Background
Alcohol use disorder (AUD) is a highly prevalent public health problem associated with considerable individual and societal costs. Abstinence from alcohol is the most widely accepted ...target of treatment for AUD, but it severely limits treatment options and could deter individuals who prefer to reduce their drinking from seeking treatment. Clinical validation of reduced alcohol consumption as the primary outcome of alcohol clinical trials is critical for expanding treatment options. One potentially useful measure of alcohol treatment outcome is a reduction in the World Health Organization (WHO, International Guide for Monitoring Alcohol Consumption and Related Harm. Geneva, Switzerland, 2000) risk levels of alcohol use (very high risk, high risk, moderate risk, and low risk). For example, a 2‐shift reduction in WHO risk levels (e.g., high risk to low risk) has been used by the European Medicines Agency (2010, Guideline on the Development of Medicinal Products for the Treatment of Alcohol Dependence. UK) to evaluate nalmefene as a treatment for alcohol dependence (AD; Mann et al. 2013, Biol Psychiatry 73, 706–13).
Methods
The current study was a secondary data analysis of the COMBINE study (n = 1,383; Anton et al., ) to examine the association between reductions in WHO risk levels and reductions in alcohol‐related consequences and mental health symptoms during and following treatment in patients with AD.
Results
Any reduction in WHO risk drinking level during treatment was associated with significantly fewer alcohol‐related consequences and improved mental health at the end of treatment and for up to 1 year posttreatment. A greater reduction in WHO risk drinking level predicted a greater reduction in consequences and greater improvements in mental health.
Conclusions
Changes in WHO risk levels appear to be a valid end point for alcohol clinical trials. Based on the current findings, reductions in WHO risk drinking levels during treatment reflect meaningful reductions in alcohol‐related consequences and improved functioning.
As a chronic disorder, the optimal management of alcohol dependence should include reductions in alcohol consumption. The World Health Organization (WHO) risk levels provide targets for alcohol risk reduction that are strongly associated with meaningful reductions in alcohol‐related consequences. This figure shows the average Drinker Inventory of Consequences (DrInC) total scores by change in WHO risk level from baseline to end of treatment (left figure) and one year posttreatment (right figure).
A crucial limit to measurement efficiencies of superconducting circuits comes from losses involved when coupling to an external quantum amplifier. Here, we realize a device circumventing this problem ...by directly embedding an artificial atom, comprised of a transmon qubit, within a flux-pumped Josephson parametric amplifier. This configuration is able to enhance dispersive measurement without exposing the qubit to appreciable excess backaction. Near-optimal backaction is obtained by engineering the circuit to permit high-power operation that reduces information loss to unmonitored channels associated with the amplification and squeezing of quantum noise. By mitigating the effects of off-chip losses downstream, the on-chip gain of this device produces end-to-end measurement efficiencies of up to 80%. Our theoretical model accurately describes the observed interplay of gain and measurement backaction and delineates the parameter space for future improvement. The device is compatible with standard fabrication and measurement techniques and, thus, provides a route for definitive investigations of fundamental quantum effects and quantum control protocols.
AIM: To investigate the utility of scintigraphic studies in predicting response to laparoscopic fundoplication(LF) for chronic laryngopharyngeal reflux symptoms.METHODS: Patients with upper ...aero-digestive symptoms that remained undiagnosed after a period of 2 mo were studied with conventional p H and manometric studies. Patients mainly complained of cough, sore throat, dysphonia and globus. These patients were imaged after ingestion of 99m-technetium diethylene triamine pentaacetic acid. Studies were quantified with time activity curves over the pharynx, upper and lower oesophagus and background. Late studies of the lungs were obtained for aspiration. Patients underwent LF with post-operative review at 3 mo after surgery.RESULTS: Thirty four patients(20 F, 14 M) with an average age of 57 years and average duration of symptoms of 4.8 years were studied. Twenty four hour p H and manometry studies were abnormal in all patients. On scintigraphy, 27/34 patients demonstrated pharyngeal contamination and a rising or flat pharyngeal curve. Lung aspiration was evident in 50% of patients. There was evidence of pulmonary aspiration in 17 of 34 patients in the delayed study(50%). Pharyngeal contamination was found in 27 patients. All patients with aspiration showed pharyngeal contamination. In the 17 patients with aspiration, graphical time activity curve showed rising activity in the pharynx in 9 patients and a flat curve in 8 patients. In those 17 patients without pulmonary aspiration, 29%(5 patients) had either a rising or flat pharyngeal graph. A rising or flat curve predicted aspiration with a positive predictive value of 77% and a negative predictive valueof 100%. Over 90% of patients reported a satisfactory symptomatic response to LF with an acceptable sideeffect profile. CONCLUSION: Scintigraphic reflux studies offer a good screening tool for pharyngeal contamination and aspiration in patients with gastroesophageal reflux disease.
Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal ...dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data.
We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease.
We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS.
MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy.
•Day’s sensation-seeking independent from day’s urgency was associated with day’s risk-taking and alcohol use.•Few self-reported risky behaviors were threatening to safety, health, or ...wellbeing.•Young adults’ risk-taking and alcohol use in daily life is more likely to be driven by the desire to experience novel and stimulating sensations than by rash action.
To examine the dynamic expression of sensation-seeking and urgency in daily life and the implications for alcohol use and risk-taking during young adulthood.
Daily diary surveys were administered to young adults (n = 77) aged 18–25 years every evening for 21 days to assess day’s sensation-seeking, urgency, risk-taking, and alcohol use.
Days of higher than usual sensation-seeking are also days of higher than usual risk-taking and are more likely to be alcohol use days than days of lower than usual sensation-seeking. Day’s urgency was not associated with day’s alcohol use or risk-taking. We extracted 10 themes from self-reports of the day’s riskiest behavior: transportation (29.9%), social (22.8%), recreation (17.4%), work (14.8%), school (13.5%), food (9.5%), sleep (9.2%), substance use (5.8%), other (5.2%), and jaywalking (1.5%), and 14.6% of self-reported risky behaviors were considered threatening to safety, health, or wellbeing.
Risks taken during daily life have mostly positive outcomes and a minority represent threats to safety, health, and wellbeing. Risk-taking and alcohol use in young adult’s daily lives is more likely to be driven by the desire to experience novel and exciting experiences than by rash action.
Pathogenesis of Atherosclerosis Falk, Erling
Journal of the American College of Cardiology,
04/2006, Letnik:
47, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Pathogenesis of Atherosclerosis
Erling Falk
Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease of medium-sized and large arteries fuelled by lipid. The most devastating ...consequences of atherosclerosis, such as heart attack and stroke, are caused by superimposed thrombosis. Approximately 76% of all fatal coronary thrombi are precipitated by plaque rupture. Ruptured plaques are characterized by a large lipid-rich core, a thin fibrous cap that contains few smooth muscle cells and many macrophages, angiogenesis, adventitial inflammation, and outward remodeling. Thus, ruptured plaques and, by inference, rupture-prone plaques have characteristic pathoanatomical features that might be useful for their detection in vivo by imaging.
Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease of medium-sized and large arteries fuelled by lipids. Endothelial cells, leukocytes, and intimal smooth muscle cells are the major players in the development of this disease. The most devastating consequences of atherosclerosis, such as heart attack and stroke, are caused by superimposed thrombosis. Therefore, the vital question is not why atherosclerosis develops but rather why atherosclerosis, after years of indolent growth, suddenly becomes complicated with luminal thrombosis. If thrombosis-prone plaques could be detected and thrombosis averted, atherosclerosis would be a much more benign disease. Approximately 76% of all fatal coronary thrombi are precipitated by plaque rupture. Plaque rupture is a more frequent cause of coronary thrombosis in men (∼80%) than in women (∼60%). Ruptured plaques are characterized by a large lipid-rich core, a thin fibrous cap that contains few smooth muscle cells and many macrophages, angiogenesis, adventitial inflammation, and outward remodeling. Plaque rupture is the most common cause of coronary thrombosis. Ruptured plaques and, by inference, rupture-prone plaques have characteristic pathoanatomical features that might be useful for their detection in vivo by imaging. This article describes the pathogenesis of atherosclerosis, how it begets thrombosis, and the possibility to detect thrombosis-prone plaques and prevent heart attack.
In disciplines outside of communication, papers with women as first and last (i.e. senior) authors attract fewer citations than papers with men in those positions. Using data from 14 communication ...journals from 1995 to 2018, we find that reference lists include more papers with men as first and last author, and fewer papers with women as first and last author, than would be expected if gender were unrelated to referencing. This imbalance is driven largely by the citation practices of men and is slowly decreasing over time. The structure of men's co-authorship networks partly accounts for the observed over-citation of men by other men. We discuss ways researchers might approach gendered citations in their work.
DNA double strand breaks (DSBs) in repetitive sequences are a potent source of genomic instability, owing to the possibility of non-allelic homologous recombination (NAHR). Repetitive sequences are ...especially at risk during meiosis, when numerous programmed DSBs are introduced into the genome to initiate meiotic recombination. In the repetitive ribosomal DNA (rDNA) array of the budding yeast Saccharomyces cerevisiae, meiotic DSB formation is prevented in part through Sir2-dependent heterochromatin formation. Here we show that the edges of the rDNA array are exceptionally susceptible to meiotic DSBs, revealing an inherent heterogeneity in the rDNA array. We find that this localized DSB susceptibility necessitates a border-specific protection system consisting of the meiotic ATPase Pch2 and the origin recognition complex subunit Orc1. Upon disruption of these factors, DSB formation and recombination increased specifically in the outermost rDNA repeats, leading to NAHR and rDNA instability. Notably, the Sir2-dependent heterochromatin of the rDNA itself was responsible for the induction of DSBs at the rDNA borders in pch2Δ cells. Thus, although the activity of Sir2 globally prevents meiotic DSBs in the rDNA, it creates a highly permissive environment for DSB formation at the junctions between heterochromatin and euchromatin. Heterochromatinized repetitive DNA arrays are abundant in most eukaryotic genomes. Our data define the borders of such chromatin domains as distinct high-risk regions for meiotic NAHR, the protection of which may be a universal requirement to prevent meiotic genome rearrangements that are associated with genomic diseases and birth defects.
SNO+ is a large liquid scintillator-based experiment located 2 km underground at SNOLAB, Sudbury, Canada. It reuses the Sudbury Neutrino Observatory detector, consisting of a 12 m diameter acrylic ...vessel which will be filled with about 780 tonnes of ultra-pure liquid scintillator. Designed as a multipurpose neutrino experiment, the primary goal of SNO+ is a search for the neutrinoless double-beta decay (0νββ) of 130Te. In Phase I, the detector will be loaded with 0.3% natural tellurium, corresponding to nearly 800 kg of 130Te, with an expected effective Majorana neutrino mass sensitivity in the region of 55–133 meV, just above the inverted mass hierarchy. Recently, the possibility of deploying up to ten times more natural tellurium has been investigated, which would enable SNO+ to achieve sensitivity deep into the parameter space for the inverted neutrino mass hierarchy in the future. Additionally, SNO+ aims to measure reactor antineutrino oscillations, low energy solar neutrinos, and geoneutrinos, to be sensitive to supernova neutrinos, and to search for exotic physics. A first phase with the detector filled with water will begin soon, with the scintillator phase expected to start after a few months of water data taking. The 0νββ Phase I is foreseen for 2017.
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