Peripheral nerve interfaces (PNIs) allow us to extract motor, sensory, and autonomic information from the nervous system and use it as control signals in neuroprosthetic and neuromodulation ...applications. Recent efforts have aimed to improve the recording selectivity of PNIs, including by using spatiotemporal patterns from multi-contact nerve cuff electrodes as input to a convolutional neural network (CNN). Before such a methodology can be translated to humans, its performance in chronic implantation scenarios must be evaluated. In this simulation study, approaches were evaluated for maintaining selective recording performance in the presence of two chronic implantation challenges: the growth of encapsulation tissue and rotation of the nerve cuff electrode. Performance over time was examined in three conditions: training the CNN at baseline only, supervised re-training with explicitly labeled data at periodic intervals, and a semi-supervised self-learning approach. This study demonstrated that a selective recording algorithm trained at baseline will likely fail over time due to changes in signal characteristics resulting from the chronic challenges. Results further showed that periodically recalibrating the selective recording algorithm could maintain its performance over time, and that a self-learning approach has the potential to reduce the frequency of recalibration.
Birmingham, UK, 1990-2010.
To identify predictors in contacts for completion of screening and of a positive screening outcome, i.e., a diagnosis of latent tuberculous infection (LTBI) or active ...tuberculosis (TB).
A retrospective cohort study of TB notifications for a European city.
A total of 46,158 contacts were identified from 7365 index cases. Over the study period 17,471 (40.9%) failed to complete screening. Active TB or LTBI was diagnosed in 2220 (7.0%) contacts of cases of pulmonary TB (PTB) and in 222 (2.7%) contacts of cases of extra-pulmonary TB (EPTB). The proportion of contacts offered LTBI treatment increased (P < 0.001) over the study period. Age, ethnicity, sex and use of interferon-gamma release assays (IGRA) were the most important predictors of screening completion, with working age adult males who were Black or from the Indian subcontinent least likely to complete. Age, smear positivity status of the index case and IGRA usage were the most important predictors of a positive screening outcome (active TB or LTBI diagnosed).
Contact tracing of both PTB and EPTB index cases is useful for active case finding. The findings of this study can be used to target screening and improve the effectiveness and efficiency of local contact tracing programmes.
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production ...and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.
This paper studies the impact performance of Steel–Concrete–Steel (SCS) sandwich beams consisting of a lightweight concrete core sandwiched between two face plates that are connected by J-hook ...connectors. Impact tests were carried out by dropping free weights on to sandwich beams to investigate their structural response against impact loads. Test results revealed that the proposed J-hook connectors provide an effective means to interlock the top and bottom steel face plates, preventing them from separation during impact. The use of fibres in concrete core and J-hook connectors for composite action enhances the overall structural integrity of the sandwich beams when compared with those without such enhancement. An elastic–plastic analysis method is developed to predict the force-indentation relationship of sandwich sections subjected to local impact. Dynamic analysis based on the local force-indentation relationship is carried out to predict the impact force and global response behavior of the sandwich beams. The predicted results are compared with those obtained from the tests to validate their accuracy so that they can be used to evaluate the performance of sandwich beams under low velocity hard impact.
Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty for patients who require treatment of single-compartment osteoarthritis, especially for young patients. To ...satisfy this requirement, new patient-specific prosthetic designs have been introduced. The patient-specific UKA is designed on the basis of data from preoperative medical images. In general, knee implant design with increased conformity has been developed to provide lower contact stress and reduced wear on the tibial insert compared with flat knee designs. The different tibiofemoral conformity may provide designers the opportunity to address both wear and kinematic design goals simultaneously. The aim of this study was to evaluate wear prediction with respect to tibiofemoral conformity design in patient-specific UKA under gait loading conditions by using a previously validated computational wear method.
Three designs with different conformities were developed with the same femoral component: a flat design normally used in fixed-bearing UKA, a tibia plateau anatomy mimetic (AM) design, and an increased conforming design. We investigated the kinematics, contact stress, contact area, wear rate, and volumetric wear of the three different tibial insert designs.
Conforming increased design showed a lower contact stress and increased contact area. In addition, increased conformity resulted in a reduction of the wear rate and volumetric wear. However, the increased conformity design showed limited kinematics.
