Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Static stretching of the hamstring muscle for injury prevention in football codes: a systematic review

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future

A mediation approach to understanding socio-economic inequalities in maternal health-seeking behaviours in Egypt.

BACKGROUND: The levels and origins of socio-economic inequalities in health-seeking behaviours in Egypt are poorly understood. This paper assesses the levels of health-seeking behaviours related to maternal care (antenatal care [ANC] and facility delivery) and their accumulation during pregnancy and childbirth. Secondly, it explores the mechanisms underlying the association between socio-economic position (SEP) and maternal health-seeking behaviours. Thirdly, it examines the effectiveness of targeting of free public ANC and delivery care. METHODS: Data from the 2008 Demographic and Health Survey were used to capture two latent constructs of SEP: individual socio-cultural capital and household-level economic capital. These variables were entered into an adjusted mediation model, predicting twelve dimensions of maternal health-seeking; including any ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more visits during pregnancy), facility delivery, and private delivery. ANC and delivery care costs were examined separately by provider type (public or private). RESULTS: While 74.2% of women with a birth in the 5-year recall period obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the complete maternal care package (timely and regular facility-based ANC as well as facility delivery) for their most recent live birth. Both socio-cultural capital and economic capital were independently positively associated with receiving any ANC and delivering in a facility. The strongest direct effect of socio-cultural capital was seen in models predicting private provider use of both ANC and delivery. Despite substantial proportions of women using public providers reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge public care was not effectively targeted to women with lowest economic resources. CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to inequalities in maternal health-seeking in Egypt. Future studies should therefore examine the objective and perceived quality of care from different types of providers. Improvements in the targeting of free public care could help reduce the existing SEP-based inequalities in maternal care coverage in the short term

Ocean stratification and low melt rates at the Ross Ice Shelf grounding zone

Ocean‐driven melting of ice shelves is a primary mechanism for ice loss from Antarctica. However, due to the difficulty in accessing the sub‐ice shelf ocean cavity, the relationship between ice shelf melting and ocean conditions is poorly understood, particularly near the grounding zone, where the ice transitions from grounded to floating. We present the first borehole oceanographic observations from the grounding zone of the Ross Ice Shelf, Antarctica's largest ice shelf by area. Contrary to predictions that tidal currents near grounding zones mix the water column, we found that Ross Ice Shelf waters were vertically stratified. Current velocities at middepth in the ocean cavity did not change significantly over measurement periods at two different parts of the tidal cycle. The observed stratification resulted in low melt rates near this portion of the grounding zone, inferred from phase‐sensitive radar observations. These melt rates were generally <10 cm/year, which is lower than average for the Ross Ice Shelf (∼20 cm/year). Melt rates may be higher at portions of the grounding zone that experience higher subglacial discharge or stronger tidal mixing. Stratification in the cavity at the borehole site was prone to diffusive convection as a result of ice shelf melting. Since diffusive convection influences vertical heat and salt fluxes differently than shear‐driven turbulence, this process may affect ice shelf melting and merits further consideration in ocean models of sub‐ice shelf circulation

Shared Spatial Situation Awareness as a Team Performance Indicator in Collaborative Spatial Orientation Task

International audienceThe present study investigates the link between time taken by a team to perform a spatial orientation task and the evaluation of spatial shared situational awareness (SSA). Paired in teams, volunteers have to collaborate to send a vehicle to a specific location on a computer simulation as quickly as they can. The roles and information they have to reach that goal are different. Every 45 seconds participants are asked to mark on their map the location they believe the vehicle to be. Along with its real position, these marks are used to objectively evaluate spatial SSA. First results allow us to divide participants into three groups in accordance with Endsley's distinction of Shared SA evaluation. Interestingly, fastest teams were not the ones with the most accurate and shared spatial representation of the situation. Potential use of such indicators in team training is outlined

A proposed quantitative methodology for the evaluation of the effectiveness of Human Element, Leadership and Management (HELM) training in the UK

In 2006, a review of maritime accidents found that non-technical skills (NTSs) are the single largest contributing factor towards such incidents. NTSs are composed of both interpersonal and cognitive elements. These include things such as situational awareness, teamwork, decision making, leadership, management and communication skills. In a crisis situation, good NTSs allow a deck officer to quickly recognise that a problem exists and then harness the resources that are at their disposal to safely and efficiently bring the situation back under control. This paper has two aims. The first is to develop a methodology which will enable educators to quantitatively assess the impact of Maritime and Coastguard Agency (MCA)-approved Human Element, Leadership and Management (HELM) training on deck officer’s NTSs with a view to identifying further training requirements. The second is to determine whether the HELM training provided to develop the NTSs of trainee deck officers is fit for purpose. To achieve these aims, a three-phase approach was adopted. Initially, a taxonomy for deck officer’s NTSs is established, behavioural markers are identified and the relative importance of each attribute is calculated using the analytical hierarchy process (AHP). Subsequently, a set of scenarios were identified for the assessment of deck officer’s NTSs in a ship bridge simulator environment. A random selection of students that have completed the Chief Mate (CM) programme was performed, and data regarding their NTS-related performance in the scenarios was collected. Finally, the collected data was fed into the evidential reasoning (ER) algorithm, utility values were produced and, having established these values, the effectiveness of the HELM training that the students have received was then evaluated

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Parents' knowledge and behaviour concerning sunning their babies; a cross-sectional, descriptive study

BACKGROUND: For centuries, sunlight has been used for therapeutic purposes. Parents still sun their infants to treat neonatal jaundice, nappy rash or mostly to supply vitamin D for bone development as a consequence of health beliefs. In this study we aimed to assess knowledge and behaviour of parents about benefits of sunlight and sun protection. METHODS: In this study, parents attending to governmental primary healthcare units for their children's routine vaccinations, upon their informed consent, were consecutively enrolled during one month. Data were collected by a semi-structured questionnaire. RESULTS: The mean age of 118 enrolled parents and their babies were 27.9 ± 6.5 years and 8.3 ± 5.8 months, respectively. Most of the participants were mothers (93.2%), housewives (81.4%) with an educational level of ≥6 years (71.2%). Sunlight was considered beneficial for bone development (86.4%), diaper rash (5.9%) and neonatal jaundice (12.7%). In case of neonatal jaundice 72.0% of the participants reported that they would consult a physician. Most of the participants (82.2%) were sunning their babies outdoors. Nearly half (49.7%) of them got this information from medical staff. Fifty two percent of the parents were sunning their babies before 10–11 a.m. and/or after 3 p.m. Only 13.6% of parents reported using sunscreen for their babies, and the majority of them were using sun protecting factor ≥ 15. One forth of the sunscreen users was using sunscreen according to their physicians' advice. CONCLUSION: Most of the participants were aware of the benefits of sunlight; especially for bone development. However they were displaying inappropriate behaviour while sunning their babies for health reasons. More education should be given to parents about the danger of sunlight at primary health care units while advising to sun their babies, if any

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Seeing the woods for the trees: the problem of information inefficiency and information overload on operator performance

One of the recurring questions in designing dynamic control environments is whether providing more information leads to better operational decisions. The idea of having every piece of information is increasingly tempting (and in safety critical domains often mandatory) but has become a potential obstacle for designers and operators. The present research study examined this challenge of appropriate information design and usability within a railway control setting. A laboratory study was conducted to investigate the presentation of different levels of information (taken from data processing framework, Dadashi et al., 2014) and the association with, and potential prediction of, the performance of a human operator when completing a cognitively demanding problem solving scenario within railways. Results indicated that presenting users only with information corresponding to their cognitive task, and in the absence of other, non task-relevant information, improves the performance of their problem solving/alarm handling. Knowing the key features of interest to various agents (machine or human) and using the data processing framework to guide the optimal level of information required by each of these agents could potentially lead to safer and more usable designs