What does high value care for musculoskeletal conditions mean and how do you apply it in practice? A consensus statement from a research network of physiotherapists in New South Wales, Australia.

OBJECTIVES: To develop a physiotherapist-led consensus statement on the definition and provision of high-value care for people with musculoskeletal conditions. DESIGN: We performed a three-stage study using Research And Development/University of California Los Angeles Appropriateness Method methodology. We reviewed evidence about current definitions through a rapid literature review and then performed a survey and interviews with network members to gather consensus. Consensus was finalised in a face-to-face meeting. SETTING: Australian primary care. PARTICIPANTS: Registered physiotherapists who are members of a practice-based research network (n=31). RESULTS: The rapid review revealed two definitions, four domains of high value care and seven themes of high-quality care. Online survey responses (n=26) and interviews (n=9) generated two additional high-quality care themes, a definition of low-value care, and 21 statements on the application of high value care. Consensus was reached for three working definitions (high value, high-quality and low value care), a final model of four high value care domains (high-quality care, patient values, cost-effectiveness, reducing waste), nine high-quality care themes and 15 statements on application. CONCLUSION: High value care for musculoskeletal conditions delivers most value for the patient, and the clinical benefits outweigh the costs to the individual or system providing the care. High-quality care is evidence based, effective and safe care that is patient-centred, consistent, accountable, timely, equitable and allows easy interaction with healthcare providers and healthcare systems.

Effect of Applied Pressure on the Electrical Resistance of Carbon Nanotube Fibers.

Carbon nanotubes (CNTs) can be spun into fibers as potential lightweight replacements for copper in electrical current transmission since lightweight CNT fibers weigh <1/6th that of an equivalently dimensioned copper wire. Experimentally, it has been shown that the electrical resistance of CNT fibers increases with longitudinal strain; however, although fibers may be under radial strain when they are compressed during crimping at contacts for use in electrical current transport, there has been no study of this relationship. Herein, we apply radial stress at the contact to a CNT fiber on both the nano- and macro-scale and measure the changes in fiber and contact resistance. We observed an increase in resistance with increasing pressure on the nanoscale as well as initially on the macro scale, which we attribute to the decreasing of axial CNT…CNT contacts. On the macro scale, the resistance then decreases with increased pressure, which we attribute to improved radial contact due to the closing of voids within the fiber bundle. X-ray photoelectron spectroscopy (XPS) and UV photoelectron spectroscopy (UPS) show that applied pressure on the fiber can damage the π-π bonding, which could also contribute to the increased resistance. As such, care must be taken when applying radial strain on CNT fibers in applications, including crimping for electrical contacts, lest they operate in an unfavorable regime with worse electrical performance.

Pressure dependent conduction of individual multi-walled carbon nanotubes: the effect of mechanical distortions.

Multi-walled carbon nanotubes (MWCNTs) show an oscillation in electrical resistance (from I-V measurements) during mechanical distortion in which peak separation is inversely correlated with the diameter of the MWCNTs. These results provide the first experimental support of the theoretical prediction that distortion causes Van Hove singularities and Dirac cones in MWCNTs to misalign and cause the opening of the band gap, and suggest that when fabricating contacts for CNTs for device applications, the pressure caused by the contact deposition method must be taken into account for manufacturing devices with consistent properties.

Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.

Inducing upwards band bending by surface stripping ZnO nanowires with argon bombardment.

Metal oxide semiconductors such as ZnO have attracted much scientific attention due their material and electrical properties and their ability to form nanostructures that can be used in numerous devices. However, ZnO is naturally n-type and tailoring its electrical properties towards intrinsic or p-type in order to optimise device operation have proved difficult. Here, we present an x-ray photon-electron spectroscopy and photoluminescence study of ZnO nanowires that have been treated with different argon bombardment treatments including with monoatomic beams and cluster beams of 500 atoms and 2000 atoms with acceleration volte of 0.5 keV-20 keV. We observed that argon bombardment can remove surface contamination which will improve contact resistance and consistency. We also observed that using higher intensity argon bombardment stripped the surface for nanowires causing a reduction in defects and surface OH- groups both of which are possible causes of the n-type nature and observed a shift in the valance band edge suggest a shift to a more p-type nature. These results indicate a simple method for tailoring the electrical characteristic of ZnO.

Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effectiveness of Weight-Loss Interventions for Reducing Pain and Disability in People With Common Musculoskeletal Disorders: A Systematic Review With Meta-Analysis.

OBJECTIVE: To assess the effectiveness of weight-loss interventions on pain and disability in people with knee and hip osteoarthritis (OA) and spinal pain. DESIGN: Intervention systematic review. LITERATURE SEARCH: Twelve online databases and clinical trial registries. STUDY SELECTION CRITERIA: Randomized controlled trials of any weight-loss intervention (eg, diet, physical activity, surgical, pharmaceutical) that reported pain or disability outcomes in people with knee or hip OA or spinal pain. DATA SYNTHESIS: We calculated mean differences or standardized mean differences (SMDs) and 95% confidence intervals (CIs). We used the Cochrane risk of bias tool to assess risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation tool to judge credibility of evidence. RESULTS: Twenty-two trials with 3602 participants were included. There was very low- to very low-credibility evidence for a moderate effect of weight-loss interventions on pain intensity (10 trials, n = 1806; SMD, -0.54; 95% CI: -0.86, -0.22; I2 = 87%, P<.001) and a small effect on disability (11 trials, n = 1821; SMD, -0.32; 95% CI: -0.49, -0.14; I2 = 58%, P<.001) compared to minimal care for people with OA. For knee OA, there was low- to moderate-credibility evidence that weight-loss interventions were not more effective than exercise only for pain intensity and disability, respectively (4 trials, n = 673; SMD, -0.13; 95% CI: -0.40, 0.14; I2 = 55%; 5 trials, n = 737; SMD, -0.20; 95% CI: -0.41, 0.00; I2 = 32%). CONCLUSION: Weight-loss interventions may provide small to moderate improvements in pain and disability for OA compared to minimal care. There was limited and inconclusive evidence for weight-loss interventions targeting spinal pain. J Orthop Sports Phys Ther 2020;50(6):319-333. Epub 9 Apr 2020. doi:10.2519/jospt.2020.9041.

An index of geospatial disadvantage predicts both obesity and unmeasured body weight.

Neighborhood context impacts health. Using an index of geospatial disadvantage measures to predict neighborhood socioeconomic disparities would support area-based allocation of preventative resources, as well as the use of location as a clinical risk factor in care of individual patients. This study tested the association of the Area Deprivation Index (ADI), a neighborhood-based index of socioeconomic contextual disadvantage, with elderly obesity risk. We sampled 5066 Medicare beneficiaries at the University of Missouri between September 1, 2013 and September 1, 2014. We excluded patients with unknown street addresses, excluded body mass index (BMI) lower than 18 or higher than 62 as probable errors, and excluded patients with missing BMI data. We used a plot of simple proportions to examine the association between ADI and prevalence of obesity, defined as BMI of 30 and over. We found that obesity was significantly less prevalent in the least-disadvantaged ADI decile (decile 1) than in all other deciles (p < 0.05) except decile 7. Obesity prevalence within the other deciles (2-6 and 8-10) was not significantly distinguishable except that decile 2 was significantly lower than decile 4. Patients with missing BMI data were more likely to reside in the most disadvantaged areas. There was a positive association between neighborhood disadvantage and obesity in this Midwestern United States Medicare population. The association of missing BMI information with neighborhood disadvantage may reflect unmeasured gaps in care delivery to the most disadvantaged patients. These preliminary results support the continued study of neighborhood socioeconomic measures to identify health disparities in populations.

Experimental Measurement of Angular and Overlap Dependence of Conduction between Carbon Nanotubes of Identical Chirality and Diameter.

Measurement of the angular and overlap dependence of the conduction between two identical carbon nanotubes (CNTs), with the same diameter and chirality, has only been possible through theoretical calculations; however, our observation of increased resistance adjacent to the junction between two CNTs facilitates such measurements. Since electrical resistance was found to increase with increased diameter ratio, applying 10 V to one of dissimilar diameter CNTs results in cleavage at the junction. Manipulation of the resulting identical CNTs (created by cutting a single CNT) allows for the direct measurement of the angular and parallel overlap conduction. Angular (13° < θ < 63°) dependence shows two minima (22° and 44°) and a maximum at 30°, and conduction between parallel CNTs increases with overall tip separation but shows a sinusoidal relationship with contact length, consistent with the concept of atomic scale registry.

Investigation into the effects of surface stripping ZnO nanosheets.

