Utilization and barriers to eye care following school-wide pediatric vision screening.

OBJECTIVE: In August 2018, Ontario introduced the Child Visual Health and Vision Screening Protocol outlining school-based senior kindergarten (aged 4-6 years) vision screening. We determine the prevalence of children at risk based on screening in an Ontario community and follow up to determine resource utilization after screening. METHODS: Vision screening data (HOTV, Randot, Autorefractor) from 41 schools (1127 children) were collected for the 2018-2019 and 2019-2020 school years. Phone follow-up was conducted 1-1.5 years after screening to determine whether an optometry visit occurred, if glasses were prescribed, and potential barriers to accessing eye care. Independent t tests were used to compare time to follow-up between groups, and χ2 testing was used for associations between material and social deprivation. RESULTS: Overall screening resulted in a 32.2% referral rate within our region. Of the referred children who responded, the rate of seeking out eye care was 69.9% (n = 64), and 65.2% of these visits were prompted specifically by vision screening, and 34.4% of referred children respondents were prescribed glasses. There was a significant relationship between receiving a referral and living in a more materially deprived (p = 0.001) and a more socially deprived area (p = 0.006). The most frequently reported barriers were related to insufficient insurance coverage for eye care or glasses, COVID-19-related difficulties, and scheduling conflicts. CONCLUSION: Our vision screening program identified and referred more than one third of children screened for follow-up eye examinations, with children in more deprived neighbourhoods being more frequently referred. Around two thirds of referred children sought care, and one third were prescribed glasses in the follow-up sample.

COVID-19 Vaccine Uptake in Southeastern Ontario, Canada: Monitoring and Addressing Health Inequities.

CONTEXT: Implementation of a population-based COVID-19 vaccine strategy, with a tailored approach to reduce inequities in 2-dose coverage, by a mid-sized local public health agency in southeastern Ontario, Canada. PROGRAM: Coverage maps and crude and age-standardized coverage rates by material and social deprivation, urban/rural status, and sex were calculated biweekly and reviewed by local public health planners. In collaboration with community partners, the results guided targeted strategies to enhance uptake for marginalized populations. EVALUATION: The largest gaps in vaccine coverage were for those living in more materially deprived areas and rural residents-coverage was lower by 10.9% (95% confidence interval: -11.8 to -10.0) and 9.3% (95% confidence interval: -10.4 to -8.1) for these groups compared with living in less deprived areas and urban residents, respectively. The gaps for all health equity indicators decreased statistically significantly over time. Targeted strategies included expanding clinic operating hours and availability of walk-in appointments, mobile clinics targeted to marginalized populations, leveraging primary care partners to provide pop-up clinics in rural and materially and socially deprived areas, and collaborating with multiple partners to coordinate communication efforts, especially in rural areas. DISCUSSION: The scale and scope of monitoring and improving local vaccine uptake are unprecedented. Regular review of health equity indicators provided critical situational awareness for decision makers, allowing partners to align and tailor strategies locally and in collaboration with one another. Health care providers and pharmacies/pharmacists are key partners who require innovative support to increase uptake in marginalized groups. Continued engagement of other community partners such as schools, municipalities, and local service groups is also crucial. A "hyper local" approach is needed along with commitment from partners in all sectors and at all levels to reduce barriers to vaccination that lie further upstream for marginalized groups.

Fetal alcohol spectrum disorder and confabulation in psycholegal settings: A beginner's guide for criminal justice, forensic mental health, and legal interviewers.

Fetal alcohol spectrum disorders (FASD) are neurodevelopmental/neurobehavioral conditions caused by prenatal alcohol exposure (PAE). Impairments caused by PAE contribute to the over-representation of individuals with FASD in the United States juvenile and adult criminal justice systems. These same impairments can equally impact on individuals with FASD who are witnesses to or victims of crime who also have to navigate the complexities of the criminal justice system. Difficulties include increased susceptibility to confabulation throughout the legal process that, in turn, can contribute to increased rates of poor outcomes including false confessions and wrongful convictions. Individuals with FASD are particularity at risk of confabulation when they are subjected to tactics, such as stressful and anxiety-provoking situations, threats, and leading, suggestive, or coercive questioning. Many professionals in the forensic context are unfamiliar with FASD or related confabulation risk and may unintentionally utilize tactics that intensify impacts of pre-existing impairment. This article serves as a beginner's guide for professionals working in criminal justice settings by (a) providing research-based overviews of FASD and confabulation, (b) describing how FASD may lead to confabulation, and (c) suggesting ways that professionals can modify protocols when interacting with individuals with FASD. Suggestions in this article hold the potential to decrease the risk of confabulation in the criminal justice system and decrease problematic outcomes, such as false confessions and wrongful convictions among individuals with FASD.

Fetal alcohol spectrum disorders (FASD) and youth firesetting: A call on criminal justice, emergency responder, and fire prevention specialists to become informed.

Central nervous system damage resulting from prenatal exposure to alcohol, often referred to as fetal alcohol spectrum disorders (FASD), commonly manifests as lacking cognitive functioning, problem solving, impulsivity, memory, executive functioning, and social skill deficits. For individuals with FASD, these brain-based deficits translate into impulsive behaviors and poorly thought-out decision-making, coupled with an inability to anticipate and recognize the sometimes very severe consequences of their behaviors. Not unexpectedly, individuals with FASD frequently find themselves disproportionately involved in the criminal justice system and mental health services. For some individuals with FASD, these behaviors can also include firesetting. First responders, like other health and legal professionals, are often unable to recognize the behavioral indicators of FASD, primarily due to a lack of training. As a result, firesetting behaviors are often attributed to deliberate, willful acts of delinquency, a desire to damage property, thrill seeking, or as attempts for personal gain, rather than being viewed as maladaptive attempts to solve problems by individuals who lack the tools to do this in more appropriate ways. These same skill deficits also present when individuals with FASD are interviewed about their involvement in such behaviors, sometimes resulting in confabulation, suggestibility, and false confessions. Further education and training in FASD are vital for first responders if they are to better support individuals with FASD and minimize their chances of becoming involved in firesetting behaviors. Furthermore, this training and education will help ensure that first responders can intervene in more appropriately when crisis situations do occur. This article will outline key behavioral symptoms of FASD as well as provide first responders with suggestions as to how to best support individuals when FASD is suspected. The brief quote that follows highlights some of the key challenges facing individuals with FASD and how poor decision-making and impulsiveness can result in severe consequences for the individual and those around them.

Fetal alcohol spectrum disorder (FASD) and suggestibility: A survey of United States federal case law.

This article summarizes four federal criminal cases that illustrate how suggestibility can impact defendants with FASD in the criminal justice system. Four cases were identified via a Google Scholar search of "suggestibility" and "fetal alcohol" in the federal case law database. These cases are illustrative of how FASD can affect legal defendants, including vulnerability to peer pressure, being easily manipulated, insufficient comprehension of legal proceedings, difficulty in assisting legal counsel, learning impairment, acquiescence or higher levels of suggestibility, and difficulty understanding consequences. The cases presented here provided the most comprehensive discussion of FASD and suggestibility issues but are by no means an exhaustive review of case law. Because defendants with FASD are the focal point of this article, we intentionally excluded cases involving eyewitness suggestibility, the suggestibility of child witnesses, and the suggestibility of those under hypnosis. Therefore, this review has been developed to explicate and illustrate problems common to FASD defendants within legal settings, especially regarding risk for suggestibility. The information provided from this discussion may better guide legal professionals who regularly come into contact with persons affected by FASD on how to more readily detect this neurodevelopmental condition and mitigate the likelihood of injustice during criminal proceedings. Additionally, we include suggestions on how to attenuate miscarriages of justice as a result of faulty confessions, wrongful convictions, and vulnerability of suggestibility in persons affected by FASD.

