73 research outputs found

    Characteristics of general practice care: What do senior citizens value? A qualitative study

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    <p>Abstract</p> <p>Background</p> <p>In view of the increasing number of senior citizens in our society who are likely to consult their GP with age-related health problems, it is important to identify and understand the preferences of this group in relation to the non-medical attributes of GP care. The aim of this study is to improve our understanding about preferences of this group of patients in relation to non-medical attributes of primary health care. This may help to develop strategies to improve the quality of care that senior citizens receive from their GP.</p> <p>Methods</p> <p>Semi-structured interviews (N = 13) with senior citizens (65-91 years) in a judgement sample were recorded and transcribed verbatim. The analysis was conducted according to qualitative research methodology and the frame work method.</p> <p>Results</p> <p>Continuity of care providers, i.e. GP and practice nurses, GPs' expertise, trust, free choice of GP and a kind open attitude were highly valued. Accessibility by phone did not meet the expectations of the interviewees. The interviewees had difficulties with the GP out-of-office hours services. Spontaneous home visits were appreciated by some, but rejected by others. They preferred to receive verbal information rather than collecting information from leaflets. Distance to the practice and continuity of caregiver seemed to conflict for respondents.</p> <p>Conclusions</p> <p>Preferences change in the process of ageing and growing health problems. GPs and their co-workers should be also aware of the changing needs of the elderly regarding non-medical attributes of GP care. Meeting their needs regarding non-medical attributes of primary health care is important to improve the quality of care.</p

    Distinct Merkel Cell Polyomavirus Molecular Features in Tumour and Non Tumour Specimens from Patients with Merkel Cell Carcinoma

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    Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease

    Miz1 Is a Critical Repressor of cdkn1a during Skin Tumorigenesis

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    The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15Ink4), cdkn1a (p21Cip1), and cdkn1c (p57Kip2). Whether Miz1-mediated repression is important for control of cell proliferation in vivo and for tumor formation is unknown. Here we show that deletion of the Miz1 POZ domain, which is critical for Miz1 function, restrains the development of skin tumors in a model of chemically-induced, Ras-dependent tumorigenesis. While the stem cell compartment appears unaffected, interfollicular keratinocytes lacking functional Miz1 exhibit a reduced proliferation and an accelerated differentiation of the epidermis in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Tumorigenesis, proliferation and normal differentiation are restored in animals lacking cdkn1a, but not in those lacking cdkn2b. Our data demonstrate that Miz1-mediated attenuation of cell cycle arrest pathways via repression of cdkn1a has a critical role during tumorigenesis in the skin

    Quantitative Analysis of Viral Load per Haploid Genome Revealed the Different Biological Features of Merkel Cell Polyomavirus Infection in Skin Tumor

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    Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen’s disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119–42.8) and AK (0.02–0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection

    Processes, sediments, and stratigraphy of the Fly River Delta

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    Voluminous rainfall and rugged, tectonically active mountains are two primary ingredients that make Indo-Pacific islands incredible suppliers of sediment to the ocean. It is estimated that six islands alone (Papua New Guinea (PNG), Sulawesi, Borneo, Sumatra, Java, Timor) supply 20–25% of the total annual sediment load transported to the ocean globally (Milliman et al., 1999). Many rivers draining these islands discharge onto broad, low-gradient continental shelves characterized by large tidal ranges, and these are locations for tide-dominated deltas. The Fly River of PNG is one example

    Dynamics of hypersaline coastal waters in the Great Barrier Reef

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    The coastal waters of the Great Barrier Reef (GBR) are hypersaline (salinity ~ 37) during the dry season as a result of evaporation greatly exceeding rainfall, of shallow waters, and of the presence of numerous bays along the coast preventing rapid flushing. These hypersaline waters are not flushed out by salinity-driven baroclinic currents because these waters are vertically well-mixed. Instead these waters are transported by a longshore residual current and thus form a coastal boundary layer of hypersaline waters. As a result the hypersalinity distribution is 2-D with both cross-shelf and longshore gradients of salinity. The cross-shelf gradients are largely controlled by turbulent diffusion, while the longshore gradients are controlled by the residual currents that transport hypersaline waters longshore south ward in the central and southern regions of the GBR. Because every bay supplies hypersaline waters, the width of the coastal hypersaline layer increases southwards. Steady state is reached in about 100 days, which is the typical duration of the dry season. The dynamics of the GBR hypersaline coastal boundary layer thus differ from the classical inverse hypersaline systems, e.g. in Saloum River Estuary, Laguna San Ignacio, Mission Bay, Tomales Bay, San Diego Bay, Hervey Bay, Shark Bay, Coorong Coast Lagoon, Spencer Gulf, Gulf of California and many others where the salinity gradient is mainly 1-D with a dominant along-channel salinity gradient

    The age and the flushing time of the Great Barrier Reef Waters

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    A numerical model of the Great Barrier Reef (GBR) was verified using water current data from twenty sites, and applied to estimate the flushing time and age of waters. These timescales were calculated under different wind and oceanic inflow conditions. The age of oceanic waters intruding in the GBR was estimated to be between 3 and 5 months on leaving the GBR, depending on the location; the largest residence time prevailed in the southern GBR matrix where the age was the highest within the high density reef matrix, indicating veering of the mean currents around the GBR matrix. The flushing time depends on the size of the domain, and was estimated to be 67 days for the whole central GBR. For the flushing of coastal waters the wind had two effects. Firstly, it increased the flushing times by generating wind-driven currents, transporting some water back to the source; this process is comparable to that of an estuary, where water that leaves the estuary at ebb tide may return at flood tide, a process parameterized by the return coefficient. The return coefficient in the GBR due to wind reversals may be as large as 50% at the timescale of the wind. Secondly, in the southern and central regions of the GBR, the southeasterly tradewind deflected the southward flowing oceanic inflow seaward, away from the inner shelf and towards the outer shelf, making room for a wind-driven current of opposite direction on the inner shelf. Thus the intrusion of oceanic water in the GBR depends on the wind over the GBR. The veering of the mean currents around the GBR reef matrix and the wind over the shelf influencing the oceanic circulation demonstrate small scales (the GBR shelf) influencing the large scale oceanic circulation

    Contaminant exchange rates in estuaries – New formulae accounting for advection and dispersion

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    The transport timescales of water in an estuary are important measurements for monitoring pollution threats to the estuarine ecosystem. In this study we re-evaluated the application of simple analytical solutions to estimate these timescales and found that the Land Ocean Interaction Costal Zone model (LOICZ) uses similar equation as from the fresh water fraction model, and thus often resulting in shortened transport timescales. Therefore, the LOICZ model is neither based upon the well-known Knudsen relation nor Fischer formulation. Three transport timescales, namely water renewal, residence time and exposure time were calculated using analytical solutions for a range of estuaries worldwide. The analytical results were compared with available estimates of residence times from numerical models. The theoretical formulation from the LOICZ, the fresh water fraction model, and a newly proposed modified LOICZ model were used to calculate water renewal. Residence times and exposure times were calculated using the Constituent-oriented Age and Residence time Theory (CART). The modified LOICZ model was found to be the most comparable to residence times from numerical models, with r2 ∼ 0.7. In addition to the proposed modified LOICZ model (which uses Fischer formulation), we have developed an advection–dispersion timescale diagram. This graphic conceptual model provides a visual representation of the relative contribution of advective and dispersive processes to water renewal for different estuaries. Estuaries can be categorized as either dominated by dispersion, dominated by advection, or having dispersion and advection of similar magnitud
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