Long-term Evaluation of Machine Learning Based Methods for Air Emission Monitoring.

Machine learning (ML) techniques have been researched and used in various environmental monitoring applications. Few studies have reported the long-term evaluation of such applications. Discussions regarding the risks and regulatory frameworks of ML applications in environmental monitoring have been rare.

Upscaling ground-based backpack gamma-ray spectrometry to spatial resolution of UAV-based gamma-ray spectrometry for system validation.

Advances in the development of gamma-ray spectrometers have resulted in devices that are ideal for use in conjunction with the increasingly reliable systems of autonomously flying uncrewed aerial vehicles (UAVs) that have recently become available on the market. Airborne gamma-ray spectrometry (GRS) measurements have many different applications. Here, the technique is applied to a former uranium mining and processing site, which is characterized by relatively low specific activities and, hence, low count rates, requiring relatively large detectors and correspondingly big size UAVs.

Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology.

Systematics, biogeography and phylogenomics of northern bog lemmings (Cricetidae), cold-temperate rodents of conservation concern under global change.

Northern bog lemmings, () , are currently being assessed for protections under the U.S. Endangered Species Act.

Genetic drift drives rapid speciation of an Arctic insular endemic shrew (Sorex pribilofensis).

Episodes of Quaternary environmental change shaped the genomes of extant species, influencing their response to contemporary environments, which are changing rapidly. Island endemics are among the most vulnerable to such change, accounting for a disproportionate number of recent extinctions. To prevent extinctions and conserve island biodiversity it is vital to combine knowledge of species' ecologies with their complex evolutionary histories.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009).

Discovery of 2-amino-3-amido-5-aryl-pyridines as highly potent, orally bioavailable, and efficacious PERK kinase inhibitors.

The protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of the three endoplasmic reticulum (ER) transmembrane sensors of the unfolded protein response (UPR) that regulates protein synthesis, alleviates cellular ER stress and has been implicated in tumorigenesis and prolonged cancer cell survival. In this study, we report a series of 2-amino-3-amido-5-aryl-pyridines that we have identified as potent, selective, and orally bioavailable PERK inhibitors. Amongst the series studied herein, compound (28) a (R)-2-Amino-5-(4-(2-(3,5-difluorophenyl)-2-hydroxyacetamido)-2-ethylphenyl)-N-isopropylnicotinamide has demonstrated potent biochemical and cellular activity, robust pharmacokinetics and 70% oral bioavailability in mice.

Multiple comparisons in non-inferiority trials: Reaction to recent regulatory guidance on multiple endpoints in clinical trials.

We consider analysis of active control, non-inferiority clinical trials with multiple primary endpoints for assessing efficacy of an investigational treatment. Many of the issues with multiple endpoints for non-inferiority trials are similar to issues for superiority trials, but there are important differences. Because non-inferiority trials typically make decisions with confidence interval bounds instead of p-values, care must be taken in adjusting for multiple hypotheses.

A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.

Unlabelled: The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo.

Molecular and biochemical characterization of a benzenoid/phenylpropanoid meta/para-O-methyltransferase from Rauwolfia serpentina roots.

The monoterpenoid indole alkaloids, reserpine and rescinnamine contain 3, 4, 5-trimethoxybenzoate or 3, 4, 5-trimethoxycinnamate, respectively, within their structures and they accumulate in different plant organs and particularly within roots of Rauwolfia serpentina. This plant also accumulates acylated sugars substituted with 3, 4, 5-trimethoxybenzoate and 3, 4, 5-trimethoxycinnamate. In the present study, transcriptome and metabolome analyses of R.

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

Background: Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers.

Methods: In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug.

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.

Background: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown.

Methods: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days.

FBO Leaders' Perceptions of the Psycho-social Contexts for Rural Latinos.

Latinos comprise the largest minority rural population in the US, and they are often exposed to adverse social health determinants that can detrimentally affect their mental health. Guided by community-based participatory research (CBPR) principles, this study aimed to describe faith-based organizations (FBOs) leaders' perceptions of the contexts affecting the mental well-being of rural Latino immigrants and potential approaches to mental health promotion for these immigrants. This is a descriptive, qualitative arm of a larger study in which community-academic members have partnered to develop a culturally-tailored mental health promotion intervention among rural Latinos.

