Facilitating access to voluntary and community services for patients with psychosocial problems: a before-after evaluation

Background: Patients with psychosocial problems may benefit from a variety of community, educational, recreational and voluntary sector resources, but GPs often under-refer to these through lack of knowledge and time. This study evaluated the acceptability and effectiveness of graduate primary care mental health workers (GPCMHWs) facilitating access to voluntary and community sector services for patients with psychosocial problems. Methods: Patients with psychosocial problems from 13 general practices in London were referred to a GPCMHW Community Link scheme providing information and support to access voluntary and community resources. Patient satisfaction, mental health and social outcomes, and use of primary care resources, were evaluated. Results: 108 patients consented to take part in the study. At three-month follow-up, 63 (58%) had made contact with a community service identified as suitable for their needs. Most were satisfied with the help provided by the GPCMHW in identifying and supporting access to a suitable service. There was a reduction in the number of patients with a probable mental health problem on the GHQ-12 from 83% to 52% (difference 31% (95% CI, 17% – 44%). Social adjustment improved and frequencies of primary care consultations and of prescription of psychotropic medications were reduced. Conclusion: Graduates with limited training in mental health and no prior knowledge of local community resources can help patients with psychosocial problems access voluntary and community services, and patients value such a scheme. There was some evidence of effectiveness in reducing psychosocial and mental health problems

The development of social class sensitive proxies for infant mortality at the PCT level: An appraisal of candiate indicators for the commission for health improvement

The main aim of the work is to identify social class-sensitive proxies for infant mortality at Primary Care Trust level that could be used in the CHI performance ratings process for PCTs in 2003/4

Genomic, Evolutionary and Functional Analyses of Diapause in Drosophila Melanogaster

Understanding the genetic basis of adaptation has been and remains to be one major goal of ecological and evolutionary genetics. The variation in diapause propensity in the model organism Drosophila melanogaster represents different life-history strategies underlying adaptation to regular and widespread environmental heterogeneity, thus provides an ideal model to study the genetic control of ecologically important complex phenotype. This work employs global genomic and transcriptomic approaches to identify genetic polymorphisms co-segregating with diapause propensity, as well as genes that are differentially regulated at the transcriptional level as a function of the diapause phenotype. I show that genetic polymorphisms co-segregating with diapause propensity are found throughout all major chromosomes, demonstrating that diapause is a multi-genic trait. I show that diapause in D. melanogaster is an actively regulated phenotype at the transcriptional level, suggesting that diapause is not a simple physiological or reproductive quiescence. I also demonstrate that genetic polymorphisms co-segregating with diapause propensity, as well as genes differentially expressed as a function of diapause are enriched for clinally varying and seasonal oscillating SNPs, supporting the hypothesis that natural variation in diapause propensity underlies adaptation to spatially and temporally varying selective pressures. In addition to global genomic and transcriptomic screens, I also performed functional analysis of one candidate polymorphism on the gene Crystalllin, which represents an intersection of multiple global screens related to seasonal adaptation. I show that this polymorphism affects patterns of gene expression and a subset of fitness-related phenotypes including diapause, in an environment-specific manner. Taken together, this work provide a holistic view of the genetic basis of a complex trait underlying climatic adaptation in wild populations of D. melanogaster, linking genetic polymorphism, gene regulation, organismal phenotype, population dynamics and environmental parameters

Genomic, Evolutionary and Functional Analyses of Diapause in Drosophila Melanogaster

Understanding the genetic basis of adaptation has been and remains to be one major goal of ecological and evolutionary genetics. The variation in diapause propensity in the model organism Drosophila melanogaster represents different life-history strategies underlying adaptation to regular and widespread environmental heterogeneity, thus provides an ideal model to study the genetic control of ecologically important complex phenotype. This work employs global genomic and transcriptomic approaches to identify genetic polymorphisms co-segregating with diapause propensity, as well as genes that are differentially regulated at the transcriptional level as a function of the diapause phenotype. I show that genetic polymorphisms co-segregating with diapause propensity are found throughout all major chromosomes, demonstrating that diapause is a multi-genic trait. I show that diapause in D. melanogaster is an actively regulated phenotype at the transcriptional level, suggesting that diapause is not a simple physiological or reproductive quiescence. I also demonstrate that genetic polymorphisms co-segregating with diapause propensity, as well as genes differentially expressed as a function of diapause are enriched for clinally varying and seasonal oscillating SNPs, supporting the hypothesis that natural variation in diapause propensity underlies adaptation to spatially and temporally varying selective pressures. In addition to global genomic and transcriptomic screens, I also performed functional analysis of one candidate polymorphism on the gene Crystalllin, which represents an intersection of multiple global screens related to seasonal adaptation. I show that this polymorphism affects patterns of gene expression and a subset of fitness-related phenotypes including diapause, in an environment-specific manner. Taken together, this work provide a holistic view of the genetic basis of a complex trait underlying climatic adaptation in wild populations of D. melanogaster, linking genetic polymorphism, gene regulation, organismal phenotype, population dynamics and environmental parameters

Optimising the use of ICTs by health & social care professionals in the community

This research was commissioned as part of the Department of Health's Information and Communication Technology (ICT) Research Initiative, to identify ways in which ICTs might provide benefits to health and social care professionals working across boundaries and to the clients/ patients that they serve. The project aimed to examine the use of existing ICTs in supporting isolated users in the community (principally professionals but also lay users), and to consider ways in which use of such ICTs might be improved, focusing initially on non-person identifiable information. A single patient group was selected as the main focus of the study - older people (and their carers). This group was chosen because the needs of older people and their carers reflect those of the wider isolated populations served by health and social welfare professionals in terms of their clinical, psychological and social care needs. Other isolated groups might include the physically disabled, the mentally ill, or those socially and potentially service isolated through geography, lifestyles or other factors. Older people would be represented in all these categories. Therefore, a study focusing on the information needs of professionals who support older patients or clients should provide findings that are generalisable to other groups, such as those mentioned above. Furthermore, it was evident that this is an important group on which to focus in terms of inter-agency working because of the various policy initiatives that aim to enhance working between professionals across the health and social care interface in relation to older people

A Rapid and Sensitive Method for Measuring NAcetylglucosaminidase Activity in Cultured Cells

A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG) activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB) due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4- Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG), in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB), a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in enzyme replacement therapy, gene therapy, and combination therapies

Improving the quality of extreme precipitation estimates using satellite passive microwave rainfall retrievals

2017 Summer.Includes bibliographical references.Satellite rainfall estimates are invaluable in assessing global precipitation. As a part of the Global Precipitation Measurement (GPM) mission, a constellation of orbiting sensors, dominated by passive microwave imagers, provides a full coverage of the planet approximately every 2-3 hours. Several decades of development have resulted in passive microwave rainfall retrievals that are indispensable in addressing global precipitation climatology. However, this prominent achievement is often overshadowed by the retrieval's performance at finer spatial and temporal scales, where large variability in cloud morphology poses an obstacle for accurate rainfall measurements. This is especially true over land, where rainfall estimates are based on an observed mean relationship between high frequency (e.g., 89 GHz) brightness temperature (Tb) depression (i.e., the ice-scattering signature) and rainfall rate. In the first part of this study, an extreme precipitation event that caused historical flooding over south-east Europe is analyzed using the GPM constellation. Performance of the rainfall retrieval is evaluated against ground radar and gage reference. It is concluded that satellite observations fully address the temporal evolution of the event but greatly underestimate total rainfall accumulation (by factor of 2.5). A primary limitation of the rainfall algorithm is found to be its inability to recognize variability in precipitating system structure. This variability is closely related to the structure of the precipitation regime and the large-scale environment. To address this influence of rainfall physics on the overall retrieval bias, the second part of this study utilizes TRMM radar (PR) and radiometer (TMI) observations to first confirm that the Tb-to-rain-rate relationship is governed by the amount of ice in the atmospheric column. Then, using the Amazon and Central African regions as testbeds, it demonstrates that the amount of ice aloft is strongly linked to a precipitation regime. A correlation found between the large-scale environment and precipitation regimes is then further examined. Variables such as Convective Available Potential Energy (CAPE), Cloud Condensation Nuclei (CCN), wind shear, and vertical humidity profiles are found to be capable of predicting a precipitation regime and explaining up to 40% of climatological biases. Dry over moist air conditions are favorable for developing intense, well organized systems such as MCSs in West Africa and the Sahel. These systems are characterized by strong Tb depressions and above average amounts of ice aloft. As a consequence, microwave retrieval algorithms misinterpret these non-typical systems assigning them unrealistically high rainfall rates. The opposite is true in the Amazon region, where observed raining systems exhibit relatively little ice while producing high rainfall rates. Based on these findings, in the last part of the study, the GPM operational retrieval (GPROF) for the GMI sensor is modified to offer additional information on atmospheric conditions to its Bayesian-based algorithm. When forming an estimate, the modified algorithm is allowed to use this ancillary information to filter out a priori states that do not match the general environmental condition relevant to the observation and thus reduce the difference between the assumed and observed variability in ice-to-rain ratio. The results are compared to the ground Multi-Radar Multi-Sensor (MRMS) network over the US at various spatial and temporal scales demonstrating outstanding potentials in improving the accuracy of rainfall estimates from satellite-borne passive microwave sensors over land