A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety

Utilization of internet-delivered cognitive behavioural therapy (iCBT) for treating depression and anxiety disorders in stepped-care models, such as the UK’s Improving Access to Psychological Therapies (IAPT), is a potential solution for addressing the treatment gap in mental health. We investigated the effectiveness and cost-effectiveness of iCBT when fully integrated within IAPT stepped-care settings. We conducted an 8-week pragmatic randomized controlled trial with a 2:1 (iCBT intervention: waiting-list) allocation, for participants referred to an IAPT Step 2 service with depression and anxiety symptoms (Trial registration: ISRCTN91967124). The primary outcomes measures were PHQ-9 (depressive symptoms) and GAD-7 (anxiety symptoms) and WSAS (functional impairment) as a secondary outcome. The cost-effectiveness analysis was based on EQ-5D-5L (preference-based health status) to elicit the quality-adjust life year (QALY) and a modified-Client Service Receipt Inventory (care resource-use). Diagnostic interviews were administered at baseline and 3 months. Three-hundred and sixty-one participants were randomized (iCBT, 241; waiting-list, 120). Intention-to-treat analyses showed significant interaction effects for the PHQ-9 (b = −2.75, 95% CI −4.00, −1.50) and GAD-7 (b = −2.79, 95% CI −4.00, −1.58) in favour of iCBT at 8-week and further improvements observed up to 12-months. Over 8-weeks the probability of cost-effectiveness was 46.6% if decision makers are willing to pay £30,000 per QALY, increasing to 91.2% when the control-arm’s outcomes and costs were extrapolated over 12-months. Results indicate that iCBT for depression and anxiety is effective and potentially cost-effective in the long-term within IAPT. Upscaling the use of iCBT as part of stepped care could help to enhance IAPT outcomes. The pragmatic trial design supports the ecological validity of the findings

The injury epidemiology of cyclists based on a road trauma registry

<p>Abstract</p> <p>Background</p> <p>Bicycle use has increased in some of France's major cities, mainly as a means of transport. Bicycle crashes need to be studied, preferably by type of cycling. Here we conduct a descriptive analysis.</p> <p>Method</p> <p>A road trauma registry has been in use in France since 1996, in a large county around Lyon (the Rhône, population 1.6 million). It covers outpatients, inpatients and fatalities. All injuries are coded using the Abbreviated Injury Scale (AIS). Proxies were used to identify three types of cycling: learning = children (0-10 years old); sports cycling = teenagers and adults injured outside towns; cycling as means of transport = teenagers and adults injured in towns. The study is based on 13,684 cyclist casualties (1996-2008).</p> <p>Results</p> <p>The percentage of cyclists injured in a collision with a motor vehicle was 8% among children, 17% among teenagers and adults injured outside towns, and 31% among those injured in towns. The percentage of serious casualties (MAIS 3+) was 4.5% among children, 10.9% among adults injured outside towns and 7.2% among those injured in towns. Collisions with motor-vehicles lead to more internal injuries than bicycle-only crashes.</p> <p>Conclusion</p> <p>The description indicates that cyclist type is associated with different crash and injury patterns. In particular, cyclists injured in towns (where cycling is increasing) are generally less severely injured than those injured outside towns for both types of crash (bicycle-only crashes and collisions with a motor vehicle). This is probably due to lower speeds in towns, for both cyclists and motor vehicles.</p

Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods

ФИЗИОЛОГИЧЕСКИЙ СТАТУС ЛАКТИРУЮЩИХ ГОЛШТИНСКИХ КОРОВ В УСЛОВИЯХ СИБИРИ

The authors found out the differentiation of animals according to hematological and biochemical indicators in the herd ofHolsteincows in spring and summer. Variability of characteristics varied from 7.6 to 36.9%; it was the lowest one according to the number of erythrocytes, hemoglobulin and blood serum crude protein. All the indicators varied more in autumn whereas quantitative characteristics of hematological status didn’t vary significantly in autumn except the growing number of erythrocytes. The authors observed the following tendency in respect to biochemical indicators of protein, fat and carbohydrate metabolism. The authors found out that slight reducing of features variability in autumn, the concentration of total protein and glucose in blood serum rose. That was explained by seasonal peculiarities of animal feeding. Population analysis found out the features that mostly have deviations from the norm. About 93% of animals had lower concentration hemoglobin in spring and about 84% of cows had lower number of erythrocytes. The authors observed higher concentration of cholesterol in half herd of cows in spring and autumn. Favourable changes in concentration of total protein occurred in autumn. The most part of animals had less active glutamyl pyruvic transaminase (GPT) in all the seasons of the year. In spring glutamyl pyruvic transaminase, effect and alkaline phosphatase effect was stringer effect was stronger and exceeded the norm in 57 and 20% of animals. The analysis of hematological and biochemical indicators has shown that their level and variation in blood depends on a season at different degrees. This occurs due to feeding factors and overall health. The issue on parameters of physiological status and their confirmation to the standards must be clarified depending upon a breed, productivity and physiological statusВ стаде голштинских коров выявлена дифференциация животных по гематологическим и биохимическим характеристикам крови в весенний и осенний периоды. Изменчивость признаков варьировала от 7,6 до 36,9% и была наименьшей по количеству эритроцитов, гемоглобина, общего белка сыворотки крови. Практически по всем гематологическим показателям коэффициент вариации возрастал в осенний период. В то же время среди количественных характеристик гематологического статуса достоверных сезонных изменений, за исключением роста содержания эритроцитов в осенний период, не выявлено. В отношении биохимических показателей, характеризующих белковый, жировой и углеводный обмен, наблюдалась следующая тенденция. При некотором снижении вариабельности признаков в осенний период отмечен достоверный рост содержания общего белка и глюкозы в сыворотке крови, что, очевидно, связано с сезонными особенностями кормления животных. Популяционный анализ позволил установить признаки, по которым наиболее часто наблюдаются отклонения от границ нормы. Отмечено, что до 93% животных имели содержание гемоглобина в весенний период ниже показателей, приведенных другими авторами. В этот же сезон почти у 84% коров был снижен уровень эритроцитов. Отмечено превышение количества холестерина у половины коров и в осенний, и в весенний период. Благоприятные изменения произошли в осенний период по содержанию общего белка. Большинство животных характеризовались пониженной активностью аланинаминотрансферазы (АЛТ) во все сезоны года. В весенний сезон активность аспартатаминотрансферазы (АСТ) и щелочной фосфатазы (ЩФ) была выше нормы соответственно у 57 и 20% особей. Таким образом, анализ гематологических и биохимических показателей показал, что их уровень и изменчивость в крови лактирующих коров в разной степени подвержены сезонным колебаниям. Очевидной причиной этого могут быть кормовые факторы и общее состояние организма, в связи с чем необходимо обратить внимание на обеспечение стабильности технологии. Вопрос о соответствии параметров физиологического статуса нормам требует уточнения в зависимости от породы, продуктивности и физиологического состояния животных

Immunoscreening of the extracellular proteome of colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.</p> <p>Methods</p> <p>For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.</p> <p>Results</p> <p>From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.</p> <p>Conclusions</p> <p>Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.</p

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage