DETERMINING INITIAL KNEE JOlNT LOADiNG DURING A SINGLE LIMB DROP LANDING: REDUCING SOFT TISSUE ERRORS

This study examined the influence of modeling approaches on lower limb on transient knee joint moments during single leg landings. A typical GDoF joint model was compared to a constrained 3DoF model. For peak moments and rates of moment increases there was no difference between joint models. Earlier, and greater moments were obtained using data from a 3D-printed plate moulded to each individual's tibia. Maintaining high frequencies in the dataset using the 3D-printed plate was important for determining initial joint loading and associated risk factors for sports injuries

Perceptions of a short animated film on adverse childhood experiences: a mixed methods evaluation

OBJECTIVES: An evaluation of a short animated film on adverse childhood experiences (ACEs) to explore attitudes and sentiment towards the film including, for a subsample of professionals, associations between attitudes and personal experience of ACEs. DESIGN: Mixed-method exploratory design. SETTING: Professionals and the general public. PARTICIPANTS: A short online survey with 239 professionals. Interaction and user sentiment towards with the film on social media (Twitter, YouTube). PRIMARY AND SECONDARY OUTCOME MEASURES: Survey: participants’ attitudes towards the film including feelings invoked, learning gained and ACE count prevalence. Twitter user and YouTube viewer sentiment (positive, negative or neutral) and interaction (likes, retweets or comments) with the film. RESULTS: Attitudes to the film were positive: 94.1% and 93.7%, respectively, agreed that it provided a helpful explanation of ACEs and trusted that the film was credible. Of those who reported ACE exposure, 88.9% agreed that those with ACEs would benefit from watching the film. Despite 50.6% reporting that the film had made them feel sad or upset, the majority (66.4%) reported they found the film hopeful or encouraging. Across 358 publicly available tweets from 313 users, 39.1% of tweets expressed positive sentiment, with only 1.4% negative (59.5% neutral). However, there was no association between tweet sentiment and interaction. Thirteen YouTube versions of the film received 171 812 views, 97.3% (n=889/914) ratings were positive (ie, ‘thumbs up’). CONCLUSIONS: Despite being emotionally arousing, many professionals reflected positive impacts of the film including a perceived increased ability to discuss ACEs. Public sentiment demonstrated a positive reaction to and acceptability of the film. Understanding the professional and public response to materials developed to increase ACE awareness, such as the film explored here, is important given the growing number of international movements which seek to increase ACE awareness, prevent ACEs and mitigate their lifelong negative effects

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

Footwear insoles with higher frictional properties enhance performance by reducing in-shoe sliding during rapid changes of direction

A novel 3D motion capture analysis assessed the efficacy of insoles in maintaining the foot position on the midsole platform inside the shoe during rapid change of direction manoeuvres used in team sports. An insole (TI) with increased static (35%) and dynamic (49%) coefficient of friction compared to a regular insole (SI) was tested. Change of direction performance was faster (p<.001) and perceived to be faster (p<.001) in TI compared to SI. Participants utilised greater coefficient of friction in TI compared to SI during a complete turn, but not during a 20 degree side-cut. In-shoe foot sliding reduced across the forefoot and midfoot during the braking phase of the turn and in the rearfoot during the side-cut in TI. Greater in-shoe foot sliding occurred in the turn than the side-cut across all foot regions. Results provide guidance for athletic footwear design to help limit in-shoe foot sliding and improve change of direction performance

Communicating content: development and evaluation of icons for academic document triage through visualisation and perception

This work seeks to identify key features and characteristics for the design of icons that can support the tasks of information seekers in academic document triage interfaces. Such icons are meant to act as visual links to the specific elements or sections in an academic document. We suggest that icons in triage interfaces are better able to communicate information, provide feedback and enable faster user interactions than text, particularly in mobile-based interfaces. Through investigation of visualisation and perception processes, we are able to propose five primary icon categories, the two most dominant being iconic and symbolic: iconic representations mostly apply to graphically and spatially distinct document elements (i.e. Title, Abstract, Tables and Figures), externalising the elements’ surface propositions. Symbolic representations are largely associated with elements of greater semantic value (Introduction, Conclusion, Full text and Author), drawing upon the elements’ deep propositions

Genome Sequencing Shows that European Isolates of Francisella tularensis Subspecies tularensis Are Almost Identical to US Laboratory Strain Schu S4

BACKGROUND: Francisella tularensis causes tularaemia, a life-threatening zoonosis, and has potential as a biowarfare agent. F. tularensis subsp. tularensis, which causes the most severe form of tularaemia, is usually confined to North America. However, a handful of isolates from this subspecies was obtained in the 1980s from ticks and mites from Slovakia and Austria. Our aim was to uncover the origins of these enigmatic European isolates. METHODOLOGY/PRINCIPAL FINDINGS: We determined the complete genome sequence of FSC198, a European isolate of F. tularensis subsp. tularensis, by whole-genome shotgun sequencing and compared it to that of the North American laboratory strain Schu S4. Apparent differences between the two genomes were resolved by re-sequencing discrepant loci in both strains. We found that the genome of FSC198 is almost identical to that of Schu S4, with only eight SNPs and three VNTR differences between the two sequences. Sequencing of these loci in two other European isolates of F. tularensis subsp. tularensis confirmed that all three European isolates are also closely related to, but distinct from Schu S4. CONCLUSIONS/SIGNIFICANCE: The data presented here suggest that the Schu S4 laboratory strain is the most likely source of the European isolates of F. tularensis subsp. tularensis and indicate that anthropogenic activities, such as movement of strains or animal vectors, account for the presence of these isolates in Europe. Given the highly pathogenic nature of this subspecies, the possibility that it has become established wild in the heartland of Europe carries significant public health implications

The AMP-activated protein kinase beta 1 subunit modulates murine erythrocyte development

Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. In the work described here, we studied the role of the beta 1 subunit in erythrocytes and observed microcytic anemia with compensatory extramedullary hematopoiesis together with splenomegaly and increased osmotic resistance

Disruption of the potassium channel regulatory subunit Kcne2 causes iron-deficient anemia

Iron homeostasis is a dynamic process that is tightly controlled to balance iron uptake, storage, and export. Reduction of dietary iron from the ferric to the ferrous form is required for uptake by solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both processes are proton dependent and have led to the suggestion of the importance of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated channel subfamily E, member 2 (KCNE2), in combination with potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1 results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on iron absorption has not, to our knowledge, been investigated. Here we report that Kcne2-deficient mice, in addition to the previously reported phenotypes, also present with iron-deficient anemia. Interestingly, impaired function of KCNQ1 results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients. We speculate that impaired function of KCNE2 could result in the same clinical phenotype

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead