"Modeling Diffusive Search by Non-Adaptive Sperm: Empirical and Computational Insights".

During fertilization, mammalian sperm undergo a winnowing selection process that reduces the candidate pool of potential fertilizers from ~106-1011 cells to 101-102 cells (depending on the species). Classical sperm competition theory addresses the positive or 'stabilizing' selection that acts on sperm phenotypes within populations of organisms but does not strictly address the developmental consequences of sperm traits among individual organisms that are under purifying selection during fertilization. It is the latter that is of utmost concern for improving assisted reproductive technologies (ART) because 'low fitness' sperm may be inadvertently used for fertilization during interventions that rely heavily on artificial sperm selection, such as intracytoplasmic sperm injection (ICSI). Importantly, some form of sperm selection is used in nearly all forms of ART (e.g., differential centrifugation, swim-up, or hyaluronan binding assays, etc.). To date, there is no unifying quantitative framework (i.e., theory of sperm selection) that synthesizes causal mechanisms of selection with observed natural variation in individual sperm traits. In this report, we reframe the physiological function of sperm as a collective diffusive search process and develop multi-scale computational models to explore the causal dynamics that constrain sperm 'fitness' during fertilization. Several experimentally useful concepts are developed, including a probabilistic measure of sperm 'fitness' as well as an information theoretic measure of the magnitude of sperm selection, each of which are assessed under systematic increases in microenvironmental selective pressure acting on sperm motility patterns.

Impact of Primary Container Closure System on PS80 Oxidation and the Mechanistic Understanding.

PURPOSE: Polysorbate oxidation can potentially lead to protein degradation and loss of potency, which has been a challenge for the pharmaceutical industry for decades. Many factors have been reported to impact polysorbate oxidation rate, including types of elemental impurities, peroxide content, pH, light exposure, grades of polysorbate, etc. Even though there are many publications in this field, the impact of primary container closure system on PS80 oxidation has not been systematically studied or reported. The purpose of the current study is to close this gap. METHODS: Placebo PS80 formulations were prepared and filled into different container-closure systems (CCS), including different types of glass vials and polymer vials. Oleic acid content was monitored on stability as a surrogate value for PS80 content, which will decline upon oxidation. ICP-MS analysis and metal spiking studies were carried out to correlate the PS80 oxidation rate with metals leached from primary containers. RESULTS: PS80 degrades via oxidation at the fastest rate in glass vials with high coefficient of expansion (COE), followed by glass vials with low coefficient of expansion, while polymer vials minimized the oxidation of PS80 in most formulation conditions explored in this paper. ICP-MS analysis demonstrated that 1) 51 COE glass has more metal leachables than 33 COE glass in this study; and 2) More metal leachables correlates with faster PS80 oxidation. Metal spiking studies confirmed the hypothesis that aluminum and iron have a synergistic catalysis effect on PS80 oxidation. CONCLUSIONS: Primary containers of drug products play a significant role in the rate of PS80 oxidation. This study revealed a new major contributor to PS80 oxidation and potential mitigation strategy for biological drug products.

Thalamo-cortical and cerebello-cortical functional connectivity in development.

The thalamus is a critical relay center for neural pathways involving sensory, motor, and cognitive functions, including cortico-striato-thalamo-cortical and cortico-ponto-cerebello-thalamo-cortical loops. Despite the importance of these circuits, their development has been understudied. One way to investigate these pathways in human development in vivo is with functional connectivity MRI, yet few studies have examined thalamo-cortical and cerebello-cortical functional connectivity in development. Here, we used resting-state functional connectivity to measure functional connectivity in the thalamus and cerebellum with previously defined cortical functional networks in 2 separate data sets of children (7-12 years old) and adults (19-40 years old). In both data sets, we found stronger functional connectivity between the ventral thalamus and the somatomotor face cortical functional network in children compared with adults, extending previous cortico-striatal functional connectivity findings. In addition, there was more cortical network integration (i.e. strongest functional connectivity with multiple networks) in the thalamus in children than in adults. We found no developmental differences in cerebello-cortical functional connectivity. Together, these results suggest different maturation patterns in cortico-striato-thalamo-cortical and cortico-ponto-cerebellar-thalamo-cortical pathways.

Buprenorphine Prescribing and Dosing Limits: Evidence and Policy Goals.

