Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

On the character of states near the Fermi level in (Ga,Mn)As: impurity to valence band crossover

We discuss the character of states near the Fermi level in Mn doped GaAs, as revealed by a survey of dc transport and optical studies over a wide range of Mn concentrations. A thermally activated valence band contribution to dc transport, a mid-infrared peak at energy hbar omega approx 200 meV in the ac- conductivity, and the hot photoluminescence spectra indicate the presence of an impurity band in low doped (<<1% Mn) insulating GaAs:Mn materials. Consistent with the implications of this picture, both the impurity band ionization energy inferred from the dc transport and the position of the mid-infrared peak move to lower energies and the peak broadens with increasing Mn concentration. In metallic materials with > 2% doping, no traces of Mn-related activated contribution can be identified in dc-transport, suggesting that the impurity band has merged with the valence band. No discrepancies with this perception are found when analyzing optical measurements in the high-doped GaAs:Mn. A higher energy (hbar omega approx 250 meV) mid-infrared feature which appears in the metallic samples is associated with inter-valence band transitions. Its red-shift with increased doping can be interpreted as a consequence of increased screening which narrows the localized-state valence-band tails and weakens higher energy transition amplitudes. Our examination of the dc and ac transport characteristics of GaAs:Mn is accompanied by comparisons with its shallow acceptor counterparts, confirming the disordered valence band picture of high-doped metallic GaAs:Mn material.Comment: 10 pages, 12 figure

Single-Band Model for Diluted Magnetic Semiconductors: Dynamical and Transport Properties and Relevance of Clustered States

Dynamical and transport properties of a simple single-band spin-fermion lattice model for (III,Mn)V diluted magnetic semiconductors (DMS) is here discussed using Monte Carlo simulations. This effort is a continuation of previous work (G. Alvarez, Phys. Rev. Lett. 89, 277202 (2002)) where the static properties of the model were studied. The present results support the view that the relevant regime of J/t (standard notation) is that of intermediate coupling, where carriers are only partially trapped near Mn spins, and locally ordered regions (clusters) are present above the Curie temperature T_C. This conclusion is based on the calculation of the resistivity vs. temperature, that shows a soft metal to insulator transition near T_C, as well on the analysis of the density-of-states and optical conductivity. In addition, in the clustered regime a large magnetoresistance is observed in simulations. Formal analogies between DMS and manganites are also discussed.Comment: Revtex4, 20 figures. References updated, minor changes to figures and tex

Differential diagnosis of illness in travelers arriving from sierra Leone, Liberia, or guinea: A cross-sectional study from the Geosentinel surveillance network

Background: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. Objective: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. Design: Descriptive, using GeoSentinel records. Setting: 57 travel or tropical medicine clinics in 25 countries. Patients: 805 ill returned travelers and new mmigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. Measurements: Frequencies of demographic and travelrelated characteristics and illnesses reported. Results: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non–P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n= 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. Limitation: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. Conclusion: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality

Tomorrow’s Digital Worker : A Critical Review and Agenda for Building Digital Competency Models

In competency management studies, scholars call for the importance of digital savviness to hire, train, and develop new digital workers. Yet, the knowledge about the development of such a competence is still scarce. For this endeavor, we followed a systematic literature review to identify a sample of 103 published scientific articles and book chapters dealing with the development and implementation of competency tools in the past 10 years. To our surprise, our review suggests that the landscape of competency tools is surprisingly obsolete and that contemporary requirements of digitization have not yet been incorporated into updated usable competency tools. Through this review our hope is to provide competency managers and researchers with a framework to advance and upgrade their competency tools to address the gap between existing know how and the needed expertise of the digital world.© 2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Leadership Proceedings of the AHFE 2020 Virtual Conferences on Human Factors, Business Management and Society, and Human Factors in Management and Leadership, July 16-20, 2020, USA. The final authenticated version is available online at: https://doi.org/10.1007/978-3-030-50791-6_14fi=vertaisarvioitu|en=peerReviewed

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe