and communication of the students. The teachers consider that these activities are essential in the training process to get closer to the real contexts of the classroom.ResumenEste artículo presenta los resultados de una investigación sobre las contribuciones del análisis de situaciones auténticas en las clases al desarrollo profesional del maestro principiante que enseña Estadísticas. Para esto, consideramos las reflexiones que se produjeron en tres episodios de formación de docentes de matemáticas incluidos en un curso de especialización, realizado en la Zona Oeste de Río de Janeiro, Brasil, constituindo una discusión sobre los procesos formativos de este profesional. En estés tres episodios, los maestros analizaron registros de video de una clase de 8º grado de escuela básica, en la Red Municipal de Río de Janeiro, abordando representaciones estadísticas. Examinaron el contenido relacionado con la tarea propuesta, el potencial didáctico de la tarea y las respuestas de los estudiantes. Se realizó un análisis cualitativo de la naturaleza interpretativa de las transcripciones de audio de las discusiones de los maestros en los episodios de capacitación y los informes que produjeron en base a un guion preparado por el capacitador. Los resultados muestran que el análisis de las tareas y respuestas de los estudiantes y el análisis de los videos proporcionaron información sobre la enseñanza de la Estadística, en particular con respecto a las acciones del maestro mediante el razonamiento y la comunicación del estudiante. Los maestros consideran que estas actividades son fundamentales en el proceso formativo para acercarse a los contextos reales de la clase.Palavras-chave: Formação, Ensino da Estatística, Desenvolvimento profissional.Keywords: Teacher training, Statistics Teaching, Professional development.Palabras claves: Entrenamiento, Enseñanza de Estadística, Desarrollo profesional.ReferencesAMERICAN EDUCATIONAL RESEARCH ASSOCIATION. Code of ethics. Educational Researcher, Flórida, v. 40, n. 3, p. 145-156. 2011.BARDIN, Laurence. Análise de conteúdo (L. de A. Rego A. Pinheiro, Trads.). Lisboa: Edições, 70, (Obra original publicada em 1977), 288 p.BATANERO, Carmen; GODINO, Juan; ROA, Rafael. 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