A quasi-score statistic for homogeneity testing against covariate-varying heterogeneity.

In statistical modeling, it is often of interest to evaluate non-negative quantities that capture heterogeneity in the population such as variances, mixing proportions and dispersion parameters. In instances of covariate-dependent heterogeneity, the implied homogeneity hypotheses are nonstandard and existing inferential techniques are not applicable. In this paper, we develop a quasi-score test statistic to evaluate homogeneity against heterogeneity that varies with a covariate profile through a regression model.

The Predictive Value of Developmental Assessments at 1 and 2 for Intelligence Quotients at 6.

Intelligence is an important individual difference factor related to mental health, academic achievement, and life success, yet there is a lack of research into its early cognitive predictors. This study investigated the predictive value of infant developmental assessment scores for school-age intelligence in a large, heterogeneous sample of single- and twin-born subjects (N = 521). We found that Early Learning Composite (ELC) scores from the Mullen Scales of Early Learning have similar predictive power to that of other infant tests.

Exchange-repulsion energy in QM/EFP.

The effective fragment potential (EFP) is a quantum mechanics (QM)-based model designed to accurately describe intermolecular interactions. Hybrid QM/EFP calculations combine quantum mechanical methods with an EFP embedding to study complex systems in which many-body effects are relevant. As in EFP-only calculations, non-bonded interactions between the QM region and EFP fragments are computed as a sum of electrostatic, polarization, dispersion, and exchange-repulsion energies.

Quantifying the effects of pollen nutrition on honey bee queen egg laying with a new laboratory system.

Honey bee populations have been declining precipitously over the past decade, and multiple causative factors have been identified. Recent research indicates that these frequently co-occurring stressors interact, often in unpredictable ways, therefore it has become important to develop robust methods to assess their effects both in isolation and in combination. Most such efforts focus on honey bee workers, but the state of a colony also depends on the health and productivity of its queen.

Rescue therapies for seizure emergencies: New modes of administration.

A subgroup of patients with drug-resistant epilepsy have seizure clusters, which are a part of the continuum of seizure emergencies that includes prolonged episodes and status epilepticus. When the patient or caregiver can identify the beginning of a cluster, the condition is amenable to certain treatments, an approach known as rescue therapy. Intravenous drug administration offers the fastest onset of action, but this route is usually not an option because most seizure clusters occur outside of a medical facility.

Using a Smoking Cessation Quitline to Promote Lung Cancer Screening.

Objective We assessed whether in-depth messaging delivered via a smoking cessation quitline results in participants: (1) speaking to their physician, or (2) insurance company regarding lung cancer screening (LCS). MethodsEligible participants lived in New York State and met the United States Preventive Services Task Force eligibility criteria for LCS (N = 1000). A randomized trial was conducted among New York State Smokers' Quitline participants to assess the impact of a brochure containing information on risks, benefits, and costs associated with LCS (control group) versus the brochure supplemented with phone-based in-depth messaging (treatment group).

Radiation exposure and coronary artery calcium scans in the society for heart attack prevention and eradication cohort.

Coronary artery calcium (CAC) scoring is used in asymptomatic patients to improve their clinically predicted risk for future cardiovascular events. Current CT protocols seek to reduce radiation exposure without diminishing image quality. Reported radiation exposure remains widely variable (0.

Selective IL-23 Inhibition by Risankizumab Modulates the Molecular Profile in the Colon and Ileum of Patients With Active Crohn's Disease: Results From a Randomised Phase II Biopsy Sub-study.

Background And Aims: We aimed to investigate the underlying mechanism of action of risankizumab, a monoclonal antibody targeting the IL-23 p19 subunit, previously reported to induce clinical and endoscopic remission in a randomised phase II study in patients with active Crohn's disease.

Methods: Ileum and colon biopsies obtained at screening and Week 12 from a subgroup of patients [n = 106] in the risankizumab phase II study were analysed by transcriptome-wide RNA-Seq profiling. Univariate associations were assessed using linear modelling.

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

Rationale: Epidemiologic studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM) is among the most harmful urban pollutants and is closely linked to respiratory disease.

MOdified NARanjo Causality Scale for ICSRs (MONARCSi): A Decision Support Tool for Safety Scientists.

Introduction: Within the field of Pharmacovigilance, the most common approaches for assessing causality between a report of a drug and a corresponding adverse event are clinical judgment, probabilistic methods and algorithms. Although multiple methods using these three approaches have been proposed, there is currently no universally accepted method for assessing drug-event causality in ICSRs and variability in drug-event causality assessments is well documented.

Objective: This study describes the development and validation of an Individual Case Safety Report (ICSR) Causality Decision Support Tool to assist Safety Professionals (SPs) performing causality assessments.

Partial likelihood estimation of isotonic proportional hazards models.

