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SUMMARY Digital psychiatry has become increasingly important and understanding of certain aspects is essential for practising clinicians. This article discusses electronic patient records (EPRs), from their origins to current and future use, the growth and embedding of outcome measurements, the use of social media, and learning and research in virtual arenas.

Covariate adjusted response adaptive designs are developed with ordinal categorical responses for phase III clinical trial involving multiple treatments. Stochastic ordering principle is used to order the treatments according to effectiveness and consequently allocation functions are developed by combining the cumulative odds ratios suitably. The performance of the proposed designs is investigated through relevant exact as well as large sample measures. To investigate the performance in a real situation, a real clinical trial involving lung cancer patients is further redesigned using the proposed allocation design.

In Bangladesh, recently drug addiction is considered as a major problem, because our young generation is highly involved with the issue. Drug is now the curse of a society. This curse has polluted our society to its core. 200 million people around the world are into drug abuse most of who are teenagers. Bangladesh does not produce drugs, but the global environment has made it a dangerous place for drug abuse. Besides, urbanization, population growth, widespread use of the internet and lack of awareness has made drug abuse an epidemic. The drug scenario in Bangladesh has changed with time. Drug addiction is turning to the national problem from social problem. It creates many other problems. This study conducted to identify the core cause of drug addiction of young generation. To conduct this research, questionnaire survey and case study have conducted. Case study tried to bring out the core factor responsible for the drug addiction of young generation and questionnaire survey expressed the people’s perception toward drug addiction. These research findings suggest that influence of peer group; weak family bonding, affluence and shortage of money are the key responsible factor for the drug addiction of young generation in Bangladesh.

Time management plays a very important role in personal and professional life. Several studies have demonstrated that judicious use of time positively affects academic performance. This study was carried out to assess the relationship between time management and academic achievement of the students of Sylhet Agricultural University. Moreover, the study aimed to know if there was any gender difference in time management. Based on the literature review on time management, survey research has been identified as the most prominent design to study time management. The time management questionnaire developed by Britton and Tesser was used as a study tool for its reliability and validity. A total of 187 students were selected from Sylhet Agricultural University as respondents for the study. Data were analyzed using descriptive statistics, t-test, and ANOVA. The results of this study do not suggest a significant relationship between time management and academic achievement. However, females manage time better than males in short-range and long-range planning.

The main goal of this article is to look into the relationship between nature and man as it is portrayed in the poetry of Derek Walcott and Kaiser Haq, two renowned poets from two distinct realms, namely St. Lucia and Bangladesh, respectively. Taking into consideration the rising level of environmental awareness, both poets have attempted to produce poetry that integrates man with nature. The poetry, particularly nature poetry, of these poets is explored in order to undertake study from an individual viewpoint, but there has yet to be a major examination into a comparative technique by adopting an ecocritical approach. In this study, the researchers attempt to uncover the nature of poetry disguised inside the chosen poems of the legendary poets by examining the creative and aesthetic characteristics of their works. This study examines the interaction between man and the environment via the lens of an ecocritical approach in a comparative manner. In this research, one poem by Kaiser Haq, "Poor Man Eating," and one poem by Derek Walcott, "Map of the New World," are examined from the perspective of environmental awareness. By concentrating on these poems and using an ecocritical perspective, this study attempts to demonstrate how the poet is sensitive to nature and how people are concerned about the environment.

In this paper, stein-type two-stage sampling procedure is carried out for fixed accuracy confidence interval estimation of the common variance (

Compromising ethics and precision in the context of a multiarmed clinical trial, an optimal order adjusted response adaptive design is proposed for survival outcomes subject to independent random censoring. The operating characteristics of the proposed design and the follow-up inference are studied both theoretically as well as empirically and are compared with those of the competitors. Applicability of the developed design is further illustrated through redesigning a real clinical trial with survival responses.

In clinical trials, fixed randomizations in a prefixed proportion (e.g. 1:1 or 2:1 for two treatment trials) may be adopted to allocate the entering patients among the competing treatments. However, such an allocation procedure ignores the knowledge obtained from the accrued information on the performance of the treatments until that point. However, while allocating, a fixed randomization may favor the most and the least effective treatments in a prefixed manner, and hence becomes instrumental to induce a conflict with the "individual ethics" requirement. Adaptive allocation designs are considered instead, for their ability to dynamically settle the issue of running randomization towards the treatment doing better - all using the available data but with a scope to compromise in statistical precision. Although most of the developments are pertinent to binary, continuous and survival responses, ordinal categorical responses are natural outcomes in many disciplines of clinical trials like Orthopedics and Ophthalmology. Therefore, to balance between ethics and precision in the context of a multi-treatment clinical trial producing ordinal categorical responses, an optimal response adaptive design is derived by minimizing a measure of "precision" subject to constrained number of "failures" ensuring higher number of assignments to the "best" treatment. Related design and inference-based characteristics are extensively studied - both theoretically and empirically. Further, the practical applicability of the developed design is envisaged through re-designing of a real clinical trial, where the responses are immediate and are measured in ordinal categorical scale.

The aim of this paper is to detect parametric faults in multi-input analog circuits by solving for the coefficients of a polynomial regression model using traditional linear least squares techniques, with some care applied in the solution. The multi-input circuit output is expressed in terms of more than one input variables using polynomial coefficients. In the proposed approach, the value of each component of the circuit under test (CUT) is varied within its tolerance limit using Monte-Carlo simulation to calculate its fault free polynomial coefficient bounds. The CUT is then declared fault free or faulty based on the result of the comparison of its estimated polynomial coefficients with the fault free coefficients. To the best of our knowledge, parametric fault detection in multi-input analog circuits using polynomial regression modelling is attempted for the first time in the literature. The effectiveness of the proposed method is demonstrated via two case studies, namely, a lead lag circuit and the PI compensator of a peak-current-mode-controlled buck-type switching converter.

This work deals with nonparametric test procedures for comparing effects of two treatments in two period parallel group design, where each subject receives the same treatment over the two periods. The procedures are based on consistent estimators of relative treatment effects in each period and that of covariate adjusted effects with responses in period 1 as covariates. Related asymptotic results are obtained followed by necessary simulation studies to evaluate the performance of the tests. AMS 2010 subject classifications: 62G10 62J15

Uniformly minimum variance unbiased (UMVU) estimators of reliability function (both stress–strength and mission time) and the associated variance are derived for a class of generalization of Lindley distribution. The application of the results is further validated by a real data study.AMS 2020 subject classification: 62N05 62F10

Thermal stability of mechanically alloyed nanocrystalline AlxCoCrFeNi (x = 0, 0.3, 0.6, 1 mol) high entropy alloys (HEAs) has been investigated for the low and intermediate temperature range of 673–1073 K. Single phase FCC structure is observed in the as milled CoCrFeNi. A mixture of FCC and BCC phases is exhibited by × = 0.3, 0.6 and 1, alloys where the volume fraction of BCC increases with increasing Al content. Phase evolution in heat-treated AlxCoCrFeNi HEAs proceeds via increasing BCC fraction at 673 K, followed by subsequent reduction at elevated temperatures. For each alloy, the major phase observed in as milled condition and it is retained even after prolonged exposure at the 1073 K. Al favors the formation of the BCC phase due to its high affinity to form ordered B2 structures with constituent elements Co, Fe and Ni. Thermal exposure of AlxCoCrFeNi HEAs also leads to the formation of Cr7C3, owing to the higher negative free energy of carbide formation for Cr among other constituents. Transmission electron microscopy (TEM) investigations substantiated that nanostructure of milled powder is maintained even after the heat treatment. Grain growth factor for quinary HEAs is relatively lower than quaternary CoCrFeNi owing to their slower rates of diffusion.

Cancer is referred to as the "Emperor of all maladies" accounting for the second-highest mortality rates worldwide. Major factors associated with cancer lethality are uncontrolled proliferation, metastasis, and frequent recurrence. The conventional therapeutic drugs used in cancer therapy have been associated with numerous damaging side-effects that call for the use of alternative therapeutic options. The natural plant compounds (NPCs) have been found to be effective against diverse groups of diseases including cancer. Among the different types, the polyphenolic phytochemicals like curcumin, (-)epigallocatechin-3-gallate, Resveratrol, and nimbolide which are predominant parts of daily dietary intake have proved their potency in reducing the aggressive properties of cancer. Here, we have highlighted the mechanisms through which these NPCs influence growth, metastatic potential, and the drug-resistant behavior of different cancer types. Moreover, we have also emphasized on their function as modulators of the immune system as well as the metabolic properties of the tumor. The role of these phytochemicals in reducing cancer progression has been highlighted when administered unaided or in combination with similar group of compounds. Moreover, their ability to enhance the drug-sensitivity of cancer cells which accounts for their use in combination with conventional chemotherapeutics has also been discussed in this article. Therefore, co-administration of these phytochemicals with chemically similar group members or with conventional chemotherapeutics may prove to be an effective treatment strategy for cancer.

The Uniformly Minimum Variance Unbiased (UMVU) and the Maximum Likelihood (ML) estimations of R = P(X ≤ Y) and the associated variance are considered for independent discrete random variables X and Y. Assuming a discrete uniform distribution for X and the distribution of Y as a member of the discrete one parameter exponential family of distributions, theoretical expressions of such quantities are derived. Similar expressions are obtained when X and Y interchange their roles and both variables are from the discrete uniform distribution. A simulation study is carried out to compare the estimators numerically. A real application based on demand-supply system data is provided.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Background: A range of evidence for the effectiveness of one-to-one peer support in mental health services is emerging. Levels of engagement with peer support vary with limited studies showing few individual participant characteristics predicting engagement. Implementation factors that might predict engagement have not been considered. Methods: Data were analysed from the intervention arm of the ENRICH trial of one-to-one peer support for discharge from acute psychiatric inpatient care. Two outcomes were considered: (1) a measure of ‘engaged with peer worker’; (2) number of face-to-face contacts with peer worker post-discharge. Two sets of independent variables were analysed against each outcome: (1) pre-randomisation participant characteristics; (2) implementation factors measured pre-discharge. Analyses used logistic and zero-inflated negative binomial regression models according to outcome structure. Results: Data were analysed for 265 participants randomised to peer support who had a known peer worker. Non-heterosexual participants had increased odds of engaging with peer support compared to heterosexual participants, OR = 4.38 (95% CI: 1.13, 16.9, p = .032). Longer duration of first contact with peer worker ( OR = 1.03, 95% CI: 1.00, 1.04, p Conclusions: Implementation of peer support should include a focus on relationship building in the first session of peer support. The potential for peer support to break down barriers to accessing mental health services experienced by people from marginalised communities warrants further investigation.

Background and purpose: The cystic fibrosis transmembrane conductance regulator (CFTR) gene is a tumor suppressor in colorectal cancer (CRC). People with cystic fibrosis, caused by biallelic germline mutations in CFTR, have a higher risk developing CRC. We also found that loss of CFTR is implicated in sporadic CRC. In a study of 90 persons diagnosed with stage II CRC, the 23% of patients with lowest CFTR expression had 30% lower disease-free survival at 3 years. The cause of decreased CFTR expression in this group is not known. We analyzed the TCGA COADREAD study to identify associations between low expression of CFTR and cancer-causing genetic alterations. Of these alterations, only BRAF-V600E mutation correlated with low expression of CFTR. The BRAF-V600E mutation is found in ~10% of CRC and is associated with global promoter hypermethylation leading to down regulation of tumor suppressor genes. Accordingly, our hypothesis was that BRAF-V600E mutation contributes to low expression of CFTR via CFTR promoter DNA methylation. Methods: In the TCGA COADREAD database 283 primary colorectal cancers diagnosed at stages II, III and IV had full information needed for this study: CFTR mRNA expression, somatic mutation, overall survival (OS), and DNA methylation status. OS was visualized using Kaplan-Meier analysis. Association between CFTR expression and methylation was determined by Pearson correlation coefficient (PCC) analysis. Associations between mutations and CFTR expression or methylation were determined by Point Biserial correlation coefficient (PBS) analysis. Results: Kaplan-Meier analysis of the 283 cases showed that overall survival was worse in the 25% of cases with lowest CFTR expression (p=0.035). The BRAF-V600E mutation was significantly associated with lower CFTR expression (PBS r=-0.38, p Citation Format: Patricia Scott, Anna Prizment, Rahul Bhattacharya, Zachary Blankenheim, Nathan Pankratz, Timothy Starr, Robert Cormier. The oncogenic mutation BRAF-V600E is associated with colorectal cancers expressing low levels of CFTR mRNA [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A027.

A multi-arm response-adaptive allocation design is developed for circular treatment outcomes. Several exact and asymptotic properties of the design are studied. Stage-wise treatment selection procedures based on the proposed response-adaptive design are also suggested to exclude the worse performing treatment(s) at earlier stages. Detailed simulation study is carried out to evaluate the proposed selection procedures. The applicability of the proposed methodologies is illustrated through a real clinical trial data on cataract surgery.

Explicit expression of the Stress - Strength reliability function, R=P(X≤Y) is derived, when the stress (X) and strength (Y) distributions are different members of the Power series family of distri...

In the present work, the concept of mechanically activated annealing (MAA) has been applied to produce nanocrystalline Al0.3CoCrFeNi high-entropy alloys (HEAs) with reduced contamination levels. Phase evolution during conventional mechanical alloying (MA), MAA and subsequent consolidation by spark plasma sintering (SPS) have been studied in detail. Complete alloying is obtained after 15 h of MA, while milling time of 5 h and annealing at 1100 °C for 1 h have been used to achieve alloy formation during MAA. Both the MA–SPS and MAA–SPS routes have shown major FCC phase. The contamination of WC observed during MA was successfully eliminated during MAA, while the volume fraction of Cr7C3 reduced from 20% during MA–SPS to 10% after MAA–SPS. This method can serve as an effective way to produce nanostructured HEAs with minimum contamination.

Aims Protective efficacy of N‑acetylcysteine (NAC) was assessed against sub-acute diisopropyl phosphorofluoridate (DFP) poisoning in mice. Main methods Mice were allocated into nine groups of six each: vehicle control; DFP (0.125 LD50 ≈ 0.483 mg/kg bwt, s.c.); DFP + Atropine (ATR, 10 mg/kg bwt, i.p., 0 min); DFP + Pralidoxime (2-PAM, 30 mg/kg bwt, i.m., 0 min); DFP + NAC (150 mg/kg bwt, i.p., −60 min); DFP + ATR + NAC; DFP + 2-PAM + NAC; DFP + ATR + 2-PAM; and DFP + ATR + 2-PAM + NAC. Animals received various treatments for 21 d daily. Plasma butyrylcholinesterase (BChE) was measured after 7, 14 and 21 d of exposure. Brain acetylcholinesterase (AChE) and reduced glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) were measured (brain, liver and kidney) after 21 d of exposure. Histopathology, immunohistochemistry, and Western blot for inducible nitric oxide synthase (iNOS) and c-fos were also performed. Key findings DFP significantly reduced BChE and AChE levels. Diminished GSH, CAT, SOD (brain and liver), GPx, GR, and elevated MDA (Brain) levels were also observed. DFP caused notable histopathology (brain, liver and kidney) and over expression of iNOS, and c-fos proteins (brain). NAC enhanced the protective efficacy of ATR and 2-PAM in most parameters, without any appreciable protection in iNOS and c-fos expression. Significance NAC as an adjunct with ATR and 2-PAM, exhibited marked beneficial effects against sub-acute DFP poisoning, indicating its possible implications in the management of OP poisoning.

A two stage randomized design is developed for two treatment clinical trials in which response variables are exponential and the observations are censored by using failure censoring and time censoring in the first and second stages respectively. The censoring time for the second stage is determined from the outcomes of the first stage. An application to testing for the equality of treatment effects is given along with a comparative study with relevant properties. Resumen Se desarrolla un diseño aleatorizado en dos etapas para dos ensayos clínicos de tratamiento en los que las variables de respuesta son exponenciales y las observaciones se censuran utilizando la censura por fallo y la censura temporal en la primera y segunda etapas, respectivamente. El tiempo de censura para la segunda etapa se determina a partir de los resultados de la primera etapa. Una aplicación para probar la igualdad de efectos del tratamiento se da junto con un estudio comparativo con propiedades relevantes.

This report describes novel thiol-modified N-acetylmannosamine (ManNAc) analogs that extend metabolic glycoengineering (MGE) applications of Ac5ManNTGc, a non-natural monosaccharide that metabolically installs the thio-glycolyl of sialic acid into human glycoconjugates. We previously found that Ac5ManNTGc elicited non-canonical activation of Wnt signaling in human embryoid body derived (hEBD) cells but only in the presence of a high affinity, chemically compatible scaffold. Our new analogs Ac5ManNTProp and Ac5ManNTBut overcome the requirement for a complementary scaffold by displaying thiol groups on longer, N-acyl linker arms, thereby presumably increasing their ability to interact and crosslink with surrounding thiols. These new analogs showed increased potency in human neural stem cells (hNSCs) and human adipose stem cells (hASCs). In the hNSCs, Ac5ManNTProp upregulated biochemical endpoints consistent with Wnt signaling in the absence of a thiol-reactive scaffold. In the hASCs, both Ac5ManNTProp and Ac5ManNTBut suppressed adipogenic differentiation, with Ac5ManNTBut providing a more potent response, and they did not interfere with differentiation to a glial lineage (Schwann cells). These results expand the horizon for using MGE in regenerative medicine by providing new tools (Ac5ManNTProp and Ac5ManNTBut) for manipulating human stem cells.

Circular or directional outcomes are natural responses in many clinical trials (e.g. orthopedics, ophthalmology, sports medicine). Traditionally, clinical trials use equal allocation throughout the trial without utilizing the information contained in the sequentially observed responses in the running trial. Adaptive allocation designs are data-dependent alternatives to assign a greater number of subjects to the better performing treatments using the available data of the running trial in a convenient way. However, adaptive designs for circular responses are rare and, therefore, in the current work, we develop a multi-treatment response-adaptive randomization for circular treatment outcomes considering both the ethics and efficiency requirements. Apart from assessing the proposed allocation design empirically, the applicability of the design in real clinical trials is also enumerated from a practitioner’s viewpoint.

The COVID-19 pandemic caused by SARS-CoV-2 has been showing a speedy growth in the number of infected patients with a remarkable mortality rate, thus it has become a worldwide public health concern. From March 8, 2020, the disease was confirmed to start spreading in Bangladesh. Since then, people got infected so exponentially that the country positions at the list of top infected countries in the world. Therefore, the objective of this comprehensive review was representing overall scenario of COVID-19 in different sectors of Bangladesh, particularly prioritizing the health sector. Up to 14 September 2020, 339,332 confirmed cases and 4,759 deaths were reported. An alarming fact is that while the global mutation rate of coronavirus is 7.23 % in average, the rate is 12.6 % in Bangladesh. Although the government ruled preventive strategies such as nationwide lockdown, social distancing, contact monitoring, quarantine and isolation, it was difficult to implement those due to lack of public awareness, inappropriate attitudes and so on. Moreover, the overburdened healthcare system had a weak response at initial stage because of insufficient healthcare facilities. Consequently, this pandemic affected severely almost all the important sectors of the country, specifically the economy, agriculture and health sectors. Hence, focusing on healthcare system as well as maintaining social distance and other essential precautions can limit the spread of infection and help to alleviate the severity of the pandemic.

Enhanced metastasis and disease recurrence accounts for the high mortality rates associated with cancer. The process of Epithelial-Mesenchymal Transition (EMT) contributes towards the augmentation of cancer invasiveness along with the gain of stem-like and the subsequent drug-resistant behavior. Apart from the well-established transcriptional regulation, EMT is also controlled post-transcriptionally by virtue of alternative splicing (AS). Numerous genes including Fibroblast Growth Factor receptor (FGFR) as well as CD44 are differentially spliced during this trans-differentiation process which, in turn, governs cancer progression. These splicing alterations are controlled by various splicing factors including ESRP, RBFOX2 as well as hnRNPs. Here, we have depicted the mechanisms governing the splice isoform switching of FGFR and CD44. Moreover, the role of the splice variants generated by AS of these gene transcripts in modulating the metastatic potential and stem-like/chemoresistant behavior of cancer cells has also been highlighted. Additionally, the involvement of splicing factors in regulating EMT/invasiveness along with drug-resistance as well as the metabolic properties of the cells has been emphasized. Tumorigenesis is accompanied by a remodeling of the cellular splicing profile generating diverse protein isoforms which, in turn, control the cancer-associated hallmarks. Therefore, we have also briefly discussed about a wide variety of genes which are differentially spliced in the tumor cells and promote cancer progression. We have also outlined different strategies for targeting the tumor-associated splicing events which have shown promising results and therefore this approach might be useful in developing therapies to reduce cancer aggressiveness in a more specific manner.