Categorical differentiation of the unipolar and bipolar disorders

There has been a longstanding debate as to whether the bipolar disorders differ categorically or dimensionally, with some dimensional or spectrum models including unipolar depressive disorders within a bipolar spectrum model. We analysed manic/hypomanic symptom data in samples of clinically diagnosed bipolar I, bipolar II and unipolar patients, employing latent class analyses to determine if separate classes could be identified. Mixture analyses were also undertaken to determine if a unimodal, bimodal or a trimodal pattern was present. For both a refined 15-item set and an extended 30-item set of manic/hypomanic symptoms, our latent class analyses favoured three-class solutions, while mixture analyses identified trimodal distributions of scores. Findings argue for a categorical distinction between unipolar and bipolar disorders, as well as between bipolar I and bipolar II disorders. Future research should aim to consolidate these results in larger samples, particularly given that the size of the unipolar group in this study was a salient limitation

Differentiating mania/hypomania from happiness using a machine learning analytic approach.

Background: This study aimed to improve the accuracy of bipolar disorder diagnoses by identifying symptoms that help to distinguish mania/hypomania in bipolar disorders from general ‘happiness’ in those with unipolar depression. Methods: An international sample of 165 bipolar and 29 unipolar depression patients (as diagnosed by their clinician) were recruited. All participants were required to rate a set of 96 symptoms with regards to whether they typified their experiences of manic/hypomanic states (for bipolar patients) or when they were ‘happy’ (unipolar patients). A machine learning paradigm (prediction rule ensembles; PREs) was used to derive rule ensembles that identified which of the 94 non-psychotic symptoms and their combinations best predicted clinically-allocated diagnoses. Results: The PREs were highly accurate at predicting clinician bipolar and unipolar diagnoses (92% and 91% respectively). A total of 20 items were identified from the analyses, which were all highly discriminating across the two conditions. When compared to a classificatory approach insensitive to the weightings of the items, the ensembles were of comparable accuracy in their discriminatory capacity despite the unbalanced sample. This illustrates the potential for PREs to supersede traditional classificatory approaches. Limitations: There were considerably less unipolar than bipolar patients in the sample, which limited the overall accuracy of the PREs. Conclusions: The consideration of symptoms outlined in this study should assist clinicians in distinguishing between bipolar and unipolar disorders. Future research will seek to further refine and validate these symptoms in a larger and more balanced sample

The bipolar disorders: A case for their categorically distinct status based on symptom profiles

Background: It is unclear whether the bipolar disorders (i.e. BP-I/BP-II) differ dimensionally or categorically. This study sought to clarify this issue. Methods: We recruited 165 patients, of which 69 and 96 had clinician-assigned diagnoses of BP-I and BP-II respectively. Their psychiatrists completed a data sheet seeking information on clinical variables about each patient, while the patients completed a different data sheet and scored a questionnaire assessing the prevalence and severity of 96 candidate manic/hypomanic symptoms. Results: We conducted a series of analyses examining a set (and two sub-sets) of fifteen symptoms that were significantly more likely to be reported by the clinically diagnosed BP-I patients. Latent class analyses favoured two-class solutions, while mixture analyses demonstrated bimodality, thus arguing for a BP-I/BP-II categorical distinction. Statistically defined BP-I class members were more likely when manic to have experienced psychotic features and over-valued ideas. They were also more likely to have been hospitalised, and to have been younger when they received their bipolar diagnosis and first experienced a depressive or manic episode. Limitations: The lack of agreement between some patients and managing clinicians in judging the presence of psychotic features could have compromised some analyses. It is also unclear whether some symptoms (e.g. grandiosity, noting mystical events) were capturing formal psychotic features or not. Conclusions: Findings replicate our earlier study in providing evidence to support the modelling of BP-I and BP-II as categorically discrete conditions. This should advance research into aetiological factors and determining optimal (presumably differing) treatments for the two conditions

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6 × S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans

Global Diversity Hotspots and Conservation Priorities for Sharks

Sharks are one of the most threatened groups of marine animals, as high exploitation rates coupled with low resilience to fishing pressure have resulted in population declines worldwide. Designing conservation strategies for this group depends on basic knowledge of the geographic distribution and diversity of known species. So far, this information has been fragmented and incomplete. Here, we have synthesized the first global shark diversity pattern from a new database of published sources, including all 507 species described at present, and have identified hotspots of shark species richness, functional diversity and endemicity from these data. We have evaluated the congruence of these diversity measures and demonstrate their potential use in setting priority areas for shark conservation. Our results show that shark diversity across all species peaks on the continental shelves and at mid-latitudes (30–40 degrees N and S). Global hotspots of species richness, functional diversity and endemicity were found off Japan, Taiwan, the East and West coasts of Australia, Southeast Africa, Southeast Brazil and Southeast USA. Moreover, some areas with low to moderate species richness such as Southern Australia, Angola, North Chile and Western Continental Europe stood out as places of high functional diversity. Finally, species affected by shark finning showed different patterns of diversity, with peaks closer to the Equator and a more oceanic distribution overall. Our results show that the global pattern of shark diversity is uniquely different from land, and other well-studied marine taxa, and may provide guidance for spatial approaches to shark conservation. However, similar to terrestrial ecosystems, protected areas based on hotspots of diversity and endemism alone would provide insufficient means for safeguarding the diverse functional roles that sharks play in marine ecosystems

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

ABCtoolbox: a versatile toolkit for approximate Bayesian computations

BACKGROUND: The estimation of demographic parameters from genetic data often requires the computation of likelihoods. However, the likelihood function is computationally intractable for many realistic evolutionary models, and the use of Bayesian inference has therefore been limited to very simple models. The situation changed recently with the advent of Approximate Bayesian Computation (ABC) algorithms allowing one to obtain parameter posterior distributions based on simulations not requiring likelihood computations. RESULTS: Here we present ABCtoolbox, a series of open source programs to perform Approximate Bayesian Computations (ABC). It implements various ABC algorithms including rejection sampling, MCMC without likelihood, a Particle-based sampler and ABC-GLM. ABCtoolbox is bundled with, but not limited to, a program that allows parameter inference in a population genetics context and the simultaneous use of different types of markers with different ploidy levels. In addition, ABCtoolbox can also interact with most simulation and summary statistics computation programs. The usability of the ABCtoolbox is demonstrated by inferring the evolutionary history of two evolutionary lineages of Microtus arvalis. Using nuclear microsatellites and mitochondrial sequence data in the same estimation procedure enabled us to infer sex-specific population sizes and migration rates and to find that males show smaller population sizes but much higher levels of migration than females. CONCLUSION: ABCtoolbox allows a user to perform all the necessary steps of a full ABC analysis, from parameter sampling from prior distributions, data simulations, computation of summary statistics, estimation of posterior distributions, model choice, validation of the estimation procedure, and visualization of the results

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Background Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. Results We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureusinfection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. Conclusions S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells

Public health interventions for Aedes control in the time of Zikavirus- A metareview on effectiveness of vector control strategies

Background: There is renewed interest in effective control measures to control Zika and dengue vectors. A synthesis of published systematic reviews with a focus on grading of intervention evidence is warranted to determine the reliability of evidence for control strategies. Methodology: We conducted a meta-review (a systematic review of systematic reviews) assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to 11 May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors. Data extraction was performed independently in duplicate using a standardised form and validity of the evidence in each review was assessed using GRADE criteria. Findings: 13 eligible systematic reviews that investigated the effect of community interventions on entomological parameters (such as vector density) or disease incidence were included. Quality of evidence was mostly low to very low due to poor reporting of study design, observational methodologies, heterogeneity, and indirect outcomes, hindering an evidence-based recommendation. Biological controls seem to achieve better reduction of entomological indices than chemical controls, while educational campaigns can reduce breeding habitats and interrupt disease transmission cycle. Integrated control strategies may not add efficiency to educational campaigns. Conclusions: Despite decades of Aedes mosquito abatement programmes, mosquito populations are widely established and abundant, and associated with a significant disease burden. The efficiency of any control programme is dependent on local settings and resources. More good quality primary studies for the control of Aedes transmitted diseases are still required