An individual-based rurality measure and its health application: A case study of Latino immigrants in North Florida, USA.

Rurality has been frequently noted by researchers as pathways to understand human health in rural and remote areas. Current measures of rurality are mostly oriented to places, not individuals, and have not accounted for individual mobility, thus inappropriate for studying health and well-being at an individual level. This research proposed a new concept of individual-based rurality by integrating personal activity spaces.

Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity.

Background: Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors.

Methods: Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily.

Rural Latinos' mental wellbeing: a mixed-methods pilot study of family, environment and social isolation factors.

Upon immigration to the rural areas in the US, Latino families may experience cultural, geographic, linguistic and social isolation, which can detrimentally affect their wellbeing by acting as chronic stressors. Using a community engagement approach, this is a pilot mixed-method study with an embedded design using concurrent qualitative and quantitative data. The purpose of this study is to evaluate family and social environments in terms of protective factors and modifiable risks associated with mental well-being in Latino immigrants living in rural areas of Florida.

I Didn't Ask to Come to this Country…I was a Child: The Mental Health Implications of Growing Up Undocumented.

Growing up as an undocumented immigrant and transitioning to "illegal" adulthood can expose the person to adverse social determinants, which can detrimentally affect mental health by acting as chronic stressors. Although there have been several attempts to reform immigration, none have been entirely successful. Recently, the Dream Act and the path toward citizenship may be important steps for reducing mental health disparities among the undocumented, immigrant population.

7-deoxyloganetic acid synthase catalyzes a key 3 step oxidation to form 7-deoxyloganetic acid in Catharanthus roseus iridoid biosynthesis.

Iridoids are key intermediates required for the biosynthesis of monoterpenoid indole alkaloids (MIAs), as well as quinoline alkaloids. Although most iridoid biosynthetic genes have been identified, one remaining three step oxidation required to form the carboxyl group of 7-deoxyloganetic acid has yet to be characterized. Here, it is reported that virus-induced gene silencing of 7-deoxyloganetic acid synthase (7DLS, CYP76A26) in Catharanthus roseus greatly decreased levels of secologanin and the major MIAs, catharanthine and vindoline in silenced leaves.

Recent Statistical Contributions to Medical Device Development.

Clinical trials in the development of new medical device products are in many ways analogous to clinical trials in the development of new drug or biologic products. However, the differences are important and not always intuitive to a statistician with only experience supporting development of drug and biologic products. In this paper we discuss some of the interesting differences with focus on the statistical innovation that is coming out of the medical device area.

Selection of hypothesis weights and ordering when testing multiple hypotheses in clinical trials.

This article discusses the problem of selecting free parameters of multiple testing procedures in confirmatory Phase III clinical trials with multiple objectives, including hypothesis weights and hypothesis ordering. We identify classes of multiple testing procedures that provide different interpretations of these parameters. This includes basic single-step procedures (Bonferroni procedure) that employ fixed hypothesis weights, as well as more powerful stepwise procedures (Holm, fallback, and chain procedures) that reweight the hypotheses during the testing process.

CBPR: building partnerships with latinos in a rural area for a wellness approach to mental health.

Using Community-Based Participatory Research, this study describes the ongoing collaboration between Latino community leaders and academic partners to develop a mental health promotion intervention for rural Latinos in Florida. Two strategies were used: (1) Community Advisory Board (CAB) members completed a Latino Community Partners Survey (LCPS) and (2) scribe notes were taken during CAB meetings. The LCPS demonstrated not only the CAB's knowledge about the community but the readiness of leaders to get involved in the community-academic partnership.

Multiple testing procedures in two pivotal clinical trials for approval of a new pharmaceutical product.

We consider analysis of two identical pivotal trials with correlated multiple hypotheses evaluated by the fixed-sequence, weighted Holm, or fallback procedure. For approval, at least one hypothesis must be rejected in both studies. Various weights are considered for the fallback and weighted Holm procedure to provide separation in a single study.