WATCH: A Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors.

This article proposes a Workflow for Assessing Treatment effeCt Heterogeneity (WATCH) in clinical drug development targeted at clinical trial sponsors. WATCH is designed to address the challenges of investigating treatment effect heterogeneity (TEH) in randomized clinical trials, where sample size and multiplicity limit the reliability of findings. The proposed workflow includes four steps: analysis planning, initial data analysis and analysis dataset creation, TEH exploration, and multidisciplinary assessment.

Students Who Perceive Instructors to Have a Fixed Mindset Report a Greater Sense of Academic Misfit That Leads to Lower Chemistry Grades.

Student mindset beliefs about the malleability of intelligence have been linked to student outcomes. However, recent meta-analyses showed mixed findings on how student mindset impacts their outcomes depending on the environment and context, such as the mindset that the instructor projects in the classroom. The current work utilizes Social Cognitive Theory to elucidate the relationship among student perceptions of faculty mindset, affective factors (belonging, self-efficacy, and utility value), and behavioral factors (course grade) using a Diversity, Equity, and Inclusion (DEI) lens within the chemistry context at a demographically diverse institution.

Regression without regrets -initial data analysis is a prerequisite for multivariable regression.

Statistical regression models are used for predicting outcomes based on the values of some predictor variables or for describing the association of an outcome with predictors. With a data set at hand, a regression model can be easily fit with standard software packages. This bears the risk that data analysts may rush to perform sophisticated analyses without sufficient knowledge of basic properties, associations in and errors of their data, leading to wrong interpretation and presentation of the modeling results that lacks clarity.

Initial data analysis for longitudinal studies to build a solid foundation for reproducible analysis.

Initial data analysis (IDA) is the part of the data pipeline that takes place between the end of data retrieval and the beginning of data analysis that addresses the research question. Systematic IDA and clear reporting of the IDA findings is an important step towards reproducible research. A general framework of IDA for observational studies includes data cleaning, data screening, and possible updates of pre-planned statistical analyses.

All that Glitters Is not Gold: Type-I Error Controlled Variable Selection from Clinical Trial Data.

Clinical trials are primarily conducted to estimate causal effects, but the data collected can also be invaluable for additional research, such as identifying prognostic measures of disease or biomarkers that predict treatment efficacy. However, these exploratory settings are prone to false discoveries (type-I errors) due to the multiple comparisons they entail. Unfortunately, many methods fail to address this issue, in part because the algorithms used are generally designed to optimize predictions and often only provide the measures used for variable selection, such as machine learning model importance scores, as a byproduct.

Predicting subgroup treatment effects for a new study: Motivations, results and learnings from running a data challenge in a pharmaceutical corporation.

We present the motivation, experience, and learnings from a data challenge conducted at a large pharmaceutical corporation on the topic of subgroup identification. The data challenge aimed at exploring approaches to subgroup identification for future clinical trials. To mimic a realistic setting, participants had access to 4 Phase III clinical trials to derive a subgroup and predict its treatment effect on a future study not accessible to challenge participants.

Perceived Barriers to Equitable Participation in the Learning Assistant Program.

To build a more diverse STEM workforce, institutions seek to increase the representation of diverse groups in faculty and mentoring positions. The Learning Assistant (LA) near-peer student support program has the potential to bring diverse students into highly visible and impactful mentoring roles early in their college careers, benefiting both LAs and students in LA-supported courses. However, the demographic characteristics of potential students interested in the LA Program and the subsequent barriers to entry have yet to be investigated.

A deep learning approach to private data sharing of medical images using conditional generative adversarial networks (GANs).

Clinical data sharing can facilitate data-driven scientific research, allowing a broader range of questions to be addressed and thereby leading to greater understanding and innovation. However, sharing biomedical data can put sensitive personal information at risk. This is usually addressed by data anonymization, which is a slow and expensive process.

DMC reports in the 21st century: towards better tools for decision-making.

Data Monitoring Committees (DMCs) have the important task to protect the safety of current and future patients during the conduct of a clinical study. Unfortunately, their work is often made difficult by voluminous DMC reports that are poorly structured and difficult to digest. In this article, we suggest improved solutions.

Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE.

Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE.

Public Health Messaging for Wildfire Smoke: Cast a Wide Net.

Wildfire smoke events are increasing in British Columbia (BC), Canada and environmental and public health agencies are responsible for communicating the health-related risks and mitigation strategies. To evaluate and identify opportunities for improving public communications about wildfire smoke and associated health risks we collaborated with end-users and developed a 32-question online survey. The survey was deployed province-wide from 29 September to 31 December 2020 following a severe wildfire smoke episode, which impacted large parts of BC.

Effective Visual Communication for the Quantitative Scientist.

Effective visual communication is a core competency for pharmacometricians, statisticians, and, more generally, any quantitative scientist. It is essential in every step of a quantitative workflow, from scoping to execution and communicating results and conclusions. With this competency, we can better understand data and influence decisions toward appropriate actions.

How can we make better graphs? An initiative to increase the graphical expertise and productivity of quantitative scientists.

Graphics are at the core of exploring and understanding data, communicating results and conclusions, and supporting decision-making. Increasing our graphical expertise can significantly strengthen our impact as professional statisticians and quantitative scientists. In this article, we present a concerted effort to improve the way we create graphics at Novartis.

Tree rings reveal globally coherent signature of cosmogenic radiocarbon events in 774 and 993 CE.

Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the C content in 484 individual tree rings formed in the periods 770-780 and 990-1000 CE.

Discovery of a Fluorinated Enigmol Analog with Enhanced in Vivo Pharmacokinetic and Anti-Tumor Properties.

The orally bioavailable 1-deoxy-sphingosine analog, Enigmol, has demonstrated anticancer activity in numerous in vivo settings. However, as no Enigmol analog with enhanced potency in vitro has been identified, a new strategy to improve efficacy in vivo by increasing tumor uptake was adopted. Herein, synthesis and biological evaluation of two novel fluorinated Enigmol analogs, CF3-Enigmol and CF2-Enigmol, are reported.

Old World megadroughts and pluvials during the Common Era.

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other "Old World" climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the "Old World Drought Atlas" (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available.

Novel synthesis and biological evaluation of enigmols as therapeutic agents for treating prostate cancer.

Enigmol is a synthetic, orally active 1-deoxysphingoid base analogue that has demonstrated promising activity against prostate cancer. In these studies, the pharmacologic roles of stereochemistry and N-methylation in the structure of enigmols were examined. A novel enantioselective synthesis of all four possible 2S-diastereoisomers of enigmol (2-aminooctadecane-3,5-diols) from l-alanine is reported, which features a Liebeskind-Srogl cross-coupling reaction between l-alanine thiol ester and (E)-pentadec-1-enylboronic acid as the key step.

Do women spend more time in the restroom than men?

120 college students were observed entering and exiting a public restroom. A significant sex difference was found (Cohen d = .34).

Temporal and spatial variations in lice numbers on salmon farms in the Hardanger fjord 2004-06.

The long and narrow Hardanger fjord in western Norway has a high density of salmon farms and has had severe salmon lice, Lepeophtheirus salmonis, problems. In the years 2004-06, salmon lice numbers were recorded in selected salmon farms in the fjord as part of a larger research project. Most farm sites participated in a strategic control programme and were deloused between November and January in each year.

The use of prevalence as a measure of lice burden: a case study of Lepeophtheirus salmonis on Scottish Atlantic salmon, Salmo salar L., farms.

This study investigates the benefits of using prevalence as a summary measure of sea lice infestation on farmed Atlantic salmon, Salmo salar L. Aspects such as sampling effort, the relationship between abundance and prevalence arising from the negative binomial distribution, and how this relationship can be used to indicate the degree of aggregation of lice on a site at a given time point are discussed. As a case study, data were drawn from over 50 commercial Atlantic salmon farms on the west coast of Scotland between 2002 and 2006.