ZnO nanosheets are polycrystalline nanostructures that are used in devices including solar cells and gas sensors. However, for efficient and reproducible device operation and contact behaviour the conductivity characteristics must be controlled and surface contaminants removed. Here we use low doses of argon bombardment to remove surface contamination and make reproducible lower resistance contacts. Higher doses strip the surface of the nanosheets altering the contact type from near-ohmic to rectifying by removing the donor-type defects, which photoluminescence shows to be concentrated in the near-surface. Controlled doses of argon treatments allow nanosheets to be customised for device formation.

Spatial and Contamination-Dependent Electrical Properties of Carbon Nanotubes.

Two-point probe and Raman spectroscopy have been used to investigate the effects of vacuum annealing and argon bombardment on the conduction characteristics of multiwalled carbon nanotubes (MWCNTs). Surface contamination has a large effect on the two-point probe conductivity measurements which results in inconsistent and nonreproducible contacts. The electric field under the contacts is enhanced which results in overlapping depletion regions when probe separations are small (<4 µm) causing very high resistances. Annealing at 200 and 500 °C reduced the surface contamination on the MWCNT, but high resistance contacts still did not allow intrinsic conductivity measurements of the MWCNT. The high resistance measured due to the overlapping depletion regions was not observed after annealing to 500 °C. Argon bombardment reduced the surface contamination more than vacuum annealing at 500 °C but caused a slight increase in the defects concentration, enabling the resistivity of the MWCNT to be calculated, which is found to be dependent on the CNT diameter. The observations have significant implications for future CNT-based devices.

A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations.

PURPOSE: The craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis. METHODS: A 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively. RESULTS: Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. Clinically significant variants were also identified in ALX4, EFNA4, ERF, and FGF10. CONCLUSION: These findings support the clinical utility of a massively parallel sequencing panel for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen syndrome.

Surface sensitivity of four-probe STM resistivity measurements of bulk ZnO correlated to XPS.

Multi-probe instruments based on scanning tunnelling microscopy (STM) are becoming increasingly common for their ability to perform nano- to atomic-scale investigations of nanostructures, surfaces and in situ reactions. A common configuration is the four-probe STM often coupled with in situ scanning electron microscopy (SEM) that allows precise positioning of the probes onto surfaces and nanostructures enabling electrical and scanning experiments to be performed on highly localised regions of the sample. In this paper, we assess the sensitivity of four-probe STM for in-line resistivity measurements of the bulk ZnO surface. The measurements allow comparisons to established models that are used to relate light plasma treatments (O and H) of the surfaces to the resistivity measurements. The results are correlated to x-ray photoelectron spectroscopy (XPS) and show that four-probe STM can detect changes in surface and bulk conduction mechanisms that are beyond conventional monochromatic XPS.

XPS investigation of titanium contact formation to ZnO nanowires.

Ti is often used to form an initial Ohmic interface between ZnO and Au due to its low work function, and the TiO2/ZnO heterojunction is also of great importance for many practical applications of nanoparticles. Here, Ti has been controllably deposited onto hydrothermally grown ZnO nanowires and the formation of metal-semiconductor contact has been investigated using x-ray photoelectron spectroscopy (XPS), photoluminescence (PL) spectroscopy and scanning electron microscopy. XPS results showed that that the Ti initially reacts with surface oxygen species to form TiO2, and further deposition results in the formation of oxides with oxidation state numbers lower than four, and eventually metallic Ti on top of the TiO2. The formation of TiC was also observed. XPS showed that the onset of metallic Ti coincided with a Zn 3p core level shift to lower binding energy, indicating upwards band bending and the formation of a rectifying contact. Annealing caused a near-complete conversion of the metallic Ti to TiO2 and caused the Zn 3p to shift back to its original higher binding energy, resulting in downwards band bending and a more Ohmic contact. PL measurements showed that the optical properties of the nanowires are not affected by the contact formation.

The Effect of Neighborhood Disadvantage on Diabetes Prevalence.

Patient socioeconomic data is not usually included in medical records nor easily accessible to clinicians, yet socioeconomic disadvantage can be an important guide to disease management. This study evaluated the neighborhood-level Area Deprivation Index (ADI), a measure of neighborhood socioeconomic disadvantage, as a factor in diabetes mellitus prevalence. Electronic health records at an academic hospital system identified 4,770 Medicare beneficiaries. Logistic regression of diabetes diagnosis (ICD9=250.x) against ADI quintile, age, gender, and race/ethnicity found all these patient characteristics to be significantly associated. Diabetes prevalence was lowest in the least disadvantaged quintile of neighborhoods after adjusting for age, gender, and race/ethnicity. The positive non-linear association of diabetes prevalence with ADI demonstrates the power of this index to practically quantify socioeconomic disadvantage. The ADI may be suitable for clinical decision support, and for informing the policy changes which are needed to reduce socioeconomic disparities in diabetes prevalence and other health outcomes.

