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Population responses to environmental variation ultimately depend on within-individual and among-individual variation in labile phenotypic traits that affect fitness and resulting episodes of selection. Yet complex patterns of individual phenotypic variation arising within and between time periods, as well as associated variation in selection, have not been fully conceptualized or quantified. We highlight how structured patterns of phenotypic variation in dichotomous threshold traits can theoretically arise and experience varying forms of selection, shaping overall phenotypic dynamics. We then fit novel multistate models to 10 years of band-resighting data from European shags to quantify phenotypic variation and selection in a key threshold trait underlying spatioseasonal population dynamics: seasonal migration versus residence. First, we demonstrate substantial among-individual variation alongside substantial between-year individual repeatability in within-year phenotypic variation (“flexibility”), with weak sexual dimorphism. Second, we demonstrate that between-year individual variation in within-year phenotypes (“supraflexibility”) is structured and directional, consistent with the threshold trait model. Third, we demonstrate strong survival selection on within-year phenotypes—and hence on flexibility—that varies across years and sexes, including episodes of disruptive selection representing costs of flexibility. By quantitatively combining these results, we show how supraflexibility and survival selection on migratory flexibility jointly shape population-wide phenotypic dynamics of seasonal movement.

BACKGROUND There are limited qualitative data describing general pediatric hospitalizations through the caregivers’ lens, and most focus on one particular challenge or time during the hospitalization. This qualitative study aimed to address a gap in the description of the breadth and depth of personal challenges caregivers may face during the entire hospitalization, irrespective of severity of patient illness or diagnosis, and explored caregiver-suggested interventions. METHODS Caregivers of pediatric patients on the hospitalist service at a Pacific Northwest children’s hospital were interviewed to explore their hospitalization experience and solicit feedback for potential interventions. Content was coded iteratively using a framework analysis until thematic saturation was met. Findings were triangulated through 2 focus groups, 1 with parent advisors and the other with hospital physicians and nurses. RESULTS Among 14 caregivers (7 each of readmitted and newly admitted patients) and focus group participants, emergent domains on difficulties faced with their child’s hospitalization were anchored on physiologic (sleep, personal hygiene, and food), psychosocial (feelings of isolation, mental stress), and communication challenges (information flow between families and the medical teams). Caregivers recognized that addressing physiologic and psychosocial needs better enabled them to advocate for their child and suggested interventions to ameliorate hospital challenges. CONCLUSIONS Addressing physiologic and psychosocial needs may reduce barriers to caregivers optimally caring and advocating for their child. Downstream consequences of unaddressed caregiver challenges should be explored in relation to participation in hospital care and confidence in shared decision-making, both vital components for optimization of family-centered care.

This paper brings contemporary debate in analytic philosophy of religion regarding the notion of worship into conversation with Jewish sources and attempts to identify the most promising philosophical grounds for a Jewish account of the putative obligatoriness of worship. Some philosophers have recently debated the notion of worship, focusing in particular on the claim that human beings have an obligation to worship God and on whether and how such an obligation might be adequately grounded. I first canvass the major bases for worshipping God that have featured in this debate. I then turn to some relevant liturgical and philosophical sources of Jewish tradition, identifying grounds for the obligatoriness of (exclusively) worshipping God that have been advanced in those sources. I next consider which grounds of the putative obligatoriness of worship are the most promising for a Jewish account in terms of both philosophical cogency and rootedness in Jewish tradition. I argue that a version of a divine command grounding of prayer in a Soloveitchikian mode is both well-rooted in Judaism and also plausibly surmounts philosophical objections to divine command accounts. In the final section, I briefly raise the issue of whether the concept of worship is truly well-suited to a Jewish context, suggesting that the rich Hebrew notions of avodah and tefillah are perhaps more appropriate in articulating a fully adequate Jewish understanding of the pertinent issues. In particular, I argue that these notions fit well with the Soloveitchikian divine command grounding of the obligation to worship God.