We consider the estimation of the semiparametric proportional hazards model with an unspecified baseline hazard function where the effect of a continuous covariate is assumed to be monotone. Previous work on nonparametric maximum likelihood estimation for isotonic proportional hazard regression with right-censored data is computationally intensive, lacks theoretical justification, and may be prohibitive in large samples. In this paper, partial likelihood estimation is studied.

Multiple-Institution Comparison of Resident and Faculty Perceptions of Burnout and Depression During Surgical Training.

Importance: Prior studies demonstrate a high prevalence of burnout and depression among surgeons. Limited data exist regarding how these conditions are perceived by the surgical community.

Objectives: To measure prevalence of burnout and depression among general surgery trainees and to characterize how residents and attendings perceive these conditions.

Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection.

Background: The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.

Methods: In 14 U.S.

Drug-induced linear IgA bullous dermatosis in a patient with a vancomycin-impregnated cement spacer.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering rash caused by IgA autoantibodies against the epidermal basement membrane zone. It commonly is drug induced, often in association with systemic vancomycin. We report a case of a previously healthy 77-year-old man who developed a diffuse macular rash and hemorrhagic bullae on the left leg 10 days after placement of a vancomycin-impregnated cement spacer (VICS) during a revision knee arthroplasty and initiation of postoperative treatment with intravenous (IV) vancomycin.

Evolution of Drug Development: Integrating the Patient Perspective Into Early Research.

Soaring drug development costs, increasingly stringent regulatory requirements, and demanding market access environments have necessitated that pharmaceutical companies examine their research processes in order to provide novel and meaningful solutions for patients. In this paper, we describe an initiative that aims to incorporate a better appreciation of the exam room experience of both patients and practitioners into the drug development pathway from the earliest point of research. Focusing on 4 core pillars-medical value, patient need, scientific rationale, and market environment-an integrated analytic process is undertaken so as to facilitate early identification of ideal target populations and criteria that will need to be met for successful entry into the treatment continuum.

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

Context.—: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications.

Objectives.

The Inhibitory NKR-P1B:Clr-b Recognition Axis Facilitates Detection of Oncogenic Transformation and Cancer Immunosurveillance.

Natural killer (NK) cells express receptors specific for MHC class I (MHC-I) molecules involved in "missing-self" recognition of cancer and virus-infected cells. Here we elucidate the role of MHC-I-independent NKR-P1B:Clr-b interactions in the detection of oncogenic transformation by NK cells. Ras oncogene overexpression was found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells, mediated in part via the Raf/MEK/ERK and PI3K pathways.

On the analysis of discrete time competing risks data.

Regression methodology has been well developed for competing risks data with continuous event times, both for the cause-specific hazard and cumulative incidence functions. However, in many applications, including those from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, the event times may be observed discretely. Naive application of continuous time regression methods to such data is not appropriate.

PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy.

Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8 T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches.

A Comparative Study of Carvedilol Versus Metoprolol Initiation and 1-Year Mortality Among Individuals Receiving Maintenance Hemodialysis.

Background: Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population.

Study Design: A retrospective cohort study using a new-user design.

Organizational Leadership and Adaptive Reserve in Blood Pressure Control: The Heart Health NOW Study.

Purpose: Our purpose was to assess whether a practice's adaptive reserve and high leadership capability in quality improvement are associated with population blood pressure control.

Methods: We divided practices into quartiles of blood pressure control performance and considered the top quartile as the benchmark for comparison. Using abstracted clinical data from electronic health records, we performed a cross-sectional study to assess the association of top quartile hypertension control and (1) the baseline practice adaptive reserve (PAR) scores and (2) baseline practice leadership scores, using modified Poisson regression models adjusting for practice-level characteristics.

Strengthening One Health Through Investments in Agricultural Preparedness.

There are links among agriculture and zoonotic diseases, transboundary diseases in domesticated and wild animals, climate patterns, and human population migrations. A natural or intentionally occurring high-consequence infectious disease ("biothreat") often has no geographic boundaries and has the potential to result in disease epidemics in humans, animals, or both. Although significant strides have been made globally in preparing for a natural or intentional introduction of an emerging and/or zoonotic disease, much remains to be accomplished.

Competing Risk of Death With End-Stage Renal Disease in Diabetic Kidney Disease.

The concept of competing risks is particularly relevant to survival analyses of diabetic ESRD given the high likelihood of death prior to ESRD. Approaches such as Kaplan-Meier curves and Cox regression models operate on the assumption that there are no competing risks for the event of interest, yielding uninterpretable and generally biased estimates in the presence of competing risks. The cumulative incidence function and Fine-Gray regression are more appropriate methodologies for survival analysis when competing risks are present.

The impact of current smoking on outcomes after infrainguinal bypass for claudication.

Objective: Although smoking cessation is a benchmark of medical management of intermittent claudication, many patients require further revascularization. Currently, revascularization among smokers is a controversial topic, and practice patterns differ institutionally, regionally, and nationally. Patients who smoke at the time of revascularization are thought to have a poor prognosis, but data on this topic are limited.