The pathways to psychiatric care: a cross-cultural study

This paper describes the referral pathways taken by 1554 patients newly referred to the mental health services in 11 countries, and documents factors associated with delays in referral. The pathways in centres relatively well provided with psychiatric staff were dominated by general practitioners and to a lesser extent hospital doctors: the relatively less well resourced centres showed a variety of pathways with native healers often playing an important part. Delays were remarkably short in all centres regardless of psychiatric resources, but in some centres we found longer delays on pathways involving native healers. Somatic problems were a common presentation in all centres, and in some centres there was a tendency for patients presenting with somatic problems to have longer delays than those with symptoms of depression or anxiety. The implications of these findings are discussed in the context of an ongoing programme of WHO research activities aimed at improving the quality of mental illness care available in community setting

Numerical and experimental studies of a capillary-tube embedded PCM component for improving indoor thermal environment

This paper aims to analyse the thermal characteristics of a novel system of Capillary Tubes embedded in a Phase Change Material (CT-PCM) as part of active building environmental design for energy conservation and the improvement of indoor thermal environment. The CT-PCM system is proposed based on the concept that low-grade energy utilisation potential could be harnessed and maximised by buildings’ radiant heating/cooling systems and phase change material. The CT-PCM component is first built in the laboratory, and the thermal characteristics of the CT-PCM are investigated through a set of thermal response experiments. In addition, a simplified model is developed to assess the long-term thermal performance of the CT-PCM system for its application during a strategical system design stage. To ensure the robustness of the numerical model in the assessment of the thermal performance of the system, the developed model is evaluated against the experiments under a set of dynamic thermal boundary conditions. The evaluation process revealed that when the flow rate of thermal fluids in the CT-PCM system is more than 800 ml/min, the simulation results of the proposed simplified model is in a good agreement with the experiment. When the flow rate in the capillary tube is smaller than 800 ml/min, the correction factors are derived to address the non-uniformity of temperature distribution

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Scaling Relations and Overabundance of Massive Clusters at Z ≳ 1 from Weak-Lensing Studies with the Hubble Space Telescope

We present weak gravitational lensing analysis of 22 high-redshift (z 1) clusters based on Hubble Space Telescope images. Most clusters in our sample provide significant lensing signals and are well detected in their reconstructed two-dimensional mass maps. Combining the current results and our previous weak-lensing studies of five other high-z clusters, we compare gravitational lensing masses of these clusters with other observables. We revisit the question whether the presence of the most massive clusters in our sample is in tension with the current ΛCDM structure formation paradigm. We find that the lensing masses are tightly correlated with the gas temperatures and establish, for the first time, the lensing mass-temperature relation at z 1. For the power-law slope of the M-TX relation (MT α), we obtain α = 1.54 ± 0.23. This is consistent with the theoretical self-similar prediction α = 3/2 and with the results previously reported in the literature for much lower redshift samples. However, our normalization is lower than the previous results by 20%-30%, indicating that the normalization in the M-TX relation might evolve. After correcting for Eddington bias and updating the discovery area with a more conservative choice, we find that the existence of the most massive clusters in our sample still provides a tension with the current ΛCDM model. The combined probability of finding the four most massive clusters in this sample after the marginalization over cosmological parameters is less than 1%

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE:

Wire Marking Results in a Small but Significant Reduction in Avian Mortality at Power Lines: A BACI Designed Study

10 paginas, 4 figuras y 4 tablesBackground: Collision with electric power lines is a conservation problem for many bird species. Although the implementation of flight diverters is rapidly increasing, few well-designed studies supporting the effectiveness of this costly conservation measure have been published. Methodology/Principal Findings: We provide information on the largest worldwide marking experiment to date, including carcass searches at 35 (15 experimental, 20 control) power lines totalling 72.5 km, at both transmission (220 kV) and distribution (15 kV-45 kV) lines. We found carcasses of 45 species, 19 of conservation concern. Numbers of carcasses found were corrected to account for carcass losses due to removal by scavengers or being overlooked by researchers, resulting in an estimated collision rate of 8.2 collisions per km per month. We observed a small (9.6%) but significant decrease in the number of casualties after line marking compared to before line marking in experimental lines. This was not observed in control lines. We found no influence of either marker size (large vs. small spirals, sample of distribution lines only) or power line type (transmission vs. distribution, sample of large spirals only) on the collision rate when we analyzed all species together. However, great bustard mortality was slightly lower when lines were marked with large spirals and in transmission lines after marking. Conclusions: Our results confirm the overall effectiveness of wire marking as a way to reduce, but not eliminate, bird collisions with power lines. If raw field data are not corrected by carcass losses due to scavengers and missed observations, findings may be biased. The high cost of this conservation measure suggests a need for more studies to improve its application, including wire marking with non-visual devices. Our findings suggest that different species may respond differently to marking, implying that species-specific patterns should be explored, at least for species of conservation concern.We thank A. Garcıa Fernandez and M. Carrasco for their assistance during the field work. We also thank J. Camaño and J. Velasco of HENARSA, and the electric companies Iberdrola, Union Fenosa and Red Electrica de España for their cooperation. S. Young reviewed the English. RB was contracted within the project CGL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation and later supported by a postdoctoral grant from Junta de Comunidades de Castilla-La Mancha. C. Ponce, C. Palacın, CM and BM were supported by contracts CSICHENARSA. This study was carried out within the Preventive, corrective and compensatory measures to balance the impact of the M-50 and R-2 highways on the population of great bustards and other steppe-land birds in the Important Bird Area Talamanca-Camarma and the Site of Community Importance Cuenca de los rıos Jarama y Henares, supported by a contract HENARSA-CSIC. Additional financial support was provided by project GL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis

The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia-reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic downregulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for <i>in vivo</i> use

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London