Our results indicated that increased conformity provided improvements in wear but resulted in limited kinematics. Therefore, increased conformity should be avoided in fixed-bearing patient-specific UKA design. We recommend a flat or plateau AM tibial insert design in patient-specific UKA.
: Y-G. Koh, K-M. Park, H-Y. Lee, K-T. Kang. Influence of tibiofemoral congruency design on the wear of patient-specific unicompartmental knee arthroplasty using finite element analysis.
2019;8:156-164. DOI: 10.1302/2046-3758.83.BJR-2018-0193.R1.
Abstract
Background
Taxi driving has been associated with the risk of various diseases (e.g. cardiovascular disease, hypertension, diabetes, hyperlipaemia, back pain). Little is known about the ...relationship between health conditions and driving fitness of older taxi drivers who continue to work.
Aims
To investigate the (i) prevalence of medical conditions and (ii) relationship between age and medical conditions, with on-road driving tests in the relicensing process of older taxi drivers aged ≥70 years, prior to the mandatory retirement age of 75 years.
Methods
We analysed retrospectively all relicensing records (N = 855) of taxi drivers aged 70, 73 and 74 years that were submitted from April 2014 to April 2015.
Results
All passed their medical fitness screening. Ninety-eight per cent passed their driving tests. Thirty-one per cent, 36% and 24% reported none, one and two medical conditions, respectively. These included hypertension (56%), eye disease (25%; cataracts 19%), diabetes (24%), corrected hearing impairment (14%), hyperlipaemia (12%) and heart disease (9%). Deafness (P < 0.001) was associated with older age. No past medical condition affected driving outcome.
Conclusion
Older Singaporean taxi drivers were healthy and generally competent drivers. Early effective preventive health screening and modifiable lifestyle intervention are recommended in older taxi drivers.
Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and ...elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.
Background
Adults with intellectual disabilities (ID) face significant barriers to screening participation. We determined predictors for regular cardiovascular health screening at baseline among ...adults with ID in Singapore, and evaluated the effectiveness of a 3‐month screening intervention.
Methods
The study population involved all adults with ID aged ≥40 years receiving services from the Movement for the Intellectually Disabled of Singapore (MINDS), the largest such provider in Singapore. Over 3 months in 2011, adult clients not screened regularly at baseline for hypertension, diabetes and dyslipidaemia were offered free and convenient blood pressure, fasting blood glucose and lipid testing; data on other cardiovascular disease risk factors were also collected. Chi‐square and logistic regression identified predictors of regular screening at baseline.
Results
Participation was 95.0% (227/239). At baseline, among adults with ID, 61.8% (118/191), 24.8% (52/210) and 18.2% (34/187) had gone for regular hypertension, diabetes and dyslipidaemia screening respectively; post intervention, rates rose to 96.9%, 89.5% and 88.8% respectively. Prevalence of cardiovascular disease risk factors (22.5% with hypertension, 10.6% with diabetes, 34.8% with dyslipidaemia, 10.7% obese and 90.6% lacking regular exercise) was high compared against the general population. While receiving residential services was associated with regular hypertension screening, receiving non‐residential services and being independently mobile were associated with regular participation in fasting blood tests (all P < 0.05).
Conclusion
Cardiovascular disease risk factors are common among adults with ID and clinicians should proactively screen such populations. Provision of free and convenient screening for cardiovascular disease risk improved screening participation.
► CFRP. ► Circular tubular structure. ► Retrofitting of steel braces. ► Buckling strength.
Although the application of carbon fibre reinforced polymer (CFRP) on strengthening of concrete structures ...have been reported widely, there are relatively few applications to steel structures, especially to tubular steel structures. In order to investigate the performance of circular tubular steel braces retrofitted with CFRP, long hot finished circular hollow steel braces (88.9mm×4mm) wrapped with CFRP sheets are tested to study the effects of CFRP on overall buckling behavior. Based on the experimental results, a numerical model has been developed to predict the axial load capacity, lateral and axial displacements accounting for the initial out-of-straightness, material and geometric nonlinearities. It is found that CFRP layers could increase both the strength and stiffness of the brace considerably.
There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's ...early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness.
Prospective data from 505 mother-child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models.
Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034).
Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.
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