Journal articles on the topic '818/.54'

In this work the analysis on description of rural settlements boundaries of the Republic of Bashkortostan, based on the experience of other sub-federal units of Russian Federation was made. A range of weak points in collected input data was defined. In total, of 54 municipal districts of the Republic of Bashkortostan (818 rural settlements), 44 districts showed nonconformity of feed data details to regulatory requirements. And the main reason for this is a low quality of input materials such as base maps at scale 1

The reverse-yield factor (RF) database was developed for qualitatively and quantitatively disaggregating Japanese composite foods into raw primary commodity (RPC) ingredients. Representative equations for four types (dried, salted, fermented and mixed foods) were developed to calculate RFs using the food content and composition data for composite foods listed in the Standard Tables of Food Composition in Japan—2020—(STFCJ), published by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Out of 1150 composite foods identified in the STFCJ, RFs for 54 dried, 41 salted, 40 fermented and 818 mixed foods were obtained. RFs for 197 mixed foods could not be calculated because these foods were produced from ingredients with no specified information and/or through complex processing. The content and composition of Japanese composite foods would be interpreted representatively by RFs in the developed database.

Society long has been concerned about the behavior of its youth. Today, because of the easy accessibility of more dangerous drugs, more lethal weapons, and automotive transportation, this concern is greater. In 1989 there were 1 744 818 arrests among those under 18 years and 585 521 arrests in the age group under 15 years. Although the overall arrest rate for males has increased only 5% over the past 10 years, violent crimes such as murder and rape have increased significantly (>60% and >27%, respectively). Further, motor vehicle thefts have increased even more (72%). The overall arrest rate for females under 18 years of age has increased 13%, with aggravated assault and motor vehicle theft (>69% and 54%, respectively) chiefly responsible for the increase. These figures would be even more staggering if they included youth who commit delinquent acts but do not come into contact with legal authorities. Not only do pediatricians, because of their relationship with youth and their families, have an opportunity to affect those factors that may lead to delinquent behavior, but they have an obligation to provide for the medical and mental health needs of these youth. Legal Considerations Legally, a youth is considered a delinquent if he or she commits an act that violates the law and if the violation comes to the attention of the police or the court system.

La forma más conveniente de fraccionar el fertilizante nitrogenado varía de acuerdo al tipo de suelo, manejo del cultivo y a las condiciones climáticas. El objetivo del presente trabajo fue determinar la mejor forma de fraccionar el nitrógeno en el cultivo de papa en el Valle de Toluca, bajo condiciones de temporal. En 2006 se estableció un experimento en el que se probaron tres dosis de nitrógeno (100, 200 y 300 kg N ha-1) fraccionadas en 1, 2 y 4 partes que se aplicaron a la siembra, 18, 34 y 47 días después de la emergencia de las plantas (DDE). Además se incluyó un tratamiento sin nitrógeno. Durante el ciclo vegetativo del cultivo se hicieron cuatro determinaciones de la concentración de nitrato en el extracto celular de los pecíolos foliares (ECP) a los 25, 40, 54 y 68 DDE, para ello se usó un medidor CARDY. Los máximos rendimientos de 42.4 y 42.1 t ha-1 se obtuvieron con 200 kg N ha-1 cuando el nitrógeno se fraccionó en una o dos partes respectivamente. La concentración de nitrato en el ECP a los 25 DDE asociada con los máximos rendimientos fue de 1 818 y 1 812 mg L-1 de N-NO3 respectivamente. Los análisis de nitratos en el ECP indicaron que al fraccionar en cuatro partes el nitrógeno, se propiciaron def iciencias de este elemento durante las primeras etapas de desarrollo de las plantas que y las aplicaciones tardías ocasionaron alteraciones fisiológicas en detrimento de la producción de tubérculos.

Abstract Abstract 1940 INTRODUCTION: Dose escalation of chemotherapy and radiation in conditioning regimens has been associated with lower relapse rates but not significantly improved overall survival in allogeneic transplants because of higher treatment related mortality. The advent of IV BU has allowed more precise dosing of this drug and permitted dose escalation to a greater degree than in the past. METHODS: Test dose (.8 mg/kg) IV BU was administered one week prior to start of the conditioning regimen and the desired AUC calculated from the Bu clearance. Starting at a standard AUC of 4800/24 hours, target dose levels were escalated in 20% increments to 5760, 6912, 7603 and 8663 uM-min/24 hours. BU was administered from day −7 to −3 by 90 hour continuous infusion accompanied by fludarabine, 30 mg/m2/d on days −7 to −3. All pts received tacrolimus and either alemtuzamab alone or ATG+/− low dose MTX for GVH prohylaxis. Standard antibiotic prophylaxis and supportive care was provided. RESULTS: 55 high risk pts, median age 39 (22–54), 20 MRD, 35 MUD, 26 AML, 7 ALL, 2 APL, 1 biphenotypic leukemia, 8 MDS, 5 NHL, 2 HD, 1 CLL, 1 CML, 1 CMML, 1 MF were enrolled on this IRB approved study. 30 patients received alemtuzamab, 19 ATG + MTX and 6 MTX only. Mean achieved AUCs were 4973(14 pts), 5638(7 pts), 7131(25 pts), 7053(7 pts), and 8680(2 pts) uM-min/24 hrs. The MTD was dose level 3 (target 6912, achieved 7131 uM-min). Grade 4 DLTs were grade 4 mucositis in 2/2 at level 5 and 1/7 at level 4 and 1/7 reversible VOD at level 4. One additional grade 5 toxicity was seen at dose level 1(liver failure), level 2 (mucositis) and level 3 (VOD). The incidence of grade 4 or 5 VOD was 2/55 or 4%. Median AUC for the entire group was 6312 uMol-min with the median in the group below the overall median being 5484 and the group above the median being 7394 uMol-min/24 hours; a 35% difference in dose between the lower and higher median values and a 54% increase over a standard AUC dose of 4800 uMol-min. When analyzed by AUC, pts above the median had a higher median overall survival (OS), 353 days vs 183 days (HR.48, p =.058) for those below the median and longer relapse-free survival (RFS), 818 vs 187 days (HR.47, p =.039). When divided by AUC in tertiles (median AUC values of 5106 (19 pts), 6431 (19 pts), and 7693 (17 pts) uMol-min/24 hrs respectively), the median OS in days for each group were 298, 353, and Not Reached and median RFS were 191, 353, and 818 days. Three group comparison using Cox model yielded p-values of.063 and.053 levels for RFS and OS, respectively. 2-year OS and RFS for the below and above median groups were.27 and.20 and.62 and.57, respectively. 2-year OS and RFS for the lowest, medium and highest AUC groups in the tertile analysis were.24 and.20.41 and.35, and.70 and.63, respectively. In multivariable analysis, higher AUC dose, use of ATG rather than alemtuzamab and having a MUD all demonstrated a trend toward improved outcomes with AUC being the strongest predictor. CONCLUSION: High AUC levels of busulfan can be safely achieved with targeted PK dosing and continuous IV infusion leading to improved overall survival and decreased relapse rates in patients undergoing allogeneic transplantation with either ATG or alemtuzamab as part of their GVHD prophylaxis. Disclosures: Shea: Otsuka Pharmaceuticals: Research Funding.

AbstractData from experimental programmes designed to investigate the effect of chemical structure of fats upon their apparent digestible energy (DE) value for pigs were subjected to regression analysis. For growing pigs, over the approximate live-weight range 30 to 90 kg, 25 data points were available, with fats evaluated having a range in the ratio of unsaturated to saturated fatty acids (U/S) from 0·66 to 15·67 and in free fatty acid (FFA) content from 8 to 818 g/kg. Sixteen data points were available for young pigs of approximately 12 kg live weight with a range in U/S from 0·62 to 5·71 and in FFA content from 54 to 756 g/kg. The wide range of values for U/S and FFA content had been obtained by blending different fats and, therefore, represented both the range and extremes likely to be found in the formulation of pig diets. Derivation of prediction equations for DE were based upon a series of non-linear regression analyses employing, in sequence, U/S, U/S + FFA content and U/S × FFA content. The DE offats could be predicted from U/S and FFA content with equations accounting for 0·802 and 0·768 of the variation in DE values for growing and young pigs respectively. The most appropriate equation for pigs of all live weights employed U/S and FFA content additively (U/S + FFA content). The equation for growing pigs was DE (MJ/kg) = 36·898 – (0·0046FFA (g/kg)) — 7·33e(–0·906U/S) and for young pigs was DE (MJ/kg) = 37·890 — (0·0051FFA (g/kg)) –8·20e(–0·515U/S). Comparisons revealed that differences between the two age groups, with lower values achieved with younger pigs, -were more pronounced the lower U/S and the higher FFA content of the fat.

Abstract The significance of conditioning regimen intensity on the outcomes of T-cell replete HLA-haploidentical transplants is not known. This study compared outcomes of commonly used myeloablative (MAC) to reduced intensity (RIC) conditioning regimens in 1325 such transplants (AML; n=818; ALL; n=286 and MDS; n=221) in the US between 2008 and 2016. The median age of the study population was 54 years (18 - 70). Most patients (80%) with AML and ALL were in first or subsequent remission; 83% of those with MDS had refractory anemia with excess blasts at transplantation. Fifty-one percent of patients with AML and ALL had intermediate disease risk index (DRI). In contrast, 50% of patients with MDS had high or very high DRI. Patients received MAC (n=526; 40%) or RIC (n=799; 60%) transplant conditioning regimens and a uniform graft-versus-host disease (GVHD) prophylaxis: post-transplant cyclophosphamide, calcineurin inhibitor and mycophenolate. Approximately 50% of patients reported a HCT-CI score of 0-2 in MAC and RIC groups. Sixty-six percent of MAC and 42% of RIC recipients received peripheral blood grafts. Total body irradiation (TBI) + fludarabine (TBI/Flu; 33%) and busulfan with cyclophosphamide with/without Flu (Bu/Cy ± Flu; 36%) were the predominant MAC regimens. Other MAC regimens included TBI/Cy or other agents (10%), Flu/Bu4 (13%), melphalan (140 mg/m2) + Flu ± thiotepa (Flu/Mel ± TT; 9%). TBI (200cGy)/Cy/Flu (84%) was the predominant RIC regimen. Other RIC regimens included TBI 200cGy + Bu or Mel + Flu (7%), Flu/Bu2 (1%) and Flu/Mel (100mg/m2) ± TT (5mg/kg) (8%). The primary endpoint was disease-free survival (relapse or death). Cox regression models were built to study the effect of conditioning regimens on transplant outcomes after adjusting for other factors significantly associated with outcomes. Differences in transplant-outcomes were observed between ages 18-54 years and 55-70 years. The effect of age was further tested within the 18-54 and 55-70 age groups and there were no differences in outcome. In patients aged 18-54 years (n=689), 55% received MAC and 54% received RIC regimens. In patients aged 55-70 years (n=636), 22% received MAC and 78% received RIC regimens. Table 1 shows the effect (hazard ratio; HR) of conditioning regimen intensity in the two age groups adjusted for HCT-CI, recipient CMV serostatus, disease, DRI and graft type and the 2-year probabilities for the outcomes of interest. In patients aged 18-54 years who were equally likely to receive MAC or RIC regimens, relapse risks were higher after RIC regimens that resulted in lower disease-free survival. There were no differences in non-relapse mortality (NRM) or overall survival by conditioning regimen intensity. In patients aged 55-70 years who were more likely to receive RIC regimen, NRM was lower after RIC but without an advantage for relapse, disease-free or overall survival. Figure 1A and 1B show the 2-year probability of disease-free survival by conditioning regimen intensity in patients aged 18-54 and 55-70 years, respectively. Consistent with the main analysis, a subset analysis limited to AML also confirmed higher relapse (HR 1.43, p=0.03) and lower disease-free survival (HR 1.38, p=0.02) after RIC regimens in patients aged 18-54 years but not in patients aged 55-70 years. Acute GVHD (HR 1.01, p=0.94) and chronic GVHD (HR 0.82, p=0.14) did not differ by conditioning regimen intensity. Table 2 compares the effect of TBI- and non-TBI containing MAC and RIC regimens adjusted for age, HCT-CI, recipient CMV serostatus, disease, DRI and graft type. NRM risks were higher after RIC non-TBI compared to RIC TBI regimens. The predominant RIC non-TBI regimen was Flu/Mel (100mg/m2) ± TT (5mg/kg). In conclusion, a MAC regimen offers higher disease-free survival for those aged 18-54 years and can tolerate MAC regimens. For patients who are unable to tolerate MAC regimens, regardless of their age, TBI200 cGy/Cy/Flu is preferred to Flu/Mel ± TT to minimize NRM risks. Disclosures Shah: Juno Pharmaceuticals: Honoraria; Lentigen Technology: Research Funding; Exelexis: Equity Ownership; Geron: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Oncosec: Equity Ownership. Brunstein:Gamidacell: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Hamadani:Celgene Corporation: Consultancy; Merck: Research Funding; Janssen: Consultancy; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Cellerant: Consultancy; Takeda: Research Funding; Ostuka: Research Funding; MedImmune: Consultancy, Research Funding. McGuirk:Gamida Cell: Research Funding; Kite Pharma: Honoraria, Other: travel accommodations, expenses, speaker ; Fresenius Biotech: Research Funding; Pluristem Ltd: Research Funding; Bellicum Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Other: speaker, Research Funding. Vasu:Boehringer Ingelheim Inc: Membership on an entity's Board of Directors or advisory committees. Waller:Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Cambium Medical Technologies: Consultancy, Equity Ownership; Celldex: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kalytera: Consultancy.

The Peipsi-Pskov Lake is the largest freshwater body in Europe, ranking fourth in area and fifth in volume. It is characterized by shallow water and a high level of trophy. The water in the lake is poorly mineralized and has little transparency due to suspended sediments and the development of plankton. Phytoplankton acts as a primary link in trophic chains, quickly reacts to changes in the aquatic environment and serves as a convenient object in monitoring studies.The average concentrations of total nitrogen in the lake during the observation period were in the range of 525-818 µg/dm3. The content of ammonium, nitrate, and nitrite nitrogen in the samples was mostly below the detection limits. The values of total phosphorus varied from 20 µg/dm3 to 54 µg/dm3, and its concentrations were lower than the sensitivity of the method during the flood recession.The maximum values of total nitrogen and phosphorus were recorded in August: in Lake Peipsi - 1.12 mg/dm3 and 0.09 mg/dm3, in Lake Pskov - 1.59 mg/dm3 and 0.14 mg/dm3, respectively. BOD5 values ranged from 1.96 mg/dm3 in autumn to 4.26 mg/dm3 in summer.During the growing season of 2020, 244 species taxa of phytoplankton from 8 phylums were identified in the Peipsi-Pskov Lake: Chlorophyta, Bacillariophyta, Cyanobacteria, Chrysophyta, Euglenophyta, Cryptophyta, Dinophyta and Xanthophyta. Floristic complex was characterized as сhlorophyta-diatom-cyanobacterial.The number of phytoplankton varied between 2.1 and 16.2 million cells/l depending on the season. The average number was 7.6 million cells/l. The biomass values ranged from 0.9 g/m3 to 3.6 g/m3. The average biomass was 2.3 g/m3.According to the ecological and geographical characteristics of the lake, widespread freshwater forms of microalgae predominated, preferring stagnant-flowing, slightly alkaline waters.Saprobiological analysis showed that the waters of the Peipsi-Pskov Lake were classified as moderately polluted, class III of water purity quality.

ObjectivesDifferences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We performed a systematic review and meta-analysis to clarify these differences.MethodsPubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO.ResultsA total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year.ConclusionsThis meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies.

This paper presents the sharpest near-IR images of the massive cluster R 136 to date, based on the extreme adaptive optics of the SPHERE focal instrument implemented on the ESO Very Large Telescope and operated in its IRDIS imaging mode.The crowded stellar population in the core of the R 136 starburst compact cluster remains still to be characterized in terms of individual luminosities, age, mass and multiplicity. SPHERE/VLT and its high contrast imaging possibilities open new windows to make progress on these questions.Stacking-up a few hundreds of short exposures in J and Ks spectral bands over a field of view (FoV) of 10.9″ × 12.3″ centered on the R 136a1 stellar component, enabled us to carry a refined photometric analysis of the core of R 136. We detected 1110 and 1059 sources in J and Ks images respectively with 818 common sources. Thanks to better angular resolution and dynamic range, we found that more than 62.6% (16.5%) of the stars, detected both in J and Ks data, have neighbours closer than 0.2′′ (0.1′′). The closest stars are resolved down to the full width at half maximum (FWHM) of the point spread function (PSF) measured by Starfinder. Among resolved and/or detected sources R 136a1 and R 136c have optical companions and R 136a3 is resolved as two stars (PSF fitting) separated by 59 ± 2 mas. This new companion of R 136a3 presents a correlation coefficient of 86% in J and 75% in Ks. The new set of detected sources were used to re-assess the age and extinction of R 136 based on 54 spectroscopically stars that have been recently studied with HST slit-spectroscopy (Crowther et al. 2016, MNRAS, 458, 624) of the core of this cluster. Over 90% of these 54 sources identified visual companions (closer than 0.2′′). We found the most probable age and extinction for these sources are 1.8+1.2-0.8 Myr, AJ = (0.45 ± 0.5) mag and AK = (0.2 ± 0.5) mag within the photometric and spectroscopic error-bars. Additionally, using PARSEC evolutionary isochrones and tracks, we estimated the stellar mass range for each detected source (common in J and K data) and plotted the generalized histogram of mass (MF with error-bars). Using SPHERE data, we have gone one step further and partially resolved and studied the initial mass function covering mass range of (3–300) M⊙ at the age of 1 and 1.5 Myr. The density in the core of R 136 (0.1–1.4 pc) is estimated and extrapolated in 3D and larger radii (up to 6 pc). We show that the stars in the core are still unresolved due to crowding, and the results we obtained are upper limits. Higher angular resolution is mandatory to overcome these difficulties.

Background: The two most common SARS-CoV-2 vaccines in the UK, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca), employ different immunogenic mechanisms. Compared to BNT162b2, two-dose immunisation with ChAdOx1 induces substantially lower peak anti-spike antibody (anti-S) levels and is associated with a higher risk of breakthrough infections. To provide preliminary indication of how a third booster BNT162b2 dose impacts anti-S levels, we performed a cross-sectional analysis using capillary blood samples from vaccinated adults participating in Virus Watch, a prospective community cohort study in England and Wales. Methods: Blood samples were analysed using Roche Elecsys Anti-SARS-CoV-2 S immunoassay. We analysed anti-S levels by week since the third dose for vaccines administered on or after 1 September 2021 and stratified the results by second-dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability. Results: Anti-S levels peaked at two weeks post-booster for BNT162b2 (22,185 U/mL; 95%CI: 21,406-22,990) and ChAdOx1 second-dose recipients (19,203 U/mL; 95%CI: 18,094-20,377). These were higher than the corresponding peak antibody levels post-second dose for BNT162b2 (12,386 U/mL; 95%CI: 9,801-15,653, week 2) and ChAdOx1 (1,192 U/mL; 95%CI: 818-1735, week 3). No differences emerged by second dose vaccine type, age, sex or clinical vulnerability. Anti-S levels declined post-booster for BNT162b2 (half-life=44 days) and ChAdOx1 second dose recipients (half-life=40 days). These rates of decline were steeper than those post-second dose for BNT162b2 (half-life=54 days) and ChAdOx1 (half-life=80 days). Conclusions: Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but levels are projected to be similar after six months for BNT162b2 recipients. Higher peak anti-S levels post-booster may partially explain the increased effectiveness of booster vaccination compared to two-dose vaccination against symptomatic infection with the Omicron variant. Faster waning trajectories post-third dose may have implications for the timing of future booster campaigns or four-dose vaccination regimens for the clinically vulnerable.

Objective:External validation of symptom severity classification levels for the PostConcussion Symptom Inventory (PCSI).Participants and Methods:Two distinct samples of parents and children, ages 8-18, participated from a: (1) prospective multicenter cohort study (Predicting Persistent Post-concussive Problems in Pediatrics, 5P) (Zemek et al., 2016), including parents (n=2,852), adolescents (n=1,087; mean age=15.13; 54% male), and children (n=1,271; mean age=10.70; 65% male) and (2) published clinic sample at Children’s National Hospital (CN) including parents (n=1,197; adolescents, n=835; children, n=326) (Gioia et al., 2019). Participants completed the age-specific Post-Concussion Symptom Inventory (PCSI): Mean time postinjury = 8 hours (5P), 6 days (PCSI2), generating a post-pre-injury difference (RAPID) score. The distribution of the RAPID scores for the Total Symptom and 4 subscales (physical, emotional, cognitive, sleep/fatigue) were examined to define 4 symptom severity classification levels (minimal - within the CI for recovered, low <20th %tile, moderate 21-79th %tile, high >80th %tile) for the respective samples. These severity distributions were compared between the two distinct datasets.Results:ANOVAs were performed to examine group differences in the mean scores for each of the 4 classification levels. No significant differences were found for all the RAPID score distributions with minimal effect sizes (<.1% variance) for the parents, adolescents and children. PCSI RAPID Total Score ranges for the severity classifications were as follows: Minimal-Parent and adolescent groups 5P<=5, Clinic <=5; Children: 5P<=3, Clinic<=3; Low- Parents 5P 6-15, Clinic 6-13; Adolescents 5P 6-19, Clinic 6-16; Children: 5P 4-7, Clinic: 4-7; Moderate-Parents 5P 16-49, Clinic 14-47; Adolescents 5P 20-56, Clinic 17-51; Children 5P 8-17, Clinic: 818; High- Parents: 5P>=50, Clinic >=48; Adolescents 5P >=57, Clinic >=52; Children 5P >=18, Clinic >=19).Conclusions:Our findings reveal a parallel distribution of RAPID scores in the two distinct 5P and Clinic patient populations, yielding nearly identical severity classification level parameters across all five PCSI symptom domains (total score, physical, cognitive, emotional, and sleep/fatigue). The present investigation provides evidence of validity for the use of these severity classification levels across the ED and specialty clinic settings.

Abstract Abstract 1360 The arbitrary cut-off of 5000/μL chronic lymphocytic leukemia (CLL)-phenotype cells in peripheral blood is generally used to separate monoclonal B-cell lymphocytosis (MBL) from CLL. However, a major concern is the biological differentiation, if any, between MBL and CLL. We tried to address the issue therefore analyzing 261 Rai stage 0 patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) prospective multicentre trial designed to validate biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk. In this cohort, biological characteristics of 105 (40.2%) patients who would be reclassified as MBL using the 2008 CLL diagnostic criteria were compared with those of the remaining 156 patients who had more than 5000/μL CLL-phenotype cells in peripheral blood and fulfilled diagnostic criteria of CLL. Male to female ratio was similar for MBL and CLL (54/53 vs. 92/66, P=0.21) as was median age (58.18 vs 58.18, P=0.98). Median absolute number of cells with CLL phenotype in peripheral blood was 3120/μL (range,400-4959) in MBL and 9925/μL (range, 5020–110000) in CLL (P<0.0001). No difference in the CD38 status (P=0.48),ZAP-70 expression (P=0.29) or cytogenetic abnormalities as detected by FISH [trisomy 12 (P=0.24); deletion 11q (P=0.68); del17p (P=0.09)] was found between patients with MBL and CLL. The only feature differentiating CLL from MBL was represented by an excess of patients with unmutated IgVH disease in the former group (CLL,69.2% vs. MBL, 30.8%: P=0.04). In addition, patients with CLL had an about 2-fold risk of having IgVH germline status in comparison to patients with MBL (OR,1.80; 95% CI, 1.02–3.13; P=0.04). Since the arbitrary cut-off of 5000/μL CLL-phenotype cells in peripheral blood failed to identify a peculiar biological profile for either MBL or CLL, we wondered whether a different B-cell threshold based on disease clinical outcome better stratified patients according to biological risk. In an independent cohort including 818 Rai stage 0 patients registered in a GIMEMA (Gruppo Italiano Malattie EMatologiche Maligne dell'Adulto) database, we demonstrated that a count of 10000/ μL B-cells is the best lymphocyte threshold to predict time to first therapy (TFT). When this cut-off was applied to the GISL series we found that the distribution of main high-risk features [CD38, P=0.83; trisomy 12,P=0.36; del11q,P=0.85; del17,P=0.37) was similar between patients with B-cell lymphocytes higher and lower than 10000/ μL. Only an excess of cases with unmutated IgVH (P=0.04) and slightly increase of ZAP-70 (P=0.06) characterized patients B-cell higher than 10000 μL. In conclusion, present data obtained from a prospective multicentre study indicate that biological characteristics of CLL are found also in MBL and there is no general predominance of good risk variables in MBL in comparison to CLL. This implies that MBL may not be considered a distinct disease but as an early stage of CLL. Disclosures: Musto: Celgene: Honoraria; Janssen Cilag: Honoraria.

INTRODUCTION: Rates of mental illness are disproportionately higher among medical residents. Neurosurgical trainees are no exception and may be more likely to suffer from depression, anxiety, and/or burnout than other residents. An assessment of the prevalence of mental illness in U.S. neurosurgical residents in the post-COVID-19 era is lacking in the literature and understanding the risk factors is vital to combating these mental health disorders. METHODS: Cross-sectional study analyzing responses to a 28-question survey from March-May 2023 distributed to U.S. neurosurgery residents. The survey included demographic and program-specific information, as well as Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) screening questions. PHQ-9 and GAD-7 scores >5 represent at least mild depression and anxiety, respectively. RESULTS: Forty-eight responses were included in the analysis, which consisted of 35 males (74%), 36 married respondents (77%), and 27 junior residents (56%, PGY-1 to 4). Twenty-four residents (50%) screened positive for depression, 19 residents (40%) screened positive for anxiety, and 26 residents (54%) reported feeling burned out. Depressed residents were highly more likely to also suffer from anxiety (70%, p < 0.0001) and burnout (79%, p = 0.001). Further, junior residents (63%, p = 0.042), female residents (83%, p = 0.008), and residents on a neurosurgical rotation (60%, p = 0.036) were more likely to screen positive for depression. However, being married (p = 0.318), practicing in one’s home state (p = 0.724), having a 24-hour call system (0.188), having formal didactic time (p = 0.125), and having program-led wellness initiatives (p = 0.069) were not protective. CONCLUSIONS: Half of U.S. neurosurgery residents who responded screened positive for depression, 40% screened positive for anxiety, and 54% felt burned out. Depression was strongly correlated with both anxiety and burnout. Neurosurgery residents who were female, in their junior years, and on-service were at particularly high risk for depression.

Abstract An alkaline phosphatase (ALPase) from Saccharomyces cerevisiae strain 257 was purified 345-fold with specific activity of 54 533 nmol × min−1 × mg protein−1 . It was shown to be a dimeric protein (apparent mol. wt. approx. 130 kDa) with optimum activity at pH 8.6 - 8.8 and good stability at 50 °C. The ALPase was a non-specific enzyme hydrolyzing a wide variety of monophosphate esters. The enzyme showed protein phosphatase activity and this activity was not Mg2+ - dependent in contrast to p-nitrophenyl phosphate (pNPP) activity. The Km value for pNNP hydrolysis was determined to be 2.2 × 10−5 м. Orthophosphate inhibited the enzyme in a competitive mode with the Ki of 2.3 x 10−4 м. Phosphate transfer of the ALPase is almost zero with all alcohols tested except for Tris.

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

Abstract Introduction: Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and, according to guidelines, should receive extended oral anticoagulation (OAC). OAC prevents recurrence in most patients but may cause major bleeding. Patients with a low recurrence risk could therefore benefit from limited OAC duration. The Vienna prediction model (VPM) estimates the recurrence risk of patients with a first unprovoked deep vein thrombosis (DVT) of the leg and/or pulmonary embolism (PE) based on the patient's sex, site of index VTE and D-Dimer measured after stopping OAC (Eichinger et al., Circulation 2010). In a prospective cohort management study, we evaluated whether the VPM can identify patients with an unprovoked VTE at low recurrence risk. Methods: The study was performed between January 2013 and May 2021 at two tertiary Austrian hospitals. Patients &gt;18 years with a first symptomatic DVT of the leg and/or symptomatic PE were eligible. The diagnosis of VTE was established by compression ultrasonography (CUS), spiral computed tomography, or lung scanning. We excluded patients with previous VTE, VTE provoked by a temporary risk factor including surgery, trauma, pregnancy, immobilisation, or female hormone intake, with cancer, OAC duration longer than 7 months or OAC for reasons other than VTE. OAC was discontinued 3 to 7 months after VTE diagnosis. D-Dimer was measured by a quantitative assay 3 weeks later and the probability of recurrence was estimated by the VPM. In patients with &lt;180 risk points (corresponding to a predicted one-year recurrence risk of &lt;4.4%), OAC was not resumed. CUS of both legs was performed at the time of discontinuation of OAC for reference baseline imaging in case of suspected recurrence. Patients were seen after 3, 12 and 24 months or at recurrence. Patients with a high recurrence risk (&gt;180 VPM risk points) were excluded and their management was left to the discretion of their local practitioner. The main outcome measure was independently adjudicated recurrence of symptomatic DVT of the leg and/or symptomatic PE. The study was approved by the local ethics committees and all patients gave written informed consent. Statistical analysis: Baseline characteristics of patients were described by median and interquartile range (IQR) or by absolute frequency and percentage. The cumulative risk of recurrent VTE after discontinuation of OAC was estimated using the Kaplan-Meier method. Recurrence risk was also predicted with the VPM for each patient, and predictions were averaged over the study group. Results: Of 818 eligible patients, 520 (65%) had a risk score of &lt;180 points and were classified as being at low risk of recurrence. They were included in the study and did not resume OAC. Their median age was 52 (42-65) years, and 289 (56%) were men. 226 (43%) patients had PE, 206 (40%) proximal and 88 (17%) distal DVT as index VTE. Median duration of anticoagulation was 3.9 (3.3-5.7) months, and the median time of follow-up was 23.9 (23.8, 23.9) months. Ten (1.9%) patients were lost to follow-up.52 patients (of which 30 were male) had non-fatal recurrent VTE (5.8 events per 100 patient-years, 95% CI 4.4-7.7). 28 (54%) patients had PE, 17 (33%) proximal and 7 (13%) distal DVT at recurrence. The cumulative risk of recurrence at one and two years was 5.2% (95% CI 3.2-7.2) and 11.2% (95% CI 8.3-14), respectively (Figure 1). The corresponding predicted recurrence risk for the study group was 4% and 7%, respectively. Conclusion: The VPM identifies patients with unprovoked VTE at low risk of recurrence. Applying the VPM refines risk stratification which could facilitate treatment decisions on the duration of OAC for patients and physicians. The model was well calibrated at one year. The apparent underestimation of the recurrence risk at two years could be countered by recalibration. Figure 1 Figure 1. Disclosures Eichinger: Takeda: Speakers Bureau; Daiichi-Sankyo: Speakers Bureau; BMS: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau; Boehringer-Ingelheim: Speakers Bureau; CSL Behring: Speakers Bureau.

