Socioeconomic deprivation and age are barriers to the online collection of patient reported outcome measures in orthopaedic patients

Introduction: Questionnaires are used commonly to assess functional outcome and satisfaction in surgical patients. Although these have in the past been administered through written forms, there is increasing interest in the use of new technology to improve the efficiency of collection. The aim of this study was to assess the availability of internet access for a group of orthopaedic patients and the acceptability of online survey completion. Methods: A total of 497 patients attending orthopaedic outpatient clinics were surveyed to assess access to the internet and their preferred means for completing follow-up questionnaires. Results: Overall, 358 patients (72%) reported having internet access. Lack of access was associated with socioeconomic deprivation and older age. Multivariable regression confirmed increased age and greater deprivation to be independently associated with lack of internet access. Out of the total group, 198 (40%) indicated a preference for assessment of outcomes via email and the internet. Conclusions: Internet access was not universal among the patients in our orthopaedic clinic. Reliance on internet collection of PROMs may introduce bias by not including results from patients in older age groups and those from the more deprived socioeconomic groups

Noninvasive Prenatal Diagnosis for Cystic Fibrosis: Implementation, Uptake, Outcome, and Implications

BACKGROUND: Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive NIPD for a recessive condition, cystic fibrosis (CF). // METHODS: Definitive NIPD for CF was developed using next-generation sequencing. Validation was performed on 13 cases from 10 families before implementation. All cases referred for CF NIPD were reviewed to determine turnaround times, genotyping results, and pregnancy outcomes. // RESULTS: Of 38 referrals, 36 received a result with a mean turnaround of 5.75 days (range, 3-11 days). Nine cases were initially inconclusive, with 3 reported unaffected because the low-risk paternal allele was inherited and 4 cases in which the high-risk paternal allele was inherited, receiving conclusive results following repeat testing. One case was inconclusive owing to a paternal recombination around the mutation site, and one case was uninformative because of no heterozygosity. Before 2016, 3 invasive referrals for CF were received annually compared with 38 for NIPD in the 24 months since offering a definitive NIPD service. // CONCLUSIONS: Timely and accurate NIPD for definitive prenatal diagnosis of CF is possible in a public health service laboratory. The method detects recombinations, and the service is well-received as evidenced by the significant increase in referrals. The bioinformatic approach is gene agnostic and will be used to expand the range of conditions tested for

Traumatic brain injury: a comparison of diffusion and volumetric magnetic resonance imaging measures

Cognitive impairment after traumatic brain injury remains hard to predict. This is partly because axonal injury, which is of fundamental importance, is difficult to measure clinically. Advances in MRI allow axonal injury to be detected after traumatic brain injury, but the most sensitive approach is unclear. Here, we compare the performance of diffusion tensor imaging, neurite orientation dispersion and density-imaging and volumetric measures of brain atrophy in the identification of white-matter abnormalities after traumatic brain injury. Thirty patients with moderate-severe traumatic brain injury in the chronic phase and 20 age-matched controls had T1-weighted and diffusion MRI. Neuropsychological tests of processing speed, executive functioning and memory were used to detect cognitive impairment. Extensive abnormalities in neurite density index and orientation dispersion index were observed, with distinct spatial patterns. Fractional anisotropy and mean diffusivity also indicated widespread abnormalities of white-matter structure. Neurite density index was significantly correlated with processing speed. Slower processing speed was also related to higher mean diffusivity in the corticospinal tracts. Lower white-matter volumes were seen after brain injury with greater effect sizes compared to diffusion metrics; however, volume was not sensitive to changes in cognitive performance. Volume was the most sensitive at detecting change between groups but was not specific for determining relationships with cognition. Abnormalities in fractional anisotropy and mean diffusivity were the most sensitive diffusion measures; however, neurite density index and orientation dispersion index may be more spatially specific. Lower neurite density index may be a useful metric for examining slower processing speed

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Time-Delay Interferometry

Equal-arm interferometric detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers), the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called Time-Delay Interferometry (or TDI). This article provides an overview of the theory and mathematical foundations of TDI as it will be implemented by the forthcoming space-based interferometers such as the Laser Interferometer Space Antenna (LISA) mission. We have purposely left out from this first version of our ``Living Review'' article on TDI all the results of more practical and experimental nature, as well as all the aspects of TDI that the data analysts will need to account for when analyzing the LISA TDI data combinations. Our forthcoming ``second edition'' of this review paper will include these topics.Comment: 51 pages, 11 figures. To appear in: Living Reviews. Added conten

Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

Background: Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings: Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance: This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system

Symptoms predicting psychosocial impairment in bulimia nervosa

Purpose The current study aimed to determine which particular eating disorder (ED) symptoms and related features, such as BMI and psychological distress, uniquely predict impairment in bulimia nervosa (BN). Methods Two hundred and twenty-two adults with BN completed questionnaires assessing ED symptoms, general psychological distress, and psychosocial impairment. Regression analyses were used to determine predictors which account for variance in impairment. Results Four variables emerged as significant predictors of psychosocial impairment: concerns with eating; concerns with weight and shape; dietary restraint; and general psychological distress. Conclusions Findings support previous work highlighting the importance of weight and shape concerns in determining ED-related impairment. Other ED symptoms, notably dietary restraint and concerns with eating, were also significant predictors as was psychological distress. Results suggest that cognitive aspects of EDs, in addition to psychological distress, may be more important determinants of impairment than behavioural symptoms, such as binge eating or purging

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

FaIRv2.0.0: a generalized impulse response model for climate uncertainty and future scenario exploration

Here we present an update to the FaIR model for use in probabilistic future climate and scenario exploration, integrated assessment, policy analysis, and education. In this update we have focussed on identifying a minimum level of structural complexity in the model. The result is a set of six equations, five of which correspond to the standard impulse response model used for greenhouse gas (GHG) metric calculations in the IPCC's Fifth Assessment Report, plus one additional physically motivated equation to represent state-dependent feedbacks on the response timescales of each greenhouse gas cycle. This additional equation is necessary to reproduce non-linearities in the carbon cycle apparent in both Earth system models and observations. These six equations are transparent and sufficiently simple that the model is able to be ported into standard tabular data analysis packages, such as Excel, increasing the potential user base considerably. However, we demonstrate that the equations are flexible enough to be tuned to emulate the behaviour of several key processes within more complex models from CMIP6. The model is exceptionally quick to run, making it ideal for integrating large probabilistic ensembles. We apply a constraint based on the current estimates of the global warming trend to a million-member ensemble, using the constrained ensemble to make scenario-dependent projections and infer ranges for properties of the climate system. Through these analyses, we reaffirm that simple climate models (unlike more complex models) are not themselves intrinsically biased “hot” or “cold”: it is the choice of parameters and how those are selected that determines the model response, something that appears to have been misunderstood in the past. This updated FaIR model is able to reproduce the global climate system response to GHG and aerosol emissions with sufficient accuracy to be useful in a wide range of applications and therefore could be used as a lowest-common-denominator model to provide consistency in different contexts. The fact that FaIR can be written down in just six equations greatly aids transparency in such contexts