Monolithic silicon microlens arrays for far-infrared astrophysics.

Future far-infrared astrophysics observatories will require focal plane arrays containing thousands of ultrasensitive, superconducting detectors, each of which require efficient optical coupling to the telescope fore-optics. At longer wavelengths, many approaches have been developed, including feedhorn arrays and macroscopic arrays of lenslets. However, with wavelengths as short as 25 µm, optical coupling in the far infrared remains challenging. In this paper, we present an approach to fabricate far-infrared monolithic silicon microlens arrays using grayscale lithography and deep reactive ion etching. The fabricated microlens arrays presented here are designed for two different wavebands: 25-40 µm and 135-240 µm. The microlens arrays have sags as deep as 150 µm, are hexagonally packed with a pixel pitch of 900 µm, and have an overall size as large as 80 by 15 mm. We compare an as-fabricated lens profile to the design profile and calculate that the fabricated lenses would achieve 84% encircled power for the designed detector, which is only 3% less than the designed performance. We also present methods developed for antireflection coating microlens arrays and for a silicon-to-silicon die bonding process to hybridize microlens arrays with detector arrays.

Bioisosteric Tactics in the Discovery of Tetflupyrolimet: A New Mode-of-Action Herbicide.

The last new herbicidal modes-of-action with commercial significance were introduced to the marketplace multiple decades ago. Serious weed resistance to most herbicidal classes have since emerged with widespread use. Aryl pyrrolidinone anilides represent an entirely new mode-of-action class of herbicides that interfere with de novo pyrimidine biosynthesis in plants via inhibition of dihydroorotate dehydrogenase. The chemical lead for this new herbicide class discovery was identified from high-volume sourced greenhouse screening that required structural reassignment of the hit molecule followed by an extensive synthetic optimization effort. With excellent grass weed control and pronounced safety on rice, the selected commercial development candidate has a proposed common name of tetflupyrolimet and represents the first member of the new HRAC (Herbicide Resistance Action Committee) Group 28. This paper describes the discovery path to tetflupyrolimet with an added focus on the bioisosteric modifications pursued in optimization, including replacements of the lactam core itself.

A bending rigidity parameter for stress granule condensates.

Interfacial tension plays an important role in governing the dynamics of droplet coalescence and determining how condensates interact with and deform lipid membranes and biological filaments. We demonstrate that an interfacial tension-only model is inadequate for describing stress granules in live cells. Harnessing a high-throughput flicker spectroscopy pipeline to analyze the shape fluctuations of tens of thousands of stress granules, we find that the measured fluctuation spectra require an additional contribution, which we attribute to elastic bending deformation. We also show that stress granules have an irregular, nonspherical base shape. These results suggest that stress granules are viscoelastic droplets with a structured interface, rather than simple Newtonian liquids. Furthermore, we observe that the measured interfacial tensions and bending rigidities span a range of several orders of magnitude. Hence, different types of stress granules (and more generally, other biomolecular condensates) can only be differentiated via large-scale surveys.

Mobilising a workforce to combat COVID-19: An account, reflections, and lessons learned.

With the declaration of coronavirus 2019 (COVID-19) as a pandemic, intensive care units across the globe began to prepare for large numbers of patients. For many years, UK Intensive Care Units (ICUs) have been at high capacity, while facing staffing shortages. In order to prepare for the predicted increased work caring for large numbers with COVID-19, staff were redeployed from other clinical areas to help. Many of these staff had no previous ICU experience. In this article, we share our experiences redeploying medical staff from an extensive range of backgrounds, and how we utilised those staff to maximise use of their existing skills, together with reflections from a variety of redeployed staff members.

Assessment of Fatigue and Recovery in Sport: Narrative Review.

Fatigue is a phenomenon associated with decreases in both physical and cognitive performances and increases in injury occurrence. Competitive athletes are required to complete demanding training programs with high workloads to elicit the physiological and musculoskeletal adaptations plus skill acquisition necessary for performance. High workloads, especially sudden rapid increases in training loads, are associated with the occurrence of fatigue. At present, there is limited evidence elucidating the underlying mechanisms associating the fatigue generated by higher workloads and with an increase in injury risk. The multidimensional nature and manifestation of fatigue have led to differing definitions and dichotomies of the term. Consequently, a plethora of physiological, biochemical, psychological and performance markers have been proposed to measure fatigue and recovery. Those include self-reported scales, countermovement jump performance, heart rate variability, and saliva and serum biomarker analyses. The purpose of this review is to provide an overview of fatigue and recovery plus methods of assessments.

Association of Sports Participation With Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between participating in sport and osteoarthritis is not fully understood. PURPOSE: To investigate the association between osteoarthritis and participating in sports not listed in previous reviews: American football, archery, baseball, bobsleigh, curling, handball, ice hockey, shooting, skeleton, speed skating, and wrestling. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: We searched 4 electronic databases and hand searched recent/in-press editions of relevant journals. The criteria for study selection were case-control studies, cohort studies, nested case-control studies, and randomized trials with a control group that included adults to examine the effect of exposure to any of the included sports on the development of osteoarthritis. RESULTS: The search returned 6197 articles after deduplication. Nine studies were included in the final review, covering hip, knee, and ankle osteoarthritis. There were no studies covering archery, baseball, skeleton, speed skating, or curling. The 6 sports included in the review were analyzed as a collective; the results of the meta-analysis indicated that participation in the sports analyzed was associated with an increased risk of developing osteoarthritis of the hip (relative risk [RR] = 1.67 [95% confidence interval (CI), 1.15-2.41]; P = .04), knee (RR = 1.60 [95% CI, 1.23-2.08]; P < .001), and ankle (RR = 7.08 [95% CI, 1.24-40.51]; P = .03) as compared with controls. Meta-analysis suggested a significantly increased likelihood of developing hip osteoarthritis through participating in wrestling (RR = 1.78 [95% CI, 1.20-2.64]; P = .004) and ice hockey (RR = 1.70 [95% CI, 1.27-2.29]; P < .001), while there was no significant difference through participating in handball (RR = 2.50 [95% CI, 0.85-7.36]; P = .10). Likelihood of developing knee osteoarthritis was significantly increased in wrestling (RR = 2.22 [95% CI, 1.59-3.11]) and ice hockey (RR = 1.52 [95% CI, 1.18-1.96]; both P < .002). According to the meta-analysis, shooting did not have a significant effect on the RR of knee osteoarthritis as compared with other sports (RR = 0.43 [95% CI, 0.06-2.99]; P = .39). CONCLUSION: The likelihood of developing hip and knee osteoarthritis was increased for ice hockey and wrestling athletes, and the risk of developing hip osteoarthritis was increased for handball athletes. The study also found that participation in the sports examined, as a collective, resulted in an increased risk of developing hip, knee, and ankle osteoarthritis.

Incidence and risk factors for poor ankle functional recovery, and the development and progression of posttraumatic ankle osteoarthritis after significant ankle ligament injury (SALI): the SALI cohort study protocol.

BACKGROUND: Ankle sprains are one of the most common musculoskeletal injuries, accounting for up to 5% of all Emergency Department visits in the United Kingdom. Ankle injury may be associated with future ankle osteoarthritis. Up to 70% of ankle osteoarthritis cases may be associated with previous ankle injury. There is limited research regarding the association between ankle sprain and ankle osteoarthritis development. The current study aims to phenotype those who suffer significant ankle ligament injuries, identify potential risk factors for ankle injuries and subsequent poor recovery, examine why individuals may develop osteoarthritis, and what factors influence this chance. METHODS: In this multicentre cohort study participants were recruited from nine Emergency Departments and two Urgent Care Centres in the United Kingdom. Participants (aged 18-70 years old) were defined as those who had suffered an isolated acute ankle sprain, which was Ottawa Ankle Rules positive, but negative for a significant ankle fracture on x-ray. Age and sex matched controls were also recruited. The controls were individuals who had not suffered a significant ankle injury, including ankle pain, function affected for more than 7 days, or the ankle caused them to report to an Emergency Department. Data is collected through a series of seven questionnaires (at baseline, 3 months, 1 year, 3 years, 5 years, 10 years, and 15 years later). The questionnaires include four sections (demographic questions; index injury, and injury history questions; functional assessment questions; and quality of life questions) and are designed to collect detailed information about the individual, their injury, potential risk factors for ankle sprains and ankle osteoarthritis, plus their medical history and any medication consumed. DISCUSSION: The Significant Ankle Ligament Injury (SALI) study aims to add to the limited knowledge regarding which factors can predict ankle sprains, complaints, and osteoarthritis. This is important because despite ankle sprains being regarded as a benign injury that resolves quickly, residual symptoms are not uncommon months and years after the injury.

Lynx x-ray microcalorimeter.

Lynx is an x-ray telescope, one of four large satellite mission concepts currently being studied by NASA to be a flagship mission. One of Lynx's three instruments is an imaging spectrometer called the Lynx x-ray microcalorimeter (LXM), an x-ray microcalorimeter behind an x-ray optic with an angular resolution of 0.5 arc sec and ∼2 m2 of area at 1 keV. The LXM will provide unparalleled diagnostics of distant extended structures and, in particular, will allow the detailed study of the role of cosmic feedback in the evolution of the Universe. We discuss the baseline design of LXM and some parallel approaches for some of the key technologies. The baseline sensor technology uses transition-edge sensors, but we also consider an alternative approach using metallic magnetic calorimeters. We discuss the requirements for the instrument, the pixel layout, and the baseline readout design, which uses microwave superconducting quantum interference devices and high-electron mobility transistor amplifiers and the cryogenic cooling requirements and strategy for meeting these requirements. For each of these technologies, we discuss the current technology readiness level and our strategy for advancing them to be ready for flight. We also describe the current system design, including the block diagram, and our estimate for the mass, power, and data rate of the instrument.

The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined Burn and Radiation Wounds.

In a scenario involving a nuclear detonation during war or a terrorist attack, acute radiation exposure combined with thermal and blast effects results in severe skin injury. Although the cutaneous injury in such a scenario may not be lethal, it may lead to inflammation, delayed wound healing and loss of the skin barrier, resulting in an increased risk of infection. In this study, we tested the potential use of timolol, a beta-adrenergic receptor antagonist, to improve epidermal wound closure after combined burn and radiation injury using an ex vivo human skin culture model. Daily application of 10 µ M timolol after combined injury (burn and 10 Gy ex vivo irradiation) increased wound epithelialization by 5-20%. In addition, exposure to 10 Gy significantly suppressed epidermal keratinocyte proliferation by 46% at 48 h postirradiation. Similar to what has been observed in a thermal burn injury, the enzyme phenylethanolamine N-methyltransferase (PNMT), which generates epinephrine, was elevated in the combined thermal burn and radiation wounds. This likely resulted in elevated tissue levels of this catecholamine, which has been shown to delay healing. Thus, with the addition of timolol to the wound to block the binding of locally generated epinephrine to the beta-adrenergic receptor, healing is improved. This work suggests that by antagonizing local epinephrine action within the wound, a beta-adrenergic receptor antagonist such as timolol may be a useful adjunctive treatment to improve healing in the combined burn and radiation injury.

Salvage of Combat Hindfoot Fractures in 2003-2014 UK Military.

BACKGROUND: Hindfoot fractures pose a considerable challenge to military orthopaedic surgeons, as combat injuries are typically the result of energy transfers not seen in civilian practice. This study aimed to characterize the pattern of hindfoot injuries sustained by UK military casualties in recent conflicts, define the early amputation and infection rate, and identify factors associated with poor early outcomes. METHODS: The UK Joint Theatre Trauma Registry was searched for British military casualties sustaining a hindfoot fracture from Iraq and Afghanistan between 2003 and 2014. Data on the injury pattern and management were obtained along with 18-month follow-up data. Statistical analysis was performed with the chi-square test and binomial logistic regression analysis. The threshold for significance was set at P < .05. One hundred fourteen patients sustained 134 hindfoot injuries. Eighteen-month follow-up was available for 92 patients (81%) and 114 hindfeet (85%). RESULTS: The calcaneus was fractured in 116 cases (87%): 54 (47%) were managed conservatively, 32 (28%) underwent K-wire fixation, and 30 (26%) underwent internal fixation. Nineteen patients (17%) required transtibial amputation during this time. A deep infection requiring operative treatment occurred in 13 cases (11%) with Staphylococcus aureus, the most common infectious organism (46%). A deep infection was strongly associated with operative fracture management ( P = .0016). When controlling for multiple variables, the presence of a deep infection was significantly associated with a requirement for amputation at 18 months ( P = .023). There was no association between open fractures and a requirement for amputation at 18 months ( P = .640), nor was conservative management associated with a requirement for amputation ( P = .999). Thirty-six fractures (32%) required unplanned revision surgery within the first 18 months following salvage, of which 19 (53%) involved amputation. CONCLUSION: A deep infection was the sole variable significantly associated with a requirement for amputation by 18 months. These results suggest that attempts at salvaging these injuries are at the limits of orthopaedic technical feasibility. LEVEL OF EVIDENCE: Level III, comparative series.

The Plastic Surgeon as Employee: A Pilot Survey of the California Society of Plastic Surgeons.

INTRODUCTION: Plastic surgeons endure years of training yet remain poorly equipped to negotiate first employment contracts. Our aims were to evaluate typical plastic surgeon employment contracts and assess contract comprehensiveness. We sought elements that should be included to better preserve varied interests. METHODS: A brief, anonymous, e-mailed survey was sent to California Society of Plastic Surgeons members and responses collected over 2 months. We collected information such as years in practice, geographic area, types of practices and number of surgeons within them, and legal standing of partnerships. We asked whether respondents sought legal assistance and specific elements were elaborated. We asked how content they were with their contracts while allowing commentary. RESULTS: Our survey generated 113 responses. 50.0% of respondents reported being in practice for at least 20 years; 2.68% had been in practice for up to 5 years. 62.5% reported being in private practice and 27.7% reported being in academia. In-state geographic distribution of respondents accounted for 85.6%, whereas 14.4% reported practicing out-of-state.Practice size was diverse, with 41.4% of respondents having worked in a group practice of 3 or more, 27.9% in partnership, and 23.4% in solo practice. For partnerships, 29.9% had made formal legal arrangements, whereas 20.6% had made informal arrangements. 74.5% of respondents did not seek legal assistance.Malpractice coverage varied from 51.6% with claims-made, to 21.7% with tail, to 33.0% with no coverage at all. 63.9% reported having no group disability policy. 26.4% reported annual income of less than US $100,000; 49.1% reported US $101,000 to US $200,000; 17.9% reported US $201,000 to US $300,000; 6.60% reported greater than US $300,000. Using a 5-point scale, 7.69% of respondents reported being "extremely dissatisfied" with their first employment contracts (score of 1), whereas 24.0% were "perfectly happy" (5).Eighty-two respondents offered advice. Common themes included seeking legal counsel; considering eventual solo practice; planning long-term; seeking mentorship; and cautioning against third party interests. CONCLUSIONS: New plastic surgeons will find themselves employed by institutions. Seeking attorneys familiar with the profession is advisable. Lack of awareness regarding malpractice options and disability coverage are 2 areas of concern. We reveal critical contract elements that surgeons should negotiate to ensure smooth transition to practice.

A retrospective look at anthranilic diamide insecticides: discovery and lead optimization to chlorantraniliprole and cyantraniliprole.

Anthranilic diamides are an important commercial synthetic class of insecticides (IRAC Group 28) that bind to the ryanodine receptor with selective potency against insect versus mammalian forms of the receptor. The first commercialized diamide, chlorantraniliprole, has exceptional activity against lepidopteran pests. The second anthranilamide product, cyantraniliprole, has excellent cross-spectrum activity against a range of insect orders, including both lepidopteran and hemipteran pests. Here, a retrospective look is presented on the discovery of the class, along with chemistry highlights of the lead evolution to both products. © 2016 Society of Chemical Industry.

Fabrication of petal-shaped masks for suppression of the on-axis Poisson spot in telescope systems.

The presence of a bright (Poisson) spot in the geometrical shadow of circular/spherical shapes has been known for the past two centuries. A broad class of telescopes that involve simultaneous transmit and receive require suppression of the reflected light from the secondary mirror on the detector. For instance, the on-axis design of optical telescope for the evolved Laser Interferometric Space Antenna (eLISA), a re-scoped version of the baseline LISA mission concept, requires suppression of reflected laser light from the secondary mirror on the detector. In the past few years, the hypergaussian functions with petal-shaped realization have been shown to significantly suppress intensity along the optical axis. This work reports on fabrication of a series of petal-shaped masks using a variety of techniques such as 3D printing, photolithography, and wire Electro Discharge Machining. These masks are designed and fabricated to operate in the range of Fresnel numbers between 4 and 120. This paper discusses the challenges, successes, and failures of each fabrication technique and the optical performance of typical masks with suggestions for potential follow up work.

Tubulin modulating antifungal and antiproliferative pyrazinone derivatives.

A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.

Impact of selective alveolar decortication on bisphosphonate burdened alveolar bone during orthodontic tooth movement.

OBJECTIVE: To investigate the effect of Selective Alveolar Decortication (SADc) facilitated orthodontic tooth movement (OTM) on bisphosphonate burdened alveolar bone in a rodent model. DESIGN: OTM was accomplished by protraction of the maxillary right first molars. Four groups were included of which two groups were pre-treated for three months with alendronate sodium (BP+TM+SADc and BP+TM group) and two groups were given saline (TM+SADc and TM group). Selective alveolar decortication surgery was performed on day 1 of appliance insertion. OTM measurements were obtained at 0, 4, and 8 weeks using in-vivo µCT. Tissues were analysed by histology and EPMA. RESULTS: Tooth movement of 0.39 mm and 0.75 mm in the BP+TM+SADc group at 4 and 8 weeks respectively was achieved with 113% increase in tooth movement compared to BP+TM group at 4 weeks. In comparison, SADc+TM group showed 0.63 mm and 2.1 mm of tooth movement at 4 weeks and 8 weeks respectively with only 6% increase at 4 weeks and 2% increase at 8 weeks compared to TM group. Severe interproximal and buccal bone loss around the first permanent molar in the BP+TM+SADc group was seen with µCT imaging and histology. Animals in BP+TM+SADc group histologically showed signs of osteonecrotic bone with irregular borders, loss of osteocytes and absence of osteocytic lacunae. CONCLUSION: This study demonstrated selective alveolar decortication accelerates tooth movement in a bisphosphonate burdened alveolar bone in the short term but the potential of such an invasive injury can have adverse effects.

Antibiotic prophylaxis for infective endocarditis: Knowledge and implementation of American Heart Association Guidelines among dentists and dental hygienists in Alberta, Canada.

BACKGROUND: Knowledge and interpretation of the 2007 American Heart Association (AHA) guidelines regarding infective endocarditis (IE) prophylaxis among the dental community is not well established. The authors' aim was to determine how dentists and dental hygienists interpret the 2007 AHA guidelines. METHODS: The authors sent a cross-sectional survey to a random sample of 450 dental hygienists and 450 dentists in Alberta, Canada. The survey ascertained whether the practitioner would recommend IE prophylaxis to a high-risk cardiac patient undergoing a variety of dental procedures and for a variety of cardiac lesions in patients requiring gingival manipulation. RESULTS: One hundred forty-nine hygienists (33%) and 194 dentists (43%) completed the survey. Use of prophylaxis for specific dental procedures was heterogeneous; 43% of hygienists recommended prophylaxis for polishing, 46% did not, and 11% replied "sometimes." Hygienists were more likely than dentists to inappropriately recommend IE prophylaxis for low-risk lesions including mitral valve prolapse (54% of hygienists versus 42% of dentists recommending prophylaxis; P = .037) and hypertrophic cardiomyopathy (23% versus 15%; P = .057). The authors also observed a failure to recommend IE prophylaxis for high-risk lesions, including mechanical valve (that is, 81% of hygienists and 91% of dentists recommending prophylaxis; P = .008). CONCLUSIONS: There is heterogeneity within the dental community with respect to IE prophylaxis. Dental hygienists are more likely than dentists to recommend IE prophylaxis for low-risk cardiac lesions. Both dentists and hygienists did not consistently recommend prophylaxis for all high-risk cardiac lesions. PRACTICAL IMPLICATIONS: Greater emphasis on IE prophylaxis education is required in training programs and continuing professional development.

Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction without Microsurgery Fellowship Training.

BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap breast reconstruction requires complex microsurgical skills. Herein, we examine whether DIEP flap breast reconstruction can be performed safely without microsurgical fellowship training. METHODS: A total of 28 patients and 34 DIEP flaps were included in the study. We reviewed the medical records of patients for donor site and flap-related complications and analyzed the correlation between the complications and preoperative risk factors. We also performed a literature review to compare complication rates in our series with the literature. RESULTS: We observed total flap necrosis in 1 patient (2.9%), partial flap necrosis in 5 patients (14.7%), infection in 1 patient (2.9%), hematoma/seroma in 3 patients (8.8%), donor site complications in 5 patients (18.5%), venous occlusion in 4 patients (11.7%), and arterial occlusion in 1 patient (2.9%). We did not observe any correlation between complications and preoperative risk factors. Literature review yielded 18 papers that met our inclusion criteria. Partial flap necrosis rate was significantly higher in our series compared with literature (14.7% vs 1.6%, P = 0.003). Venous complication rate was marginally higher in our series compared with literature (11.7% vs 3.3%, P = 0.057). However, total flap loss rate in our series was comparable with the literature (2.9% vs 2.2%, P = 0.759). CONCLUSION: With proper training during plastic surgery residency, DIEP flap can be performed with acceptable morbidity.