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Introduction The authors tested the hypothesis that the EEG feature generalized polyspike train (GPT) is associated with drug-resistant idiopathic generalized epilepsy (IGE). Methods The authors conducted a single-center case-control study of patients with IGE who had outpatient EEGs performed between 2016 and 2020. The authors classified patients as drug-resistant or drug-responsive based on clinical review and in a masked manner reviewed EEG data for the presence and timing of GPT (a burst of generalized rhythmic spikes lasting less than 1 second) and other EEG features. A relationship between GPT and drug resistance was tested before and after controlling for EEG duration. The EEG duration needed to observe GPT was also calculated. Results One hundred three patients were included (70% drug-responsive and 30% drug-resistant patients). Generalized polyspike train was more prevalent in drug-resistant IGE (odds ratio, 3.8; 95% confidence interval, 1.3-11.4; P = 0.02). This finding persisted when controlling for EEG duration both with stratification and with survival analysis. A median of 6.5 hours (interquartile range, 0.5-12.7 hours) of EEG recording was required to capture the first occurrence of GPT. Conclusions The findings support the hypothesis that GPT is associated with drug-resistant IGE. Prolonged EEG recording is required to identify this feature. Thus, >24-hour EEG recording early in the evaluation of patients with IGE may facilitate prognostication.

Computer aided diagnosis have made a significant breakthrough in skin lesion diagnosis employing deep learning (DL) frameworks over the years, but it hardly reveals the transparency of the DL architecture. To mitigate this issue, this article proposes an image visibility filter (IVF) based DL framework for skin lesion diagnosis. The proposed IVF-DL network employs a ResNet architecture where visibility patches, extracted from the image visibility graph (IVG), are used as the convolutional kernels to extract salient features from dermoscopic images. The primary aim of this article is not only to classify skin lesions but also to depict the interpretable results after each residual block in a supervised manner. An optimal performance has been obtained by tuning three hyperparameters of the proposed method. Furthermore, the final interpretable result has been analyzed via IVG to resemble its spatial characteristics. Experimental results reveal the efficacy of the proposed method both qualitatively and quantitatively.

Context Pre-hypertension remains a significant public health challenge and appropriate intervention is required to stop its progression to hypertension and/or cardiovascular diseases. Objective To study the effects of individualized homeopathic medicines (IH) against placebo in intervening with the progression of pre-hypertension to hypertension. Design Double-blind, randomized, two parallel arms, placebo-controlled trial. Setting Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India. Patients Ninety-two patients suffering from pre-hypertension; randomized to receive either IH (n = 46) or identical-looking placebo (n = 46). Interventions IH or placebo in the mutual context of lifestyle modification (LSM) advices including dietary approaches to stop hypertension (DASH) and brisk exercises. Main outcome measures Primary – systolic and diastolic blood pressure (SBP and DBP); secondary – Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) scores; all measured at baseline, and every month, up to 3 months. Results After 3 months of intervention, the number of patients having progression from pre-hypertension to hypertension between groups were similar without any significant differences in between (all P>0.05). Reduction in BP and MYMOP-2 scores were non-significantly higher (all P>0.05) in the IH group than placebo with small effect sizes. Lycopodium clavatum, Thuja occidentalis and Natrum muriaticum were the most frequently prescribed medicines. No harms or serious adverse events were reported from either group. Thus, there was a small, but non-significant direction of effect favoring homeopathy, which ultimately rendered the trial as inconclusive. [Trial registration: CTRI/2018/10/016,026; UTN: U1111–1221–8251]

Purpose: Uveal melanoma (UM) is a rare disease and the most common primary intraocular malignancy in adults, with a high risk of metastases. Reliable prognostication systems are based on anatomic features, as in the tumor-node-metastasis staging of the American Joint Committee on Cancer (AJCC) system, or on genetic information, as in The Cancer Genome Atlas (TCGA) system. Prior evidence suggests that combining both systems may be beneficial. We evaluated the benefit of combining the TCGA and AJCC systems in a large cohort of patients.Design: Retrospective case series of patients with UM.Participants: Nine hundred seventy-nine patients with a choroidal or ciliary body melanoma treated at the Wills Eye Hospital between 1998 and 2020, 94% of whom received eye-sparing treatment.Methods: Tumors were classified into 4 TCGA groups based on chromosome copy number: A (disomy 3, normal 8q), B (disomy 3, any 8q gain), C (monosomy 3, 1 extra copy of 8q), and D (monosomy 3, multiple 8q gain). The eighth edition of the AJCC staging manual was used for AJCC staging. Cox regression and the log-rank test were used for survival analysis.Main Outcome Measure: Metastasis-free survival.Results: Combining information of the 2 systems improved prognostication in intermediate groups: in TCGA group C, we saw an increased rate of metastasis in AJCC stage III (28%) compared with stage 11 (8.9%); the same was seen in AJCC stage II, going from TCGA group C (8.9%) to group D (46%), and in AJCC stage III, going from group C (28%) to group D (49%). In patients with AJCC stage II or III disease, loss of chromosome 3 and gain of 8q (TCGA groups C and D) significantly worsened the prognosis, with multiple 8q gain (TCGA group D) having a greater impact.Conclusions: Combining information from AJCC stages and TCGA groups yields a better predictive power even in this set of relatively small tumors. We propose that physicians take both systems into account whenever possible, especially in moderate-risk groups. (C) 2021 by the American Academy of Ophthalmology.

The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.

Processing in memory (PIM) architecture, with its ability to perform ultra-low-latency parallel processing, is regarded as a more suitable alternative to von Neumann computing architectures for implementing data-intensive applications such as Deep Neural Networks (DNN) and Convolutional Neural Networks (CNN). In this article, we present a Look-up Table (LUT) based PIM architecture aimed at CNN/DNN acceleration that replaces logic-based processing with pre-calculated results stored inside the LUTs in order to perform complex computations on the DRAM memory platform. Our LUT-based DRAM-PIM architecture offers superior performance at a significantly higher energy-efficiency compared to the more conventional bit-wise parallel PIM architectures, while at the same time avoids fabrication challenges associated with the in-memory implementation of logic circuits. Alongside, the processing elements can be programmed and re-programmed to perform virtually any operation, including operations of Convolutional, Fully Connected, Pooling, and Activating Layers of CNN/DNN. Furthermore, it is capable of operating on several combinations of bit-widths of the operand data and thereby offers a wider range of flexibility across performance, precision, and efficiency. Transmission Gate (TG) realization of the circuitry ensures minimal footprint from the PIM architecture. Our simulations demonstrate that the proposed architecture can perform AlexNet inference at a nearly 13× faster rate and 125× more efficiency compared to state-of-the-art GPU and also provides 1.35× higher throughput at 2.5× higher energy-efficiency than another recent DRAM-implemented LUT-based PIM architecture in its baseline operation mode. Moreover, it offers 12× higher frame-rate at 9× more efficiency per frame for the lowest operand precision setting, with respect to its own baseline operation mode.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Physical unclonable function (PUF) is an important circuit component for realizing cyber-physical security of data and electronic systems. In this work, we present a low-cost PUF implementation using metal-insulator-metal (MIM)-type PECVD SiO₂-based one-time programmable memory (OTPM) devices. We present a custom Verilog-A compact model of OTPM devices for complete PUF hardware implementation in the 180-nm CMOS technology. The implementation of PUF scheme based on a novel differential bit cell using OTPM devices shows strong performance in terms of uniqueness, reliability, and uniformity without additional overheads in terms of bit error correction and postprocessing.

The effect of chronic graft-versus-host disease (cGVHD) on the risk of nonrelapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research (CIBMTR) analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (age ≥60 years). We included 4429 adults age ≥40 years who underwent a first HLA-matched peripheral blood stem cell alloHCT for acute myelogenous leukemia or myelodysplastic syndrome between 2008 and 2017. We compared outcomes of 4 groups—older adults (≥60 years) and younger adults (40 to 59 years) with cGVHD and older and younger adults without cGVHD—to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse, and overall survival (OS). We treated cGVHD as a time-dependent covariate. The severity of cGVHD was based on the CIBMTR clinical definitions. cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher for older adults versus younger adults. Adults who developed cGVHD as a group had longer OS compared with age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild to moderate cGVHD was associated with longer OS. Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse, and longer OS. Older adults had a higher risk of NRM, but the increased risk of NRM associated with cGVHD did not differ based on age. The development of mild to moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing the risk of relapse. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

With increase in urbanization and Earth Sciences research into urban areas, the need to quickly and accurately segment urban rooftop maps has never been greater. Current machine learning techniques...

Aim: In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV® (RONAPREVE® outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use. Results & methodology: Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters. Discussion & conclusion: This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.

With technological advancement, the automobile industry is undergoing a design evolution. There has been an increase in the use of electrically actuated systems; electronics-based control systems, ...

To describe the surgical outcomes and implant complications in 1,800 patients undergoing evisceration with primary implant.An Electronic Medical Record-driven analysis of 1,800 patients undergoing evisceration with primary implant between 2013 and 2019. Implant sizing was performed intra-operatively to place the largest implant without tension on the wound closure. Outcome measures included implant complications, prosthesis measurements, and incidence of a good aesthetic outcome. Good outcome was defined as2 mm enophthalmos and grade 1 or less superior sulcus deformity with a custom ocular prosthesis.Eighteen hundred eyes of 1800 patients were included. The mean age at surgery was 36 ± 21 years (median 32 years). Implants used were poly(methyl methacrylate) (PMMA) in 1737 (97%) and porous polyethylene in 63 (3%) patients. Two-petal sclerotomy was performed in 1512 (88%) and four-petal sclerotomy in 165 (10%) patients. The mean diameter of the implant used was 19.35 ± 1.18 mm (median 20, range 10-22 mm). The implant extrusion rate was 3% (56) and implant displacement was seen in none. The mean prosthesis volume and thickness were 2.22 ± 0.67 ml (median 2, range 1-6.5 ml) and 6 ± 1 mm (median 6, range 2-9 mm). The mean difference in prosthesis projection on Hertel's exophthalmometer was 0.28 ± 1 mm (median 0, range 0-1 mm). Good outcome was observed in 93%. The mean follow-up period was 351 ± 386 days (median 194).Evisceration with empirically selected primary orbital implant placement is associated with minimal implant complications and gives a good aesthetic outcome in 93% of the patients.

Over the last half-decade or so, since 2015, data privacy has become an important concern for organizations and consumers alike. Rules and regulations associated with data protection and privacy ha...

