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The sensorimotor system has the constant challenge of dealing with the naturally occurring variability in our movements. Here, we investigated the potential roles of muscular co-contraction and visuomotor feedback responses to regulate movement variability. When we visually amplified movements, we found that the sensorimotor system primarily uses muscular co-contraction to regulate movement variability. Interestingly, we found that muscular co-contraction was modulated relative to inherent visuomotor feedback responses, suggesting an interplay between impedance and feedback control.

White matter deficits are a common neuropathologic finding in neurologic disorders, including HIV-associated neurocognitive disorders (HAND). In HAND, the persistence of white matter alterations despite suppressive antiretroviral (ARV) therapy suggests that ARVs may be directly contributing to these impairments. Here, we report that a frontline ARV, bictegravir (BIC), significantly attenuates remyelination following cuprizone-mediated demyelination, a model that recapitulates acute demyelination, but has no impact on already formed mature myelin. Mechanistic studies in vitro revealed that treatment with BIC leads to significant decrease in mature oligodendrocytes accompanied by lysosomal de-acidification and impairment of lysosomal degradative capacity with no alterations in lysosomal membrane permeability or total lysosome number. Activation of the endolysosomal cation channel TRPML1 prevents both lysosomal de-acidification and impairment of oligodendrocyte differentiation by BIC. Lastly, we show that de-acidification of lysosomes by compounds that raise lysosomal pH is sufficient to prevent maturation of oligodendrocytes. Overall, this study has uncovered a critical role for lysosomal acidification in modulating oligodendrocyte function and has implications for neurologic diseases characterized by lysosomal dysfunction and white matter abnormalities.Table of ContentsMain PointsThe antiretroviral, bictegravir, inhibited remyelination through OPC differentiation blockade and had no effect on mature myelinBictegravir inhibits oligodendrocyte differentiation through de-acidification of lysosomes and this was prevented via activation of the lysosomal channel TRPML1De-acidification of lysosomes by other drugs (e.g. bafilomycin A) is sufficient to inhibit oligodendrocyte maturationTable of Contents Image

An improved Singleton-type upper bound is presented for the list decoding radius of linear codes, in terms of the code parameters [n,k,d] and the list size L. L-MDS codes are then defined as codes that attain this bound (under a slightly stronger notion of list decodability), with 1-MDS codes corresponding to ordinary linear MDS codes. Several properties of such codes are presented; in particular, it is shown that the 2-MDS property is preserved under duality. Finally, explicit constructions for 2-MDS codes are presented through generalized Reed-Solomon (GRS) codes., Comment: Main changes from v1: replaced Theorem 4 by a stronger result and added Corollary 5, Lemma 8, and Corollary 9

On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response (1,2). CDC's emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17-October 6, 2022, a total of 26,384 probable and confirmed* U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity

Objectives. To describe prevalence of breast milk feeding among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and examine associations between breast milk feeding, timing of maternal infection before delivery, and rooming-in status during delivery hospitalization. Methods. We performed a retrospective cohort study using data from Massachusetts, Minnesota, Nebraska, Pennsylvania, and Tennessee of whether people with confirmed SARS-CoV-2 infection during pregnancy in 2020 initiated breast milk feeding at birth. Results. Among 11 114 (weighted number) people with SARS-CoV-2 infection in pregnancy, 86.5% (95% confidence interval [CI] = 82.4%, 87.6%) initiated breast milk feeding during birth hospitalization. People with infection within 14 days before delivery had significantly lower prevalence of breast milk feeding (adjusted prevalence ratio [APR] = 0.88; 95% CI = 0.83, 0.94) than did those with infection at least 14 days before delivery. When stratified by rooming-in status, the association between timing of infection and breast milk feeding remained only among infants who did not room in with their mother (APR = 0.77; 95% CI = 0.68, 0.88). Conclusions. Pregnant and postpartum people with SARS-CoV-2 infection should have access to lactation support and be advised about the importance of breast milk feeding and how to safely feed their infants in the same room. (Am J Public Health. 2022;112(S8):S787–S796. https://doi.org/10.2105/AJPH.2022.307023 )

There exists growing evidence that animal personality (consistent between individual differences in behavior) can influence an individual’s fitness. Furthermore, limitations in behavioral plasticity may cause personality-mediated tradeoffs to occur, for example, between speed and accuracy in decision making. We explored whether various measures of personality could predict speed-accuracy tradeoffs in mate selection using Pharaoh cicadas (Magicicada septendecim) and examined the phenotypic traits predicting male mating performance and advertisement rates. We assessed whether male exploration behavior, boldness, and weight could predict a male’s overall copulation attempt rate (the number of attempted copulations with conspecifics of either sex), the number of errors a male made when selecting a mate (the number of same-sex copulation attempts), and male reproductive performance (whether a male successfully copulated with a female). We also assessed whether personality-dependent variation in male advertisement rate (the number of calling song bouts) might underpin the correlation between exploration behavior and mating performance. Although male exploration behavior did not predict male advertisement rate, we found that faster-exploring males exhibited higher overall rates of attempted copulations while also attempting more same-sex copulations, compared to slower-exploring males, suggesting a personality-mediated speed-accuracy tradeoff. Despite making more mate choice errors, however, faster explorers were more likely to successfully copulate with females, compared to slower explorers, indicating that speed may be favored over accuracy in systems where heavily male-biased sex ratios lead to scramble competition. Overall, this work highlights the role of personality in sexual selection and demonstrates that personality can influence speed-accuracy trade-offs in mating.

The National Academies recently issued a consensus study report summarizing the state of the art and research needs relating to Human-AI teaming, especially in the context of dynamic, high-risk environments such as multi-domain military operations. This consensus study was conducted by the National Academies Board on Human-Systems Integration (BOHSI). This panel, organized by BOHSI, brings together prominent researchers, including several members of the consensus committee, to discuss the state of the art and research frontiers for development of effective human-AI teams that can operate resiliently in complex, data intensive, and dynamically paced environments.

High-throughput profiling of key enzyme activities of carbon, nitrogen, and antioxidant metabolism is emerging as a valuable approach to integrate cell physiological phenotyping into a holistic functional phenomics approach. However, the analyses of the large datasets generated by this method represent a bottleneck, often keeping researchers from exploiting the full potential of their studies. We address these limitations through the exemplary application of a set of data evaluation and visualization tools within a case study. This includes the introduction of multivariate statistical analyses that can easily be implemented in similar studies, allowing researchers to extract more valuable information to identify enzymatic biosignatures. Through a literature meta-analysis, we demonstrate how enzyme activity profiling has already provided functional information on the mechanisms regulating plant development and response mechanisms to abiotic stress and pathogen attack. The high robustness of the distinct enzymatic biosignatures observed during developmental processes and under stress conditions underpins the enormous potential of enzyme activity profiling for future applications in both basic and applied research. Enzyme activity profiling will complement molecular -omics approaches to contribute to the mechanistic understanding required to narrow the genotype-to-phenotype knowledge gap and to identify predictive biomarkers for plant breeding to develop climate-resilient crops.

We routinely have physical interactions with others, whether it be handing someone a glass of water or jointly moving a heavy object together. These sensorimotor interactions between humans typically rely on visual feedback and haptic feedback. Recent single participant studies have highlighted that the unique noise and time delays of each sense must be considered to estimate the state, such as the position and velocity, of one's own movement. However we know little on how visual feedback and haptic feedback are used to estimate the state of another person. Here we tested how humans utilize visual feedback and haptic feedback to estimate the state of their partner during a collaborative sensorimotor task. Across two experiments, we show that visual feedback dominated over haptic feedback during collaboration. Specifically, we found that visual feedback led to comparatively lower task-relevant movement variability, smoother collaborative movements, and faster trial completion times. We also developed an optimal feedback controller that considered the noise and time delays of both visual feedback and haptic feedback to estimate the state of a partner. This model was able to capture both lower task-relevant movement variability and smoother collaborative movements. Taken together, our empirical and modeling results support the idea that visual accuracy is more important than haptic speed to perform state-estimation of a partner during collaboration.

Cleft palate is a common craniofacial disorder involving multiple genetic and environmental predisposing factors. Currently, limited insight exists into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis. This study utilized thePax9-deficient mouse genetic model of cleft palate to investigate the role ofPax9in osteogenic differentiation. Single-nucleus transcriptomics and chromatin accessibility assays validated by whole-transcriptome and single-molecule spatial transcriptomics suggest a relationship between separatePax9+and osteogenic populations. Loss ofPax9resulted in premature osteogenic differentiation and bone maturation. The spatially restricted osteogenic domains inPax9−/−mice are bounded byDkk2, which normally interfaces withPax9in the mesenchyme. Together, these results confirm a regulatory role for the Wnt pathway in patterning of palatal bone, offering novel insights into the complex nature of developmental signaling and osteodifferentiation in the palate.SUMMARY STATEMENTNovel evidence of Wnt-mediated osteogenic differentiation and patterning of palatal bone is presented in a murine cleft palate model.Dkk2is implicated as a spatial regulator of palate ossification zones, in concert withPax9.

