Pre-injury stimulant use in isolated severe traumatic brain injury: effect on outcomes.

PURPOSE The aim of this study was to assess the impact of pre-injury stimulant use (amphetamine, cocaine, methamphetamine and/or ecstasy) on outcomes after isolated severe traumatic brain injury (TBI). METHODS Retrospective 2017 TQIP study, including adult trauma patients (≥16 years old) who underwent drug and alcohol screening on admission and sustained an isolated severe TBI (head AIS ≥3). Patients with significant extracranial trauma (AIS ≥3) were excluded. Epidemiological and clinical characteristics, procedures and outcome variables were collected. Patients with isolated stimulant use were matched 1:1 for age, gender, mechanism of injury, head AIS and overall comorbidities, with patients with negative toxicology and alcohol screen. Outcomes in the two groups were compared with univariable and multivariable regression analysis. RESULTS 681 patients with isolated TBI and stimulant use were matched with 681 patients with negative toxicology and alcohol screen. The incidence of hypotension and CGS <9 was similar in the two groups. In multivariable regression analysis, stimulant use was not independently associated with mortality (OR 0.95, 95% CI 0.61-1.49). However, stimulant use was associated with longer hospital length of stay (HLOS) (RC 1.13, 95%CI 1.03-1.24). CONCLUSION Pre-injury stimulant use is common in patients admitted for severe TBI, but was not independently associated with mortality when compared to patients with negative toxicology. However, stimulant use was associated with a significant longer HLOS

Spatial protected area decisions to reduce carbon emissions from forest extraction

Protected areas (PAs) can mitigate climate change by reducing carbon emissions that result from forest loss. Carbon emissions from forest degradation are a large component of forest loss and are often driven by the extraction decisions of resource-dependent households. PA policies must reflect how villagers use forests to be effective. Here, a spatial Nash equilibrium of extractors’ uncoordinated forest extraction pattern decisions establishes a baseline of forest-use patterns. Using that baseline, a manager chooses the location and enforcement level of PAs to maximize the avoided forest degradation in the landscape and in the PAs. Optimal PA locations depend on the labour market and the distance between forest patches. A combination of wage-improving projects and appropriately located PAs increases avoided forest degradation

LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study

Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsies

Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity

We are grateful to members of the D.S. laboratory and Dr. E. Fernández-Malavé for discussions and critical reading of the manuscript. We appreciate the support of A. Tomás-Loba, G. Sabio, P. Martín, A. Tsilingiri, A.R. Ramiro, C.L. Abram, C.A. Lowell, J.M. García-Lobo, M. Molina, and M.C. Rodríguez for providing reagents and support. We thank the staff at the Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) facilities for technical support. M.M.-L. received a Formación de Personal Universitario (FPU) fellowship (AP2010-5935) from the Spanish Ministerio de Educación. S.I. is funded by grant SAF2015-74561-JIN from the Spanish Ministerio de Ciencia, Innovación, y Universidades (MCIU) and Fondos Europeos de Desarrollo Regional (FEDER). G.D.B and D.M.R. are supported by the Wellcome Trust and the MRC Centre for Medical Mycology at the University of Aberdeen. S.L.L. is supported by the Swiss National Science Foundation (PP00P3_150758). Work in the D.S. laboratory is funded by the CNIC and grant SAF2016-79040-R from MCIU, the Agencia Estatal de Investigación, and FEDER; B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MCIU, and FEDER; the Acteria Foundation; the Constantes y Vitales prize (Atresmedia); La Marató de TV3 Foundation (201723); the European Commission (635122-PROCROP H2020), and the European Research Council (ERC-2016-Consolidator Grant 725091). The CNIC is supported by the MCIU and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).Peer reviewedPublisher PD

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

<p>Abstract</p> <p>Background</p> <p>There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).</p> <p>Methods</p> <p>This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.</p> <p>Results</p> <p>Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.</p> <p>Conclusion</p> <p>Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, <it>Candida </it>infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.</p

CD or not CD, that is the question - a digital interobserver agreement study in coeliac disease

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of IgA tTG and haemoglobin (Hb) data improves the inter-observer agreement of diagnosis.DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase one, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase two, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited inter-observer agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the important of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using AI.<br/

A multi-layer network approach to MEG connectivity analysis

Recent years have shown the critical importance of inter-regional neural network connectivity in supporting healthy brain function. Such connectivity is measurable using neuroimaging techniques such as MEG, however the richness of the electrophysiological signal makes gaining a complete picture challenging. Specifically, connectivity can be calculated as statistical interdependencies between neural oscillations within a large range of different frequency bands. Further, connectivity can be computed between frequency bands. This pan-spectral network hierarchy likely helps to mediate simultaneous formation of multiple brain networks, which support ongoing task demand. However, to date it has been largely overlooked, with many electrophysiological functional connectivity studies treating individual frequency bands in isolation. Here, we combine oscillatory envelope based functional connectivity metrics with a multi-layer network framework in order to derive a more complete picture of connectivity within and between frequencies. We test this methodology using MEG data recorded during a visuomotor task, highlighting simultaneous and transient formation of motor networks in the beta band, visual networks in the gamma band and a beta to gamma interaction. Having tested our method, we use it to demonstrate differences in occipital alpha band connectivity in patients with schizophrenia compared to healthy controls. We further show that these connectivity differences are predictive of the severity of persistent symptoms of the disease, highlighting their clinical relevance. Our findings demonstrate the unique potential of MEG to characterise neural network formation and dissolution. Further, we add weight to the argument that dysconnectivity is a core feature of the neuropathology underlying schizophrenia

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts