Vibronic Structure in Room Temperature Photoluminescence of the Halide Perovskite Cs3Bi2Br9

We report a study on the optical properties of the layered polymorph of vacancy-ordered triple perovskite Cs3Bi2Br9. The electronic structure, determined from density functional theory calculations, shows the top of the valence band and bottom of the conduction band minima are, unusually, dominated by Bi s and p states, respectively. This produces a sharp exciton peak in the absorption spectra with a binding energy that was approximated to be 940 meV, which is substantially stronger than values found in other halide perovskites and, instead, more closely reflects values seen in alkali halide crystals. This large binding energy is indicative of a strongly localized character and results in a highly structured emission at room temperature as the exciton couples to vibrations in the lattice

Mechanisms of Hearing Loss after Blast Injury to the Ear

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the bodyﾒs most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction

Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity

Excitement and controversy have followed neuregulin (NRG1) since its discovery as a putative schizophrenia susceptibility gene; however, the mechanism of action of the associated risk haplotype (HapICE) has not been identified, and specific genetic variations, which may increase risk to schizophrenia have remained elusive. Using a postmortem brain cohort from 37 schizophrenia cases and 37 controls, we resequenced upstream of the type I–IV promoters, and the HapICE repeat regions in intron 1. Relative abundance of seven NRG1 mRNA transcripts in the prefrontal cortex were determined and compared across diagnostic and genotypic groups. We identified 26 novel DNA variants and showed an increased novel variant load in cases compared with controls (χ2=7.815; P=0.05). The average nucleotide diversity (θ=10.0 × 10−4) was approximately twofold higher than that previously reported for BDNF, indicating that NRG1 may be particularly prone to genetic change. A greater nucleotide diversity was observed in the HapICE linkage disequilibrium block in schizophrenia cases (θ(case)=13.2 × 10−4; θ(control)=10.0 × 10−4). The specific HapICE risk haplotype was associated with increased type III mRNA (F=3.76, P=0.028), which in turn, was correlated with an earlier age of onset (r=−0.343, P=0.038). We found a novel intronic five-SNP haplotype ∼730 kb upstream of the type I promoter and determined that this region functions as transcriptional enhancer that is suppressed by SRY. We propose that the HapICE risk haplotype increases expression of the most brain-abundant form of NRG1, which in turn, elicits an earlier clinical presentation, thus providing a novel mechanism through which this genetic association may increase risk of schizophrenia

INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.</p> <p>Methods/design</p> <p>The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m²) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.</p> <p>Discussion</p> <p>The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.</p> <p>Study number</p> <p>EMR 63325-012</p> <p>Trial Registration</p> <p>Clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015443">NCT01015443</a></p

Global Transcriptome Profiling of the Pine Shoot Beetle, Tomicus yunnanensis (Coleoptera: Scolytinae)

Background: The pine shoot beetle Tomicus yunnanensis (Coleoptera: Scolytinae) is an economically important pest of Pinus yunnanensis in southwestern China. Developed resistance to insecticides due to chemical pesticides being used for a long time is a factor involved in its serious damage, which poses a challenge for management. In addition, highly efficient adaptation to divergent environmental ecologies results in this pest posing great potential threat to pine forests. However, the molecular mechanisms remain unknown as only limited nucleotide sequence data for this species is available. Methodology/Principal Findings: In this study, we applied next generation sequencing (Illumina sequencing) to sequence the adult transcriptome of T. yunnanensis. A total of 51,822,230 reads were obtained. They were assembled into 140,702 scaffolds, and 60,031 unigenes. The unigenes were further functionally annotated with gene descriptions, Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genome (KEGG). In total, 80,932 unigenes were classified into GO, 13,599 unigenes were assigned to COG, and 33,875 unigenes were found in KO categories. A biochemical pathway database containing 219 predicted pathways was also created based on the annotations. In depth analysis of the data revealed a large number of genes related to insecticides resistance and heat shock protein genes associated with environmental stress. Conclusions/Significance: The results facilitate the investigations of molecular resistance mechanisms to insecticides an

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

Background: Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques - including site-based monitoring, genetic analyses, mark-recapture studies and telemetry - can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings: To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine-to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance: The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework - including maps and supporting metadata - will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis

The influences of nursing transformational leadership style on the quality of nurses’ working lives in Taiwan: a cross-sectional quantitative study

- Background: Taiwan’s NHI system is one of the most successful health care models for countries around the globe. However, little research has demonstrated the mental health issues associated with nursing transformational leadership style under the NHI system, especially in the quality of nurses’ working lives in Taiwan. It is important to know the relationship between transformational leadership style and the mental health of nurses, organisational commitment and job satisfaction. The research aimed to understand the influences of nursing transformational leadership style on the quality of nurses’ working lives in Taiwan. The research hypothesis was that transformational leadership styles would have positive influence on the quality of nurses’ working lives. - Methods: This was a cross-sectional quantitative study. Nurses from each type of hospital ownership (private, public and religious) were recruited. Participation was voluntary and signed informed consent was obtained. The inclusion criteria were nurses with at least one year’s work experience in the hospitals. Self-administrated questionnaires were used. A total of 807 participants were contacted and 651 questionnaires were fully completed (response rate 80.7 %). A theory driven model was used to test the research hypotheses using structural equation modelling performed with AMOS 16.0. - Results: Transformational leadership contributes significantly to supervisor support. Workplace support, particularly from the supervisor, is an important mediator variable that explains the relationship between transformational leadership and job satisfaction. Organisational commitment was the strongest factor relevant to the general health well-being in Taiwanese nurses than job satisfaction. The hypothesized positive relationships between transformational leadership and all variables were supported by the data. - Conclusions: Our findings have important consequences for organisational health. Our model demonstrates a complete picture of the work relationships on the quality of nurses’ working lives. The results provided information about the subordinates’ perceptions of transformational nursing leadership styles and mental health outcomes in different hospital settings, as well as identified organisational factors that could improve the quality of nurses’ working lives

Commitment of cultural minorities in organizations:Effects of leadership and pressure to conform

PURPOSE: In this study, we investigated the commitment of cultural minorities and majorities in organizations. We examined how contextual factors, such as pressure to conform and leadership styles, affect the commitment of minority and majority members. DESIGN/METHODOLOGY/APPROACH: A field study was conducted on 107 employees in a large multinational corporation. FINDINGS: We hypothesize and found that cultural minorities felt more committed to the organization than majority members, thereby challenging the existing theoretical view that cultural minorities will feel less committed. We also found that organizational pressure to conform and effective leadership increased the commitment of minorities. IMPLICATIONS: Our findings indicate that organizational leaders and researchers should not only focus on increasing and maintaining the commitment of minority members, but should also consider how majority members react to cultural socialization and integration processes. The commitment of minority members can be further enhanced by effective leadership. ORIGINALITY/VALUE: In this study, we challenge the existing theoretical view based on similarity attraction theory and relational demography theory, that cultural minorities would feel less committed to the organization. Past research has mainly focused on minority groups, thereby ignoring the reaction of the majority to socialization processes. In this study, we show that cultural minorities can be more committed than majority members in organizations. Therefore, the perceptions of cultural majority members of socialization processes should also be considered in research on cultural diversity and acculturation

Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Importance: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. Objectives To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Design, Setting, and Participants: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Main Outcomes and Measures: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Results: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. Conclusions and Relevance: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science