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The classic double bubble theorem says that the least-perimeter way to enclose and separate two prescribed volumes in ℝN is the standard double bubble. We seek the optimal double bubble in ℝN with density, which we assume to be strictly log-convex. For N = 1 we show that the solution is sometimes two contiguous intervals and sometimes three contiguous intervals. In higher dimensions we think that the solution is sometimes a standard double bubble and sometimes concentric spheres (e.g. for one volume small and the other large).

Abstract Despite the constant development of antimicrobial resistance (AMR), few new antimicrobials are currently becoming available clinically. Alternative approaches, such as different mechanisms to fund their use, are being explored to encourage development of new antimicrobials.

Abstract Background This paper aimed to explore the palliative care (PC) needs and barriers to access among cancer patients in a rural region of North India with a high cancer burden. Methods A Participatory action research (PAR) approach was employed. Situational assessment, community sensitization workshops (CSWs) and door-to-door surveys were planned, conducted and developed over three PAR cycles. A parallel convergent mixed-methods approach was adopted wherein the quantitative data from door-to-door surveys and qualitative data from CSWs and investigator field notes were collected and analyzed to provide a comprehensive understanding of PC needs and barriers to access. Descriptive statistics and thematic analysis were used. Results A total of 27 CSWs involving 526 stakeholders were conducted. A total of 256 cancer patients were assessed for PC needs and symptom burden using the Supportive and Palliative Care Indicators (SPICT-4ALL) and the Edmonton Symptom Assessment System (ESAS) tool, respectively. Based on the SPICT assessment, all patients (n = 256) satisfied general and/or cancer-specific indicators for PC. The majority (56.6%) had ≥ one moderate-severe symptom, with the most common symptoms being tiredness, pain and loss of appetite. Analysis of qualitative findings generated three themes: unmet needs, burden of caregiving, and barriers and challenges. Cancer affected all domains of patients’ and their families’ lives, contributing to biopsychosocial suffering. Social stigma, discrimination, sympathizing attitudes and lack of emotional and material support contributed to psychosocial suffering among cancer patients and their caregivers. Lack of awareness, nearby healthcare facilities, transportation, essential medicines, trained manpower and education in PC, collusion, fear of social discrimination, faulty perceptions and misconceptions about cancer made access to PC difficult. Conclusions The study emphasize the need for and provide a roadmap for developing context-specific and culturally appropriate CBPC services to address the identified challenges and needs. The findings point towards education of CHWs in PC; improving community awareness about cancer, PC, government support schemes; ensuring an uninterrupted supply of essential medicines; and developing active linkages within the community and with NGOs to address the financial, transportation, educational, vocational and other social needs as some of the strategies to ensure holistic CBPC services. Trial registration Clinical Trial Registry of India (CTRI/2023/04/051357).

Abstract Biologically produced silver nanoparticles are becoming a more appealing option than chemically produced antioxidants and antimicrobial agents, because they are safer, easier to manufacture and have medicinal properties at lower concentrations. In this work, we employed the aqueous pomegranate peel extract (PPE) to synthesize silver nanoparticles (PPE-AgNPs), as peel extract is a rich source of phytochemicals which functions as reducing agent for the synthesis of PPE-AgNPs. Additionally, the PPE was examined quantitatively for total phenolics and total flavonoids content. PPE-AgNPs were characterized using analytical techniques including UV–Vis spectroscopy, DLS, FTIR, XRD, HRTEM and FESEM, evaluated in vitro against the plant pathogenic microbes and also for antioxidant activities. Analytical techniques (HRTEM and FESEM) confirmed the spherical shape and XRD technique revealed the crystalline nature of synthesized PPE-AgNPs. Quantitative analysis revealed the presence of total phenolics (269.93 ± 1.01 mg GAE/g) and total flavonoids (119.70 ± 0.83 mg CE/g). Biosynthesized PPE-AgNPs exhibited significant antibacterial activity against Klebsiella aerogenes and Xanthomonas axonopodis, antifungal activity against Colletotrichum graminicola and Colletotrichum gloesporioides at 50 µg/mL concentration. The antioxidant potential of biosynthesized PPE-AgNPs was analysed via ABTS (IC50 4.25 µg/mL), DPPH (IC50 5.22 µg/mL), total antioxidant (86.68 g AAE/mL at 10 µg/mL) and FRAP (1.93 mM Fe(II)/mL at 10 µg/mL) assays. Cytotoxicity of PPE-AgNPs was valuated using MTT assay and cell viability of 83.32% was determined at 100 µg/mL concentration. These investigations suggest that synthesized PPE-AgNPs might prove useful for agricultural and medicinal purposes in the future.

