944 research outputs found
Prohibition on research involving psychiatric patients subject to coercion
This paper compares legislation on clinical research conducted on patients subject to coercion in the Scandinavian countries and the UK, examines it from a human rights perspective, and problematizes the Danish legal model as the only one employing a total ban on this kind of research. Reference is made to the consequences to evidence-based psychiatric care improvements and international ethical principle statements generally entitling psychiatric patients to treatment under similar ethical and scientific conditions as patients with other illnesses, given the absolute premise that the patient does not object to research participation and always retains the right to withdraw
Long-term glycaemic control with metformin– sulphonylurea–pioglitazone triple therapy in PROactive (PROactive 17)
peer reviewedAims We assessed the long-term glycaemic effects and the safety profile of triple therapy with the addition of pioglitazone vs. placebo in patients with Type 2 diabetes treated with combined metformin–sulphonylurea therapy in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive).
Methods In a post-hoc analysis, we identified patients treated with metformin plus sulphonylurea combination therapy and not receiving insulin at baseline (n = 1314). In those patients, we compared the effects of pioglitazone (force-titrated to 45 mg⁄ day, n = 654) vs. placebo (n = 660) on glycated haemoglobin (HbA1c) reduction, concomitant changes in medications
and initiation of permanent insulin use (defined as daily insulin use for a period of ‡ 90 days or ongoing use at death ⁄ final visit).
Results Significantly greater reductions in HbA1c and greater proportions of patients with HbA1c at target were noted with pioglitazone vs, placebo, despite a decrease in the use of other oral glucose-lowering agents. Therewas an approximate twofold increase in progression to permanent insulin use in the placebo group vs. the pioglitazone group: 31.1 vs. 16.1%, respectively,
when added to combination therapy. The overall safety of themetformin–sulphonylurea–pioglitazone triple therapy was good.
Conclusions Intensifying an existing dual oral therapy regimen to a triple oral regimen by adding pioglitazone to the classical metformin–sulphonylurea combination resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The advantages and disadvantages of adding pioglitazone instead of adding basal insulin should be assessed
further
Evolutionary relationships of Aurora kinases: Implications for model organism studies and the development of anti-cancer drugs
BACKGROUND: As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family. RESULTS: Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A. CONCLUSIONS: In this study, we found that invertebrate Aurora-A and Aurora-B kinases are highly divergent protein families from their chordate counterparts. Furthermore, while the Aurora-A family is ubiquitous among all vertebrates, the Aurora-B and Aurora-C families in humans arose from a gene duplication event in mammals. These findings show the importance of understanding evolutionary relationships in the interpretation and transference of knowledge from studies of model organism systems to human cellular biology. In addition, given the important role of Aurora kinases in cancer, evolutionary analysis and comparisons of ATP-binding domains suggest a rationale for designing dual action anti-tumor drugs that inhibit both Aurora-B and Aurora-C kinases
Factors Affecting the Degradation Processes for Dextran
Author Institution: Departments of Bacteriology and Chemistry, The Ohio State University, Columbus 1
Quantum Chessboards in the Deuterium Molecular Ion
We present a new algorithm for vibrational control in deuterium molecules
that is feasible with current experimental technology. A pump mechanism is used
to create a coherent superposition of the D2+ vibrations. A short, intense
infrared control pulse is applied after a chosen delay time to create selective
interferences. A `chessboard' pattern of states can be realized in which a set
of even- or odd-numbered vibrational states can be selectively annihilated or
enhanced. A technique is proposed for experimental realization and observation
of this effect using 5 fs pulses of 790 nm radiation, with intermediate
intensity (5e13 W/cm2)Comment: 12 pages, 5 figure
Mapping surface hoar from near-infrared texture in a laboratory