The opioid misuse epidemic is a serious public health crisis. Opioid-involved deaths continue to rise and the potency of illicitly manufactured synthetic opioids has increased, creating challenges for the healthcare system to provide multifaceted specialized care. Elements of the regulation around buprenorphine, 1 of 3 drugs approved to treat opioid use disorder (OUD), constrain treatment options for patients and providers alike. Updates to this regulatory framework, particularly around dosing and access to care, would enable providers to better treat the changing landscape of opioid misuse. Specific actions to this end are to: (1) Increase buprenorphine dosing flexibility based on FDA labeling which drives payor policies; (2) Restrict local government and institutional impositions of arbitrary access and dosing limits for buprenorphine; and (3) Liberalize buprenorphine initiation and maintenance via telemedicine for OUD.

Assessing the Sampleability of Bennu's Surface for the OSIRIS-REx Asteroid Sample Return Mission.

NASA's first asteroid sample return mission, OSIRIS-REx, collected a sample from the surface of near-Earth asteroid Bennu in October 2020 and will deliver it to Earth in September 2023. Selecting a sample collection site on Bennu's surface was challenging due to the surprising lack of large ponded deposits of regolith particles exclusively fine enough ( ≤ 2 cm diameter) to be ingested by the spacecraft's Touch-and-Go Sample Acquisition Mechanism (TAGSAM). Here we describe the Sampleability Map of Bennu, which was constructed to aid in the selection of candidate sampling sites and to estimate the probability of collecting sufficient sample. "Sampleability" is a numeric score that expresses the compatibility of a given area's surface properties with the sampling mechanism. The algorithm that determines sampleability is a best fit functional form to an extensive suite of laboratory testing outcomes tracking the TAGSAM performance as a function of four observable properties of the target asteroid. The algorithm and testing were designed to measure and subsequently predict TAGSAM collection amounts as a function of the minimum particle size, maximum particle size, particle size frequency distribution, and the tilt of the TAGSAM head off the surface. The sampleability algorithm operated at two general scales, consistent with the resolution and coverage of data collected during the mission. The first scale was global and evaluated nearly the full surface. Due to Bennu's unexpected boulder coverage and lack of ponded regolith deposits, the global sampleability efforts relied heavily on additional strategies to find and characterize regions of interest based on quantifying and avoiding areas heavily covered by material too large to be collected. The second scale was site-specific and used higher-resolution data to predict collected mass at a given contact location. The rigorous sampleability assessments gave the mission confidence to select the best possible sample collection site and directly enabled successful collection of hundreds of grams of material.

A Quality Improvement Initiative to Reduce Screen Time in a Children's Hospital.

OBJECTIVES: The American Academy of Pediatrics strongly recommends that children age 2 and under should have little to no digital media exposure. However, most children are exposed to regular screen time at home. This may also be true for hospitalized children. Through education and access to alternatives, we aimed to reduce screen exposure in our children's hospital for children 2 and under. METHODS: Between January 2020 and May 2021, we designed and implemented a quality improvement intervention to educate staff and caregivers on the American Academy of Pediatrics screen time recommendations and offer alternatives for hospitalized children. Our primary aim was to decrease screen time exposure for children age 2 and under by 50% within 12 months of project initiation. Balancing measures included staff perception of workload when using screens and perceived parental acceptance of screens being turned off. RESULTS: During baseline data collection period, screens were on for an average of 63% of the audits. Following interventions, the average was reduced to 40%. The outcome measure met special cause with 8 consecutive points below the center line. There was a significant increase in staff who reported offering screen alternatives after intervention. Staff perception of workload and perceived parental acceptance was unchanged. CONCLUSIONS: Through implementation of this quality improvement initiative, we reduced screen time by approximately 37% without impacting staff workload. Most importantly, we were able to educate staff and model best practices for caregivers, which may carry into the home, leading to a reduction of screen time and improved health overall.

The Impact of COVID-19 on Patient, Family Member, and Stakeholder Research Engagement: Insights from the PREPARE NOW Study.

BACKGROUND: Little is known about the impact of COVID-19 on patient, family member, and stakeholder patient-centered outcomes research engagement. OBJECTIVE: To answer the research questions: (1) What is the impact of COVID-19 on the lives of patients with kidney disease and their families? (2) What is the impact of COVID-19 on research engagement for patient and family member research team members who are themselves at very high risk for poor COVID-19 outcomes? and (3) How can we help patients, family members, and stakeholder team members engage in research during COVID-19? DESIGN: We conducted virtual semi-structured interviews with patient and family member co-investigators and kidney disease stakeholders from the PREPARE NOW study during November 2020. The interview guide included questions about participants' experiences with the impact of COVID-19 on research engagement. PARTICIPANTS: Seven patient and family member co-investigators and eight kidney disease stakeholders involved in a kidney disease patient-centered outcomes research project participated in the interviews, data analysis, and writing this manuscript. APPROACH: We used a content analysis approach and identified the main themes using an inductive process. KEY RESULTS: Respondents reported three main ways that COVID-19 has impacted their lives: emotional impact, changing behaviors, and changes in health care delivery. The majority of respondents reported no negative impact of COVID-19 on their ability to engage in this research project. Suggestions for patient-centered outcomes research during COVID-19 and other emergencies include virtual research activities; active engagement; and promoting trust, honesty, transparency, and authenticity. CONCLUSIONS: COVID-19 has had a significant negative impact on patient, family member, and stakeholder research team members; however, this has not resulted in less research engagement. TRIAL REGISTRATION: Clinicaltrials.gov NCT02722382.

Urine Trouble: Reducing Midstream Clean Catch Urine Contamination Among Children 3-17 Years Old.

BACKGROUND: Children, caregivers, and clinicians often prefer midstream clean catch technique to urethral catheterization for obtaining urine cultures. However, contamination is common, potentially resulting in unnecessary medical intervention and cost. With this resident-led initiative, we aimed to reduce pediatric midstream clean catch urine culture contamination over 6 months. METHODS: A bundled intervention was implemented in the emergency department, inpatient units, and outpatient clinics at our institution. Baseline contamination rates were collected April 2016 to September 2017; the intervention was introduced October 2017 to March 2018 and evaluated April 2018 to September 2018. Sustainability was measured October 2018 to September 2020. Balancing measures included rates of repeat urine cultures, positive cultures, and contaminated cultures by urethral catheterization. RESULTS: Rates of midstream clean catch urine culture contamination were 45.3% preintervention and 30.9% postintervention, a 14.7% (95% confidence interval: 8.0% to 21.5%) absolute decrease. Before and after intervention, girls and patients 16 to 17 years old had the highest rates of midstream clean catch contamination. Six months postintervention, the rate of repeat urine culture decreased from 4.9% to 0.9% with no change in positive culture results or contaminated cultures by urethral catheterization. Over the subsequent 2 years, the impact of the intervention decreased (rate of contamination over 30 months postintervention: 38.4%, a 7.3% [95% confidence interval: 2.9% to 11.6%] absolute decrease; rate of repeat urine culture: 3.2%). CONCLUSIONS: An intervention to improve midstream clean catch urine culture collection was associated with a clinically meaningful decrease in contamination. Impact of the resident-led intervention decreased over time.

Pediatric Complexity Tool Best Practice Alert: Early Identification of Care Coordination for Children with Special Health Care Needs.

Care coordination programs continue to be developed for children with special health care needs (CSHCN). The goals for these programs are to improve access, increase communication, and decrease the overall length of stay for CSHCN. Care coordination optimizes resources to support children's health and well-being early in their hospitalization and facilitates a smooth discharge process and transition to home. Providing care coordination for CSHCN requires collaboration from many disciplines. To achieve high-quality care coordination, early identification of medically complex pediatric patients on admission is optimal. For more efficient and timelier enrollment into our care coordination program, we created a best practice alert within our electronic medical record to help overcome the challenges in timely identification of CSHCN. The best practice alert has helped us to provide care coordination benefits to our patients earlier in their hospital course. The purpose of this paper is to describe a quality improvement initiative to improve the early identification of CSHCN on hospital admission through the development of a best practice alert.

Kamishibai Cards: A Conversation About Patient Safety.

BACKGROUND: Kamishibai (K) cards are a quality improvement process focused on improved bundle compliance and promotion of peer-to-peer feedback that the health system has used for a few years. PROBLEM: Changing personnel structure and an emphasis on patient outcomes prompted a need to revamp the K Card process. APPROACH: A team approach was used to redesign the process resulting in a program that moved from utilization of champions to engaging all bedside nurses and having a standard completion requirement for all units. In 2 phases spanning 16 weeks, the nurse managers, point-of-care educators, and all bedside nurses were trained in the process using a computer-based training module and validated in the application of the process. OUTCOMES: By the end of the 16-week period, the completion compliance target was reached, and the system began to see a decrease in central line and Foley catheter device usage days. CONCLUSION: The result of the project design was a peer-to-peer feedback mechanism, which promotes evidence-based practices and system standards.

Association of Marijuana, Mental Health, and Tobacco in Colorado.

OBJECTIVES: Marijuana's evolving legality may change marijuana use patterns in adults. Co-use of marijuana and tobacco are strongly associated, and populations with mental health disorders are disproportionately likely to use either substance, but neither association has been assessed in the context of legal recreational marijuana. We assessed the associations of tobacco smoking with marijuana use and with mental health disorders in Colorado in 2015. METHODS: Data came from a population-based survey of adults (n = 8023). Multiple logistic regressions were used with current tobacco smoking as the primary outcome. Past 30-day marijuana use and mental health status were the independent variables of interest. Covariates included age, sex, ethnicity, poverty level, and education. RESULTS: Adults who used marijuana in the past 30 days had 3.4 (95% confidence interval [CI] 2.7, 4.2) greater odds of currently smoking tobacco compared to adults who had not recently used marijuana, after adjusting for sociodemographic and economic factors. A mental health disorder was independently associated with tobacco smoking (adjusted odds ratio [OR] 1.7, 95% CI 1.4, 2.1). Prevalence of co-use among adults self-reporting a mental health disorder was significantly higher compared those without a mental health disorder (11.1% vs 4.3%; P < 0.0001). CONCLUSIONS: This study examined the associations between mental health, marijuana use, and tobacco smoking after the legalization of recreational marijuana in Colorado. Adults using marijuana and/or self-reporting a mental health disorder were more likely to smoke tobacco and should be targeted for cessation interventions.

Athleisure: A qualitative investigation of a multi-billion-dollar clothing trend.

Clothes play a ubiquitous, yet under-appreciated social role. In the context of body image, clothes may both reflect and facilitate wearers' ideals and anxieties about their physical appearance. Athleisure, referring to athletic-inspired workout apparel that explicitly accentuates wearers' physiques, is a hitherto unexamined clothing trend worth tens of billions of dollars annually (and growing) in the United States consumer market alone. We conducted the first qualitative examination of athleisure by interviewing 20 women who regularly wore athleisure. Four master themes emerged from the data: (1) the athleisure lifestyle, (2) the conditional nature of athleisure, (3) athleisure embodiment, and (4) athleisure-linked cognitive dissonance. Our results suggest that wearing athleisure communicates to others an adherence to the lifestyles depicted in fitspiration - a class of social media imagery that glorifies thin-fit bodies. Participants articulated that athleisure encouraged them to feel more confident and athletic; athleisure also emphasized the women's physiques, and whether they aligned with the thin-fit ideal. Thus, the act of wearing athleisure motivated participants to engage in fitspiration-based activities. Given the (a) massive public demand for athleisure, and (b) industry projections for continued growth in athleisure spending, our findings compel additional research on the connections between clothing and body image.

Parents' Experience During a Child's Resuscitation: Getting Through It.

PURPOSE: The purpose of this study was to elucidate the experiences of parents during their child's resuscitation in the hospital setting. DESIGN AND METHODS: This qualitative descriptive study took place in a 280 bed children's hospital with parents whose children experienced resuscitation while they were present in the room or nearby. Semi-structured interviews were conducted between one and twelve months following a child's resuscitation. A rigorous thematic analysis was performed. RESULTS: This study elucidates parent experience during a child's resuscitation using four overarching themes; "Overwhelming chaos", "Getting through it", "Cognitive presence" and "Joy mixed with heartache". Parents described their experience to be stressful, yet identified things that helped them get through it and make sense of the experience. CONCLUSIONS: During a child's resuscitation parents perceived a sense of overwhelming chaos, yet still had an innate need to be present and know what was going on. While emotional support was appreciated, most important was to receive real time clinical information from healthcare staff and to see and feel that the team was personally invested in their child. PRACTICE IMPLICATIONS: During a child's resuscitation, parents should be allowed to choose their level of presence to meet their individual needs. A clinical staff member should answer questions and share clinical information with parents. In addition, clinicians should allow themselves to connect with parents on a personal level. This research provides a foundation for further study, including parents' experience after experiencing a child's resuscitation.

The cost of diagnostic uncertainty: a prospective economic analysis of febrile children attending an NHS emergency department.

BACKGROUND: Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health outcomes. METHODS: We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children (aged < 16 years), attending Alder Hey Children's Hospital, an NHS-affiliated paediatric care provider in the North West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations, radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note identification to determine rates of potentially avoidable AB prescribing. RESULTS: Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28 [95% CI £82.39-£2993.37] per child, (p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0-5.1-fold] higher resource use than consultants (p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1% were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95% CI 6.5-13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate 'red flag', treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% of bootstrap simulations. CONCLUSION: The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED resources is highest among infants (aged less than 3 months) and those infants managed by lesser experienced doctors, independent of clinical severity. Diagnostic advances which could increase confidence to withhold antibiotics may yield considerable efficiency gains in these groups, where the perceived risks of failing to identify potentially life-threatening bacterial infections are greatest.

Pediatric melanoma: Characterizing 256 cases from the Colorado Central Cancer Registry.

BACKGROUND: Melanoma is a rare diagnosis in the pediatric population. Differences in incidence, presentation, and survival distinguish pediatric melanoma from adult melanoma. In order to improve our understanding of pediatric melanoma, our case series investigates differences in incidence, age of onset, and anatomic site between male and female pediatric melanoma patients in Colorado between 1988 and 2015. METHODS: All data were gathered from the Colorado Central Cancer Registry. A request for de-identified data on pediatric melanoma patients between 1988 and 2015 was made by the University of Colorado Department of Dermatology. Chi-square tests were used to compare the differences reported in melanoma between sex, age-groups, and site of lesion. RESULTS: A total of 256 cases of melanoma were reported in Colorado in patients < 20 years of age between 1988 and 2015. Overall incidence of pediatric melanoma in Colorado increased from 1988 to 1999 but declined from 2001 to 2011. There was a significant predominance of female cases in the 10-14 age-group (P = 0.0477) and 15-19 age-group (P = 0.0472). Both groups had increased incidence of melanoma with increasing age. The mean age of onset for both sexes was 16 years old. Boys were more likely to have melanoma of the scalp and neck (P = 0.0523) and less likely to have melanoma of the leg (P = 0.0049). CONCLUSION: Among the pediatric population, girls 10-14 and 15-19 years old are at a significantly increased risk of melanoma compared to boys in these age-groups. Our study found sex-specific differences in anatomic site consistent with prior literature. Further investigations should aim to identify causes for these sex-specific differences in order to better guide public health initiatives.

Parents' Experience When Present During a Child's Resuscitation: An Integrative Review.

Understanding perceptions of parents is necessary to meet parents' needs during a child's resuscitation. Parent presence at pediatric resuscitations has been slow to become consistent practice in all hospital settings and remains controversial. The purpose of this integrative review was to synthesize research on parents' experience while present during a child's resuscitation to improve understanding for health care providers and to facilitate application in practice. Nine studies met inclusion criteria, identifying four major themes. Parents experienced conflicting emotions, articulated a need for communication and support, reported that being physically present was comforting, and described their reactions to the experience. The available research on parents' experience during presence at their child's resuscitation offers a foundation for further detailed study. Further study is needed about parents' perspective of support needed while present during a child's resuscitation, as well as about any long-term effects of presence on parent stress and coping.

Rhetoric of representation: the disempowerment and empowerment of consumer leaders.

Policy mandates consumer involvement in decisions at all levels of the mental health system. One barrier to this involvement is the expectation that consumers involved in systemic work represent broader consumer experiences. To examine how the rhetoric of 'representation' was used in relation to consumer involvement in mental health, a qualitative exploratory design was employed using interviews for data collection. Participants were consumers (n = 6) working with public or private mental health organizations in Australia, and colleagues (n = 3) or managers (n = 5) of these consumers. Discursive psychological principles informed the analytic process, to explore contexts in which 'representativeness' was used to empower and disempower consumers. The findings suggest there is a lack of clarity about what is meant by representation in the mental health sector. Expecting individual consumer leaders to be representative of consumer views more broadly disempowered them in their roles. Some participants instead discussed ways that organizations should be responsible for seeking representation from more consumer leaders, thus empowering consumers working in the sector. Using the term 'representative' to refer to consumers working in mental health does not reflect the value of the consumer perspective and is not well understood within the sector. Comprehensive training should be provided so that mental health service providers are clear regarding the expectations of people in these roles.

'It depends what you mean by leadership': An analysis of stakeholder perspectives on consumer leadership.

Contemporary mental health policies call for increased involvement of consumers in leadership across mental health service design, delivery, and evaluation. However, consumer leadership is not currently well understood within academia or in mental health services themselves. This study investigates how consumer leadership is currently conceptualized by stakeholders at the service delivery level. To this end, semistructured interviews were conducted with 14 mental health organization members identifying as consumer leaders, colleagues supporting consumer leaders, or organization executives. Interview data were analysed using an inductive thematic analysis to develop a broad understanding of participants' perceptions of consumer leadership. Findings indicate constructions of consumer leadership within mental health organizations can be understood in relation to four themes: consumer leadership roles, requirements, purpose, and process. Inconsistencies across participants' perceptions of consumer leadership were identified as constituting barriers to its development, highlighting the need to better clarify the nature of consumer leadership.