The impact of preexposure prophylaxis uptake on sexual and injection-related behaviors among women who inject drugs is poorly understood. Over 24 weeks, preexposure prophylaxis uptake among women who inject drugs was associated with increased sharing of injection equipment but not syringes and no changes in condomless sex, providing limited evidence of risk compensation in this vulnerable population.

There is a paucity of research examining multivariate base rates (MBRs) of elevated scores in pediatric rating scales of cognition. We present novel MBR information on the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) for several clinical groups: Attention-Deficit/Hyperactivity Disorder Combined Presentation (ADHD-C); ADHD Inattentive Presentation (ADHD-I); Autism Spectrum Disorder (ASD); and Specific Learning Disorder with impairment in Reading (SLD-R). Participants included children diagnosed as having ADHD-C (

The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC).We assessed birth and follow-up data from infants with birth HC measurements3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly. We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and longitudinal HC measurements between 2 and 12 months of age. Two or more HC measurements were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was3 cm/month in the first 3 months or HC was consistently25th percentile during follow-up.Of 6,799 liveborn infants in USZPIR, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%.About one-third of infants in USZPIR with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in longitudinal studies can reduce misclassification of microcephaly.

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.

From a baby’s babbling to a songbird practicing a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species, neural firing, gait patterns, and reaching behaviour. Past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here we test a fundamentally different idea—that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint, and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development, or when recovering from a neurological disorder to discover and learn new motor actions.

Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥ 1 follow-up exam after 14 days of age or with ≥ 1 visit with development reported, respectively. Results: Among 2,248 infants, 9.9% were born preterm, and 10.0% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1,881 children ≥ 1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥ 1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. Conclusion: Understanding the prevalence of developmental delays and healthcare needs these children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families.

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.

Image sensors, most notably the Charge Coupled Device (CCD), have revolutionized observational astronomy as perhaps the most important innovation after photography. Since the 50th anniversary of the invention of the CCD has passed in 2019, it is time to review the development of detectors for the visible wavelength range, starting with the discovery of the photoelectric effect and first experiments to utilize it for the photometry of stars at Sternwarte Babelsberg in 1913, over the invention of the CCD, its development at the Jet Propulsion Laboratory, to the high performance CCD and CMOS imagers that are available off-the-shelf today., Comment: 9 pages, 10 figures. Presented at SDW2022, accepted for publication in Special Issue of Astronomische Nachrichten

Most image restoration methods in astronomy rely upon probabilistic tools that infer the best solution for a deconvolution problem. They achieve good performances when the point spread function (PSF) is spatially invariant in the image plane. However, this condition is not always satisfied in real optical systems. We propose a new method for the restoration of images affected by static and anisotropic aberrations using Deep Neural Networks that can be directly applied to sky images. The network is trained using simulated sky images corresponding to the T80-S Telescope optical model, a 80-cm survey imager at Cerro Tololo (Chile), which are synthesized using a Zernike polynomial representation of the optical system. Once trained, the network can be used directly on sky images, outputting a corrected version of the image that has a constant and known PSF across its field of view. The method is to be tested on the T80-S Telescope. We present the method and results on synthetic data.

Objective Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in Phase 2 and 3 belimumab trials was not reflective of the racial distribution observed in the lupus population. This study assessed efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified black race. Methods EMBRACE (GSK Study BEL115471; NCT01632241): 52-week multicenter, double-blind (DB), placebo-controlled trial in adults of self-identified black race with active SLE, receiving monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26-week open-label extension phase included patients who completed the DB phase. The primary endpoint was SLE Responder Index response rate at Week 52 with modified proteinuria scoring adapted from the SLEDAI-2K (SRI-S2K). Key secondary endpoints included: Week 52 SRI response rate, time to first severe flare, and reductions in prednisone dose. Results The modified intention-to-treat population comprised 448 patients (96.9% female; mean [standard deviation] age: 38.8 [11.42] years). The primary endpoint (SRI-S2K response rate at Week 52) was not achieved (belimumab 48.7%, placebo 41.6%; p=0.1068); however, numerical improvements favoring belimumab were observed, especially in patients with high baseline disease activity or renal manifestations. The safety profile of belimumab was generally consistent with previous SLE trials. Adverse events were the primary reason for DB phase withdrawals (belimumab 5.4%; placebo 6.7%). Conclusions The primary endpoint of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry.