Background Continuous positive airway pressure (CPAP) is a primary mode of respiratory support for preterm infants. Animal studies have shown long-term detrimental effects on lung/airway development, particularly airway (AW) hyper-reactivity, as an unfortunate consequence of neonatal CPAP. Since the hyaluronan (HA) synthesizing enzyme hyaluronan synthase-3 (HAS3) is involved in various adult pulmonary disorders, the present study used a neonatal mouse model to investigate the role of HAS3 in CPAP-induced AW hyper-reactivity. Methods Male and female neonatal mice were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for 7 days. At postnatal day 21 (2 weeks after CPAP ended), airway (AW) hyper-reactivity and HAS3 expression were assessed with and without in vitro HAS3 siRNA treatment. Results MRIs of 3-day-old mice confirmed that CPAP increased lung volume with incrementing inflation pressures. CPAP increased AW reactivity in both male and female mice, which was associated with increased airway smooth muscle and epithelial HAS3 immunoreactivity. CPAP did not affect HA accumulation, but HAS3 siRNA reversed CPAP-induced AW hyper-reactivity and reduced HAS3 expression. Conclusions These data in mice implicate a role for HAS3 in long-term effects of CPAP in the developing airway in the context of preterm birth and CPAP therapy. Impact Neonatal CPAP increases airway smooth muscle and epithelial HAS3 expression in mice. CPAP-induced airway hyper-reactivity is modulated by HAS3. These data enhance our understanding of the role mechanical forces play on lung development. These data are a significance step toward understanding CPAP effects on developing airway. These data may impact clinical recognition of the ways that CPAP may contribute to wheezing disorders of former preterm infants.

Background Post‐COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C‐reactive protein (CRP), interleukin 6 (IL6) as well as N‐terminal probrain natriuretic peptide (NT‐proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. Methodology This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017‐June 2018), with 71 MISC patients over a period of 6 months (July 2020‐December 2020). The non‐parametric Mann‐Whitney U test was used to test for similarity in distributions of the samples of CRP, NT‐proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. Results Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT‐proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P 935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

Wildfire spread is a stochastic phenomenon driven by a multitude of geophysical and anthropogenic factors. In this study, we propose a spatiotemporal data-driven risk assessment framework to understand the effect of various geophysical/anthropogenic factors on wildfire size, leveraging a systematic machine learning approach. We apply this framework in the state of California—the most vulnerable US state to wildfires. Using county-level annual wildfire data from 2001-2015, and various geophysical (e.g., landcover, wind, surface temperature) and anthropogenic features (e.g., population density, housing type), we trained, tested, and validated a suite of ensemble tree-based learning algorithms to identify and evaluate the key factors associated with wildfire size. The extreme gradient boosting (XGBoost) algorithm outperformed all the other models in terms of generalization performance, categorization of important features, and risk performance. We found that standard deviations of meteorological variables with long-tailed distributions play a key role in predicting wildfire size. Specifically, the top ten factors associated with high risk of larger wildfires include larger standard deviations of surface temperature and vapor pressure deficit, higher wind gust, more grassy and barren land covers, lower night-time boundary layer height and higher population density. Our proposed risk assessment framework will help federal/state decision-makers to adequately plan for wildfire risk mitigation and resource allocation strategies.

Background: A basic understanding of biostatistics is essential, both for designing quality research and evaluating medical literature. We evaluated the understanding of biostatistics and interpretation of research results among homeopathic fresh graduates’ (House Staffs; HSs) and postgraduate trainees’ (PGTs) in West Bengal, India. Methods: A cross-sectional survey of homeopathic HSs and PGTs in the four government homeopathic schools in West Bengal, India, using a pre-tested, valid and reliable biostatistics multiple choice knowledge, confidence and attitude test questionnaire. Results: Internal consistency of the used questionnaires was acceptable (Cronbach’s α = 0.611 – 0.672). Response rate was only 55.6%. Research journal reading habit was seriously lacking. No one had ever taken any research courses or possessed any advanced degrees or diplomas. The overall mean% correct on statistical knowledge was very poor, 1.0% (95% CI 0.1 – 1.9%) vs. 10.0% (95% CI 8.6 – 11.6%) for HSs and PGTs (P < 0.0001). Comparatively, higher knowledge scores were found in respondents from Mahesh Bhattacharyya Homeopathic Medical College and Hospital (P = 0.003). No one could interpret an unadjusted odds ratio, Kaplan-Meier analysis results, and determine strength of evidence for risk factors. Percentages of correct answers for all other knowledge-based questions ranged between only 2.7 – 9.5%. Respondents’ self-assessed confidence in ability to understand biostatistics ranged between 41 – 60%. Positive attitude towards biostatistics was elicited in 16 – 63% respondents. Conclusions: The respondents seriously lacked knowledge in biostatistics needed to interpret research results. Training programs needs to undergo massive and immediate transformation to include more effective biostatistics training in curricula to encourage meaningful research.

While one in five children in the USA are now obese, and more than three-quarters receive at least one drug during childhood, there is limited dosing guidance for this vulnerable patient population. Physiologically based pharmacokinetic modeling can bridge the gap in the understanding of how pharmacokinetics, including drug distribution and clearance, changes with obesity by incorporating known obesity-related physiological changes in children. The objective of this study was to develop a virtual population of children with obesity to enable physiologically based pharmacokinetic modeling, then use the novel virtual population in conjunction with previously developed models of clindamycin and trimethoprim/sulfamethoxazole to better understand dosing of these drugs in children with obesity. To enable physiologically based pharmacokinetic modeling, a virtual population of children with obesity was developed using national survey, electronic health record, and clinical trial data, as well as data extracted from the literature. The virtual population accounts for key obesity-related changes in physiology relevant to pharmacokinetics, including increased body size, body composition, organ size and blood flow, plasma protein concentrations, and glomerular filtration rate. The virtual population was then used to predict the pharmacokinetics of clindamycin and trimethoprim/sulfamethoxazole in children with obesity using previously developed physiologically based pharmacokinetic models. Model simulations predicted observed concentrations well, with an overall average fold error of 1.09, 1.24, and 1.53 for clindamycin, trimethoprim, and sulfamethoxazole, respectively. Relative to children without obesity, children with obesity experienced decreased clindamycin and trimethoprim/sulfamethoxazole weight-normalized clearance and volume of distribution, and higher absolute doses under recommended pediatric weight-based dosing regimens. Model simulations support current recommended weight-based dosing in children with obesity for clindamycin and trimethoprim/sulfamethoxazole, as they met target exposure despite these changes in clearance and volume of distribution.

Introduction: The nationwide shortage of pediatric cardiologists in medically underserved areas poses a challenge to congenital heart disease (CHD) screening requiring echocardiography, resulting i...

PurposeThe primary aim of this paper is to study a dark side of e-HRM concerning its parallel effect on human resource (HR) socialization and HR service delivery and the consequent impact of perceived HR effectiveness.Design/methodology/approachThe current study started with an in-depth review of the extant literature in the field of e-HRM to derive a set of constructs. Based on the theoretical foundation of the identified constructs, the current study went on to derive a set of hypotheses, which was subsequently validated using the uses the quantitative technique of PLS-SEM. A primary survey, in the form of a structured questionnaire, was used as the source for data collection on a sample size of 276 from the Indian industrial domain. Careful attention was paid to eliminate the common method bias in the study.FindingsThe findings of this study show a simultaneous significant full mediation effect of both HR service delivery and HR socialization is the relationship between e-HRM and HR effectiveness. However, e-HRM has a strong and significant negative effect on HR socialization. Though HR socialization is positively related to HR effectiveness, the significantly reduced level of HR socialization as a consequence of adaption of e-HRM had negatively affected the perceived HR effectiveness.Originality/valueAlthough the dark side of e-HRM has been recognized by academicians and practitioners alike, its implications have seldom been studied in the academic literature. The current study intends to shed some light on this important, but sparsely discussed topic. Further, this study makes significant and meaningful contributions in the literature of e-HRM by empirically studying together the positive and negative consequences of e-HRM and its effects on HR effectiveness. Several e-HRM scholars have discussed the implications of e-HRM adoption and highlighted the negative impacts of e-HRM, and traversing the same path, the current study advances the literature by empirically investigating the effect of e-HRM on the dehumanization of HR processes and practices.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and 30% of all cases of CRC are believed to have a familial component and up to one-third of these (10%) are hereditary. Pathogenic germline variants in multiple genes have been associated with predisposition to hereditary CRC or polyposis. Lynch syndrome (LS) is the most common hereditary CRC syndrome, caused by variants in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 and is inherited in a dominant manner. Heritable conditions associated with colonic polyposis include familial adenomatous polyposis (FAP) associated with APC pathogenic variants, MUTYH-associated polyposis (MAP) caused by biallelic MUTYH pathogenic variants, and polymerase proofreading-associated polyposis (PPAP) caused by POLE or POLD1 pathogenic variants. Given the overlapping phenotypes of the cancer syndromes along with the limited sensitivity of using clinical criteria alone, a multigene panel testing approach to diagnose these conditions using next-generation sequencing (NGS) is effective and efficient. This technical standard is not recommended for use in the clinic for patient evaluation. Please refer to National Comprehensive Cancer Network (NCCN) clinical practice guidelines to determine an appropriate testing strategy and guide medical screening and management. This 2021 edition of the American College of Medical Genetics and Genomics (ACMG) technical standard supersedes the 2013 edition on this topic.

Purpose Obesity increases the risk of incident chronic kidney disease (CKD) and is one of the strongest risk factors for new-onset CKD even in the absence of metabolic risk factors. Weight loss has been shown to reduce renal hyperfiltration and proteinuria. Metabolic bariatric surgery (MBS) remains an effective treatment for obesity and its metabolic-related complications. However, literature on its impact on renal function remains limited. Materials and methods This was an observational retrospective study in a tertiary centre in Singapore. MBS cases performed at the centre between 2008 and 2019 were included. The primary outcome measures were estimated glomerular filtration rate (eGFR), calculated using the CKD epidemiology collaboration equation, and albuminuria (defined as urine albumin-creatinine ratio (uACR) > 3.5 mg/mmol) at baseline and 1-year post-MBS. Results Five hundred fifty-seven patients were included. One-year post-MBS, median eGFR increased from 110.9 mL/min/1.73 m2 (IQR 92.4 to 121.5) to 112.6 mL/min/1.73 m2 (IQR 97.3 to 122.3), p Conclusions MBS had a positive impact on renal function with modest but statistically significant improvement in eGFR and reduction in albuminuria at 1-year post-surgery. Longer-term data is required to investigate the durability of this impact.

Water is probably the most inevitable substance for the survival of life on Earth. Though Earth has an infinite source of water, most of it is of no use since it is saline ocean water. Ignoring the water stored in continental glaciers, the only source of freshwater is groundwater. This resource is now under huge stress due to unplanned and over-use. Now the time has come to take groundwater management as a serious concern. Here, an attempt has been made to capture different issues of groundwater management, its applicability, and limitation in terms of the present state of research. This article discusses the feasibility of groundwater management in terms of groundwater quantity, artificial recharge to aquifer and groundwater quality both chemical and bacteriological. A holistic approach has been adopted to discuss technological advancements to address the groundwater management issues like desalination and membrane filtration, its limitations, and future scope of improvement. Thermal pollution of groundwater and its impact on saline water intrusion to coastal aquifers have been addressed in the discussion. The effect of global climate change on the hydrosphere and its impact on groundwater management have also been incorporated. One of the mitigations to global warming is exploring different sources of green energy. One of them and the most explored options is geothermal energy. The use of geothermal heat for electricity generation and space heating has also been included in the discussion with technological limitations which is always an open area of research.

Extramedullary disease (EMD) is an aggressive form of multiple myeloma (MM). Confirming the presence of plasma cells outside the bone marrow makes the diagnosis of EMD. There is no clear consensus on the management of EMD in MM, and this entity continues to remain an unmet need. Rapidly controlling EMD to prevent end-organ damage is a priority. Retrospectively, we reviewed our database for patients with EMD that received treatment with bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide (VDPACE) plus an immune modulator (IMiD) regimen. We identified 21 patients with a median age of 61 years. Ten patients received a VDPACE based regimen as a bridge to autologus stem cell transplant (ASCT). After a median follow-up of 51.4 months, the median overall survival (OS) and progression-free survival were 14.9 months (95% CI: 7.8-NA) and 5.5 months (95% CI: 3.9-NA), respectively. The overall response rate was 76%, with a manageable safety profile. Interestingly, these results were similar regardless of the presence of high-risk cytogenetics. The safety profile was acceptable. In conclusion, a salvage VDPACE-based regimen plus an IMiD remains an effective and safe bridging therapy to future ASCT and immunotherapy in relapsed/refractory multiple myeloma patients with EMD.

Objective: Congenital anomaly is one of the most important causes & being the 5th most common cause of neonatal mortality & morbidity. It may present as a structural or functional abnormality. These defects occur due to defective embryogenesis. Associated factors may be maternal age, maternal TORCH infection, drugs, genetic factors. Antenatal USG reduces the incidence.Materials and Methods: A cross-sectional study was done in the Pediatric department over 1 year. Diagnosis of all congenital anomalies was done by the concerned pediatrician& pediatric surgeon. Data was collected in the specified format.Results: A total of 10205 cases of age group 1 month to 5 years presented to the paediatric OPD, out of which 193 children were diagnosed as congenital anomalies in 1 year. Males were found to be affected the most. The most common system involved was found to be the genitourinary system (36.78%). The second most common system involved was the gastrointestinal system (33.67%). The least common system involved was the musculoskeletal system.Conclusion: Congenital anomalies are a major cause of neonatal & infantile mortality & morbidity. Routine screening with a level II targeted scan for all the pregnant mothers should be mandatory. Adequate nutrition, parental education & Rubella vaccination of the mother can decrease the prevalence of congenital anomalies to some extend.

Background Multiple myeloma (MM) is an incurable hematologic malignancy, and outcomes remain poor for patients with triple-class relapsed/refractory MM (RRMM). Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes of the KCd on triple-class RRMM patients at our institution. Patients and methods Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 were included in our analysis. The regimen KCd consisted of 28 days cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16, cyclophosphamide 300 mg/m2 IV weekly, and dexamethasone (20-40) mg orally weekly. Results Patients received a median of 6 (3-10) prior regimens. The median number of cycles administered was 4 (1-11) cycles. Overall response rate was 52%, 6 patients (26%) achieved very good partial response (VGPR), 6 patients (26%) achieved partial response (PR), and 5 patients (22%) achieved stable disease (SD). Progression-free survival (PFS) and Overall-survival (OS) were 4 and 11.9 months, respectively. There was no reported treatment-related mortality. The most common grade ≥3 adverse events were neutropenia (26%), thrombocytopenia (56.5%), and anemia (56.5%). Conclusions KCd showed clinically meaningful efficacy and manageable safety profile in patients with triple-class RRMM in real-world.

Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.

Many governments seek the private sector to meet their development goals. One possible means to enlist this support is to impose mandatory or ‘hard’ corporate social responsibility (CSR) requirements on large companies. To shed light on how mandatory CSR could be helpful in this regard, we study the case of India, where the government has required large companies to spend a fraction of their income towards development as CSR since 2014. We analyzed the expenses of leading Indian companies and found statistically significant similarities among these companies in their spending pattern across the different categories, which we interpret as isomorphism. By looking for the government's motivation and the companies' motivations – both perceive the priorities in unmet social needs – we present a conceptual model to explain this isomorphism in CSR expenditure across different categories. The model suggests that governments may find mandatory CSR helpful to direct corporations in achieving development goals.

Following bariatric surgery, accurate charting of weight loss and regain is crucial. Various preoperative factors affect postoperative weight loss, including age, sex, ethnicity, and surgical type. These are not considered by current weight loss metrics, limiting comparison of weight loss outcomes between patients or centers and across time. Patients (n=1022) who underwent sleeve gastrectomy (n=809) and gastric bypass (n=213) from 2008 to 2020 in a single center were reviewed. Weight loss outcomes (% total weight loss) were measured for 60 months postoperatively. Longitudinal centile lines were plotted using the post-estimation predictions of quantile regression models, adjusted for type of procedure, sex, ethnicity, and baseline BMI. Median regression showed that %TWL was 1.0% greater among males than females (β = +1.1, 95% CI: +0.6 to +1.7, P =

OBJECTIVE To compile available evidence to better understand the management of leg ulcers in sickle cell disease (SCD), as well as describe potential therapeutic steps that may be required to improve the quality of life of patients with SCD leg ulcers. DATA SOURCES MEDLINE, PubMed, EMBASE, and Web of Science databases. STUDY SELECTION A comprehensive search was conducted to retrieve relevant studies using the keywords "sickle cell disease and leg ulcer," "ulcer treatments, diagnosis and sickle cell," and "wound sickle cell." Studies published through July 2020 were included. DATA EXTRACTION Two independent authors selected all studies that assessed the relationship between leg ulcer and SCD identified from online databases. DATA SYNTHESIS The authors have summarized updated information on pathophysiology (vasculopathy linked to chronic hemolysis and endothelial dysfunction), diagnosis, and available treatment options to unravel the dermohematologic connection between leg ulcers and SCD. CONCLUSIONS It is the authors' hope that this detailed discussion of the information available on leg ulcers and SCD will lead to a better appreciation of this clinical problem by the clinicians and researchers and in turn have a long-term positive effect on the quality of life of patients with SCD. Researchers should design new trials considering these insights and potential therapeutic approaches based on current knowledge.

Subhasish Pramanik,1 Lakshmi Kanta Mondal,2 Suman Kalyan Paine,3 Sneha Jain,2 Subhankar Chowdhury,1 Upasana Ganguly,4 Sayantan Ghosh,2 Chiranjit Bose,1 Koena Bhattacharjee,2 Gautam Bhaduri5 1Institute of Post Graduate Medical Education and Research (IPGMER), Kolkata, 700020, India; 2Regional Institute of Ophthalmology (RIO), Medical College and Hospital, Kolkata, 700073, India; 3National Institute of Biomedical Genomics (NIBMG), Kalyani, West Bengal, India; 4Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Haryana, India; 5MGM Medical College, Kishanganj, Bihar, IndiaCorrespondence: Lakshmi Kanta MondalRegional Institute of Ophthalmology, Medical College, Kolkata, IndiaTel +91 9830830216Email Lakshmi.mondal62@gmail.comPurpose: In the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser photocoagulation, for the treatment of diabetic macular edema (DME) in the Indian population.Methods: Retrospective data were collected in the Regional Institute of Ophthalmology, Kolkata, India between January 2018 and June 2019. Seventy-seven eyes received 3 consecutive monthly intravitreal injections of RBZ (0.5 mg) and were followed by prompt laser photocoagulation (within 7– 10 days after the third injection). Similarly, 51 eyes received 3 consecutive monthly intravitreal injections of BVZ (1.25 mg), an off-label drug, and were followed by prompt laser therapy. Safety assessments of the therapy, as well as surrogate markers of biochemical derangements related to diabetic retinopathy (DR), were also investigated at the end of 12 months.Results: Seventy-seven subjects who were given a treatment of RBZ+laser therapy showed average 6.87± 5.53 letters gain in their best-corrected visual acuity (BCVA) score, whereas the ones treated with off-label BVZ+ laser therapy demonstrated improvement in BCVA of an average 6.82± 5.76 letters in “Early Treatment Diabetic Retinopathy Study” (ETDRS) chart. The study also highlights the cost-effectiveness of both RBZ+laser and BVZ+laser therapies for the treatment of DME in DR. The results demonstrated that a subject has to pay 20.951 times more cost (in INR) for RBZ+laser therapy compared to BVZ+laser therapy, to get an almost similar outcome.Conclusion: BVZ is found to be the more attractive option for treating DME in DR for its cost-friendliness over RBZ in terms of BCVA outcome, as well as the safety perspectives, at least for the economically backward population in developing countries, like India.Keywords: diabetic retinopathy, diabetic macular edema, ranibizumab, bevacizumab, laser therapy, cost-effectiveness

The aims of this pilot investigation were to calculate the levels of sensitivity and specificity of salivary glands ultrasonography (SGUS) in diagnosing Sjögren syndrome (SS) and to assess the ultrasonographic findings of parotid and submandibular glands.Patients diagnosed with SS or dry mouth and healthy controls were enrolled. Bilateral parotid and submandibular glands were assessed for (1) parenchymal inhomogeneity (PIH), (2) median size of the glands, (3) visibility of glandular posterior borders, and (4) size of sialolith, if present.This study included 34 female patients, of whom 12 had SS (35.3%), 12 had dry mouth (35.3%), and 10 were healthy controls (29.4%). Patients with SS showed higher PIH scores in all glands with the median differences being statistically higher in the right and left parotids and left submandibular glands (P.001, P = .012, and P.001, respectively). SGUS, with a PIH cutoff ≥2, showed a sensitivity of 100% and a specificity of 81.6% for detecting SS. The majority of SS had invisible glandular posterior borders (P.001). Median size of the glands and size of the sialolith did not show any statistically significant differences between groups.SGUS is a noninvasive imaging modality with good sensitivity and specificity that might be valuable as a diagnostic aid for SS.

A pandemic, as defined by the World Health Organization [1], is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people. Presently, the COVID-19 pandemic is raging through the USA, and as time is progressing, the larger undercurrent of neuropsychiatric ailments and disorders is making its presence felt. At the time of writing this paper, in the last week of November 2020, 1 year after the detection of the first case of COVID-19 in Wuhan, China, there have been over 57.8 million cases and 1.3 million deaths worldwide [2]. Most patients with COVID-19 present initially with fever (83%–99%), cough (59%–82%), fatigue (44%–70%), anorexia (40%–84%), and shortness of breath (31%–40%) [3]. However, the signs and symptoms present at the illness onset may vary widely and involve various organ systems. Recent literature is beginning to shed light on the impact of COVID-19 on the nervous system and its neuropsychiatric sequelae. Studies describing the association between COVID-19 and neuropsychiatric symptoms are limited. Large-scale cohort studies are currently not available in the extant literature. A recent study assessing the potential relationship between COVID-19 and psychiatric disorders found a reciprocal relationship between the two [4]. This study included 62,354 patients diagnosed with COVID-19 with the primary outcomes being the incidence and hazard ratios for psychiatric disorders, dementia, and insomnia during the first 14 to 90 days after a diagnosis of COVID-19 was established. The authors observed that the patients recovering from COVID-19 had a significantly higher rate of psychiatric disorders. There was a 5.8% probability of being newly diagnosed with a psychiatric illness within 90 days post COVID-19 diagnosis. The most frequently acquired psychiatric diagnosis was anxiety disorder, with a probability of outcome within 90 days of 4.7%. Among anxiety disorders, adjustment disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and panic disorder were the most frequent. The probability of a new diagnosis of mood disorder within 14 to 90 days after COVID-19 diagnosis was 2%. Interestingly, previous psychiatric illness was found to be independently associated with an increased risk of being diagnosed with COVID-19. A diagnosis of a psychiatric disorder 1 year prior to the onset of the COVID-19 pandemic was associated with a 65% increased risk of COVID-19 compared with a cohort matched for established physical risk factors for COVID-19, but without a psychiatric diagnosis. This finding held ground in sensitivity analyses. In this article, we will review and discuss the existing evidence regarding various neuropsychiatric manifestations of COVID-19, including delirium, cognitive impairment, psychosis, depression, suicide, mania, and anxiety in patients with COVID-19 and COVID-19 survivors. We will also discuss the neurobiological mechanisms that are hypothesized to be involved in developing neuropsychiatric symptoms. Furthermore, we will discuss the potential role of medications used for treatment of COVID-19 in causing/worsening neuropsychiatric symptoms. Lastly, we will review the psychosocial factors contributing to the psychiatric presentations of infected individuals considering how important psychosocial factors are in the occurrence of primary psychiatric disorders.

Purpose The purpose of this study was to evaluate the incidence, clinical features, microbiology, risk factors, and treatment outcomes in cases of ocular surface squamous neoplasia (OSSN) with coexisting microbial keratitis (MK). Methods This was a retrospective case-control study from a cohort of 939 cases with OSSN. Results Twenty eyes (2%) with OSSN and MK were included in the study group and 100 age-matched eyes with only OSSN as controls. Most common presentation was a combination of pain, redness, watering, and decreased vision (50%) over a median duration of 14 days. Mean corneal surface involvement by MK was 48% with corneal perforation in 6 cases (30%). Microbiology showed 10 culture positive cases for Gram-positive organisms (n = 5), fungus (n = 4), or mixed infection (n = 1). In the salvaged eyes, MK resolved in 9 eyes (90%) on medical treatment at a mean duration of 30 days and keratoplasty was performed in 1 eye. OSSN treatment included wide excisional biopsy (n = 9/18; 50%), extended enucleation (n = 7/18; 39%), and orbital exenteration in 1. Over a mean follow-up of 12 months, vision salvage was achieved in 7 of 18 (39%) and globe salvage in 10 of 18 (55%). Logistic regression analysis showed the following significant risk factors for MK in OSSN: male sex, human immunodeficiency virus seropositivity, increasing tumor diameter, limbal epicenter, temporal quadrant, noduloulcerative morphology, pigmentation, scleral invasion, keratin, and corneal component of the OSSN lesion. Conclusions Rarely, MK can coexist with OSSN leading to a poor treatment outcome. Male sex, human immunodeficiency virus seropositivity, large limbal pigmented OSSN lesion with keratin and corneal component, noduloulcerative morphology, and scleral invasion were risk factors for this association.

BackgroundTechnology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication.MethodsWe implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them.ResultsWe decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period.ConclusionsIn a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.).

The function and management of the reservoir are fully dependent on the past history of the average weather. With the increase of global warming, there is an increase in temperature in the atmosphere, which results in melting ice in the polar region, increasing sea water labels, etc. These have bad impacts on our environment like floods and drought. It is difficult to predict the weather due to rapid changes in the climates. Then the offseason rainwater can be used to manage the crisis of the uncertain situation. This paper introduces a novel fuzzy model to redistribute reservoir water for different purposes based on the offseason rain intensity. The model has been developed for the period of the non-monsoon season with the set of parameters like inflow, outflow, rain intensity, water demand among the power generation, civil utilization, harvesting, industrial production, etc. The model has been optimized to obtain water distribution based on requirements for different purposes and maximize revenues.

BACKGROUND: Meropenem is a broad-spectrum carbapenem antibiotic approved by the U.S. Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections (cIAIs) in infants < 3 months of age. The impact of maturation in glomerular filtration rate (GFR) and tubular secretion by renal transporters on meropenem pharmacokinetics, and the effect on meropenem dosing, remains unknown. We applied physiologically based pharmacokinetic (PBPK) modeling to characterize meropenem’s disposition in preterm and term infants. METHODS: An adult meropenem PBPK model was developed in PK-Sim(®) (v. 8) and scaled to infants accounting for renal transporter ontogeny and GFR maturation. The PBPK model was evaluated using 645 plasma concentrations from 181 infants (gestational age 23–40 weeks; postnatal age 1–95 days). PBPK model-based simulations were performed to evaluate meropenem dosing in the product label for infants < 3 months of age treated for cIAIs. RESULTS: Our model predicted plasma concentrations in infants in agreement with the observed data (average fold error of 0.90). The PBPK model-predicted clearance in a virtual infant population was successfully able to capture the post hoc estimated clearance of meropenem in this population, estimated by a previously published model. For 90% of virtual infants, a 4 mg/L target plasma concentration was achieved for > 50% of the dosing interval following product label–recommended dosing. CONCLUSION: Our PBPK model supports the meropenem dosing regimens recommended in the product label for infants < 3 months of age.

In this case study of a research and development facility construction project at a large biopharmaceutical organization, we explored how digital investments must be accompanied by a partnership approach and a transformation of the cultural values of an organization tied to operational principles. The project faced considerable challenges, including a highly constrained market environment, time and cost constraints, and a multiyear organization transformation with a diverse mix of stakeholder objectives. Despite these challenges, the project was brought in under budget and on schedule, achieving other objectives that often seem at odds with each other (best-in-class sustainability ratings, quality scores from customers, and with a remarkably low number of change requests). We found that significant stakeholder engagement early in the architect and contractor selection process leads to the right contract management process and ultimately successful outcomes. A key insight from this case involves the need for differentiated supplier relationship management for procurement-project team integration.