Abstract Introduction Total (-7) or partial (7q-) monosomy 7 is frequent in malignant myeloid disorders, observed in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. Monosomy 7 is associated with poor outcome, high susceptibility to infections and poor response to chemotherapy. A therapeutic benefit for 5-azacytidine was previously described (Fenaux et al., 2009). The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with monosomy 7 in a multicentric, retrospective German cohort study. Patients and methods Currently, 231 patients with MDS/AML following MDS and monosomy 7 were included. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, age ≥18 years, bone marrow blast count ≤30% and presence of -7 or 7q-. The data was assembled from centers in Düsseldorf, (n=120; 52%), Cologne (n=38; 17%), Freiburg (n=31; 13%), Göttingen (n=14; 6%), Munich (n=13; 6%), Dresden (n=11; 5%) and Mannheim (n=4; 2%). The median age in the study cohort was 67 years, 65% of patients were males. 29/231 patients (13%) were diagnosed as AML following MDS. MDS/AML was therapy-associated in 24 patients (11%). Regarding IPSS, 38 (19%) were classified as low/intermediate 1 risk and 165 (81%) as intermediate-2/high-risk. According to IPSS-R, 2 (1%) were assigned to the very-low/low risk group, 31 (16%) to the intermediate group, 52 (27%) to the high-risk group and 107 (56%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), demethylating agents (DMA; either 5-azacytidine or decitabine), and others. Results A best supportive care regimen was chosen in nearly half of the patients (49%). The remaining patients received 1-4 sequential therapies (1: 29%; 2: 11%; 3: 10%; 4: 1%). As the first line therapy, 64 patients (54%) received DMA, 24 (20%) an allo-Tx, 9 (8%) HDC, 5 (4%) LDC, and 16 (14%) were treated with other therapies. The best prognosis was observed in patients eligible for allo-Tx: The median OS in transplanted patients was 924 days as compared to 361 days (p<0.01) in patients not eligible for transplantation. In the latter cohort, patients who received DMA at any course of their disease did not differ from those receiving other therapies: The median OS was 468 days in patients treated with DMA as compared to 325 on those with alternative therapies (p not significant) and the median time to AML-transformation was 580 versus 818 days (p not significant), respectively. However, by classifying patients according to IPSS- and IPSS-R, it became obvious that patients with an IPSS high-risk or an IPSS-R very high risk showed a clear benefit from DMA: In the first group, median OS was 444 days in DMA-treated and 201 days in non-DMA-treated patients (p=0.048), in the latter group, median OS 444 days in the DMA-treated and 203 days in the non-DMA treated cohort (p=0.017). Comparable results were observed regarding AML-free survival: Median time to AML was 580 (DMA) vs. 186 (no DMA) days in IPSS high risk patients (p=0.031) and 580 (DMA) vs. 273 (no DMA) days in the IPSS-R very high risk group (p not significant). Conclusions Patients with MDS, partial or total monosomy 7 and a high risk according to IPSS or a very high risk according to IPSS-R show a pronounced benefit when treated with DMA, regarding overall- as well as AML-free survival. Further results from the ongoing data analysis will be presented in detail. The study was supported by research funding from Celgene. Disclosures: Schanz: Celgene: Research Funding. Braulke:Celgene: Research Funding. Germing:Celgene: Honoraria, Research Funding. Schmitz:Novartis: Research Funding; Celegene: Consultancy, Research Funding, Speakers Bureau. Götze:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Research Funding. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Abstract Abstract 2041 Introduction: Allogeneic hematopoietic cell transplantation (HCT) following reduced-intensity conditioning (RIC) using fludarabine (FLU) and busulfan (BU) is a treatment option for heavily pretreated or comorbid patients. There is limited published experience with this approach in patients aged ≥65 years, and the influence of patient age on outcome remains to be evaluated. Methods: Retrospective analysis of 79 consecutive adult patients (median age 60 years, range 30–74, f=34, m=45) after allogeneic HCT using FLU (30 mg/m2, day -6 to -2) and BU (0.8 mg/kg q 6 hrs from day -4 to -2) for RIC at our institution from 2005 to 2012. Antithymocyte globulin, calcineurin inhibitor combined with mycophenolate mofetil (n=18) or methotrexate (n=61) were used as graft-versus-host disease (GVHD) prophylaxis. For statistical analysis, patients were grouped in 2 age categories: Patients <65 years (group A, n=59, median age 57 years) and patients ≥65 years (group B, n=20, median age 67 years). Results: Diagnoses were acute myeloid leukemia (AML, A=22, B=10), myelodysplastic syndrome (MDS, A=14, B=6) and myeloproliferative disease (MPD, A=23, B=4). At time of HCT, 34% of patients in A and 50% in B were in complete remission (p=0.20). Grafts either from matched related (MRD, A=13, B=1), matched unrelated (MUD, A=21, B=8) or mismatched unrelated (MMUD, A=25, B=11) donors were used. In all patients, grafts consisted of G-CSF mobilized peripheral blood stem cells (median CD34+ cells/kg, A=6.0×106, B=7.4×106, p=0.52). CMV disparity was equally distributed between both groups (p=0.39). Median time to neutrophil count >500/μl was 21 days in group A and 20 days in group B (p=0.24). Median time to platelet recovey >20,000/μl was 18 days in group A and 16 days in group B (p=0.36). Complete donor chimerism in peripheral blood was established in group A and B after a median of 45 and 34 days, respectively (p=0.11). Because of mixed chimerism or relapse after HCT, 21 patients (A=16, B=5, p=0.85) received CD3+ donor lymphocyte infusions (A: median 10×106/kg, range 1–140×106/kg; B: median 13×106/kg, range 3–177×106/kg; p=0.77) after a median of 131 and 119 days, respectively (p=0.64). Current overall survival (OS) is 44/79 patients with a median follow-up of 818 days (range 53–2386) of patients alive resulting in a Kaplan-Meier estimated 3-year event-free survival (EFS) and OS of 42% and 52%, respectively. Although not statistically significant, AML was associated with an adverse outcome (3-year OS 37% compared to 60% for MDS, p=0.19 and 63% for MPS, p=0.09). The use of a related donor was not superior to an unrelated donor (3-year OS 49% compared to 44% for MUD, p=0.48 and 57% for MMUD, p=0.72). For the whole cohort, complete donor chimerism in peripheral blood on day +100 was associated with an improved survival (3-year OS 76% vs. 38%, p=0.002). The elderly subgroup showed a similar outcome compared to the younger patients (3-year OS in A 44% vs. 53% in B, p=0.90). Cumulative incidence of non-relapse mortality (NRM) adjusted for relapse as competing risk was 23% in group A and 10% in group B at 3 years (p=0.31). Cumulative incidence of relapse at 3 years with death due to NRM as competing risk was 34% in group A and 54% in group B (p=0.61). Causes of death were relapse (A=13, B=6), sepsis (A=7, B=0), GVHD (A=3, B=1) and others (A=4, B=1). CMV reactivation after HCT occurred comparably in both groups (A=19, B=7, p=0.82). Incidence of acute GVHD≥2 was similar in group A and B (10% vs. 15%, p=0.56) and had no significant influence on survival of the whole cohort (3-year OS 60% vs. 51%, p=0.94). Incidence of chronic GVHD was 41% in A (limited=15, extensive=9) and 55% in B (limited=8, extensive=3) (p=0.27). Analyzing the whole cohort, extensive chronic GVHD (3-year OS 31%) showed a trend towards an adverse outcome compared to limited (3-year OS 57%, p=0.07) or absent (3-year OS 55%, p=0.22) chronic GVHD. Conclusion: RIC with FLU/BU for allogeneic HCT is an important treatment option in the elderly patient population. Age itself has no negative impact on survival. Complete donor chimerism on day +100 is associated with an improved OS. Disclosures: Off Label Use: Conditioning in elderly patients.

Abstract Crucible CPM Rex 54 HS is a cobalt-bearing high speed tool steel that is produced by the proprietary Crucible Particle Metallurgy (CPM) process. It combines the wear properties of the popular high vanadium M4 grade with the red hardness of the cobalt-bearing M35/Crucible CPM Rex 45 HS grades. Crucible CPM Rex 54 HS may be used as an upgrade for improved red hardness over M3 or M4 without giving up the abrasion resistance, or as an upgrade for improved wear resistance over M35 or Crucible CPM Rex 45 HS without giving up the red hardness. This datasheet provides information on composition, physical properties, microstructure, hardness, and elasticity. It also includes information on wear resistance as well as heat treating and surface treatment. Filing Code: TS-818. Producer or source: Crucible Industries LLC.

A field experiment was conducted to know the crop weather relationships under different sowing windows and hybrids in maize at the College of Agriculture, University of Agricultural and Horticultural Sciences, Shivamogga, Karnataka, during Kharif 2015. The experimental site is situated at 14°01 to 14°11 North latitude and 75°401 to 75°421 East longitude with an altitude of 650 meters above mean sea level. The experiment was laid out in a randomized complete block design (RCBD) with a factorial concept and replicated thrice. There were eight treatment combinations, including four-date of sowing (15th June, 30th June, 15th July and 30th July) and two hybrids (PAC-740 and CP-818). Maize sown on 15th June recorded significantly higher grain yield (7632.57 kg ha-1) as compared to other dates of sowing and among the hybrids, CP-818 (7060.72 kg ha-1) was found superior than PAC-740 (6776.93 kg ha-1). Grain yield had a highly significant positive correlation with weather parameters such as cumulative pan evaporation (0.85**), cumulative solar radiation (0.83**), cumulative rainfall (0.79**) and average relative humidity (0.75**) during silking to maturity stage. The variation in grain yield was primarily affected by average maximum temperature (69%) followed by cumulative sunshine hours (68%) and cumulative pan evaporation (66%) during sowing to maturity and lower variation was observed in average relative humidity (54%) during silking to maturity. From the present findings it can be inferred that sowing maize on June 15th with CP-818 hybrid can be a better option to get higher productivity in southern transition zone of Karnataka.

Abstract Background Despite fractures of Isolated Weber B being prevalent, there is a lack of clarity regarding the relative effectiveness of surgical versus conservative treatment. This systematic review and meta-analysis aimed to investigate the clinical effects and complications of surgical versus conservative treatment of the Isolated Weber B ankle fractures. Methods This study involved thorough searches across multiple electronic databases, including PubMed, Cochrane, Embase, and Web of Science, to identify all relevant publications on Isolated Weber B ankle fractures repaired through surgical versus conservative treatment. Through a comprehensive meta-analysis, several outcomes were evaluated, including post-operative function, complications and reoperation rate. Result Six articles involving 818 patients who met the inclusion criteria. Among these participants, 350 were male and 636 were female. 651 patients received conservative treatment, while 396 underwent surgical intervention. The findings indicate no significant differences in OMAS, FAOQ, PCS, MCS scores, and return to work between surgical and non-surgical treatments for isolated Weber B ankle fractures. However, compared with surgical treatment, non-surgical treatment has a higher AOFAS score(MD = -5.31, 95% CI = [-9.06, -1.55], P = 0.20, I2 = 39%), lower VAS score(MD = 0.72, 95% CI = [0.33, 1.10], P = 0.69, I2 = 0%), lower complication rate (RR = 3.06, 95% CI = [1.58, 6.01], P = 0.05, I2 = 54%), and lower reoperation rate(RR = 8.40, 95% CI = [1.57, 45.06], P = 0.05, I2 = 67%). Conclusion

ObjectiveDescribe the landscape of tobacco-related topics, funders and institutional networks in Africa.Data sourcesWe searched PubMed, Embase and African Index Medicus for published articles from January 1996 to August 2018 in any language.Study selectionTwo researchers independently reviewed titles and abstracts for a focus on nicotine or tobacco product(s) and describe data or recommendations specific to Africa. Ultimately, 818 articles were identified.Data extractionThree independent coders conducted qualitative analyses of articles and extracted funders, study populations, countries of research focus, research topics, tobacco products, study design and data source. A bibliometric analysis estimated coauthorship networks between the countries of authors’ primary institutional affiliation.Data synthesisAll 54 African countries were represented in two or more articles. The coauthorship network included 2714 unique authors representing 90 countries. Most articles employed a cross-sectional study design with primary data collection, focused on cigarettes and studied use behaviour. Few articles examined tobacco farming or interventions for cessation or prevention. The most frequently cited funder was the US National Institutes of Health (27.2%). A range of coauthorship patterns existed between African institutions with some coauthoring with one institution while others coauthored with 761 institutions in other African countries.ConclusionsThe literature review identified the need for implementation research for tobacco control interventions and policies, economic and development impacts of tobacco use research, and tobacco industry and tobacco production and farming research. Numbers of research collaborations between institutions in Africa vary, suggesting the need for regional institutional capacity building.

Context and objectives: Several authors approach epidemiological studies on dermatoses using an etiological diagnostic approach; the Willaniste school being mostly reserved for learners of dermatology and/or non-dermatologist doctors. The objective of this study is to determine the profile of dermatoses in children using exclusively the type of elementary lesion. Methods: In a retrospective, analytical and descriptive study, the data of children with dermatoses followed in the Dermatology Service of the University Clinics of Kinshasa between June 1, 2009 and December 31, were collected. The parameters of interest included epidemiological and clinical characteristics. Results: The hospital frequency of dermatoses in children (DC) according to the lesional diagnostic approach is 40.89% (818/1994). Their median age was 60 months (QEI 60-65.9) with a female predominance (55.7%, sex ratio of 1.25/1). There were more infants (30.6%). DC predominated in the dry season (54%). The entangled (21.02%) and vesicular (20.29%) lesional types were the most numerous, with ringworm of the scalp (31.9%) and atopic dermatitis (54.2%) respectively. The papular, erythematous, tumor and entangled lesion types were related to sex and age; pustular and tumor exclusively related to the season, in a statistically significant way (p ˂ 0.05). Taken as a whole, the most frequent dermatoses were atopic dermatitis (11%), prurigo strophulus (10.8%), impetigo (7.4%), Tinea capitis (6.7%) and scabiosis (6.4%). Conclusion: The importance of this work lies in the interest of taking into account the two approaches, lesional and etiological of dermatoses, for their global management and research studies. Indeed, the lesional approach, also important in the study of dermatoses, appears to our knowledge to be poor in references in the literature. Keywords: Dermatoses, Children, Lesional diagnostic approach, Kinshasa

IntroductionStroke is a leading cause of death and disability worldwide. Recurrent strokes are seven times more lethal than initial ones, with 54% leading to long-term disability. Substantial recurrent stroke risk disparities exist among ancestral groups. Notably, Africans face double the risk and higher fatality rates compared to Europeans. Although genetic studies, particularly GWAS, hold promise for uncovering biological insights into recurrent stroke, they remain underexplored. Our study addresses this gap through meta-analyses of recurrent stroke GWAS, considering specific ancestral groups and a combined approach.MethodsWe utilized four independent study cohorts for African, European, and Combined ancestry recurrent stroke GWAS with genotyping, imputation, and strict quality control. We harmonized recurrent stroke phenotype and effect allele estimates across cohorts. The logistic regression GWAS model was adjusted for age, sex, and principal components. We assessed how well genetic risk of stroke informs recurrent stroke risk using Receiver Operating Characteristic (ROC) curve analysis with the GIGASTROKE Consortium's polygenic risk scores (PRS).ResultsHarmonization included 4,420 participants (818 African ancestry and 3,602 European ancestry) with a recurrent stroke rate of 16.8% [median age 66.9 (59.1, 73.6) years; 56.2% male]. We failed to find genome-wide significant variants (p &lt; 5e−8). However, we found 18 distinct suggestive (p &lt; 5e−6) genetic loci with high biological relevance consistent across African and European ancestries, including PPARGC1B, CCDC3, OPRL1, and MYH11 genes. These genes affect vascular stenosis through constriction and dilation. We also observed an association with SDK1 gene, which has been previous linked with hypertension in Nigerian and Japanese populations). ROC analysis showed poor performance of the ischemic stroke PRS in discriminating recurrent stroke status (area under the curve = 0.48).DiscussionOur study revealed genetic associations with recurrent stroke not previously associated with incident ischemic stroke. We found suggestive associations in genes previously linked with hypertension. We also determined that knowing the genetic risk of incident stroke does currently not inform recurrent stroke risk. We urgently need more studies to understand better the overlap or lack thereof between incident and recurrent stroke biology.

Recent basic and clinical data demonstrated that the intrarenal renin-angiotensin system (RAS) plays an important role in the progression of chronic kidney disease (CKD). The urinary angiotensinogen (AGT) excretion rate could be a novel biomarker for the activity of the RAS in the kidney. We previously reported that the healthy volunteers do not have a circadian rhythm of AGT level in urine (Hypertension. 2011;57:e78) or in plasma (Hypertension. 2012;60:A399). However, the circadian rhythm of AGT level in urine and in plasma in patients with CKD has not been reported yet. Therefore, this study was performed to investigate the circadian rhythm of AGT level in urine and in plasma in patients with CKD. We recruited 6 CKD patients with continuous proteinuria admitted to the Kagawa University Hospital from 06/2011 to 10/2011 for the purpose of diagnostic renal biopsy. Plasma samples were collected at 06:00, 12:00, and 18:00. Urine samples were collected at 06:00, 09:00, 12:00, and 18:00. Plasma renin activities (PRAs), plasma and urinary AGT concentrations, and urinary albumin (Alb) concentration were measured using commercially available kits. The urinary concentrations of AGT and Alb were normalized by the urinary concentration of creatinine (Cr) (UAGT/Cr and UAlb/Cr, respectively). PRA (2.07 +/- 0.77 ng of angiotensin I/mL/hr at 06:00, 2.45 +/- 0.77 at 12:00, and 2.58 +/- 0.76 at 18:00, P = 0.8853) or plasma AGT (19.9 +/- 2.4 μg/mL at 06:00, 24.1 +/- 3.1 at 12:00, and 23.0 +/- 3.9 at 18:00, P = 0.6300) did not show a circadian rhythm. Moreover, UAlb/Cr (511 +/- 319 mg/g Cr at 06:00, 827 +/- 459 at 09:00, 1479 +/- 862 at 12:00, and 1370 +/- 818 at 18:00, P = 0.6964) or UAGT/Cr (54 +/- 22 μg/g Cr at 06:00, 119 +/- 41 at 09:00, 350 +/- 194 at 12:00, and 198 +/- 104 at 18:00, P = 0.3035) did not show a circadian rhythm. In conclusion, in addition to healthy volunteers, patients with CKD do not have a circadian rhythm of AGT level in urine or in plasma.

Abstract Funding Acknowledgements Type of funding sources: None. Background There is a need to better predict the risk of atrial arrhythmia (AA) and stroke in patients with hypertrophic cardiomyopathy (HCM). Purpose We sought to look at atrial remodeling and atrial function by echocardiography in a HCM-cohort to assess the association with occurrence of AA and stroke. Methods We retrospectively studied 216 patients diagnosed for HCM (mean age 52 ± 16 years) from 2015 to 2020. All patients underwent transthoracic echocardiography with the assessment of left atrial volume (LAV) and peak left atrial strain (PLAS). Patients were followed-up for 2,9 years for the development of a composite endpoint comprising occurrence of atrial arrhythmias and/or stroke. Results 78 patients had an event (24 stroke and 54 documented atrial arrhythmia). Univariate comparison analysis showed that LAV (37.2 ± 15.7 vs. 47 ± 20 ml/m², p = 0.0001) and anteroposterior LA diameter (41.7 ±7.58 vs. 45.8 ± 8.9 mm; p = 0.0006) were significantly higher in patients who met the composite endpoint, whereas PLAS was significantly impaired (27.1 ± 9.77 vs. 20.4 ± 10.5%; p &lt; 0.0001). Other echographic parameters associated with the composite endpoint were mean E/e" ratio (0.65 [0.55-0.85] vs. 0.60 [0.45-0.75]; p = 0.0204) and tricuspid annular peak systolic velocity (S") (cm/s) (13.3 ± 2.92 vs. 12.2 ± 3.26; p = 0.0148). NTproBNP level (216 vs. 818 ; p &lt; 0.0001), history of hypertension (42.3% vs. 62.3%; p = 0.005) and age at diagnosis (50.3 ± 16.7 vs. 57.1 ± 14.4; p = 0.0035) were the clinical parameters different between groups. In a multivariable analysis, PLAS was the only independent maker associated with the occurrence of AA and stroke, particularly for stroke with an odd ratio of 0.53 ([0.32-0.86]; p = 0.00097). Interestingly, 19 of 28 stroke patients (67%) did not experience any documented AA. Conclusion The decrease of PLAS is strongly associated with the risk of stroke, even in patients without documented atrial arrhythmia. Its use to guide the indication for an implantable holter monitoring and perhaps a prophylactic oral anticoagulation in HCM requires further investigation. Abstract Figure. Impaired PLAS in an HCM patient

Abstract Background Comfort of patients with medical students is important and promotes appropriate clinical reasoning and skills development in the students. There is however limited data in this field in Uganda. In this study, we examined the attitudes and comfort of patients attending care at the medical and obstetrics/gynecology specialties in teaching hospitals of three public universities in Uganda. Methods We conducted a cross sectional study among patients attending care at teaching hospitals for three public universities; Makerere University (Mak), Mbarara University of Science and Technology (MUST), and Gulu University (GU). Logistic regression was used to determine the magnitude of associations between independent and dependent variables. Two-sided p < 0.05 was considered statistically significant. Results Eight hundred fifty-five patients participated in the study. Majority were aged 18 — 39 years (54%, n = 460), female (81%, n = 696) and married (67%, n = 567). Seventy percent (n = 599) of participants could recognize and differentiate medical students from qualified physicians, and had ever interacted with medical students (65%, n = 554) during earlier consultations. Regarding attitudes of patients towards presence of medical students during their consultations, most participants (96%; n = 818) considered involvement of medical students in patients’ care as essential ingredient of training of future doctors. Most participants prefer that medical students are trained in the tertiary public hospitals (80%; n = 683) where they attend care. Participants who were single/never married were 68% less likely to recognize and differentiate medical students (aOR = 0.32, 95%CI: 0.22 — 0.53) from other members of the healthcare team as compared with married participants. Participants with university education had 55% lower odds of being comfortable with presence of medical students during consultation compared to those with primary education (aOR = 0.45, 95%CI: 0.21 — 0.94). Participants from MUST teaching hospital had twofold higher odds of being comfortable with presence of medical students compared to participants from Mak teaching hospitals (aOR = 2.01; 95%CI: 1.20 — 3.39). Conclusion Patients are generally comfortable with medical students’ involvement in their care; they prefer to seek care in hospitals where medical students are trained so that the students may contribute to their care. Medical students need to introduce themselves appropriately so that all patients can know them as doctors in training; this will promote patients’ autonomy and informed decisions.

