Efficacy Of Prophylactic Knee Bracing In Conservative Management Of Knee Pain In Recreational Athletes

Patellofemoral pain is extremely common in recreational athletes. Patellofemoral symptoms can severely restrict participation in athletic activities, and may also progress into osteoarthritis in later life

Interaction between hydrocephalus shunt and pressure waves

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Performance optimization of a leagility inspired supply chain model: a CFGTSA algorithm based approach

Lean and agile principles have attracted considerable interest in the past few decades. Industrial sectors throughout the world are upgrading to these principles to enhance their performance, since they have been proven to be efficient in handling supply chains. However, the present market trend demands a more robust strategy incorporating the salient features of both lean and agile principles. Inspired by these, the leagility principle has emerged, encapsulating both lean and agile features. The present work proposes a leagile supply chain based model for manufacturing industries. The paper emphasizes the various aspects of leagile supply chain modeling and implementation and proposes a new Hybrid Chaos-based Fast Genetic Tabu Simulated Annealing (CFGTSA) algorithm to solve the complex scheduling problem prevailing in the leagile environment. The proposed CFGTSA algorithm is compared with the GA, SA, TS and Hybrid Tabu SA algorithms to demonstrate its efficacy in handling complex scheduling problems

Dust-free quasars in the early Universe

The most distant quasars known, at redshifts z=6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands. This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z=6 quasar was shown not to have any detectable emission from hot dust, but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z=6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z=6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.Comment: To be published in Nature on the 18 March 2010

Alternative splicing modifies the effect of mutations in COL11A1 and results in recessive type 2 Stickler syndrome with profound hearing loss.

BACKGROUND: Stickler syndromes types 1, 2 and 3 are usually dominant disorders caused by mutations in the genes COL2A1, COL11A1 and COL11A2 that encode the fibrillar collagens types II and XI present in cartilage and vitreous. Rare recessive forms of Stickler syndrome exist that are due to mutations in genes encoding type IX collagen (COL9A1 type 4 Stickler syndrome and COL9A2 type 5 Stickler syndrome). Recently, recessive mutations in the COL11A1 gene have been demonstrated to result in fibrochondrogenesis, a much more severe skeletal dysplasia, which is often lethal. Here we demonstrate that some mutations in COL11A1 are recessive, modified by alternative splicing and result in type 2 Stickler syndrome rather than fibrochondrogenesis. METHODS: Patients referred to the national Stickler syndrome diagnostic service for England, UK were assessed clinically and subsequently sequenced for mutations in COL11A1. Additional in silico and functional studies to assess the effect of sequence variants on pre-mRNA processing and collagen structure were performed. RESULTS: In three different families, heterozygous COL11A1 biallelic null, null/missense or silent/missense mutations, were found. They resulted in a recessive form of type 2 Stickler syndrome characterised by particularly profound hearing loss and are clinically distinct from the recessive types 4 and 5 variants of Stickler syndrome. One mutant allele in each family is capable of synthesising a normal α1(XI) procollagen molecule, via variable pre-mRNA processing. CONCLUSION: This new variant has important implications for molecular diagnosis and counselling families with type 2 Stickler syndrome

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

Psychological interventions for depression and anxiety in patients with coronary heart disease, heart failure or atrial fibrillation

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and costs of psychological interventions (alone, or with CR or pharmacotherapy, or both) in adults who have a diagnosis of CHD, HF or AF compared to no intervention, or treatment as usual, on psychological and clinical outcomes

Elective Modernism and the Politics of (Bio) Ethical Expertise

In this essay I consider whether the political perspective of third wave science studies – ‘elective modernism’ – offers a suitable framework for understanding the policy-making contributions that (bio)ethical experts might make. The question arises as a consequence of the fact that I have taken inspiration from the third wave in order to develop an account of (bio)ethical expertise. I offer a précis of this work and a brief summary of elective modernism before considering their relation. The view I set out suggests that elective modernism is a political philosophy and that although its use in relation to the use of scientific expertise in political and policy-making process has implications for the role of (bio)ethical expertise it does not, in the final analysis, provide an account that is appropriate for this latter form of specialist expertise. Nevertheless, it is an informative perspective, and one that can help us make sense of the political uses of (bio)ethical expertise

Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis

Background: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. Methods: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi-attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. Results: Overall, 80 per cent of the patients reported difficulty in one or more dimensions preimplant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. Conclusion: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long-term, durable improvement