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24 p.-10 fig., The cucumber mosaic virus (CMV) 2b viral suppressor of RNA silencing (VSR) is a potent counter-defense and pathogenicity factor that inhibits antiviral silencing by titration of short double-stranded RNAs. It also disrupts microRNA-mediated regulation of host gene expression by binding ARGONAUTE 1 (AGO1). But in Arabidopsis thaliana complete inhibition of AGO1 is counterproductive to CMV since this triggers another layer of antiviral silencing mediated by AGO2, de-represses strong resistance against aphids (the insect vectors of CMV), and exacerbates symptoms. Using confocal laser scanning microscopy, bimolecular fluorescence complementation, and co-immunoprecipitation assays we found that the CMV 1a protein, a component of the viral replicase complex, regulates the 2b-AGO1 interaction.By binding 2b protein molecules and sequestering them in P-bodies, the 1a protein limits the proportion of 2b protein molecules available to bind AGO1, which ameliorates 2b-induced disease symptoms, and moderates induction of resistance to CMV and to its aphid vector.However, the 1a protein-2b protein interaction does not inhibit the ability of the 2b protein to inhibit silencing of reporter gene expression in agroinfiltration assays. The interaction between the CMV 1a and 2b proteins represents a novel regulatory system in which specific functions of a VSR are selectively modulated by another viral protein. The finding also provides a mechanism that explains how CMV, and possibly other viruses, modulates symptom induction and manipulates host-vector interactions., Major funding for this project was provided to JPC by the UK Biotechnological and Biological Sciences Research Council (Grant numbers BB/J011762/1 and GCRF BB/P023223/1. Additional funding was obtained from the Leverhulme Trust (Grant numbers RPG-2012-667 and F/09741/F: https://www.leverhulme.ac.uk/) to JPC, and Newton Trust (http://www.newtontrust.cam.ac.uk/: grant number 12.07/I) to AMM.

Outcomes after Strasberg grade E bile duct injury have been widely reported. However, there are comparatively few reports of outcomes after Strasberg A to D bile duct injury. Therefore, the aim of this study was to comprehensively evaluate the long-term clinical and economic impact of Strasberg A to D bile duct injury.Patients with Strasberg A to D bile duct injury were identified from a prospectively collected and maintained database. Long-term biliary complication rates, as well as treatment costs were then estimated, and compared across Strasberg injury grades.A total of N = 120 patients were identified, of whom N = 49, 13, 20, and 38 had Strasberg grade A, B, C, and D bile duct injury, respectively. Surgical repair was most commonly performed in Strasberg grade D injuries (74% vs 8%-20% in lower grades, P.001). By 5 years post bile duct injury, the estimated long-term biliary complication rate was 40% in Strasberg grade D injuries, compared with 15% in Strasberg grade A (P = .022). A significant difference in total treatment and follow-up costs was also detected (P.001), being highest in Strasberg grade D injuries (mean £11,048/US$14,252 per patient) followed by the Strasberg grade B group (mean £10,612/US$13,689 per patient).Strasberg grade A to D injuries lead to considerable long-term morbidity and cost. Strasberg grade D injuries are typically managed surgically and result in the highest complication rate and treatment costs. Strasberg grade B injuries lead to a similar complication rate and treatment cost but are often managed without surgery.

Background Several studies have reported the effect of bile duct injury (BDI) on health-related quality of life (HRQOL) with conflicting results. This systematic review aims to study the impact of patient and treatment factors on HRQOL after BDI. Methods A search of the PubMed database was performed and studies were reviewed as per the PRISMA guidelines. Selected studies (n = 11) were then divided into two subgroups depending on whether they found HRQOL to be similar or worse between BDI and control groups. Pooled rates of surgical repair and major BDI were calculated for each of these subgroups. Results Surgical repair rates were 99% (95% CI: 96%–99%) in studies where the BDI patients had similar outcomes to controls, compared to 78% (40%–100%) where their outcomes were significantly worse (p = 0.091). The major BDI rate was 51% (95% CI: 42%–61%) in studies where the BDI patients had similar outcomes to controls, compared to 72% (41%–94%) where their outcomes were significantly worse (p = 0.322). Considerable heterogeneity was present within the two subgroups (I2: 68–99%). Discussion HRQOL may be adversely affected amongst patients with BDI who do not undergo surgical repair. Significant heterogeneity of data suggests the need for standardised HRQOL tools and injury severity systems when assessing outcomes after BDI.

Aims The aims of the study were two-fold: i) examine the validity and reliability of high-speed kicking actions using foot-mounted inertial measurement unit’s (IMU), ii) quantify soccer players within-microcycle and inter-positional differences in both the frequency and speed of technical actions. Methods During the in-season phase (25 weeks) of the UK domestic season, 21 professional soccer player ball releases, high-speed ball releases and ball release index were analysed. Pearson product-moment correlation coefficient and confidence intervals were used to determine the validity between the systems, whilst a general linear mixed model analysis approach was used to establish estimated marginal mean values for total ball releases, high-speed ball releases and ball release index. Results Good concurrent validity was observed for ball release velocity and high-speed kicks against a high-speed camera (r2- 0.96, CI 0.93–0.98). Ball releases, high-speed ball releases and ball release index all showed main effects for fixture proximity (p>0.001), playing positions (p>0.001) and across different training categories (p>0.001). The greatest high-speed ball releases were observed on a match-day (MD)+1 (17.6 ± 11.9; CI- 16.2 to 19) and MD-2 (16.8 ± 15; CI- 14.9 to 18.7), with MD+1 exhibiting the highest number of ball releases (161.1 ± 51.2; CI- 155.0 to 167.2) and ball release index (145.5 ± 45.2; CI- 140.1 to 150.9) across all fixture proximities. Possessions (0.3 ± 0.9; CI- 0.3 to 0.4) and small-sided games (1.4 ± 1.6; CI- 1.4 to 1.5), had the lowest values for high-speed ball releases with technical (6.1 ± 7.2; CI- 5.7 to 6.6) and tactical (10.0 ± 10.5; CI- 6.9 to 13.1) drills showing the largest high-speed ball releases. Conclusions The present study provides novel information regarding the quantification of technical actions of professional soccer players. Insights into absolute and relative frequency and intensity of releases in different drill types, provide practitioners with valuable information on technical outputs that can be manipulated during the process of planning training programmes to produce desired outcomes. Both volume and speed of ball release actions should be measured, when monitoring the technical actions in training according to fixture proximity, drill type and player position to permit enhanced training prescription.

Publisher Copyright: © 2021 The Authors Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1–3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response—energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

The thermoneutral zone (TNZ) defines the range of ambient temperatures at which resting metabolic rate (MR) is at a minimum. While the TNZ lower limit has been characterized, it is still unclear whether there is an upper limit, that is, beyond which MR during rest increases, and if so, what physiological upregulations explain this. We take the first step to fill this knowledge gap by measuring MR and multiple physiological variables in participants exposed to ambient heat stress while resting. Thirteen participants were exposed for an hour to 28℃‐50% relative humidity (RH) air, and both 40 and 50℃ each in 25% RH and humid (50% RH) conditions. Core and skin temperatures, blood pressure, sweat‐, heart‐, and breathing‐rate, minute ventilation, and movement levels were recorded throughout each condition. MR increased 35% (p = .015) during exposure to 40℃‐25% RH compared to baseline and a further 13% (p = .000) at in 50℃‐50%RH. This was not explained by increased fidgeting (p = .26), suggesting physiological upregulation. However, while greater heat stress invoked increases in heart rate (64%, p = .000), minute ventilation (78%, p = .000), and sweat rate (74%. p = .000) when comparing 50℃‐50% RH with baseline, the exact size of their relative energy cost is unclear and, therefore, so is their contribution to this increase in MR. Our study shows clear evidence that resting MR increases in humans at high temperature—there is a metabolic upper critical temperature, at least as low as 40℃. Further studies should pinpoint this value and fully explain this increased MR., Little research has been performed to characterize the upper human thermoneutral zone (TNZ). To find out if the resting metabolic rate (RMR) increases above the TNZ, 13 participants were exposed to a series of hot ambient temperatures. Our study found that RMR did, indeed, increase and, thus, is the first to provide evidence of a metabolic upper critical temperature.

OBJECTIVES To measure variation in spending and inpatient prices associated with the primary care physician (PCP) practice to which patients are attributed. STUDY DESIGN Cross-sectional analysis of claims data. METHODS We used random effect models to estimate case mix-adjusted spending across large PCP practices within 3-digit zip codes. We compare inpatient prices for patients in high-spending practices with those in low-spending practices. RESULTS The physician practice to which a patient was attributed is associated with significant differences in spending after controlling for patient comorbidities and geography. Patients attributed to practices in the top quartile of total medical expenses have about 30% higher spending than patients attributed to practices in the bottom quartile of adjusted spending in their 3-digit zip code. If patients attributed to practices in the top 2 quartiles had spending equivalent to those in the median practice, total spending would drop by 8%. Price variation accounts for a meaningful amount of the variation, with inpatient prices 17% higher in top-quartile vs bottom-quartile practices. We cannot disaggregate the large variation in utilization into practice patterns and unmeasured case mix (including unmeasured differences in patients' socioeconomic status) vs random health shocks, but correlation in spending patterns across years suggests that some persistent differences in spending patterns exist. CONCLUSIONS There are meaningful opportunities to reduce spending by changing patient PCP selection, encouraging patients to use lower-priced specialists and hospitals, and eliminating wasteful care. Attention must be paid to the best ways to reap these savings.

Objectives The incidence of hip fracture is high and increasing globally due to an aging population. Morbidity and mortality from these injuries are high at baseline and worse without prompt surgical treatment to facilitate early mobilization. Due to resource constraints, surgeons in low-income countries often must adapt available materials to meet these surgical needs. The objective of this study is to assess functional outcomes after surgical fixation of intertrochanteric femur fractures with the Surgical Implant Generation Network (SIGN) intramedullary nail augmented by a lateral SIGN plate. Design Prospective case series. Setting Juba Teaching Hospital, Tertiary Referral Hospital for South Sudan. Participants Adult patients with intertrochanteric hip fractures. Intervention SIGN nail augmented by a lateral plate. Main outcome measurements Primary outcome was hip function as measured by a modified Harris Hip Score (mHHS) at 1-year after surgery. Secondary endpoints were the occurrence of reoperation or infection at 1-year after surgery. Results Thirty patients were included, 16 (53%) men and 14 (47%) women, with a mean age of 62 years. Fractures were classified as AO/OTA Type 31A1 in 12 (40%) patients, 31A2 in 15 (50%) patients, and 31A3 in 3 (10%) patients. Mean mHHS at 1-year was 75.10 ± 21.2 with 76% categorized as excellent or good scores. There was 1 (3%) infection and 2 (7%) reoperations. Conclusions The SIGN nail augmented by a lateral plate achieved good or excellent hip function in the majority of patients with intertrochanteric hip fractures. This may be a suitable alternative to conventional implants for hip fracture patients in low-resource settings to allow mobilization.

Complications and litigation after bile duct injury (BDI) result in clinical and economic burden. The aim of this study was to comprehensively evaluate the long-term clinical and economic impact of major BDI.Patients with long-term follow-up after Strasberg E BDI were identified. Costs of treatment and litigation were the primary outcome. Relationships between these outcomes and repair factors, like timing of repair and surgeon expertise, were secondary outcomes.Among 139 patients with a median follow up of 10.7 years, 40% of patients developed biliary complications. Repairs by non-specialist surgeons had significantly higher follow up and treatment costs than those by specialists (£25,814 vs. £14,269, p 0.001). Estimated litigation costs were higher in delayed than immediate repairs (£23,295 vs. £12,864). As such, the lowest average costs per BDI are after immediate specialist repair and the highest after delayed non-specialist repair (£27,133 vs. £49,109, ×1.81 more costly, p 0.001). Repair by a non-specialist surgeon (HR: 4.00, p 0.001) and vascular injury (HR: 2.35, p = 0.013) were significant independent predictors of increased complication rates.Costs of major BDI are considerable. They can be reduced by immediate on-table repair by specialist surgeons. This must therefore be considered the standard of care wherever possible.

OBJECTIVES (1) To determine the infection rate after fixation of open tibial shaft fractures using the Surgical Implant Generation Network (SIGN) intramedullary nail in low- and middle-income countries (LMICs) and (2) to identify risk factors for infection. DESIGN Prospective cohort study using an international online database. SETTING Multiple hospitals in LMICs worldwide. PATIENTS/PARTICIPANTS A total of 1061 open tibia fractures treated with the SIGN nail in LMICs between March 2000 and February 2013. INTERVENTION Intravenous antibiotic administration, surgical debridement, and definitive intramedullary nailing within 14 days of injury. MAIN OUTCOME MEASUREMENTS Deep or superficial infection at follow-up, implant breakage/loosening, angular deformity >10 degrees, repeat surgery, radiographic union, weight bearing, and ability to kneel. RESULTS The overall infection rate was 11.9%. Infection rates by the Gustilo and Anderson classification were type 1: 5.1%, type II: 12.6%, type IIIa: 12.5%, type IIIb: 29.1%, and type IIIc: 16.7% (P = 0.001 between groups). Patients who developed infection had a longer mean time from injury to definitive surgery (4.7 vs. 3.9 days, P = 0.03) and from injury to wound closure (13.7 vs. 3.6 days, P < 0.001). Distal fractures had a higher infection rate than midshaft fractures (13.3% vs. 8.2%, P = 0.03). Infection rates were not associated with time from injury to initial debridement, time from injury to initial antibiotic administration, or total duration of antibiotics. CONCLUSIONS Open tibia fractures can be managed effectively using the SIGN intramedullary nail in LMICs with an overall infection rate of 11.9%. Risk factors for infection identified include more severe soft-tissue injury, delayed nailing, delayed wound closure, and distal fracture location. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND There are few validated instruments that serve as a proxy for fracture-healing after lower-extremity trauma in low-resource settings. The squat-and-smile test (S&S) has been under development by SIGN (Surgical Implant Generation Network) Fracture Care International to monitor outcomes of lower-extremity long-bone fractures after intramedullary nailing in resource-limited settings. The goals of this study were to develop and identify domains of the S&S test. METHODS The S&S domains were developed through an iterative process, and consensus was achieved regarding 3: squat depth, support needed to squat, and facial expression. Adult patients with an OTA/AO type-32 femoral shaft fracture were included in this retrospective study and had the S&S administered at 6 weeks and 3, 6, and 12 months postoperatively. Two authors independently assessed photographs of the patients performing the S&S. S&S domains were correlated with the EuroQol 5-Dimensions (EQ-5D) index score, and comparisons were made between S&S domains and reoperation status. Interrater and test-retest reliability was assessed using the kappa statistic. Sensitivity and specificity analyses were performed. RESULTS Six hundred and nine S&S images were evaluated for 231 patients. Each domain improved over time and correlated positively with EQ-5D scores (p < 0.05). Squat depth and support needed to squat correlated with the need for a reoperation (p ≤ 0.01), and both had high specificity (0.95 and 0.97, respectively) for ruling out the need for a reoperation at 1 year. All 3 domains had high test-retest reliability (κ = 0.95, 0.92, and 0.96). Squat depth and need for support also had strong interrater reliability (κ = 0.75 and 0.78). CONCLUSIONS The S&S is a potential tool for monitoring clinical and functional outcome of femoral shaft fractures in low-resource settings. Our data support the binary assessment of squat depth and need for support, but not facial expression, as a proxy for fracture-healing. Future prospective studies in external populations are warranted to evaluate the validity, reliability, and responsiveness of the S&S. CLINICAL RELEVANCE The S&S provides a valuable proxy for femoral shaft fracture assessment for middle to low-income countries because it is locally relevant (based on squatting), it is easy to administer, and assessment can be performed remotely via mobile telephone or text messaging.

Importance: Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.Objective: To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.Design, Setting, and Participants: This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.Main Outcomes and Measures: MDD and physical activity.Results: GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = -0.08 in mean acceleration per MDD vs control status; 95% CI, -0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, -0.008 to 0.05; P = .15).Conclusions and Relevance: Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.

OBJECTIVE To evaluate femoral growth after placement of retrograde intramedullary nails in the treatment of pediatric femoral shaft fractures. DESIGN Retrospective case series. SETTING Large urban trauma center in Mongolia. PATIENTS/PARTICIPANTS Twenty-nine pediatric patients who sustained a diaphyseal femoral shaft fracture were included in the study. INTERVENTION Retrograde intramedullary nail fixation with the standard, fin, or pediatric fin Surgical Implant Generation Network nail across an open distal femoral physis. MAIN OUTCOME MEASURES The main outcome measure was the distance traveled by the intramedullary nail with respect to the distal femoral condyles and distal femoral physis from initial surgery to follow-up. RESULTS The mean age of patients was 10.7 years (range: 7-14 years). Follow-up occurred at a mean of 292 days (range: 53-714 days). Both condyle distance and physis distance were significantly positively correlated with follow-up days, with Pearson R values of 0.90 (P < 0.001) and 0.84 (P < 0.001), respectively. Multiple regression analysis revealed that follow-up days was the only significant predictor of physis distance, whereas age, sex, percent growth plate violation, and nail fully traversing physis were not significant predictors. The nail completely crossed the physis in 5 patients and no growth arrests were found. CONCLUSIONS This is the first study, to our knowledge, to evaluate treating femoral shaft fractures with a retrograde nail across an open distal femoral physis. In the pediatric population, the use of a retrograde femoral intramedullary nails does not seem to cause growth arrest of the injured femur during the postoperative period and may be a reasonable treatment option when other surgical options are not available. Additional study is necessary to further evaluate the safety profile. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Purpose:. The Surgical Implant Generation Network (SIGN) intramedullary nail was designed for use in resource limited settings which often lack fluoroscopy, specialized fracture tables, and power reaming. A newer design iteration, the SIGN Fin nail, was developed to further simplify retrograde femoral nailing by making proximal interlocking screw placement unnecessary. Instead, the leading end of the Fin nail achieves stability through an interference fit within the proximal femoral canal. While the performance of the traditional SIGN nail has been reported previously, no large series has examined long-term clinical and radiographic outcomes of femoral shaft fractures treated with the SIGN Fin nail. Methods:. The SIGN online surgical database was used to identify all adult femoral shaft fractures treated with the SIGN Fin nail since its introduction. All patients with minimum 6 month clinical and radiographic follow-up were included in the analysis. Available demographic, injury, and surgical characteristics were recorded. Fracture alignment was evaluated on final follow-up radiographs using a previously validated on-screen protractor tool. Coronal and sagittal plane alignment measurements were recorded as deviation from anatomic alignment (DFAA), with units in degrees. Fracture healing was assessed on final follow-up radiographs, with union defined as any bridging callus and/or cortical remodeling across one cortex on orthogonal views. Clinical outcomes available in the database included knee range of motion (ROM) greater than 90° and weight-bearing status at final follow-up. Clinical and radiographic outcomes were then compared between patients with united and nonunited fractures. Results:. The database query identified 249 femoral shaft fractures stabilized with the Fin nail in 242 patients who had minimum 6 month clinical and radiographic follow-up. Final follow-up radiographs were performed at an average of 48 weeks postoperatively. Average coronal and sagittal plane alignment measured on final follow-up radiographs were 2.18° and 2.58°, respectively. The rate of malalignment (DFAA > 10° in either plane) at final follow-up was 6%. Two hundred twenty-nine fractures (92%) were united at final follow-up. Overall, 209 (84%) of patients achieved full weight bearing and 214 (86%) achieved knee ROM >90° at final follow-up. Compared to patients with united fractures, those with nonunion were less likely to achieve full weight bearing (20% vs 90%, P 90° (30% vs 91%, P

The obesity epidemic in humans is juxtaposed by observations of passerine birds exhibiting fine-scale body mass regulation. The ecology literature is replete with research into why these animals regulate body weight, citing tradeoffs between competing pressures such as emaciation and predation. Yet studies on the underlying mechanisms of mass regulation in these animals are scarce. Maintaining or decreasing weight could obviously be achieved by limiting food intake. However, there are numerous reasons why an animal may not control ingestion, at least precisely. This Opinion article investigates the plausibility of possible behavioural and physiological mechanisms to adaptively maintain or decrease body mass in birds and other animals. Candidate behavioural mechanisms include exercising and fidgeting, while physiological mechanisms could include reducing digestive efficiency or mitochondrial efficiency.

Objectives To report the clinical results after treatment of pediatric femoral shaft fractures with the SIGN Fracture Care International (SIGN) pediatric and standard fin nails. Design Retrospective review of prospectively collected data. Setting Sixteen global SIGN centers from 2003 to 2013. Patients/participants One hundred twelve pediatric patients who sustained a diaphyseal pediatric femoral shaft fracture. Intervention Intramedullary fixation with the standard or pediatric SIGN nail. Main outcome measurements Main outcome measurements include clinical and radiographic healing and postoperative complications. Results The mean age of the pediatric fin patients was 9.4 years (4-15) and 11.2 years (4-18) for the standard fin patients. Painless weight bearing was achieved in 94.7% and 94.5% of the patients at the last follow-up. In total, 23 patients had repeat surgery for the removal of implant. Failure of implant with bending of the nail and/or a valgus or varus deformity (>10 degrees) was noted in 7/57 (12.3%) of the patients treated with the pediatric fin nail, of which 6/7 were >10 years old. Five of these 7 patients were classified as technical errors attributed to inadequate nail diameter, length, or initial malreduction. No complications were noted at any age in the standard fin nail group. Conclusions In resource-poor settings, SIGN pediatric fin and standard fin nails seem to be an effective treatment option for femoral shaft fractures. In patients with larger canals, the surgeon should consider using the standard fin nail for improved stability and to minimize potential complications. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Digital, Introduction. Switching from polluting (e.g. wood, crop waste, coal) to clean (e.g. gas, electricity) cooking fuels can reduce household air pollution exposures and climate-forcing emissions. While studies have evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role of different multilevel factors in household fuel switching, outside of interventions and across diverse community settings, is not well understood. Methods. We examined longitudinal survey data from 24 172 households in 177 rural communities across nine countries within the Prospective Urban and Rural Epidemiology study. We assessed household-level primary cooking fuel switching during a median of 10 years of follow up (∼2005–2015). We used hierarchical logistic regression models to examine the relative importance of household, community, sub-national and national-level factors contributing to primary fuel switching. Results. One-half of study households (12 369) reported changing their primary cooking fuels between baseline and follow up surveys. Of these, 61% (7582) switched from polluting (wood, dung, agricultural waste, charcoal, coal, kerosene) to clean (gas, electricity) fuels, 26% (3109) switched between different polluting fuels, 10% (1164) switched from clean to polluting fuels and 3% (522) switched between different clean fuels. Among the 17 830 households using polluting cooking fuels at baseline, household-level factors (e.g. larger household size, higher wealth, higher education level) were most strongly associated with switching from polluting to clean fuels in India; in all other countries, community-level factors (e.g. larger population density in 2010, larger increase in population density between 2005 and 2015) were the strongest predictors of polluting-to-clean fuel switching. Conclusions. The importance of community and sub-national factors relative to household characteristics in determining polluting-to-clean fuel switching varied dramatically across the nine countries examined. This highlights the potential importance of national and other contextual factors in shaping large-scale clean cooking transitions among rural communities in low- and middle-income countries., Ciencias Médicas y de la Salud

Environmental conditions play a major role in shaping the spatial distributions of pathogens, which in turn can drive local adaptation and divergence in host genetic diversity. Haemosporidians, such as Plasmodium (malaria), are a strong selective force, impacting survival and fitness of hosts, with geographic distributions largely determined by habitat suitability for their insect vectors. Here, we have tested whether patterns of fine‐scale local adaptation to malaria are replicated across discrete, ecologically differing island populations of Berthelot's pipits Anthus berthelotii. We sequenced TLR4, an innate immunity gene that is potentially under positive selection in Berthelot's pipits, and two SNPs previously identified as being associated with malaria infection in a genome‐wide association study (GWAS) in Berthelot's pipits in the Canary Islands. We determined the environmental predictors of malaria infection, using these to estimate variation in malaria risk on Porto Santo, and found some congruence with previously identified environmental risk factors on Tenerife. We also found a negative association between malaria infection and a TLR4 variant in Tenerife. In contrast, one of the GWAS SNPs showed an association with malaria risk in Porto Santo, but in the opposite direction to that found in the Canary Islands GWAS. Together, these findings suggest that disease‐driven local adaptation may be an important factor in shaping variation among island populations., We have investigated patterns of fine‐scale local adaptation to malaria between two ecologically divergent populations of an island bird. Our results found contrasting associations with malaria infection at candidate immune loci between the islands, suggesting that disease‐driven local adaptation may be an important factor in shaping variation among island populations.

Injuries involving the hip and femur, like many others, have two peaks of incidence. One is in the elderly involving fragility fractures and two are high-energy injuries involving more active members of society.

Published in final edited form as: Nat Genet. 2019 March ; 51(3): 431–444. doi:10.1038/s41588-019-0344-8., Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture, we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD., The iPSYCH project is funded by the Lundbeck Foundation (grant numbers R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH and PGC samples was supported by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789 to MJD), and NIMH (5U01MH094432–02 to MJD). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514–01 to M O’Donovan and ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Drs. S De Rubeis and JD Buxbaum were supported by NIH grants MH097849 (to JDB) and MH111661 (to JDB), and by the Seaver Foundation (to SDR and JDB). Dr J Martin was supported by the Wellcome Trust (grant no: 106047). O. Andreassen received funding from Research Council of Norway (#213694, #223273, #248980, #248778), Stiftelsen KG Jebsen and South-East Norway Health Authority. We thank the research participants and employees of 23andMe for making this work possible.

There is considerable interest in why the process of ageing varies between individuals, both in humans and other animals. However, in animals, ageing in terms of survival (demographic senescence) is understood in considerably more detail than in terms of decline in the body’s functional capacity (functional senescence). Oxidative damage is probably an important component of the ageing process in many species. Oxidative stress typically increases as a result of physical activity, and many animals exhibit long and intense periods of active behaviour. These observations raise a question that has not yet been addressed: while in humans, at least, activity is considered beneficial to health, could high intensity activity play a part in the rate that wild animals age? Studies to date suggest that increased ‘effort’ can lead to reduced survival in free-living animals, but ‘effort’ refers to different processes in different studies, and is rarely clarified or quantified. To understand the role of activity in functional senescence, studies must measure the detailed activity of free-ranging animals, possibly describing it in terms of intensity, frequency and duration, coupled with records of resultant physiological and DNA damage.

BackgroundMajor depressive disorder (MDD) has a high personal and socio-economic burden and more than 60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait.MethodsPolygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756).ResultsNo significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results.DiscussionWe identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

Highlights • Non-persistent transmission is the most common mode for aphid-mediated virus transmission. • Many non-persistently transmitted viruses indirectly modify aphid behavior in ways that may enhance transmission. • Mathematical modeling confirms that enhancing host attractiveness while deterring aphid settling enhances local transmission. • Modeling predicts that encouraging settling promotes winged aphid production, which may enhance long distance transmission. • Disrupting host-vector interactions may provide a sustainable means to protect crops., Aphids vector many plant viruses in a non-persistent manner i.e., virus particles bind loosely to the insect mouthparts (stylet). This means that acquisition of virus particles from infected plants, and inoculation of uninfected plants by viruliferous aphids, are rapid processes that require only brief probes of the plant’s epidermal cells. Virus infection alters plant biochemistry, which causes changes in emission of volatile organic compounds and altered accumulation of nutrients and defence compounds in host tissues. These virus-induced biochemical changes can influence the migration, settling and feeding behaviours of aphids. Working mainly with cucumber mosaic virus and several potyviruses, a number of research groups have noted that in some plants, virus infection engenders resistance to aphid settling (sometimes accompanied by emission of deceptively attractive volatiles, that can lead to exploratory penetration by aphids without settling). However, in certain other hosts, virus infection renders plants more susceptible to aphid colonisation. It has been suggested that induction of resistance to aphid settling encourages transmission of non-persistently transmitted viruses, while induction of susceptibility to settling retards transmission. However, recent mathematical modelling indicates that both virus-induced effects contribute to epidemic development at different scales. We have also investigated at the molecular level the processes leading to induction, by cucumber mosaic virus, of feeding deterrence versus susceptibility to aphid infestation. Both processes involve complex interactions between specific viral proteins and host factors, resulting in manipulation or suppression of the plant’s immune networks.

OBJECTIVES This study is a systematic review and meta-analysis of the clinical outcomes and pooled complication rate of femoral, tibial, and humeral fracture fixation using SIGN nails. We aimed at comparing the pooled rate of adverse events based on the country of study origin, acute versus delayed fracture fixation, and length of follow-up. METHODS We searched PubMed/MEDLINE/Cochrane databases from 2000 to 2016 for English language studies. There was substantial heterogeneity among included studies. Therefore, we used subgroup analysis of varying adverse events and removal of potential outlier studies based on the "remove one" sensitivity analysis to address the heterogeneity across studies. A funnel plot was drawn and inspected visually to assess publication bias. We reported pooled complication rates for each adverse event with 95% prediction interval. RESULTS There were 14 studies with 47,169 cases across 58 different low- and middle-income countries. The average age was 33 ± 14 years, with 83% men and 17% women. Sixty percent of SIGN nails used in these 14 studies were used in femur fracture fixation, 38% in tibial shaft fractures, and the remaining 2% for humeral shaft fractures. Approximately 23% of patients had follow-up data recorded. All studies that measured clinical outcome indicated that >90% achieved full weight-bearing status, favorable range of motion (knee range of motion >90 degrees according to the SIGN database), and radiographic or clinical union depending on the specific variable(s) measured in each study. The overall complication rate was 5.2% (4.4%-6.4%). Malalignment (>5 degrees of angulation in any plane) was the most common complication (7.6%), followed by delayed/nonunion (6.9%), infection (5.9%), and hardware failure, (3.2%). CONCLUSIONS Overall, the use of SIGN nails in fixing femoral, tibial, and humeral shaft fractures demonstrates good results with a high rate of return to full weight-bearing and radiographic/clinical union. The most common complications when using the SIGN nail are malalignment, delayed/nonunion, infection, and hardware failure. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Retrograde femoral nailing in skeletal immature patients would broaden the surgical options for fracture care and reconstructive procedures but involves violation of the open, active distal femoral physis with the potential for growth disturbance. The tolerance for putting a large diameter metal implant across the physis is largely unknown. The purpose of this pilot investigation was to define the upper limit of cross-sectional violation with a metal implant before causing premature growth arrest or inhibition using a sheep model.Eighteen sheep underwent placement of a retrograde, intramedullary implant at 3-months of age through an open distal femoral physis. The cross-sectional area of the physis was measured preoperatively and implants were selected that violated 3% to 8% of the cross-sectional area of the physis. Growth across the distal femoral physis was examined radiographically following surgery. Following euthanasia, both operative and no operative femurs were removed to compare differences in maximal lengths.The distal femora grew an average of 10.6±2.2 mm radio graphically after implantation. When compared with control specimens, only operative specimens with 8% of physeal violation demonstrated significant growth discrepancy with operative femurs measuring2.1 mm in length compared with the contralateral control femur. Histologic analysis did not demonstrate any significant physeal bars formation.Distal femoral growth continues across the physis when 3% to 7% of the cross-sectional area of the physis is violated using a retrograde intramedullary implant. Specimens with 8% of growth violation demonstrated significant growth inhibition. As such, retrograde nailing through the distal femoral physis appears safe up to 7%. On the basis of previous anatomic data in humans and average nail sizes, violations of6% of the physis with pediatric retrograde nailing would be uncommon. These findings suggest that retrograde nailing may be a viable option and merits further study.Level IV-case series.

OBJECTIVES The purpose of this study was to evaluate the effectiveness of SIGN Pediatric and Fin nails in treating pediatric diaphyseal femur fractures. DESIGN Prospective case series. SETTING Level I trauma center from 2010 to 2013. PATIENT/PARTICIPANTS Eighteen patients (13 male and 5 female) with pediatric diaphyseal femur fractures who did not achieve skeletal maturity. INTERVENTION Femoral nailing was done using either SIGN Pediatric or Fin nail with hand-reaming without using bone-grafting or image intensifier. MAIN OUTCOME MEASUREMENTS Patients were evaluated for infection, radiographic parameters, range of movements, time to weight-bearing (partial and complete), revision surgery (if needed), and complications. RESULTS The average age of patients was 10.2 (±2.1) (range: 6-13) years and average time between injury and surgery was 13 (1-112) days. Fin nail was used in 13 patients, and Pediatric nail in 5 patients. There were no infections in either group. The average time for full weight-bearing was 7.07 weeks in the Fin nail group, and 8.4 weeks in the Pediatric nail group. No repeat surgeries were performed, and there was no case of avascular necrosis of femur head, limb length discrepancy, or any other complication. CONCLUSIONS SIGN Pediatric and Fin nails are an effective treatment modality for pediatric diaphyseal femur fractures with excellent fracture healing with no major complications. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Every country struggles with how best to meet the demand for health care services with the available resources. This commentary offers a perspective on the Israeli physician workforce and the analyses of Horowitz et al., which found age and gender differences in physician productivity and career longevity, differences across specialties, and a sizeable fraction of licensed Israeli physicians living abroad. Workforce planning can be subject to data collection and statistical uncertainties, but even more important are the assumptions and forecasts related to demand for services and organizational arrangements for care delivery. Readers should be cautious in analyzing productivity just by counting hours or years worked, and comparisons across countries may not account for differences in the nature of physician work. The question of whether Israel has enough physicians for the future has to go “beyond the count” to looking at the roles of other health professionals, the use of new technologies and new team configurations, and the overall efficiency and effectiveness of health care delivery systems such as hospitals, ambulatory care clinics, and community-based care.

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017.

The objective of this study was to describe the probability of detecting seven serogroups of enterohemorrhagic Escherichia coli (EHEC-7) of public health importance in fecal samples from beef cow-calf herds and to identify explanatory factors., American Association of Bovine Practitioners Proceedings of the Annual Conference, 2017

The aim of the current study was to compare bone loading due to physical activity between lean, and overweight and obese individuals. Fifteen participants (lower BMI group: BMI 2, n = 7; higher BMI group: 25 kg/m2 2, n = 8) wore a tri-axial accelerometer on 1 day to collect data for the calculation of bone loading. The International Physical Activity Questionnaire (short form) was used to measure time spent at different physical activity levels. Daily step counts were measured using a pedometer. Differences between groups were compared using independentt-tests. Accelerometer data revealed greater loading dose at the hip in lower BMI participants at a frequency band of 0.1–2 Hz (P = .039, Cohen’sd = 1.27) and 2–4 Hz (P = .044,d = 1.24). Lower BMI participants also had a significantly greater step count (P = .023,d = 1.55). This corroborated with loading intensity (d ≥ 0.93) and questionnaire (d = 0.79) effect sizes to indicate higher BMI participants tended to spend more time in very light activity, and less time in light and moderate activity. Overall, participants with a lower BMI exhibited greater bone loading due to physical activity; participants with a higher BMI may benefit from more light and moderate level activity to maintain bone health.

Objectives To document the current state of pelvic and acetabular surgery in the developing world and to identify critical areas for improvement in the treatment of these complex injuries. Design A 50-question online survey. Setting International, multicenter. Patients/participants One hundred eighty-one orthopaedic surgeons at Surgical Implant Generation Network (SIGN) hospitals, which represent a cross-section of institutions in low- and middle-income countries that treat high-energy musculoskeletal trauma. Interventions Administration and analysis of 50-question survey. Main outcome measures Surgeon training and experience; hospital resources; volume and patterns of pelvic/acetabular fracture management; postoperative protocols and resources for rehabilitation; financial responsibilities for patients with pelvic/acetabular fractures. Results Complete surveys were returned by 75 institutions, representing 61.8% of the global SIGN nail volume. Although 96% of respondents were trained in orthopaedic surgery, 53.3% have no formal training in pelvic or acetabular surgery. Emergency access to the operating room is available at all responding sites, but computed tomography scanners are available at only 60% of sites, and a mere 21% of sites have access to angiography for pelvic embolization. Cannulated screws (53.3%) and pelvic reconstruction plates (56%) are available at just over half of the sites, and 68% of sites do not have pelvic reduction clamps and retractors. 21.3% of sites do not have access to intraoperative fluoroscopy. Responding hospitals see an average of 38.8 pelvic ring injuries annually, with 24% of sites treating them all nonoperatively. Sites treated an average of 22.5 acetabular fractures annually, with 34.7% of institutions treating them all nonoperatively. Patients travel up to 1000 km or 20 hours for pelvic/acetabular treatment at some sites. Although 78.7% of sites have inpatient physical or occupational therapy services, only 17% report access to home physical therapy, and only 9% report availability of nursing or rehabilitation facilities postdischarge. At over 80% of hospitals, patients and their families are at least partially responsible for payment of surgical, implant, hospital, and outpatient fees. Government aid is available for inpatient fees at over 40% of sites, but outpatient services are subsidized at only 28% of sites. Conclusions We report the current state of pelvic and acetabular surgery in low- and middle-income countries. Our results identify significant needs in surgeon training, hospital resources, availability of instruments and implants, and access to appropriate postoperative rehabilitation services for pelvic and acetabular surgery in the developing world. Targeted programs designed to overcome these barriers are required to advance the care of pelvic and acetabular fractures in the developing world.

Assessments of growth can provide information needed to understand how fish populations respond to changing environmental conditions and management actions, including ecosystem experimentation. We estimated growth rates and parameter uncertainty from otoliths of endangered Humpback Chub Gila cypha from the Colorado River in Grand Canyon, Arizona. We then compared growth of Humpback Chub < age 2 that were 1) occupying the mainstem Colorado River during a period of variable discharge and cooler water temperatures (1980–1998; epoch 1), 2) occupying the Colorado River during a period of moderate discharge variability and warmer water (2001–2011; epoch 2), and 3) occupying the unregulated Little Colorado River. Because growth rates of juvenile Humpback Chub (< age 2) may be more sensitive to changes in environmental conditions than adult fish, we used analysis of covariance and linear models to compare growth of juvenile fish (slopes) between epochs and capture sites (mainstem Colorado River vs. Little Colorado River). Our analysis of covariance results were ambiguous (age × epoch × site interaction; P = 0.06). However, individual linear regressions of size and age by epoch and site suggest biologically important differences in growth, as evidenced by slower growth in the Colorado River in epoch 1 than in epoch 2, and slower growth in the Colorado River compared with the Little Colorado River for all time periods. Overall our results 1) provide information on growth and growth variability useful for parameterizing models to assess population viability and 2) provide empirical information on how growth of juvenile and adult Humpback Chub growth may respond to changing environmental conditions.

After decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced-based argument for the fundamental role of surgery and anaesthesia within cost-effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.

We present the first data on the metabolic costs of horizontal jumping in humans, using this tractable model to explore variations in energy expenditure with substrate properties, and consider these findings in light of kinematic data. Twenty-four participants jumped consistently at the rate of 1 jump per 5 s between opposing springboards separated by either a short (1.2 m) or long (1.8 m) gap. Springboards were either ‘firm’ or ‘compliant’. Respiratory gas exchange was measured using a back-mounted portable respiratory gas analyser to represent rate of energy expenditure, which was converted to energy expenditure per metre jumped. Video data were recorded to interpret kinematic information. Horizontal jumping was found to be between around 10 and 20 times the energy cost of cursorial locomotion per unit distance moved. There is considerable evidence from the data that jumping 1.8 m from a compliant springboard (134.9 mL O2 m−1) is less costly energetically than jumping that distance from a firm springboard (141.6 mL O2 m−1), albeit the effect size is quite small within the range of compliances tested in this study. However, there was no evidence of an effect of springboard type for jumps of 1.2 m. The kinematic analyses indicate possible explanations for these findings. Firstly, the calf muscle is likely used more, and the thigh muscles less, to take-off from a firm springboard during 1.8 m jumps, which may result in the power required to take-off being produced less efficiently. Secondly, the angle of take-off from the compliant surface during 1.8 m jumps is closer to the optimal for energetic efficiency (45°), possible due to the impulse provided by the surface as it returns stored energy during the final stages of the take-off. The theoretical effect on energy costs due to a different take-off angle for jumps of only 1.2 m is close to negligible.

Acute confusion and hyponatraemia are common presentations in acute medicine. We report two cases of anti-voltage gated potassium channel (VGKC) antibody-related limbic encephalitis highlighting the variable presentation of this condition. Both patients were thoroughly investigated with MRI scan of brain, lumbar puncture, EEG as well as infective and autoimmune screens for encephalitis. Anti-VGKC antibodies were positive for both patients and prompt treatment with immunotherapy yielded good recovery. Patients presenting with confusion and seizures who have no demonstrable infectious or metabolic cause should have investigation for an autoimmune cause expedited. In addition, psychiatric presentations with atypical features such as drowsiness should prompt similar investigations. The outcome of anti-VGKCrelated limbic encephalitis is improved with early treatment employing steroids or immunotherapy.

Objective To evaluate the use and effectiveness of two “in-home” strategies for delivering diabetes prevention programming using cable television. Methods An individually randomized, two-arm intervention trial including adults with diabetes risk factors living in two US cities. Interventions involved a 16-session lifestyle intervention delivered via “video-on-demand” cable television, offered alone versus in combination with web-based lifestyle support tools. Repeated measures longitudinal linear regression with imputation of missing observations was used to compare changes in body weight. Results A total of 306 individuals were randomized and offered the interventions. After 5 months, 265 (87%) participants viewed at least 1, and 110 (36%) viewed ≥9 of the video episodes. A total of 262 (86%) participants completed a 5-month weight measurement. In intention-to-treat analysis with imputation of missing observations, mean weight loss at 5 months for both treatment groups combined was 3.3% (95% CI 0.7-5.0%), regardless of intervention participation (with no differences between randomized groups (P = 0.19)), and was 4.9% (95% CI 2.1-6.5%) for participants who viewed ≥9 episodes. Conclusions In-home delivery of evidence-based diabetes prevention programming in a reality television format, offered with or without online behavioral support tools, can achieve modest weight losses consistent with past implementation studies of face-to-face programs using similar content.

Surgeons in low-resource settings manage an increasing number of patients presenting with high-energy fractures. The number of surgeons and the operating time available are frequently not adequate to treat these fractures in a timely manner. A common cause of delay in treating fractures is waiting for the patient to accumulate sufficient funding to pay for the surgery, including the surgical implant. The donation of the SIGN intramedullary nail interlocking screw system obviates a major delay in timing of surgery. The SIGN intramedullary nail has been designed to be used in low-resource settings as it can be placed without fluoroscopy or electricity. The SIGN-trained surgeons are very skillful in hand reaming the canal, placing the nail, and interlocking screws without fluoroscopy. As more is learned about fracture healing, the SIGN system continues to evolve. The SIGN system is expanding to include deformity correction and soft tissue coverage.

Aims: Advances in genomics and molecular diagnostic testing are expanding, but national data on which to base clinical, regulatory and reimbursement policies in the USA are lacking. The study objective is to provide current estimates of utilization/spending trends for private and public payers. Patients & methods: Healthcare utilization/expenditure claims data for 32 million individuals across the USA in 2008–2011 were analyzed. Genetic testing and molecular diagnostic usage was categorized by major testing groups: infectious disease, cancer and inherited/other acquired conditions. Results: Per-person testing cost grew by 14% per year between 2008 and 2011, primarily resulting from increased utilization. Spending per person for Medicare and Medicaid was higher than for commercially insured patients. Expenditure across the USA was estimated at US$5.5 billion in 2011, up 13% from 2010. Discussion: Greater understanding of usage and technology diffusion requires increased data transparency and granularity. Conclusion & future perspective: The use of genetic testing and molecular diagnostics will grow over the next 5 years, with uncertainty about the precise diffusion trajectory. By strengthening the capacity to capture and analyze trends in this changing area of medicine, we increase our chances of promoting positive change to the benefit of patients.

➤The burden of musculoskeletal trauma is high worldwide, disproportionately affecting the poor, who have the least access to quality orthopaedic trauma care.➤Orthopaedic trauma care is essential, and must be a priority in the horizontal development of global health systems.➤The education of surgeons, nonphysician clinicians, and ancillary staff in low and middle income countries is central to improving access to and quality of care.➤Volunteer surgical missions from rich countries can sustainably expand and strengthen orthopaedic trauma care only when they serve a local need and build local capacity.➤Innovative business models may help to pay for care of the poor. Examples include reducing costs through process improvements and cross-subsidizing from profitable high-volume activities.➤Resource-poor settings may foster innovations in devices or systems with universal applicability in orthopaedics.

The tree canopy is an energetically challenging environment to traverse. Along with compliant vegetation, gaps in the canopy can prove energetically costly if they force a route-extending detour. Arboreal apes exhibit diverse locomotion strategies, including for gap crossing. Which one they employ in any given scenario may be influenced by the energy costs to do so, which are affected by the details of the immediate environment in combination with their body size. Measuring energetics of arboreal apes is not tractable; thus our knowledge in this area is limited. We devised a novel, custom-made experimental set-up to record the energy expenditure of parkour athletes tree-swaying, jumping and vertical climbing. The latter strategy was vastly more expensive, indicating that when energy economy is the focus arboreal apes will prioritize routes that limit height changes. Whether tree-swaying or jumping was most economical for the athletes depended upon interactions between tree stiffness, the distance to cross, number of tree-sways required and their own mass. Updated analysis of previous interspecific correlations suggests that whether the relative costs to vertical climb are size-invariant across primate species is complicated by details of the climbing context.

Background: As the population ages, the developing world industrializes, and more urban centers emerge, the burden of orthopedic trauma will steadily increase. SIGN Fracture Care International has developed a unique intramedullary device for fixation of hip fractures in low-resource settings lacking fluoroscopy. The purpose of this study is to report the safety profile and complication rate for a consecutive series of hip fracture patients managed using this implant. Methods: We conducted a retrospective analysis of the first 170 patients treated with the SIGN Hip Construct (SHC) from 2009 to 2014 using the SIGN Online Surgical Database (SOSD). Patients with follow-up greater than 12 weeks and adequate radiographs were included. Data recorded include patient demographics, time-to-surgery, union rate, AO/OTA classification, complications, neck-shaft angle, and clinical outcomes including painless weight bearing and knee flexion greater than 90°. Results: Of 170 patients, 71 met inclusion criteria with mean follow-up of 39 weeks. Mean age was 49.5 and by WHO, regions were Africa (27), Eastern Mediterranean (21), Western Pacific (17), Americas (3), and Southeast Asia (3). Fractures included intertrochanteric (55), subtrochanteric (7), femoral neck (4), and combined (5). Reduction quality was good in 35 (49%), acceptable in 19 (27%), and poor in 17 (24%). Major complications consisted of varus collapse (6), non- or delayed union (3), intra-articular screw (5), and infection (3). Average postoperative neck-shaft angle was 126° and 119.3° at final follow-up. Conclusions: This is the first comprehensive report of a novel implant for hip fractures specifically designed for low-resource settings. The early clinical data and outcomes suggest that the SHC can be safely inserted in the absence of fluoroscopy, and facilitates early mobilization while maintaining acceptable reduction until union.

The main influence a trauma surgeon has on fracture healing is soft-tissue care and stabilization of the fracture. Treatment of long-bone diaphyseal and many metaphyseal fractures is best accomplished by intramedullary (IM) nail interlocking screw systems. In settings where resources are in abundance, interlocking screws are typically placed using C-arm imaging, fracture tables, and other specialized equipment. These are not available in many developing countries, and therefore creativity is necessary to accomplish equivalent results. This chapter will describe innovations to accomplish placement of the IM nail and interlocking screws without these technological aids. The chapter is divided into sections for femur, tibia, humerus, hip, and pediatric femoral fractures.

International audience; Returning to the shore after a feeding sojourn at sea, king penguins often undertake a relativelylong terrestrial journey to the breeding colony carrying a heavy, mostly frontal, accumulationof fat along with food in the stomach for chick-provisioning. There they mustsurvive a fasting period of up to a month in duration, during which their complete reliance onendogenous energy stores results in a dramatic loss in body mass. Our aim was to determineif the king penguin’s walking gait changes with variations in body mass.We investigatedthis by walking king penguins on a treadmill while instrumented with an accelerationdata logger. The stride frequency, dynamic body acceleration (DBA) and posture of fat (prefasting;13.2 kg) and slim (post fasting; 11 kg) king penguins were assessed while theywalked at the same speed (1.4km/h) on a treadmill. Paired statistical tests indicated no evidencefor a difference in dynamic body acceleration or stride frequency between the twobody masses however there was substantially less variability in both leaning angle and theleaning amplitude of the body when the birds were slimmer. Furthermore, there was someevidence that the slimmer birds exhibited a decrease in waddling amplitude. We suggestthe increase in variability of both leaning angle and amplitude, as well as a possibly greatervariability in the waddling amplitude, is likely to result from the frontal fat accumulation whenthe birds are heavier, which may move the centre of mass anteriorly, resulting in a less stableupright posture. This study is the first to use accelerometry to better understand the gaitof a species within a specific ecological context: the considerable body mass change exhibitedby king penguins.

Background: The fields of surgery and trauma care have largely been neglected in the global health discussion. As a result the idea that surgery is not safe or cost effective in resource-limited settings has gone unchallenged. The SIGN Online Surgical Database (SOSD) is now one of the largest databases on trauma surgery in low- and middle-income countries (LMIC). We wished to examine infection rates and risk factors for infection after IM nail operations in LMIC using this data. Methods: The SOSD contained 46,722 IM nail surgeries in 58 different LMIC; 46,113 IM nail operations were included for analysis. Results: The overall follow-up rate was 23.1 %. The overall infection ratewas 1.0 %, 0.7 %for humerus, 0.8 %for femur, and 1.5 % for tibia fractures. If only nails with registered follow-up (n = 10,684) were included in analyses, infection rates were 2.9 % for humerus, 3.2 % for femur, and 6.9 % for tibia fractures. Prophylactic antibiotics reduced the risk of infection by 29 %. Operations for non-union had a doubled risk of infection. Risk of infection was reduced with increasing income level of the country. Conclusions: The overall infection rates were low, and well within acceptable levels, suggesting that it is safe to do IM nailing in low-income countries. The fact that operations for non-union have twice the risk of infection compared to primary fracture surgery further supports the use of IM nailing as the primary treatment for femur fractures in LMIC. publishedVersion

Aims A possible explanation for increased levels of attractiveness of faces when under the influence of alcohol is the reduced ability to perceive bilateral asymmetry. This study tested the degree of preference by alcohol-dosed and non-alcohol-dosed participants for symmetrical faces and their ability to detect facial symmetry, while controlling for other explanations. Design Volunteers were recruited to a random allocation experiment with three conditions: alcoholic drink (alcohol dosed), non-alcoholic drink (placebo) and diluted orange cordial (control). Data on concentration, personality and demographics were collected. Dependent variables were symmetry preference and detection. Setting Laboratory, University of Roehampton. Participants A total of 101 participants, mainly students (41 alcohol-dosed, 40 placebo, 20 control). Measurements Participants provided verbal responses to images of faces which were presented on a computer screen for 5 seconds each; the first task required a preference judgement and the second task consisted of a forced-choice response of whether or not a face was symmetrical. Levels of concentration, weight and level of alcohol dose were measured, and demographics plus additional psychological and health information were collected using a computer-based questionnaire. Findings In contrast to a previous investigation, there was no difference in symmetry preference between conditions (P = 0.846). In agreement with previous findings, participants who had not drunk alcohol were better at detecting whether a face was symmetrical or asymmetrical (P = 0.043). Measures of concentration did not differ between conditions (P = 0.214–0.438). Gender did not affect ability to detect symmetry in placebo or alcohol-dosed participants (P = 0.984, 0.499); however, alcohol-dosed females were shown to demonstrate greater symmetry preference than alcohol-dosed males (P = 0.004). Conclusions People who are alcohol-dosed are subtly less able to perceive vertical, bilateral asymmetry in faces, with gender being a possible moderating factor.