As of November 9, 2022, a total of 28,730 cases of monkeypox (mpox) had been reported in the United States,* primarily among adult cisgender men reporting recent male-to-male sexual contact (1). Transgender and gender-diverse persons, who constitute an estimated 0.5% of the U.S. adult population

Plasma metabolites such as triglyceride (TRIG) can be useful indicators of when birds are in a state of fattening or fasting, although the challenges of processing, storing, and analyzing field-collected plasma samples may limit its use by field ornithologists. We evaluated the use of a field-usable point-of-care (POC) analyzer (CardioChek PA analyzer) for measuring TRIG concentrations in the plasma of male American Woodcock (Scolopax minor) captured during their spring courtship period and compared those measures to those from standard laboratory analyses of the same plasma samples. Plasma TRIG measured in the field with the POC analyzer was highly repeatable and precise, but not accurate compared to lab-measured values. The inaccuracy of the POC analyzer may be due to the effects of environmental conditions on the analyzer’s function or to specific problems associated with analyzing woodcock blood. We conclude that the field-usable POC analyzer does not provide an accurate alternative method for measuring circulating TRIG in woodcock during cold springs in northern breeding areas. Given the analyzer has proven accurate for estimating circulating TRIG in some other bird species, we outline a two-phase pilot study that field ornithologists can use to understand the operating limits of this analyzer for their target species prior to field use.

BACKGROUND In accordance with worldwide data, the Robert Koch Institute (RKI) has reported a constant increase of syphilis cases in Germany over the past decade. METHODS We analysed the data of all patients, referred to a Department of Ophthalmology in a tertiary referral centre in Dusseldorf, Germany between 2008 and 2019, who were tested for syphilis. The epidemiologic, demographic, clinical, diagnostic and therapeutic data were retrieved from the records and evaluated in a retrospective, descriptive, non-comparative study. RESULTS Syphilis serology was positive in 32/1840 (1.7%) patients, and was evenly distributed over this period. 26 (81.3%) were male, 19 (59.4%) belonged to a risk group. Ocular syphilis was the primary diagnosis for 29 patients (90.6%). The most frequent manifestation was uveitis (n = 20, 62.5%). By the end of therapy, 19 patients (59.4%) had an improved visual acuity. CONCLUSION The incidence of ocular syphilis cases has remained stable over the last decade.

The Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) is a standardized rating (self, parent, and teacher) scale of executive functioning in children and adolescents. Here, we provide multivariate base rate (MBR) information (for the Self, Parent, and Teacher forms), which is not included in the BRIEF2 Professional Manual. Participants were children and adolescents for the BRIEF2 Self-Report (ages = 11-18; N = 803), Parent-Report (ages = 5-18; N = 1,400), and Teacher-Report (ages = 5-18; N = 1,400) standardization samples. We focused on cumulative (e.g., % of sample with oneor more elevated scores) MBRs across scales, which were examined at three elevation levels on each form: T≥ 60, ≥65, and ≥70. Across forms, MBRs predictably decreased with increasing number of elevated scores and at higher cutoffs. The cumulative MBR of having at least one score at T≥ 60 was common (37.5-42.2%), but less frequent at T≥ 70 (15.4-17.4%). The probability of having elevated scores on all scales was very low, irrespective of form, age, or elevation threshold (T≥ 60 = 2.4-4.4%; T≥ 65 = 1.0-1.4%; T≥ 70 = 0.0-0.7%). There was no clinically meaningful relation between demographic factors (age, gender, race, and parental education) and MBRs. These data provide clinicians and researchers with an enhanced way of concurrently interpreting multiple BRIEF2 scales.

The Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) is a standardized rating scale of subjective executive functioning. We provide univariate and multivariate base rates (BRs) for scale/index scores in the clinical range ( T scores ≥65), reliable change, and inter-rater information not included in the Professional Manual. Participants were adults (ages = 18–90 years) from the BRIEF-A self-report ( N = 1,050) and informant report ( N = 1,200) standardization samples, as well as test–retest ( n = 50 for self, n = 44 for informant) and inter-rater ( n = 180) samples. Univariate BRs of elevated T scores were low (self-report = 3.3%–15.4%, informant report = 4.5%–16.3%). Multivariate BRs revealed the common occurrence of obtaining at least one elevated T-score across scales (self-report = 26.5%–37.3%, informant report = 22.7%–30.3%), whereas virtually none had elevated scores on all scales. Test–retest scores were highly correlated (self = .82–.94; informant = .91–.96). Inter-rater correlations ranged from .44 to .68. Significant ( p < .05) test–retest T-score differences ranged from 7 to 12 for self-report, from 6 to 8 for informant report, and from 16 to 21 points for inter-rater T-score differences. Applications of these findings are discussed.

