Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations

Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years

Relationship of menopausal status and climacteric symptoms to sleep in women undergoing chemotherapy

Goals of workThe goal of this study was to examine the relationship between menopausal symptoms, sleep quality, and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer.Patients and methodsData on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12 weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses, participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre-Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri-Peri), and post-menopausal before and after chemotherapy (Post-Post).Main resultsResults suggested that women within the Pre-Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre-Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri-Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep.ConclusionsContrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings

Communication, advice exchange and job satisfaction of nursing staff: a social network analyses of 35 long-term care units

Background: The behaviour of individuals is affected by the social networks in which they are embedded. Networks are also important for the diffusion of information and the influence of employees in organisations. Yet, at the moment little is known about the social networks of nursing staff in healthcare settings. This is the first study that investigates informal communication and advice networks of nursing staff in long-term care. We examine the structure of the networks, how they are related to the size of units and characteristics of nursing staff, and their relationship with job satisfaction. Methods: We collected social network data of 380 nursing staff of 35 units in group projects and psychogeriatric units in nursing homes and residential homes in the Netherlands. Communication and advice networks were analyzed in a social network application (UCINET), focusing on the number of contacts (density) between nursing staff on the units. We then studied the correlation between the density of networks, size of the units and characteristics of nursing staff. We used multilevel analyses to investigate the relationship between social networks and job satisfaction of nursing staff, taking characteristics of units and nursing staff into account. Results: Both communication and advice networks were negatively related to the number of residents and the number of nursing staff of the units. Communication and advice networks were more dense when more staff worked part-time. Furthermore, density of communication networks was positively related to the age of nursing staff of the units. Multilevel analyses showed that job satisfaction differed significantly between individual staff members and units and was influenced by the number of nursing staff of the units. However, this relationship disappeared when density of communication networks was added to the model. Conclusions: Overall, communication and advice networks of nursing staff in long-term care are relatively dense. This fits with the high level of cooperation that is needed to provide good care to residents. Social networks are more dense in small units and are also shaped by characteristics of staff members. The results furthermore show that communication networks are important for staff's job satisfaction. (aut. ref.

Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly

The apolipoprotein E (APOE) genotype is a genetic risk factor for dementia, Alzheimer’s disease, and cardiovascular disease (CVD). It includes three alleles (e2, e3, e4) that are located on chromosome 19q3.2. The e3 allele is the most common and is more common in people of Northern European ancestry and less common in those of Asian ancestry. Those with at least one e4 allele are at increased risk for CVD outcomes. It is well established that the presence of an e4 allele is linked to higher low-density lipoprotein cholesterol levels, even at young ages. Even though most CVD occurs in older people, there are few studies of the effects of APOE on CVD in older people. This review addresses recent research on the links between APOE, CVD, and vascular mechanisms by which APOE may affect CVD in the elderly

Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.A special acknowledgement to Karl Deisseroth from Stanford University, for providing viral constructs and for comments on the manuscript, and to Alan Dorval from the University of Utah, for providing mouse strains. Thanks to Luis Jacinto, Joao Oliveira and Joana Silva that helped in some technical aspects of the experiments. C.S.-C., B.C., A.D.-P. and S.B. are recipients of Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/51992/2012; SFRH/BD/98675/2013; SFRH/BD/90374/2012; SFRH/BD/89936/2012). A.J.R. is a FCT Investigator (IF/00883/2013). This work was co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Part of the work was supported by the Janssen Neuroscience Prize (1st edition).info:eu-repo/semantics/publishedVersio