Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts

Developmental prosopagnosia (DP) is characterised by a severe and relatively selective deficit in face recognition, in the absence of neurological injury. Because public and professional awareness of DP is low, many adults and children are not identified for formal testing. This may partly result from the lack of appropriate screening tools that can be used by non-experts in either professional or personal settings. To address this issue, the current study sought to (a) explore when DP can first be detected in oneself and another, and (b) identify a list of the condition’s everyday behavioural manifestations. Questionnaires and interviews were administered to large samples of adult DPs, their unaffected significant others, and parents of children with the condition; and data were analysed using inductive content analysis. It was found that DPs have limited insight into their difficulties, with most only achieving realisation in adulthood. Nevertheless, the DPs’ reflections on their childhood experiences, together with the parental responses, revealed specific indicators that can potentially be used to spot the condition in early childhood. These everyday hallmark symptoms may aid the detection of individuals who would benefit from objective testing, in oneself (in adults) or another person (for both adults and children)

Overview of the Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) project

The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) seeks to characterize 20 OB-dominated young clusters and their environs at distances d ≤ 4 kpc using imaging detectors on the Chandra X-ray Observatory, Spitzer Space Telescope, and the United Kingdom InfraRed Telescope. The observational goals are to construct catalogs of star-forming complex stellar members with well-defined criteria and maps of nebular gas (particularly of hot X-ray-emitting plasma) and dust. A catalog of MYStIX Probable Complex Members with several hundred OB stars and 31,784 low-mass pre-main sequence stars is assembled. This sample and related data products will be used to seek new empirical constraints on theoretical models of cluster formation and dynamics, mass segregation, OB star formation, star formation triggering on the periphery of H II regions, and the survivability of protoplanetary disks in H II regions. This paper gives an introduction and overview of the project, covering the data analysis methodology and application to two star-forming regions: NGC 2264 and the Trifid Nebula. © 2013. The American Astronomical Society. All rights reserved.We thank J. Forbrich and P. Teixeira (Univ. Vienna) for useful discussion about NGC 2264. The MYStIX project is supported at Penn State by NASA grant NNX09AC74G, NSF grant AST-0908038, and theChandra ACIS Team contract SV4- 74018 (PIs: G. Garmire & L. Townsley), issued by the Chandra X-ray Center, which is operated by the Smithsonian Astrophysical Observatory for and on behalf of NASA under contract NAS8-03060. M. S. Povich was supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-0901646. This research made use of data products from the Chandra Data Archive and the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory (California Institute of Technology) under a contract with NASA. The United Kingdom Infrared Telescope is operated by the Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the U.K. This work is based in part on data obtained as part of the UKIRT Infrared Deep Sky Survey and in part on data obtained in UKIRT Director’s Discretionary Time. This research used data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. The HAWK-I near-infrared observations were collected with the High Acuity Wide-field K-band Imager instrument on the ESO 8 m Very Large Telescope at Paranal Observatory, Chile, under ESO programme 60.A-9284(K). This research has also made use of NASA’s Astrophysics Data System Bibliographic Services, the SIMBAD database operated at the Centre de Donnees ´ Astronomique de Strasbourg, and SAOImage DS9 software developed by Smithsonian Astrophysical Observatory

Development of an evidence-based checklist for the detection of drug related problems in type 2 diabetes

Objective To develop an evidence-based checklist to identify potential drug related problems (PDRP) in patients with type 2 diabetes. Setting The evidence based checklist was applied to records of ambulatory type 2 diabetes patients in New South Wales, Australia. Method After comprehensive review of the literature, relevant medication groups and potential drug related problems in type 2 diabetes were identified. All the relevant information was then structured in the form of a checklist. To test the utility of the evidence-based checklist a cross-sectional retrospective study was conducted. The PDRP checklist was applied to the data of 148 patients with established type 2 diabetes and poor glycaemic control. The range and extent of DRPs in this population were identified, which were categorized using the PCNE classification. In addition, the relationship between the total as well as each category of DRPs and several of the patients’ clinical parameters was investigated. Main outcome measure: Number and category of DRPs per patient. Results The PDRP checklist was successfully developed and consisted of six main sections. 682 potential DRPs were identified using the checklist, an average of 4.6 (SD = 1.7) per patient. Metabolic and blood pressure control in the study subjects was generally poor: with a mean HbA1c of 8.7% (SD = 1.5) and mean blood pressure of 139.8 mmHg (SD = 18.1)/81.7 mmHg (SD = 11.1). The majority of DRPs was recorded in the categories ‘therapy failure’ (n = 264) and ‘drug choice problem’ (n = 206). Potentially non-adherent patients had a significantly higher HbA1c than patients who adhered to therapy (HbA1c of 9.4% vs. 8.5%; P = 0.01). Conclusion This is the first tool developed specifically to detect potential DRPs in patients with type 2 diabetes. It was used to identify DRPs in a sample of type 2 diabetes patients and demonstrated the high prevalence of DRPs per patient. The checklist may assist pharmacists and other health care professionals to systematically identify issues in therapy and management of their type 2 diabetes patients and enable earlier intervention to improve metabolic control

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

NMR assignment of the C-terminal actin-binding domain of talin.

Talin is a large dimeric 270 kDa adapter protein which binds the cytoplasmic face of a subset of integrin beta-subunits and couples them to the actin cytoskeleton. Here we report the near complete 15N, 13C and 1H chemical shift assignments for the C-terminal actin-binding domain

Is Human Cytomegalovirus Infection Associated with Hypertension? The United States National Health and Nutrition Examination Survey 1999–2002

PURPOSE: Recent studies have implicated the human cytomegalovirus (HCMV) as a possible pathogen for causing hypertension. We aimed to study the association between HCMV infection and hypertension in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed data on 2979 men and 3324 women in the NHANES 1999-2002. We included participants aged 16-49 years who had valid data on HCMV infection and hypertension. RESULTS: Of the participants, 54.7% had serologic evidence of HCMV infection and 17.5% had hypertension. There were ethnic differences in the prevalence of HCMV infection (P<0.001) and hypertension (P<0.001). The prevalence of both increased with age (P<0.001). Before adjustment, HCMV seropositivity was significantly associated with hypertension in women (OR = 1.63, 95% CI = 1.25-2.13, P = 0.001) but not in men. After adjustment for race/ethnicity, the association between HCMV seropositivity and hypertension in women remained significant (OR = 1.55, 95% CI = 1.20-2.02, P = 0.002). Further adjustment for body mass index, diabetes status and hypercholesterolemia attenuated the association (OR = 1.44, 95% CI = 1.10-1.90, P = 0.010). However, after adjusting for age, the association was no longer significant (OR = 1.24, 95% CI = 0.91-1.67, P = 0.162). CONCLUSIONS: In this nationally representative population-based survey, HCMV seropositivity is associated with hypertension in women in the NHANES population. This association is largely explained by the association of hypertension with age and the increase in past exposure to HCMV with age.published_or_final_versio

Qualitative meta-synthesis of user experience of computerised therapy for depression and anxiety

Objective: Computerised therapies play an integral role in efforts to improve access to psychological treatment for patients with depression and anxiety. However, despite recognised problems with uptake, there has been a lack of investigation into the barriers and facilitators of engagement. We aimed to systematically review and synthesise findings from qualitative studies of computerised therapies, in order to identify factors impacting on engagement. Method: Systematic review and meta-synthesis of qualitative studies of user experiences of computer delivered therapy for depression and/or anxiety. Results: 8 studies were included in the review. All except one were of desktop based cognitive behavioural treatments. Black and minority ethnic and older participants were underrepresented, and only one study addressed users with a comorbid physical health problem. Through synthesis, we identified two key overarching concepts, regarding the need for treatments to be sensitive to the individual, and the dialectal nature of user experience, with different degrees of support and anonymity experienced as both positive and negative. We propose that these factors can be conceptually understood as the ‘non-specific’ or ‘common’ factors of computerised therapy, analogous to but distinct from the common factors of traditional face-to-face therapies. Conclusion: Experience of computerised therapy could be improved through personalisation and sensitisation of content to individual users, recognising the need for users to experience a sense of ‘self’ in the treatment which is currently absent. Exploiting the common factors of computerised therapy, through enhancing perceived connection and collaboration, could offer a way of reconciling tensions due to the dialectal nature of user experience. Future research should explore whether the findings are generalisable to other patient groups, to other delivery formats (such as mobile technology) and other treatment modalities beyond cognitive behaviour therapy. The proposed model could aid the development of enhancements to current packages to improve uptake and support engagement

The structure of the C-terminal actin-binding domain of talin

Talin is a large dimeric protein that couples integrins to cytoskeletal actin. Here, we report the structure of the C-terminal actin-binding domain of talin, the core of which is a five-helix bundle linked to a C-terminal helix responsible for dimerisation. The NMR structure of the bundle reveals a conserved surface-exposed hydrophobic patch surrounded by positively charged groups. We have mapped the actin-binding site to this surface and shown that helix 1 on the opposite side of the bundle negatively regulates actin binding. The crystal structure of the dimerisation helix reveals an antiparallel coiled-coil with conserved residues clustered on the solvent-exposed face. Mutagenesis shows that dimerisation is essential for filamentous actin (F-actin) binding and indicates that the dimerisation helix itself contributes to binding. We have used these structures together with small angle X-ray scattering to derive a model of the entire domain. Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament

Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans

Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation

Talin is a 270-kDa protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM domain comprised of F1, F2 and F3 domains, but it is atypical in that F1 contains a large insert and is preceded by an extra domain F0. Although F3 contains the binding site for β-integrin tails, F0 and F1 are also required for activation of β1-integrins. Here, we report the solution structures of F0, F1 and of the F0F1 double domain. Both F0 and F1 have ubiquitin-like folds joined in a novel fixed orientation by an extensive charged interface. The F1 insert forms a loop with helical propensity, and basic residues predicted to reside on one surface of the helix are required for binding to acidic phospholipids and for talin-mediated activation of β1-integrins. This and the fact that basic residues on F2 and F3 are also essential for integrin activation suggest that extensive interactions between the talin FERM domain and acidic membrane phospholipids are required to orientate the FERM domain such that it can activate integrins