Investigating the impact of nicotine on executive functions using a novel virtual reality assessment

Aims Nicotine is known to enhance aspects of cognitive functioning in abstinent smokers but the effects on specific areas of executive functions, and in non-smokers are inconclusive. This may be due in part to the poor sensitivity of tests used to assess executive functions. This study used a new virtual reality assessment of executive functions known as JEF (the Jansari assessment of Executive Functions) to address this issue. Design 2x2 design manipulating group (smokers and never-smokers) and drug (nicotine [4mg for smokers; 2mg for never smokers] vs placebo gum). Setting School of Psychology; University of East LondonParticipants 72 participants (aged 18 to 54). 36 minimally-deprived (2 hr) smokers and 36 never-smokers.Measurements Components of executive function were measured using the virtual reality paradigm JEF, which assesses eight cognitive constructs simultaneously as well as providing an overall performance measure. Results Univariate ANOVAs revealed that nicotine improved overall JEF performance, time-based prospective memory and event-based prospective memory in smokers (p < 0.01) but not in never-smokers. Action-based prospective memory was enhanced in both groups (p < 0.01) and never-smokers out-performed smokers on selective thinking and adaptive thinking (p < 0.01). Conclusions. Overall executive functioning and prospective memory can be enhanced by nicotine gum in abstinent smokers. That smokers were only minimally deprived suggests that JEFis a sensitive measure of executive functioning and that prospective memory is particularly susceptible to disruption by abstinence

Improved modelling of helium and tritium production for spallation targets

Reliable predictions of light charged particle production in spallation reactions are important to correctly assess gas production in spallation targets. In particular, the helium production yield is important for assessing damage in the window separating the accelerator vacuum from a spallation target, and tritium is a major contributor to the target radioactivity. Up to now, the models available in the MCNPX transport code, including the widely used default option Bertini-Dresner and the INCL4.2-ABLA combination of models, were not able to correctly predict light charged particle yields. The work done recently on both the intranuclear cascade model INCL4, in which cluster emission through a coalescence process has been introduced, and on the de-excitation model ABLA allows correcting these deficiencies. This paper shows that the coalescence emission plays an important role in the tritium and $^3He$ production and that the combination of the newly developed versions of the codes, INCL4.5-ABLA07, now lead to good predictions of both helium and tritium cross sections over a wide incident energy range. Comparisons with other available models are also presented.Comment: 6 pages, 9 figure

Franck-Condon Factors and Radiative Lifetime of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} Transition of Ytterbium Monoflouride, YbF

The fluorescence spectrum resulting from laser excitation of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} (0,0) band of ytterbium monofluoride, YbF, has been recorded and analyzed to determine the Franck-Condon factors. The measured values are compared with those predicted from Rydberg-Klein-Rees (RKR) potential energy curves. From the fluorescence decay curve the radiative lifetime of the A^{2}\Pi_{1/2} state is measured to be 28\pm2 ns, and the corresponding transition dipole moment is 4.39\pm0.16 D. The implications for laser cooling YbF are discussed.Comment: 5 pages, 5 figure

Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH, representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in difH defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division

Evaluation of a nutrition supplementation programme in the Northern Cape Province of South Africa

AIM: This study aimed at assessing the effectiveness regarding implementation and impact of a take-home nutrition supplementation programme, the Protein Energy Malnutrition (PEM) Scheme, that targets malnourished pre-school children and pregnant and lactating women in the Northern Cape Province of South Africa. METHODOLOGY: In assessing implementation of the PEM Scheme, a cross-sectional descriptive study was undertaken over a 6-month period in the six regions of the Northern Cape Province. Interviews were conducted with programme managers and health personnel at clinics who were responsible for implementing the PEM Scheme. In assessing the impact of the PEM Scheme on growth, a retrospective review was done of the clinic records (including anthropometric data) of children enrolled in the PEM Scheme over a 1-year period. RESULTS: About 76% of the budget allocated to the PEM Scheme had been utilised over the 1-year period. The budget for the following financial year was based solely on food supplements purchased in the previous year. Coverage of malnourished pre-school children and eligible pregnant and lactating women for enrolment was estimated to be 50% and 60%, respectively. Eighty-five per cent of health facilities in the province participated in the PEM Scheme. Some of the main problems identified included: lack of training, inappropriate targeting of certain groups, incorrect application especially of discharge criteria for pregnant and lactating women, inadequate assessment for nutrition-related disease, inadequate nutrition counselling and no standardised monitoring. Of the 319 children enrolled over a year, the mean age was 16.2 (standard deviation 16.2) months, 41% had been low-birth-weight and 18% had been diagnosed with tuberculosis. Ten per cent of the children with a weight-for-age Z-score of <-2 moved into the normal Z-score range after being on the PEM Scheme for a mean duration of 8 months. There was an overall improvement in the weight-for-age Z-scores of 25% of the sample, with a significant difference between the mean weight-for-age Z-scores at enrolment and follow-up This was mainly related to significant improvement in the mean weight-for-age Z-scores of children <2 years. CONCLUSIONS: Numerous problems with the PEM Scheme have been identified which could have limited its impact. Recommendations are proposed for improving the effectiveness and impact of the PEM Scheme in the province

Proposed vitamin A supplementation programme for South Africa - design, coverage and cost

Background. A national survey of the micronutrient status of preschool children in South Africa established that vitamin A deficiency is a significant public health problem, requiring urgent attention. A number of immediate and long-term intenrentions were recommended, including the introduction of a vitamin A supplementation programme and a food fortification programme.Objectives. The aim of the study was to assist in the development and implementation of a national vitamin A supplementation programme at primary health care facilities for mothers and children. This was achieved by determining the design, coverage and cost of a national primary health care facility vitamin A supplementation programme.Methods. Based on an extensive review of the literature, the main components of a primary health care facility vitamin A supplementation programme were identified. The annual, recurrent cost of each of the programme component wer estimated for the nine provinces in South Africa. Immunisation coverage rates were used as a proxy for estimating the coverage of the programme.Results. The main components of the programme were identified as: promotion, training, purchase of vitamin A capsules, distribution of vitamin A capsules to primary health care facilities, clistribution of cap ule to the programme beneficiaries, and monitoring and evaluation. The programme would operate from primary health care facililities and would target all children between 6 and 24  months of age and newly delivered mothers. It was estimated that the programme would cover 74% of children and 95% of postpartum women nationally. The total annual, recurrent cost of the national programme was estimated at R16.4 million. The bulk of the costs would include personnel costs, comprising 68% of the total costs. Other costs included promotion (27%), vitamin A capsules (4%) and training (1%). The cost of the programme would vary significantly by province, but the provinces' average total cost per beneficiary would be similar.Conclusion. A primary health care facility vitamin A supplementation programme has been designed and accompanied by an estimated overall cost and coverage for implementation. The findings of the study showed that the programme would be financially feasible and would reach the majority of children under 24 months of age. It is recommended that further research be undertaken to extend the programme to the more 'hard to reach' population using other stategies such as mass immunisation campaigns

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103)

Purpose Bevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2-negative disease. Patients and Methods Patients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease-free survival (IDFS). Results Four thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade ≥ 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation

1H, 15N, and 13C chemical shift assignments of neuronal calcium sensor-1 homolog from fission yeast

The neuronal calcium sensor (NCS) proteins regulate signal transduction processes and are highly conserved from yeast to humans. We report complete NMR chemical shift assignments of the NCS homolog from fission yeast (Schizosaccharomyces pombe), referred to in this study as Ncs1p. (BMRB no. 16446)