Sensomotoric Orthoses, Ankle-Foot Orthoses, and Children with Cerebral Palsy: The Bigger Picture

Ankle–foot orthoses (AFOs) and sensomotoric orthoses (SMotOs) are two—clinically relevant, yet under researched—types of lower limb orthoses used in children with cerebral palsy (CP). Quality of life is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Evaluating the effect of these two types of orthoses on quality of life in children with CP has not been reported on. The aim of this case study series was to synthesise and enrich the volume of evidence reported to inform real world applications of SMotO use in children with CP. Participants recruited were children with CP who performed the Berg Balance Scale, Timed Up-and-Go, the Gross Motor Function Measure and/or the Edinburgh Visual Gait Score in AFOs, SMotOs and barefoot where able. Qualitative data included videos of gait, a questionnaire and pedographs. Eight participants completed 39 quantitative and six qualitative measures, with the Edinburgh Visual Gait Score (EVGS) reporting the highest response. A general improvement was seen in gross motor skills and gait when wearing the SMotOs compared to AFOs and some parents reported that SMotOs were preferred. The reader is able to correlate the quantitative results with the qualitative evidence presented

Community Resilience Research: UK Case Studies, Lessons and Recommendations report to the Cabinet Office and Defence Science and Technology Laboratory.

This report presents four case studies carried out for the Community Resilience project funded by DSTL and supported by the Civil Contingency Secretariat (CCS), Cabinet Office. The work for this project was carried out between September and December 2011. The aim of the Community Resilience project was to develop a better understanding of the role of community resilience in emergency response and recovery situations in order to inform Cabinet Office / Civil Contingencies Secretariat policy on community resilience and to inform the development of future work

Exploring and mapping the knowledge and practice terrain

Postprin

Community resilience to climate change: an evidence review

The concept of community resilience to climate change in the UK has a diverse range of meanings and associated activities. This review of evidence and practice explores this varied and contested field to build the evidence base and help support the development of community resilience to climate change. The report shows: •the variety of actions being carried out across the UK that can be classed as improving resilience of communities to climate change; •the barriers and facilitators to improving resilience to climate change for communities; •the value of a framework to understand resilience of communities to climate change that emphasises existing capacities of communities, engagement and empowerment of citizens, and multi-level governance; and •examples of innovative actions to improve resilience of communities to climate change with a focus on four case studies, which are further explored in a separate report

Bias correction of high-resolution regional climate model precipitation output gives the best estimates of precipitation in Himalayan catchments

The need to provide accurate estimates of precipitation over catchments in the Hindu Kush, Karakoram, and Himalaya mountain ranges for hydrological and water resource systems assessments is widely recognised, as is identifying precipitation extremes for assessing hydro‐meteorological hazards. Here, we investigate the ability of bias‐corrected Weather Research and Forecasting model output at 5 km grid spacing to reproduce the spatiotemporal variability of precipitation for the Beas and Sutlej river basins in the Himalaya, measured by 44 stations spread over the period 1980 to 2012. For the Sutlej basin, we find that the raw (uncorrected) model output generally underestimated annual, monthly, and (particularly low‐intensity) daily precipitation amounts. For the Beas basin, the model performance was better, although biases still existed. It is speculated that the cause of the dry bias over the Sutlej basin is a failure of the model to represent an early‐morning maximum in precipitation during the monsoon period, which is related to excessive precipitation falling upwind. However, applying a non‐linear bias‐correction method to the model output resulted in much better results, which were superior to precipitation estimates from reanalysis and two gridded datasets. These findings highlight the difficulty in using current gridded datasets as input for hydrological modelling in Himalayan catchments, suggesting that bias‐corrected high‐resolution regional climate model output is in fact necessary. Moreover, precipitation extremes over the Beas and Sutlej basins were considerably under‐represented in the gridded datasets, suggesting that bias‐corrected regional climate model output is also necessary for hydro‐meteorological risk assessments in Himalayan catchments

Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway

The alarm cytokine interleukin‐1β (IL‐1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL‐1β production typically requires two signals: first, priming by recognition of pathogen‐associated molecular patterns leads to the production of immature pro‐IL‐1β; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL‐1β from its pro‐form. However, despite the important role of IL‐1β in controlling local and systemic inflammation, its overall regulation is still not fully understood. Here we demonstrate that peritoneal tissue‐resident macrophages use an active inhibitory pathway, to suppress IL‐1β processing, which can otherwise occur in the absence of a second signal. Programming by the transcription factor Gata6 controls the expression of prostacyclin synthase, which is required for prostacyclin production after lipopolysaccharide stimulation and optimal induction of IL‐10. In the absence of secondary signal, IL‐10 potently inhibits IL‐1β processing, providing a previously unrecognized control of IL‐1β in tissue‐resident macrophages

Validation of loci at 2q14.2 and 15q21.3 as risk factors for testicular cancer.

Testicular germ cell tumor (TGCT), the most common cancer in men aged 18 to 45 years, has a strong heritable basis. Genome-wide association studies (GWAS) have proposed single nucleotide polymorphisms (SNPs) at a number of loci influencing TGCT risk. To further evaluate the association of recently proposed risk SNPs with TGCT at 2q14.2, 3q26.2, 7q36.3, 10q26.13 and 15q21.3, we analyzed genotype data on 3,206 cases and 7,422 controls. Our analysis provides independent replication of the associations for risk SNPs at 2q14.2 (rs2713206 at P = 3.03 × 10-2; P-meta = 3.92 × 10-8; nearest gene, TFCP2L1) and rs12912292 at 15q21.3 (P = 7.96 × 10-11; P-meta = 1.55 × 10-19; nearest gene PRTG). Case-only analyses did not reveal specific associations with TGCT histology. TFCP2L1 joins the growing list of genes located within TGCT risk loci with biologically plausible roles in developmental transcriptional regulation, further highlighting the importance of this phenomenon in TGCT oncogenesis

International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

Since the discovery of Toll, in the fruit fly Drosophila melanogaster, as the first described pattern recognition receptor (PRR) in 1996, many families of these receptors have been discovered and characterized. PRRs play critically important roles in pathogen recognition to initiate innate immune responses that ultimately link to the generation of adaptive immunity. Activation of PRRs leads to the induction of immune and inflammatory genes, including proinflammatory cytokines and chemokines. It is increasingly clear that many PRRs are linked to a range of inflammatory, infectious, immune, and chronic degenerative diseases. Several drugs to modulate PRR activity are already in clinical trials and many more are likely to appear in the near future. Here, we review the different families of mammalian PRRs, the ligands they recognize, the mechanisms of activation, their role in disease, and the potential of targeting these proteins to develop the anti-inflammatory therapeutics of the future

IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-β Production Inhibits Fungal Clearance

Candida spp. elicit cytokine production downstream of various pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs), Toll-like receptors (TLRs) and nucleotide oligomerisation domain (NOD)-like receptors (NLRs). IL-12 family members, IL-12p70 and IL-23, are important for host immunity against Candida spp. Herein we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to select Candida spp. We demonstrate a novel mechanism for C. parapsilosis-mediated induction of IL-27 in a TLR7-, MyD88- and NOD2-dependent manner. Our data revealed that IFN-β is induced by C. parapsilosis, which in turn signals through the interferon-α/β receptor (IFNAR) and STAT1/2 to induce IL-27. Moreover, IL 27R (WSX-1) deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared to WT mice. This was associated with increased levels of pro-inflammatory cytokines in the serum and increased IFN-γ and IL-17 responses in the spleens of IL-27R deficient mice. Thus our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-β and IL-27 and we have identified an important role for IL-27 in the immune response against C. parapsilosis. Overall these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens