Heimdallr, Baldr, and Solarstein: designing the next generation of VLTI instruments in the Asgard suite.

High angular resolution imaging is an increasingly important capability in contemporary astrophysics. Of particular relevance to emerging fields such as the characterization of exoplanetary systems, imaging at the required spatial scales and contrast levels results in forbidding challenges in the correction of atmospheric phase errors, which in turn drives demanding requirements for precise wavefront sensing. Asgard is the next-generation instrument suite at the European Southern Observatory's Very Large Telescope Interferometer (VLTI), targeting advances in sensitivity, spectral resolution, and nulling interferometry. In this paper, we describe the requirements and designs of three core modules: Heimdallr, a beam combiner for fringe tracking, low order wavefront correction, and visibility science; Baldr, a Zernike wavefront sensor to correct high order atmospheric aberrations; and Solarstein, an alignment and calibration unit. In addition, we draw generalizable insights for designing such system and discuss integration plans.

Understanding the role of physical activity on the pathway from intra-articular knee injury to post-traumatic osteoarthritis disease in young people: a scoping review protocol.

INTRODUCTION: The prevalence of intra-articular knee injuries and reparative surgeries is increasing in many countries. Alarmingly, there is a risk of developing post-traumatic osteoarthritis (PTOA) after sustaining a serious intra-articular knee injury. Although physical inactivity is suggested as a risk factor contributing to the high prevalence of the condition, there is a paucity of research characterising the association between physical activity and joint health. Consequently, the primary aim of this review will be to identify and present available empirical evidence regarding the association between physical activity and joint degeneration after intra-articular knee injury and summarise the evidence using an adapted Grading of Recommendations Assessment, Development and Evaluations. The secondary aim will be to identify potential mechanistic pathways through which physical activity could influence PTOA pathogenesis. The tertiary aim will be to highlight gaps in current understanding of the association between physical activity and joint degeneration following joint injury. METHODS: A scoping review will be conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist and best-practice recommendations. The review will be guided by the following research question: what is the role of physical activity in the trajectory from intra-articular knee injury to PTOA in young men and women? We will identify primary research studies and grey literature by searching the electronic databases Scopus, Embase: Elsevier, PubMed, Web of Science: all databases, and Google Scholar. Reviewing pairs will screen abstracts, full texts and will extract data. Data will be presented descriptively using charts, graphs, plots and tables. ETHICS AND DISSEMINATION: This research does not require ethical approval due to the data being published and publicly available. This review will be submitted for publication in a peer-reviewed sports medicine journal irrespective of discoveries and disseminated through scientific conference presentations and social media. TRIAL REGISTRATION NUMBER: https://osf.io/84pnh/.

Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRPα.

Targeting the CD47-signal-regulatory protein α (SIRPα) pathway represents a novel therapeutic approach to enhance anti-cancer immunity by promoting both innate and adaptive immune responses. Unlike CD47, which is expressed ubiquitously, SIRPα expression is mainly restricted to myeloid cells and neurons. Therefore, compared to CD47-targeted therapies, targeting SIRPα may result in differential safety and efficacy profiles, potentially enabling lower effective doses and improved pharmacokinetics and pharmacodynamics. The development of effective SIRPα antagonists is restricted by polymorphisms within the CD47-binding domain of SIRPα, necessitating pan-allele reactive anti-SIRPα antibodies for therapeutic intervention in diverse patient populations. We immunized wild-type and human antibody transgenic chickens with a multi-allele and multi-species SIRPα regimen in order to discover pan-allelic and pan-mammalian reactive anti-SIRPα antibodies suitable for clinical translation. A total of 200 antibodies were isolated and screened for SIRPα reactivity from which approximately 70 antibodies with diverse SIRPα binding profiles, sequence families, and epitopes were selected for further characterization. A subset of anti-SIRPα antibodies bound to both human SIRPα v1 and v2 alleles with high affinity ranging from low nanomolar to picomolar, potently antagonized the CD47/SIRPα interaction, and potentiated macrophage-mediated antibody-dependent cellular phagocytosis in vitro. X-ray crystal structures of five anti-SIRPα antigen-binding fragments, each with unique epitopes, in complex with SIRPα (PDB codes 6NMV, 6NMU, 6NMT, 6NMS, and 6NMR) are reported. Furthermore, some of the anti-SIRPα antibodies cross-react with cynomolgus SIRPα and various mouse SIRPα alleles (BALB/c, NOD, BL/6), which can facilitate preclinical to clinical development. These properties provide an attractive rationale to advance the development of these anti-SIRPα antibodies as a novel therapy for advanced malignancies. Abbreviations: ADCC: antibody-dependent cellular cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; CFSE: carboxyfluorescein succinimidyl ester; Fab: fragment antigen binding; Fc: fragment crystallizable; FcγR: Fcγ receptor; Ig: immunoglobulin; IND: investigational new drug; MDM⊘: monocyte-derived macrophage; NOD: non-obese diabetic; scFv: single chain fragment variable; SCID: severe combined immunodeficiency; SIRP: signal-regulatory protein.

Early complications of revision total knee arthroplasty in morbidly obese patients.

INTRODUCTION: Morbid obesity is a known risk factor for complications and failure following primary total knee arthroplasty. Complications following revision total knee arthroplasty (rTKA) in the morbidly obese (BMI > 40) have not been well described. A retrospective cohort study was designed to investigate the early complications of rTKA in morbidly obese patients. METHODS: Revision TKA procedures were performed between January 2009 and December 2012 at a single institution. Comparisons were made between patients with a normal BMI (18.5-25) and patients with morbid obesity (BMI > 40). RESULTS: Thirty-three of 141 morbidly obese patients (23.4%) had a complication compared to 10 of 96 patients with a BMI 18.5-25 (10.4%) (p = 0.011). Morbidly obese patients were younger (69.3 vs. 61.4 years, p < 0.0001), and their most frequent complication in comparison with patients with normal BMI was wound healing problems (p = 0.01). CONCLUSION: Morbidly obese patients are at a significantly increased rate of early complications following rTKA compared to a normal weight cohort, especially with regard to wound complications. The morbidly obese group was significantly younger at the time of rTKA. In addition, this study highlights the importance of risk stratification for morbidly obese patients undergoing rTKA.

Synthesis, stereochemical characterization, and antimicrobial evaluation of a potentially nonnephrotoxic 3'-C-acethydrazide puromycin analog.

Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3'-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 µM concentration.

Relationship between geometry of the extensor mechanism of the knee and risk of anterior cruciate ligament injury.

The complex inter-segmental forces that are developed across an extended knee by body weight and contraction of the quadriceps muscle group transmits an anteriorly directed force on the tibia that strain the anterior cruciate ligament (ACL). We hypothesized that a relationship exists between geometry of the knees extensor mechanism and the risk of sustaining a non-contact ACL injury. Geometry of the extensor mechanism was characterized using MRI scans of the knees of 88 subjects that suffered their first non-contact ACL injury and 88 matched control subjects with normal knees that were on the same team. The orientation of the patellar tendon axis was measured relative to the femoral flexion-extension axis to determine the extensor moment arm (EMA), and relative to tibial long axis to measure coronal patellar tendon angle (CPTA) and sagittal patellar tendon angle (SPTA). Associations between these parameters and ACL injury risk were tested with and without adjustment for flexion and internal rotation position of the tibia relative to the femur during MRI data acquisition. After adjustment for internal rotation position of the tibia relative to the femur there were no associations between EMA, CPTA, and SPTA and risk of suffering an ACL injury. However, increased internal rotation position of the tibia relative to the femur was significantly associated with increased risk of ACL injury in female athletes both in univariate analysis (Odds Ratio = 1.16 per degree of internal rotation of the tibia, p = 0.002), as well as after adjustment for EMA, CPTA, and SPTA.: © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:965-973, 2017.

Shoulder pain and dysfunction in young surf lifesavers.

OBJECTIVES: To determine the incidence and prevalence of significantly interrupting shoulder pain (SIP) in young surf lifesavers and to determine association with training dosage and the 'combined elevation test'. PARTICIPANTS: 54 surf lifesavers aged 10-18 from the Gold Coast, Australia. METHODS AND OUTCOME MEASURES: Retrospective survey of SIP and training dosage. Cross-sectional measures of the combined elevation test. DESIGN: Retrospective. RESULTS: 56.5% of female surf lifesavers reported a history of SIP compared to males with 48.5%. Females had a higher combined elevation score compared to males, 28.32 ± SD 8.52 cm and 26.09 ± SD 6.64 cm, respectively. Young surf lifesavers had an incidence rate of 2.1 SIP episodes per thousand hours of training, an incidence proportion of 51.9% and prevalence of 18.5%. Combined elevation had low level positive trends with training dosages and statistically significant negative correlation with board paddling sessions per week (r = -0.287, p ≤ 0.05). Those with a history of SIP had a statistically significant higher number of sessions (p = 0.008), duration (p = 0.015) and distance (p = 0.005) swimming per week. CONCLUSION: Young surf lifesavers with a history of SIP have greater swimming dosage not associated with a decreased combined elevation score. More board paddling sessions per week decreased the combined elevation score of young surf lifesavers.

Kepler-62: a five-planet system with planets of 1.4 and 1.6 Earth radii in the habitable zone.

We present the detection of five planets--Kepler-62b, c, d, e, and f--of size 1.31, 0.54, 1.95, 1.61 and 1.41 Earth radii (R⊕), orbiting a K2V star at periods of 5.7, 12.4, 18.2, 122.4, and 267.3 days, respectively. The outermost planets, Kepler-62e and -62f, are super-Earth-size (1.25 R⊕ < planet radius ≤ 2.0 R⊕) planets in the habitable zone of their host star, respectively receiving 1.2 ± 0.2 times and 0.41 ± 0.05 times the solar flux at Earth's orbit. Theoretical models of Kepler-62e and -62f for a stellar age of ~7 billion years suggest that both planets could be solid, either with a rocky composition or composed of mostly solid water in their bulk.

Laser-driven hard-x-ray generation based on ultrafast selected energy X-ray absorption spectroscopy measurements of Ni compounds.

Three Ni compounds were studied by ultrafast selected energy x-ray absorption spectroscopy using a laser-driven electron x-ray source with a tungsten target. The measured K edges of these Ni compounds using this self-referencing method were made identical to those measured with synchrotron x-ray sources. This enabled us to determine the absolute peak positions of tungsten Lalpha(1) and Lalpha(2) emitted from this source to be within 1 eV of those from the neutral tungsten atoms, which strongly suggested that the x rays were emitted from high energy electrons interacting with tungsten atoms in the solid target. This is the best evidence to date that directly supports the cold atom x-ray generation theory.