Abstract Introduction: The coexistence of acromegaly and Cushing’s syndrome is quite rare. Case reports with this association have been described in the literature, including both ACTH-dependent and ACTH-independent Cushing’s syndrome. In these cases, when considering ACTH-independent hypercortisolism, the main etiology reported is adrenal adenoma. We will describe the case of an acromegalic patient with ACTH-independent cushing syndrome due to adrenal cortical carcinoma. Clinical Case: A 62-year-old male patient with acromegaly diagnosed by headache investigation. He had a previous medical history of T2DM for 20 years, grade III obesity (BMI 40.3), hypertension, obstructive sleep apnea and depression. Initial investigation showed IGF-1 levels of 818 ng/mL (81–225), GH: 3.39 ng/mL (&lt;0.97), prolactin diluted: 2.578 ng/mL (2.1–17, 7), LH: &lt;0.07 mIU/mL (1.5–9.3), FSH: 0.6 mIU/mL (1.4–18.1), total Testosterone: 51 ng/dL (241- 827) Cortisol at 8 AM: 15 µg/dL, TSH: 1.54 µg/dL (0.55–4.78), free T4: 1.0 ng/dL (0.89–1.76) and brain MRI with a large expansive sella turcica process, invading the right cavernous sinus, with growth to the sphenoid sinus and suprasellar compressing the optic chiasm, suggestive of pituitary macroadenoma. He underwent transsphenoidal resection with histology confirming a prolactin and GH co-secretory pituitary adenoma with Ki-67: 5%. He started treatment with octreotide LAR (30 mg/month) and cabergoline (3.5 mg/week) and underwent 25 radiotherapy sessions. Three years after the diagnosis of acromegaly, the patient underwent CT scan of the abdomen, which identified a 3.8 cm left adrenal nodular lesion that evolved in the 12-month control exam to nodular image with lobulated contours (5.0 x 3.4 cm) and non-contrast phase density &gt; 25 HU. At that time, he had two 24-hour cortisoluria samples: 640.9 and 637 µg/24hs (54–403) and ACTH &lt;5.0 pg/mL (&lt;46).The patient underwent videolaparoscopic adrenalectomy confirming the pathology of the lesion compatible with adrenal cortical carcinoma with invasion of the capsule and peri-adrenal adipose tissue and Ki-67: 20%. Even after primary resection of the adrenal lesion, the patient evolves with local and metastatic progression of the disease, dying a few months later, due to infectious complications of a new surgical approach. Conclusions: To the best of our knowledge, this is the first case of ACTH-independent Cushing’s syndrome caused by adrenocortical carcinoma in an acromegalic patient.

Abstract Background Gout affects 2.5% of adults in the UK but is often poorly managed. It can impair health-related quality of life (HRQOL), yet little is known about which people with gout are at risk of worse outcomes. We investigated factors associated with change in HRQOL over a three-year period in people living with gout in primary care. Methods People with gout registered with 20 general practices in the West Midlands completed the Gout Impact Scale (GIS), Short-Form-36 Physical Function subscale (PF10) and health assessment questionnaire disability index (HAQ-DI) at five time-points (baseline & 6, 12, 24 and 36 months) via postal questionnaire. Linear mixed modelling (LMM) with multivariate adjustment for baseline and time-varying covariates was used to investigate gout-specific, comorbid and socio-demographic factors associated with change in the Concern Overall (GIS-CO), PF10 and HAQ-DI over three years. Higher scores are worse for GIS-CO and HAQ-DI, but better for PF10. Results Of 1,184 baseline respondents, 818 (80%), 721 (73%), 696 (75%), 605 (68%) responded at 6, 12, 24 and 36 months respectively. Mean age (SD) at baseline was 65.6 (12.5) years. 990 (84%) were male, 494 (42%) reported &gt;2 gout flares in the previous year, 624 (54%) were taking allopurinol and 318 (27%) had an eGFR&lt;60mL/min/1.73m2. Factors identified as being associated with a deterioration in HRQOL over three years (table), were gout flare frequency (GIS-CO, PF10), history of oligo/polyarticular flares (GIS-CO, HAQ-DI), having a flare currently (GIS-CO), allopurinol use (PF10), having body pain (GIS-CO, PF10, HAQ-DI), higher pain severity (GIS-CO, PF10, HAQ-DI), number of comorbidities (PF10), eGFR &lt;60mL/min/1.73m2 (PF10, HAQ-DI), anxiety (GIS-CO), depression (PF10, HAQ-DI), and older age (PF10, HAQ-DI). Factors associated with an improvement in HRQOL were longer gout duration (GIS-CO), older age (GIS-CO), lower socioeconomic deprivation (PF10, HAQ-DI) and more frequent alcohol consumption (PF10, HAQ-DI). Conclusion Gout-specific, comorbid and socio-demographic factors associated with change in HRQOL over a three-year period in people living with gout in primary care were identified, highlighting people at risk of worse outcomes over three years and at greatest need of urate-lowering therapy and other targeted interventions. Disclosures L. Watson None. J. Belcher None. E. Nicholls None. P. Chandratre None. M. Blagojevic-Bucknall None. S. Hider None. S.A. Lawton None. C.D. Mallen None. S. Muller None. K. Rome None. E. Roddy None.

Introduction & Objective: Efsitora is an insulin receptor agonist designed to have a flat pharmacokinetic profile and long half-life enabling weekly dosing. While these features may provide stable glucose levels, their impact on hypo risk is less clear. A phase 1 study was conducted to assess hypo risk using controlled, experimental conditions that mimic hypo risk situations that may be encountered in daily life. Methods: This single-site, open-label, 2-period, fixed-sequence (glargine-efsitora) study was conducted in 54 participants with T2D previously on basal insulin (BMI 21.8-39.7 kg/m2, HbA1c 6.5-9.4%). After titration to stable fasting glucose (FG) with glargine or efsitora, the incidence of hypo was assessed during 3 test conditions: prolonged fasting 24-hrs (PF), PF with exercise (EX), and after receiving a double dose (DD) of study insulin. Results: Mean FG at start of tests was 6 mg/dL lower with PF and EX and 10 mg/dL lower with DD in the efsitora group compared to glargine. Incidence of Level 1 hypo (≥54 to &lt;70 mg/dL) was not significantly different under any test condition: incidence efsitora vs glargine, difference in proportion (95%CI) for PF: 44.7 vs 42.6%, 2.1 (-17.2, 21.4); EX: 65.9 vs 50.0%, 15.9 (-3.0, 34.8); DD: 68.1 vs 61.7%, 6.4 (-12.8, 25.6). Level 1 hypo resolved spontaneously or after 15g oral glucose. Level 2 (&lt;54 mg/dL) was infrequent in both treatments and all test conditions. No severe hypo occurred in this study. Mean nadir glucose for hypo was similar between treatments and test conditions ranging from 62.8-66.3 mg/dL. Duration of hypo events was also similar between treatments ranging from 76.6 to 115.2 mins depending on the test condition. Conclusion: Once weekly efsitora did not increase the incidence, duration, or severity of hypo compared to once daily glargine during periods of provocation in patients with T2D. Disclosure T. Heise: Research Support; ADOCIA, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk A/S. Consultant; Gan&Lee Pharmaceuticals. Speaker's Bureau; Eli Lilly and Company. Research Support; Altimmune Inc., Sanofi, Zealand Pharma A/S, BIOTON, Civica Foundation, Enyo Pharma, Gan&Lee Pharmaceuticals, Nanexa AB, SamChunDang Pharm. Co. G. Andersen: Employee; Profil Institut für Stoffwechselforschung GmbH. E.J. Pratt: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Leohr: None. T. Fukuda: Employee; Eli Lilly and Company. Q. Wang: Employee; Eli Lilly and Company. C.M. Kazda: Employee; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Eli Lilly and Company. R.M. Bergenstal: Other Relationship; Abbott. Research Support; Arkray Marketing. Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur. Other Relationship; Dexcom, Inc., Eli Lilly and Company. Consultant; embecta, Hygieia. Research Support; Insulet Corporation. Consultant; MannKind Corporation. Other Relationship; Medtronic, Novo Nordisk. Consultant; Onduo LLC, Roche Diabetes Care. Other Relationship; Sanofi. Research Support; Tandem Diabetes Care, Inc. Other Relationship; UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Funding This research was funded by Eli Lilly and Company.

Abstract Context: Athletic directors are charged with making impactful decisions for secondary school athletic programs that mitigate risk for stakeholders involved. This includes decision-making regarding the provision of medical care for student-athletes. To date, limited research has explored athletic directors' perceptions of athletic training. Objective: To evaluate public school athletic directors' knowledge and perceptions of the athletic trainer (AT) role. Design: Concurrent mixed methods. Setting: Cross-sectional online questionnaire. Patients or Other Participants: Athletic directors representing all 50 states and the District of Columbia (n=954; 818 males, 133 females, 3 preferred not to answer; age = 47.8 ± 9.1 years; years in current role = 9.8 ± 8.3). Intervention(s): Questionnaire composed of demographics, various quantitative measures assessing athletic directors' knowledge and perceived value of ATs, and open-ended questions allowing for expansion on their perspectives. Main Outcome Measure(s): Descriptive statistics were reported, with key quantitative findings presented as count response and overall percentages. Qualitative data were analyzed using the general inductive approach. Results: A majority of respondents recognized the ATs' role in injury prevention (99.8%), first aid/wound care (98.8%), therapeutic interventions (93.8%), and emergency care (91.6%). Approximately 61% (n=582) identified AT employment as a top sport safety measure, and 77% (n=736) considered an AT to be extremely valuable to student-athlete health and safety. Athletic directors appeared to recognize the value of ATs as they provide “peace of mind” and remove the responsibility of making medical decisions from coaches and administration. Conclusions: Athletic directors appeared to recognize the value ATs bring to the secondary school setting and demonstrated adequate knowledge regarding ATs' roles and responsibilities. Educational efforts for this population should focus on AT-related tasks that are not frequently seen in the public eye, yet add to perceived value, in order to potentially influence hiring decisions.

Background: Pharmacological and clinical evidence suggest that sulfonylurea (SU) medications may improve acute ischemic stroke (AIS) outcomes. The SHINE trial studied intensive vs standard blood sugar management in patients presenting with AIS and hyperglycemia. We investigated whether pre-existing SU use impacted functional outcomes in SHINE. Methods: SHINE data collection forms were reviewed to identify AIS patients taking SUs at the time of study enrollment. Our primary outcome compared the adjusted 90-day utility weighted modified Rankin Scale (UW-mRS) score in the SU and non-SU cohorts. The UW-mRS score was adjusted for age, baseline NIHSS, baseline glucose, and reperfusion therapy. Pre-specified analyses of the 90-day UW-mRS scores assessed for heterogeneity of SU effect across the following subgroups: age, stroke severity, reperfusion therapy, type of SU, and SHINE study arm. Results: In total, 1066 SHINE subjects with a final diagnosis of AIS were included (SU=248 [23.3%], non-SU=818 [76.7%]). Baseline demographics were generally similar (Table 1). Calculated 90-day mean UW-mRS score were higher in the non-SU group compared to the SU group: mean 0.617 ± 0.012 versus mean 0.566 ± 0.022 (Diff 0.051, 95% CI 0.001-0.1) without heterogeneity of treatment effect (Figure 1). Conclusion: Contrary to our hypothesis and published literature, our retrospective analysis of the SHINE trial demonstrated better functional outcomes in the non-SU cohort. This may be due to selection bias with inadequate controlling for baseline risk factors present in the SU cohort. Definitive prospective studies are required.

Вивчення зумовленості сприйняття особистістю грошей, кредитних продуктів виявляється все більш затребуваним проблемним полем досліджень, про що свідчать новітні публікації як західних, так і українських вчених. Проте у більшості досліджень вивчаються лише окремі передумови особистісного сприйняття грошей та кредитів. Мета дослідження – емпіричне вивчення психологічних особливостей сприйняття кредитних продуктів банківських установ здобувачами вищої освіти. Виходячи з мети, завданнями дослідження були такі: визначення типів грошових настановлень у здобувачів, вивчення чинників, які впливають на ставлення здобувачів вищої освіти до грошей, визначення обізнаності здобувачів у питаннях діяльності банківських установ, поведінки користувачів банківських кредитів і доцільності користування кредитними послугами банків. Нами було використано такі методики: методики «Шкала грошових уявлень та поведінки» (Money Beliefand Behaviour Scale) (авт. А. Фернем), анкета О.Г. Ходакевич «Моє ставлення до грошей», опитувальник «Ставлення до горошей та кредиту здобувачів вищої освіти» (авт. С.В. Шевченко), методика «Шкала грошових уявлень та поведінки» (А. Фермен, модифікація М.В. Сімків). Визначено, що в юнацькому віці своєрідно виявляється система базисних ставлень до грошей: у ставленні до себе збільшується ступінь адекватності сприйняття кредитів, водночас оцінка кредитних продуктів здійснюється на основі власних уявлень, які подекуди бувають ілюзорними і поверхневими, зростає ступінь довіри до банківських установ, а власний образ грошей і кредиту менше залежить від оцінок інших. Водночас ускладнення перебігу процесу економічної соціалізації підростаючого покоління нерідко призводить до виникнення неконструктивного сприйняття грошей і кредитів: від надання їм дуже великого значення, бажання збагатитися будь-яким шляхом (аж до незаконних дій) до повного нівелювання їх значення. Література Білоконь, І.В. (2007). 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Photo by niu niu on Unsplash ABSTRACT Shackling prisoners has been implemented as standard procedure when transporting prisoners in labor and during childbirth. This procedure ensures the protection of both the public and healthcare workers. However, the act of shackling pregnant prisoners violates the principles of ethics that physicians are supposed to uphold. This paper will explore how shackling pregnant prisoners violates the principle of justice and beneficence, making the practice unethical. INTRODUCTION Some states allow shackling of incarcerated pregnant women during transport and while in the hospital for labor and delivery. Currently, only 22 states have legislation prohibiting the shackling of pregnant women.[1] Although many states have anti-shackling laws prohibiting restraints, these laws also contain an “extraordinary circumstances” loophole.[2] Under this exception, officers shackle prisoners if they pose a flight risk, have any history of violence, and are a threat to themselves or others.[3] Determining as to whether a prisoner is shackled is left solely to the correctional officer.[4] Yet even state restrictions on shackling are often disregarded. In shackling pregnant prisoners during childbirth, officers and institutions are interfering with the ability of incarcerated women to have safe childbirth experiences and fair treatment. Moreover, physicians cannot exercise various ethical duties as the law constrains them. In this article, I will discuss the physical and mental harms that result from the use of restraints under the backdrop of slavery and discrimination against women of color particularly. I argue that stereotypes feed into the phenomenon of shackling pregnant women, especially pregnant women of color. I further assert that shackling makes it difficult for medical professionals to be beneficent and promote justice. BACKGROUND Female incarceration rates in the United States have been fast growing since the 1980s.[5] With a 498 percent increase in the female incarceration population between 1981 and 2021, the rates of pregnancy and childbirth by incarcerated people have also climbed.[6],[7] In 2021, over 1.2 million women were incarcerated in the United States.[8] An estimated 55,000 pregnant women are admitted to jails each year.[9],[10] Many remain incarcerated throughout pregnancy and are transported to a hospital for labor and delivery. Although the exact number of restrained pregnant inmates is unclear, a study found that 83 percent of hospital prenatal nurses reported that their incarcerated patients were shackled.[11] I. Harms Caused by Shackling Shackling has caused many instances of physical and psychological harm. In the period before childbirth, shackled pregnant women are at high risk for falling.[12] The restraints shift pregnant women’s center of gravity, and wrist restraints prevent them from breaking a fall, increasing the risk of falling on their stomach and harming the fetus.[13] Another aspect inhibited by using restraints is testing and treating pregnancy complications. Delays in identifying and treating conditions such as hypertension, pre-eclampsia, appendicitis, kidney infection, preterm labor, and especially vaginal bleeding can threaten the lives of the mother and the fetus.[14] During labor and delivery, shackling prevents methods of alleviating severe labor pains and giving birth.[15] Usually, physicians recommend that women in labor walk or assume various positions to relieve labor pains and accelerate labor.[16] However, shackling prevents both solutions.[17] Shackling these women limits their mobility during labor, which may compromise the health of both the mother and the fetus.[18] Tracy Edwards, a former prisoner who filed a lawsuit for unlawful use of restraints during her pregnancy, was in labor for twelve hours. She was unable to move or adjust her position to lessen the pain and discomfort of labor.[19] The shackles also left the skin on her ankles red and bruised. Continued use of restraints also increases the risk of potentially life-threatening health issues associated with childbirth, such as blood clots.[20] It is imperative that pregnant women get treated rapidly, especially with the unpredictability of labor. Epidural administration can also become difficult, and in some cases, be denied due to the shackled woman’s inability to assume the proper position.[21] Time-sensitive medical care, including C-sections, could be delayed if permission from an officer is required, risking major health complications for both the fetus and the mother.[22] After childbirth, shackling impedes the recovery process. Shackling can result in post-delivery complications such as deep vein thrombosis.[23] Walking prevents such complications but is not an option for mothers shackled to their hospital beds.[24] Restraints also prevent bonding with the baby post-delivery and the safe handling of the baby while breast feeding.[25] The use of restraints can also result in psychological harm. Many prisoners feel as though care workers treat them like “animals,” with some women having multiple restraints at once— including ankles, wrists, and even waist restraints.[26] Benidalys Rivera describes the feeling of embarrassment as she was walking while handcuffed, with nurses and patients looking on, “Being in shackles, that make you be in stress…I about to have this baby, and I’m going to go back to jail. So it’s too much.”[27] Depression among pregnant prisoners is highly prevalent. The stress of imprisonment and the anticipation of being separated from their child is often overwhelming for these mothers.[28] The inhumane action has the potential to add more stress, anxiety, and sadness to the already emotionally demanding process of giving birth. Shackling pregnant prisoners displays indifference to the medical needs of the prisoner.[29] II. Safety as a Pretense While public safety is an argument for using shackles, several factors make escape or violence extremely unlikely and even impossible.[30] For example, administering epidural anesthesia causes numbness and eliminates flight risk.[31] Although cited as the main reason for using shackles, public safety is likely just an excuse and not the main motivator for shackling prisoners. I argue that underlying the shackling exemplifies the idea that these women should not have become pregnant. The shackling reflects a distinct discrimination: the lawmakers allowing it perhaps thought that people guilty of crimes would make bad mothers. Public safety is just a pretense. The language used to justify the use of restraint of Shawanna Nelson, the plaintiff in Nelson v. Correctional Medical Services, discussed below, included the word “aggressive.”[32] In her case, there was no evidence that she posed any danger or was objectively aggressive. Officer Turnesky, who supervised Nelson, testified that she never felt threatened by Nelson.[33] The lack of documented attempts of escape and violence from pregnant prisoners suggests that shackling for flight risk is a false pretense and perhaps merely based on stereotypes.[34] In 2011, an Amnesty International report noted that “Around the USA, it is common for restraints to be used on sick and pregnant incarcerated women when they are transported to and kept in hospital, regardless of whether they have a history of violence (which only a minority have) and regardless of whether they have ever absconded or attempted to escape (which few women have).”[35] In a 2020 survey of correctional officers in select midwestern prisons, 76 percent disagreed or strongly disagreed with restraining pregnant women during labor and delivery.[36] If a correctional officer shackles a pregnant prisoner, it is not because they pose a risk but because of a perception that they do. This mindset is attributed to select law enforcement, who have authority to use restraints.[37] In 2022, the Tennessee legislature passed a bill prohibiting the use of restraints on pregnant inmates. However, legislators amended the bill due to the Tennessee Sherriff Association’s belief that even pregnant inmates could pose a “threat.”[38] Subjecting all prisoners to the same “precautions” because a small percentage of individuals may pose such risks could reflect stereotyping or the assumption that all incarcerated people pose danger and flight risk. To quell the (unjustified) public safety concern, there are other options that do not cause physical or mental harm to pregnant women. For example, San Francisco General Hospital does not use shackles but has deputy sheriffs outside the pregnant women’s doors.[39] III. Historical Context and Race A. Slavery and Post-Civil War The treatment of female prisoners has striking similarities to that of enslaved women. Originally, shackling of female slaves was a mechanism of control and dehumanization.[40] This enabled physical and sexual abuses. During the process of intentionally dehumanizing slaves to facilitate subordination, slave owners stripped slave women of their feminine identity.[41] Slave women were unable to exhibit the Victorian model of “good mothering” and people thought they lacked maternal feelings for their children.[42] In turn, societal perception defeminized slave women, and barred them from utilizing the protections of womanhood and motherhood. During the post-Civil War era, black women were reversely depicted as sexually promiscuous and were arrested for prostitution more often than white women.[43] In turn, society excluded black women; they were seen as lacking what the “acceptable and good” women had.[44] Some argue that the historical act of labeling black women sexually deviant influences today’s perception of black women and may lead to labeling them bad mothers.[45] Over two-thirds of incarcerated women are women of color.[46] Many reports document sexual violence and misconduct against prisoners over the years.[47] Male guards have raped, sexually assaulted, and inappropriately touched female prisoners. Some attribute the physical abuse of black female prisoners to their being depicted or stereotyped as “aggressive, deviant, and domineering.”[48] Some expect black women to express stoicism and if they do not, people label them as dangerous, irresponsible, and aggressive.[49] The treatment of these prisoners mirrors the historical oppression endured by black women during and following the era of slavery. The act of shackling incarcerated pregnant women extends the inhumane treatment of these women from the prison setting into the hospital. One prisoner stated that during her thirty-hour labor, while being shackled, she “felt like a farm animal.”[50] Another pregnant prisoner describes her treatment by a guard stating: “a female guard grabbed me by the hair and was making me get up. She was screaming: ‘B***h, get up.’ Then she said, ‘That is what happens when you are a f***ing junkie. You shouldn’t be using drugs, or you wouldn’t be in here.”[51] Shackling goes beyond punishing by isolation from society – it is an additional punishment that is not justified. B. Reproductive Rights and “Bad Mothers” As with slaves not being seen as maternal, prisoners are not viewed as “real mothers.” A female prison guard said the following: “I’m a mother of two and I know what that impulse, that instinct, that mothering instinct feels like. It just takes over, you would never put your kids in harm’s way. . . . Women in here lack that. Something in their nature is not right, you know?”[52] This comment implies that incarcerated women lack maternal instinct. They are not in line with the standards of what society accepts as a “woman” and “mother” and are thought to have abandoned their roles as caretakers in pursuit of deviant behaviors. Without consideration of racial discrimination, poverty issues, trauma, and restricted access to the child right after delivery, these women are stereotyped as bad mothers simply because they are in prison. Reminiscent of the treatment of female black bodies post-civil war and the use of reproductive interventions (for example, Norplant and forced sterilization) in exchange for shorter sentences, I argue that shackles are a form of reproductive control. Justification for the use of shackles even includes their use as a “punitive instrument to remind the prisoner of their punishment.”[53] However, a prisoner’s pregnancy should have no relevance to their sentence.[54] Using shackles demonstrates to prisoners that society tolerates childbirth but does not support it.[55] The shackling is evidence that women are being punished “for bearing children, not for breaking the law.”[56] Physicians and healthcare workers, as a result, are responsible for providing care for the delivery and rectifying any physical problems associated with the restraints. The issues that arise from the use of restraints place physicians in a position more complex than they experience with regular healthy pregnancies. C. Discrimination In the case of Ferguson v. City of Charleston, a medical university subjected black woman to involuntary drug testing during pregnancy. In doing so, medical professionals collaborated with law enforcement to penalize black women for their use of drugs during pregnancy.[57] The Court held the drug tests were an unreasonable search and violated the Fourth Amendment. Ferguson v. City of Charleston further reveals an unjustified assumption: the medical and legal community seemed suspicious of black women and had perhaps predetermined them more likely to use drugs while pregnant. Their fitness to become mothers needed to be proven, while wealthy, white women were presumed fit.[58] The correctional community similarly denies pregnant prisoners’ medical attention. In the case of Staten v. Lackawanna County, an African American woman whose serious medical needs were treated indifferently by jail staff was forced to give birth in her cell.[59] This woman was punished for being pregnant in prison through the withholding of medical attention and empathy. IV. Failure to Follow Anti-Shackling Laws Despite 22 states having laws against shackling pregnant prisoners, officers do not always follow these laws. In 2015, the Correctional Association of New York reported that of the 27 women who gave birth under state custody, officers shackled 23 women in violation of the anti-shackling laws.[60] The lawyer of Tracy Edwards, an inmate who officers shackled unlawfully during her twelve-hour labor stated, “I don’t think we can assume that just because there’s a law passed, that’s automatically going to trickle down to the prison.”[61] Even with more restrictions on shackling, it may still occur, partly due to the stereotype that incarcerated women are aggressive and dangerous. V. Constitutionality The Eighth Amendment protects people from cruel and unusual punishment. In Brown vs. Plata, the court stated, “Prisoners retain the essence of human dignity inherent in all persons.”[62] In several cases, the legal community has held shackling to be unconstitutional as it violates the Eighth Amendment unless specifically justified. In the case of Nelson v. Correctional Medical Services, a pregnant woman was shackled for 12 hours of labor with a brief respite while she pushed, then re-shackled. The shackling caused her physical and emotional pain, including intense cramping that could not be relieved due to positioning and her inability to get up to use a toilet.[63] The court held that a clear security concern must justify shackling. The court cited a similar DC case and various precedents for using the Eighth Amendment to hold correctional facilities and hospitals accountable.[64] An Arkansas law similarly states that shackling must be justified by safety or risk of escape.[65] If the Thirteenth Amendment applied to those convicted of crimes, shackling pregnant incarcerated people would be unconstitutional under that amendment as well as the Eighth. In the Civil Rights Cases, Congress upheld the right “to enact all necessary and proper laws for the obliteration and prevention of slavery with all its badges and incidents.”[66] Section two of the Thirteenth Amendment condemns any trace or acts comparable to that of slavery. Shackling pregnant prisoners, stripping them of their dignity, and justification based on stereotypes all have origins in the treatment of black female slaves. Viewed through the lens of the Thirteenth Amendment, the act of shackling would be unconstitutional. Nonetheless, the Thirteenth Amendment explicitly excludes people convicted of a crime. VI. Justice As a result of the unconstitutional nature of shackling, physicians should have a legal obligation, in addition to their ethical duty, to protect their patients. The principle of justice requires physicians to take a stand against the discriminatory treatment of their patients, even under the eye of law enforcement.[67],[68] However, “badge and gun intimidation,” threats of noncompliance, and the fear of losing one’s license can impede a physician’s willingness to advocate for their patients. The American College of Obstetricians and Gynecologists (ACOG) finds the use of physical restraints interferes with the ability of clinicians to practice medicine safely.[69] ACOG, The American Medical Association, the National Commission on Correctional Health Care, and other organizations oppose using restraints on pregnant incarcerated people.[70] Yet, legislators can adopt shackling laws without consultation with physicians. The ACOG argues that “State legislators are taking it upon themselves to define complex medical concepts without reference to medical evidence. Some of the penalties [faced by OBGYNs] for violating these vague, unscientific laws include criminal sentences.”[71] Legislation that does not consider medical implications or discourages physicians’ input altogether is unjust. In nullifying the voice of a physician in matters pertaining to the patient’s treatment, physicians are prevented from fulfilling the principle of justice, making the act of shackling patients unethical. VII. Principle of Beneficence The principle of beneficence requires the prevention of harm, the removal of harm, and the promotion of good.[72] Beneficence demands the physician not only avoid harm but benefit patients and promote their welfare.[73] The American Board of Internal Medicine Foundation states that physicians must work with other professionals to increase patient safety and improve the quality of care.[74] In doing so, physicians can adequately treat patients with the goal of prevention and healing. It is difficult to do good when law enforcement imposes on doctors to work around shackles during labor and delivery. Law enforcement leaves physicians and healthcare workers responsible not only to provide care for the delivery, but also rectify any ailments associated with the restraints. The issues arising from using restraints place physicians in a position more complex than they experience with other pregnancies. Doctors cannot prevent the application of the shackles and can only request officers to take them off the patient.[75] Physicians who simply go along with shackling are arguably violating the principle of beneficence. However, for most, rather than violating the principle of beneficence overtly, physicians may simply have to compromise. Given the intricate nature of the situation, physicians are tasked with minimizing potential harm to the best of their abilities while adhering to legal obligations.[76] It is difficult to pin an ethics violation on the ones who do not like the shackles but are powerless to remove them. Some do argue that this inability causes physicians to violate the principle of beneficence.[77] However, promoting the well-being of their patients within the boundaries of the law limits their ability to exercise beneficence. For physicians to fulfill the principle of beneficence to the fullest capacity, they must have an influence on law. Protocols and assessments on flight risks made solely by the officers and law enforcement currently undermine the physician’s expertise. These decisions do not consider the health and well-being of the pregnant woman. As a result, law supersedes the influence of medicine and health care. CONCLUSION People expect physicians to uphold the four major principles of bioethics. However, their inability to override restraints compromises their ability to exercise beneficence. Although pledging to enforce these ethical principles, physicians have little opportunity to influence anti-shackling legislation. Instead of being included in conversations regarding medical complexities, legislation silences their voices. Policies must include the physician's voice as they affect their ability to treat patients. Officers should not dismiss a physician's request to remove shackles from a woman if they are causing health complications. A woman's labor should not harm her or her fetus because the officer will not remove her shackles.[78] A federal law could end shackling pregnant incarcerated people. Because other options are available to ensure the safety of the public and the prisoner, there is no ethical justification for shackling pregnant prisoners. An incarcerated person is a human being and must be treated with dignity and respect. To safeguard the well-being of incarcerated women and the public, it is essential for advocates of individual rights to join forces with medical professionals to establish an all-encompassing solution. - [1] Ferszt, G. G., Palmer, M., & McGrane, C. (2018). 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