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

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

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

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

Modeling of crack propagation in weak snowpack layers using the discrete element method

Dry-snow slab avalanches are generally caused by a sequence of fracture processes including (1) failure initiation in a weak snow layer underlying a cohesive slab, (2) crack propagation within the weak layer and (3) tensile fracture through the slab which leads to its detachment. During the past decades, theoretical and experimental work has gradually led to a better understanding of the fracture process in snow involving the collapse of the structure in the weak layer during fracture. This now allows us to better model failure initiation and the onset of crack propagation, i.e., to estimate the critical length required for crack propagation. On the other hand, our understanding of dynamic crack propagation and fracture arrest propensity is still very limited. To shed more light on this issue, we performed numerical propagation saw test (PST) experiments applying the discrete element (DE) method and compared the numerical results with field measurements based on particle tracking. The goal is to investigate the influence of weak layer failure and the mechanical properties of the slab on crack propagation and fracture arrest propensity. Crack propagation speeds and distances before fracture arrest were derived from the DE simulations for different snowpack configurations and mechanical properties. Then, in order to compare the numerical and experimental results, the slab mechanical properties (Young's modulus and strength) which are not measured in the field were derived from density. The simulations nicely reproduced the process of crack propagation observed in field PSTs. Finally, the mechanical processes at play were analyzed in depth which led to suggestions for minimum column length in field PSTs