146 research outputs found
Transfer of Communication Skills to the Workplace during Clinical Rounds : Impact of a Program for Residents
peer reviewe
Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)
Background: The English National Health Service has made a major investment in nine partnerships between
higher education institutions and local health services called Collaborations for Leadership in Applied Health
Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and
implement research through sustained interactions between academics and health services. CLAHRCs provide a
natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery.
This protocol describes an externally funded evaluation that focuses on implementation mechanisms and
processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances.
Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which
deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see
it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual
framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to
Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth
comparative case studies of research implementation using multiple data collection methods including
interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of
data collection. We will test the wider applicability of emerging findings with a wider community using an
interpretative forum.
Discussion: The idea that collaboration between academics and services might lead to more applicable health
research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is
limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for
implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g.,
Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge
translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts
particularly with respect to integrated stakeholder involvement
Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer
The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4–5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct “epochs”, or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system
The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells
The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug
Coevolution between a Family of Parasite Virulence Effectors and a Class of LINE-1 Retrotransposons
Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota) are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVRk1 powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVRk1 gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1) the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2) the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome
'I believe that the staff have reduced their closeness to patients': an exploratory study on the impact of HIV/AIDS on staff in four rural hospitals in Uganda
<p>Abstract</p> <p>Background</p> <p>Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff.</p> <p>Methods</p> <p>A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews.</p> <p>Results</p> <p>HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences.</p> <p>Conclusion</p> <p>HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process.</p
Roles of ecdysteroids for progression of reproductive cycle in the fresh water crustacean Daphnia magna
Microarray-Based Transcriptomic Analysis of Differences between Long-Term Gregarious and Solitarious Desert Locusts
Desert locusts (Schistocerca gregaria) show an extreme form of phenotypic plasticity and can transform between a cryptic solitarious phase and a swarming gregarious phase. The two phases differ extensively in behavior, morphology and physiology but very little is known about the molecular basis of these differences. We used our recently generated Expressed Sequence Tag (EST) database derived from S. gregaria central nervous system (CNS) to design oligonucleotide microarrays and compare the expression of thousands of genes in the CNS of long-term gregarious and solitarious adult desert locusts. This identified 214 differentially expressed genes, of which 40% have been annotated to date. These include genes encoding proteins that are associated with CNS development and modeling, sensory perception, stress response and resistance, and fundamental cellular processes. Our microarray analysis has identified genes whose altered expression may enable locusts of either phase to deal with the different challenges they face. Genes for heat shock proteins and proteins which confer protection from infection were upregulated in gregarious locusts, which may allow them to respond to acute physiological challenges. By contrast the longer-lived solitarious locusts appear to be more strongly protected from the slowly accumulating effects of ageing by an upregulation of genes related to anti-oxidant systems, detoxification and anabolic renewal. Gregarious locusts also had a greater abundance of transcripts for proteins involved in sensory processing and in nervous system development and plasticity. Gregarious locusts live in a more complex sensory environment than solitarious locusts and may require a greater turnover of proteins involved in sensory transduction, and possibly greater neuronal plasticity
A realist approach to eliciting the initial programme theory of the antiretroviral treatment adherence club intervention in the Western Cape Province, South Africa
BACKGROUND: The successful initiation of people living with HIV/AIDS on antiretroviral therapy (ART) in South Africa has
engendered challenges of poor retention in care and suboptimal adherence to medication. The adherence club
intervention was implemented in the Metropolitan area of the Western Cape Province to address these challenges. The
adherence club programme has shown potential to relieve clinic congestion, improve retention in care and
enhance treatment adherence in the context of rapidly growing HIV patient populations being initiated on ART.
Nevertheless, how and why the adherence club intervention works is not clearly understood. We aimed to elicit an
initial programme theory as the first phase of the realist evaluation of the adherence club intervention in the Western
Cape Province.
METHODS: The realist evaluation approach guided the elicitation study. First, information was obtained from an exploratory
qualitative study of programme designers’ and managers’ assumptions of the intervention. Second, a document review of
the design, rollout, implementation and outcome of the adherence clubs followed. Third, a systematic review of available
studies on group-based ART adherence support models in Sub-Saharan Africa was done, and finally, a scoping review of
social, cognitive and behavioural theories that have been applied to explain adherence to ART. We used the
realist evaluation heuristic tool (Intervention-context-actors-mechanism-outcome) to synthesise information from the
sources into a configurational map. The configurational mapping, alignment of a specific combination of attributes,
was based on the generative causality logic – retroduction.
RESULTS: We identified two alternative theories: The first theory supposes that patients become encouraged,
empowered and motivated, through the adherence club intervention to remain in care and adhere to the treatment.
The second theory suggests that stable patients on ART are being nudged through club rules and regulations
to remain in care and adhere to the treatment with the goal to decongest the primary health care facilities.
CONCLUSION: The initial programme theory describes how (dynamics) and why (theories) the adherence club
intervention is expected to work. By testing theories in “real intervention cases” using the realist evaluation
approach, the theories can be modified, refuted and/or reconstructed to elicit a refined theory of how and
why the adherence club intervention works
The evolutionary significance of polyploidy
Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity
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