Source Data Verification (SDV) quality in clinical research: A scoping review.

Introduction: The value of Source Data Verification (SDV) has been a common theme in the applied Clinical Translational Science literature. Yet, few published assessments of SDV quality exist even though they are needed to design risk-based and reduced monitoring schemes. This review was conducted to identify reports of SDV quality, with a specific focus on accuracy.

An overview of drug-induced sodium channel blockade and changes in cardiac conduction: Implications for drug safety.

The human voltage-gated sodium channel Na1.5 (hNa1.5/SCN5A) plays a critical role in the initiation and propagation of action potentials in cardiac myocytes, and its modulation by various drugs has significant implications for cardiac safety.

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.

Persistent Threat Avoidance Following Negative Reinforcement Is Not Associated with Elevated State Anxiety.

Obsessive-compulsive disorder (OCD) is a debilitating illness consisting of obsessions and compulsions. OCD severity and treatment response are correlated with avoidant behaviors thought be performed to alleviate obsession-related anxiety. However, little is known about either the role of avoidance in the development of OCD or the interplay between anxiety states and avoidance behaviors.

Recent advances in correlative cryo-light and electron microscopy.

Correlative light and electron microscopy (CLEM) pipelines serve to integrate the imaging modalities of fluorescence light microscopy (FLM) and cryogenic electron microscopy (cryo-EM) to produce contextually relevant high-resolution structural snapshots of biological systems. Innovations in sample preparation, instrumentation, imaging, and data processing have advanced the field of cryo-EM. This review focuses on prior work and recent developments in the field of cryo- EM that support further integration of technologies for correlative microscopy workflows.

Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction.

The potential for unintended drug induced changes in cardiac contractility is a major concern in medicines development. Whilst direct left ventricular pressure (LVP) measurement is the gold standard for measuring cardiac contractility in vivo, it is resource intensive and poses a welfare burden on research animals. In contrast, arterial blood pressure (BP) measurement has fewer challenges.

Assessment of corrected JT-peak (JTpc) and Tpeak-to-Tend (TpTec) as proarrhythmia biomarkers in non-human primates: Outcome from a HESI consortium.

Introduction: Corrected QT interval (QTc)is an established biomarker for drug-induced Torsade de Pointe (TdP), but with concerns for a false positive signal. Clinically, JTpc and TpTec have emerged as ECG sub-intervals to differentiate predominant hERG vs. mixed ion channel blocking drugs that prolong QTc.

Deciphering Natural Killer Cell Cytotoxicity Against Medulloblastoma in vitro and in vivo: Implications for Immunotherapy.

Purpose: Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK).

Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.

Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown.

Non-targeted effects of radiation therapy for glioblastoma.

Radiotherapy is recommended for the treatment of brain tumors such as glioblastoma (GBM) and brain metastases. Various curative and palliative scenarios suggest improved local-regional control. Although the underlying mechanisms are not yet clear, additional therapeutic effects have been described, including proximity and abscopal reactions at the treatment site.

Turbulent Properties of Stationary Flows in Porous Media.

In this study, we investigate the flow dynamics in a fixed bed of hydrogel beads using particle tracking velocimetry to compute the velocity field in the middle of the bed for moderate Reynolds numbers (Re=[124,169,203,211]). We discover that even though the flow is stationary at the larger scales, it exhibits complex multiscale spatial dynamics reminiscent of those observed in classical turbulence. We find evidence of the presence of an inertial range and a direct energy cascade, and are able to obtain a value for a "porous" Kolmogorov constant of C_{2}=3.

Collaborative science in action: A 20 year perspective from the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee.

The Health and Environmental Sciences Institute (HESI) is a nonprofit organization dedicated to resolving global health challenges through collaborative scientific efforts across academia, regulatory authorities and the private sector. Collaborative science across non-clinical disciplines offers an important keystone to accelerate the development of safer and more effective medicines. HESI works to address complex challenges by leveraging diverse subject-matter expertise across sectors offering access to resources, data and shared knowledge.

Development of a pharmaceutical database as an aid to the nonclinical detection of drug-induced cardiac toxicity.

The Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee designed and created a publicly accessible database with an initial set of 128 pharmacologically defined pharmaceutical agents, many with known cardiotoxic properties. The database includes specific information about each compound that could be useful in evaluating hypotheses around mechanisms of drug-induced cardiac toxicity or for development of novel cardiovascular safety assays. Data on each of the compounds was obtained from published literature and online sources (e.

Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening.

Traditional approaches to preclinical drug safety assessment have generally protected human patients from unintended adverse effects. However, these assessments typically occur too late to make changes in the formulation or in phase 1 and beyond, are highly dependent on animal studies and have the potential to lead to the termination of useful drugs due to liabilities in animals that are not applicable in patients. Collectively, these elements come at great detriment to both patients and the drug development sector.

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome.

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons.

Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium-pilocarpine rat model.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [F]-FDG PET.

Analyzing captive breeding outcomes to inform reintroduction practice: lessons from the pookila ().

Captive breeding is often used to produce individuals for reintroduction programs in order to reestablish a species in an area where it has become locally extinct. To maximize the likelihood of establishing a self-sustaining population in the wild, an analysis of data from captive breeding programs is commonly undertaken to (1) increase the of individuals and rate at which they can be released, and (2) maintain or improve the genetic and phenotypic of individuals. Here we demonstrate how the knowledge gained from these analyses can also be applied to decision-making during the design of subsequent reintroductions to further advance a reintroduction program toward success.

Genetic mixing in conservation translocations increases diversity of a keystone threatened species, Bettongia lesueur.

Translocation programmes are increasingly being informed by genetic data to monitor and enhance conservation outcomes for both natural and established populations. These data provide a window into contemporary patterns of genetic diversity, structure and relatedness that can guide managers in how to best source animals for their translocation programmes. The inclusion of historical samples, where possible, strengthens monitoring by allowing assessment of changes in genetic diversity over time and by providing a benchmark for future improvements in diversity via management practices.

Surface Modification of Brass via Ultrashort Pulsed Direct Laser Interference Patterning and Its Effect on Bacteria-Substrate Interaction.

In recent decades, antibiotic resistance has become a crucial challenge for human health. One potential solution to this problem is the use of antibacterial surfaces, i.e.

The incidence of spontaneous arrhythmias in telemetered beagle dogs, Göttingen Minipigs and Cynomolgus non-human primates: A HESI consortium retrospective analysis.

Introduction: Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry.

Methods: A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (n = 131), Göttingen minipigs (n = 108) and cynomolgus non-human primates (NHP; n = 78) were analyzed.

Bleeding complication following a shave biopsy in a patient taking ibrutinib.

Ibrutinib is an oral Bruton tyrosine kinase inhibitor approved for use in patients with B-cell malignancies and has been shown to increase progression-free survival in patients with chronic lymphocytic leukemia (CLL). Ibrutinib is known to increase bleeding risk in patients with CLL. We report a patient with CLL on ibrutinib who experienced significant and prolonged bleeding after a routine superficial tangential shave biopsy for suspected squamous cell carcinoma.

Clickable -Glycosyl Scaffold for the Development of a Dual Fluorescent and [F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging.

Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable -glycosyl scaffold to gather the different elements.