Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness.

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM

A feldspar-nepheline achondrite clast in Parnallee

A feldspar-nepheline clast (FELINE) has been identified in Parnallee (LL3.6). Plagioclase is An_, Ab_ and nepheline contains 0.24-3.12wt% Cl. The calculated bulk composition is mildly alkaline, with 3.5wt% Na_2O. Plagioclase has heavy REE depletion and a positive Eu anomaly (Eu/Eu^*=65). Nepheline has lower total REE than plagioclase. On a three isotope plot, the oxygen isotope composition of FELINE falls near the Carbonaceous Chondrites Anyhdrous Minerals Line, beneath the Terrestrial Fractionation Line. This suggests that the parental material had carbonaceous chondrite affinities. It was derived from a melt with moderately enriched LREE and Eu (13.5×CI), which probably underwent an influx of Na-, Cl-rich fluids during crystallisation. This LREE-enrichment suggests that Ca-pyroxene crystallised in the parent body residue during a melt extraction event. REE abundances and the oxygen isotope signature are consistent with an origin as a lost plagiophile melt fraction complementary to the ureilites. FELINE provides further evidence that achondritic fragments with an igneous, exotic origin are an important component of chondritic meteorites

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

Metamorphism and aqueous alteration in low petrographic type ordinary chondrites

In order to investigate the relative importance of dry metamorphism and aqueous alteration in the history of chondruies, chondruies were hand-picked from the Semarkona (petrographic type 3.0), Bishunpur (3. 1), Chainpur (3.4), Dhajala (3.8) and Allegan (5) chondrites, and matrix samples were extracted from the first three ordinary chondrites. The thermoluminescence (TL) properties of all the samples were measured, and appropriate subsets of the samples were analyzed by electron-microprobe and radiochemical neutron activation and the water and H-isotopic composition determined. The TL data for chondrules from Semarkona and Bishunpur scatter widely showing no unambiguous trends, although group B1 chondrules tend to have lower sensitivities and lower peak temperatures compared with group A5 chondrules. It is argued that these data reflect the variety of processes accompanying chondrule formation. The chondrules show remarkably uniform contents of the highly labile elements, indicating mineralogical control on abundance and volatile loss from silicates and loss and recondensation of mobile chalcophiles and siderophiles in some cases. Very high D/H values (up to approx. 8000% SMOW) are observed in certain Semarkona chondrules, a confirmation of earlier work. With increasing petrographic type, mean TL sensitivities of the chondrules increase, the spread of values within an individual meteorite decreases, and peak temperatures and peak widths show trends indicating that the TL is mainly produced by feldspar and that dry, thermal metamorphism is the dominant secondary process experienced by the chondrules. The TL sensitivities of matrix samples also increase with petrographic type. Chainpur matrix samples show the same spread of peak temperatures and peak widths as Chainpur chondruies, indicating metamorphism-related changes in the feldspar are responsible for the TL of the matrix. The TL data for the Semarkona and Bishunpur matrix samples provide, at best, only weak evidence for aqueous alteration, but the matrix contains H with approximately terrestrial D/H values, even though it contains much water. Secondary processes (probably aqueous alteration) presumably lowered the D/H of the matrix and certain chondrules. While chondrule properties appear to be governed primarily by formation processes and subsequent metamorphism, the matrix of Semarkona has a more complex history involving aqueous alteration as a meteorite-wide process

Using network theory to identify the causes of disease outbreaks of unknown origin.

The identification of undiagnosed disease outbreaks is critical for mobilizing efforts to prevent widespread transmission of novel virulent pathogens. Recent developments in online surveillance systems allow for the rapid communication of the earliest reports of emerging infectious diseases and tracking of their spread. The efficacy of these programs, however, is inhibited by the anecdotal nature of informal reporting and uncertainty of pathogen identity in the early stages of emergence. We developed theory to connect disease outbreaks of known aetiology in a network using an array of properties including symptoms, seasonality and case-fatality ratio. We tested the method with 125 reports of outbreaks of 10 known infectious diseases causing encephalitis in South Asia, and showed that different diseases frequently form distinct clusters within the networks. The approach correctly identified unknown disease outbreaks with an average sensitivity of 76 per cent and specificity of 88 per cent. Outbreaks of some diseases, such as Nipah virus encephalitis, were well identified (sensitivity = 100%, positive predictive values = 80%), whereas others (e.g. Chandipura encephalitis) were more difficult to distinguish. These results suggest that unknown outbreaks in resource-poor settings could be evaluated in real time, potentially leading to more rapid responses and reducing the risk of an outbreak becoming a pandemic

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

College students and use of K2: an emerging drug of abuse in young persons

<p>Abstract</p> <p>Background</p> <p>K2 or "spice" has emerged as a popular legal alternative to marijuana among adolescents and young adults. However, no data has been published assessing prevalence of and associations with ever K2 use in any population. This study's aims were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2, and to access the association between K2 and other drug use.</p> <p>Findings</p> <p>Ever use of K2 was reported by 69 (8%) of the sample of 852 college students. Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2. Ever use of K2 was reported by 69 (8%) of the sample. Among these 69 individuals, 61 (88%) had used a cigarette and 25 (36%) had used a hookah to smoke K2. In multivariate analyses, K2 use was more common in males (vs. females, adjusted Odds Ratio (aOR) = 2.0, 95% Confidence Interval (CI) = 1.2-3.5, <it>p </it>= 0.01) and 1^stor 2^ndyear college students (vs. 3^rdyear or above, aOR = 2.4, 95% CI = 1.2-5.0, <it>p </it>= 0.02).</p> <p>Conclusions</p> <p>Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Although DEA had banned five synthetic cannabinoids recently, clinicians and public health officials concerned with substance abuse in youth should be aware of and monitor the use of this drug in college students over time.</p