“It’s not pain it’s discomfort”: development and investigation of a discomfort measurement scale.

Logically, anecdotally and empirically, there appears to be a shared understanding of the difference between 'pain' and 'discomfort'. Although discomfort is commonly referred to in medical literature, it has never been objectively measured or its properties examined. This study devised a visual analogue discomfort scale (VAS-D) and obtained a sample of n=128 outpatient musculoskeletal physiotherapy patients who complete it alongside a traditional visual analogue pain scale (VAS-P) and the EQ5D-5L. Demographic data was also collected. The purpose of the investigation was to preliminarily validate the VAS-D as a psychometric index. Scale scores and correlations are examined in the entire sample and in sub-samples split by gender and pain severity. Scale correlations were primarily moderate indicating the VAS-D measures a related but distinct construct to pain and there was a statistically significant difference between discomfort scores when compared to pain. This indicates the VAS-D measures a related, but distinct construct to pain. 7.8% of respondents endorsed the VAS-D but scored zero on the VAS-P. The relationships between pain and discomfort scores held face validity, adding empirical evidence to a theoretical relationship between the constructs. As a preliminary study, it appears the VAS-D is a valid scale that is distinct from a VAS-P. Data supports a hypothesis that VAS-P scores may be lower or even absent in the concurrent presence of a VAS-D measure. Clinical implications and direction for future investigation are briefly discussed

The Value of Pain Coping Constructs in Subcategorising Back Pain Patients according to Risk of Poor Outcome

Background. Subcategorising patients with chronic low back pain (CLBP) could improve patient outcomes and facilitate prioritisation of treatment resources. Objective. This study aimed to develop a subcategorising method for individuals with CLBP using the Coping Strategies Questionnaire 24 (CSQ24) and to investigate the methods potential validity. Methods. 196 patients were recruited from a physiotherapy outpatients department. All participants completed a battery of questionnaires before and after treatment including the CSQ24 and a measure of pain, disability, and mood. At discharge participants also completed a global subjective outcomes scale consisting of a 6-point Likert scale. All participants received usual physiotherapy. Results. Cut-off values for the CSQ24 were calculated using triangulation of the findings from three different statistical methods. Cut-off values were identified for the Catastrophising and Cognitive Coping subscales of the CSQ24. Participants were categorised into low, medium, and high risk of a poor outcome. The cut-off values for these were ≥21 on Cognitive Coping and ≤9 on Catastrophising for low risk and ≤15 on Cognitive Coping for high risk, with all other patients being classified as being at moderate risk. Conclusion. Further validation is required before this approach can be recommended for clinical practice

Exploring the longitudinal stability of the CSQ24 in a back pain population.

Objective: The CSQ24 is a shortened version of the Coping Strategies Questionnaire and includes 24 items and four factors-Catastrophizing, Diversion, Reinterpreting, and Cognitive Coping. The factor structure of the CSQ has been a matter for debate for some time. This study aimed to explore the stability of the factor structure of the CSQ24 using repeated measurements in a back pain population at assessment, after physiotherapy treatment, and at 6 and 12 months after treatment. Method: A consecutive sample of 194 adults with chronic low back pain was recruited over 24 months. They completed the CSQ24, with other measures of pain, disability and mood, on 4 occasions. Ninety-six participants satisfactorily completed and returned both 6- and 12-month longitudinal follow-up questionnaires. Results: Exploratory Factor Analysis showed, at each time point, a 4-factor structure of Catastrophizing, Cognitive Coping, Diversion, and Reinterpreting. Within each factor, the factor scores at each time point were significantly correlated and showed good internal reliability. This stability was demonstrated against a background of significant change in measures of pain, disability, and mood. Conclusions: These results provide support for the 4-factor structure of the CSQ24 and its longitudinal stability. Argument is provided for the need to explore the longitudinal stability of related tools in populations that undergo change as a result of treatment

Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.

WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1(-/-) mice lack any obvious limb or skeletal defects, Sost(-/-) mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost(-/-); Sostdc1(-/-) mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost(-/-) and Sost(-/-); Sostdc1(-/-) mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling

Resilience of health-care workers in the UK; a cross-sectional survey

Background Working for the UK National Health Service (NHS) requires working for organisations under financial pressures and frequent restructures, which can lead to anxiety over continuing employment and income. There are currently no studies to date that have examined the influence of personal resilience across all professions and demographics in the NHS. This study aims to quantify resilience within an NHS trust and explore the contribution of demographic variables of gender, age, years of service, pay grade, hours worked, job role, and division worked to the resilience response of employees. The study also explores the relationship between resilience levels and absence rates, as a marker for health and well-being amongst NHS staff. Methods This study consists of a cross-sectional on-line survey of staff employed in an NHS Trust. All trust employees were asked to complete a Resilience Scale (RS-25), and demographic questions including age, sex, length of service, NHS pay grade (banding), division, job role and number of hours worked per week. Trust level sickness absence rates were also collected during this period. Results were analysed using descriptive statistics, bivariate comparisons and chi-squared tests. Results Data was gained from 845 employees; a significant association between gender and resilience found females scoring higher on the resilience scale; x 2(5) =18.30, p < 0.05. A weak positive correlation between age and resilience found older employees displaying a higher level of resilience; r = 0.11, p <0.05. Results also suggest employees working between 18.75-37.5 hours a week have higher levels of resilience. Ancillary staff scored low on resilience compared to all other staff groups which showed moderate resilience. Clinical staff scored lower on resilience compared to both administrative staff and clinical staff with line management responsibilities. No correlations were found between absence rates and resilience. Conclusion This study gives a snapshot of the resilience of employees in a NHS trust. It is the first of its kind to take into consideration all job roles, divisions and the banding system within a trust. The results also indicate that resilience levels may not be a mediating factor for the health and well-being of NHS staff

Importance of decision support implementation in emergency department vancomycin dosing

INTRODUCTION: The emergency department (ED) plays a critical role in the management of life-threatening infection. Prior data suggest that ED vancomycin dosing is frequently inappropriate. The objective is to assess the impact of an electronic medical record (EMR) intervention designed to improve vancomycin dosing accuracy, on vancomycin dosing and clinical outcomes in critically ill ED patients. METHODS: Retrospective before-after cohort study of all patients (n=278) treated with vancomycin in a 60,000-visit Midwestern academic ED (March 2008 and April 2011) and admitted to an intensive care unit. The primary outcome was the proportion of vancomycin doses defined as “appropriate” based on recorded actual body weight. We also evaluated secondary outcomes of mortality and length of stay. RESULTS: The EMR dose calculation tool was associated with an increase in mean vancomycin dose ([14.1±5.0] vs. [16.5±5.7] mg/kg, p<0.001) and a 10.3% absolute improvement in first-dose appropriateness (34.3% vs. 24.0%, p=0.07). After controlling for age, gender, methicillin-resistant staphylococcus aureus infection, and Acute Physiology and Chronic Health Evaluation II score, 28-day in-hospital mortality (odds ratio OR 1.72; 95% CI [0.76–3.88], p=0.12) was not affected. CONCLUSION: A computerized decision-support tool is associated with an increase in mean vancomycin dose in critically ill ED patients, but not with a statistically significant increase in therapeutic vancomycin doses. The impact of decision-support tools should be further explored to optimize compliance with accepted antibiotic guidelines and to potentially affect clinical outcome

Design and development of MOSFIRE: the Multi-Object Spectrometer For Infra-Red Exploration at the Keck Observatory

MOSFIRE is a unique multi-object spectrometer and imager for the Cassegrain focus of the 10 m Keck 1 telescope. A refractive optical design provides near-IR (0.97 to 2.45 μm) multi-object spectroscopy over a 6.14' x 6.14' field of view with a resolving power of R~3,270 for a 0.7" slit width (2.9 pixels in the dispersion direction), or imaging over a field of view of 6.8' diameter with 0.18" per pixel sampling. A single diffraction grating can be set at two fixed angles, and order-sorting filters provide spectra that cover the K, H, J or Y bands by selecting 3rd, 4th, 5th or 6th order respectively. A folding flat following the field lens is equipped with piezo transducers to provide tip/tilt control for flexure compensation at the 0.1 pixel level. A special feature of MOSFIRE is that its multiplex advantage of up to 46 slits is achieved using a cryogenic Configurable Slit Unit or CSU developed in collaboration with the Swiss Centre for Electronics and Micro Technology (CSEM). The CSU is reconfigurable under remote control in less than 5 minutes without any thermal cycling of the instrument. Slits are formed by moving opposable bars from both sides of the focal plane. An individual slit has a length of 7.1" but bar positions can be aligned to make longer slits. When masking bars are removed to their full extent and the grating is changed to a mirror, MOSFIRE becomes a wide-field imager. Using a single, ASIC-driven, 2K x 2K H2-RG HgCdTe array from Teledyne Imaging Sensors with exceptionally low dark current and low noise, MOSFIRE will be extremely sensitive and ideal for a wide range of science applications. This paper describes the design and testing of the instrument prior to delivery later in 2010