The effects of surface stripping ZnO nanorods with argon bombardment.

ZnO nanorods are used in devices including field effects transistors, piezoelectric transducers, optoelectronics and gas sensors. However, for efficient and reproducible device operation and contact behaviour, surface contaminants must be removed or controlled. Here we use low doses of argon bombardment to remove surface contamination and make reproducible lower resistance contacts. Higher doses strip the surface of the nanorods allowing intrinsic surface measurements through a cross section of the material. Photoluminescence finds that the defect distribution is higher at the near-surface, falling away in to the bulk. Contacts to the n-type defect-rich surface are near-Ohmic, whereas stripping away the surface layers allows more rectifying Schottky contacts to be formed. The ability to select the contact type to ZnO nanorods offers a new way to customize device behaviour.

Effects of Vacuum Annealing on the Conduction Characteristics of ZnO Nanosheets.

ZnO nanosheets are a relatively new form of nanostructure and have demonstrated potential as gas-sensing devices and dye sensitised solar cells. For integration into other devices, and when used as gas sensors, the nanosheets are often heated. Here we study the effect of vacuum annealing on the electrical transport properties of ZnO nanosheets in order to understand the role of heating in device fabrication. A low cost, mass production method has been used for synthesis and characterisation is achieved using scanning electron microscopy (SEM), photoluminescence (PL), auger electron spectroscopy (AES) and nanoscale two-point probe. Before annealing, the measured nanosheet resistance displayed a non-linear increase with probe separation, attributed to surface contamination. Annealing to 300 °C removed this contamination giving a resistance drop, linear probe spacing dependence, increased grain size and a reduction in the number of n-type defects. Further annealing to 500 °C caused the n-type defect concentration to reduce further with a corresponding increase in nanosheet resistance not compensated by any further sintering. At 700 °C, the nanosheets partially disintegrated and the resistance increased and became less linear with probe separation. These effects need to be taken into account when using ZnO nanosheets in devices that require an annealing stage during fabrication or heating during use.

Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.

Williams Syndrome Transcription Factor (WSTF) is one of ∼25 haplodeficient genes in patients with the complex developmental disorder Williams Syndrome (WS). WS results in visual/spatial processing defects, cognitive impairment, unique behavioral phenotypes, characteristic "elfin" facial features, low muscle tone and heart defects. WSTF exists in several chromatin remodeling complexes and has roles in transcription, replication, and repair. Chromatin remodeling is essential during embryogenesis, but WSTF's role in vertebrate development is poorly characterized. To investigate the developmental role of WSTF, we knocked down WSTF in Xenopus laevis embryos using a morpholino that targets WSTF mRNA. BMP4 shows markedly increased and spatially aberrant expression in WSTF-deficient embryos, while SHH, MRF4, PAX2, EPHA4 and SOX2 expression are severely reduced, coupled with defects in a number of developing embryonic structures and organs. WSTF-deficient embryos display defects in anterior neural development. Induction of the neural crest, measured by expression of the neural crest-specific genes SNAIL and SLUG, is unaffected by WSTF depletion. However, at subsequent stages WSTF knockdown results in a severe defect in neural crest migration and/or maintenance. Consistent with a maintenance defect, WSTF knockdowns display a specific pattern of increased apoptosis at the tailbud stage in regions corresponding to the path of cranial neural crest migration. Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS.

WSTF does it all: a multifunctional protein in transcription, repair, and replication.

Williams syndrome transcription factor (WSTF) has emerged as an incredibly versatile nuclear protein. WSTF and the ATP-dependent chromatin remodeling complexes in which it exists, WINAC, WICH, and B-WICH, have been studied in a variety of organisms. This research has revealed roles for WSTF in a number of diverse molecular events. WSTF function includes chromatin assembly, RNA polymerase I and III gene regulation, vitamin D metabolism, and DNA repair. In addition to functioning as a subunit of several ATP-dependent chromatin remodeling complexes, WSTF binds specifically to acetylated histones and is itself a histone kinase as well as a target of phosphorylation. This review will describe the three known WSTF-containing complexes and discuss their various roles as well as mechanisms of regulating WSTF activity.