Background: COVID-19 convalescent plasma is one of the experimental therapies used widely in moderately sick COVID-19 patients. However, there are a few risks involved in plasma transfusion; notably, transfusion-related acute lung injury (TRALI) caused by antibodies against human leukocyte antigens (HLA). This study was designed to assess the prevalence of anti-HLA antibodies in convalescent plasma donors using the single antigen bead method. Study design and methods: This was a hospital-based observational study of consecutive plasma donors. A total of 252 samples were screened for anti-HLA Class I and Class II antibodies using the microbead assay with the identification of anti-HLA Ab in positive samples being performed using a single antigen bead assay. Luminex-based normalized background cutoff ratios of 10.8 for Class I and 6.9 for Class II and mean fluorescence intensity cutoffs of 2500 for Class I and 1500 for Class II were used for screening and the single bead assay, respectively. Results: Of 252 screened samples, 28 (11.1 %) were positive for Class I, Class II or both Class I and Class II anti-HLA antibodies in donors with no history of a previous immunizing event. Moreover, 20/252 (7.9%) donors without any history of prior immunization had specific anti-HLA antibodies of Class I or Class II or both by the single bead assay. Conclusions: The high prevalence of anti-HLA antibodies in our cohort of donors raises an urgent and immediate need for anti-HLA antibody screening in all convalescent plasma donors for safe therapy of COVID-19 patients.

Abstract Introduction There is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders). Methods This open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2–2.5 mg/kg once daily for a period of 8–12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800–1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria. Results In the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25–11) compared to 7 months (IQR 3.5–12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468). Conclusions The efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure. Registration of the study with Clinical Trials Registry of India ( http://ctri.nic.in ;CTRI/2021/06/034421) (Dt: 28/06/2021).

Ahitagni Biswas,1 Lakhan Kashyap,1 Aanchal Kakkar,2 Chitra Sarkar,2 Pramod Kumar Julka1 1Department of Radiotherapy & Oncology, 2Department of Pathology, All India Institute of Medical Sciences, New Delhi, India Abstract: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

IntroductionThere is a complex relationship between housing status and substance use, where substance use reduces housing opportunities and being unhoused increases reasons to use substances, and the associated risks and stigma. MethodsIn this descriptive analysis of people without housing who died of accidental substance-related acute toxicity in Canada, we used death investigation data from a national chart review study of substance-related acute toxicity deaths in 2016 and 2017 to compare sociodemographic factors, health histories, circumstances of death and substances contributing to death of people who were unhoused and people not identified as unhoused, using Pearson chi-square test. The demographic distribution of people who died of acute toxicity was compared with the 2016 Nationally Coordinated Point-In-Time Count of Homelessness in Canadian Communities and the 2016 Census. ResultsPeople without housing were substantially overrepresented among those who died of acute toxicity in 2016 and 2017 (8.9% versus $lt;1% of the overall population). The acute toxicity event leading to death of people without housing occurred more often in an outdoor setting (24%); an opioid and/or stimulant was identified as contributing to their death more frequently (68%–82%; both contributed in 59% of their deaths); and they were more frequently discharged from an institution in the month before their death (7%). ConclusionWe identified several potential opportunities to reduce acute toxicity deaths among people who are unhoused, including during contacts with health care and other institutions, through harm reduction supports for opioid and stimulant use, and by creating safer environments for people without housing.

IntroductionIl existe une relation complexe entre le statut résidentiel et la consommation de substances. En effet, la consommation de substances réduit les perspectives de logement et le fait d’être sans logement augmente les raisons de consommer des substances ainsi que les risques et la stigmatisation qui y sont associés. MéthodologieDans cette analyse descriptive des personnes sans logement qui ont perdu la vie en raison d’une intoxication aiguë accidentelle liée à une substance au Canada, nous avons utilisé les données relatives aux enquêtes sur les décès tirées d’une étude nationale d’examen des dossiers concernant les décès par intoxication aiguë due à une substance en 2016 et 2017, afin de comparer les facteurs sociodémographiques, les antécédents médicaux, les circonstances du décès et les substances ayant contribué au décès des personnes sans logement et des personnes non identifiées comme sans logement, au moyen du test du khi carré de Pearson. Nous avons comparé le profil démographique des personnes décédées d’une intoxication aiguë aux données du Dénombrement ponctuel coordonné de l’itinérance dans les collectivités canadiennes de 2016 et du Recensement de 2016. RésultatsLes personnes sans logement étaient nettement surreprésentées parmi les personnes décédées d’une intoxication aiguë en 2016 et 2017 (8,9 % contre moins de 1 % de la population générale). L’intoxication aiguë ayant entraîné le décès des personnes sans logement a eu lieu plus souvent à l’extérieur (24 %); un opioïde ou un stimulant a plus fréquemment contribué à leur décès (68 % à 82 %; les deux substances ont été responsables de 59 % des décès) et ces personnes avaient plus souvent été libérées d’un établissement correctionnel ou été autorisées à sortir d’un établissement de soins de santé au cours du mois précédant leur décès (7 %). ConclusionNous présentons plusieurs possibilités de réduire les décès attribuables à une intoxication aiguë chez les personnes sans logement, notamment lors de la prise de contact avec les services de santé et d’autres établissements, par des mesures de soutien à la réduction des méfaits liés à la consommation d’opioïdes et de stimulants ainsi que par la création d’environnements plus sûrs pour les personnes sans logement.

Introduction: Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods: The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC – benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results: A retrospective analysis of urine cytology. The patient’s ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions: Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters.