Heterogeneity and Utility of Pharmaceutical Company Sharing of Individual-Participant Data Packages.

Importance: The pharmaceutical industry has made substantial investments in developing processes for sharing individual-participant data (IPD) from clinical trials. However, the utility and completeness of shared IPD and supporting documents must be evaluated to ensure the potential for scientific advancements from the data sharing ecosystem can be realized. Objective: To assess the utility and completeness of IPD and supporting documents provided from industry-sponsored clinical trials. Design, Setting, and Participants: From February 9, 2022, to February 9, 2023, 91 of 203 clinical trials supporting US Food and Drug Administration registrations of anticancer medicines for the treatment of solid tumors from the past decade were confirmed as eligible for IPD request. This quality improvement study performed a retrospective audit of the utility and completeness of the IPD and supporting documents provided from the 91 clinical trials for a planned meta-analysis. Exposures: Request for IPD from 91 clinical oncology trials indicated as eligible for the request. Main Outcomes and Measures: The utility and completeness of the IPD and supporting documents provided. Results: The IPD packages were obtained from 70 of 91 requested clinical trials (77%). The median time to data provision was 123 (range, 117-352) days. Redactions were observed in 18 of the acquired IPD packages (26%) for outcome data, 11 (16%) for assessment variables, and 19 (27%) for adjustment data. Additionally, 20 IPD packages (29%) lacked a clinical study report, 4 (6%) had incomplete or missing data dictionaries, and 20 (29%) were missing anonymization or redaction description files. Access to IPD from 21 eligible trials (23%) was not granted. Conclusions and Relevance: In this quality improvement study, there was substantial variability within the provided IPD packages regarding the completeness of key data variables and supporting documents. To improve the data sharing ecosystem, key areas for enhancement include (1) ensuring that clinical trials are eligible for IPD sharing, (2) making eligible IPD transparently accessible, and (3) ensuring that IPD packages meet a standard of utility and completeness.

Particle motion on burned and vegetated hillslopes.

Climate change is causing increasingly widespread, frequent, and intense wildfires across the western United States. Many geomorphic effects of wildfire are relatively well studied, yet sediment transport models remain unable to account for the rapid transport of sediment released from behind incinerated vegetation, which can fuel catastrophic debris flows. This oversight reflects the fundamental inability of local, continuum-based models to capture the long-distance particle motions characteristic of steeplands. Probabilistic, particle-based nonlocal models may address this deficiency, but empirical data are needed to constrain their representation of particle motion in real landscapes. Here we present data from field experiments validating a generalized Lomax model for particle travel distance distributions. The model parameters provide a physically intuitive mathematical framework for describing the transition from light- to heavy-tailed distributions along a continuum of behavior as particle size increases and slopes get steeper and/or smoother. We show that burned slopes are measurably smoother than vegetated slopes, leading to 1) lower rates of experimental particle disentrainment and 2) runaway motion that produces the heavy-tailed travel distances often associated with nonlocal transport. Our results reveal that surface roughness is a key control on steepland sediment transport, particularly after wildfire when smoother surfaces may result in the preferential delivery of coarse material to channel networks that initiate debris flows. By providing a first-order framework relating the statistics of particle motion to measurable surface characteristics, the Lomax model both advances the development of nonlocal sediment transport theory and reveals insights on hillslope transport mechanics.

The Drug Abuse Prevention and Control Act of 1970: Retrospective Assessments of Disparate Treatment and Consequential Impact.

Although the basic paradigm of the U.S. federal drug policy targeting the supply and demand reduction has not changed since its enactment in 1970, there have been seriously undesirable disparate treatments and impacts among various population groups. Although U.S. Congress could not define what is discrimination, it did provide two major criteria for the assessment of discriminatory practices as follows: (a) disparate treatment-basing a key decision on association with any of the five prohibited individual's demographic classifications (race, color, religion, sex, or national origin); and (b) disparate impact-correlation between any of the five prohibited demographic classifications and the key outcomes. In reference to those criteria, this article describes evidence-based indicators of national failure of the Comprehensive Drug Abuse Prevention and Control Act.

Male county jail inmates: a profile and self-reported human service needs by race.

With the enactment of the Second Chance Act in 2008, social workers have a greater opportunity for intervention to break the cycle of recidivism. To develop interventions, however, social workers require profiles of incarcerated people and their perceived human service needs. Unfortunately, previous research has focused on prison and not jail inmates and lacks race-differential data. In this article the authors address this gap in the literature by describing the scope of the problem and presenting a profile of male inmates and their perceived service needs by race upon entry into a major urban county jail.

Avoiding type III, IV, and V errors through collaborative research.

Major types of empirical errors reviewed by a number of leading research textbooks include discussions of Type I and Type II errors. However, applied human service researchers can commit other types of errors that should be avoided. The potential benefits of the applied, collaborative research (in contrast to traditional participatory research) include an assurance that the study begins with the "right" questions that are important for community residents. Such research practice also helps generate useful research findings for decisions regarding redistribution of resources and resolving community issues. The aim of collaborative research is not merely to advance scientific understanding, but also to produce empirical findings that are usable for addressing priority needs and problems of distressed communities. A review of a case example (Garfield Community Assessment Study) illustrates the principles and practices of collaborative research.

Genetic diversity of Ectocarpus (Ectocarpales, Phaeophyceae) in Peru and northern Chile, the area of origin of the genome-sequenced strain.

• The origin of the Ectocarpus strain used for genome sequencing (the 'genome strain') was Peru, where no Ectocarpus had been reported previously. To study the genetic diversity in the region and to increase the number of individuals from this area available for genetic experiments, 119 new Ectocarpus strains were isolated from eight localities along the 3000 km of coastline from central Peru to central Chile. • Internal transcribed spacer 1 (ITS1) genotyping revealed nine different genotypes, five of which were endemic to the area studied and three of which were previously unknown. • Individuals of the same genotype as the genome strain occurred from Peru to northernmost Chile, representing 61% of the samples in this area, from which five more genotypes were isolated. Further south, down to central Chile, most individuals belonged to Ectocarpus siliculosus, Ectocarpus fasciculatus and Ectocarpus crouaniorum. In sexual crosses, the genome strain and the new isolates of the same genotype were fully compatible. • Sequences from four nuclear and cytoplasmic genetic markers (ITS1, ITS2, Rubisco spacer and Cytochrome-c oxidase subunit 3 (cox3)) separated the genome strain from the known species of Ectocarpus. It may in future be recognized as a separate species.

Copper stress proteomics highlights local adaptation of two strains of the model brown alga Ectocarpus siliculosus.

Ectocarpus siliculosus is a cosmopolitan brown alga with capacity to thrive in copper enriched environments. Analysis of copper toxicity was conducted in two strains of E. siliculosus isolated from (i) an uncontaminated coast in southern Peru (Es32) and (ii) a copper polluted rocky beach in northern Chile (Es524). Es32 was more sensitive than Es524, with toxicity detected at 50 microg/L Cu, whereas Es524 displayed negative effects only when exposed to 250 microg/L Cu. Differential soluble proteome profiling for each strain exposed to sub-lethal copper levels allowed to identify the induction of proteins related to processes such as energy production, glutathione metabolism as well as accumulation of HSPs. In addition, the inter-strain comparison of stress-related proteomes led to identify features related to copper tolerance in Es524, such as striking expression of a PSII Mn-stabilizing protein and a Fucoxanthine chlorophyll a-c binding protein. Es524 also expressed specific stress-related enzymes such as RNA helicases from the DEAD box families and a vanadium-dependent bromoperoxidase. These observations were supported by RT-qPCR for some of the identified genes and an enzyme activity assay for vanadium-dependent bromoperoxidase. Therefore, the occurrence of two different phenotypes within two distinct E. siliculosus strains studied at the physiological and proteomic levels strongly suggest that persistent copper stress may represent a selective force leading to the development of strains genetically adapted to copper contaminated sites.