Light curves and colours of the ejecta from Dimorphos after the DART impact.

On 26 September 2022, the Double Asteroid Redirection Test (DART) spacecraft struck Dimorphos, a satellite of the asteroid 65803 Didymos1. Because it is a binary system, it is possible to determine how much the orbit of the satellite changed, as part of a test of what is necessary to deflect an asteroid that might threaten Earth with an impact. In nominal cases, pre-impact predictions of the orbital period reduction ranged from roughly 8.8 to 17 min (refs. 2,3). Here we report optical observations of Dimorphos before, during and after the impact, from a network of citizen scientists' telescopes across the world. We find a maximum brightening of 2.29 ± 0.14 mag on impact. Didymos fades back to its pre-impact brightness over the course of 23.7 ± 0.7 days. We estimate lower limits on the mass contained in the ejecta, which was 0.3-0.5% Dimorphos's mass depending on the dust size. We also observe a reddening of the ejecta on impact.

Marine phytoplankton functional types exhibit diverse responses to thermal change.

Marine phytoplankton generate half of global primary production, making them essential to ecosystem functioning and biogeochemical cycling. Though phytoplankton are phylogenetically diverse, studies rarely designate unique thermal traits to different taxa, resulting in coarse representations of phytoplankton thermal responses. Here we assessed phytoplankton functional responses to temperature using empirically derived thermal growth rates from four principal contributors to marine productivity: diatoms, dinoflagellates, cyanobacteria, and coccolithophores. Using modeled sea surface temperatures for 1950-1970 and 2080-2100, we explored potential alterations to each group's growth rates and geographical distribution under a future climate change scenario. Contrary to the commonly applied Eppley formulation, our data suggest phytoplankton functional types may be characterized by different temperature coefficients (Q10), growth maxima thermal dependencies, and thermal ranges which would drive dissimilar responses to each degree of temperature change. These differences, when applied in response to global simulations of future temperature, result in taxon-specific projections of growth and geographic distribution, with low-latitude coccolithophores facing considerable decreases and cyanobacteria substantial increases in growth rates. These results suggest that the singular effect of changing temperature may alter phytoplankton global community structure, owing to the significant variability in thermal response between phytoplankton functional types.

Balance Right in Multiple Sclerosis (BRiMS): a feasibility randomised controlled trial of a falls prevention programme.

BACKGROUND: Balance, mobility impairments and falls are problematic for people with multiple sclerosis (MS). The "Balance Right in MS (BRiMS)" intervention, a 13-week home and group-based exercise and education programme, aims to improve balance and minimise falls. This study aimed to evaluate the feasibility of undertaking a multi-centre randomised controlled trial and to collect the necessary data to design a definitive trial. METHODS: This randomised controlled feasibility study recruited from four United Kingdom NHS clinical neurology services. Patients ≥ 18 years with secondary progressive MS (Expanded Disability Status Scale 4 to 7) reporting more than two falls in the preceding 6 months were recruited. Participants were block-randomised to either a manualised 13-week education and exercise programme (BRiMS) plus usual care, or usual care alone. Feasibility assessment evaluated recruitment and retention rates, adherence to group assignment and data completeness. Proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls) and economic data were collected at baseline, 13 and 27 weeks, and participants completed daily paper falls diaries. RESULTS: Fifty-six participants (mean age 59.7 years, 66% female, median EDSS 6.0) were recruited in 5 months; 30 randomised to the intervention group. Ten (18%) participants withdrew, 7 from the intervention group. Two additional participants were lost to follow up at the final assessment point. Completion rates were > 98% for all outcomes apart from the falls diary (return rate 62%). After adjusting for baseline score, mean intervention-usual care between-group differences for the potential primary outcomes at week 27 were MS Walking Scale-12v2: - 7.7 (95% confidence interval [CI] - 17.2 to 1.8) and MS Impact Scale-29v2: physical 0.6 (CI - 7.8 to 9), psychological - 0.4 (CI - 9.9 to 9). In total, 715 falls were reported, rate ratio (intervention:usual care) for falls 0.81 (0.41 to 2.26) and injurious falls 0.44 (0.41 to 2.23). CONCLUSIONS: Procedures were practical, and retention, programme engagement and outcome completion rates satisfied a priori progression criteria. Challenges were experienced in completion and return of daily falls diaries. Refinement of methods for reporting falls is therefore required, but we consider a full trial to be feasible. TRIAL REGISTRATION: ISRCTN13587999 Date of registration: 29 September 2016.

Prediction of Active Microwave Backscatter Over Snow-Covered Terrain Across Western Colorado Using a Land Surface Model and Support Vector Machine Regression.

The main objective of this article is to develop a physically constrained support vector machine (SVM) to predict C-band backscatter over snow-covered terrain as a function of geophysical inputs that reasonably represent the relevant characteristics of the snowpack. Sentinel-1 observations, in conjunction with geophysical variables from the Noah-MP land surface model, were used as training targets and input datasets, respectively. Robustness of the SVM prediction was analyzed in terms of training targets, training windows, and physical constraints related to snow liquid water content. The results showed that a combination of ascending and descending overpasses yielded the highest coverage of prediction (15.2%) while root mean square error (RMSE) ranged from 2.06 to 2.54 dB and unbiased RMSE ranged from 1.54 to 2.08 dB, but that the combined overpasses were degraded compared with ascending-only and descending-only training target sets due to the mixture of distinctive microwave signals during different times of the day (i.e., 6 A.M. versus 6 P.M. local time). Elongation of the training window length also increased the spatial coverage of prediction (given the sparsity of the training sets), but resulted in introducing more random errors. Finally, delineation of dry versus wet snow pixels for SVM training resulted in improving the accuracy of predicted backscatter relative to training on a mixture of dry and wet snow conditions. The overall results suggest that the prediction accuracy of the SVM was strongly linked with the first-order physics of the electromagnetic response of different snow conditions.

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease-associated psychological morbidity.

BACKGROUND: Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+ NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. OBJECTIVES: To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. METHODS: We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. RESULTS: Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)-17A, IL-17F, IL-21 and IL-23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL-17F, IL-17E and IL-23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL-22 and IL-17E are positively and significantly associated with depression. CONCLUSIONS: Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+ CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)-6, tumour necrosis factor-α, IL-1ß and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL-33, IL-31 and IL-17E (IL-25), in addition to the type 17 cytokines IL-17A, IL-21, IL-23 and IL-17F. Levels of IL-17E and IL-22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17- and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17- and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T-cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.

The impact of emergency department patient-controlled analgesia (PCA) on the incidence of chronic pain following trauma and non-traumatic abdominal pain.

The effect of patient-controlled analgesia during the emergency phase of care on the prevalence of persistent pain is unkown. We studied individuals with traumatic injuries or abdominal pain 6 months after hospital admission via the emergency department using an opportunistic observational study design. This was conducted using postal questionnaires that were sent to participants recruited to the multi-centre pain solutions in the emergency setting study. Patients with prior chronic pain states or opioid use were not studied. Questionnaires included the EQ5D, the Brief Pain Inventory and the Hospital Anxiety and Depression scale. Overall, 141 out of 286 (49% 95%CI 44-56%) patients were included in this follow-up study. Participants presenting with trauma were more likely to develop persistent pain than those presenting with abdominal pain, 45 out of 64 (70%) vs. 24 out of 77 (31%); 95%CI 24-54%, p < 0.001. There were no statistically significant associations between persistent pain and analgesic modality during hospital admission, age or sex. Across both abdominal pain and traumatic injury groups, participants with persistent pain had lower EQ5D mobility scores, worse overall health and higher anxiety and depression scores (p < 0.05). In the abdominal pain group, 13 out of 50 (26%) patients using patient-controlled analgesia developed persistent pain vs. 11 out of 27 (41%) of those with usual treatment; 95%CI for difference (control - patient-controlled analgesia) -8 to 39%, p = 0.183. Acute pain scores at the time of hospital admission were higher in participants who developed persistent pain; 95%CI 0.7-23.6, p = 0.039. For traumatic pain, 25 out of 35 (71%) patients given patient-controlled analgesia developed persistent pain vs. 20 out of 29 (69%) patients with usual treatment; 95%CI -30 to 24%, p = 0.830. Persistent pain is common 6 months after hospital admission, particularly following trauma. The study findings suggest that it may be possible to reduce persistent pain (at least in patients with abdominal pain) by delivering better acute pain management. Further research is needed to confirm this hypothesis.