Discussion Panel Abstract: The recent Boeing 737MAX accidents crystalized for the public the complexity of anticipating system and operator performance and developing a system design that prevents catastrophic outcomes. The operational situations, progression of flightcrew actions, and system behaviors that led to the two accidents had not been anticipated by the manufacturer or the regulator. These accidents were only the most recent examples of our failure to anticipate and manage operational complexities and operator performance. The art and science of human factors has yet to perfect risk assessment (or safety assessment) for complex systems. In the not-so-distant past, system risk assessment made estimates of human error probabilities (HEPs) for specific operational tasks, which were combined with estimated equipment failure rates to produce an overall risk estimate. Indeed, these Human Reliability Analysis (HRA) techniques have evolved over decades and are still being developed (e.g., IDHEAS-ECA, Xing et al., 2020), partly because they satisfy the need for a simple quantitative threshold that can be used by industry and regulators: if risk probability is too high, change the design or some other aspect of operations. Through the years, there have been critiques of the HRA approach (e.g., Hollnagel, 1998) that led to revisions, such as focusing on cognitive functions instead of operator tasks, but not to the basic quantitative risk-estimation approach. Other approaches to assessing risk/safety have wandered down other paths: attempting to capture system complexity from an operator’s perspective (Roth, Mumaw, Lewis, 1994; Nuclear Regulatory Commission, 2000), or better documenting the many ways in which system operators manage complexity daily to find ways to improve their capacity (Hollnagel, Woods, & Leveson, 2006). These approaches have used different measures than HEPs; e.g., measures of operator performance, measures of interface usability/design, measures of task complexity, and the analysis of system constraints. In this panel, we offer different perspectives on risk/safety assessment as it relates to operator performance in complex systems. Foundational to assessment is deciding the nature of safety and the role of operator performance. Another important question is, as you move away from simple quantitative measures, how do you establish safety thresholds? That is, what guidance can we give to industry and regulators regarding how to measure safety and how to decide that action is required on the basis of safety.

Sedation Practice in Intensive Care Evaluation (SPICE-III) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation.to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age.We included 1177 patients randomized in SPICE-III to receive dexmedetomidine and given supplemental propofol, stratified by age (65 or ≤65 years). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine, while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression, adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality.Younger patients 598/1177(50.8%) received a significantly higher dose of both sedatives compared with older patients, to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 mcg/kg/h) was associated with reduced adjusted mortality in younger, but not older patients. This was consistent with multivariable regression modelling [hazard ratio: 0.59(95% Confidence Interval 0.43-0.78),P0.0001], adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality [HR:1.30(95%CI 1.03-1.65), P=0.029].In patients ≤ 65 years sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registration available at www.gov, ID: NCT01728558.

Background Primary health care (PHC) is built on interprofessional collaboration (IPC) between health and social professions. According to international frameworks, interprofessional communication, client-centred care, collaborative leadership, role clarification, team functioning and interprofessional conflict resolution are essential for IPC. As of April 2022, 36 PHC units were registered in Austria. This study aims to explore the perspectives of health care professionals on IPC in PHC in Austria. Methods Between October 2021 and March 2022, 15 guided group interviews were conducted with a total of 57 representatives of the professional groups biomedical analytics, dietetics, medical training therapy, medicine, midwifery, nursing, occupational therapy, office assistance, orthoptics, pharmacy, physiotherapy, psychotherapy, radiology technology, social work and speech therapy. The data was analysed using qualitative content analysis according to Mayring. Results Interdisciplinary counselling and prevention services, monitoring, acute interventions and treatment of chronic diseases are seen as fields of action for increased IPC in PHC. Interprofessional relationships are established during joint home visits and weekly multiprofessional meetings, when communication is collegial. Challenges mentioned for the IPC in PHC were i.e. role ambiguity, lack of time for networking or unclear legal regulations. Taking over responsibility as well as the ability to delegate and to deal with conflict, a sense of justice and willingness to accept criticism are core competences required for IPC in PHC. Conclusions The interviewees aim to get more involved in PHC, but not all feel optimally prepared for the necessary collaboration in this setting. In their view, specific training content, focusing on the unique structure of PHC, the roles of all the involved professional groups and conflict management, is necessary to successfully shape IPC in the interest of the clients. Key messages

The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane.