Stationary entangled radiation from micromechanical motion.

Mechanical systems facilitate the development of a hybrid quantum technology comprising electrical, optical, atomic and acoustic degrees of freedom1, and entanglement is essential to realize quantum-enabled devices. Continuous-variable entangled fields-known as Einstein-Podolsky-Rosen (EPR) states-are spatially separated two-mode squeezed states that can be used for quantum teleportation and quantum communication2. In the optical domain, EPR states are typically generated using nondegenerate optical amplifiers3, and at microwave frequencies Josephson circuits can serve as a nonlinear medium4-6. An outstanding goal is to deterministically generate and distribute entangled states with a mechanical oscillator, which requires a carefully arranged balance between excitation, cooling and dissipation in an ultralow noise environment. Here we observe stationary emission of path-entangled microwave radiation from a parametrically driven 30-micrometre-long silicon nanostring oscillator, squeezing the joint field operators of two thermal modes by 3.40 decibels below the vacuum level. The motion of this micromechanical system correlates up to 50 photons per second per hertz, giving rise to a quantum discord that is robust with respect to microwave noise7. Such generalized quantum correlations of separable states are important for quantum-enhanced detection8 and provide direct evidence of the non-classical nature of the mechanical oscillator without directly measuring its state9. This noninvasive measurement scheme allows to infer information about otherwise inaccessible objects, with potential implications for sensing, open-system dynamics and fundamental tests of quantum gravity. In the future, similar on-chip devices could be used to entangle subsystems on very different energy scales, such as microwave and optical photons.

The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium: a nationwide interrupted time series analysis.

BACKGROUND: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake. METHODS: An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses. RESULTS: In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI -61.61 to -14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI -880.113 to -19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648-3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797-2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI -203.128 to -100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536-1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant. CONCLUSIONS: The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.

Niacin supplementation impairs exercise performance.

Several pre-workout supplements contain niacin, although the exercise performance effects of niacin are poorly understood. The purpose of the present study was to examine the performance effects of niacin versus caffeine as a pre-workout supplement. Twenty-five untrained males were recruited to complete three identical ramped aerobic cycling exercise trials. Participants were administered caffeine (CA) at 5 mg/kg body weight, 1000 mg niacin (NI), or a methylcelluloce placebo (PL) supplement prior to each trial. NI treatment induced significantly higher respiratory exchange ratio (RER) during exercise compared to the CA treatment, but not the PL treatment (PL=0.87±0.08, NI=0.91±0.08, CA=0.87±0.08; p=0.02). Similarly, exercise time to exhaustion (in minutes) was significantly different between the NI treatment and the CA treatment, but not the PL treatment (PL=27.45±4.47, NI=26.30±4.91, CA=28.76±4.86; p<0.01). Habitual caffeine use (p=0.16), habitual aerobic exercise (p=0.60), and habitual resistance exercise (p=0.10) did not significantly affect RER. Similarly, habitual caffeine use (p=0.72), habitual aerobic exercise (p=0.08), and habitual resistance exercise (p=0.39) did not significantly affect total work performed. The elevated RER and decreased time to exhaustion in the NI treatment suggests limited lipid availability during exercise and impaired exercise performance.

Exposed water ice on the nucleus of comet 67P/Churyumov-Gerasimenko.