MOSFIRE, the multi-object spectrometer for infra-red exploration at the Keck Observatory

This paper describes the as-built performance of MOSFIRE, the multi-object spectrometer and imager for the Cassegrain focus of the 10-m Keck 1 telescope. MOSFIRE provides near-infrared (0.97 to 2.41 μm) multi-object spectroscopy over a 6.1' x 6.1' field of view with a resolving power of R~3,500 for a 0.7" (0.508 mm) slit (2.9 pixels in the dispersion direction), or imaging over a field of view of ~6.9' diameter with ~0.18" per pixel sampling. A single diffraction grating can be set at two fixed angles, and order-sorting filters provide spectra that cover the K, H, J or Y bands by selecting 3rd, 4th, 5th or 6th order respectively. A folding flat following the field lens is equipped with piezo transducers to provide tip/tilt control for flexure compensation at the <0.1 pixel level. Instead of fabricated focal plane masks requiring frequent cryo-cycling of the instrument, MOSFIRE is equipped with a cryogenic Configurable Slit Unit (CSU) developed in collaboration with the Swiss Center for Electronics and Microtechnology (CSEM). Under remote control the CSU can form masks containing up to 46 slits with ~0.007-0.014" precision. Reconfiguration time is < 6 minutes. Slits are formed by moving opposable bars from both sides of the focal plane. An individual slit has a length of 7.0" but bar positions can be aligned to make longer slits in increments of 7.5". When masking bars are retracted from the field of view and the grating is changed to a mirror, MOSFIRE becomes a wide-field imager. The detector is a 2K x 2K H2-RG HgCdTe array from Teledyne Imaging Sensors with low dark current and low noise. Results from integration and commissioning are presented

Germline TERT promoter mutations are rare in familial melanoma.

Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that a rare promoter variant of TERT (c.-57 T>G) is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families. The identification of POT1 and TERT germline mutations highlights the importance of telomere integrity in melanoma biology.The authors would like to thank the families for their willingness to participate; and Rajiv Kumar for the provision of mutation positive samples. The collection of samples in the UK population-ascertained sample set was funded by Cancer Research UK (awards C588/A19167 and C8216/A6129) and by the NIH (CA83115). The work of N.A.G. and R.v.D was supported by the Dutch Cancer Society (UL 2012-5489). D.J.A and C.D.R.E are supported by Cancer Research UK, ERC Combat Cancer and the Wellcome Trust. N.K.H is supported by a fellowship from the National Health and Medical Research Council of Australia. A.M.D. and K.A.P. were supported by CRUK grant (C8197/A16565) and The Isaac Newton Trust. K.M.B. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10689-015-9841-

SARS-CoV-2 viability on sports equipment is limited, and dependent on material composition

OBJECTIVES The control of the COVID-19 pandemic in the UK has necessitated restrictions on amateur and professional sports due to the perceived infection risk to competitors, via direct person to person transmission, or possibly via the surfaces of sports equipment. The sharing of sports equipment such as tennis balls was therefore banned by some sport’s governing bodies. We sought to investigate the potential of sporting equipment as transmission vectors of SARS-CoV-2. Methods Ten different types of sporting equipment, including balls from common sports, were inoculated with 40μl droplets containing clinically relevant concentrations of live SARS-CoV-2 virus. Materials were then swabbed at time points relevant to sports (1, 5, 15, 30, 90 minutes). The amount of live SARS-CoV-2 recovered at each time point was enumerated using viral plaque assays, and viral decay and half-life was estimated through fitting linear models to log transformed data from each material. RESULTS At one minute, SARS-CoV-2 virus was recovered in only seven of the ten types of equipment with the low dose inoculum, one at five minutes and none at 15 minutes. Retrievable virus dropped significantly for all materials tested using the high dose inoculum with mean recovery of virus falling to 0.74% at 1 minute, 0.39% at 15 minutes and 0.003% at 90 minutes. Viral recovery, predicted decay, and half-life varied between materials with porous surfaces limiting virus transmission. CONCLUSIONS This study shows that there is an exponential reduction in SARS-CoV-2 recoverable from a range of sports equipment after a short time period, and virus is less transferrable from materials such as a tennis ball, red cricket ball and cricket glove. Given this rapid loss of viral load and the fact that transmission requires a significant inoculum to be transferred from equipment to the mucous membranes of another individual it seems unlikely that sports equipment is a major cause for transmission of SARS-CoV-2. These findings have important policy implications in the context of the pandemic and may promote other infection control measures in sports to reduce the risk of SARS-CoV-2 transmission and urge sports equipment manufacturers to identify surfaces that may or may not be likely to retain transferable virus