To identify variability in reported hearing outcomes for intratympanic (IT) steroid treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) by comparing outcomes using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline with other published criteria.Retrospective chart review.Tertiary otology practice.Patients with ISSNHL treated with IT steroid between April 2003 and December 2020.IT steroid injection and audiometric evaluation.1) Rates of full, partial, or no recovery using the AAO-HNS guideline versus other reported criteria, and 2) correlation analyses of demographic and clinical variables with response to IT steroid.Using AAO-HNS reporting criteria, full recovery of the pure-tone average was noted in 25.68% of patients. Applying eight other published outcomes criteria to this patient cohort classified full recovery in 14.87 to 40.54% of patients. Similarly, AAO-HNS criteria classified "no recovery" in 51.35% of our patients, whereas applying the other reported criteria showed an average rate of 62.16% no recovery and as high as 82.43% of patients without recovery. Younger age ( p = 0.003; effect size, 0.924) and IT injection within a week of onset ( p0.001; effect size, 1.099) positively correlated with full recovery. There was no impact of prior or concurrent oral steroids, or number of steroid injections on outcome.Great variability exists in the literature for assessment of IT steroid outcomes in ISSNHL. Standard reporting of outcomes as per the AAO-HNS SSNHL guideline is recommended to consistently characterize IT steroid efficacy and allow comparison across studies.

To characterize the degree to which individual coping strategies may influence speech perception after cochlear implantation.Retrospective cohort study.Tertiary referral center.Adult, postlingually deaf cochlear implant recipients.The Coping Orientation to Problems Experience inventory, a validated, multidimensional self-reported coping scale, was administered preoperatively.Speech perception was measured using consonant-nucleus-consonant (CNC) phoneme and word scores, AzBio sentence accuracy in quiet and noise, and Hearing in Noise Test sentences in quiet preoperatively and at 1, 3, and 6 months postoperatively. Quality of life was measured with the Hearing Implant Sound Quality Index and the Nijmegen Cochlear Implant Questionnaire.Thirty-six patients were included in this study. Mean age at surgery was 70.7 ± 11.4 years. Acceptance was associated with a decreased AzBio in noise score in the 6 months after CI (regression coefficient b = -0.05; 95% confidence interval [CI], -0.07 to -0.03; p0.01). Denial was associated with a decreased AzBio in quiet score (b = -0.05; 95% CI, -0.09 to -0.01; p0.05), whereas humor was associated with an increased AzBio in quiet score (b = 0.02; 95% CI, 0.01 to 0.04; p0.05). Humor was also associated with an increased Hearing in Noise Test score (b = 0.05; 95% CI, 0.02 to 0.07; p0.05). Denial was associated with decreased CNC word (b = -0.04; 95% CI, -0.06 to -0.02; p0.01) and phoneme (b = -0.04; 95% CI, -0.07 to -0.02; p0.01) scores, whereas substance use was associated with increased CNC word (b = 0.03; 95% CI, 0.01 to 0.05, p0.01) and phoneme (b = 0.04; 95% CI, 0.02 to 0.06; p0.01) scores. Scores on self-reported quality of life measures were not significantly correlated with coping strategies.A variety of adaptive and maladaptive coping strategies are used by postlingually deaf adult cochlear implant users. Denial and acceptance may be more predictive of poor speech performance, whereas humor and substance use may be more predictive of improved speech performance.

Introduction: Local antimicrobial delivery via calcium sulfate (CaSO4) beads is used as an adjunctive treatment for periprosthetic joint infection. There is limited clinical information describing the performance of antimicrobial-loaded CaSO4 (ALCS) in large-scale applications. We developed a simulated large joint model to study properties of eluting ALCS. Methods: The in vitro testing platform was an adapted standardized model for tribological testing of prosthetic total hips and total knees (ASTM F732). The model was 70 mL total fluid volume, 25 % bovine serum, and 75 % phosphate-buffered saline, using ISO standard 14242-1 for human synovial fluid simulation. Four brands of CaSO4 were evaluated. Each 10 mL of CaSO4 was loaded with 1.2 grams (g) of tobramycin and 1 g of vancomycin powders. A 35 mL bead volume, equaling 175 beads, of each product was placed in incubated flasks. The test period was 6 weeks with scheduled interval fluid exchanges. Fluid samples were tested for antibiotic and calcium concentrations and pH. Results: Antibiotic elution showed an initial burst on Day 1, followed by a logarithmic reduction over 1 week. Tobramycin fully eluted within 2.5 weeks. Vancomycin showed sustained release over 6 weeks. Calcium ion concentrations were high, with gradual decrease after 3 weeks. All four CaSO4 products were inherently acidic. Fluid became more acidic with the addition of antibiotics primarily driven by vancomycin. Discussion: Clinicians should be cognizant of tobramycin elution burst with ALCS in large loads. The main driver of acidic pH levels was vancomycin. We propose that joint complications may result from lowered fluid acidity, and we suggest clinical study of synovial pH.

Existing cochlear implant (CI) outcomes research demonstrates a high degree of variability in device effectiveness among experienced CI users. Increasing evidence suggests that verbal learning and memory (VLM) may have an influence on speech recognition with CIs. This study examined the relations in CI users between visual measures of VLM and speech recognition in a series of models that also incorporated spectro-temporal discrimination. Predictions were that (1) speech recognition would be associated with VLM abilities and (2) VLM would contribute to speech recognition outcomes above and beyond spectro-temporal discrimination in multivariable models of speech recognition.This cross-sectional study included 30 adult postlingually deaf experienced CI users who completed a nonauditory visual version of the California Verbal Learning Test-Second Edition (v-CVLT-II) to assess VLM, and the Spectral-Temporally Modulated Ripple Test (SMRT), an auditory measure of spectro-temporal processing. Participants also completed a battery of word and sentence recognition tasks.CI users showed significant correlations between some v-CVLT-II measures (short-delay free- and cued-recall, retroactive interference, and "subjective" organizational recall strategies) and speech recognition measures. Performance on the SMRT was correlated with all speech recognition measures. Hierarchical multivariable linear regression analyses showed that SMRT performance accounted for a significant degree of speech recognition outcome variance. Moreover, for all speech recognition measures, VLM scores contributed independently in addition to SMRT.Measures of spectro-temporal discrimination and VLM were associated with speech recognition in CI users. After accounting for spectro-temporal discrimination, VLM contributed independently to performance on measures of speech recognition for words and sentences produced by single and multiple talkers.3 Laryngoscope, 2022.

Receptor downregulation is instrumental for many therapeutic interventions. Receptor knockout through gene-editing technologies is efficient but can introduce off-target mutations and chromothripsis. Regulation of gene expression at the protein level is a promising alternative. Here, we present results showing the targeted T cell antigen receptor (TCR) degradation using chimeric E3 fusion proteins that we call Receptor Targeting Chimeras (ReceptorTAC). We show that TCR degradation is dependent on enzymatically active, membrane-anchored E3 ligase variants. TCR specificity was achieved by direct fusion of an E3 domain to the CD3ζ transmembrane sequence. Jurkat and primary T cells stably expressing the ReceptorTAC constructs showed significantly reduced responses to TCR stimulation. We also used our ReceptorTAC technology to generate TCR-deficient, claudin18.2-specific CAR T cells, where the activity of the CAR was unaffected by the expression of the ReceptorTAC. These data indicate that our ReceptorTAC molecule can be used to generate allogeneic CAR T cells.

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to reproductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young., This meta-analysis was financed by the grant of the Polish National Science Centre (Narodowe Centrum Nauki) (no. 2017/27/B/NZ8/00465) awarded to Lucyna Hałupka.

Migration is a widespread strategy for escaping unfavourable conditions during winter, but the extent to which populations that segregate during the breeding season aggregate during the non-breeding season is poorly understood. Low non-breeding season aggregation may be associated with higher likelihood of overlap with threats, but with fewer populations affected, whereas high aggregation may result in a lower probability of exposure to threats, but higher overall severity. We investigated non-breeding distributions and extent of population aggregation in 2 sympatrically breeding auks. We deployed geolocation-immersion loggers on common guillemots Uria aalge and razorbills Alca torda at 11 colonies around the northern UK and tracked their movements across 2 non-breeding seasons (2017-18 and 2018-19). Using 290 guillemot and 135 razorbill tracks, we mapped population distributions of each species and compared population aggregation during key periods of the non-breeding season (post-breeding moult and mid-winter), observing clear interspecific differences. Razorbills were largely distributed in the North Sea, whereas guillemot distributions were spread throughout Scottish coastal waters and the North, Norwegian and Barents Seas. We found high levels of aggregation in razorbills and a strong tendency for colony-specific distributions in guillemots. Therefore, razorbills are predicted to have a lower likelihood of exposure to marine threats, but more severe potential impact due to the larger number of colonies affected. This interspecific difference may result in divergent population trajectories, despite the species sharing protection at their breeding sites. We highlight the importance of taking whole-year distributions into account in spatial planning to adequately protect migratory species.

OBJECTIVE Our aim was to understand the breadth of the hospital-to-home experience from the caregiver perspective using a mixed method approach. METHODS Caregivers of children who experienced an inpatient admission (N = 184) completed a hospital-to-home transition questionnaire after discharge. Twenty-six closed-ended survey items captured child’s hospitalization, discharge, and postdischarge experiences and were analyzed using descriptive statistics. Four additional free-response items allowed caregivers to expand on specific challenges or issues. A conventional content analysis coding framework was applied to the free responses. RESULTS Ninety-one percent of caregivers reported satisfaction with the hospital experience and 88% reported they understood how to manage their child’s health after discharge. A majority of survey respondents (74%) provided answers to 1 or more of the qualitative free-response items. In the predischarge period, qualitative responses centered on concerns related to finances or available resources and support, communication, hospital environment, and the discharge process. Responses for the postdischarge time period centered on family well-being (child health, other family member health), finances (bills, cost of missed work), and medical follow-up (supplies, appointments, instruction). CONCLUSIONS Caregivers were generally satisfied with their hospital experience; however, incorporating survey items specifically related to family stressors either through closed- or open-ended questions gave a richer context for caregiver-identified concerns. Basing future quality improvement efforts on supporting caregiver needs and identifying stressors before discharge may make for a more robust and successful transition to home.

We have created an experimental procedure for determining the temperature coefficient of resistivity, αR, for introductory physics laboratories. As in the procedure from Henry, this method examines the relationship between temperature and resistivity to establish αR within 10% of the accepted value.

1. Actuarial senescence, the decline of survival with age, is well documented in the wild. Rates of senescence vary widely between taxa, to some extent also between sexes, with the fastest life histories showing the highest rates of senescence. Few studies have investigated differences in senescence among populations of the same species, although such variation is expected from population-level differences in environmental conditions, leading to differences in vital rates and thus life histories. 2. We predict that, within species, populations differing in productivity (suggesting different paces of life) should experience different rates of senescence, but with little or no sexual difference in senescence within populations of monogamous, monomorphic species where the sexes share breeding duties. 3. We compared rates of actuarial senescence among three contrasting populations of the Atlantic puffin Fratercula arctica. The dataset comprised 31 years (1990–2020) of parallel capture–mark–recapture data from three breeding colonies, Isle of May (North Sea), Røst (Norwegian Sea) and Hornøya (Barents Sea), showing contrasting productivities (i.e. annual breeding success) and population trends. We used time elapsed since first capture as a proxy for bird age, and productivity and the winter North Atlantic Oscillation Index (wNAO) as proxies for the environmental conditions experienced by the populations within and outside the breeding season, respectively. 4. In accordance with our predictions, we found that senescence rates differed among the study populations, with no evidence for sexual differences. There was no evidence for an effect of wNAO, but the population with the lowest productivity, Røst, showed the lowest rate of senescence. As a consequence, the negative effect of senescence on the population growth rate (λ) was up to 3–5 times smaller on Røst (Δλ = −0.009) than on the two other colonies. 5. Our findings suggest that environmentally induced differences in senescence rates among populations of a species should be accounted for when predicting effects of climate variation and change on species persistence. There is thus a need for more detailed information on how both actuarial and reproductive senescence influence vital rates of populations of the same species, calling for large-scale comparative studies. actuarial senescence, capture–mark– recapture, environmental conditions, intraspecific variation, life-history trade-offs, long-term data, population viability, seabirds Raising offspring increases ageing: Differences in senescence among three populations of a long-lived seabird, the Atlantic puffin Å fostre avkom øker aldring: Forskjeller i aldersbetinget ovelevelse mellom tre populasjoner av en lenge-levende sjøfugl: lunde

Industrial forage fish fisheries may reduce prey availability affecting diet and breeding success of marine predators. However, evidence for fisheries effects on predator demography remains rare, hindering evaluation of their impact on populations. Using 25 years of data on the commercial lesser sandeel fishery in the north-western North Sea, we evaluated the effectiveness of the closure in safeguarding breeding success of four seabird species - black-legged kittiwake, common guillemot, Atlantic puffin and razorbill. We also tested for effects of a scientific fishery in the closed area on breeding success. We quantified how changes in the diet of chicks for the four seabird species were influenced by the abundance of sandeels and the alternative prey species, European sprat, and the potential prey behavioural disturbance effects of sandeel fishing on the prey. Finally, we examined how changes in chick diet and prey abundance have shaped long-term variation in seabird breeding success. The period of fishery operation was associated with a decline in kittiwake breeding success in colonies with foraging ranges overlapping the closed area, from 52 % of young fledged pre-fishery to 23 % during fishery operation. Breeding success increased by approximately 10 % in the period following fishery closure to 2018. We document wide uncertainty around this increase in breeding success, partly driven by variation in the responses of individual colonies. For guillemot, razorbill and puffin we found no evidence for negative effects of the fishery on breeding success, nor for positive effects arising from its closure. We found no evidence for an impact on breeding success of the scientific fishery. The proportion of sandeel in chick diet was positively associated with breeding success in the four species, albeit with only weak evidence for puffin. Fishing effort was associated with a decreased proportion of sandeel in puffin diet, a lower proportion of the sandeel component of the diet consisting of 0-group in kittiwake, razorbill and puffin, and with decreased kittiwake breeding success. Our findings provide quantitative evidence for how forage fish fisheries may impact seabird demography, highlighting the species-specific nature of responses, and the difficulties in teasing apart drivers amongst ongoing environmental change. Time-area fisheries closures show promise as a tool for positively affecting productivity in some seabird species. However, we identify important caveats around its effectiveness for strategic seabird conservation and aspirations of net gain.

Dissecting joint micro-evolutionary and plastic responses to environmental perturbations fundamentally requires quantifying interacting components of genetic and environmental variation underlying expression of key traits. This ambition is particularly challenging for phenotypically discrete traits where multiscale decompositions are required to handle non-linear transformations of underlying genetic and environmental variation into phenotypic variation, especially when effects have to be estimated from incomplete field observations. We devised a novel joint multistate capture-recapture and quantitative genetic animal model, and fitted this model to full-annual-cycle resighting data from partially migratory European shags (Gulosus aristotelis) to estimate key components of genetic, environmental and phenotypic variance in the ecologically critical discrete trait of seasonal migration versus residence. We demonstrate non-trivial additive genetic variance in latent liability for migration, resulting in estimated micro-evolutionary responses following two episodes of strong survival selection. Yet, underlying additive genetic effects interacted with substantial permanent individual and temporary environmental effects to generate complex non-additive effects, causing large intrinsic gene-by-environment interaction variance in phenotypic expression. Our findings reveal how temporal dynamics of seasonal migration result from combinations of instantaneous micro-evolution and within-individual phenotypic inertia, and highlight how plastic phenotypic variation could expose cryptic genetic variation underlying discrete traits to complex forms of selection.

A series of small-molecule YEATS4 binders have been discovered as part of an ongoing research effort to generate high-quality probe molecules for emerging and/or challenging epigenetic targets. Analogues such as

The impact of COVID-19 on university students is multi-faceted and varies depending on the student profile. A study was conducted at a regional university in the Midwest. A quick-reaction or pulse ...

OBJECTIVES. To compare intraoperative intracochlear electrocochleography (ECochG) with hearing preservation outcomes in cochlear implant (CI) subjects. DESIGN. Intraoperative electrocochleography was performed in adult CI subjects who were recipients of Advanced Bionics’ Bionics LLC precurved HiFocus(™) MidScala or straight HiFocus(™) SlimJ electrode arrays. ECochG responses were recorded from the most apical electrode contact during insertion. No changes to the insertions were made due to ECochG monitoring. No information about insertion resistance was collected. ECochG drops were estimated as the change in amplitude from peak (defined as maximum amplitude response) to drop (largest drop) point after the peak during insertion was measured following the peak response. .Audiometric thresholds from each subject were obtained before and approximately one month after CI surgery. The change in pure tone average (PTA) for frequencies between 125 Hz and 500 Hz was measured after surgery. No post-operative CT scans were collected as part of this study. RESULTS. A total of 68 subjects from 5 surgical centers participated in the study. The study sample included 30 MidScala and 38 SlimJ electrodes implanted by approximately 20 surgeons who contributed to the study. Although a wide range of results were observed, there was a moderate positive correlation (Pearson Correlation coefficient r = 0.56, p < 0.01) between the size of the ECochG drop and the magnitude of PTA change. This trend was present for both the MidScala and SlimJ arrays. The SlimJ and MidScala arrays produced significantly different hearing loss after surgery. CONCLUSION. Large ECochG amplitude drops observed during electrode insertion indicated poorer hearing preservation. Although the outcomes were variable, this information may be helpful to guide surgical decision-making when contemplating full electrode insertion and the likelihood of hearing preservation.

Identifying drivers of population trends in migratory species is difficult, as they can face many stressors while moving through different areas and environments during the annual cycle. To understand the potential of migrants to adjust to perturbations, it is critical to study the connection of different areas used by different populations during the annual cycle (i.e. migratory connectivity). Using a large-scale tracking data set of 662 individual seabirds from 2 sympatric auk meta-populations (common guillemots Uria aalge and Brünnich’s guillemots U. lomvia) breeding in 12 colonies throughout the Northeast Atlantic, we estimated migratory connectivity in seasonal space use as well as occupied environmental niches. We found strong migratory connectivity, within and between species. This was apparent through a combination of seasonal space use and occupied environmental niches. Brünnich’s guillemot populations grouped into 2 and common guillemot populations into 5 previously undescribed spatiotemporal clusters. Common guillemot populations clustered in accordance with the variable population trends exhibited by the species, while Brünnich’s guillemot populations are declining everywhere where known within the study area. Individuals from different breeding populations in both species were clustered in their space and environmental use, utilising only a fraction of the potential species-wide range. Further, space use varied among seasons, emphasising the variable constraints faced by both species during the different stages of their annual cycle. Our study highlights that considering spatiotemporal dynamics, not only in space but also in occupied environmental niches, improves our understanding of migratory connectivity and thus population vulnerability in the context of global change. Environmental niche · Inter-population mixing · Large-scale spatiotemporal dynamics · Light-level geolocation · Murres · Population spread · Seasonality © The authors 2021. Open Access under Creative Commons by Attribution Licence. Use, distribution and reproduction are un - restricted. Authors and original publication must be credited.

The aim of this study was to gain an understanding of how the Jordanian government has responded and continues to respond to the COVID-19 pandemic. It utilizes the interpretive policy analysis approach through document analysis. The analysis showed that Jordan created social protection policies to assist people who lost their jobs or whose work was suspended due to the coronavirus. The economic policies build solidarity and facilitate the private sector’s recovery. The health care measures firmly applied included lockdown, wearing masks, and restrictions on gatherings and public events. Jordan uses hard power and imposes sanctions on any violation that threatens the lives of others.