Although water vapour is the main species observed in the coma of comet 67P/Churyumov-Gerasimenko and water is the major constituent of cometary nuclei, limited evidence for exposed water-ice regions on the surface of the nucleus has been found so far. The absence of large regions of exposed water ice seems a common finding on the surfaces of many of the comets observed so far. The nucleus of 67P/Churyumov-Gerasimenko appears to be fairly uniformly coated with dark, dehydrated, refractory and organic-rich material. Here we report the identification at infrared wavelengths of water ice on two debris falls in the Imhotep region of the nucleus. The ice has been exposed on the walls of elevated structures and at the base of the walls. A quantitative derivation of the abundance of ice in these regions indicates the presence of millimetre-sized pure water-ice grains, considerably larger than in all previous observations. Although micrometre-sized water-ice grains are the usual result of vapour recondensation in ice-free layers, the occurrence of millimetre-sized grains of pure ice as observed in the Imhotep debris falls is best explained by grain growth by vapour diffusion in ice-rich layers, or by sintering. As a consequence of these processes, the nucleus can develop an extended and complex coating in which the outer dehydrated crust is superimposed on layers enriched in water ice. The stratigraphy observed on 67P/Churyumov-Gerasimenko is therefore the result of evolutionary processes affecting the uppermost metres of the nucleus and does not necessarily require a global layering to have occurred at the time of the comet's formation.

Determinants of prescribing decisions for off-patent biological medicines in Belgium: a qualitative study.

BACKGROUND: A competitive market for off-patent biologicals leads to more affordable and high-quality healthcare. In recent years, Belgium has been characterized by its low use of biosimilars and by its shifts from off-patent biologicals toward new alternative therapies. Yet, the prescribing decisions involved in these observations are poorly understood. This study aims to better understand prescribing choices among Belgian physicians in the ambulatory care setting. METHODS: This study consisted of two phases. First, a scoping literature review to identify determinants of prescribing choices was conducted. Scientific databases (Embase and PubMed) were searched until 4 November 2021. Second, the nominal group technique (NGT) was employed during focus group discussions with Belgian physicians to consider and validate these determinants for off-patent biologicals in the Belgian context. The qualitative data resulting from the literature review and focus group discussions were analyzed using the thematic framework method. RESULTS: Fifty-three scientific articles that discussed elements that determine prescribing choices were identified. Out of these, 17 determinants of prescribing choices were found. These were divided into five categories: (1) product-related, (2) physicians' personal, (3) healthcare system-related, (4) patient-related, and (5) determinants related to the pharmaceutical company or brand. Nineteen Belgian physicians from different therapeutic areas that regularly prescribe biologicals then participated in focus group discussions. Using the NGT, the group discussions revealed that prescribing choices for off-patent biologicals are determined by a complex set of elements. Clinical data, geographical region, working environment, pharmaceutical marketing, patient profile, clinical guidelines, and preference of key opinion leaders (KOL) were considered most influential. Physicians indicated that the importance of these determinants differs depending on product classes or therapeutic domain. CONCLUSIONS: Multiple elements determine the choice of an off-patent biological or biosimilar product. The importance of each of these determinants varies depending on the context in which the prescribing choice is made. To increase the prescription of best-value biologicals in the Belgian ambulatory care, a set of synergistic measures is required including information for healthcare providers (HCP) and patients, prescribing feedback, prescribing targets, tangible incentives, KOL involvement, guidelines regarding pharmaceutical promotion, and regular revision of reimbursement modalities.

Sustainable employability of teachers with hearing loss.

OBJECTIVE: In many countries the retirement age is rising. Consequently, age-related hearing loss is an increasing occupational health problem. This study examined the association between hearing loss and sustainable employability of teachers. DESIGN: For this cross-sectional study a survey and an online hearing screening test were used. Sustainable employability was measured with the Capability Set for Work Questionnaire (CSWQ), examining seven work values. CSWQ-scores of teachers with poor, insufficient, and good hearing were investigated with ordinal regression analyses. Work values and discrepancies between the importance and achievement of the values were examined by chi-square tests. STUDY SAMPLE: Dutch teachers (N = 737) of whom 146 (20%) had insufficient and 86 (12%) poor hearing. RESULTS: Teachers with insufficient (OR = 0.64; 95% CI 0.46-0.89) and poor (OR = 0.55; 95% CI 0.36-0.83) hearing had lower CSWQ-scores compared with good hearing teachers. Adjustment for covariates, in particular for self-rated health, attenuated the associations. Compared with good hearing teachers, teachers with poor hearing reported more discrepancies in using their knowledge and skills and setting their own goals at work. CONCLUSIONS: Hearing loss was negatively associated with sustainable employability of teachers. This emphasises the importance of assessing the hearing status of teachers.

The diurnal cycle of water ice on comet 67P/Churyumov-Gerasimenko.

Observations of cometary nuclei have revealed a very limited amount of surface water ice, which is insufficient to explain the observed water outgassing. This was clearly demonstrated on comet 9P/Tempel 1, where the dust jets (driven by volatiles) were only partially correlated with the exposed ice regions. The observations of 67P/Churyumov-Gerasimenko have revealed that activity has a diurnal variation in intensity arising from changing insolation conditions. It was previously concluded that water vapour was generated in ice-rich subsurface layers with a transport mechanism linked to solar illumination, but that has not hitherto been observed. Periodic condensations of water vapour very close to, or on, the surface were suggested to explain short-lived outbursts seen near sunrise on comet 9P/Tempel 1. Here we report observations of water ice on the surface of comet 67P/Churyumov-Gerasimenko, appearing and disappearing in a cyclic pattern that follows local illumination conditions, providing a source of localized activity. This water cycle appears to be an important process in the evolution of the comet, leading to cyclical modification of the relative abundance of water ice on its surface.

Recognizing Cutibacterium acnes as a cause of infectious pericarditis: A case report and review of literature.

Cutibacterium acnes is an anaerobic bacterium commonly thought of as a culture contaminant rather than a pathogen. We present a case of Cutibacterium acnes pericarditis in a 22-year-old immunocompetent woman managed with surgical pericardial window and a 4-week course of penicillin G and review related literature on Cutibacterium acnes pericarditis.

The Effect of Aspartate and Sodium Bicarbonate Supplementation on Muscle Contractile Properties Among Trained Men.

Farney, TM, MacLellan, MJ, Hearon, CM, Johannsen, NM, and Nelson, AG. The effect of aspartate and sodium bicarbonate supplementation on muscle contractile properties among trained men. J Strength Cond Res 34(3): 763-770, 2020-The focus of this investigation was to examine the effects of aspartate and NaHCO3 supplementation on muscle contractile properties within trained men. Eleven men (21.9 ± 1.5 years) ingested supplementation as 4 conditions all separated by 1 week and included the following: placebo (PLA), L-aspartate (12.5 mg) (ASP), NaHCO3 (0.3 g·kg) (SBC), or combination of ASP and SBC (CBO). For each day of testing, participants performed 1 high-intensity exercise session along with a pre- and postexercise (pre- or postex) isometric mid thigh pull test to measure peak force (PF) production and rate of force development (RFD). Blood was collected for all testing sessions before and after the high-intensity exercise to determine ammonia accumulation (AMM). Exercise sessions consisted of 4 exercises: barbell thrusters, squat jumps, lunge jumps, and forward jumps, with the total amount of work being equated for all 4 exercises across all 4 testing sessions. Participants performed the exercises in the aforementioned order, which was designated as 1 round. Each participant performed 3 rounds, with the work-to-rest ratio being 20-second work, 30-second rest. A 1-minute rest was given between the rounds. There were no treatment effects (p > 0.05) for PF, RFD, or AMM. However, there was a significant main effect for supplement consumption for the total time of work with the ASP, SBC, and CBO treatments having a lower time to completion compared with the PLA treatment. Ammonia was significantly elevated postexercise (p = 0.004), whereas there were no differences from preexercise to postexercise for PF or RFD (p > 0.05). The only significant treatment × time interaction was for RFD (p = 0.03) with CBO increasing postexercise, with the other 3 treatments all decreasing postexercise. The combination of ASP and SBC together may have the potential to reduce fatigue by mitigating the effects of metabolic by-product accumulation.

The Effect of Vinegar Supplementation on High-Intensity Cycling Performance within Recreationally Trained Individuals.

Background and objectives: To investigate the effects of vinegar ingestion upon high-intensity cycle performance in recreationally trained individuals. Materials and methods: Twenty-two participants consumed one of the following in a randomized order on four separate visits: (1) 29 mL of vinegar along with 451 mL of water, (2) 39 g of sucrose along with 441 mL of water, (3) 29 mL of vinegar and 39 g of sucrose along with 412 mL of water, or (4) 480 mL of water alone. For each of the experimental testing sessions, all participants completed in order: (1) high-intensity cycle test 1, (2) fatiguing cycle test, (3) high-intensity cycle test 2, (4) supplement consumption, (5) 90 min rest period, and (6) high-intensity cycle test 3. Total time to exhaustion (TTE) and average heart rate (HR) for each set of sprints was used in analysis. Results: There was no supplement by time interaction or significant main treatment effect observed (p > 0.05) for either TTE or HR. However, there was a main time effect observed, with TTE (p = 0.0001) being lower for cycle test 2 than both cycle test 1 and cycle test 3, and cycle test 3 being lower than cycle test 1. HR (p = 0.0001) was lower for cycle test 3 than both cycle test 1 and cycle test 2, but HR for cycle test 1 did not differ significantly from HR for cycle test 2. Conclusions: The addition of vinegar or sucrose alone, or in combination, was ineffective in improving cycle sprinting TTE when performing three cycle tests.

The arrival of biosimilar monoclonal antibodies in oncology: clinical studies for trastuzumab biosimilars.

The monoclonal antibody trastuzumab (Herceptin®), which targets the human epidermal growth factor receptor 2 (HER2), is approved for the treatment of early breast and advanced breast and gastric cancer in which HER2 is overexpressed. Several biosimilar versions of trastuzumab are expected to enter the European market over the course of 2018 and 2019. The biosimilar development pathway consists of a comprehensive comparability exercise between the biosimilar candidate and the reference product, primarily focussing on data from analytical studies. Clinical studies for biosimilar candidates follow a different design to those for a new biological, as the aim is not to independently establish clinical benefit, but to confirm biosimilarity between the two agents. The different trastuzumab biosimilar candidates have followed diverse pathways in their clinical development, with differences in clinical trial design (equivalence or non-inferiority design), patient population (those with metastatic or early breast cancer) and endpoint (overall response rate or pathological complete response). These differences in approach in phase 3 testing must be viewed in the totality of evidence demonstrating biosimilarity. Adequate information on the biosimilar approval pathway, the nature of the biosimilarity exercise and how the clinical development of a biosimilar is tailored to meet the licensing requirements can help informed decision making in clinical practice.

Uterine fluid proteome changes during diapause and resumption of embryo development in roe deer (Capreolus capreolus).

The uterine microenvironment during pre-implantation presents a pro-survival milieu and is essential for embryo elongation in ruminants. The European roe deer (Careolus capreolus) pre-implantation embryo development is characterised by a 4-month period of reduced development, embryonic diapause, after which the embryo rapidly elongates and implants. We investigated the uterine fluid proteome by label-free liquid chromatography tandem mass spectrometry at four defined stages covering the phase of reduced developmental pace (early diapause, mid-diapause and late diapause) and embryo elongation. We hypothesised that embryo development during diapause is halted by the lack of signals that support progression past the blastocyst stage. Three clusters of differentially abundant proteins were identified by a self-organising tree algorithm: (1) gradual reduction over development; (2) stable abundance during diapause, followed by a sharp rise at elongation; and (3) gradual increase over development. Proteins in the different clusters were subjected to gene ontology analysis. 'Cellular detoxification' in cluster 1 was represented by alcohol dehydrogenase, glutathione S-transferase and peroxiredoxin-2. ATP-citrate synthase, nucleolin, lamin A/C, and purine phosphorylase as cell proliferation regulators were found in cluster 2 and 'cortical cytoskeleton', 'regulation of substrate adhesion-dependent cell spreading' and 'melanosome' were present in cluster 3. Cell cycle promoters were higher abundant at elongation than during diapause, and polyamines presence indicates their role in diapause regulation. This study provides a comprehensive overview of proteins in the roe deer uterine fluid during diapause and forms a basis for studies aiming at understanding the impact of the lack of cell cycle promoters during diapause.

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam.

AIMS: This study explores the impact of paediatric patient related factors and choice of formulation on the dissolution characteristics of nifedipine and lorazepam, 2 drug substances regularly applied in very young patients and in compounded formulations. METHODS: Dissolution experiments were designed to reflect clinical practice in a paediatric hospital, with respect to dosage forms, feeding regimens and methods of administration. Solubility studies addressed the influence of age and prandial state. Drug solubility and dissolution experiments were conducted in biorelevant media and adapted age-specific (neonate and infant) media. Dissolution studies were performed with the mini-paddle apparatus and the flow-through cell apparatus. RESULTS: Dissolution of nifedipine formulations was not affected by age-related changes of the fasted state simulated gastrointestinal fluids, and by disintegration of the formulation before administration. However, a significant difference in nifedipine's dissolution rate from commercial tablets and compounded capsules was observed. The dissolution of lorazepam tablets was affected by fasted- vs fed-state media, but it was deemed less likely to be clinically relevant. The significant effect of fed-state media on nifedipine's solubility was considered to have possible clinical relevance since very young patients are almost continuously in a fed state. CONCLUSION: The in vitro results obtained from these studies reveal the potential of biorelevant solubility and dissolution studies reflecting clinical practice to predict drug performance in paediatric patients.

Use of Biosimilars in Pediatric Inflammatory Bowel Disease: An Updated Position Statement of the Pediatric IBD Porto Group of ESPGHAN.

Biologic therapies have changed the outcome of both adult and pediatric patients with Inflammatory Bowel Disease (IBD). In September 2013, the first biosimilar of infliximab was introduced into the pharmaceutical market. In 2015, a first position paper on the use of biosimilars in pediatric IBD was published by the ESPGHAN IBD Porto group. Since then, more data have accumulated for both adults and children demonstrating biosimilars are an effective and safe alternative to the originator. In this updated position statement, we summarize current evidence and provide joint consensus statements regarding the recommended practice of biosimilar use in children with IBD.

Manipulation of oral medication for children by parents and nurses occurs frequently and is often not supported by instructions.

AIM: Due to a lack of age-appropriate formulations, administration of drugs to children remains a challenge. This study aimed to identify the problems experienced in both the outpatient setting and the clinical setting. METHODS: Between June 2017 and January 2018, we performed a cross-sectional, prospective study at the Sophia Children's Hospital, The Netherlands. The study comprised of a structured interview on drug manipulations with parents visiting the outpatient clinic, and an observational study of drug manipulations by nurses at the wards. RESULTS: A total of 201 questionnaires were collected, accounting for 571 drugs and 169 manipulations (30%). Drug substances that were most often mentioned as manipulated were macrogol (n = 23), esomeprazole (n = 15), paracetamol (n = 8), methylphenidate (n = 7) and melatonin (n = 7). Of all manipulated medicines, 93/169 (55%) were manipulated according to the instructions or recommendations of the Summary of Product Characteristics (SmPC) or patient information leaflet. During the observational study, manipulation was performed by 21/35 of observed nurses (60%), of whom 11 deviated from the hospital protocol for manipulation or SmPC (52%). CONCLUSION: Manipulation was a widely used method to administer drugs to children. Validated information regarding manipulation of drugs for both parents and nursing staff is needed.

Sonic hedgehog signaling controls gut epithelium homeostasis following intestinal ischemia-reperfusion in a rat.

PURPOSE: One of the major regulators of gastrointestinal tract development is the hedgehog signaling pathway. The purpose of this study was to evaluate the role of sonic hedgehog (SHh) signaling 24 and 48 h following intestinal ischemia-reperfusion (IR) in a rat. MATERIALS AND METHODS: Male rats were divided into four experimental groups: (1) Sham-24 h rats underwent laparotomy and were sacrificed after 24 h, (2) Sham-48h rats underwent laparotomy and were sacrificed after 48 h, (3) IR-24h rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 24 h of reperfusion, and (4) IR-48 h rats underwent ischemia for 20 min followed by 48 h of reperfusion. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined by immunohistochemistry 24 and 48 h following IR. SHh-related genes and protein expression were determined using real-time PCR, Western blot and immunohistochemistry. RESULTS: IR-24 rats demonstrated a significant decrease in Shh, Ihh, GIL and Ptch2 mRNA in jejunum and ileum compared to Sham-24 animals that was accompanied by a significant decrease in the number of SHH-positive cells (Immunohistochemistry) in jejunum (2.5-fold decrease) and ileum (37%). After 48 h, IR rats demonstrated a significant increase in Dhh, Ihh, Gil and PTCH2 mRNA in jejunum as well as in Dhh, Ihh, SMO, GIL, PTCH2 mRNA in ileum compared to IR-24 animals that was coincided with increased number of SHH-positive cells in jejunum (2.6-fold increase) and ileum (1.4-fold increase). CONCLUSIONS: 24 h following intestinal IR, inhibited cell turnover was associated with inhibited SHh signaling pathway. Signs of intestinal recovery appeared 48 h after IR and were correlated with increase in SHh signaling pathway activity.

Characterization of a non-human primate model for the study of testicular peritubular cells-comparison with human testicular peritubular cells.

STUDY QUESTION: Are monkey testicular peritubular cells (MKTPCs) from the common marmoset monkey (Callithrix jacchus) a suitable translational model for the study of human testicular peritubular cells (HTPCs)? SUMMARY ANSWER: MKTPCs can be isolated and propagated in vitro, retain characteristic markers for testicular peritubular cells and their proteome strongly (correlation coefficient of 0.78) overlaps with the proteome of HTPCs. WHAT IS KNOWN ALREADY: Smooth-muscle-like peritubular cells form the wall of seminiferous tubules, transport sperm, are immunologically active, secrete a plethora of factors and may contribute to the spermatogonial stem cell niche. Mechanistic studies are hampered by heterogeneity of human samples. STUDY DESIGN, SIZE, DURATION: We established a culture method for MKTPCs and characterized these cells from six young adult animals (2-3 years). To examine whether they qualify as a translational model we also examined HTPCs from seven men and compared the proteomes of both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used explant cultures to obtain MKTPCs, which express smooth muscle markers (calponin (CNN1), smooth muscle actin (ACTA2)), lack FSH-receptors (FSHR) and LH-receptors (LHCGR), but possess androgen receptors (AR). MKTPCs can be passaged at least up to eight times, without discernable phenotypic changes. Mass-spectrometry-based analyses of the MKTPC and HTPC proteomes were performed. MAIN RESULTS AND THE ROLE OF CHANCE: We established a method for isolation and cultivation of MKTPCs, and provide a comprehensive analysis of their protein repertoire. The results let us conclude that MKTPCs are suitable as a non-human primate model to study peritubular cell functions. LARGE SCALE DATA: List of identified proteins in MKTPCs by liquid chromatography-tandem mass spectrometry is accessible at the ProteomeXchange (identifier PXD009394). LIMITATIONS, REASON FOR CAUTION: This is an in vitro cellular non-human primate model used to provide a window into the role of these cells in the human testis. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies with HTPCs from patients revealed a degree of heterogeneity, possibly due to age, lifestyle and medical history of the individual human donors. We anticipate that the new translational model, derived from young healthy non-human primates, may allow us to circumvent these issues and may lead to a better understanding of the role of peritubular cells. STUDY FUNDING AND COMPETION OF INTEREST(S): This work was supported by grants from the Deutsche Forschungsgemeinschaft (MA 1080/27-1; AR 362/9-1; BE 2296/8-1). The authors declare no competing financial interests.

