The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

Same space, different standards : a review of cumulative effects assessment practice for marine mammals

The lead author is a PhD student, whose stipend during the undertaking of this work was provided by a James Watt scholarship (Heriot-Watt University). Financial support enabling the open access publication of this research was provided by Natural England - the government’s adviser for the natural environment in England.Marine mammals are vulnerable to a variety of acute and chronic anthropogenic stressors, potentially experiencing these in isolation, successively and/or simultaneously. Formal assessment of the likely impact(s) of the cumulative effects of multiple stressors on a defined population is carried out through a Cumulative Effects Assessment (CEA), which is a mandatory component of the Environmental Impact Assessment (EIA) process in many countries. However, for marine mammals, the information required to feed into CEA, such as thresholds for disturbance, frequency of multiple (and simultaneous) exposures, interactions between stressors, and individual variation in response, is extremely limited, though our understanding is slowly improving. The gaps in knowledge make it challenging to effectively quantify and subsequently assess the risk of individual and population consequences of multiple disturbances in the form of a CEA. To assess the current state of practice for assessing cumulative effects on marine mammals within UK waters, 93 CEAs were reviewed across eleven maritime industries. An objective framework of thirteen evaluative criteria was used to score each assessment on a scale of 13-52 (weak - strong). Scores varied significantly by industry. On average, the aquaculture industry produced the lowest scoring CEAs, whilst the large offshore windfarm industry (≥ 20 turbines) scored highest, according to the scoring criteria used. There was a significant increase in scores over the sample period (2009-2019), though this was mostly attributed to five industries (cable, large and small offshore wind farms, tidal and wave energy). There was inconsistency in the language used to define and describe cumulative effects and a lack of routinely applied methodology. We use the findings presented here, along with a wider review of the literature, to provide recommendations and discussion points aimed at supporting the standardisation and improvement of CEA practice. Although this research focused on how marine mammals were considered within UK CEAs, recommendations made are broadly applicable to assessments conducted for other receptors, countries and/or environments. Adoption of these proposals would help to ensure a more consistent approach, and would aid decision-makers and practitioners in mitigating any potential impacts, to ensure conservation objectives of marine mammal populations are not compromised.Publisher PDFPeer reviewe

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo-perceptual deficits.

BackgroundPeople with Parkinson's disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo-perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD.ObjectiveWe developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias.MethodsWe assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks.ResultsPeople with PD were worse than controls at object recognition, showing no deficits in other visuo-perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias.ConclusionsOnline tests can detect visuo-perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo-perceptual tests may be developed to identify at-risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Vernix caseosa peritonitis – no longer rare or innocent: a case series

<p>Abstract</p> <p>Introduction</p> <p>Vernix Caseosa peritonitis is a rare post caesarean section complication with only 19 case reports in the literature to date. Vernix caseosa spilt at the time of caesarean section is thought to incite an inflammatory reaction, causing symptoms resembling an acute abdomen.</p> <p>Case Presentation</p> <p>We discuss three Caucasian patients (aged 32 to 43 years) who presented in our health sector in Sydney with vernix caseosa peritonitis. Each had a protracted course with significant comorbidities requiring surgical and medical intervention. This contrasts with other reports suggesting that a rapid resolution can be expected.</p> <p>This cluster may be a consequence of the rising caesarean section rate, a heightened local awareness of the condition and possibly a result of leaving material in the paracolic gutters intraoperatively.</p> <p>Conclusion</p> <p>Our aim is to increase awareness among our obstetric and surgical colleagues of the characteristic clinical presentation and intra-operative findings of vernix caseosa peritonitis. We also point out that, in contrast to those presented here, not all patients require laparotomy.</p

Assessing cognitive dysfunction in Parkinson's disease: an online tool to detect visuo-perceptual deficits

Background: People with Parkinson's disease (PD) who develop visuo‐perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo‐perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo‐perceptual deficits in PD. Objective: We developed an online platform to test visuo‐perceptual function. We hypothesised that (1) visuo‐perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. Methods: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. Results: People with PD were worse than controls at object recognition, showing no deficits in other visuo‐perceptual tests. Specifically, they were worse at identifying skewed images (P  &lt; .0001); at detecting hidden objects (P  = .0039); at identifying objects in peripheral vision (P  &lt; .0001); and at detecting biological motion (P  = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. Conclusions: Online tests can detect visuo‐perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo‐perceptual tests may be developed to identify at‐risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Additional rare variant analysis in Parkinson's Disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance

Oligogenic inheritance implies a role for several genetic factors in disease etiology. We studied oligogenic inheritance in Parkinson’s (PD) by assessing the potential burden of additional rare variants in established Mendelian genes and/or GBA, in individuals with and without a primary pathogenic genetic cause in two large independent cohorts totaling 7,900 PD cases and 6,166 controls. An excess (≥30%) of cases with a recognized primary genetic cause had ≥1 additional rare variants in Mendelian PD genes, as compared with no known mutation PD cases (17%) and unaffected controls (16%), supporting our hypothesis. Carriers of additional Mendelian gene variants have younger ages at onset (AAO). The effect of additional Mendelian variants in LRRK2 G2019S mutation carriers, of which ATP13A2 variation is particularly common, may account for some of the variation in penetrance. About 10% of no known mutation PD cases harbor a rare GBA variant compared to known pathogenic mutation PD cases (8%) and controls (5%), with carriers having earlier AAOs. Together, the data suggest that the oligogenic inheritance of rare Mendelian variants may be important in patient with a primary pathogenic cause, whereas GBA increases risk across all forms of PD. This study highlights potential genetic complexity of Mendelian PD. The identification of potential modifying variants provides new insights into disease mechanisms by potentially separating relevant from benign variants and by the interaction between genes in specific pathways. In the future this may be relevant to genetic testing and counselling of PD patients and their families

Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data.

BACKGROUND: Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. METHODS: We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. FINDINGS: We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0-55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5-61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). INTERPRETATION: Clinicians should be alert to the possibility of 22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both. FUNDING: UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, "Investissements d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, “Investissements d'Avenir” ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/S1474-4422(16)00071-