Surface hoar crystals are snow grains that form when water vapor deposits on the snow surface. Once buried, surface hoar creates a weak layer in the snowpack that can later cause large avalanches to occur. The formation and persistence of surface hoar are highly spatiotemporally variable, making its detection difficult. Remote-sensing technology capable of detecting the presence and spatial distribution of surface hoar would be beneficial for avalanche forecasting, but this capability has yet to be developed. Here, we hypothesize that near-infrared (NIR) texture, defined as the spatial variability of reflectance magnitude, may produce an optical signature unique to surface hoar due to the distinct shape and orientation of the grains. We tested this hypothesis by performing reflectance experiments in a controlled cold laboratory environment to evaluate the potential and accuracy of surface hoar mapping from NIR texture using a near-infrared hyperspectral imager (NIR-HSI) and a lidar operating at 1064 nm. We analyzed 41 snow samples, three of which were surface hoar and 38 of which consisted of other grain morphologies. When using NIR-HSI under direct and diffuse illumination, we found that surface hoar displayed higher NIR texture relative to all other grain shapes across numerous spectral bands and a wide range of spatial resolutions (0.5–50 mm). Due to the large number of spectral- and spatial-resolution combinations, we conducted a detailed samplewise case study at 1324 nm spectral and 10 mm spatial resolution. The case study resulted in the median texture of surface hoar being 1.3 to 8.6 times greater than that of the 38 other samples under direct and diffuse illumination (p < 0.05 in all cases). Using lidar, surface hoar also exhibited significantly increased NIR texture in 30 out of 38 samples, but only at select (5–25 mm) spatial resolutions. Leveraging these results, we propose a simple binary classification algorithm to map the extent of surface hoar on a pixelwise basis using both the NIR-HSI and lidar instruments. The NIR-HSI under direct and diffuse illumination performed best, with a median accuracy of 96.91 % and 97.37 %, respectively. Conversely, the median classification accuracy achieved with lidar was only 66.99 %. Further, to assess the repeatability of our method and demonstrate its mapping capacity, we ran the algorithm on a new sample with mixed microstructures, with an accuracy of 99.61 % and 96.15 % achieved using NIR-HSI under direct and diffuse illumination, respectively. As NIR-HSI detectors become increasingly available, our findings demonstrate the potential of a new tool for avalanche forecasters to remotely assess the spatiotemporal variability of surface hoar, which would improve avalanche forecasts and potentially save lives.</p
Hydrography and circulation in the Filchner Depression, Weddell Sea, Antarctica
Cold and dense ice shelf water (ISW) emerging from the Filchner-Ronne Ice Shelf cavity in the southwestern Weddell Sea flows northward through the Filchner Depression to eventually descend the con- tinental slope and contribute to the formation of bottom water. New ship-born observations of hydrogra- phy and currents from Filchner Depression in January 2013 suggest that the northward flow of ISW takes place in a middepth jet along the eastern flank of the depression, thus questioning the traditional view with outflow along the western flank. This interpretation of the data is supported by results from a regional numerical model, which shows that ISW flowing northward along the eastern coast of Berkner Island turns eastward and crosses the depression to its eastern side upon reaching the Filchner ice front. The ice front represents a sudden change in the thickness of the water column and thus a potential vorticity barrier. Transport estimates of northward ISW flux based on observations ranges from 0.2 to 1.0 Sv.publishedVersio
Quality of care for patients with type 2 diabetes in general practice according to patients' ethnic background: a cross-sectional study from Oslo, Norway
<p>Abstract</p> <p>Background</p> <p>In recent decades immigration to Norway from Asia, Africa and Eastern Europe has increased rapidly. The aim of this study was to assess the quality of care for type 2 diabetes mellitus (T2DM) patients from these ethnic minority groups compared with the care received by Norwegians.</p> <p>Methods</p> <p>In 2006, electronic medical record data were screened at 11 practices (49 GPs; 58857 patients). 1653 T2DM patients cared for in general practice were identified. Ethnicity was defined as self-reported country of birth. Chi-squared tests, one-way ANOVAs, multiple regression, linear mixed effect models and generalized linear mixed models were used.