Satellite sensor requirements for monitoring essential biodiversity variables of coastal ecosystems.

The biodiversity and high productivity of coastal terrestrial and aquatic habitats are the foundation for important benefits to human societies around the world. These globally distributed habitats need frequent and broad systematic assessments, but field surveys only cover a small fraction of these areas. Satellite-based sensors can repeatedly record the visible and near-infrared reflectance spectra that contain the absorption, scattering, and fluorescence signatures of functional phytoplankton groups, colored dissolved matter, and particulate matter near the surface ocean, and of biologically structured habitats (floating and emergent vegetation, benthic habitats like coral, seagrass, and algae). These measures can be incorporated into Essential Biodiversity Variables (EBVs), including the distribution, abundance, and traits of groups of species populations, and used to evaluate habitat fragmentation. However, current and planned satellites are not designed to observe the EBVs that change rapidly with extreme tides, salinity, temperatures, storms, pollution, or physical habitat destruction over scales relevant to human activity. Making these observations requires a new generation of satellite sensors able to sample with these combined characteristics: (1) spatial resolution on the order of 30 to 100-m pixels or smaller; (2) spectral resolution on the order of 5 nm in the visible and 10 nm in the short-wave infrared spectrum (or at least two or more bands at 1,030, 1,240, 1,630, 2,125, and/or 2,260 nm) for atmospheric correction and aquatic and vegetation assessments; (3) radiometric quality with signal to noise ratios (SNR) above 800 (relative to signal levels typical of the open ocean), 14-bit digitization, absolute radiometric calibration <2%, relative calibration of 0.2%, polarization sensitivity <1%, high radiometric stability and linearity, and operations designed to minimize sunglint; and (4) temporal resolution of hours to days. We refer to these combined specifications as H4 imaging. Enabling H4 imaging is vital for the conservation and management of global biodiversity and ecosystem services, including food provisioning and water security. An agile satellite in a 3-d repeat low-Earth orbit could sample 30-km swath images of several hundred coastal habitats daily. Nine H4 satellites would provide weekly coverage of global coastal zones. Such satellite constellations are now feasible and are used in various applications.

Visually-guided saccades attenuate postural sway under non-fatigued, fatigued, and stretched states.

Muscular fatigue, which reduces force output and position sense, often leads to increased sway and potential balance impairments. In contrast, visually-guided saccadic eye movements (saccades) can attenuate sway more than fixating gaze on an external target. The goals of this study were to determine whether the use of saccades could reduce the increased postural sway in a fatigued state and to better understand the contributions to fatigue-induced increased sway. We compared the effects of gazing at a fixation point (FP) and performing saccades (SAC) on various spatial and temporal measures of the center of pressure (CoP) while participants stood as still as possible on a force plate. Participants used either a narrow or wide base of support and performed three trials for each eye movement condition (SAC, FP) in three states (non-fatigued-NF, stretched-S, and fatigued-F). Calf raises to exhaustion induced ankle fatigue. Extreme plantar- and dorsi-flexion induced stretch. SAC significantly decreased sway and increased time-series complexity (sample entropy) compared to FP. F increased sway and decreased time-series complexity compared to NF and S states, which were similar. Reduced force production, which accompanies muscle fatigue and stretching, did not account for increased sway associated with acute bouts of ankle muscle fatigue. Increased position sense often associated with muscle stretching likely compensated for any reduced force output for S, while the decreased position sense associated with F probably explained the increased sway in this state. Performing saccadic eye movements during quiet stance can help reduce sway under various states.

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.