Investigating the Effects of Knee Flexion during the Eccentric Heel-Drop Exercise

This study aimed to characterise the biomechanics of the widely practiced eccentric heel-drop exercises used in the management of Achilles tendinosis. Specifically, the aim was to quantify changes in lower limb kinematics, muscle lengths and Achilles tendon force, when performing the exercise with a flexed knee instead of an extended knee. A musculoskeletal modelling approach was used to quantify any differences between these versions of the eccentric heel drop exercises used to treat Achilles tendinosis. 19 healthy volunteers provided a group from which optical motion, forceplate and plantar pressure data were recorded while performing both the extended and flexed knee eccentric heel-drop exercises over a wooden step when barefoot or wearing running shoes. This data was used as inputs into a scaled musculoskeletal model of the lower limb. Range of ankle motion was unaffected by knee flexion. However, knee flexion was found to significantly affect lower limb kinematics, inter-segmental loads and triceps muscle lengths. Peak Achilles load was not influenced despite significantly reduced peak ankle plantarflexion moments (p < 0.001). The combination of reduced triceps lengths and greater ankle dorsiflexion, coupled with reduced ankle plantarflexion moments were used to provide a basis for previously unexplained observations regarding the effect of knee flexion on the relative loading of the triceps muscles during the eccentric heel drop exercises. This finding questions the role of the flexed knee heel drop exercise when specifically treating Achilles tendinosis

Organ procurement organizations Internet enrollment for organ donation: Abandoning informed consent

BACKGROUND: Requirements for organ donation after cardiac or imminent death have been introduced to address the transplantable organs shortage in the United States. Organ procurement organizations (OPOs) increasingly use the Internet for organ donation consent. METHODS: An analysis of OPO Web sites available to the public for enrollment and consent for organ donation. The Web sites and consent forms were examined for the minimal information recommended by the United States Department of Health and Human Services for informed consent. Content scores were calculated as percentages of data elements in four information categories: donor knowledge, donor consent reinforcement, donation promotion, and informed consent. RESULTS: There were 60 Web sites for organ donation enrollment serving the 52 states. The median percent (10 percentile-90 percentile) content scores of the Web sites for donor knowledge, donor consent reinforcement, and donation promotion were 33% (20–47), 79% (57–86), and 75% (50–100), respectively. The informed consent score was 0% (0–33). The content scores for donor knowledge and informed consent were significantly lower than donor consent reinforcement and donation promotion for all Web sites (P < .05). The content scores for the four categories were similar among the 11 regions of the United Network for Organ Sharing. CONCLUSION: The Web sites and consent forms for public enrollment in organ donation do not fulfill the necessary requirements for informed consent. The Web sites predominantly provide positive reinforcement and promotional information rather than the transparent disclosure of organ donation process. Independent regulatory oversight is essential to ensure that Internet enrollment for organ donation complies with legal and ethical standards for informed consent

LittleDarwin: a Feature-Rich and Extensible Mutation Testing Framework for Large and Complex Java Systems

Mutation testing is a well-studied method for increasing the quality of a test suite. We designed LittleDarwin as a mutation testing framework able to cope with large and complex Java software systems, while still being easily extensible with new experimental components. LittleDarwin addresses two existing problems in the domain of mutation testing: having a tool able to work within an industrial setting, and yet, be open to extension for cutting edge techniques provided by academia. LittleDarwin already offers higher-order mutation, null type mutants, mutant sampling, manual mutation, and mutant subsumption analysis. There is no tool today available with all these features that is able to work with typical industrial software systems.Comment: Pre-proceedings of the 7th IPM International Conference on Fundamentals of Software Engineerin

Joint neutron/X-ray crystal structure of a mechanistically relevant complex of perdeuterated urate oxidase and simulations provide insight into the hydration step of catalysis

Cofactor-independent urate oxidase (UOX) is an ~137 kDa tetrameric enzyme essential for uric acid (UA) catabolism in many organisms. UA is first oxidized by O2 to dehydroisourate (DHU) via a peroxo intermediate. DHU then undergoes hydration to 5-hydroxyisourate (5HIU). At different stages of the reaction both catalytic O2 and water occupy the 'peroxo hole' above the organic substrate. Here, high-resolution neutron/X-ray crystallographic analysis at room temperature has been integrated with molecular dynamics simulations to investigate the hydration step of the reaction. The joint neutron/X-ray structure of perdeuterated Aspergillus flavus UOX in complex with its 8-azaxanthine (8AZA) inhibitor shows that the catalytic water molecule (W1) is present in the peroxo hole as neutral H2O, oriented at 45° with respect to the ligand. It is stabilized by Thr57 and Asn254 on different UOX protomers as well as by an O-H∙ ∙ ∙π interaction with 8AZA. The active site Lys10-Thr57 dyad features a charged Lys10-NH3+ side chain engaged in a strong hydrogen bond with Thr57OG1, while the Thr57OG1-HG1 bond is rotationally dynamic and oriented toward the π system of the ligand, on average. Our analysis offers support for a mechanism in which W1 performs a nucleophilic attack on DHUC5 with Thr57HG1 central to a Lys10-assisted proton-relay system. Room-temperature crystallography and simulations also reveal conformational heterogeneity for Asn254 that modulates W1 stability in the peroxo hole. This is proposed to be an active mechanism to facilitate W1/O2 exchange during catalysis

Observational Evidence of For-Profit Delivery and Inferior Nursing Home Care: When Is There Enough Evidence for Policy Change?

This research was financially supported by the Social Sciences and Humanities Research Council

Heterogeneous reaction of ClONO2_{2} with TiO2_{2} and SiO2_{2} aerosol particles: implications for stratospheric particle injection for climate engineering

Deliberate injection of aerosol particles into the stratosphere is a potential climate engineering scheme. Particles injected into the stratosphere would scatter solar radiation back to space, thereby reducing the temperature at the Earth's surface and hence the impacts of global warming. Minerals such as TiO$_{2}$ or SiO$_{2}$ are among the potentially suitable aerosol materials for stratospheric particle injection due to their greater light-scattering ability than stratospheric sulfuric acid particles. However, the heterogeneous reactivity of mineral particles towards trace gases important for stratospheric chemistry largely remains unknown, precluding reliable assessment of their impacts on stratospheric ozone, which is of key environmental significance. In this work we have investigated for the first time the heterogeneous hydrolysis of ClONO$_{2}$ on TiO$_{2}$ and SiO$_{2}$ aerosol particles at room temperature and at different relative humidities (RHs), using an aerosol flow tube. The uptake coefficient, γ(ClONO$_{2}$), on TiO$_{2}$ was ∼ 1.2 × 10$^{-3}$ at 7 % RH and remained unchanged at 33 % RH, and increased for SiO$_{2}$ from ∼ 2 × 10$^{-4}$ at 7 % RH to  ∼ 5 × 10$^{-4}$ at 35 % RH, reaching a value of  ∼ 6 × 10$^{-4}$ at 59 % RH. We have also examined the impacts of a hypothetical TiO$_{2}$ injection on stratospheric chemistry using the UKCA (United Kingdom Chemistry and Aerosol) chemistry–climate model, in which heterogeneous hydrolysis of N$_{2}$O$_{5}$ and ClONO$_{2}$ on TiO$_{2}$ particles is considered. A TiO$_{2}$ injection scenario with a solar-radiation scattering effect very similar to the eruption of Mt Pinatubo was constructed. It is found that, compared to the eruption of Mt Pinatubo, TiO$_{2}$ injection causes less ClO$_{x}$ activation and less ozone destruction in the lowermost stratosphere, while reduced depletion of N$_{2}$O$_{5}$ and NO$_{x}$ in the middle stratosphere results in decreased ozone levels. Overall, no significant difference in the vertically integrated ozone abundances is found between TiO$_{2}$ injection and the eruption of Mt Pinatubo. Future work required to further assess the impacts of TiO$_{2}$ injection on stratospheric chemistry is also discussed.Financial support provided by EPSRC grant EP/I01473X/1 and the Isaac Newton Trust (Trinity College, University of Cambridge, UK) is acknowledged. We thank NCAS-CMS for modelling support. Model integrations have been performed using the ARCHER UK National Supercomputing Service. We acknowledge the ERC for support through the ACCI project (project number: 267760). M. J. Tang would like to thank the CAS Pioneer Hundred Talents programme and State Key Laboratory of Organic Geochemistry for providing starting grants

Invited commentary to the paper ‘Zinc status and its association with the health of adolescents: a review of studies in India’

We are pleased to view the article based on Dr. Rama Kawade's thesis illustrating the importance of micronutrient adequacy, especially zinc, and associated health implications in Indian adolescent girls. This brief commentary addresses three major aspects in which Kawade's work has made a significant contribution; nutrition and health issues of adolescents, rising importance of zinc in terms of deficiency problems being addressed, and development of dietary interventions to alleviate micronutrient deficiencies

The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial

<p>Abstract</p> <p>Background</p> <p>Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered.</p> <p>Methods</p> <p>Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation.</p> <p>Results</p> <p>The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement.</p> <p>Conclusions</p> <p>This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER).</p

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; 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: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Induction of Tachykinin Production in Airway Epithelia in Response to Viral Infection

The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. We have previously demonstrated the most dramatic phenotype described for the substance P encoding gene preprotachykinin-A (PPT-A) to date in controlling the host immune response to the murine gammaherpesvirus 68, in the lung.In this study we have utilised transgenic mice engineered to co-ordinately express the beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT-A expression. Using a combination of these mice and conventional immunohistology we now demonstrate that PPT-A gene expression and substance P peptide are induced in cells of the respiratory tract including tracheal, bronchiolar and alveolar epithelial cells and macrophages after viral infection. This induction was observed 24h post infection, prior to observable inflammation and the expression of pro-inflammatory chemokines in this model. Induced expression of the PPT-A gene and peptide persisted in the lower respiratory tract through day 7 post infection.Non-neuronal PPT-A expression early after infection may have important clinical implications for the progression or management of lung disease or infection aside from the well characterised later involvement of the tachykinins during the inflammatory response