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Recommendations for achieving generalized instructional outcomes often overlook the capacity for generative learning for most verbally competent humans. Four children (ages 5-8) participated in this project. In Study 1, we provided decontextualized discrete trial teaching to establish arbitrary relations between colors, pictures of characters, and researcher motor actions. All participants engaged in derivative responding, providing evidence of relational framing. Subsequently, we demonstrated that, with no additional instruction, these derivatives contributed to effective action within a socially valid context (i.e., Candyland gameplay). Study 2 extended the demonstration by teaching frames of opposition. Following teaching, all participants engaged in novel and contextually appropriate responding that entailed the derivation of both coordination and opposition between untrained stimuli. This outcome demonstrates how teaching simple relations can result in learning that manifests at higher levels of complexity (i.e., relational networking), providing some evidence that there can be socially valid benefits to decontextualized discrete trial instruction.

Abstract Background Though Dialectical Behavior Therapy (DBT) and other treatment models for individuals with Borderline Personality Disorder (BPD) have shown to be efficient in inpatient and outpatient settings, there is a general shortage of these treatments. In Germany, most resources are spent on inpatient treatments and unspecific crisis interventions, while it is difficult to implement the necessary team structures in an outpatient setting. This study is testing an alternative approach focussing on outpatient treatment: Integrated Care Borderline (ICB) provides DBT for persons with severe BPD within the structures of an Assertive Community Treatment (ACT). ICB is team-based, integrating psychiatric and social support as well as crisis interventions into a DBT-strategy. Methods ICB was compared to TAU in a prospective, randomized controlled trial. This study is part of RECOVER, a comprehensive stepped care approach in Germany, which enrolled a total of 891 participants. 146 persons were diagnosed with BPD as main diagnosis. Of these, 100 were allocated to the highest level of severe mental illness (SMI) and randomly assigned to either ICB (n = 50) or TAU (n = 50). Data were collected at baseline and 12 months later. The main outcomes were psychosocial functioning (GAF), severity of BPD (BSL-23) and other mental symptoms (BSI, PHQ-9, GAD-7, self-harm), employment status (VILI), as well as hospital days and associated costs. Results Data show a significant increase of psychosocial functioning and a significant decrease of BPD and other psychiatric symptoms in both groups (r = .28 – .64), without any significant differences between the groups. The proportion of self-harming persons decreased in both groups without statistical significance. Patients were significantly more likely to be employed after a year of treatment in ICB (p = .001), but not in the TAU group (p = .454). Analyses showed a significant difference between the groups (p = .032). Moreover, psychiatric hospital days were significantly reduced in ICB (-89%, p

Background: Patient-reported outcome measures (PROMs) correlate with heart failure (HF) severity among adults and are adjunct tools in clinical care. Limited data exist regarding the validity of PROMs in pediatric HF. Hypothesis: Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric Fatigue correlates with HF severity, measured by the New York University Pediatric Heart Failure Index (NYU PHFI). Methods: Children ≥8 and

In all vertebrates, maintaining trunk posture primarily depends on descending commands originating from brainstem vestibulospinal nuclei. Despite being broadly outlined across species, the detailed anatomical and operational structure of these vestibulospinal networks remains poorly understood. Xenopus frogs have previously served as an excellent model for exploring such anatomical and functional aspects in relation to the animal’s behavioral requirements. In this study, we examined the reflex motor reactions induced by vestibular stimulation in pre-metamorphic tadpoles. Our findings indicate that natural vestibular stimulation in the horizontal plane yields greater efficacy compared to stimulation in other planes, a phenomenon replicated in a frequency-dependent manner through specific galvanic stimulation (GVS) of the horizontal semicircular canals. With the exception of a very rostral cluster of neurons that receive vestibular inputs and project to the spinal cord, the overall anatomical segregation of vestibulospinal nuclei in the brainstem mirrors that observed in juvenile frogs. However, our results suggest closer similarities to mammalian organization than previously acknowledged. Moreover, we demonstrated that vestibulospinal cells project not only to spinal motoneurons in rostral segments but also to more distal segments that undergo regression during metamorphosis. Lastly, we illustrated how vestibular-induced spinal reflexes change during larval development, transitioning from tail swim-based activity to rostral trunk bursting responses, likely anticipating postural control in post-metamorphic frogs.

Abstract Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP on autophagic flux compared with the positive control treatment of Torin1. In high-throughput microplate experiments, we found that autophagy induction was more robust in early passages of HEK cells. Despite limiting studies to early passages for maximum sensitivity, a range of NAS structures failed to reliably induce autophagy or interact with Torin1 or starvation effects. To probe NAS in a system where AlloP effects have been shown previously, we surveyed astrocytes and again saw minimal autophagy induction by AlloP. Combined with other published results, our results suggest that NAS may modulate autophagy in a cell-specific or context-specific manner. Although there is merit to cell lines as a screening tool, future studies may require assaying NAS in cells from brain regions involved in neuropsychiatric disorders.

Background:. Salivary gland obstruction can present as unilateral, episodic facial swelling. Vascular malformations as a cause of parotid duct obstruction with associated unilateral cheek swelling and pain are rare. Case description:. We describe the case of a 16-year-old female with a protracted 2-year history of unilateral facial swelling and pain that was misdiagnosed as recurrent parotitis on computed tomography and sialoendoscopy. Eventually, the 16-year-old female was diagnosed by magnetic resonance imaging to have a microcystic lymphatic malformation of the parotid duct as the cause of her cheek swelling and pain. Afterwards, the patient was referred to undergo interstitial bleomycin sclerotherapy. Conclusions:. This case demonstrates a unique microcystic lymphatic malformation producing obstructive symptoms as well as the utility of magnetic resonance imaging for the diagnosis of a patient presenting with recurrent unilateral facial pain and swelling.

Abstract The elimination of synapses during circuit remodeling is critical for brain maturation; however, the molecular mechanisms directing synapse elimination and its timing remain elusive. We show that the transcriptional regulator DVE-1, which shares homology with special AT-rich sequence-binding (SATB) family members previously implicated in human neurodevelopmental disorders, directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during the maturation of wild-type GABAergic neurons but persist into adulthood in dve-1 mutants, producing heightened motor connectivity. DVE-1 localization to GABAergic nuclei is required for synapse elimination, consistent with DVE-1 regulation of transcription. Pathway analysis of putative DVE-1 target genes, proteasome inhibitor, and genetic experiments implicate the ubiquitin-proteasome system in synapse elimination. Together, our findings define a previously unappreciated role for a SATB family member in directing synapse elimination during circuit remodeling, likely through transcriptional regulation of protein degradation processes.

Oxidation reactions are critical components of the synthetic toolbox taught to undergraduate students during introductory organic chemistry courses. However, the oxidation reactions discussed in the undergraduate curriculum are often outdated as many organic chemistry textbooks emphasize chromium-based oxidants that are no longer in regular use by practitioners, which may limit an instructor's time to allocate to discussion of other oxidants. Further, laboratory courses have since either removed oxidation experiments or replaced them with oxidative processes not discussed in lectures, thus leading to a disconnect between the two learning settings. As part of an effort to bridge this divide and modernize the oxidation reactions discussed in our curricula, we have developed a new laboratory experiment that uses a commercially available oxoammonium salt (Bobbitt's salt) to cleanly oxidize cinnamyl alcohol to cinnamaldehyde. In addition to being a safe, convenient, colorimetric, and "green oxidant" suitable for use in the undergraduate teaching laboratory, the hydride-transfer mechanism allows for overlap with key course concepts presented in both introductory and advanced lecture courses. The procedure is well-suited for small and large organic I, II, or advanced laboratory sections alike and can be completed within a standard 3-4 h laboratory period. Aside from exposing students to a modern green oxidation protocol, the experiment contains expanded opportunities for interpretation of 1H NMR, 13C NMR, and IR spectra. An optional addendum for advanced students involving Hammett correlations was also developed.

Abstract Previous studies provide evidence for an association between modifications of the gut microbiota in early life and the development of food allergies. We studied the faecal microbiota composition (16S rRNA gene amplicon sequencing) and faecal microbiome functionality (metaproteomics) in a cohort of 40 infants diagnosed with cow’s milk allergy (CMA) when entering the study. Some of the infants showed outgrowth of CMA after 12 months, while others did not. Faecal microbiota composition of infants was analysed directly after CMA diagnosis (baseline) as well as 6 and 12 months after entering the study. The aim was to gain insight on gut microbiome parameters in relation to outgrowth of CMA. The results of this study show that microbiome differences related to outgrowth of CMA can be mainly identified at the taxonomic level of the 16S rRNA gene, and to a lesser extent at the protein-based microbial taxonomy and functional protein level. At the 16S rRNA gene level outgrowth of CMA is characterized by lower relative abundance of Lachnospiraceae at baseline and lower Bacteroidaceae at visit 12 months.

Abstract Background Psychotic disorders often develop a chronic course with devastating consequences for individuals, families, and societies. Early intervention programs for people in the first 5 years after the initial psychotic episode (early psychosis) can significantly improve the outcome and are therefore strongly recommended in national and international guidelines. However, most early intervention programs still focus on improving symptoms and relapse prevention, rather than targeting educational and vocational recovery. The aim of the present study is to explore the effects of Supported Employment and Education (SEE) following the Individual Placement and Support (IPS) model in people with early psychosis. Methods The SEEearly trial compares treatment as usual (TAU) plus SEE to TAU alone in outpatient psychiatric settings. The study is a six-site, two-arm, single-blinded, superiority randomized controlled trial (RCT). Participants are randomly assigned (1:1) to the intervention or control group. Aiming to recruit 184 participants, with an assumed drop-out rate of 22%, we will be able to detect a 24% difference in the main outcome of employment/education with 90% power. We make assessments at baseline and at 6- and 12-month follow-ups. Outcome data on employment/education, medication, and current psychiatric treatment is obtained monthly through phone based short assessments. The primary outcome is steady participation for at least 50% of the 12-month follow-up in competitive employment and/or mainstream education. Secondary employment outcomes capture length of employment/education, time to first employment/education, monthly wages/educational attainment, and social return on investment (SROI). Secondary non-employment outcomes include subjective quality of life, psychopathology, substance use, relapse, hospitalization, and functional impairment. To be eligible, participants must be between 16 and 35 years, fulfill diagnostic criteria for early psychosis, and be interested in competitive employment and/or mainstream education. Discussion In SEEearly, we hypothesize that participants with psychosis, who receive TAU plus SEE, present with better primary and secondary outcomes than participants, who receive TAU alone. Positive results of this study will justify SEE as an evidence-based strategy for clinical routine treatment in people with early psychosis. Trial registration SEEearly was registered nationally and internationally in the German Clinical Trials Register (DRKS; identifier: DRKS00029660) on October 14, 2022.

Silver has been shown to improve the antibiotic effects of other drugs against both Gram- positive and -negative bacteria. In this study, we investigated the antibiotic potential of cannabidiol (CBD), cannabichromene (CBC) and cannabigerol (CBG) and their acidic counterparts (CBDA, CBCA, CBGA) against Gram-positive bacteria and further explored the additive or synergistic effects of silver nitrate or silver nanoparticles using 96-well plate growth assays and viability (CFUs- colony-forming units). All six cannabinoids had strong antibiotic effects against MRSA with minimal inhibitory concentrations (MICs) of 2 mg/L for CBG, CBD and CBCA; 4 mg/L for CBGA; and 8 mg/L for CBC and CBDA. Using 96-well checkerboard assays, CBC, CBG and CBGA showed full or partial synergy with silver nitrate; CBC, CBDA and CBGA were fully synergistic with silver nanoparticles against MRSA. Using CFU assays, combinations of CBC, CBGA and CBG with either silver nitrate or silver nanoparticles, all at half or quarter MICs, demonstrated strong, time-dependent inhibition of bacterial growth (silver nitrate) and bactericidal effects (silver nanoparticles). These data will lead to further investigation into possible biomedical applications of specific cannabinoids in combination with silver salts or nanoparticles against drug-resistant Gram-positive bacteria.

Two primary ovarian hormones that fluctuate across the female menstrual cycle—estradiol and progesterone—have been independently linked in separate literatures to nicotine reinforcement and anxiety psychopathology. We identify existing methodological limitations in these literatures, describe an example protocol that was developed to address such limitations, highlight case examples, and offer insights on the resulting advantages and challenges. This protocol was an observational, prospective, within-subjects study of female cigarette smokers who were followed over the course of a complete menstrual cycle. Non-treatment seeking, female cigarette smokers (N = 50), between the ages of 18–40 who have a normal menstrual cycle (25–35 days in length) were recruited from the community. Females with anxiety or mood psychopathology represented 38.0% of the sample. Salivary progesterone and estradiol were assessed each morning via at-home saliva collection methods. Self-reported within-day momentary ratings of anxiety and nicotine reinforcement were collected using ecological momentary assessment (EMA) via a mobile app. Protocol compliance was >85%. Within- and between-subjects heterogeneity was observed in the progesterone and estradiol, anxiety, and nicotine craving measures, especially in the context of anxiety psychopathology. We aimed to integrate the anxiety and nicotine dependence literatures and advance the empirical study of the role of ovarian hormones. This protocol reflects an intensive, yet feasible approach to collecting daily-level naturalistic data related to estradiol, progesterone, anxiety, and nicotine reinforcement.

Background. Parents with a fetus diagnosed with a complex congenital heart defect (CHD) are at high risk of negative psychological outcomes. Purpose. To explore whether parents’ psychological and decision-making outcomes differed based on their treatment decision and fetus/neonate survival status. Methods. We prospectively enrolled parents with a fetus diagnosed with a complex, life-threatening CHD from September 2018 to December 2020. We tested whether parents’ psychological and decision-making outcomes 3 months posttreatment differed by treatment choice and survival status. Results. Our sample included 23 parents (average Age [years] : 27 ± 4, range = 21–37). Most were women ( n = 18), non-Hispanic White ( n = 20), and married ( n = 21). Most parents chose surgery ( n = 16), with 11 children surviving to the time of the survey; remaining parents ( n = 7) chose comfort-directed care. Parents who chose comfort-directed care reported higher distress ( x ¯ = 1.51, s = 0.75 v. x ¯ = 0.74, s = 0.55; Mdifference = 0.77, 95% confidence interval [CI], 0.05–1.48) and perinatal grief ( x ¯ = 91.86, s = 22.96 v. x ¯ = 63.38, s = 20.15; Mdifference = 27.18, 95% CI, 6.20–48.16) than parents who chose surgery, regardless of survival status. Parents who chose comfort-directed care reported higher depression ( x ¯ = 1.64, s = 0.95 v. x ¯ = 0.65, s = 0.49; Mdifference = 0.99, 95% CI, 0.10–1.88) than parents whose child survived following surgery. Parents choosing comfort-directed care reported higher regret ( x ¯ = 26.43, s = 8.02 v. x ¯ = 5.00, s = 7.07; Mdifference = 21.43, 95% CI, 11.59–31.27) and decisional conflict ( x ¯ = 20.98, s = 10.00 v. x ¯ = 3.44, s = 4.74; Mdifference = 17.54, 95% CI; 7.75–27.34) than parents whose child had not survived following surgery. Parents whose child survived following surgery reported lower grief (Mdifference = −19.71; 95% CI, −39.41 to −0.01) than parents whose child had not. Conclusions. The results highlight the potential for interventions and care tailored to parents’ treatment decisions and outcomes to support parental coping and well-being. Highlights Question: Do the psychological and decision-making outcomes of parents differ based on their treatment decision and survival outcome following prenatal diagnosis with complex CHD? Findings: In this exploratory study, parents who decided to pursue comfort-directed care after a prenatal diagnosis reported higher levels of psychological distress and grief as well as higher decisional conflict and regret than parents who decided to pursue surgery. Meaning: The findings from this exploratory study highlight potential differences in parents’ psychological and decision-making outcomes following a diagnosis of complex CHD for their fetus, which appear to relate to the treatment approach and the treatment outcome and may require tailoring of psychological and decision support.

Falls are a common mechanism of injury in mountain biking and may be related to a loss of control of the bicycle. Traditionally, the components of bicycle control (balance and agility) are measured in standing and running, which may not reflect the skills required in mountain biking. In this paper, we present the validity of both traditional standing and novel bicycle-specific balance tests in mountain bikers. Twenty-nine male and female participants completed indoor laboratory tests and an outdoor downhill trail. Participants completed single-leg stance balance, Y-balance test, one static and four dynamic bicycle-specific balance tests, a bicycle agility test, and an outdoor downhill trail. Single-leg stance balance and Y-balance tests with eyes open had poor validity when associated with bicycle control. The static (r ​= ​−0.57, p = 0.001) and four dynamic bicycle balance tests (r ​= ​−0.51 to −0.78, p = 0.005 to 0.0001), and the bicycle agility test (r ​= ​0.87, p < 0.0001) had moderate to strong relationships with the outdoor downhill run. Single-leg stance balance and Y-balance tests with eyes open are not valid measures of performance on a mountain bike, and should not be used to assess these populations. Our novel bicycle balance tests have adequate validity to be used as measures of performance in mountain bikers.

Abstract Over time, artworks often sustain paint layer separation and air gaps within their internal structure due to storage conditions and past restoration efforts. Because of this, paint layer consolidation interventions are an essential activity for art conservators. However, it is difficult to determine the exact location and the extent of layer separation on a piece of art in a non-invasive way, and even more difficult to evaluate the success of a consolidation intervention. In this work, a fifteenth-century wood panel painting was analyzed using terahertz time-domain imaging before and after it was consolidated. Using the terahertz data, it was possible to determine the areas on the artwork in need of consolidation and aid the intervention. The analysis of the after data allowed for the control and determination of the success of the consolidation effort in a non-destructive manner.

Deze studie beschrijft de beschikbaarheid en historische ontwikkeling van niet-reanimeer (NR) beleid op afdelingen voor acute geriatrie in ziekenhuizen in Vlaanderen. Via een gestructureerde postenquête, verstuurd naar alle diensthoofden geriatrie in Vlaanderen in 2002 (N=94), werd de aanwezigheid, ontwikkeling en implementatie van NR-beleid (richtlijnen en codebladen) op de afdeling voor geriatrie bevraagd. Het responspercentage bedroeg 76,6%. De ontwikkeling van NR-beleid startte in 1985, en nam sterk toe in de jaren 1997 en 2001. In 2002 was op 86,1% van de afdelingen een NR-beleid aanwezig, meestal in de vorm van zowel institutionele richtlijnen als patiënt-specifieke codebladen. Het initiatief tot en de ontwikkeling van het NRbeleid kwam vooral tot stand vanuit het ziekenhuis. De formulieren waren niet gestandardiseerd en er was zelden plaats om de mate van betrokkenheid van de patiënt in het besluitvormingsproces te noteren. In vergelijking met andere landen kwam in Vlaanderen de ontwikkeling van NRrichtlijnen en -codebladen op ziekenhuisafdelingen voor acute geriatrie laat op gang. Het was nog steeds onvolledig in 2002. De documenten verschilden sterk qua inhoud en doel en waren eerder de uitdrukking van een defensieve houding van de instelling dan een instrument om de betrokkenheid van patiënten in beslissingen rond het levenseinde aan te moedigen.

Abstract Objectives Children with type I laryngeal clefts and sialorrhea can have posterior drooling, aspiration of oral secretions, and respiratory complications. Laryngeal cleft injection laryngoplasty (LCIL) and salivary botulinum injections (Sal‐Bot) have been used separately for short‐term treatment of type I laryngeal clefts and sialorrhea. Our goal was to evaluate combined LCIL and Sal‐Bot and create recommendations for further treatment based on response to initial treatment. Methods Retrospective chart review of nine patients who underwent direct laryngoscopy and bronchoscopy with combined LCIL and Sal‐Bot from 2012 to 2019. Charts were reviewed for patient characteristics, response to treatment, and pre and post‐op hospitalizations. Subsequent procedures were performed depending on efficacy of initial treatments. Results Nine patients were identified. All had pre‐existing neurologic conditions, gastrostomy tubes, and a history of coughing and choking on secretions. Only one patient was able to feed orally (purees). 1 U/kg of botulinum toxin per gland was injected into each parotid and submandibular gland. The average units of botulinum toxin injected was 67 U. The mean laryngeal cleft injection volume was 0.35 cc. Subsequent treatment was based on timing of symptomatic improvement and individual patient factors. Five patients had respiratory‐related hospitalizations in year preceding the procedures (median 1.5, range 1–10). Three (60%) had a reduction in respiratory‐related hospitalization 1 year post procedure (median 1, range 1–3). One patient died during the follow up period due to continued chronic respiratory failure. Conclusions This is the first study of combined laryngeal cleft injection laryngoplasty and botulinum toxin injections for patients with posterior laryngeal penetration and aspiration of oropharyngeal secretions. We highlight strategies for choosing subsequent procedures based on response to initial treatment. Level of Evidence 4.

Abstract This paper proposes a Bayesian multilevel modeling approach to incorporate response parameters from published studies into crop yield response estimation procedures when nonlimiting or limiting treatment levels are omitted or limited in agronomic experiments. Such circumstances may be encountered when data are from farmer‐led research, which may use nonstandardized experimental designs. The paper's focus is on maize yield response to nitrogen fertilizer, but the procedure is flexible enough to accommodate other factors that could affect crop yield response. A proof‐of‐concept Monte Carlo (MC) exercise supplements an empirical application. The MC simulation investigates the small sample properties of the proposed procedure. The empirical example uses field trial data for a maize planter experiment under different nitrogen (N) fertilizer rates. The planter trial compared mechanical planting methods to methods used in developing countries with limited access to mechanized planter technology. Some experiments had no check plots and all experiments lacked nonlimiting fertilizer rates. Linear and quadratic response functions with plateaus are used in the MC simulation and empirical application. MC results suggest that estimates were closest to true parameter values when priors for optimal N rates from published sources were used.

Abstract Relaxin is a pleiotropic hormone demonstrated to confer cardioprotection in animal models of myocardial infarction and ischemic heart failure by modulating inflammation, fibrosis and arrhythmogenesis. Several of these pathways in the ischemic myocardium are intricately tied with the downstream signaling of bioactive sphingolipids, which play an active role during post-infarction remodeling. In this current study, we examined the effects of relaxin on sphingosine 1-phosphate (S1P), and the potential benefits of relaxin treatment on cardiac health in a rodent model of ischemic heart failure. Acute (30 min) and sub-acute (24 h) treatment of primary cardiomyocytes with serelaxin (recombinant human relaxin-2) increased the cardiomyocyte content of S1P. In the rodent model, treatment with relaxin for 28 days following myocardial ischemia by way of permanent left coronary artery occlusion improved survival and cardiac function, reduced fibrosis and apoptosis, and mitigated the expression of several pro-inflammatory and pro-fibrotic markers. The expression of beclin-1 (autophagy marker) was also reduced. The expression of S1P was significantly higher in cardiac tissue and plasma samples extracted from serelaxin-treated mice at day 28. In conclusion, our studies show a significant protection from relaxin in ischemic heart disease, and demonstrate the association between relaxin signaling and S1P generation.

Visual perception works best when eye movement counteracts the effects of body movement. This study describes how such coordination first emerges and matures during development in frog larvae.

Abstract Introduction The clinical and economic burden of clavicle fractures in England is not well documented. This study evaluated rates of surgical treatment, post-surgical complications, reoperations and costs in patients with clavicle fractures using the Clinical Practice Research Datalink (CPRD) database. Methods CPRD data were linked to National Health Service Hospital Episode Statistics data. Patients with a diagnosis of clavicle fracture between 2010–2018 were selected in CPRD (date of fracture = index date). Of those, patients with surgical intervention within 180 days from index fracture were identified. Rates of post-surgical complications (i.e., infection, non-union, and mal-union), reoperations (for device removal or for postoperative complications), post-operative costs and median time to reoperations were evaluated up to 2 years after surgery. Results 21,340 patients with clavicle fractures were identified (mean age 35.0 years(standard deviation (SD): 26.5), 66.7% male). Surgery was performed on 672 patients (3.2% of total cohort) at an average 17.1 (SD: 25.2) days post-fracture. Complications (i.e., infection, non-union, or malunion) affected 8.1% of surgically treated clavicle fracture patients; the rate of infection was 3.5% (95% CI, 1.7%- 5.2%), non-union 4.4% (95% CI, 2.4%-6.5%), and mal-union 0.3% (95% CI, 0%-0.7%). Adjusting for age, gender, comorbidities and time to surgery, the all-cause reoperation rate was 20.2% (13.2%-30.0%) and the adjusted rate of reoperation for implant removal was 17.0% (10.7%-25.9%)—84% of all-cause reoperations were thus performed for implant removal. Median time to implant removal was 254 days. The mean cost of reoperations for all causes was £5,000. The most expensive reoperations were for cases that involved infection (mean £6,156). Conclusions Complication rates following surgical clavicle fracture care averaged 8.1%. However, reoperation rates exceed 20%, the vast majority of reoperations being performed for device removal. Technologies to alleviate secondary device removal surgeries would address a significant clinical unmet need.

We describe a fantastic new species of forest frog (Mantellidae: Gephyromantis: subgenus: Laurentomantis) from moderately high elevations in the vicinity of Andasibe, Madagascar. This region has been surveyed extensively and has a remarkably high anuran diversity with many undocumented species still being discovered. Surprisingly, by exploring areas around Andasibe that lacked biodiversity surveys, we discovered a spectacular and clearly morphologically distinct species, previously unknown to science, Gephyromantis marokoroko sp. nov., documented for the first time in 2015. The new species is well characterised by a very rugose and granular dorsum, dark brown skin with bright red mottling, sparse light orange to white spots on the ventre, vibrant red eyes and femoral glands present only in males that consist of eight medium-sized granules. Bioacoustically, the new species has a quiet advertisement call that differs from related species by having a moderate call duration, 2–4 strongly pulsed notes and a slow note repetition rate. Furthermore, it has substantial differentiation in mitochondrial DNA, with pairwise distances of 7–9% to all other related species in sequences of the mitochondrial 16S rRNA marker. Additional evidence is given through a combined four mitochondrial markers and four nuclear exons concatenated species tree, strongly supporting G. striatus as the sister species of the new species in both analyses. The discovery of this new species highlights the need for continued inventory work in high elevation rainforests of Madagascar, even in relatively well-studied regions.

Swimrun was established in Sweden in 2006. In competition athletes alternate between running and swimming multiple times. It has grown from only being hosted in Sweden to now being a global sport. The swimrun race exposes athletes to environments that require a unique set of skills. For example, participants have to negotiate ocean currents and waves. The environmental conditions change between the runs and the swims. Athletes may be exposed to hot temperatures when running in wetsuits (25 ​°C and hotter) and cold water (colder than 16 ​°C) when swimming. This sudden change in environmental conditions imposes a poorly defined physiological stress on the participants. Research on the demands of swimrun is scarce. More research is needed to improve athlete safety during events. Also, research is needed to provide insight into enhancing training methods and performance.

Abstract Rodent predators are implicated in declines of seabird populations, and removing introduced rats, often, but not always, results in the expected conservation gains. Here we investigated the relationship between small mammal (Norway rat, wood mouse and pygmy shrew) abundance and Manx shearwater breeding success on the island of Rum, Scotland, and tested whether localised rodenticide treatments (to control introduced Norway rats) increased Manx shearwater breeding success. We found that Manx shearwater breeding success was negatively correlated with late summer indices of abundance for rats and mice, but not shrews. On its own, rat activity was a poor predictor of Manx shearwater breeding success. Rat activity increased during the shearwater breeding season in untreated areas but was supressed in areas treated with rodenticides. Levels of mouse (and shrew) activity increased in areas treated with rodenticides (likely in response to lower levels of rat activity) and Manx shearwater breeding success was unchanged in treated areas (p

Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.

This article deals with the communication of inaccessible heritage. Based on a classification of different mediation tools, we propose a framework for selecting the most appropriate tools to communicate about heritage sites under restoration and, therefore, inaccessible. Furthermore, from the data already collected, we show how it is possible to use the constraints of building sites as opportunities for mediation. Finally, we apply this scheme to the case of the collegiate church of Sainte Croix in Liège, for which we end up proposing three mediation tools: the creation of a virtual visit website, the realization of 3D printed scale models, and the design and printing of a cover sheet showing the interior of the building at 1/1 scale.

BackgroundDrug overdose mortality continues to increase, now driven by fentanyl. Prevention tools such as naloxone and medications to treat opioid use disorder are not sufficient to control overdose rates; additional strategies are urgently needed. ObjectiveWe sought to adapt a behavioral intervention to prevent opioid overdose (repeated-dose behavioral intervention to reduce opioid overdose [REBOOT]) that had been successfully piloted in San Francisco, California, United States, to the setting of Boston, Massachusetts, United States, and the era of fentanyl for a full efficacy trial. MethodsWe used the assessment, decision, adaptation, production, topical experts, integration, training, and testing (ADAPT-ITT) framework for intervention adaptation. We first identified opioid overdose survivors who were actively using opioids as the population of interest and REBOOT as the intervention to be adapted. We then performed theater testing and elicited feedback with 2 focus groups (n=10) in Boston in 2018. All participants had used opioids that were not prescribed to them in the past year and experienced an opioid overdose during their lifetime. We incorporated focus group findings into our initial draft of the adapted REBOOT intervention. The adapted intervention was reviewed by 3 topical experts, and their feedback was integrated into a subsequent draft. We trained study staff on the intervention and made final refinements based on internal piloting. This paper describes the overall ADAPT-ITT process for intervention adaptation, as well as a qualitative analysis of the focus groups. Working independently, 2 authors (VMM and JA) reviewed the focus group transcripts and coded them for salient and common themes using the constant comparison method, meeting to discuss any discrepancies until consensus was reached. Codes and themes were then mapped onto the REBOOT counseling steps. ResultsFocus group findings contributed to substantial changes in the counseling intervention to better address fentanyl overdose risk. Participants described the widespread prevalence of fentanyl and said that, although they tried to avoid it, avoidance was becoming impossible. Using alone and lower opioid tolerance were identified as contributors to overdose risk. Slow shots or tester shots were acceptable and considered effective to reduce risk. Naloxone was considered an effective reversal strategy. Although calling emergency services was not ruled out, participants described techniques to prevent the arrival of police on the scene. Expert review and internal piloting improved the intervention manual through increased participant centeredness, clarity, and usability. ConclusionsWe successfully completed the ADAPT-ITT approach for an overdose prevention intervention, using theater testing with people who use opioids to incorporate the perspectives of people who use drugs into a substance use intervention. In the current crisis, overdose prevention strategies must be adapted to the context of fentanyl, and innovative strategies must be deployed, including behavioral interventions. Trial RegistrationClinicalTrials.gov NCT03838510; https://clinicaltrials.gov/ct2/show/NCT03838510

Central circuitry of the vestibular nuclei integrates sensory inputs in the adaptive control of motor behaviors such as posture, locomotion, and gaze stabilization. Thus far, such circuits have been mostly examined at mature stages, whereas their emergence and early development have remained poorly described. Here, we focused on the perinatal period of murine development, from embryonic day E14.5 to post-natal day P5, to investigate the ontogeny of two functionally distinct vestibular neuronal groups, neurons projecting to the spinal cord via the lateral vestibulospinal tract (LVST) and commissural neurons of the medial vestibular nucleus that cross the midline to the contralateral nucleus. Using transgenic mice and retrograde labeling, we found that network-constitutive GABAergic and glycinergic neurons are already established in the two vestibular groups at embryonic stages. Although incapable of repetitive firing at E14.5, neurons of both groups can generate spike trains from E15.5 onward and diverge into previously established A or B subtypes according to the absence (A) or presence (B) of a two-stage spike after hyperpolarization. Investigation of several voltage-dependent membrane properties indicated that solely LVST neurons undergo significant maturational changes in their electrophysiological characteristics during perinatal development. The proportions of A vs B subtypes also evolve in both groups, with type A neurons remaining predominant at all stages, and type B commissural neurons appearing only post-natally. Together, our results indicate that vestibular neurons acquire their distinct morpho-functional identities after E14.5 and that the early maturation of membrane properties does not emerge uniformly in the different functional subpopulations of vestibulo-motor pathways.

Summary: Background: The eye-seeking fly Musca sorbens can act as a vector for ocular Chlamydia trachomatis, causing trachoma, yet there has been very little research on control measures. We investigated whether insect repellent products, specifically insecticide-treated clothing, could provide personal protection to the user from eye-seeking flies. Methods: We first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069). Findings: Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial. Interpretation: Musca sorbens flies are sufficiently repelled by PTS to reduce fly-eye contacts for the wearer, thus possibly reducing the risk of trachoma transmission. Permethrin-treated scarves may therefore an alternative to insecticide space spraying for protection from these flies. Funding: Wellcome Trust.

[This corrects the article DOI: 10.1371/journal.pgen.1010016.].

Background Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. Methods and findings To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case–control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle–Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. Conclusions In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk. Amanda Lambert and co-workers study associations between severe mental illness and cardiovascular disease outcomes over time. Author summary Why was this study done? Previous research has identified higher incidence and mortality from cardiovascular disease (CVD) in people with severe mental illness (SMI) than those without SMI. It is not known whether the gap has changed over time. What did the researchers do and find? We conducted a comprehensive systematic review and meta-analysis of 108 cohort and case–control studies, including over 30 million participants. Compared to the general population, people with SMI, particularly schizophrenia, generally had higher levels of cardiovascular-related mortality and a higher incidence of CVD. For schizophrenia and bipolar disorder (BD), the rate ratios for coronary heart disease (CHD) mortality and cardiovascular mortality were larger in the 1990s and 2000s than in earlier studies, and the rate ratios were larger in younger people. What do these findings mean? We confirmed a strong association between SMI and incidence of and mortality from CVD. This association became stronger in the 1990s and 2000s.

Abstract Aims To ascertain the number of paediatric deaths (0–14 years) with an underlying rare disease in the Republic of Ireland between the years 2006–2016, and to analyse bed usage by a paediatric cohort of rare disease inpatients prior to in-hospital death. Background Rare diseases are often chronically debilitating and sometimes life-threatening diseases, with the majority (69.9%) of rare diseases being of paediatric onset. The Orphanet database contains information on 6172 unique rare diseases. Under-representation of rare diseases in hospital healthcare coding systems leads to a paucity of rare disease epidemiological data required for healthcare planning. Studies have cited variable incidence rates for rare disease, however the burden of rare diseases to healthcare services still remains unclear. This study represents a thorough effort to identify the percentage of child mortality and paediatric bed usage attributable to rare diseases in the Republic of Ireland, thus addressing a major gap in the rare disease field. Methods Retrospective analysis of paediatric death registration details for the Republic of Ireland in the 11-year period 2006–2016 from the National Paediatric Mortality Register. Data was subcategorised as Neonatal (0–28 days), Post Neonatal (29 days

Sphingolipids have become established participants in the pathogenesis of obesity and its associated maladies. Sphingosine kinase 1 (SPHK1), which generates S1P, has been shown to increase in liver and adipose of obese humans and mice and to regulate inflammation in hepatocytes and adipose tissue, insulin resistance, and systemic inflammation in mouse models of obesity. Previous studies by us and others have demonstrated that global sphingosine kinase 1 KO mice are protected from diet-induced obesity, insulin resistance, systemic inflammation, and NAFLD, suggesting that SPHK1 may mediate pathological outcomes of obesity. As adipose tissue dysfunction has gained recognition as a central instigator of obesity-induced metabolic disease, we hypothesized that SPHK1 intrinsic to adipocytes may contribute to HFD-induced metabolic pathology. To test this, we depleted Sphk1 from adipocytes in mice (SK1fatKO) and placed them on a HFD. In contrast to our initial hypothesis, SK1fatKO mice displayed greater weight gain on HFD and exacerbated impairment in glucose clearance. Pro-inflammatory cytokines and neutrophil content of adipose tissue were similar, as were levels of circulating leptin and adiponectin. However, SPHK1-null adipocytes were hypertrophied and had lower basal lipolytic activity. Interestingly, hepatocyte triacylglycerol accumulation and expression of pro-inflammatory cytokines and collagen 1a1 were exacerbated in SK1fatKO mice on a HFD, implicating a specific role for adipocyte SPHK1 in adipocyte function and inter-organ cross-talk that maintains overall metabolic homeostasis in obesity. Thus, SPHK1 serves a previously unidentified essential homeostatic role in adipocytes that protects from obesity-associated pathology. These findings may have implications for pharmacological targeting of the SPHK1/S1P signaling axis.

Abstract Background There is conflicting evidence regarding the association between a history of depression and risk of early menopause. In a cohort of premenopausal women, we investigated the association between depression history and ovarian reserve, as measured by anti-müllerian hormone (AMH). Methods The Harvard Study of Moods and Cycles (HSMC) was a prospective cohort study of women living in the Boston, MA metropolitan-area (1995–1999). Women aged 36–45 years at cohort entry (1995) were sampled from seven Boston metropolitan-area communities using census directories. We measured serum AMH in early-follicular phase venous blood specimens from 141 women with a Structured Clinical Interview for DSM-IV (SCID)-confirmed history of depression and 228 without such a history. We calculated prevalence ratios (PR) for the association between characteristics of depression history and low AMH (≤1.4 ng/mL), adjusting for several potential confounders. Results The prevalence of low AMH was similar among depressed (57.5%) and non-depressed (57.9%) women (Adjusted [Adj] PR = 0.90, 95% CI: 0.75, 1.08). Among depressed women, results were not appreciably different among those who had ever used antidepressants and those with comorbid anxiety. Modest inverse associations between depression and low AMH were seen among women aged 36–40 years (Adj PR = 0.75, 95% CI: 0.52, 1.09) and nulliparous women (Adj PR = 0.77, 95% CI: 0.59, 1.00). No dose-response association with greater duration or length of depressive symptoms was observed. Conclusions Overall, the prevalence of low AMH was similar for depressed and non-depressed women 36–45 years of age. Surprisingly, among younger and nulliparous women, those with a history of depression had a slightly reduced prevalence of low AMH relative to those without such a history. These results do not indicate reduced ovarian reserve among women with a history of depression.

Abstract Background As lack of awareness of rare diseases (RDs) among healthcare professionals results in delayed diagnoses, there is a need for a more efficient approach to RD training during academic education. We designed an experimental workshop that used role-play simulation with patient educators and focused on teaching “red flags” that should raise the suspicion of an RD when faced with a patient with frequently encountered symptoms. Our objective was to report our experience, and to assess the improvement in learners’ knowledge and the satisfaction levels of the participants. Results The workshop consisted of 2 simulated consultations that both started with the same frequent symptom (Raynaud phenomenon, RP) but led to different diagnoses: a frequent condition (idiopathic RP) and an RD (systemic sclerosis, SSc). In the second simulated consultation, the role of the patient was played by a patient educator with SSc. By juxtaposing 2 seemingly similar situations, the training particularly highlighted the elements that help differentiate SSc from idiopathic RP. When answering a clinical case exam about RP and SSc, students that had participated in the workshop had a higher mean mark than those who had not (14 ± 3.7 vs 9.6 ± 5.5 points out of 20, p = 0.001). Participants mostly felt “very satisfied” with this training (94%), and “more comfortable” about managing idiopathic RP and SSc (100%). They considered the workshop “not very stressful” and “very formative” (both 71%). When asked about the strengths of this training, they mentioned the benefits of being put in an immersive situation, allowing a better acquisition of practical skills and a more interactive exchange with teachers, as well as the confrontation with a real patient, leading to a better retention of semiological findings and associating a relational component with this experience. Conclusions Through the use of innovative educational methods, such as role-play simulation and patient educators, and by focusing on teaching “red flags”, our workshop successfully improved RP and SSc learning in a way that satisfied students. By modifying the workshop’s scenarios, its template can readily be applied to other clinical situations, making it an interesting tool to teach other RDs.

Abstract The effect of the United States (US) sugar program on sugar-using firm profitability from 2000 to 2017 is examined using firm financial data and the relative US-to-world sugar price ratio. Return on assets and market-to-book ratio proxy for firm financial performance. The regression results provide statistical evidence that as the US sugar price increases relative to the world sugar price, sugar-using firm financial performance improves. This is likely a result of sugar-using firms passing higher sugar costs on to consumers. An ex post analysis indicates that the statistical tests have adequate power. Findings provide guidelines for future analyses investigating the relationship between the US sugar program and sugar-using firm financial performance.

There is a need to quantify agriculture’s potential to sequester carbon (C) to inform global approaches aimed at mitigating climate change effects. Many factors including climate, crop, soil management practices, and soil type can influence the contribution of agriculture to the global carbon cycle. The objective of this study was to investigate the C sequestration potential of conservation agriculture (CA) (defined by minimal soil disturbance, maintaining permanent soil cover, and crop rotations). This study used micrometeorological methods to measure carbon dioxide (CO2) flux from several alternative CA practices in Harare, central Zimbabwe. Micrometeorological methods can detect differences in total CO2 emissions of agricultural management practices; our results show that CA practices produce less CO2 emissions. Over three years of measurement, the mean and standard error (SE) of CO2 emissions for the plot with the most consistent CA practices was 0.564 ± 0.0122 g CO2 m−2 h−1, significantly less than 0.928 ± 0.00859 g CO2 m−2 h−1 for the conventional tillage practice. Overall CA practices of no-till with the use of cover crops produced fewer CO2 emissions than conventional tillage and fallow.

This study applies a bivariate Multiple IndicatorÐMultiple Causation model to examine farm and operator characteristics associated with the likelihood of using pasture management (PM) and prescribed grazing (PGR) practices. Data are from a survey of cattle operations. Most commonly used practices included adjusting livestock and pasture fertilization. Least used were geotextiles in trafficked areas and buffering sensitive areas. Use of PM practices was income sensitive. Land stewardship and government conservation incentive views influenced PGR. Results suggest complementarities between most PGR and PM practices. However, those with higher opportunity costs and off-farm benefits (e.g., stream crossings) are not complementary with other practices.

The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.

Introduction Parents who receive the diagnosis of a life-threatening, complex heart defect in their fetus or neonate face a difficult choice between pursuing termination (for fetal diagnoses), palliative care or complex surgical interventions. Shared decision making (SDM) is recommended in clinical contexts where there is clinical equipoise. SDM can be facilitated by decision aids. The International Patient Decision Aids Standards collaboration recommends the inclusion of values clarification methods (VCMs), yet little evidence exists concerning the incremental impact of VCMs on patient or surrogate decision making. This protocol describes a randomised clinical trial to evaluate the effect of a decision aid (with and without a VCM) on parental mental health and decision making within a clinical encounter.Methods and analysis Parents who have a fetus or neonate diagnosed with one of six complex congenital heart defects at a single tertiary centre will be recruited. Data collection for the prospective observational control group was conducted September 2018 to December 2020 (N=35) and data collection for two intervention groups is ongoing (began October 2020). At least 100 participants will be randomised 1:1 to two intervention groups (decision aid only vs decision aid with VCM). For the intervention groups, data will be collected at four time points: (1) at diagnosis, (2) postreceipt of decision aid, (3) postdecision and (4) 3 months postdecision. Data collection for the control group was the same, except they did not receive a survey at time 2. Linear mixed effects models will assess differences between study arms in distress (primary outcome), grief and decision quality (secondary outcomes) at 3-month post-treatment decision.Ethics and dissemination This study was approved by the University of Utah Institutional Review Board. Study findings have and will continue to be presented at national conferences and within scientific research journals.Trial registration number NCT04437069 (Pre-results).

Bayesian analysis provides a principled way to quantify uncertainty and incorporate data and prior knowledge into parameter estimates. This paper makes the latest in Bayesian methods easier for others to use with a focus on a stochastic plateau crop production function. Previous studies have used Bayesian techniques to model stochastic plateau functions. No published work provides computation guidelines to estimate stochastic plateau functions using Bayesian approaches using computationally efficient algorithms such as Hamiltonian Monte Carlo (HMC). HMC is the default choice in Stan software, but the learning curve to master the software is steep. We provide HMC estimation instructions for a univariate stochastic plateau function using the R environment's brms and RStan. We also compare HMC estimation results with those using Gibbs sampling via Just Another Gibbs Sampler (JAGS) software using the R Interface R2jags. The programs are relatively compact and are included in the paper. Simulation results from HMC are consistent across different priors and are similar to those generated by a Gibbs sampler. This paper serves as a tutorial on the use of HMC for estimating plateau-type production functions. The code, and method, can be extended to other nonlinear models.

This research note extends Bayesian discriminant analysis procedures to the ordered and multinomial logistic likelihood functions. Use of the procedure is warranted when the researcher desires to identify the membership of individuals randomly drawn from distinct groups or locations in a population, rather than from a random sample of undifferentiated individuals from a population. An empirical application analyzes consumers’ reasons why they choose to support a beef product produced with enhanced pasture management practices.

Introduction: Abnormalities of the epiglottis and hyoid bone have been described in association with Pierre Robin Sequence (PRS). Embryologically, the epiglottis stems between the third and fourth branchial arches, while the hyoid bone develops from the second and third arches. The body of the hyoid bone completes its development by 4 months of age, and in fact can be seen on imaging in the majority of children after 9 months of age. Case: We present a case of an 18-year-old male known for PRS, who underwent a tracheostomy within a week of life and multiple airway evaluations since. Complete absence of his epiglottis was noted early on. Numerous computed tomographies (CTs) preformed during his lifetime with three-dimensional reconstruction of facial bones; however, only reported bony anomalies of the mandible and zygomatic arches. In a retrospective review of imaging by his surgeons and the center's radiologist, the body of the hyoid bone was found to be clearly absent from the earliest CT at 2 years of age. His greater cornua; meanwhile, remain present leading into soft tissue and potentially cystic content in the midline. Discussion: These anomalies bring up the question of an underreported association within PRS patients considering their close embryological origins. Aplasia of the epiglottis is well reported independently, but there have been very few studies on hyoid anomalies in this population. A larger series is needed to evaluate the frequency as well as potential clinical impact of these abnormalities in unison within the PRS population.

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.