Modeling alcohol use disorder severity: An integrative structural equation modeling approach

Background: Alcohol dependence is a complex psychological disorder whose phenomenology changes as the disorder progresses. Neuroscience has provided a variety of theories and evidence for the development, maintenance, and severity of addiction; however, clinically, it has been difficult to evaluate alcohol use disorder (AUD) severity.Objective: This study seeks to evaluate and validate a data-driven approach to capturing alcohol severity in a community sample.Method: Participants were non-treatment seeking problem drinkers (n = 283). A structural equation modeling approach was used to (a) verify the latent factor structure of the indices of AUD severity; and (b) test the relationship between the AUD severity factor and measures of alcohol use, affective symptoms, and motivation to change drinking.Results: The model was found to fit well, with all chosen indices of AUD severity loading significantly and positively onto the severity factor. In addition, the paths from the alcohol use, motivation, and affective factors accounted for 68% of the variance in AUD severity. Greater AUD severity was associated with greater alcohol use, increased affective symptoms, and higher motivation to change.Conclusion: Unlike the categorical diagnostic criteria, the AUD severity factor is comprised of multiple quantitative dimensions of impairment observed across the progression of the disorder. The AUD severity factor was validated by testing it in relation to other outcomes such as alcohol use, affective symptoms, and motivation for change. Clinically, this approach to AUD severity can be used to inform treatment planning and ultimately to improve outcomes. © 2013 Moallem, Courtney, Bacio and Ray

Risks and benefits of oxygen therapy

Mootha and Chinnery review the risks and benefits of oxygen administration in mitochondrial disease. They highlight probable harm from hyperoxia and possible benefit from hypoxia. At first sight this is counter-intuitive. It seems improbable that reducing the availability of a substrate that enables high-energy phosphate production via oxidative phosphorylation would be of benefit. But recent clinical data beyond the field of inherited metabolic disease support this approach

Evaluating Maintainability Prejudices with a Large-Scale Study of Open-Source Projects

Exaggeration or context changes can render maintainability experience into prejudice. For example, JavaScript is often seen as least elegant language and hence of lowest maintainability. Such prejudice should not guide decisions without prior empirical validation. We formulated 10 hypotheses about maintainability based on prejudices and test them in a large set of open-source projects (6,897 GitHub repositories, 402 million lines, 5 programming languages). We operationalize maintainability with five static analysis metrics. We found that JavaScript code is not worse than other code, Java code shows higher maintainability than C# code and C code has longer methods than other code. The quality of interface documentation is better in Java code than in other code. Code developed by teams is not of higher and large code bases not of lower maintainability. Projects with high maintainability are not more popular or more often forked. Overall, most hypotheses are not supported by open-source data.Comment: 20 page

A powerful bursting radio source towards the Galactic Centre

Transient astronomical sources are typically powered by compact objects and usually signify highly explosive or dynamic events. While radio astronomy has an impressive record of obtaining high time resolution observations, usually it is achieved in quite narrow fields-of-view. Consequently, the dynamic radio sky is poorly sampled, in contrast to the situation in the X- and gamma-ray bands in which wide-field instruments routinely detect transient sources. Here we report a new transient source, GCRT J1745-3009, detected in 2002 during a moderately wide-field radio transient monitoring program of the Galactic center (GC) region at 0.33 GHz. The characteristics of its bursts are unlike those known for any other class of radio transient. If located in or near the GC, its brightness temperature (~10^16 K) and the implied energy density within GCRT J1745-3009 vastly exceeds that observed in most other classes of radio astronomical sources, and is consistent with coherent emission processes rarely observed. We conclude that GCRT J1745-3009 is the first member of a new class of radio transient sources, the first of possibly many new classes to be identified through current and upcoming radio surveys.Comment: 16 pages including 3 figures. Appears in Nature, 3 March 200

Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

ACL reconstruction with unicondylar replacement in knee with functional instability and osteoarthritis

Severe symptomatic osteoarthritis in young and active patients with pre-existing deficiency of the anterior cruciate ligament and severe functionally instability is a difficult subgroup to manage. There is considerable debate regarding management of young patients with isolated unicompartment osteoarthritis and concomitant ACL deficiency. A retrospective analysis of was done in 9 patients with symptomatic osteoarthritis with ACL deficiencies and functional instability that were treated with unicompartment knee arthroplasty and ACL reconstruction between April 2002 and June 2005. The average arc of flexion was 119° (range 85° to 135°) preoperatively and 125° (range 105° to 140°). There were no signs of instability during the follow up of patients. No patients in this group were reoperated. In this small series we have shown that instability can be corrected and pain relieved by this combined procedure

NSAID Use Selectively Increases the Risk of Non-Fatal Myocardial Infarction: A Systematic Review of Randomised Trials and Observational Studies

Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.NSAID therapy carried a RR of 1.30 (95% CI, 1.20-1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89-1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%-42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%-98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04-2.50) and 0.86 (95% CI 0.51-1.47) for fatal MIs.NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi

The exceptional value of intact forest ecosystems

As the terrestrial human footprint continues to expand, the amount of native forest that is free from significant damaging human activities is in precipitous decline. There is emerging evidence that the remaining intact forest supports an exceptional confluence of globally significant environmental values relative to degraded forests, including imperilled biodiversity, carbon sequestration and storage, water provision, indigenous culture and the maintenance of human health. Here we argue that maintaining and, where possible, restoring the integrity of dwindling intact forests is an urgent priority for current global efforts to halt the ongoing biodiversity crisis, slow rapid climate change and achieve sustainability goals. Retaining the integrity of intact forest ecosystems should be a central component of proactive global and national environmental strategies, alongside current efforts aimed at halting deforestation and promoting reforestation