Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Outcomes and Endpoints

BackgroundClinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs.MethodsThe Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms.ResultsAmong hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children.ConclusionsThe DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges

Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI

<p>Abstract</p> <p>Background</p> <p>The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of <it>AGRP </it>gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).</p> <p>Methods</p> <p>We determined the complete sequence of the <it>AGRP </it>gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m²). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database.</p> <p>Results</p> <p>The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m²(mean, SE) as compared to 30.97 ± 1.03 kg/m²for the CT genotype. No association was found between rs5030980 and BMI.</p> <p>Conclusion</p> <p>This study presents an association of rare allele of <it>AGRP </it>polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.</p

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q \u3c 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans

Molecular Mechanism of the Constitutive Activation of the L250Q Human Melanocortin-4 Receptor Polymorphism †

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65471/1/j.1747-0285.2006.00362.x.pd

Low-Dosage Inhibition of DII4 Signaling Promotes Wound Healing by Inducing Functional Neo-Angiogenesis

Recent findings regarding Dll4 function in physiological and pathological conditions indicate that this Notch ligand may constitute an important therapeutic target. Dll4 appears to be a major anti-angiogenic agent, occupying a central role in various angiogenic pathways. The first trials of anti-Dll4 therapy in mice demonstrated a paradoxical effect, as it reduced tumor perfusion and growth despite leading to an increase in vascular density. This is seen as the result of insufficient maturation of the newly formed vasculature causing a circulatory defect and increased tumor hypoxia. As Dll4 function is known to be closely dependent on expression levels, we envisioned that the therapeutic anti-Dll4 dosage could be modulated to result in the increase of adequately functional blood vessels. This would be useful in conditions where vascular function is a limiting factor for recovery, like wound healing and tissue hypoxia, especially in diabetic patients. Our experimental results in mice confirmed this possibility, revealing that low dosage inhibition of Dll4/Notch signaling causes improved vascular function and accelerated wound healing

Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan

Classifying endometrial hyperplasia (EH) according to the severity of glandular crowding (simple hyperplasia (SH) vs complex hyperplasia (CH)) and nuclear atypia (simple atypical hyperplasia (SAH) vs complex atypical hyperplasia (CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case–control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma (1970–2003) at least 1 year (median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios (RRs) and 95% confidence intervals (CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium (DPEM) as the referent, AH significantly increased carcinoma risk (RR=14, 95% CI, 5–38). Risk was highest 1–5 years after AH (RR=48, 95% CI, 8–294), but remained elevated 5 or more years after AH (RR=3.5, 95% CI, 1.0–9.6). Progression risks for SH (RR=2.0, 95% CI, 0.9–4.5) and CH (RR=2.8, 95% CI, 1.0–7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)

Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions: This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients

Contested space: The contradictory political dynamics of food banking in the UK

This paper offers a critical reappraisal of the politics of food banking in the UK. Existing work has raised concerns about the institutionalisation of food banks, with charitable assistance apparently – even if inadvertently – undermining collectivist welfare and deflecting attention from fundamental injustices in the food system. This paper presents original ethnographic work that examines the neglected politics articulated within food banks themselves. Conceptualising food banks as potential spaces of encounter where predominantly middle-class volunteers come into contact with ‘poor others’ (Lawson and Elwood, 2013), we illustrate the ways food banks may both reinforce but also rework and generate new, ethical and political attitudes, beliefs and identities. We also draw attention to the limits of these progressive possibilities and examine the ways in which some food banks continue to operate within a set of highly restrictive, and stigmatising, welfare technologies. By highlighting the contradictory dynamics at work in food bank organisations, and among food bank volunteers and clients, we suggest the political role of food banks warrants neither uncritical celebration nor outright dismissal. Rather, food banks represent a highly ambiguous political space still in the making and open to contestatio

Community food program use in Inuvik, Northwest Territories

Background: Community food programs (CFPs) provide an important safety-net for highly food insecure community members in the larger settlements of the Canadian Arctic. This study identifies who is using CFPs and why, drawing upon a case study from Inuvik, Northwest Territories. This work is compared with a similar study from Iqaluit, Nunavut, allowing the development of an Arctic-wide understanding of CFP use – a neglected topic in the northern food security literature. Methods: Photovoice workshops (n=7), a modified USDA food security survey and open ended interviews with CFP users (n=54) in Inuvik. Results: Users of CFPs in Inuvik are more likely to be housing insecure, female, middle aged (35–64), unemployed, Aboriginal, and lack a high school education. Participants are primarily chronic users, and depend on CFPs for regular food access. Conclusions: This work indicates the presence of chronically food insecure groups who have not benefited from the economic development and job opportunities offered in larger regional centers of the Canadian Arctic, and for whom traditional kinship-based food sharing networks have been unable to fully meet their dietary needs. While CFPs do not address the underlying causes of food insecurity, they provide an important service for communities undergoing rapid change, and need greater focus in food policy herein