Invalid Forensic Science Testimony and Wrongful Convictions

This is the first study to explore the forensic science testimony by prosecution experts in the trials of innocent persons, all convicted of serious crimes, who were later exonerated by post-conviction DNA testing. Trial transcripts were sought for all 156 exonerees identified as having trial testimony by forensic analysts, of which 137 were located and reviewed. These trials most commonly included testimony concerning serological analysis and microscopic hair comparison, but some included bite mark, shoe print, soil, fiber, and fingerprint comparisons, and several included DNA testing. This study found that in the bulk of these trials of innocent defendants - 82 cases or 60% - forensic analysts called by the prosecution provided invalid testimony at trial - that is, testimony with conclusions misstating empirical data or wholly unsupported by empirical data. This was not the testimony of a mere handful of analysts: this set of trials included invalid testimony by 72 forensic analysts called by the prosecution and employed by 52 laboratories, practices, or hospitals from 25 states. Unfortunately, the adversarial process largely failed to police this invalid testimony. Defense counsel rarely cross-examined analysts concerning invalid testimony and rarely obtained experts of their own. In the few cases in which invalid forensic science was challenged, judges seldom provided relief. This evidence supports efforts to create scientific oversight mechanisms for reviewing forensic testimony and to develop clear scientific standards for written reports and testimony. The scientific community can through an official government entity promulgate standards to ensure the valid presentation of forensic science in criminal cases and thus the integrity and fairness of the criminal process

Invalid Forensic Science Testimony and Wrongful Convictions

This is the first study to explore the forensic science testimony by prosecution experts in the trials of innocent persons, all convicted of serious crimes, who were later exonerated by post-conviction DNA testing. Trial transcripts were sought for all 156 exonerees identified as having trial testimony by forensic analysts, of which 137 were located and reviewed. These trials most commonly included testimony concerning serological analysis and microscopic hair comparison, but some included bite mark, shoe print, soil, fiber, and fingerprint comparisons, and several included DNA testing. This study found that in the bulk of these trials of innocent defendants - 82 cases or 60% - forensic analysts called by the prosecution provided invalid testimony at trial - that is, testimony with conclusions misstating empirical data or wholly unsupported by empirical data. This was not the testimony of a mere handful of analysts: this set of trials included invalid testimony by 72 forensic analysts called by the prosecution and employed by 52 laboratories, practices, or hospitals from 25 states. Unfortunately, the adversarial process largely failed to police this invalid testimony. Defense counsel rarely cross-examined analysts concerning invalid testimony and rarely obtained experts of their own. In the few cases in which invalid forensic science was challenged, judges seldom provided relief. This evidence supports efforts to create scientific oversight mechanisms for reviewing forensic testimony and to develop clear scientific standards for written reports and testimony. The scientific community can through an official government entity promulgate standards to ensure the valid presentation of forensic science in criminal cases and thus the integrity and fairness of the criminal process

The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.

CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently inhibited cellular CHK1 activity (IC50 30-220 nM) and enhanced gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. Mouse oral bioavailability was complete (100%) with extensive tumor exposure. Genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest (pY15 CDK1) were inhibited both in vitro and in human tumor xenografts by CCT245737, causing increased DNA damage and apoptosis. Uniquely, we show CCT245737 enhanced gemcitabine antitumor activity to a greater degree than for higher doses of either agent alone, without increasing toxicity, indicating a true therapeutic advantage for this combination. Furthermore, development of a novel ELISA assay for pS296 CHK1 autophosphorylation, allowed the quantitative measurement of target inhibition in a RAS mutant human tumor xenograft of NSCLC at efficacious doses of CCT245737. Finally, CCT245737 also showed significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. In conclusion, CCT245737 is a new CHK1 inhibitor clinical development candidate scheduled for a first in man Phase I clinical trial, that will use the novel pS296 CHK1 ELISA to monitor target inhibition

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice

Federated learning enables big data for rare cancer boundary detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Recovered memories, satanic abuse, Dissociative Identity Disorder and false memories in the UK: a survey of Clinical Psychologists and Hypnotherapists

An online survey was conducted to examine psychological therapists’ experiences of, and beliefs about, cases of recovered memory, satanic / ritualistic abuse, Multiple Personality Disorder / Dissociative Identity Disorder, and false memory. Chartered Clinical Psychologists (n=183) and Hypnotherapists (n=119) responded. In terms of their experiences, Chartered Clinical Psychologists reported seeing more cases of satanic / ritualistic abuse compared to Hypnotherapists who, in turn, reported encountering more cases of childhood sexual abuse recovered for the first time in therapy, and more cases of suspected false memory. Chartered Clinical Psychologists were more likely to rate the essential accuracy of reports of satanic / ritualistic abuse as higher than Hypnotherapists. Belief in the accuracy of satanic / ritualistic abuse and Multiple Personality Disorder / Dissociative Identity Disorder reports correlated negatively with the belief that false memories were possible

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration. © 2023 the Author(s)

Opportunistic Detection of Type 2 Diabetes Using Deep Learning From Frontal Chest Radiographs

Deep learning (DL) models can harness electronic health records (EHRs) to predict diseases and extract radiologic findings for diagnosis. With ambulatory chest radiographs (CXRs) frequently ordered, we investigated detecting type 2 diabetes (T2D) by combining radiographic and EHR data using a DL model. Our model, developed from 271,065 CXRs and 160,244 patients, was tested on a prospective dataset of 9,943 CXRs. Here we show the model effectively detected T2D with a ROC AUC of 0.84 and a 16% prevalence. The algorithm flagged 1,381 cases (14%) as suspicious for T2D. External validation at a distinct institution yielded a ROC AUC of 0.77, with 5% of patients subsequently diagnosed with T2D. Explainable AI techniques revealed correlations between specific adiposity measures and high predictivity, suggesting CXRs\u27 potential for enhanced T2D screening