</p> <p>Results</p> <p>Diabetes was diagnosed at a younger age in patients from the ethnic minority groups (South Asians (SA): mean age 44.9 years, Middle East/North Africa (MENA): 47.2 years, East Asians (EA): 52.0 years, others: 49.0 years) compared with Norwegians (59.7 years, p < 0.001). HbA1c, systolic blood pressure (SBP) and s-cholesterol were measured in >85% of patients in all groups with minor differences between minority groups and Norwegians. A greater proportion of the minority groups were prescribed hypoglycaemic medications compared with Norwegians (≥79% vs. 72%, p < 0.001). After adjusting for age, gender, diabetes duration, practice and physician unit, HbA1c (geometric mean) for Norwegians was 6.9% compared to 7.3-7.5% in the minority groups (p < 0.05). The proportion with poor glycaemic control (HbA1c > 9%) was higher in minority groups (SA: 19.6%, MENA: 18.9% vs. Norwegians: 5.6%, p < 0.001. No significant ethnic differences were found in the proportions reaching the combined target: HbA1c ≤ 7.5%, SBP ≤ 140 mmHg, diastolic blood pressure (DBP) ≤ 85 mmHg and total s-cholesterol ≤5.0 mmol/L (Norwegians: 25.5%, SA: 24.9%, MENA: 26.9%, EA: 26.1%, others:17.5%).</p> <p>Conclusions</p> <p>Mean age at the time of diagnosis of T2DM was 8-15 years younger in minority groups compared with Norwegians. Recording of important processes of care measures is high in all groups. Only one in four of most patient groups achieved all four treatment targets and prescribing habits may be sub-optimal. Patients from minority groups have worse glycaemic control than Norwegians which implies that it might be necessary to improve the guidelines to meet the needs of specific ethnic groups.</p
MARCH WET AVALANCHE PREDICTION AT BRIDGER BOWL SKI AREA, MONTANA
ABSTRACT: Few avalanche forecast models are tailored specifically for wet avalanche forecasting. Bridger Bowl (intermountain climate) is a good area to develop a wet avalanche probability model. The primary archived data consists of eight variables. The archived data for March from 1968 to 2001 (1996 data unavailable) were used to develop 68 predictor variables related to temperature, snowpack settlement, and precipitation. The original dataset was divided into days with snowfall in the past 48 hours (new snow) and days without (old snow). There were 33 significant old snow variables and 22 significant new snow variables. Six variables are common to both old and new snow. The best predictor variables for old and new snow are different. The variables were analyzed with binomial logistic regression to produce probability models for old snow and for new snow wet avalanche conditions. The old snow model uses the prediction day minimum temperature and the two-day change in total snow depth as predictor variables and has a 89% overall success rate. However, the majority of this success is due to correct prediction of days without wet avalanches (96% of all correct predictions). The new snow model uses the prediction day minimum temperature and three-day cumulative new snow water equivalent as predictor variables, but is less useful. The models are applicable only to Bridger Bowl. The numerical forecast models can be used as one of the tools in the forecasting toolbox but limited data and complexity of process require that the decisions about closure remain in the hands of the ski patrol
MARCH WET AVALANCHE PREDICTION AT BRIDGER BOWL SKI AREA, MONTANA
ABSTRACT: Few avalanche forecast models are tailored specifically for wet avalanche forecasting. Bridger Bowl (intermountain climate) is a good area to develop a wet avalanche probability model. The primary archived data consists of eight variables. The archived data for March from 1968 to 2001 (1996 data unavailable) were used to develop 68 predictor variables related to temperature, snowpack settlement, and precipitation. The original dataset was divided into days with snowfall in the past 48 hours (new snow) and days without (old snow). There were 33 significant old snow variables and 22 significant new snow variables. Six variables are common to both old and new snow. The best predictor variables for old and new snow are different. The variables were analyzed with binomial logistic regression to produce probability models for old snow and for new snow wet avalanche conditions. The old snow model uses the prediction day minimum temperature and the two-day change in total snow depth as predictor variables and has a 89% overall success rate. However, the majority of this success is due to correct prediction of days without wet avalanches (96% of all correct predictions). The new snow model uses the prediction day minimum temperature and three-day cumulative new snow water equivalent as predictor variables, but is less useful. The models are applicable only to Bridger Bowl. The numerical forecast models can be used as one of the tools in the forecasting toolbox but limited data and complexity of process require that the decisions about closure remain in the hands of the ski patrol
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