Pharmaceutical sector of Bangladesh has developed profoundly after promulgation of the Drugs (Control) Ordinance, 1982. However, the health sector has not been equally developed because of lack of wellequipped drug management system and much needed patient counseling. The presence of adulterated, counterfeit and substandard drugs and the sale of drugs at high prices than the maximum retail price have also been the major problems here. The recent introduction of model pharmacies is supposed to be a hope for the people to get safe medicines at a reasonable cost. The aim of the present study was to find out the current scenario of model pharmacies in Bangladesh and to propose modern and alternative systems that could be applied in model pharmacies for better healthcare management and patient compliance. Thus, the current status of model pharmacies of Bangladesh has been evaluated using a survey-based analysis which utilized a pre-set questionnaire. The survey was conducted on 90 model pharmacies in seven districts of Bangladesh (Level 1 categorized by the Directorate General of Drug Administration, Government of the People’s Republic of Bangladesh). The results revealed that the infrastructure of the model pharmacies should be improved further. Only 33% of the model pharmacies have sitting facilities and 51% of them have washroom facilities for the waiting patients. It was found that despite all the model pharmacies (100%) should have at least 1 A-grade pharmacist in each of them, i.e. a pharmacy graduate registered with the Pharmacy Council of Bangladesh under the Pharmacy Ordinance 1976, but pharmacists were found to be present in only 26% of pharmacies during the visit. Amongst the pharmacists, 98% showed satisfaction with the decision of compulsory engagement of A-grade pharmacists in all the model pharmacies. Defying the obligatory provisions, only 38% model of pharmacies keep the required records of sold drugs. It was pleasing to observe that no physician’s sample of medicines was sold in any model pharmacies. The medicines storage facilities in controlled temperature was found in all the model pharmacies. But the A-grade pharmacists were not available in the pharmacies during holidays. It is opined that modern and ICT based techniques can be applied to modify the model pharmacies for better patient care and patient management. Dhaka Univ. J. Pharm. Sci. 20(1): 1-10, 2021 (June)

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N=1605) or PTCy (SibCy, N=403), and related haploidentical transplants receiving PTCy (HaploCy, N=757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P=0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P=0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.

In this article, we report the temperature-dependent transistor characteristic of Epi-Gd2O3/AlGaN/GaN metal oxide semiconductor high electron mobility transistor (MOSHEMT) and compare its properties with that of AlGaN/GaN metal-Schottky high electron mobility transistor (HEMT) grown on 150 mm Si (111) substrate. Introducing an epitaxial single crystalline Gd2O3 between the metal gate and AlGaN barrier not only improves the gate leakage current significantly but also enhances its thermal stability. We observe that there is no significant change in the gate leakage current even at 473 K compared to that measured at room temperature (RT) (298 K), and this is also evident in the transistor’s subthreshold behavior at 473 K. We have determined the electric field within the Gd2O3 as well as AlGaN and investigated the leakage conduction mechanism through Gd2O3. The ${I}_{ \mathrm{ON}}/{I}_{ \mathrm{OFF}}$ of the transistor was measured as high as ~108 even at 473 K with the lowest ${V}_{\text {TH}}$ shift (91.4 mV) with temperature. Our measurements also confirm the presence of polar optical phonon scattering, which directly affects the 2-D electron gas (2DEG) mobility at high temperatures and thus the electrical characteristics of HEMT and MOSHEMT.

Background and Objectives: The COVID-19 pandemic has spread across 87 million people with more than 1·8 million deaths in the world. As there is no definite treatment modality, the use of convalescent plasma has become increasingly popular worldwide. This study aimed to identify an appropriate strategy of donor recruitment and to evaluate the appropriateness of pre-set plasma donation guidelines. Material and Methods: In this prospective study conducted from May to September 2020, the donors were recruited under the following two circumstances: Group I, patients in the post-COVID-19 follow-up in the clinic, and Group II, patients recovered from COVID-19 recruited through mass and electronic media. A pre-set donor selection criteria and laboratory investigation was designed according to national and international guidelines. Approximately 500 ml of COVID-19 convalescent plasma (CCP) was collected from recovered individuals in each group by two different cell separators. The overall donor's attendance rate, deferral rate, adverse events and donor compliance was analysed and compared between the two groups. Results: There was a significant difference in attendance in relation to registration between the groups (P

Healthcare establishments are unique and complex. The Indian healthcare system comprises of public and private healthcare establishments. Different challenges are encountered by the healthcare professionals in their daily operations. The sudden emergence of COVID-19 posed a new threat to the already burdened healthcare system. The pandemic changed the healthcare paradox with newer workplace and societal challenges faced by the healthcare personnel. The purpose of this study is to identify the antecedents of workplace and societal challenges faced by the healthcare personnel. Our study conducted in Kolkata and other adjoining areas of West Bengal included respondents who volunteered for individual in-depth interviews. The sample size was kept at n = 20 after due technical considerations. Freelisting and pile sorting was done to generate clusters. The qualitative study identified five constructs with 18 items under workplace challenges and three constructs with five items under societal/community challenges. Workplace challenges included resource availability, adequacy and allocation, financial issues, perceived managerial ineffectiveness, inconsistent guidelines and perceived occupational stress, while societal/community challenges included dread disease, social adaptiveness and challenges related to essential services. A salience threshold was established and the multidimensional scaling provided four major clusters: financial support and sustainability, adaptive resilience, infection risk mitigation and healthcare facility preparedness. Suggestive actions for the identified challenges were summed as enhanced production of diagnostic kits through public–private partnership models and industrial production reforms. Enhanced testing facility for COVID-19 will help to identify new cases. Financial stresses need long-term sustainable alternative that will avoid pay cuts and unemployment. Treatment regimen, diagnostic protocols, waste disposal guidelines should be worked upon and leading national agencies be consulted for technical support, research and development.