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Frailty is associated with negative health outcomes, disability, and mortality. Physical activity is an effective intervention to improve functional health status. However, the effect of resistance training on multidimensional health in frail older adults remains unclear. This randomized controlled trial was conducted in a U.K. residential care home to assess feasibility with limited efficacy testing on health and functional outcomes and to inform a future definitive randomized controlled trial. Eleven frail older adults (>65 years) completed a 6-week machine-based resistance training protocol three times a week. Uptake and retention were greater than 80%. The measures and intervention were found to be acceptable and practicable. The analyses indicated large improvements in functional capacity, frailty, and strength in the intervention group compared with the controls. These findings support the feasibility of a definitive randomized controlled trial and reinforce the value of resistance training in this population. This trial was registered with ClinicalTrials.gov: NCT03141879.

This study used secondary data from the My Teaching Partner-Math/Science 2013-2016 randomized control trial to explore whether equitable sociocultural classroom interactions (see Curenton et al., 2019) were associated with the skills of 105 four- and five-year-olds (52% boys; drawn from 20 unique video recordings of preschool teachers/classrooms; 43% were Black, Latine, Asian, or other racially marginalized learners). Equitable interactions predicted children's skills with effect sizes ranging from small (0.01-0.44) to large (1.00). Moderation analyses revealed that when classrooms had more racially marginalized learners, teachers' use of equitable disciplinary and personalized learning practices were associated with higher executive functioning gains across prekindergarten. Findings illustrate how classroom composition can be a key indicator between equitable classroom interactions and young children's early skills.

Over the past two years, physician-scientist trainees have persevered in the face of evolving challenges presented by the ongoing coronavirus disease 2019 (COVID-19) pandemic. Research and healthcare institutions across the country continue to feel the impacts of the public health emergency. As scientists and physicians generate evidence to inform the prevention and treatment of COVID-19, physician-scientist trainees in all disciplines have adapted to the changing conditions of their education.

The efficient encapsulation of small molecule active ingredients has been a challenge for many decades across many commercial applications. Recently, successful attempts to address this issue have included deposition of thin metal shells onto liquid filled polymer microcapsules or emulsion droplets to provide an impermeable barrier to diffusion. In this work we have developed a novel method to protect small molecule active ingredients by deposition of thin mineral shells. Platinum nanoparticles are used to catalyse and direct growth of a calcium phosphate shell onto liquid filled polymer microcapsules under various reaction conditions. Findings indicate that a non-porous protective shell is formed on the majority of the microcapsule population, with small concentrations of the core material being released only from those microcapsules with defects, over a 7 days period, when conducting forced release studies into a solvent for the core oil. The resulting microcapsules show no significant cell toxicity when exposed to HEK 293 cells for 72 hours.

Michael White,1 Roger G Whittaker1,2 1Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 2Department of Clinical Neurophysiology, Royal Victoria Hospital, Newcastle upon Tyne, NE1 4LP, UKCorrespondence: Michael WhiteTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK, Tel +44 0 191 208 3281, Email Michael.white2@ncl.ac.ukAbstract: For many clinical trials, the issue of post-trial access to research treatments is straightforward. Sponsors offer a range of follow-on studies, compassionate use programs or expanded access programs to allow participants to continue accessing beneficial experimental treatments. But there are times when this is not always the case and participants are required to stop beneficial treatments and return to standard care. Guidance states that post-trial access should be made available for “those participants who still need an intervention identified as beneficial”. This broad statement has allowed sponsors to make their own interpretation of when an intervention is still “needed” and when it is “beneficial”. As a result, there have been a number of situations where participants of clinical trials have been left afterwards with feelings of abandonment. Participants involved in studies with long-term, invasive treatments can be seen as being particularly vulnerable. Optogenetic technology has the potential to offer hope to people with neurological conditions, especially people who may not respond to current approved treatments. Optogenetics typically involves two components: a gene therapy medicinal product (GTMP) that induces long-term expression of light-reactive proteins within cells, and an active implantable device to stimulate the light-sensitised cells. Neither works without the other, hence for long-term patient benefit, both must remain active and may therefore require maintenance or replacement. With the potential life-long consequences of both components and the difficulty of accessing the brain, there is a need to reconsider post-trial guidelines and whether they are suitable to support early phase optogenetic trial participants. This paper considers the ethical and regulatory requirements in place for post-trial access and care in relation to optogenetic treatments of neurological conditions. We propose that a new perspective with wider responsibilities for sponsors is required when it comes to these types of novel therapies.Keywords: optogenetics, post-trial care, clinical trial, neuroscience, trial ethics

Case overview The Gordon Institute of Business Science (GIBS), a South African based business school and one of the top ranked business schools in Africa, was yet again facing a crisis during the COVID-19 pandemic. Having emerged out of an extraordinary year of strict lockdown regulations and having managed a rapid shift to emergency remote teaching. GIBS had managed to maintain its academic programmes, ensuring the completion of the curriculum within the academic year whilst maintaining the exceptionally high standards and quality learning experience it was known for. As 2020 drew to a close, the academic programmes team and the students looked forward to starting the new year in a more “normal” mode of operation. GIBS closed for Christmas holiday with the intent on returning, in early 2021, in some form of face-to-face teaching. However, on the 27th of December 2020, the President of South Africa announced a return to level-3 lockdown as the second wave of infections swept through the country. Strict measures were once again enforced, significantly impacting GIBS’ possible return to campus in January 2021. Reflecting on the lessons learnt over the past year, the Executive Director: Academic Programmes, Professor Louise Whittaker, yet again faced the challenge of deciding how best to proceed given the circumstances. The case illustrates the need for effective change management through the application of Kotter’s 8 steps to transformation, whilst demonstrating the complexity of change management during a crisis. A particular focus on the importance of communication during a change management process in a crisis is illustrated through this case. Expected learning outcomes The learning outcomes are as follows: students need to understand that in a crisis, change management will be emergent and requires flexibility and adaptability; students will determine what concrete actions may be required during a change management process in a crisis; students will need to discern that theoretical models do not necessarily fit real world contexts, particularly in a crisis situation; and students will identify aspects that might be missing or inadequately formulated in standard models of change management. Complexity academic level The case is positioned at a post-graduate level and would be ideal as a teaching case for business school students on a Master of Business Administration programme, a specialised business masters programme or selected executive education programmes for general managers or senior executives. The case can be taught in a course in the following fields, namely, change management, leadership or strategy. Supplementary materials Teaching notes are available for educators only. Subject code CSS 11: Strategy.

Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen-host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral-human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( http://3D-SARS2.yulab.org ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments.

The quality and quantity of forage available to reproductive female ungulates during the summer can influence body condition and lactation, ultimately influencing herd production. The energetic costs of migration can influence individual fitness, thus understanding the mechanisms that drive some individuals in a partially migratory population to migrate, while others remain on winter range year-round, has important conservation and ecological implications. We examined differences in forage quality and quantity between migratory (n = 19) and resident (n = 17) summer home ranges for a population of mule deer (Odocoileus hemionus) in the John Day Basin of northeast Oregon. During 2018, we collected vegetation measurements three times throughout the summer (mid-May, mid-June, mid-July) to determine changes in dry matter digestibility (DMD; %) at three different phenological stages (emergent, mature, and cured) for three forage classes (grass, shrub, forbs). On the second visit, at the peak of the growing season, we collected biomass and cover data to determine differences in forage quantity for each forage class between the migratory and resident summer ranges. In mid-June 2019, we revisited a subsample of sites (migratory [n = 5]; resident [n = 5]) to estimate interannual variation. Migratory deer had access to overall higher quality forage at higher-elevation summer ranges. Forbs had the highest forage quality on both summer ranges. Forage quality declined across the entire study area as moisture declined and vegetation senesced. Shrub forage quality was higher (DMD = 54.1%) on resident ranges than migratory ranges (49.7%; P = 0.001). Grasses had higher biomass (26.1 Mg/ha) and cover (50.1 %) than forbs (19.2 Mg/ha; 34.7% cover) or shrubs (20.6 Mg/ha; 6.7% cover) across the entire summer range. Overall, migratory deer had access to higher-quality forage throughout the summer, yet resident deer had access to higher-quality shrub browse. This trade-off in forage availability may partially explain the persistence of a partially migratory population as a bet-hedging strategy on a landscape where low moisture availability and episodic drought and disturbance create variable foraging conditions.

Mandates that require social distancing and sheltering-in-place to stop the spread of the coronavirus have worsened an already concerning public health issue for older adults –social isolation and loneliness. Alabama Extension System at Alabama A&M University developed a program focused on helping older adults connect with family and friends. A descriptive study of 37 older adults indicated that their knowledge, ability, and comfort with implementing Zoom sessions increased significantly after completing the program. Findings show the potential use of the Zoom for Seniors program in preventing social isolation or loneliness among older adults.

Learning environments can support the development of foundational knowledge and promote children's attitudes toward learning and school. This study explores the relation between school enjoyment and general knowledge from preschool (2016-2017) to kindergarten (2017-2018) in 1359 children (M

Objective Real-time reverse transcription-polymerase chain reaction is the gold standard for the diagnosis of COVID-19, but it is necessary to utilize other tests to determine the burden of the disease and the spread of the outbreak such as IgG-, IgM-, and IgA-based antibody detection using enzyme-linked immunosorbent assay (ELISA). Materials and Methods We developed an indirect ELISA assay to quantitatively measure the amount of COVID-19 IgG, IgM, and IgA antibodies present in patient serum, dried blood, and plasma. Results The population cutoff values for positivity were determined by receiver operating characteristic curves to be 1.23 U/mL, 23.09 U/mL, and 6.36 U/mL for IgG, IgM, and IgA, respectively. After albumin subtraction, the specificity remained >98% and the sensitivity was 95.72%, 83.47%, and 82.60%, respectively, for IgG, IgM, and IgA antibodies to the combined spike subunit 1 receptor binding domain and N proteins in serum. Plasma and dried blood spot specimens were also validated on this assay. Conclusion This assay may be used for determining the seroprevalence of SARS-CoV-2 in a population exposed to the virus or in vaccinated individuals.

In the UK there has been a resistance to using multiple-choice questionnaire (MCQ) assessments to assess undergraduate students. This resistance is based on traditional legal pedagogy and the needs...

Factors affecting the origins of zoonotic coronaviruses in batsWith a presumed origin in bats, the COVID-19 pandemic has been a major source of morbidity and mortality in the human population, and the causative agent, SARS-CoV-2, aligns most closely at the genome level with the bat coronaviruses RaBtCoV4991/RaTG13 and RmYN02. The ability of bats to provide reservoirs of numerous viruses in addition to coronaviruses remains an active area of research. Unique aspects of the physiology of the chiropteran immune system may contribute to the ability of bats to serve as viral reservoirs. The coronavirus spike protein plays important roles in viral pathogenesis and the immune response. Although much attention has focused on the spike receptor-binding domain, a unique aspect of SARS-CoV-2 as compared with its closest relatives is the presence of a furin cleavage site in the S1–S2 region of the spike protein. Proteolytic activation is likely an important feature that allows SARS-CoV-2—and other coronaviruses—to overcome the species barriers and thus cause human disease. The diversity of bat species limits the ability to draw broad conclusions about viral pathogenesis, but comparisons across species and with reference to humans and other susceptible mammals may guide future research in this regard.

Extracorporeal membrane oxygenation (ECMO) is used in critical care to manage patients with severe respiratory and cardiac failure. ECMO brings blood from a critically ill patient into contact with a non-endothelialized circuit which can cause clotting and bleeding simultaneously in this population. Continuous systemic anticoagulation is needed during ECMO. The membrane oxygenator, which is a critical component of the extracorporeal circuit, is prone to significant thrombus formation due to its large surface area and areas of low, turbulent, and stagnant flow. Various surface coatings, including but not limited to heparin, albumin, poly(ethylene glycol), phosphorylcholine, and poly(2-methoxyethyl acrylate), have been developed to reduce thrombus formation during ECMO. The present work provides an up-to-date overview of anti-thrombogenic surface coatings for ECMO, including both commercial coatings and those under development. The focus is placed on the coatings being developed for oxygenators. Overall, zwitterionic polymer coatings, nitric oxide (NO)-releasing coatings, and lubricant-infused coatings have attracted more attention than other coatings and showed some improvement in in vitro and in vivo anti-thrombogenic effects. However, most studies lacked standard hemocompatibility assessment and comparison studies with current clinically used coatings, either heparin coatings or nonheparin coatings. Moreover, this review identifies that further investigation on the thrombo-resistance, stability and durability of coatings under rated flow conditions and the effects of coatings on the function of oxygenators (pressure drop and gas transfer) are needed. Therefore, extensive further development is required before these new coatings can be used in the clinic.

An important focus for clinical nurse educators is facilitating learner development and socialization. When evaluating learning, there are three domains that can be assessed: cognitive, affective, and psychomotor. The cognitive and psychomotor domains are typically well assessed in nursing education. A review of the literature published between 2015 and 2022 suggests that there has been no universal approach to how clinical nurse educators implement the affective domain for novice nurses. The affective domain consists of developing behaviors that are consistent with professional nursing standards. Prioritizing affective domain education can help novice nurses to be better prepared to work in the current state of health care in the United States. The goal of this article is to provide strategies to empower clinical nurse educators to foster opportunities that will develop the affective domain of novice nurses. [ J Contin Educ Nurs. 2023;54(2):56–57.]

Teacher consultation is commonly used to ensure that classroom-based interventions are implemented with fidelity to achieve targeted outcomes, yet the consultation process is not well understood. Consultant-teacher relationship quality is one feature of consultation that may promote intervention outcomes—both directly and indirectly via teachers’ implementation. The current study used mediation models to examine the direct links between consultant-teacher relationship quality, assessed from the perspective of the consultant and teacher, and observed dyadic teacher–child interactions, as well as the indirect effect through teachers’ implementation fidelity and dosage. Implementation data come from the Banking Time intervention (N = 168 children, 57 teachers), a dyadic teacher–child intervention that targets the quality of interactions between teachers and preschoolers perceived to display disruptive behavior. Consultants (N = 4) worked with teachers to support their implementation of specific Banking Time practices. Findings supported a direct link between consultant-reported relationship quality and teachers’ observed interactions with children; however, no evidence for an indirect effect was found. Consultant-reported relationship quality predicted implementation dosage but not fidelity. Across findings, consultant-reported relationship quality emerged as a stronger predictor of outcomes than teacher-reported relationship quality. Results have implications for school-based interventions that employ teacher consultation to support teachers.

Although we know that children who are more frequently absent from school do less well academically, we know little about whether absences matter for other domains of development and whether the timing of their absences matter. In order to address these gaps in knowledge, we examined the experiences of 1,131 kindergartners (64% Hispanic, 7% Black, 17% Asian/other, 12% White) from a mid-Atlantic state. Covariate-adjusted regression analyses showed that children who missed school more frequently did less well in terms of their academic achievement and executive function skills both in kindergarten and through the end of first grade. Importantly, however, there were no consistent differences in children's social behavior nor did outcomes vary as a function of whether their absences occurred in the fall as compared with spring. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose This study aimed to address three key gaps in existing knowledge about postgraduate researchers’ (PGRs) well-being. It investigated 1) the frequency and nature of depression, anxiety and well-being amongst PGRs, and relatedly, characteristics that convey vulnerability, 2) factors that impact PGR well-being, and 3) factors that influence help-seeking. Design/methodology/approach The mixed-methods design comprised quantitative and qualitative approaches. Using opportunity sampling, 585 PGRs registered at a large UK University completed an online survey. The perspectives of a purposive sample of academic and Professional Services staff (n = 61) involved in supporting PGRs were sought through in-depth focus groups and semi-structured interviews, which were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. Findings PGRs scored lower on measures of well-being and higher on measures of anxiety and depression than aged-matched groups in the general population. PGR well-being was positively affected by personal and professional relationships, and negatively affected by academic challenges and mental health problems. Academic supervisors were the primary source of support for students experiencing well-being difficulties. Thematic analysis revealed four domains that impact upon PGR well-being: postgraduate researcher identity; pressures and expectations of postgraduate research; complexity of the supervisor role; and pinch points in postgraduate research. Each domain had associations with help-seeking behaviours. Originality/value This study provides evidence that the PGR experience is perceived to be distinct from that of other students, and this helps understand sources of stress and barriers to help-seeking. It provides a steer as to how higher education institutions could better support the PGR learning experience.

Deepfakes, digital content created via machine learning, a form of artificial intelligence technology, are generating interest among marketers and the general population alike and are often portrayed as a “phantom menace” in the media. Despite relevance to marketing theory and practice, deepfakes—and the opportunities for benefit or deviance they provide—are little understood or discussed. This article introduces deepfakes to the marketing literature and proposes a typology, conceptual framework, and associated research agenda, underpinned by theorizing based on balanced centricity, to guide the future investigation of deepfakes in marketing scholarship. The article makes an argument for balance (i.e., situations where all stakeholders benefit), and it is hoped that this article may provide a foundation for future research and application of deepfakes as “a new hope” for marketing.

The prevalence of permanent childhood hearing impairment (PCHI) in infants admitted to a neonatal intensive care unit (NICU) is higher than that in the general population. Our study objective was to identify risk factors associated with PCHI in infants who required admission to the NICU for more than 48 h. We performed a case–control study, including infants of all gestational ages who were admitted to NICU for more than 48 h and who underwent newborn hearing screening between 2005 and 2019. Infants admitted to NICU and diagnosed with PCHI by formal audiology were classified as “cases”. The “controls” were infants who were admitted to NICU and did not have PCHI. Cases and controls (1:4) were matched based on their birth gestation, birthing place, and treating NICU. The prevalence of PCHI in infants admitted to NICU was 6.3% as compared with our general population prevalence of 0.25%. There were 77 cases and 269 controls during the study period. The median age at diagnosis of PCHI in these infants was 132 days (interquartile range 75.5–518.5). Using regression analysis, “any ventilation episodes”, presence of seizures, and major congenital anomalies were significantly associated with PCHI in infants of all gestational ages. There were higher prevalence of PCHI in preterms (

Background Cerebral small‐vessel disease (cSVD) is an important cause of stroke and vascular dementia. Most cases are multifactorial, but an emerging minority have a monogenic cause. While NOTCH3 is the best‐known gene, several others have been reported. We aimed to summarize the cerebral phenotypes associated with these more recent cSVD genes. Methods and Results We performed a systematic review (PROSPERO [International Prospective Register of Systematic Reviews]: CRD42020196720), searching Medline/Embase (conception to July 2020) for any language publications describing COL4A1/2 , TREX1 , HTRA1 , ADA2 , or CTSA pathogenic variant carriers. We extracted data about individuals’ characteristics and clinical and vascular radiological cerebral phenotypes. We summarized phenotype frequencies per gene, comparing patterns across genes. We screened 6485 publications including 402, and extracted data on 390 individuals with COL4A1 , 123 with TREX1 , 44 with HTRA1 homozygous, 41 with COL4A2 , 346 with ADA2 , 82 with HTRA1 heterozygous, and 14 with CTSA . Mean age ranged from 15 ( ADA2 ) to 59 years ( HTRA1 heterozygotes). Clinical phenotype frequencies varied widely: stroke, 9% ( TREX1 ) to 52% ( HTRA1 heterozygotes); cognitive features, 0% ( ADA2 ) to 64% ( HTRA1 homozygotes); and psychiatric features, 0% ( COL4A2 ; ADA2 ) to 57% ( CTSA ). Among individuals with neuroimaging, vascular radiological phenotypes appeared common, ranging from 62% ( ADA2 ) to 100% ( HTRA1 homozygotes; CTSA ). White matter lesions were the most common pathology, except in ADA2 and COL4A2 cases, where ischemic and hemorrhagic lesions dominated, respectively. Conclusions There appear to be differences in cerebral manifestations across cSVD genes. Vascular radiological changes were more common than clinical neurological phenotypes, and present in the majority of individuals with reported neuroimaging. However, these results may be affected by age and biases inherent to case reports. In the future, better characterization of associated phenotypes, as well as insights from population‐based studies, should improve our understanding of monogenic cSVD to inform genetic testing, guide clinical management, and help unravel underlying disease mechanisms.

Candidate phyla radiation (CPR) bacteria and DPANN archaea are unisolated, small-celled symbionts that are often detected in groundwater. The effects of groundwater geochemistry on the abundance, distribution, taxonomic diversity and host association of CPR bacteria and DPANN archaea has not been studied. Here, we performed genome-resolved metagenomic analysis of one agricultural and seven pristine groundwater microbial communities and recovered 746 CPR and DPANN genomes in total. The pristine sites, which serve as local sources of drinking water, contained up to 31% CPR bacteria and 4% DPANN archaea. We observed little species-level overlap of metagenome-assembled genomes (MAGs) across the groundwater sites, indicating that CPR and DPANN communities may be differentiated according to physicochemical conditions and host populations. Cryogenic transmission electron microscopy imaging and genomic analyses enabled us to identify CPR and DPANN lineages that reproducibly attach to host cells and showed that the growth of CPR bacteria seems to be stimulated by attachment to host-cell surfaces. Our analysis reveals site-specific diversity of CPR bacteria and DPANN archaea that coexist with diverse hosts in groundwater aquifers. Given that CPR and DPANN organisms have been identified in human microbiomes and their presence is correlated with diseases such as periodontitis, our findings are relevant to considerations of drinking water quality and human health., Metagenomics and electron microscopy are combined to analyse the diversity of episymbiotic CPR bacteria and DPANN archaea in eight groundwater communities.

A-level music, a qualification taken most often in English and Welsh school contexts around the age of 18, has been a long-standing feature of the musical training of many musicians. Historically bound up with Western European Art Music, the qualification has somewhat broadened its horizons in recent times, though with mixed success in opening up new ways of thinking about music. Recent research has highlighted the seemingly precarious nature of A-level music in many English schools. The reasons for this picture of decline are highly complex and difficult to disentangle, and are part of a much broader diminishing of creative subjects in the school curriculum. Decreasing numbers of A-level music entries run somewhat counter to popular policy discourse, which celebrates flagship announcements of £79 million given to Music Education Hubs in 2019–2020, and 2018 survey results that reported more than 700,000 children learning to play a musical instrument through music hub provision. However, behind these headlines, although there are many children having the opportunity to learn a musical instrument, few continue through to A-level and beyond. Despite its declining numbers, A-level music is recognised as a valuable qualification amongst music teachers, offering something distinct from graded music examinations and other Level 3 musical qualifications. This article presents the results of a recent nationwide survey of A-level music teachers to offer an insight into teacher perceptions of current A-level music specifications, the extent to which it prepares students for entry into higher musical education, and its appropriateness for aspiring young musicians.

STUDY QUESTION Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION This study included population-based samples from men (23–50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017–September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P LIMITATIONS, REASONS FOR CAUTION This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S) AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

The present study examined differences in school readiness skills in the fall of kindergarten between pre-K attendees and non-attenders (n = 2581) among children in a large, diverse county. Also considered was the extent to which skills associated with pre-K enrollment varied as a function of children’s background characteristics and features of their pre-K program. Results revealed pre-K attenders demonstrated better academic and executive function skills in the first months of kindergarten than non-attenders; no consistent differences were detected for teachers’ reports of children’s socioemotional adjustment. Differences in academic skills and self-regulation associated with attendance in pre-K were largest for dual language learners and children from the lowest-income families. Children enrolled in private pre-K programs demonstrated less optimal socioemotional skills at kindergarten entry.