The effects of chloroplast lipids on the stability of liposomes during freezing and drying

AbstractChloroplast thylakoids contain four classes of lipids, monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyldiacylglycerol (SQDG), and phosphatidylglycerol (cpPG). We have investigated the effects of these lipids on the stability of large unilamellar vesicles made from egg phosphatidylcholine (EPC), by substitution of different fractions of EPC in the membranes by the various chloroplast lipids. Damage to liposomes after freezing to −18°C was measured as carboxyfluorescein leakage or fusion between vesicles. The presence of all chloroplast lipids increased leakage. However, the maximum amount of leakage and the concentration dependence were dramatically different between the different lipids. Only SQDG induced vesicle fusion, while the non-bilayer lipid MGDG did not. The presence of MGDG in the membranes led to more leakage than the presence of another non-bilayer lipid, egg phosphatidylethanolamine (EPE). In EPE-containing liposomes, leakage was strongly associated with fusion. Combinations of different chloroplast lipids had an additive effect on leakage induced by freezing. Most of the leakage from galactolipid-containing vesicles occurred during the first 15min of freezing at −18°C. After a 3h incubation period, most leakage occurred between 0°C and −10°C. Lowering the temperature to −22°C had only a small additional effect. Incubation of liposomes at −10°C in the presence of 2.5M NaCl without ice crystallization, approximately the same concentration obtained by freezing to −10°C, resulted in very little leakage. Air drying of liposomes to low water contents resulted in massive leakage, both from pure EPC vesicles and from vesicles containing galactolipids. The latter vesicles showed more leakage at any given water content than EPC vesicles

Interventions for mental health problems in children and adults with severe intellectual disabilities: a systematic review

Objective Mental health problems are more prevalent in people with than without intellectual disabilities, yet treatment options have received little attention. The aim of this study was to identify and evaluate the effectiveness of pharmacological and psychological interventions in the treatment of mental health problems in children and adults with severe and profound intellectual disabilities, given their difficulties in accessing standard mental health interventions, particularly talking therapies, and difficulties reporting drug side effects. Design A systematic review using electronic searches of PsycINFO, PsycTESTS, EMBASE, MEDLINE, CINAHL, ERIC, ASSIA, Science Citation Index, Social Science Citation Index and CENTRAL was conducted to identify eligible intervention studies. Study selection, data extraction and quality appraisal were performed by two independent reviewers. Participants Study samples included at least 70% children and/or adults with severe or profound intellectual disabilities or reported the outcomes of this subpopulation separate from participants with other levels of intellectual disabilities. Interventions Eligible intervention studies evaluated a psychological or pharmacological intervention using a control condition or pre-post design. Outcomes Symptom severity, frequency or other quantitative dimension (e.g., impact), as assessed with standardised measures of mental health problems. Results We retrieved 41 232 records, reviewed 573 full-text articles and identified five studies eligible for inclusion: three studies evaluating pharmacological interventions, and two studies evaluating psychological interventions. Study designs ranged from double-blind placebo controlled crossover trials to single-case experimental reversal designs. Quality appraisals of this very limited literature base revealed good experimental control, poor reporting standards and a lack of follow-up data. Conclusions Mental ill health requires vigorous treatment, yet the current evidence base is too limited to identify with precision effective treatments specifically for children or adults with severe and profound intellectual disabilities. Clinicians therefore must work on the basis of general population evidence, while researchers work to generate more precise evidence for people with severe and profound intellectual disabilities

Satellite content and quenching of star formation in galaxy groups at z ~ 1.8

We study the properties of satellites in the environment of massive star-forming galaxies at z ~ 1.8 in the COSMOS field, using a sample of 215 galaxies on the main sequence of star formation with an average mass of ~1011M⊙. At z> 1.5, these galaxies typically trace halos of mass ≳1013M⊙. We use optical-near-infrared photometry to estimate stellar masses and star formation rates (SFR) of centrals and satellites down to ~ 6 × 109M⊙. We stack data around 215 central galaxies to statistically detect their satellite halos, finding an average of ~3 galaxies in excess of the background density. We fit the radial profiles of satellites with simple β-models, and compare their integrated properties to model predictions. We find that the total stellar mass of satellites amounts to ~68% of the central galaxy, while spectral energy distribution modeling and far-infrared photometry consistently show their total SFR to be 25-35% of the central's rate. We also see significant variation in the specific SFR of satellites within the halo with, in particular, a sharp decrease at <100 kpc. After considering different potential explanations, we conclude that this is likely an environmental signature of the hot inner halo. This effect can be explained in the first order by a simple free-fall scenario, suggesting that these low-mass environments can shut down star formation in satellites on relatively short timescales of ~0.3 Gyr

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris

Objective: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. Methods: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). Results: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. Conclusions: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS/DESIGN PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE

Measurement tools for mental health problems and mental well-being in people with severe or profound intellectual disabilities : a systematic review

Mental health problems affect people with intellectual disabilities (ID) at rates similar to or in excess of the non-ID population. People with severe ID are likely to have persistent mental health problems. In this systematic review (PROSPERO 2015:CRD42015024469), we identify and evaluate the methodological quality of available measures of mental health problems or well-being in individuals with severe or profound ID. Electronic searches of ten databases identified relevant publications. Two reviewers independently reviewed titles and abstracts of retrieved records (n = 41,232) and full-text articles (n = 573). Data were extracted and the quality of included papers was appraised. Thirty-two papers reporting on 12 measures were included. Nine measures addressed a broad spectrum of mental health problems, and were largely observational. One physiological measure of well-being was included. The Aberrant Behaviour Checklist, Diagnostic Assessment for the Severely Handicapped Scale-II and Mood, Interest and Pleasure Questionnaire are reliable measures in this population. However, the psychometric properties of six other measures were only considered within a single study – indicating a lack of research replication. Few mental health measures are available for people with severe or profound ID, particularly lacking are tools measuring well-being. Assessment methods that do not rely on proxy reports should be explored further

Study design for development of novel safety biomarkers of drug-induced liver injury by the translational safety biomarker pipeline (TransBioLine) consortium: a study protocol for a nested case–control study

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative’s TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped cases and controls with biological samples during liver injury progression to facilitate biomarker discovery, evaluation, validation and qualification.In a nested case–control design, patients who meet one of these criteria, alanine transaminase (ALT) ≥ 5 × the upper limit of normal (ULN), alkaline phosphatase ≥ 2 × ULN or ALT ≥ 3 ULN with total bilirubin > 2 × ULN, are enrolled. After completed clinical investigations, Roussel Uclaf Causality Assessment and expert panel review are used to adjudicate episodes as DILI or alternative liver diseases (acute non-DILI controls). Two blood samples are taken: at recruitment and follow-up. Sample size is as follows: 300 cases of DILI and 130 acute non-DILI controls. Additional cross-sectional cohorts (1 visit) are as follows: Healthy volunteers (n = 120), controls with chronic alcohol-related or non-alcoholic fatty liver disease (n = 100 each) and patients with psoriasis or rheumatoid arthritis (n = 100, 50 treated with methotrexate) are enrolled. Candidate biomarkers prioritised for evaluation include osteopontin, glutamate dehydrogenase, cytokeratin-18 (full length and caspase cleaved), macrophage-colony-stimulating factor 1 receptor and high mobility group protein B1 as well as bile acids, sphingolipids and microRNAs. The TransBioLine project is enabling biomarker discovery and validation that could improve detection, diagnostic accuracy and prognostication of DILI in premarketing clinical trials and for clinical healthcare application

An evaluation of a model for the systematic documentation of hospital based health promotion activities: results from a multicentre study

BACKGROUND: The first step of handling health promotion (HP) in Diagnosis Related Groups (DRGs) is a systematic documentation and registration of the activities in the medical records. So far the possibility and tradition for systematic registration of clinical HP activities in the medical records and in patient administrative systems have been sparse. Therefore, the activities are mostly invisible in the registers of hospital services as well as in budgets and balances.A simple model has been described to structure the registration of the HP procedures performed by the clinical staff. The model consists of two parts; first part includes motivational counselling (7 codes) and the second part comprehends intervention, rehabilitation and after treatment (8 codes).The objective was to evaluate in an international study the usefulness, applicability and sufficiency of a simple model for the systematic registration of clinical HP procedures in day life. METHODS: The multi centre project was carried out in 19 departments/hospitals in 6 countries in a clinical setup. The study consisted of three parts in accordance with the objectives.A: Individual test. 20 consecutive medical records from each participating department/hospital were coded by the (coding) specialists at local department/hospital, exclusively (n = 5,529 of 5,700 possible tests in total).B: Common test. 14 standardized medical records were coded by all the specialists from 17 departments/hospitals, who returned 3,046 of 3,570 tests.C: Specialist evaluation. The specialists from the 19 departments/hospitals evaluated if the codes were useful, applicable and sufficient for the registration in their own department/hospital (239 of 285). RESULTS: A: In 97 to 100% of the local patient pathways the specialists were able to evaluate if there was documentation of HP activities in the medical record to be coded.B: Inter rater reliability on the use of the codes were 93% (57 to 100%) and 71% (31 to 100%), respectively.C: The majority of the study participants found the codes to be useful (71%), applicable (92%) and sufficient (92%). CONCLUSION: Systematic registration of HP activities is relevant in clinical day life and the suggested codes proved to be applicable for international use. HP is an essential part of the clinical pathway or the value chain. This model promises to improve the documentation and thereby facilitate analysis of records for evidence based medicine as well as cost and policy analyses