Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Best practices for user consultation in flow cytometry shared resource laboratories.

This "Best Practices in User Consultation" article is the result of a 2022 International Society for the Advancement of Cytometry (ISAC) membership survey that collected valuable insights from the shared research laboratory (SRL) community and of a group discussion at the CYTO 2022 workshop of the same name. One key takeaway is the importance of initiating a consultation at the outset of a flow cytometry project, particularly for trainees. This approach enables the improvement and standardization of every step, from planning experiments to interpreting data. This proactive approach effectively mitigates experimental bias and avoids superfluous trial and error, thereby conserving valuable time and resources. In addition to guidelines, the optimal approaches for user consultation specify communication channels, methods, and critical information, thereby establishing a structure for productive correspondence between SRL and users. This framework functions as an exemplar for establishing robust and autonomous collaborative relationships. User consultation adds value by providing researchers with the necessary information to conduct reproducible flow cytometry experiments that adhere to scientific rigor. By following the steps, instructions, and strategies outlined in these best practices, an SRL can readily tailor them to its own setting, establishing a personalized workflow and formalizing user consultation services. This article provides a pragmatic guide for improving the caliber and efficacy of flow cytometry research and aggregates the flow cytometry SRL community's collective knowledge regarding user consultation.

KDOQI Commentary on the KDIGO 2022 Update to the Clinical Practice Guideline for Diabetes Management in CKD.

The Kidney Disease: Improving Global Outcomes (KDIGO) guideline for diabetes management in chronic kidney disease (CKD) was updated in 2022, just 2 years after the previous update. The need for this rapid update is reflective of the recent and unprecedented positive results of numerous clinical trials aimed at reducing kidney and cardiovascular morbidity and mortality in people with diabetes. The Kidney Disease Outcomes Quality Initiative (KDOQI) work group for diabetes in CKD, convened by the National Kidney Foundation, provides herein a commentary on these changes, particularly the implications for health care in the United States. Changes to the KDIGO guideline mirror the evolution of sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists from purely antihyperglycemic agents to cardiorenal-metabolic therapeutics, and the lower estimated glomerular filtration rate of≥20mL/min/1.73m2 for SGLT2 inhibitor initiation. New data have also brought the addition of the first-in-class, Federal Drug Administration-approved nonsteroidal mineralocorticoid receptor antagonist finerenone as an agent to reduce cardiorenal end points. While there has been significant progress in innovation, there remain serious challenges to implementation, particularly in the United States where inequities in insurance coverage and high costs limit their use, particularly in vulnerable populations, ultimately widening health care disparities.

Enhancing current guidance for psoriatic arthritis and its comorbidities: recommendations from an expert consensus panel.

OBJECTIVES: Existing guidelines for psoriatic arthritis (PsA) cover many aspects of management. Some gaps remain relating to routine practice application. An expert group aimed to enhance current guidance and develop recommendations for clinical practice that are complementary to existing guidelines. METHODS: A steering committee comprising experienced, research-active clinicians in rheumatology, dermatology and primary care agreed on themes and relevant questions. A targeted literature review of PubMed and Embase following a PICO framework was conducted. At a second meeting, recommendations were drafted and subsequently an extended faculty comprising rheumatologists, dermatologists, primary care clinicians, specialist nurses, allied health professionals, non-clinical academic participants and members of the Brit-PACT patient group, was recruited. Consensus was achieved via an online voting platform when 75% of respondents agreed in the range of 7-9 on a 9-point scale. RESULTS: The guidance comprised 34 statements covering four PsA themes. Diagnosis focused on strategies to identify PsA early and refer appropriately, assessment of diagnostic indicators, use of screening tools and use of imaging. Disease assessment centred on holistic consideration of disease activity, physical functioning and impact from a patient perspective, and on how to implement shared decision-making. For comorbidities, recommendations included specific guidance for high-impact conditions such as depression and obesity. Management statements (which excluded extant guidance on pharmacological therapies) covered multidisciplinary team working, implementation of lifestyle modifications and treat-to-target strategies. Minimising corticosteroid use was recommended where feasible. CONCLUSION: The consensus group have made evidence-based best practice recommendations for the management of PsA to enhance the existing guidelines.

Perspective: use and reuse of NMR-based metabolomics data: what works and what remains challenging.

BACKGROUND: The National Cancer Institute issued a Request for Information (RFI; NOT-CA-23-007) in October 2022, soliciting input on using and reusing metabolomics data. This RFI aimed to gather input on best practices for metabolomics data storage, management, and use/reuse. AIM OF REVIEW: The nuclear magnetic resonance (NMR) Interest Group within the Metabolomics Association of North America (MANA) prepared a set of recommendations regarding the deposition, archiving, use, and reuse of NMR-based and, to a lesser extent, mass spectrometry (MS)-based metabolomics datasets. These recommendations were built on the collective experiences of metabolomics researchers within MANA who are generating, handling, and analyzing diverse metabolomics datasets spanning experimental (sample handling and preparation, NMR/MS metabolomics data acquisition, processing, and spectral analyses) to computational (automation of spectral processing, univariate and multivariate statistical analysis, metabolite prediction and identification, multi-omics data integration, etc.) studies. KEY SCIENTIFIC CONCEPTS OF REVIEW: We provide a synopsis of our collective view regarding the use and reuse of metabolomics data and articulate several recommendations regarding best practices, which are aimed at encouraging researchers to strengthen efforts toward maximizing the utility of metabolomics data, multi-omics data integration, and enhancing the overall scientific impact of metabolomics studies.

Creating and troubleshooting microscopy analysis workflows: Common challenges and common solutions.

As microscopy diversifies and becomes ever more complex, the problem of quantification of microscopy images has emerged as a major roadblock for many researchers. All researchers must face certain challenges in turning microscopy images into answers, independent of their scientific question and the images they have generated. Challenges may arise at many stages throughout the analysis process, including handling of the image files, image pre-processing, object finding, or measurement, and statistical analysis. While the exact solution required for each obstacle will be problem-specific, by keeping analysis in mind, optimizing data quality, understanding tools and tradeoffs, breaking workflows and data sets into chunks, talking to experts, and thoroughly documenting what has been done, analysts at any experience level can learn to overcome these challenges and create better and easier image analyses.

Redefining 'state-of-the-art' for integrated population models with immigration.

Research Highlight: Christian, M., Oosthuizen, W. C., Bester, M. N., & de Bruyn, P. N. (2024). Robustly estimating the demographic contribution of immigration: Simulation, sensitivity analysis and seals. Journal of Animal Ecology. https://doi.org/10.1111/1365-2656.14053. Immigration can have profound consequences for local population dynamics and demography, but collecting data to accurately quantifying it is challenging. The recent rise of integrated population models (IPMs) offers an alternative by making it possible to estimate immigration without the need for explicit data, and to quantify its contribution to population dynamics through transient Life Table Response Experiments (tLTREs). Simulation studies have, however, highlighted that this approach can be prone to bias and overestimation. In their new study, Christian et al. address one of the root causes of this issue by improving the estimation of time variation in vital rates and immigration using Gaussian processes in lieu of traditionally used temporal random effects. They demonstrate that IPM-tLTRE frameworks with Gaussian processes produce more accurate and less biased estimates of immigration and its contribution to population dynamics and illustrate the applicability of this approach using a long-term data set on elephant seals (Mirounga leonida). Results are validated with a simulation study and suggest that immigration of breeding females has been central for population recovery of elephant seals despite the species' high female site fidelity. Christian et al. thus present new insights into population regulation of long-lived marine mammals and highlight the potential for using Gaussian process priors in IPMs. They also illustrate a suite of 'best practices' for state-of-the-art IPM-tLTRE analyses and provide an inspirational example for the kind of ecological modelling workflow that can be invaluable not just as a starting point for fellow ecologists picking up or improving their own IPM-tLTRE analyses, but also for teaching and in contexts where model estimates are used for informing management and conservation decision-making.

Chatbots That Deliver Contraceptive Support: Systematic Review.

BACKGROUND: A chatbot is a computer program that is designed to simulate conversation with humans. Chatbots may offer rapid, responsive, and private contraceptive information; counseling; and linkages to products and services, which could improve contraceptive knowledge, attitudes, and behaviors. OBJECTIVE: This review aimed to systematically collate and interpret evidence to determine whether and how chatbots improve contraceptive knowledge, attitudes, and behaviors. Contraceptive knowledge, attitudes, and behaviors include access to contraceptive information, understanding of contraceptive information, access to contraceptive services, contraceptive uptake, contraceptive continuation, and contraceptive communication or negotiation skills. A secondary aim of the review is to identify and summarize best practice recommendations for chatbot development to improve contraceptive outcomes, including the cost-effectiveness of chatbots where evidence is available. METHODS: We systematically searched peer-reviewed and gray literature (2010-2022) for papers that evaluated chatbots offering contraceptive information and services. Sources were included if they featured a chatbot and addressed an element of contraception, for example, uptake of hormonal contraceptives. Literature was assessed for methodological quality using appropriate quality assessment tools. Data were extracted from the included sources using a data extraction framework. A narrative synthesis approach was used to collate qualitative evidence as quantitative evidence was too sparse for a quantitative synthesis to be carried out. RESULTS: We identified 15 sources, including 8 original research papers and 7 gray literature papers. These sources included 16 unique chatbots. This review found the following evidence on the impact and efficacy of chatbots: a large, robust randomized controlled trial suggests that chatbots have no effect on intention to use contraception; a small, uncontrolled cohort study suggests increased uptake of contraception among adolescent girls; and a development report, using poor-quality methods, suggests no impact on improved access to services. There is also poor-quality evidence to suggest increased contraceptive knowledge from interacting with chatbot content. User engagement was mixed, with some chatbots reaching wide audiences and others reaching very small audiences. User feedback suggests that chatbots may be experienced as acceptable, convenient, anonymous, and private, but also as incompetent, inconvenient, and unsympathetic. The best practice guidance on the development of chatbots to improve contraceptive knowledge, attitudes, and behaviors is consistent with that in the literature on chatbots in other health care fields. CONCLUSIONS: We found limited and conflicting evidence on chatbots to improve contraceptive knowledge, attitudes, and behaviors. Further research that examines the impact of chatbot interventions in comparison with alternative technologies, acknowledges the varied and changing nature of chatbot interventions, and seeks to identify key features associated with improved contraceptive outcomes is needed. The limitations of this review include the limited evidence available on this topic, the lack of formal evaluation of chatbots in this field, and the lack of standardized definition of what a chatbot is.

International Delphi Study on Wound Closure and Dressing Management in Joint Arthroplasty: Part 1: Total Knee Arthroplasty.

BACKGROUND: The purpose of this modified Delphi study was to obtain consensus on wound closure and dressing management in total knee arthroplasty (TKA). METHODS: The Delphi panel included 20 orthopaedic surgeons from Europe and North America. There were 26 statements identified using a targeted literature review. Consensus was developed for the statements with up to three rounds of anonymous voting per topic. Panelists ranked their agreement with each statement on a five-point Likert scale. An a priori threshold of ≥ 75% was required for consensus. RESULTS: All 26 statements achieved consensus after three rounds of anonymous voting. Wound closure-related interventions that were recommended for use in TKA included: 1) closing in semi-flexion versus extension (superior range of motion); 2) using aspirin for venous thromboembolism prophylaxis over other agents (reduces wound complications); 3) barbed sutures over non-barbed sutures (lower wound complications, better cosmetic appearances, shorter closing times, and overall cost savings); 4) mesh-adhesives over other skin closure methods (lower wound complications, higher patient satisfaction scores, lower rates of readmission); 5) silver-impregnated dressings over standard dressings (lower wound complications, decreased infections, fewer dressing changes); 6) in high-risk patients, negative pressure wound therapy over other dressings (lower wound complications, decreased reoperations, fewer dressing changes); and 7) using triclosan-coated over non-antimicrobial-coated sutures (lower risks of surgical site infection). CONCLUSIONS: Using a modified Delphi approach, the panel achieved consensus on 26 statements pertaining to wound closure and dressing management in TKA. This study forms the basis for identifying critical evidence supported by clinical practice for wound management to help reduce variability, advance standardization, and ultimately improve outcomes during TKA. The results presented here can serve as the foundation for knowledge, education, and improved clinical outcomes for surgeons performing TKAs.

What they forgot to tell you about machine learning with an application to pharmaceutical manufacturing.

Predictive models (a.k.a. machine learning models) are ubiquitous in all stages of drug research, safety, development, manufacturing, and marketing. The results of these models are used inside and outside of pharmaceutical companies for the purpose of understanding scientific processes and for predicting characteristics of new samples or patients. While there are many resources that describe such models, there are few that explain how to develop a robust model that extracts the highest possible performance from the available data, especially in support of pharmaceutical applications. This tutorial will describe pitfalls and best practices for developing and validating predictive models with a specific application to a monitoring a pharmaceutical manufacturing process. The pitfalls and best practices will be highlighted to call attention to specific points that are not generally discussed in other resources.

Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research.

The fifth annual workshop on Principles and Techniques for Improving Preclinical Translation of Alzheimer's Disease Research was held in May 2023 at The Jackson Laboratory in Bar Harbor, Maine, USA. The workshop was established in 2018 to address training gaps in preclinical translational studies for Alzheimer's disease (AD). In addition to providing fundamental knowledge and hands-on skills essential for executing rigorous in vivo studies that are designed to facilitate translation, each year the workshop aims to provide insight on state-of-the-field technological advances and new resources including novel animal models, publicly available datasets, novel biomarkers, and new medical imaging tracers. This innovative and comprehensive workshop continues to deliver training for the greater AD research community in order to provide investigators and trainees with the knowledge and skillsets essential for enabling improved preclinical to clinical translation and accelerate the process of advancing safe and effective therapeutic interventions for AD. HIGHLIGHTS: Translational research is not typically available as a course of study at academic institutions, yet there are fundamental skillsets and knowledge required to enable successful translation from preclinical experiments to clinical efficacy. It is important that there are resources and opportunities available to researchers planning preclinical translational experiments. Here we present proceedings from the fifth annual NIA-sponsored workshop focused on enabling improved preclinical to clinical translation for Alzheimer's disease research that includes didactic lectures on state-of-the-field approaches and hands-on practicums for acquiring essential translational laboratory techniques.

The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for the Mitigation of Complications of Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to October 2023. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Establishing Best Practices in Telehealth Care for Adults with Developmental Disabilities in the United States: An e-Delphi Study.

Background: Telehealth care is now a key element of mainstream health care since the COVID-19 pandemic, with all types of health care providers joining the digital revolution. As a population experiencing health care disparities, adults with developmental disabilities and their supporters have described variable experiences with telehealth care that contribute to overall care quality and health outcomes. Methods: This e-Delphi study established consensus on best practices in telehealth care for adults with developmental disabilities in the United States. Online surveys and videoconferencing interviews were conducted with 44 expert panelists with experience with telehealth care and developmental disabilities, including adults with developmental disabilities, family members, direct support professionals, nurses, and health care providers. Results: Three rounds of surveys resulted in a set of 9 guidelines consisting of 42 items. The guidelines addressed 1) appropriate situations for telehealth care, 2) communication needs and preferences, 3) support person collaboration, 4) education and anticipatory guidance, 5) reminders, 6) coordination of care, 7) equitable and fair access, 8) privacy and safety, and 9) evidence-based practice. Conclusion: Health care providers can adopt these best practice guidelines to ensure telehealth care is provided equitably and safely to adults with developmental disabilities. Policy advocacy is needed for the uptake of these guidelines and for health care providers and adults with developmental disabilities to access the resources needed for safe and effective telehealth care use.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for Spinal Cord Stimulation Long-Term Outcome Optimization and Salvage Therapy.

INTRODUCTION: The International Neuromodulation Society (INS) has recognized a need to establish best practices for optimizing implantable devices and salvage when ideal outcomes are not realized. This group has established the Neurostimulation Appropriateness Consensus Committee (NACC)® to offer guidance on matters needed for both our members and the broader community of those affected by neuromodulation devices. MATERIALS AND METHODS: The executive committee of the INS nominated faculty for this NACC® publication on the basis of expertise, publications, and career work on the issue. In addition, the faculty was chosen in consideration of diversity and inclusion of different career paths and demographic categories. Once chosen, the faculty was asked to grade current evidence and along with expert opinion create consensus recommendations to address the lapses in information on this topic. RESULTS: The NACC® group established informative and authoritative recommendations on the salvage and optimization of care for those with indwelling devices. The recommendations are based on evidence and expert opinion and will be expected to evolve as new data are generated for each topic. CONCLUSIONS: NACC® guidance should be considered for any patient with less-than-optimal outcomes with a stimulation device implanted for treating chronic pain. Consideration should be given to these consensus points to salvage a potentially failed device before explant.

Healthcare providers' perspectives on sustaining respectful maternity care appreciated by mothers in five hospitals of Rwanda.

BACKGROUND: Childbirth reserves respect, as emphasized by the World Health Organization in 2018, and the focus towards the need for positive, dignified delivery experiences has become an integral aspect of Respectful Maternity Care (RMC). It is a known fact that RMC is pivotal for favourable birth outcomes and contributes to the satisfaction of maternity care. The absence of RMC negatively affects women's and newborns' rights. The study aimed to explore healthcare providers' perspectives on sustaining RMC actions that mothers previously reported. METHODOLOGY: This study was conducted in five hospitals in the Eastern province of Rwanda, involving 5 Focus Group Discussions (FGDs) with midwives and nurses. For interviews, we purposively selected 5-unit managers and five physicians. Additionally, 40 midwives and nurses were recruited for the FGDs. The research utilized the Dream phase of Appreciative Inquiry (AI) for interviews and Focus Groups. Data collection aimed to gain insights into Healthcare Providers' perceptions of how RMC is provided and how to establish and sustain RMC in Rwandan health facilities. Nvivo 12 was employed for organizing codes and creating a codebook, and thematic analysis was applied. RESULTS: Four themes with sub-themes emerged. Namely, 1) Women-centered care, with Compassionate care, Privacy and confidentiality maintenance, Information provision and Liberty in decision making, Effective communication, Family involvement, Cleanliness, and Equality care. 2) Professionalism compliance with Motivated staff, Teamwork, Continuous development, Quality work provision, and Community trust. 3) RMC encounters 4) RMC sustenance. CONCLUSION AND RECOMMENDATIONS: The continuous pursuit of high RMC standards in Rwanda involves improving childbirth experiences through utilizing existing resources, ongoing improvement, and sustaining achievements. Key recommended actions in this study for sustaining RMC encompass promoting women-centred care, enhancing healthcare provider attitudes, ensuring professionalism, building community trust, maintaining conducive health facility environments, and involving leadership.

Comparative review of vasectomy guidelines and novel vasal occlusion techniques.

Vasectomy is the most commonly performed urologic procedure in the United States and is a highly effective form of male contraception. The introduction of guidelines by urological societies has standardized vasectomy care. Providers should be awadre of the rationale behind these guidelines, as well as key differences among them. While few major changes to vasectomy technique have been adopted over the past 40 years, new, reversible vasal occlusive technologies may affect delivery of male contraceptive care in the future. Here, we perform a comparative review of vasectomy guidelines from six urological societies worldwide. In addition, we report on the status of several experimental vasal occlusion methods that may be available in the next decade.

Impact of a Best Practices Program in Patients with Relapsed/Refractory Multiple Myeloma Receiving Selinexor.

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.

Exploring the ethical dimensions in forensic entomology: From codes of conduct to professional accountability.

This article investigates a critical part of professional careers: adhering to a code of ethics that defines proper behavior within the context of one's specialized practice. It aims to improve the setting of forensic entomology work by highlighting the ethical issues that frequently emerge. The primary goal is to uncover common ethical issues involved in this field's everyday activities and provide informed advice on appropriate resolution options. This investigation dives into the complex interaction of religious beliefs, cultural aspects, and issues of ethics, evaluating their relevance in forensic entomology. It examines a wide range of ethical issues, from the ethics involved in collecting samples at crime scenes and morguesto the ethics created into scientific investigations, report writing, and court testimony. These guiding principles are critical in setting scientific standards and building public trust in forensic entomology's ability to provide exceptional services. Notably, regardless of whether the forensic entomology service provider is accredited by any validating organization, these ethical requirements remain critical, emphasizing their global application.