Computational Nosology and Precision Psychiatry

This article provides an illustrative treatment of psychiatric morbidity that offers an alternative to the standard nosological model in psychiatry. It considers what would happen if we treated diagnostic categories not as causes of signs and symptoms, but as diagnostic consequences of psychopathology and pathophysiology. This reformulation (of the standard nosological model) opens the door to a more natural description of how patients present—and of their likely responses to therapeutic interventions. In brief, we describe a model that generates symptoms, signs, and diagnostic outcomes from latent psychopathological states. In turn, psychopathology is caused by pathophysiological processes that are perturbed by (etiological) causes such as predisposing factors, life events, and therapeutic interventions. The key advantages of this nosological formulation include (i) the formal integration of diagnostic (e.g., DSM) categories and latent psychopathological constructs (e.g., the dimensions of the Research Domain Criteria); (ii) the provision of a hypothesis or model space that accommodates formal, evidence-based hypothesis testing (using Bayesian model comparison); and (iii) the ability to predict therapeutic responses (using a posterior predictive density), as in precision medicine. These and other advantages are largely promissory at present: The purpose of this article is to show what might be possible, through the use of idealized simulations

“There’s a big tag on my head”: exploring barriers to treatment seeking with women who use methamphetamine in Sydney, Australia

Background: Australia has a high prevalence of regular use of methamphetamine. While half of people who use methamphetamine regularly are women, they make up only one third of people seeking treatment for methamphetamine use disorder. There is a lack of qualitative research into the facilitators and barriers to treatment for women who use methamphetamine regularly. The study seeks a better understanding of the experiences and treatment preferences of women who use methamphetamine, to inform person-centred changes in practice and policy that break down barriers to treatment. Methods: We conducted semi-structured interviews with 11 women who frequently use methamphetamine (at least once a week), and who are not engaged in treatment. Women were recruited from health services surrounding a stimulant treatment centre at an inner-city hospital. Participants were asked about their methapmhetamine use and health service needs and preferences. Thematic analysis was completed using Nvivo® software. Results: Three themes were developed from participants’ responses around experiences of regular methamphetamine use and treatment needs: 1. Resistance of stigmatised identity including dependence; 2. Interpersonal violence; 3. Institutionalised stigma. A fourth set of themes on service delivery preferences were also elicited, including continuity of care, integrated health care, and provision of non-judgmental services. Conclusion: Gender-inclusive health care services for people who use methamphetamine should actively work to address stigma, support a relational approach to assessment and treatment, and seek to provide structurally competent health care that is trauma and violence informed, and integrated with other services. Findings may also have application for substance use disorders other than methamphetamine

Food Should not be Forgotten: Impacts of Combined Cash Transfer Receipt and Food Security on Child Education and Cognition in South Africa and Malawi.

Social protection can take many forms. Both cash transfers and food security may have important contributions to child cognitive development. This study examines the potential impact of combinations of cash transfers and food security status on child cognitive development and educational outcomes. Cross-sectional data for 796 HIV-affected children in the Child Community Care study were utilised for this analysis. Children and caregivers completed interview schedules comprised of standardised items on socio-demographics, household data, cash grant receipt and food security status, school achievement, and cognition. A series of logistic and linear regression models and marginal effects analyses were undertaken to explore the impacts of differing levels of social protection (none; either cash grant receipt or food secure status or, both in combination) on child educational and cognitive outcomes. Although all children lived in poverty-stricken households, 20% (157/796) of children did not live in a household in receipt of a cash grant and did not report food security; 32.4% (258/796) reported either component of social protection and, 47.9% (381/796) received both measures of social protection in combination. Compared to no social protection, being in receipt of either component of social protection was found to be significantly associated with being in the correct class for age, higher scores of non-verbal cognition, and higher working memory scores. Receiving both social protection measures in combination was found to be significantly associated with reduced educational risk scores, improved odds of being in the correct class for age, regular school attendance, missing less than a week of school in the previous two weeks, higher scores on measures of nonverbal cognition, higher working memory scores, and learning new things more easily. Educational and cognitive outcomes for children can be bolstered by social protection measures (cash grant receipt or food security). Benefits are enhanced when social protection is received in combination. Such findings support the notion of synergistic social protection responses for children living in environments impacted by high levels of HIV burden and deprivation

Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock

Importance Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock—a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS). Objectives To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events. Data Sources MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials. Study Selection Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock. Data Extraction and Synthesis Two reviewers abstracted data independently. A random-effects model was used to combine data. Main Outcomes and Measures The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS. Results Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], −0.06 [95% CI, −0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, −0.04 [95% CI, −0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, −0.07 [95% CI, −0.12 to −0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes. Conclusions and Relevance In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p> Methods: An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p> Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p> Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p&gt

An off-board quantum point contact as a sensitive detector of cantilever motion

Recent advances in the fabrication of microelectromechanical systems (MEMS) and their evolution into nanoelectromechanical systems (NEMS) have allowed researchers to measure extremely small forces, masses, and displacements. In particular, researchers have developed position transducers with resolution approaching the uncertainty limit set by quantum mechanics. The achievement of such resolution has implications not only for the detection of quantum behavior in mechanical systems, but also for a variety of other precision experiments including the bounding of deviations from Newtonian gravity at short distances and the measurement of single spins. Here we demonstrate the use of a quantum point contact (QPC) as a sensitive displacement detector capable of sensing the low-temperature thermal motion of a nearby micromechanical cantilever. Advantages of this approach include versatility due to its off-board design, compatibility with nanoscale oscillators, and, with further development, the potential to achieve quantum limited displacement detection.Comment: 5 pages, 5 figure

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.<p></p> Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.<p></p> Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.<p></p> Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.<p></p&gt

A seasonal cycle in the export of bottom water from the Weddell Sea

Dense water formed over the Antarctic continental shelf rapidly descends into the deep ocean where it spreads throughout the global ocean as Antarctic Bottom Water1, 2. The coldest and most voluminous component of this water mass is Weddell Sea bottom water1, 3, 4, 5, 6, 7. Here we present observations over eight years of the temperature and salinity stratification in the lowermost ocean southeast of the South Orkney Islands, marking the export of Weddell Sea bottom water. We observe a pronounced seasonal cycle in bottom temperatures, with a cold pulse in May/June and a warm one in October/November, but the timing of these phases varies each year. We detect the coldest bottom water in 1999 and 2002, whereas there was no cold phase in 2000. On the basis of current velocities and water mass characteristics, we infer that the pulses originate from the southwest Weddell Sea. We propose that the seasonal fluctuations of Weddell Sea bottom-water properties are governed by the seasonal cycle of the winds over the western margin of the Weddell Sea. Interannual fluctuations are linked to the variability of the wind-driven Weddell Sea gyre and hence to large-scale climate phenomena such as the Southern Annular Mode and El Niño/Southern Oscillation

Long term geological record of a global deep subsurface microbial habitat in sand injection complexes

Peer reviewedPublisher PD

Academic careers in global pulmonary and critical care medicine

The burden of respiratory and critical illness is high worldwide, yet specialist care is underrepresented in low- and middle-income countries (LMICs) [1]. For many areas of medicine, the past decade has witnessed tremendous growth in global health opportunities for trainees; however, these opportunities tend to be restricted to individual institutions and geographic regions and academic global pulmonary and critical care medicine (PCCM) remains a relatively novel concept [2]. Consequently, PCCM fellows and junior faculty at institutions with limited global health mentorship have little guidance in building successful global health careers