Creation of ultracold molecules from a Fermi gas of atoms

Since the realization of Bose-Einstein condensates (BEC) in atomic gases an experimental challenge has been the production of molecular gases in the quantum regime. A promising approach is to create the molecular gas directly from an ultracold atomic gas; for example, atoms in a BEC have been coupled to electronic ground-state molecules through photoassociation as well as through a magnetic-field Feshbach resonance. The availability of atomic Fermi gases provides the exciting prospect of coupling fermionic atoms to bosonic molecules, and thus altering the quantum statistics of the system. This Fermi-Bose coupling is closely related to the pairing mechanism for a novel fermionic superfluid proposed to occur near a Feshbach resonance. Here we report the creation and quantitative characterization of exotic, ultracold $^{40}$K$_2$ molecules. Starting with a quantum degenerate Fermi gas of atoms at T < 150 nanoKelvin we scan over a Feshbach resonance to adiabatically create over a quarter million trapped molecules, which we can convert back to atoms by reversing the scan. The small binding energy of the molecules is controlled by detuning from the Feshbach resonance and can be varied over a wide range. We directly detect these weakly bound molecules through rf photodissociation spectra that probe the molecular wavefunction and yield binding energies that are consistent with theory

Typology of adults diagnosed with mental disorders based on socio-demographics and clinical and service use characteristics

<p>Abstract</p> <p>Background</p> <p>Mental disorder is a leading cause of morbidity worldwide. Its cost and negative impact on productivity are substantial. Consequently, improving mental health-care system efficiency - especially service utilisation - is a priority. Few studies have explored the use of services by specific subgroups of persons with mental disorder; a better understanding of these individuals is key to improving service planning. This study develops a typology of individuals, diagnosed with mental disorder in a 12-month period, based on their individual characteristics and use of services within a Canadian urban catchment area of 258,000 persons served by a psychiatric hospital.</p> <p>Methods</p> <p>From among the 2,443 people who took part in the survey, 406 (17%) experienced at least one episode of mental disorder (as per the Composite International Diagnostic Interview (CIDI)) in the 12 months pre-interview. These individuals were selected for cluster analysis.</p> <p>Results</p> <p>Analysis yielded four user clusters: people who experienced mainly anxiety disorder; depressive disorder; alcohol and/or drug disorder; and multiple mental and dependence disorder. Two clusters were more closely associated with females and anxiety or depressive disorders. In the two other clusters, males were over-represented compared with the sample as a whole, namely, substance abuses with or without concomitant mental disorder. Clusters with the greatest number of mental disorders per subject used a greater number of mental health-care services. Conversely, clusters associated exclusively with dependence disorders used few services.</p> <p>Conclusion</p> <p>The study found considerable heterogeneity among socio-demographic characteristics, number of disorders, and number of health-care services used by individuals with mental or dependence disorders. Cluster analysis revealed important differences in service use with regard to gender and age. It reinforces the relevance of developing targeted programs for subgroups of individuals with mental and/or dependence disorders. Strategies aimed at changing low service users' attitude (youths and males) or instituting specialised programs for that particular clientele should be promoted. Finally, as concomitant disorders are frequent among individuals with mental disorder, psychological services and/or addiction programs must be prioritised as components of integrated services when planning treatment.</p

DIgital Alcohol Management ON Demand (DIAMOND) feasibility randomised controlled trial of a web-based intervention to reduce alcohol consumption in people with hazardous and harmful use versus a face-to-face intervention: protocol.

BACKGROUND: "Hazardous and harmful" drinkers make up approximately 23 % of the adult population in England. However, only around 10 % of these people access specialist care, such as face-to-face extended brief treatment in community alcohol services. This may be due to stigma, difficulty accessing services during working hours, a shortage of trained counsellors and limited provision of services in many places. Web-based alcohol treatment programmes may overcome these barriers and may better suit people who are reluctant or unable to attend face-to-face services, but there is a gap in the evidence base for the acceptability, effectiveness and cost-effectiveness of these programmes compared with treatment as usual (TAU) in community alcohol services. This study aims investigate the feasibility of all parts of a randomised controlled trial (RCT) of a psychologically informed web-based alcohol treatment programme called Healthy Living for People who use Alcohol (HeLP-Alcohol) versus TAU in community alcohol services, e.g. recruitment and retention, online data collection methods, and the use and acceptability of the intervention to participants. METHODS: A feasibility RCT delivered in north London community alcohol services, comparing HeLP-Alcohol with TAU. Potential participants are aged ≥18 years referred or self-referred for hazardous and harmful use of alcohol, without co-morbidities or other complex problems. The main purpose of this study is to demonstrate the feasibility of recruiting participants to the study and will test online methods for collecting baseline demographic and outcome questionnaire data, randomising participants and collecting 3-month follow-up data. The acceptability of this intervention will be measured by recruitment and retention rates, automated log-in data collection and an online service satisfaction questionnaire. The feasibility of using tailored text message, email or phone prompt to maintain engagement with the intervention will also be explored. Results of the study will inform a definitive Phase 3 RCT. RESULTS: Recruitment started on 26 September 2014 and will run for 1 year. CONCLUSION: The proposed trial will provide data to inform a fully powered non-inferiority effectiveness and cost-effectiveness RCT comparing HeLP-Alcohol with TAU. TRIAL REGISTRATION: ISRCTN31789096

The Staphylococcus aureus RNome and Its Commitment to Virulence

Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity

Comparison of face-to-face versus email guided self-help for binge eating: study protocol for a randomised controlled trial

Background Guided self-help is a recommended first-step treatment for bulimia nervosa, binge eating disorder and atypical variants of these disorders. Further research is needed to compare guided self-help that is delivered face-to-face versus via email. Methods/Design This clinical trial uses a randomised, controlled design to investigate the effectiveness of providing guided self-help either face-to-face or via e-mail, also using a delayed treatment control condition. At least 17 individuals are required per group, giving a minimum N of 51. Discussion Symptom outcomes will be assessed and estimates of cost-effectiveness made. Results are proposed to be disseminated locally and internationally (through submission to conferences and peer-reviewed journals), and will hopefully inform local service provision. The trial has been approved by an ethics review board and was registered with ClinicalTrials.gov NCT01832792 on 9 April 2013

The fractal globule as a model of chromatin architecture in the cell

The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10 Mb (Lieberman-Aiden et al. 2009). Here, we present the concept of the fractal globule, comparing it to other states of a polymer and focusing on its properties relevant for the biophysics of chromatin. We then discuss properties of the fractal globule that make it an attractive model for chromatin organization inside a cell. Next, we connect the fractal globule to recent studies that emphasize topological constraints as a primary factor driving formation of chromosomal territories. We discuss how theoretical predictions, made on the basis of the fractal globule model, can be tested experimentally. Finally, we discuss whether fractal globule architecture can be relevant for chromatin packing in other organisms such as yeast and bacteria

Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit/hyperactivity disorder: study protocol for a randomized controlled trial

Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day– night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD. Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up. This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.The trial is funded by the EU Framework Programme for Research and Innovation, Horizon 2020 (Project no. 667302). Funding period: January 2016–December 2020. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Some local funds additionally contributed to carry out this study, especially for the preparation of the interventions: FBO research activity is by the Spanish Ministry of Economy and Competitiveness – MINECO (RYC-2011-09011) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and Health (UCEES)

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented