Further insights into aspects of the EU illicit drugs market: summaries and key findings

This publication presents key findings and summaries of selected reports from the study ‘Further insights into aspects of the EU illicit drugs market’ (Trautmann, Kilmer and Turnbull, forthcoming 2013), which provides an analysis of characteristics and operations of the EU’s illicit drugs market, as called for by the European Commission. This study is a follow-up of the earlier European Commission study, which presented an analysis of the developments of the global illicit drug markets, the drug problems and drug policy responses in the period 1998-2007 (Reuter and Trautmann 2009). The discussions of that study resulted in a number of further research questions. Some of the questions considered most important by the European Commission have been put together in a call for a further analysis of the EU illicit drugs market and responses to it, focusing on a number of aspects in the following four areas: A. An analysis of specific characteristics, mechanisms and factors that govern the EU illicit drugs market, including a conceptual framework for thinking about the structure of drug suppliers in the EU, an assessment whether there have been significant shifts in how drugs are supplied in the EU and an assessment of the extent to which drug suppliers are involved in different drugs and other criminal activities. B. A detailed analysis of the size and share of the EU illicit drug market, providing an estimate of the volume of the ‘EU market’ in illicit drugs (production and trafficking), providing an estimate of the profits generated by this market, analysing whether the EU drugs market is more supply or demand driven and exploring various aspects of drug use: user types, availability and consumption estimates. C. A detailed analysis of a number of potential policy impacts on the EU drug market(s) in recent years, assessing the impact of opioid substitution treatment (OST) on the European heroin market and the impact of policy changes on two EU drug markets. D. Scanning the future – trends in the market and policy responses, exploring expert views on future key trends of the illicit drug markets and policy responses in the EU

Long-term variations in the net inflow record for Lake Malawi

Lake Malawi is the third largest lake in Africa and plays an important role in water supply, hydropower generation, agriculture and fisheries in the region. Lake level observations started in the 1890s and anecdotal evidence of variations dates back to the early 1800s. A chronology of lake level and outflow variations is presented together with updated estimates for the net inflow to the lake. The inflow series and selected rainfall records were also analysed using an unobserved component approach and, although there was little evidence of long-term trends, there was some indication of increasing interannual variability in recent decades. A weak quasi-periodic behaviour was also noted with a period of approximately 4–8 years. The results provide useful insights into the severity of drought and flood events in the region since the 1890s and the potential for seasonal forecasting of lake levels and outflows

A functional correlate of severity in alternating hemiplegia of childhood

OBJECTIVE: Mutations in ATP1A3, the gene that encodes the α3 subunit of the Na(+)/K(+) ATPase, are the primary cause of alternating hemiplegia of childhood (AHC). Correlations between different mutations and AHC severity were recently reported, with E815K identified in severe and D801N and G947R in milder cases. This study aims to explore the molecular pathological mechanisms in AHC and to identify functional correlates for mutations associated with different levels of disease severity. METHODS: Human wild type ATP1A3, and E815K, D801N and G947R mutants were expressed in Xenopus laevis oocytes and Na(+)/K(+) ATPase function measured. Structural homology models of the human α3 subunit containing AHC mutations were created. RESULTS: The AHC mutations examined all showed similar levels of reduction in forward cycling. Wild type forward cycling was reduced by coexpression with any mutant, indicating dominant negative interactions. Proton transport was measured and found to be selectively impaired only in E815K. Homology modeling showed that D801 and G947 lie within or near known cation binding sites while E815 is more distal. Despite its effect on proton transport, E815K was also distant from the proposed proton transport route. INTERPRETATION: Loss of forward cycling and dominant negativity are common and likely necessary pathomechanisms for AHC. In addition, loss of proton transport correlated with severity of AHC. D801N and G947R are likely to directly disrupt normal Na(+)/K(+) binding while E815K may disrupt forward cycling and proton transport via allosteric mechanisms yet to be elucidated

Long-term variations in the net inflow record for Lake Malawi

Lake Malawi is the third largest lake in Africa and plays an important role in water supply, hydropower generation, agriculture and fisheries in the region. Lake level observations started in the 1890s and anecdotal evidence of variations dates back to the early 1800s. A chronology of lake level and outflow variations is presented together with updated estimates for the net inflow to the lake. The inflow series and selected rainfall records were also analysed using an unobserved component approach and, although there was little evidence of long-term trends, there was some indication of increasing interannual variability in recent decades. A weak quasi-periodic behaviour was also noted with a period of approximately 4–8 years. The results provide useful insights into the severity of drought and flood events in the region since the 1890s and the potential for seasonal forecasting of lake levels and outflows

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

Selecting CMIP5 GCMs for downscaling over multiple regions

The unprecedented availability of 6-hourly data from a multi-model GCM ensemble in the CMIP5 data archive presents the new opportunity to dynamically downscale multiple GCMs to develop high-resolution climate projections relevant to detailed assessment of climate vulnerability and climate change impacts. This enables the development of high resolution projections derived from the same set of models that are used to characterise the range of future climate changes at the global and large-scale, and as assessed in the IPCC AR5. However, the technical and human resource required to dynamically-downscale the full CMIP5 ensemble are significant and not necessary if the aim is to develop scenarios covering a representative range of future climate conditions relevant to a climate change risk assessment. This paper illustrates a methodology for selecting from the available CMIP5 models in order to identify a set of 8–10 GCMs for use in regional climate change assessments. The selection focuses on their suitability across multiple regions—Southeast Asia, Europe and Africa. The selection (a) avoids the inclusion of the least realistic models for each region and (b) simultaneously captures the maximum possible range of changes in surface temperature and precipitation for three continental-scale regions. We find that, of the CMIP5 GCMs with 6-hourly fields available, three simulate the key regional aspects of climate sufficiently poorly that we consider the projections from those models ‘implausible’ (MIROC-ESM, MIROC-ESM-CHEM, and IPSL-CM5B-LR). From the remaining models, we demonstrate a selection methodology which avoids the poorest models by including them in the set only if their exclusion would significantly reduce the range of projections sampled. The result of this process is a set of models suitable for using to generate downscaled climate change information for a consistent multi-regional assessment of climate change impacts and adaptation

Pure iterative reconstruction improves image quality in computed tomography of the abdomen and pelvis acquired at substantially reduced radiation doses in patients with active Crohn disease

Objective: We assessed diagnostic accuracy and image quality of modified protocol (MP) computed tomography (CT) of the abdomen and pelvis reconstructed using pure iterative reconstruction (IR) in patients with Crohn disease (CD). Methods: Thirty-four consecutive patients with CD were referred with suspected extramural complications. Two contemporaneous CT datasets were acquired in all patients: standard protocol (SP) and MP. The MP and SP protocols were designed to impart radiation exposures of 10% to 20% and 80% to 90% of routine abdominopelvic CT, respectively. The MP images were reconstructed with model-based IR (MBIR) and adaptive statistical IR (ASIR). Results: The MP-CT and SP-CT dose length product were 88 (58) mGy.cm (1.27 [0.87] mSv) and 303 [204] mGy.cm (4.8 [2.99] mSv), respectively (P < 0.001). Median diagnostic acceptability, spatial resolution, and contrast resolution were significantly higher and subjective noise scores were significantly lower on SP-ASIR 40 compared with all MP datasets. There was perfect clinical agreement between MP-MBIR and SP-ASIR 40 images for detection of extramural complications. Conclusions: Modified protocol CT using pure IR is feasible for assessment of active CD

Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios

Purpose: Despite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification of new gene–disease associations. Methods: We analyzed 119 trios to identify both diagnostic genotypes in known genes and candidate genotypes in novel genes. We considered qualifying genotypes based on their population frequency and in silico predicted effects we also characterized the patterns of genotypes enriched among this collection of patients. Results: We obtained a genetic diagnosis for 29 (24%) of our patients. We showed that patients carried an excess of damaging de novo mutations in intolerant genes, particularly those shown to be essential in mice (P = 3.4 × 10−8). This enrichment is only partially explained by mutations found in known disease-causing genes. Conclusion: This work indicates that the application of appropriate bioinformatics analyses to clinical sequence data can also help implicate novel disease genes and suggest expanded phenotypes for known disease genes. These analyses further suggest that some cases resolved by whole-exome sequencing will have direct therapeutic implications