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Motivation 3D chromatin structure plays an important role in regulating gene expression and alterations to this structure can result in developmental abnormalities and disease. While genomic approaches like Hi-C and Micro-C can provide valuable insights in 3D chromatin architecture, the resulting datasets are extremely large and difficult to manipulate. Results Here, we present mariner , a rapid and memory efficient tool to extract, aggregate, and plot data from Hi-C matrices within the R/Bioconductor environment. Mariner simplifies the process of querying and extracting contacts from multiple Hi-C files using a parallel and block-processing approach. Modular functions allow complete workflow customization for advanced users, yet all-in-one functions are available for running the most common types of analyses. Finally, tight integration with existing Bioconductor infrastructure enables complete analysis and visualization of Hi-C data in R. Availability and implementation Available on GitHub at https://github.com/EricSDavis/mariner and on Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/mariner.html. [ABSTRACT FROM AUTHOR]

Error is a neglected epistemological category in the history of science. This neglect has been driven by the commonsense idea that its elimination is a general good, which often renders it invisible or at least not worth noticing. At the end of the sixteenth century across Europe, medicine increasingly focused on "popular errors," a genre where learned doctors addressed potential patients to disperse false belief about treatments. By the mid-seventeenth century, investigations into popular error informed the working methodology of natural philosophers, rather than just physicians. In 1646, Thomas Browne published Pseudodoxia Epidemica, a large volume on popular error. Despite Browne's formal training as a physician, this work examined only a few medical errors and instead aspired to be an encyclopedia of error. Pseudodoxia Epidemica was highly popular, running to six editions, and was known by the Fellows of the Royal Society. Influenced by Browne, alongside Bacon's theory of the idols, natural philosophic practice in the late sixteenth and seventeenth century developed a focus on error that revised traditional attention to the discovery of knowledge. Fellows such as Robert Boyle and Robert Hooke proposed new ways to secure truth under the far-reaching influence of Bacon's refutations of "natural human reason" distorted by false idols, of syllogistic logic, and of "theories," his label for traditional philosophical systems that bias thought toward falsity. In three parts, this article traces the progression in early modern scientific approaches to handling error, and especially medical error – from physicians' efforts to identify and eradicate it through collaborative effort, to the striking tension in Browne's work between seeking to eliminate error while also showing a marked tolerance for it, to the Royal Society's Baconian objective of instrumentalizing error to find truth. Error emerges as its own epistemic category that serves as a driving force toward knowledge production. [ABSTRACT FROM AUTHOR]

Transferring biomolecules from solution to vacuum facilitates a detailed analysis of molecular structure and dynamics by isolating molecules of interest from a complex environment. However, inherent in the ion desolvation process is the loss of solvent hydrogen bonding partners, which are critical for the stability of a condensed-phase structure. Thus, transfer of ions to vacuum can favor structural rearrangement, especially near solvent-accessible charge sites, which tend to adopt intramolecular hydrogen bonding motifs in the absence of solvent. Complexation of monoalkylammonium moieties (e.g., lysine side chains) with crown ethers such as 18-crown-6 can disfavor structural rearrangement of protonated sites, but no equivalent ligand has been investigated for deprotonated groups. Herein we describe diserinol isophthalamide (DIP), a novel reagent for the gas-phase complexation of anionic moieties within biomolecules. Complexation is observed to the C-terminus or side chains of the small model peptides GD, GE, GG, DF-OMe, VYV, YGGFL, and EYMPME in electrospray ionization mass spectrometry (ESI–MS) studies. In addition, complexation is observed with the phosphate and carboxylate moieities of phosphoserine and phosphotyrosine. DIP performs favorably in comparison to an existing anion recognition reagent, 1,1′-(1,2-phenylene)-bis-(3-phenylurea), that exhibits moderate carboxylate binding in organic solvent. This improved performance in ESI–MS experiments is attributed to reduced steric constraints to complexation with carboxylate groups of larger molecules. Overall, diserinol isophthalamide is an effective complexation reagent that can be applied in future work to study retention of solution-phase structure, investigate intrinsic molecular properties, and examine solvation effects. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to explore individuals with intellectual disabilities (ID) experiences of the therapeutic relationship. Design/methodology/approach: Six individuals with ID were recruited who were currently having 1:1 therapy. Semi-structured interviews focused on their experiences of the therapeutic relationship. Findings: Using interpretative phenomenological analysis, six personal experiential themes were identified. These were labelled as a person-centred experience, the importance of adaptions, "I feel like I know you", a secure base is offered, change does occur and an overlap of subjective experience. The results indicate that participants' accounts of their experiences indicated that the relationship was important to them. This research also demonstrated that the benefits and value of involving individuals with ID in qualitative research. Originality/value: To the best of the authors' knowledge, exploring the therapeutic relationship from the perspective of individuals with ID has not been previously explored in the literature. This research highlights considerations for therapists working with this population to help them facilitate positive therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Vasoconstriction is a known effect associated with ergot alkaloid consumption. The vascular contractile responses are often sustained for an extended period after exposure. Ergot alkaloids exist in two molecular configurations, the C-8-(R)-isomer (R -epimer) and the C-8-(S)-isomer (S -epimer). The sustained vascular contractile response to the R -epimers has been studied previously, unlike the S -epimers which are thought to be biologically inactive. Additionally, antagonists have been utilized to attenuate the vascular contraction associated with the R- epimers of ergot alkaloids utilizing ex vivo techniques. This study utilized an arterial tissue bath to examine and compare the sustained vascular contractile response attributed to ergocristine (R) and ergocristinine (S) using dissected bovine metatarsal arteries. The contractile blocking effect of a noncompetitive alpha-adrenergic antagonist, phenoxybenzamine (POB), was also investigated in precontracted arteries. Arteries (n = 6/epimer) were exposed to a single dose of ergocristine or ergocristinine (1 × 10−6 M in buffer). Each of the epimer doses was followed by a POB (1 × 10−3 M) or methanol (control) treatment at 90 min and the response was observed for another 90 min. Both epimers produced a sustained contractile response over the 180-min incubation period in the control groups. The R -epimer caused a greater sustained contractile response from 60 to 180 min post epimer exposure, compared to the S -epimer (P < 0.05, generalized estimating equations, independent t-test). Phenoxybenzamine caused a decrease in the contractile response induced by ergocristine and ergocristinine from 105 to 180 min, compared to the control (P < 0.05, generalized estimating equations, paired t-test). Overall, these results demonstrate the presence of a sustained vascular contractile response attributed to the R- and S -epimer of an ergot alkaloid with differences in contractile response between the epimers, suggesting differences in receptor binding mechanisms. Furthermore, this study demonstrated that a noncompetitive antagonist could attenuate the sustained arterial contractile effects of both ergot configurations ex vivo. Additional investigation into S -epimers of ergot alkaloids is needed. This research contributes to the understanding of the ergot epimer-vascular receptor binding mechanisms, which may support the investigation of different approaches of minimizing ergot toxicity in livestock. [ABSTRACT FROM AUTHOR]

The provision of opportunities to express rewarding behaviours is a promising concept to support a better quality of life for intensively farmed pigs. Play behaviour has been associated with excitement and fun, suggesting that playing animals experience pleasurable states. Pigs play intensively between 2 and 6 weeks of age and this decreases with age thereafter. To determine if the provision of play opportunities could enhance the quality of life of pigs, this study investigated if play can be promoted and sustained in pigs beyond the natural period of expression in a commercial setting. Whether play is positive for pigs and the effect of play on average daily gain and stress physiology was also explored. Growing pigs (n = 288, 10 weeks of age), housed in standard partly-slatted pens, were assigned to either a Control treatment with no play interventions (CON, 1 m2/pig); or to a Novelty (NOV) or Play pen (PLP) treatments, with play promotion between 10 and 21 weeks delivered through play sessions 3x/week. Play treatments received the intermittent provision of destructible novel objects provided either in the home pen (NOV, 1 m2/pig), or in an enclosed 'play pen' area providing extra space (PLP, 2.9 m2/pig). To understand if play is positive, the frequency and duration of anticipatory behaviour were recorded before play sessions, whilst play behaviour, along with indicators of emotional valence such as vocalization, tail, and ear postures, were recorded during play sessions on focal pigs (n = 144) at 11, 16 and 21 weeks. To explore the physiological response to play, saliva was collected pre and post play, and analysed for cortisol and alpha-amylase, and growth rate was calculated from trial entry and exit weights. Pigs in PLP and NOV played more frequently (p = 0.002) and for a longer duration of time (p < 0.001) across weeks compared to CON. NOV and PLP did not differ in play frequency and duration, except for week 21 when PLP played more frequently. Play treatments expressed more anticipatory behaviour and behavioural indicators associated with a positive experience (ears relaxed and forward, tail wagging, barks) compared to CON. Cortisol was elevated only in NOV compared to CON after the play session, but alpha-amylase and growth rate did not differ. Play was successfully promoted and sustained until the finishing period and equally expressed regardless of extra space. Pigs with play opportunities expressed indicators that play is a rewarding and motivating behaviour and could enhance the quality of life of farmed pigs when supported. • Play was promoted with extra space and novel enrichment in grow-finish pigs. • Play was expressed equally regardless of extra space when novel enrichment was given. • Expression of play until finishing period shows that play is highly motivating. • Observed behavioural indicators suggest that play is positive for pigs. • Play promotion is a proof of concept to enhance welfare of farmed pigs. [ABSTRACT FROM AUTHOR]

As a poet discussing a poet, Copus is well-placed to contemplate Mew's creative process, including how she crafted and revised her extraordinary poetry. As a new phase of Mew scholarship begins, Mew's poetry should take centre stage, with new and varied interpretations, showcasing it in in all its strangeness and, yes, its queerness. But Copus skirts over Mew's broader poetic development, apparently accepting Mew's own claims that she seldom read and was not influenced by other poets. [Extracted from the article]

Abrupt events are a feature of many palaeoclimate records during the Holocene. The best example is the 8.2 ka event, which was triggered by a release of meltwater into the Labrador Sea and resulted in a weakening of poleward heat transport in the North Atlantic. We use an objective method to identify rapid climate events in globally distributed speleothem oxygen isotope records during the Holocene. We show that the 8.2 ka event can be identified in >70% of the speleothem records and is the most coherent signal of abrupt climate change during the last 12,000 years. The isotopic changes during the event are regionally homogenous: positive oxygen isotope anomalies are observed across Asia and negative anomalies are seen across Europe, the Mediterranean, South America and southern Africa. The magnitude of the isotopic excursions in Europe and Asia are statistically indistinguishable. There is no significant difference in the duration and timing of the 8.2 ka event between regions, or between the speleothem records and Greenland ice core records. Our study supports a rapid and global climate response to the 8.2 ka freshwater pulse into the North Atlantic, likely transmitted globally via atmospheric teleconnections. [ABSTRACT FROM AUTHOR]

The vertebrate glucocorticoid stress response is an important mechanism facilitating pleiotropic phenotypic adjustments for coping with environmental change and optimizing fitness. Although circulating glucocorticoid hormones are mediators of plasticity that individuals can adjust rapidly in response to environmental challenges, they are also shaped by ecological selection. It remains unclear, however, how environmental variation on different timescales influences glucocorticoids. Here, we use an intraspecific comparative approach to determine how variation in precipitation on different timescales (months, years, decades) shapes distinct components of the glucocorticoid response. We sampled superb starlings (Lamprotornis superbus) at eight sites across Kenya in multiple years that differed in precipitation. Among-population variation in baseline glucocorticoids was shaped by both short- and long-term precipitation, whereas variation in stress-induced levels was poorly explained by precipitation on any timescale. Adrenal sensitivity, quantified via adrenocorticotropic hormone injections, was shaped by long-term precipitation and was highest in unpredictable environments. Together, these results suggest that variation in glucocorticoids can be best explained by environmental variation at timescales that extend beyond the lives of individuals, although baseline glucocorticoids also reflect short-term environmental conditions. Patterns of long-term precipitation may represent a microevolutionary selective pressure shaping the endocrine stress axis across populations and influencing how individuals cope with environmental change. [ABSTRACT FROM AUTHOR]

The role of family environments, where conflict--ranging from disagreements between young people and their parent(s) or carers to home-based circumstances where violence and/or abuse is present--is well documented in research that has examined the causes and correlates of youth homelessness. However, far less attention has focused on how young people themselves frame and understand the significance of family ruptures. This paper examines the family 'turning point' experiences embedded in the life stories of homeless youth. The study, which was biographical and longitudinal, aimed to generate an in-depth understanding of the nature of homelessness, how it emerged and its impacts on the lives of young people. Conducted in Ireland, 40 youth aged 16-24 years were recruited at baseline, with all interviews commencing with an invitation to young people to tell their 'life story'. Analysis of participants' life story narratives revealed three major family turning point experiences associated with parental absence and separation, bereavement and acute interruptions to family life. These turning points, the effects of which had a temporal character, reveal the rippling impact of family ruptures on the lives of young people who embarked on a path of leaving home and becoming homeless. The implications of the findings for enhancing engagement with the families of young people who experience homelessness are discussed. [ABSTRACT FROM AUTHOR]

The article reports that scholars of both fin-de-siecle and modernist literature is familiar with the portrait of the 1890 generation found in Ezra Pound semiautobiographical poem Hugh Selwyn Mauberley. Topics include considered among the narratives recounted by ‘Monsieur Verog' in the poem the story of poet and critic Lionel Johnson falls off a barstool to his death is the most well-known and often repeated.

Objective: To evaluate clinicopathological prognostic indicators associated with survival based on hematology and serum biochemistry profile findings at presentation of dogs with canine parvoviral enteritis (CPE). Secondary objectives were to describe the signalment, history, physical examination findings, and progression of disease while in hospital and correlate them to survival. Design: Retrospective study from medical records of dogs diagnosed with CPE between 2001 and 2018. Setting: University teaching hospital. Animals: Three hundred twenty‐two dogs diagnosed with CPE that received in‐hospital treatment. Interventions: None. Measurements and main results: Of 322 hospitalized dogs, 294 dogs (91%) survived infection with a median hospitalization time of 79 hours. Multivariable analysis showed that glucose (P = 0.04), total magnesium (P = 0.011), and the dichotomized variable of a low HCT (P = 0.033) on presentation were significantly associated with survival. For every 1 mmol/L (18 mg/dL) decrease in glucose concentration, cases had 1.85 lower odds of survival. For every 0.1 mmol/L (0.2 mEq/L) increase in total magnesium concentration, cases had 2.50 lower odds of survival. Cases with a low HCT had 10.69 lower odds of survival. On univariable analyses, non‐survivors had a lower median body weight (P = 0.006) and presented more commonly for diarrhea (P = 0.015). At least 1 episode of diarrhea (P = 0.003) and hematochezia or melena (P < 0.001) in hospital were negatively associated with outcome, in addition to the persistence of diarrhea (P = 0.026) and hyporexia (P = 0.018) in hospital for 5 to 6 days. Conclusions: Survival rates of 91% were achieved with in‐hospital treatment in this cohort of dogs. Negative biochemical prognostic indicators affecting survival include a low HCT, decreased blood glucose concentrations, and increased total serum magnesium concentrations at presentation. [ABSTRACT FROM AUTHOR]

Background: Effective governance arrangements are central to the successful functioning of health systems. While the significance of governance as a concept is acknowledged within health systems research, its interplay with health system reform initiatives remains underexplored in the literature. This study focuses on the development of new regional health structures in Ireland in the period 2018–2023, one part of a broader health system reform programme aimed at greater universalism, in order to scrutinise how aspects of governance impact on the reform process, from policy design through to implementation. Methods: This qualitative, multi-method study draws on document analysis of official documents relevant to the reform process, as well as twelve semi-structured interviews with key informants from across the health sector. Interviews were analysed according to thematic analysis methodology. Conceiving governance as comprising five domains (Transparency, Accountability, Participation, Integrity, Capacity) the research uses the TAPIC framework for health governance as a conceptual starting point and as initial, deductive analytic categories for data analysis. Results: The analysis reveals important lessons for policymakers across the five TAPIC domains of governance. These include deficiencies in accountability arrangements, poor transparency within the system and vis-à-vis external stakeholders and the public, and periods during which a lack of clarity in terms of roles and responsibilities for various process and key decisions related to the reform were identified. Inadequate resourcing of implementation capacity, competing policy visions and changing decision-making arrangements, among others, were found to have originated in and continuously reproduced a lack of trust between key institutional actors. The findings highlight how these challenges can be addressed through strengthening governance arrangements and processes. Importantly, the research reveals the interwoven nature of the five TAPIC dimensions of governance and the need to engage with the complexity and relationality of health system reform processes. Conclusions: Large scale health system reform is a complex process and its governance presents distinct challenges and opportunities for stakeholders. To understand and be able to address these, and to move beyond formulaic prescriptions, critical analysis of the historical context surrounding the policy reform and the institutional relationships at its core are needed. [ABSTRACT FROM AUTHOR]

This article describes a tradition of early medieval cosmological thought in the prose and poetry of the Old English corpus. This Old English cosmology uses a small set of cosmological building blocks and a relatively limited vocabulary to describe and explore a variety of structural models of the Universe. In these texts – which include but are not limited to the Old English Prose Boethius , Ælfric's De temporibus Anni , the Old English Phoenix , and The Order of the World – each structural model relies on a combination of terms for heaven, the firmament, and a cosmic-scale ocean and seafloor. These models, each distinct, appear to fall into two loose categories which may represent two schools of thought in vernacular cosmology. [ABSTRACT FROM AUTHOR]

Background: Team familiarity has been shown to be important for operative efficiency and number of complications, but it is unclear for which types of operations and for which team members familiarity matters the most. The objective of this study is to further our understanding of familiarity in the OR by quantifying the relative importance of familiarity among all possible core team dyads, and defining the impact of team level familiarity on outcomes. Materials and methods: Using a retrospective chart and administrative data review, five years of data from two health systems (14 hospitals) and across two procedures, (knee arthroplasty and lumbar laminectomy) were included. Multilevel modeling approach and a dominance analysis were conducted. Results: For each previous surgery that any two members of the core surgical team had participated in together, the length of surgery decreased significantly. The familiarity of the scrub and the surgeon was the most significant relationship for knee arthroplasty across the two hospitals, and laminectomies at one hospital. Conclusions: The relationship between familiarity of the surgical team and surgical efficiency may be more complex than previously articulated. Familiarity may be more important for certain types of procedures. The familiarity of certain dyads may be more important for certain types of procedures. [ABSTRACT FROM AUTHOR]

Ergot alkaloids are produced by the fungus Claviceps purpurea and their levels are carefully monitored in animal and human diets due to their harmful effects and widespread contamination of cereal crops. Ergot alkaloids exist in two forms known as the (R)- and (S)-epimers with only the former being monitored in diets in North America. The (S)-epimers of ergot alkaloids are thought to be biologically inactive and, therefore, harmless. A major mechanism by which the (R)-epimers of ergot alkaloids produce their toxic effect is through vasoconstriction. Therefore, the objective of this study was to examine the vasoactivity potential (contractile response) of four (S)-epimers, namely ergocryptinine, ergocristinine, ergocorninine, and ergotaminine utilizing an in vitro arterial tissue bath system. Bovine metatarsal arteries (n = 6, ergocryptinine and ergocorninine; n = 6, ergocristinine and ergotaminine; n = 6 arteries/(S)-epimer, total n = 12) were collected from healthy mixed-breed beef steers immediately after slaughter, cut into 3-mm arterial cross sections, and suspended in a tissue bath with continuously oxygenated Krebs–Henseleit buffer. To assess the contractile response of each (S)-epimer, a cumulative contractile dose–response curve was constructed by incubating arteries with increasing concentrations (1 × 10−11 to 1 × 10−6 M) of that (S)-epimer. Contractile responses were recorded as grams of tension and were normalized to an initial contraction of phenylephrine. Contrary to the widespread belief, all tested (S)-epimers were found vasoactive and produced a concentration-dependent arterial contractile response similar to what has been reported for the (R)-epimers. The arterial contractile response to ergotaminine was strongest and was significantly greater than that of ergocryptinine and ergocristinine at the highest concentration used (P ≤ 0.01). Our results indicate that the (S)-epimers are biologically active and are likely harmful similar to the (R)-epimers. The levels of (S)-epimers should be carefully monitored in human and animal diets worldwide. [ABSTRACT FROM AUTHOR]

The hypothalamic–pituitary–adrenal (HPA) axis regulates the secretion of glucocorticoids, hormones with diverse roles ranging from regulating daily metabolic demand to coping with sudden perturbations. As a result, glucocorticoids are thought to help vertebrates track their changing environments and coordinate plasticity in diverse phenotypes. While this endocrine system is highly plastic—where one individual can produce multiple phenotypes across varying environmental conditions—little is understood about the degree to which individuals, populations, or species differ in circulating glucocorticoid plasticity. Empirical research quantifying individual variation in glucocorticoid plasticity has increased in recent years, though the multiple complex roles of the HPA-axis make it challenging to generalize the extent to which individual variation in plasticity exists. I provide an overview of current findings on variation in glucocorticoids plasticity, and outline multiple types of glucocorticoid plasticity researchers should consider in future work to advance our understanding of the causes and consequences of individual variation in glucocorticoid plasticity. [ABSTRACT FROM AUTHOR]

Group living is predicted to arise only when the fitness benefits outweigh the costs of sociality. Group-living species—including cooperatively breeding and family-living birds and mammals—occur most frequently in environments where climatic conditions fluctuate unpredictably from year to year. The fitness consequences of group living are thus expected to vary with changing environmental conditions, though few studies have examined this possibility. We examined whether living in large social groups improves adult survivorship in cooperatively breeding superb starlings (Lamprotornis superbus). We also tested the hypothesis that larger groups buffer against harsh conditions by increasing survivorship most under periods of low rainfall. We found that group size was positively correlated with adult survival but in a sex-specific manner: female survival increased with group size across all environmental conditions, whereas male survival increased with group size only in wet years. Together with previous work in this system, our results suggest that larger groups confer survival benefits by reducing predation, rather than by improving access to food or buffering against physiological stress. Although group living does not appear to buffer against harsh conditions in adult starlings living in a fluctuating environment, living in larger groups does confer a survival advantage. [ABSTRACT FROM AUTHOR]

While access to housing has been identified as a crucial enabler to young people exiting homelessness, relatively little is known about the experiences of youth who encounter barriers in their attempts to secure housing. Mobilizing a pathways approach, this paper examines homeless young people's experiences of seeking housing in a context of housing market forces that blocked their efforts to carve a route out of homelessness. The research, which is biographical and longitudinal, was conducted in Ireland between 2013 and 2016 and involved the collection of data at two points in time. At baseline, 40 young people aged 16–24 years and 10 of their family members were recruited (Phase 1) and, at the point of follow-up two years later (Phase 2), 74% of participants were retained in the study. By Phase 2, just 24% of the study's young people were housed, pointing to significant barriers of access to housing. Moving beyond the identification of the impact of housing market forces on young people's ability to exit homelessness, the analysis examines young people's responses, focussing on the strategies used by them as they attempted to reclaim autonomy and control over their housing futures. Implications for the development of sustainable housing solutions that specifically cater to the needs of homeless youth are discussed. [ABSTRACT FROM AUTHOR]

This paper responds to the claim that behavioural science is underpinned by an unreflective positivisim that inevitably leads to poor and/or abusive practice. In fact, the philosophy of modern behavioural science is contextualistic and today its ideas are at the forefront of a range of compassionate, person centred therapies. [ABSTRACT FROM AUTHOR]

The cow-calf industry in North America is in a period of rapid consolidation with corresponding increases in herd sizes and changes in management. The objectives of this study were to examine longitudinal data on reproductive performance in cow-calf herds and identify benchmarks for the most critical measures and important sources of differences among herds. To address these questions, a surveillance network was established in western Canada to collect data between 2013 to 2017 privately owned cow-calf herds during calving (n = 105 herds) and at pregnancy testing (n = 94 herds). Data were summarized for a number of indices of herd performance. However, the values considered to be most reliable and accurate were the percentage of females not pregnant when tested by a veterinarian, the percentage of calves dead within 24 hours of birth, and the percentage of calves dead from 24 hours to weaning. The mean and variation between herds for heifers, measured using standard deviation, was greater than for cows for: non-pregnancy (cows 6.8% (mean)±3.4%(SD), heifers 9.7%±8.2%), calf death from birth to 24 hours (cows 2.1%±1.6%, heifers 3.6%±4.5%), and calf death from 24 hours to weaning (cows 2.5%±2.4%, heifers 2.9%±3.9%). Benchmarks or performance targets derived from the 25th percentiles of these data for both cows and heifers were <5% for non-pregnancy risk and <1% for calf loss within 24 hours of birth. The suggested benchmark for calf loss from 24 hours to weaning was <2% for cows and <1% for heifers. All outcomes consistently displayed greater variation between herds as compared to year to year differences within herds with the exception of calf loss before 24 hours in cows. The timing of the start of breeding season was a consistent source of variation in risks of non-pregnancy and calf losses. Cows bred in April or earlier to start calving in late December or January were at increased risk of low pregnancy percentages (p<0.001) and calf losses at birth (p<0.04), as well as increased calf loss before weaning in both cows and heifers (p<0.02). There was also an increase in the risk of non-pregnancy for cows and heifers (p<0.001) where first exposure to breeding was not until July or August. In contrast, the risks of calf loss within 24 hrs of birth (p<0.001) and from 24 hrs to weaning in cows (p<0.02) first exposed to breeding in July and August were significantly lower than for herds that had earlier breeding seasons. [ABSTRACT FROM AUTHOR]

• Flow flashiness and drying affect macroinvertebrates in southern California streams. • Hydrologic models were calibrated to minimize errors in these two flow metrics. • These models predicted biotic indices better than best overall fit models. • Ecological model calibration has great potential for environmental flow analyses. River flows exert dominant controls on in-stream biota. Quantifying linkages between hydrology and biology is important for assessing the effects of flow alteration on ecological functions. Hydrologic models are often used to quantify these flow-ecology relationships and guide management actions. Traditional model calibration techniques typically focus on a best overall fit criterion that may not be suitable for environmental flow applications where certain elements of the flow regime exert a dominant influence on biotic composition. We present an approach for hydrologic model calibration that improves the accuracy of calculated flow metrics known to be significant drivers of ecosystem response. First, we developed regional flow-ecology relationships based on streamflow gage and benthic macroinvertebrate data from southern California to determine which streamflow metrics best explain variability in taxonomic and trait-based biotic indices. Next, we developed and calibrated a series of hydrologic models to minimize error in these important flow metrics. For our study sites, flow flashiness and low flow frequency (indicative of drying) were found to best explain biotic condition. Hydrologic models calibrated specifically to minimize errors in these flow metrics predicted macroinvertebrate indices better than models calibrated to maximize fit to the overall flow regime. This ecological-calibration approach requires some a priori knowledge of flow-ecology relationships, but it produces results that can improve assessment of the impacts of changing flow regimes on biota and guide the development of strategies to mitigate ecological degradation. [ABSTRACT FROM AUTHOR]

Inappropriate management of acute stress can negatively affect cognition and task performance. Frequently occurring acute stress encounters can lead to cardiovascular and immunity deficiencies, and psychological disorders such as depression, fatigue, and burnout. Biofeedback can be used as a non-invasive, passive, continuous method of managing stress in real time. A systematic review of biofeedback as a real-time stress management intervention for non-patients was conducted to identify literature between 2000 and 2017, yielding 17 studies evaluating physiological, psychological, and/or performance metrics. Participants represent convenience samples (N = 9 studies) and deliberately selected samples, whose optimal performance under stress is critical for occupational success (N = 8 studies). Various methods to collect data, display biofeedback, induce stress, and measure performance were reported. Overall, biofeedback is an effective intervention that can be used to reduce physiological and subjective stress, and enhance performance. This is especially true among professionals, whose job performance requires appropriate stress management. [ABSTRACT FROM AUTHOR]

Analyses of the relevance of family for young people are more visible than previously within youth research. Nonetheless, understanding of the nature and meaning of family relationships for those who experience separation from their family, including homeless youth, is relatively weak. Based on selected findings from a qualitative longitudinal study, this article explores the meaning-making processes of homeless young people with explicit attention to the ways in which "family" is produced and (re)negotiated in their lives over time. Four themes are presented—family as reliable and supportive; family as interrupted and "broken"; family as fragile and elusive; and family as fluid and ambiguous—revealing the unfolding nature of young people's constructions of family and family relationships. The enduring impact of separation, dislocation, and conflict on how young people "make sense" of familial experiences is discussed, and we conclude with the practice implications arising from the findings. [ABSTRACT FROM AUTHOR]

The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors of the transforming growth factor-β (TGF-β) pathway. Using a mouse model of Loeys-Dietz syndrome (LDS) that carries a heterozygous kinase-inactivating mutation in TGF-β receptor I, we found that the effects of this mutation depend on the lineage of origin of vascular smooth muscle cells (VSMCs). Secondary heart field-derived (SHF-derived), but not neighboring cardiac neural crest-derived (CNC-derived), VSMCs showed impaired Smad2/3 activation in response to TGF-β, increased expression of angiotensin II (AngII) type 1 receptor (Agtr1a), enhanced responsiveness to AngII, and higher expression of TGF-β ligands. The preserved TGF-β signaling potential in CNC-derived VSMCs associated, in vivo, with increased Smad2/3 phosphorylation. CNC-, but not SHF-specific, deletion of Smad2 preserved aortic wall architecture and reduced aortic dilation in this mouse model of LDS. Taken together, these data suggest that aortic root aneurysm predisposition in this LDS mouse model depends both on defective Smad signaling in SHF-derived VSMCs and excessive Smad signaling in CNC-derived VSMCs. This work highlights the importance of considering the regional microenvironment and specifically lineage-dependent variation in the vulnerability to mutations in the development and testing of pathogenic models for aortic aneurysm. [ABSTRACT FROM AUTHOR]

The objective of the present study was to 1) analyze the ascending aortic proteome within a mouse model of Marfan syndrome (MFS; Fbn1C1041G/+) at early and late stages of aneurysm and 2) subsequently test a novel hypothesis formulated on the basis of this unbiased proteomic screen that links changes in integrin composition to transforming growth factor (TGF)- β-dependent activation of the rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling pathway. Ingenuity Pathway Analysis of over 1,000 proteins quantified from the in vivo MFS mouse aorta by data-independent acquisition mass spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice. We validated this pattern of Rictor activation in vivo by Western blot analysis for phosphorylation on Thr1135 in a separate cohort of mice and showed in vitro that TGF-β activates Rictor in an integrin-linked kinase-dependent manner in cultured aortic vascular smooth muscle cells. Expression of β3-integrin was upregulated in the aged MFS aorta relative to young MFS mice and wild-type mice. We showed that β3-integrin expression and activation modulated TGF-β-induced Rictor phosphorylation in vitro, and this signaling effect was associated with an altered vascular smooth muscle cell proliferative-migratory and metabolic in vitro phenotype that parallels the in vivo aneurysm phenotype in MFS. These results reveal that Rictor is a novel, context-dependent, noncanonical TGF-β signaling effector with potential pathogenic implications in aortic aneurysm. [ABSTRACT FROM AUTHOR]

The cost of reproduction results in a life-history trade-off where investment in current reproduction via costly parental care decreases subsequent fitness. Although this trade-off is thought to occur ubiquitously across animals, there is equivocal evidence that parental care behaviours are costly. A major challenge of studying the cost of parental care has been a lack of consensus over which physiological mechanisms underlie this trade-off. Here, we compare four traits believed to mediate the cost of parental care by examining whether glucocorticoids, oxidative stress, immune function or body condition represent a cost of performing offspring care and shape subsequent fitness. We use a 4 year dataset collected in free-living cooperatively breeding superb starlings (Lamprotornis superbus), a species in which parental and alloparental care effort varies widely among individuals and across years. Our results showed that within-individual change in physiology was unrelated to investment in offspring care, and physiological state during chick rearing did not predict the likelihood that an individual would breed in subsequent seasons. Instead, individuals that had elevated baseline corticosterone during incubation performed more nest guarding, suggesting that this hormone may play a preparatory role for investing in offspring care. Together, our results indicate that superb starlings modify their investment in offspring care according to their physiological state during incubation, despite there being no evidence of a short-term physiological cost of parental or alloparental care. Thus, breeding cooperatively appears to provide individuals with the flexibility to adjust their investment in offspring care and overcome any potential costs of reproduction. [ABSTRACT FROM AUTHOR]

Circulating glucocorticoid hormone concentrations are dynamic, flexible, and promote adaptive responses following perturbations in an animal's environment. As a result, circulating glucocorticoid levels are thought to shape fitness and have been suggested to be a key trait for predicting how species will cope with novel environmental change. Nevertheless, the factors that shape variation in glucocorticoid-mediated coping mechanisms remain unclear because the evolutionary underpinnings of the function and regulation of these hormones are poorly understood. Here, I summarize recent advances in our understanding of the evolution of circulating glucocorticoids, which have included (i) longitudinal studies exploring microevolutionary processes that shape within- and between-individual variation in glucocorticoids, (ii) interspecific comparative studies highlighting macro-evolutionary patterns of among-species variation in glucocorticoids, and (iii) intraspecific comparative studies which help to disentangle the relative roles of environment, life-history, and behavior in shaping among-population variation in glucocorticoids. Important avenues for future research will include exploring how natural selection may act on different components of the hypothalamus–pituitary–adrenal axis, characterizing patterns of phenotypic plasticity in circulating glucocorticoids across populations and species, as well as exploring how microevolutionary processes differ across taxa or gradients of environmental conditions. [ABSTRACT FROM AUTHOR]

This article traces the history of the Constance Naden memorial bust, commissioned in 1890 and now held in the Cadbury Research Library at the University of Birmingham. We describe the commissioning, funding and creation process, and analyse its purpose in terms of memorialization, its negotiation of gender, and how it portrays Naden as a poet, philosopher and scientist. The enduring legacies of, and reactions to the bust, are considered in the context of Birmingham's Mason Science College, where Naden studied between 1881 and 1887. We argue that Naden's bust is symptomatic of the University of Birmingham establishing its identity and that the subsequent changes in its location within the institution signify the shifting role of Naden within that legacy. Our reading of this sculptural artefact leads to several broader observations regarding poetic identity, gender, genius and female education, the establishment of universities and consolidation of civic identities via sculpture, and the memorialization of the poet. While a surface reading of the bust obscures the multifaceted nature of Naden's intellectual career, by attending to it more closely, turning the object on its plinth and locating it in its physical contexts over time, a far richer and more accurate view of the object, the person and her place in history becomes apparent. [ABSTRACT FROM AUTHOR]

The cost of parental care has long been thought to favor the evolution of cooperative breeding, because breeders can provide reduced parental care when aided by alloparents. Oxidative stress—the imbalance between reactive oxygen species and neutralizing antioxidants—has been proposed to mediate the cost of parental care, though results from empirical studies remain equivocal. We measured changes in oxidative status during reproduction in cooperatively breeding superb starlings (Lamprotornis superbus) to gain insight into the relationships among breeding status, parental care, and oxidative stress. We also compared the oxidative cost of reproduction in the cooperatively breeding superb starling to that in a sympatric non-cooperatively breeding species, the greater blue-eared glossy starling (L. chalybaeus), to determine whether cooperatively breeding individuals face reduced oxidative costs of parental care relative to non-cooperatively breeding individuals. Breeders and alloparents of the cooperative species did not differ in oxidative status throughout a breeding attempt. However, individuals of the non-cooperative species incurred an increase in reactive oxygen metabolites proportionally to an individual’s workload during offspring care. These findings suggest that non-cooperative starlings experience an oxidative cost of parental care, whereas cooperatively breeding starlings do not. It is possible that high nest predation risk and multi-brooding in the cooperatively breeding species may have favored reduced physiological costs of parental care more strongly compared to pair-breeding starlings. Reduced physiological costs of caring for young may thus represent a direct benefit that promotes cooperative breeding. [ABSTRACT FROM AUTHOR]

MARSSI (Momentary Affect Regulation – Safer Sex Intervention) is a counseling-plus-mobile health (mhealth) intervention to reduce sexual and reproductive health (SRH) risks for women with depression and high-risk sexual behavior. Due to the COVID-19 pandemic limiting in-person care, we sought to develop the counseling and mhealth app onboarding for virtual implementation. A team with SRH, adolescent medicine, motivational interviewing, cognitive behavioral therapy, and technology expertise adapted the counseling through an iterative consensus process. We identified essential aspects of the counseling, specified the content so the counseling could be delivered in person or virtually with fidelity, and considered best practices for telehealth for the focus population. Virtual counseling retained key elements from in-person counseling while including enhancements with engaging visual and audio–video aids. Instructions and programming were developed to support virtual counseling delivery and onboarding for the mhealth app component of MARSSI. After testing the virtual format in mock sessions, we implemented a small-scale feasibility study in an adolescent medicine clinic with women with depressive symptoms and high-risk sexual behavior age 18–24 years (N = 9). Participants experienced minimal technical difficulties and expressed satisfaction with the virtual format, and all were able to complete app onboarding successfully. Expanding delivery options for SRH interventions to include virtual can improve access, particularly for populations with psychological and environmental barriers to care. [ABSTRACT FROM AUTHOR]

The steroid hormone testosterone not only plays an important role in gamete production, but also influences social and aggressive behavior. Testosterone varies seasonally, peaking when competition for mates is high and declining during parental care. Surprisingly, little is known about how testosterone mediates social conflict and parental care behavior in highly social species like cooperative breeders, where group members compete for breeding opportunities and provide parental or alloparental care. We examined how testosterone differs across breeding roles in the tropical cooperatively breeding superb starling, Lamprotornis superbus . We determined whether testosterone was elevated in larger groups, and whether testosterone was negatively related to total levels of parental and alloparental care. We found that male breeders had higher testosterone than male helpers and female breeders and helpers during incubation. However, breeding males exhibited a significant decline in testosterone from incubation to chick rearing, and all individuals had similar levels during the chick rearing stage. Additionally, helpers—but not breeders—in large social groups had higher testosterone than those in small groups. Finally, testosterone was not correlated with nestling provisioning rates during chick rearing, suggesting that natural variation in the low levels of testosterone observed during periods of high parental care does not affect nestling provisioning. Together, these results offer insight into how testosterone is related to breeding roles, intra-group conflict, and parental care in a highly social species. [ABSTRACT FROM AUTHOR]

Background. Though antimicrobial stewardship programs (ASPs) are in place for patient safety, financial justification is often required. In 2016, the Infectious Diseases Society of America (IDSA) recommended that anti-infective costs be measured by patientlevel administration data normalized for patient census. Few publications use this methodology. Here, we aim to compare 3 methods of drug cost analysis during 3 phases of an ASP as an example of this recommendation's implementation. Methods. At a freestanding pediatric hospital, we retrospectively assessed anti-infective cost using pharmacy purchasing data, patient-level administration data from the electronic medical record (EMR), and patient-level administration data from the Pediatric Hospital Information Systems (PHIS) database, all normalized to patient census. Costs pre-ASP, while planning the ASP, and post- ASP were then compared for each method. Results. Significant differences in costs between the methods were observed. Pharmacy purchasing endorsed minimal financial benefit (decrease planning to post-ASP of $590 dollars per 1000 patient-days), while the EMR and PHIS data endorsed a decrease of $12 785 and $21 380 per 1000 patient-days, respectively, for a total yearly cost savings of $54 656 for pharmacy purchasing data, $1 184 336 for EMR data, and $2 117 522 for PHIS data. Conclusions. Pharmacy purchasing data underestimated cost savings compared with EMR and PHIS data, while EMR and PHIS data were comparable in magnitude of savings. At Children’s Hospital Colorado, savings justified the full cost of the ASP. EMR patient-level administration data, normalized to patient census, offers a readily available and standardized measure of anti-infective costs over time. [ABSTRACT FROM AUTHOR]

Ergot sclerotia produce toxic secondary metabolites, ergot alkaloids, that infect cereal crops and grasses. Ergot alkaloids have two isomeric configurations: the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Ergot contaminated matrices, such as cereal grains or grasses, may be stored for extended periods at various temperatures before being analyzed, utilized, or consumed. This study assessed the concentration of six common ergot alkaloids in both configurations found in naturally contaminated wheat over time (one, two, and four months) at different temperatures (room temperature, +4 °C, and −20 °C) using ultra-high-performance liquid chromatography–tandem mass spectrometry. The data indicate that the total ergot concentration within a natural contaminated sample varies over time at room temperature, +4 °C, and −20 °C. The total ergot concentration increased until month two, and decreased at month four, independent of temperature (p < 0.05). The total R-epimer concentration appeared to be less stable over time than the total S-epimer concentration. The changes in the total R and total S-epimer concentrations may have been caused by changes in the ergocristine and ergocristinine concentrations, respectively. Time and temperature should be considered when storing potentially contaminated matrices in a laboratory or practical agriculture situations. Quantification of ergot contaminated matrices should occur prior to their use to ensure the most reliable estimates of the concentration of ergot. [ABSTRACT FROM AUTHOR]

Louise Erdrich is an especially important contemporary American author because she draws together two key elements that have characterized American literature for more than a generation: a concern with issues of identity and the stylistic innovations of postmodern literature. As a nodal point for these two different traditions, Erdrich is ideally situated to illustrate the continuing relevance of French feminist theory to the collective American literary project. Because of her stylistic and conceptual innovation, Erdrich's early work provoked controversy. While authors such as Leslie Mormon Silko attacked her writing as superficially "post-modernist," we argue that it is more accurately identified with the work of French feminists like Helene Cixous and Luce Irigaray, who effected a shift from essentializing identity politics toward experimental construction of subjectivity through linguistic innovation. Erdrich's deconstruction of her female protagonists, and of gender identity more broadly, provides an effective avenue for continuing to explore the relevance o/l'ecriture feminine in contemporary American literature. [ABSTRACT FROM AUTHOR]

Administrative data are often used as a proxy for medication-administration record (MAR) data. Multicenter MAR data were compared retrospectively with administrative data from January 2010 through June 2013 from the Pediatric Health Information Systems database. We found that administrative data were more concordant with bill-upon-administration than bill-upon-dispense data. [ABSTRACT FROM AUTHOR]

• Urban and rural animals are different in their behaviors and hormones (termed coping styles), but it is unknown when such differences arise in an animal's life. • We examine the development of coping styles in European starling nestlings (Sturnus vulgaris). • Nestling stress responses develop more rapidly in urban than rural birds after they pass their peak of growth, such that urban fledglings have elevated glucocorticoid stress responses compared to rural birds. • Behavior and hormones were only weakly correlated in rural birds, and uncorrelated in urban birds supporting the two-tiered model of coping styles. Urbanization is increasing globally and altering the stressors that animals face in their everyday lives. Organisms often differ in their coping styles—both behavioral and endocrine—across urban to rural habitats. For example, urban animals are often bolder, more exploratory, and mount stronger glucocorticoid stress responses compared to their rural counterparts. While these coping styles are important in shaping fitness across the urban-to-rural gradient, it remains unclear when these differences arise in the life of organisms. We explore the development of coping styles in European starling nestlings (Sturnus vulgaris), an urban-adapted species. We test whether breathing rate, handling struggle rate, and bag struggle rate differ across sites and find no difference in the behavioral coping styles of nestlings raised in urban versus rural sites. We also explore differences in baseline and stress-induced glucocorticoids, finding that urban nestlings develop a stronger stress response than rural birds before fledging the nest. We find no significant correlations between behavioral and endocrine traits for urban or rural birds, which supports the two-tiered model of coping styles. One possibility is that behavioral and endocrine differences develop at different times over the lives of organisms. Our findings support prior work suggesting that behavioral and endocrine coping mechanisms act independently of one another, and suggests that endocrine coping mechanisms develop in early life and before differences in behavioral coping styles might arise. Future work on the mechanisms leading to early-life differences in coping styles—from genetics to maternal effects to environmental effects—is needed to best predict how urban-adapted organisms cope with environmental change. Studies across a greater number of sites will help disentangle site from urbanization effects. [ABSTRACT FROM AUTHOR]

The article discusses various papers published in this issue including one by Rocco Di Dio on unpublished working notebook of Marsilio Ficino, one by Andie Silva and Jonathan Olson on the nuance between authors and non-authorial figures, and one by Cordelia Zukerman on the dramatist William Shakespeare.