Evaluating the uncertainty of terrestrial water budget components over High Mountain Asia.

This study explores the uncertainties in terrestrial water budget estimation over High Mountain Asia (HMA) using a suite of uncoupled land surface model (LSM) simulations. The uncertainty in the water balance components of precipitation (P), evapotranspiration (ET), runoff(R), and terrestrial water storage (TWS) is significantly impacted by the uncertainty in the driving meteorology, with precipitation being the most important boundary condition. Ten gridded precipitation datasets along with a mix of model-, satellite-, and gauge-based products, are evaluated first to assess their suitability for LSM simulations over HMA. The datasets are evaluated by quantifying the systematic and random errors of these products as well as the temporal consistency of their trends. Though the broader spatial patterns of precipitation are generally well captured by the datasets, they differ significantly in their means and trends. In general, precipitation datasets that incorporate information from gauges are found to have higher accuracy with low Root Mean Square Errors and high correlation coefficient values. An ensemble of LSM simulations with selected subset of precipitation products is then used to produce the mean annual fluxes and their uncertainty over HMA in P, ET, and R to be 2.11±0.45, 1.26±0.11, and 0.85±0.36 mm per day, respectively. The mean annual estimates of the surface mass (water) balance components from this model ensemble are comparable to global estimates from prior studies. However, the uncertainty/spread of P, ET, and R is significantly larger than the corresponding estimates from global studies. A comparison of ET, snow cover fraction, and changes in TWS estimates against remote sensing-based references confirms the significant role of the input meteorology in influencing the water budget characterization over HMA and points to the need for improving meteorological inputs.

Estimating snow mass in North America through assimilation of AMSR-E brightness temperature observations using the Catchment land surface model and support vector machines.

To estimate snow mass across North America, brightness temperature observations collected by the Advanced Microwave Scanning Radiometer from 2002 to 2011 were assimilated into the Catchment model using a support vector machine (SVM) as the observation operator and a one-dimensional ensemble Kalman filter. The performance of the assimilation system is evaluated through comparisons against ground-based measurements and reference snow products. In general, there are no statistically significant skill differences between the domain-averaged, model-only ("open loop", or OL) snow estimates and assimilation estimates. The assessment of improvements (or degradations) in snow estimates is difficult because of limitations in the measurements (or products) used for evaluation. It is found that assimilation estimates agree slightly better in terms of root-mean-square error (RMSE) and Nash-Sutcliffe model efficiency with ground-based snow depth measurements than OL estimates in 82% (56 out of 62) of pixels that are colocated with at least two ground-based stations. Assimilation estimates tend to agree slightly better in terms of mean difference with reference snow products over tun-dra snow, alpine snow, maritime snow, and sparsely-vegetated, snow covered pixels. Changes in snow mass via assimilation translate into improvements (e.g.,by 22% on average in terms of RMSE, relative to OL) in cumulative runoff estimates when compared against discharge measurements in 11 out of 13 snow-dominated basins in Alaska. These results suggest that a SVM can potentially serve as an effective observation operator for snow mass estimation within a radiance assimilation system, but a better observational baseline is required to document a statistically significant improvement.

Assimilation of MODIS Snow Cover Fraction Observations into the NASA Catchment Land Surface Model.

The NASA Catchment land surface model (CLSM) is the land model component used for the Modern-Era Retrospective Analysis for Research and Applications (MERRA). Here, the CLSM versions of MERRA and MERRA-Land are evaluated using snow cover fraction (SCF) observations from the Moderate Resolution Imaging Spectroradiometer (MODIS). Moreover, a computationally-efficient empirical scheme is designed to improve CLSM estimates of SCF, snow depth, and snow water equivalent (SWE) through the assimilation of MODIS SCF observations. Results show that data assimilation (DA) improved SCF estimates compared to the open-loop model without assimilation (OL), especially in areas with ephemeral snow cover and mountainous regions. A comparison of the SCF estimates from DA against snow cover estimates from the NOAA Interactive Multisensor Snow and Ice Mapping System showed an improvement in the probability of detection of up to 28% and a reduction in false alarms by up to 6% (relative to OL). A comparison of the model snow depth estimates against Canadian Meteorological Centre analyses showed that DA successfully improved the model seasonal bias from -0.017 m for OL to -0.007 m for DA, although there was no significant change in root-mean-square differences (RMSD) (0.095 m for OL, 0.093 m for DA). The time-average of the spatial correlation coefficient also improved from 0.61 for OL to 0.63 for DA. A comparison against in situ SWE measurements also showed improvements from assimilation. The correlation increased from 0.44 for OL to 0.49 for DA, the bias improved from -0.111 m for OL to -0.100 m for DA, and the RMSD decreased from 0.186 m for OL to 0.180 m for DA.

A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study.

BACKGROUND: Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. METHODS: A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. RESULTS: Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. CONCLUSIONS: We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR.

Genetics of immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody-mediated autoimmune diseases cluster more closely with each other than autoantibody-negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.

Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial.

BACKGROUND: Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed 'Balance Right in MS' (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls. Our eventual aim is to assess the clinical and cost effectiveness of BRiMS in people with secondary progressive MS by undertaking an appropriately statistically powered, multi-centre, assessor-blinded definitive, randomised controlled trial. This feasibility study will assess the acceptability of the intervention and test the achievability of running such a definitive trial. METHODS/DESIGN: This is a pragmatic multi-centre feasibility randomised controlled trial with blinded outcome assessment. Sixty ambulant people with secondary progressive MS who self-report two or more falls in the previous 6 months will be randomly allocated (1:1) to either the BRiMS programme plus usual care or to usual care alone. All participants will be assessed at baseline and followed up at 15 weeks and 27 weeks post-randomisation. The outcomes of this feasibility trial include:Feasibility outcomes, including trial recruitment, retention and completionAssessment of the proposed outcome measures for the anticipated definitive trial (including measures of walking, quality of life, falls, balance and activity level)Measures of adherence to the BRiMS programmeData to inform the economic evaluation in a future trialProcess evaluation (assessment of treatment fidelity and qualitative evaluation of participant and treating therapist experience). DISCUSSION: The BRiMS intervention aims to address a key concern for MS service users and providers. However, there are several uncertainties which need to be addressed prior to progressing to a full-scale trial, including acceptability of the BRiMS intervention and practicality of the trial procedures. This feasibility trial will provide important insights to resolve these uncertainties and will enable a protocol to be finalised for use in the definitive trial. TRIAL REGISTRATION: ISRCTN13587999.

The cost-effectiveness of patient-controlled analgesia vs. standard care in patients presenting to the Emergency Department in pain, who are subsequently admitted to hospital.

The clinical effectiveness of patient-controlled analgesia has been demonstrated in a variety of settings. However, patient-controlled analgesia is rarely utilised in the Emergency Department. The aim of this study was to compare the cost-effectiveness of patient-controlled analgesia vs. standard care in participants admitted to hospital from the Emergency Department with pain due to traumatic injury or non-traumatic abdominal pain. Pain scores were measured hourly for 12 h using a visual analogue scale. Cost-effectiveness was measured as the additional cost per hour in moderate to severe pain avoided by using patient-controlled analgesia rather than standard care (the incremental cost-effectiveness ratio). Sampling variation was estimated using bootstrap methods and the effects of parameter uncertainty explored in a sensitivity analysis. The cost per hour in moderate or severe pain averted was estimated as £24.77 (€29.05, US$30.80) (bootstrap estimated 95%CI £8.72 to £89.17) for participants suffering pain from traumatic injuries and £15.17 (€17.79, US$18.86) (bootstrap estimate 95%CI £9.03 to £46.00) for participants with non-traumatic abdominal pain. Overall costs were higher with patient-controlled analgesia than standard care in both groups: pain from traumatic injuries incurred an additional £18.58 (€21.79 US$23.10) (95%CI £15.81 to £21.35) per 12 h; and non-traumatic abdominal pain an additional £20.18 (€23.67 US$25.09) (95%CI £19.45 to £20.84) per 12 h.

Evaluation and enhancement of permafrost modeling with the NASA Catchment Land Surface Model.

Besides soil hydrology and snow processes, the NASA Catchment Land Surface Model (CLSM) simulates soil temperature in six layers from the surface down to 13m depth. In this study, to examine CLSM's treatment of subsurface thermodynamics, a baseline simulation produced subsurface temperatures for 1980-2014 across Alaska at 9-km resolution. The results were evaluated using in situ observations from permafrost sites across Alaska. The baseline simulation was found to capture the broad features of inter- and intra-annual variations in soil temperature. Additional model experiments revealed that: (i) the representativeness of local meteorological forcing limits the model's ability to accurately reproduce soil temperature, and (ii) vegetation heterogeneity has a profound influence on subsurface thermodynamics via impacts on the snow physics and energy exchange at surface. Specifically, the profile-average RMSE for soil temperature was reduced from 2.96°C to 2.10°C at one site and from 2.38°C to 2.25°C at another by using local forcing and land cover, respectively. Moreover, accounting for the influence of soil organic carbon on the soil thermal properties in CLSM leads to further improvements in profile-average soil temperature RMSE, with reductions of 16% to 56% across the different study sites. The mean bias of climatological ALT is reduced by 36% to 89%, and the RMSE is reduced by 11% to 47%. Finally, results reveal that at some sites it may be essential to include a purely organic soil layer to obtain, in conjunction with vegetation and snow effects, a realistic "buffer zone" between the atmospheric forcing and soil thermal processes.

Investigation of the genetic overlap between rheumatoid arthritis and psoriatic arthritis in a Greek population.

OBJECTIVES: Several rheumatoid arthritis (RA) susceptibility loci have also been found to be associated with psoriatic arthritis (PsA), demonstrating that there is a degree of genetic overlap between various autoimmune diseases. We sought to investigate whether single nucleotide polymorphisms (SNPs) mapping to previously reported RA and/or PsA susceptibility loci, including PLCL2, CCL21, REL, STAT4, CD226, PTPN22, and TYK2, are associated with risk for the two diseases in a genetically homogeneous Greek population. METHOD: This study included 392 RA patients, 126 PsA patients, and 521 healthy age- and sex-matched controls from Greece. Genotyping of the SNPs was performed with Taqman primer/probe sets. Bioinformatic analysis was performed using BlastP, PyMOL, and Maestro and Desmond. RESULTS: A significant association was detected between the GC genotype of rs34536443 (TYK2) in both the PsA and RA cohorts. The C allele of this SNP was associated with PsA only. Evidence for association with PsA was also found for the GG genotype and G allele of the rs10181656 SNP of STAT4. The TC genotype of the rs763361 SNP of CD226 was associated with PsA only. CONCLUSIONS: Genetic overlap between PsA and RA was detected for the rs34536443 SNP of the TYK2 gene within a Greek population. An association of STAT4 (rs10181656) with PsA was confirmed whereas CD226 (rs763361) was associated with PsA but not with RA, in contrast to previous reports. The different findings of this study compared to previous ones highlights the importance of comparative studies that include various ethnic or racial populations.

Standing up in multiple sclerosis (SUMS): protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an incurable, unpredictable but typically progressive neurological condition. It is the most common cause of neurological disability in young adults. Within 15 years of diagnosis, approximately 50 % of affected people are unable to walk unaided, and over time an estimated 25 % depend on a wheelchair. Typically, people with such limited mobility are excluded from clinical trials. Severely impaired people with MS spend much of their day sitting, often with limited ability to change position. In response, secondary complications can occur including: muscle wasting, pain, reduced skin integrity, spasms, limb stiffness, constipation, and associated psychosocial problems such as depression and lowered self-esteem. Effective self-management strategies, which can be implemented relatively easily and cheaply within people's homes, are needed to improve or maintain mobility and reduce sedentary behaviour. However this is challenging, particularly in the latter stages of disease. Regular supported standing using standing frames is one potential option. METHODS/DESIGN: SUMS is a pragmatic multi-centre randomised controlled trial evaluating use of Oswestry standing frames with blinded outcome assessment and full economic evaluation. Participants will be randomly allocated (1:1) to either a home-based, self-management standing programme (with advice and support) along with their usual care or to usual care alone. Those in the intervention group will be asked to stand for a minimum of 30 min three times weekly over 20 weeks. Each participant will be followed-up at 20 and 36 weeks post baseline. The primary clinical outcome is motor function, assessed using the Amended Motor Club Assessment. The primary economic endpoint is quality-adjusted life years. The secondary outcomes include measures of explanatory physical impairments, key clinical outcomes, and health-related quality of life. An embedded qualitative component will explore participant's and carer's experiences of the standing programme. DISCUSSION: This is the first large scale multi-centre trial to assess the clinical and cost effectiveness of a home based standing frame programme for people who are severely impaired by MS. If demonstrated to be effective and cost-effective, we will use this evidence to develop recommendations for a health service delivery model which could be implemented across the United Kingdom. TRIAL REGISTRATION: ISRCTN69614598 DATE OF REGISTRATION: 3.2.16 (retrospectively registered).

Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis.

Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary.

Mixtures of catanionic surfactants can be superspreaders: Comparison with trisiloxane superspreader.

HYPOTHESIS: Mixed solutions of cationic and anionic surfactants show considerable synergism in their wetting behaviour, but their spreading is affected considerably by the phase separation processes. The valuable information about wetting properties of synergetic mixtures can be obtained by using mixtures in which phase separation occurs at concentrations above cmc. EXPERIMENTS: Spreading properties of mixed solutions of cationic and anionic surfactants over highly hydrophobic substrate such as polyethylene are investigated and compared with those for trisiloxane superspreader. Experiments are performed at relative humidity of 40% and 80%. Interfacial tension at water/air and water/alkane interfaces is measured to explain spreading performance. FINDINGS: Catanionic solutions can wet hydrophobic substrates nearly as effective as solutions of trisiloxane superspreader. The spreading factor reaches 70% of that of superspreader for the most effective mixed solution. The spreading slows down earlier at high surfactant concentrations. At room humidity (40%) spread area has a maximum vs concentration. However, the maximum was not observed at higher humidity 80%. Humidity does not affect the short-time spreading rate, but it influences considerably the time when spreading slows down. The spreading rate of mixed solutions is smaller than that of superspreader despite the same spreading exponent α=0.5.

Retinogenesis: stochasticity and the competency model.

The vertebrate retina is made up of seven principal cell types. These seven retinal cell types arise from multipotent retinal progenitor cells (RPCs). The competency model was proposed suggesting that RPCs undergo a series of irreversible transitions between competency states, in each of which the RPCs are competent to generate a different subset of cell types, but not retinal cells generated at previous moments. In this work, we generalize the stochastic model of neurogenesis of Barton et al. (2014), assuming that the same factor that regulates the differentiation, regulates the competency. The model reproduces the timing of production of different retinal cell types in rats such as it was experimentally measured. The results show that the evolution of the competency during retinogenesis could be explained by a single factor. Its evolution during the cell cycle and the stochastic inheritance in cell divisions determine the sequence and the overlap of production of different retinal cell types during development.