A Sequential Bayesean Approach to History Taking and Diagnosis

journal articleBiomedical Informatic

Development and evaluation of a remote training strategy for the implementation of mental health evidence-based practices in rural schools: pilot study protocol.

BACKGROUND: An increasing number of schools in rural settings are implementing multi-tier positive behavioral interventions and supports (PBIS) to address school-climate problems. PBIS can be used to provide the framework for the implementation of evidence-based practices (EBPs) to address children\u27s mental health concerns. Given the large service disparities for children in rural areas, offering EBPs through PBIS can improve access and lead to better long-term outcomes. A key challenge is that school personnel need technical assistance in order to implement EBPs with fidelity and clinical effectiveness. Providing ongoing on-site support is not feasible or sustainable in the majority of rural schools, due to their remote physical location. For this reason, remote training technology has been recommended for providing technical assistance to behavioral health staff (BHS) in under-served rural communities. OBJECTIVES: The purpose of this study is to use the user-centered design, guided by an iterative process (rapid prototyping), to develop and evaluate the appropriateness, feasibility, acceptability, usability, and preliminary student outcomes of two online training strategies for the implementation of EBPs at PBIS Tier 2. METHODS: The study will employ a pragmatic design comprised of a mixed-methods approach for the development of the training platform, and a hybrid type 2, pilot randomized controlled trial to examine the implementation and student outcomes of two training strategies: Remote Video vs. Remote Video plus Coaching. DISCUSSION: There is a clear need for well-designed remote training studies focused on training in non-traditional settings. Given the lack of well-trained mental health professionals in rural settings and the stark disparities in access to services, the development and pilot-testing of a remote training strategy for BHS in under-served rural schools could have a significant public health impact. ETHICS AND DISSEMINATION: The project was reviewed and approved by the institutional review board. Results will be submitted to ClinicalTrials.gov and disseminated to community partners and participants, peer-reviewed journals, and academic conferences. TRIAL REGISTRATION: ClinicialTrials.gov, NCT05034198 and NCT05039164

Stress-Induced Changes in the Expression of the Clock Protein PERIOD1 in the Rat Limbic Forebrain and Hypothalamus: Role of Stress Type, Time of Day, and Predictability

Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl) and oval nucleus of the bed nucleus of the stria terminalis (BNSTov). Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN), the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms

Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients: EFFECT OF SUPPLEMENTAL CALCIUM AND VITAMIN D IN HUMAN RECTUM

APC/β-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/β-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2×2 factorial chemoprevention clinical trial of supplemental calcium (1,200 mg daily) and vitamin D (1,000 IU daily), alone and in combination versus placebo, we assessed APC, β-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and one-year follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D vs. no vitamin D, the ratio of APC expression to β-catenin expression in the upper 40% (differentiation zone) of crypts (APC/β-catenin score) increased by 28% (P = 0.02), for calcium vs. no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium vs. calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D vs. no vitamin D, 8% (P = 0.31) for calcium vs. no calcium, and 12% (P = 0.21) for vitamin D + calcium vs. calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Task-specific neural adaptations to isoinertial resistance training

This study aimed to delineate the contribution of adaptations in agonist, antagonist and stabiliser muscle activation to changes in isometric and isoinertial lifting strength after short-term isoinertial resistance training (RT). Following familiarisation, 45 men (23.2±2.8 yrs) performed maximal isometric and isoinertial strength tests of the elbow flexors of their dominant arm before and after three weeks of isoinertial RT. During these tasks surface EMG amplitude was recorded from the agonist (biceps brachii short and long heads), antagonist (triceps brachii lateral head) and stabiliser (anterior deltoid, pectoralis major) muscles and normalised to either Mmax (agonists) or to maximum EMG during relevant reference tasks (antagonist, stabilisers). After training there was more than a two-fold greater increase in training task specific isoinertial than isometric strength (17 vs. 7%). There were also task specific adaptations in agonist EMG, with greater increases during the isoinertial than isometric strength task (ANOVA, training x task, P=0.005). A novel finding of this study was that training increased stabiliser muscle activation during all the elbow flexion strength tasks (P<0.001), although these were not task specific training effects. RT elicited specific neural adaptations to the training task that appeared to explain the greater increase in isoinertial than isometric strength