Fetal alcohol spectrum disorder and Risk-Need-Responsivity Model: A guide for criminal justice and forensic mental health professionals.

Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe a range of significant neurodevelopmental, brain-based disorders and impairments that result from prenatal alcohol exposure. FASD is a high prevalence but underdiagnosed group of disorders affecting between 17 and 36% of individuals in criminal justice settings. Despite being a high-impact disorder associated with lifelong impairments with a significant need for services and interventions, little research has been completed on how to best support individuals with these conditions in criminal justice settings. This article proposes a renewed focus on applying and adapting the Risk-Need-Responsivity (RNR) approach to individuals with FASD in criminal justice settings. This will assist in better determining the needs and interventions likely to effect change and reduce recidivism for this prominent criminal justice-based population. The RNR approach has been used with multiple corrections populations to determine the need and most appropriate interventions, as well as how to best allocate scarce resources. As the prevalence of FASD becomes better understood and recognized, evidence-based approaches to addressing this specific sub-population are necessary to effect change and reduce recidivism and ongoing involvement in the criminal justice system.

Enhancing Nurse Manager Resilience in a Pandemic.

Nurse managers face many daily challenges that require strong resilience and skill. The COVID-19 pandemic placed nurse managers under exceptional pressure to deliver safe staffing resources, updated infection control practices, and communication with the multidisciplinary team. During the height of the pandemic in the summer of 2020, a group of nurse managers at a health system in the Midwest engaged in a resilience-building tool to strengthen their emotional well-being and work-life balance so that they could optimize their leadership support of their clinical teams and thrive in an unprecedented time.

Suggestibility and confabulation among individuals with Fetal Alcohol Spectrum Disorder: A review for criminal justice, forensic mental health, and legal interviewers.

Fetal Alcohol Spectrum Disorders (FASD) are conditions arising from prenatal alcohol exposure which results in a range of neurodevelopmental deficits in areas including cognition, memory, language, executive functioning, emotional regulation, and adaptive functioning. Deficits in various neurodevelopmental areas can range from mild to severe, depending on many factors including the quantity and timing of alcohol exposure during the prenatal development period. During interviews in criminal justice, forensic mental health, and legal contexts (e.g., criminal investigations, cross examination, victim interviews, interviews for lawsuits, forensic evaluations, pre-sentence investigations), deficits associated with FASD may elevate the risk of suggestibility and confabulation. These issues can result in negative jurisprudence-related outcomes, including impulsive Miranda rights waivers, incorrect assumptions of competency, inaccurate or incomplete information gathering, misinterpretation of intent, witness reliability issues, court ordered treatment completion problems, probation and parole violations, false confessions, and false accusations. The aim of the present article is to explain the context in which these issues can arise and provide criminal justice, forensic mental health, and legal professionals with key guidelines that can assist in minimizing suggestibility and confabulation when interviewing persons with FASD. We hope that the suggestions and strategies presented in this article will reduce potential obstructions of justice and enhance the quality of information obtained from individuals impacted by FASD. A brief discussion is also provided to identify additional research and training opportunities needed to clarify "best practices" for professionals tasked with evaluating the challenges facing this unique population.

Development of a chemical probe against NUDT15.

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues.

Relative macrofaunal biomass reduced under an enriched salmon farm, Pelorus Sound, Aotearoa-New Zealand.

We compared changes in the benthos associated with discharges from a salmon farm at a low-flow location in Pelorus Sound, Aotearoa-New Zealand to the Pearson and Rosenberg model (PRM). As predicted by PRM, benthic enrichment resulted in significant increases in abundance of small, opportunistic macrofauna beneath salmon farm cages. In contrast, at reference sites we found fewer but larger, rare species. When estimates for biomass were calculated from macrofaunal size-classes, reference sites averaged 4.86 times more biomass and 4.35 times greater diversity than farm sites - results also consistent with the PRM. Farm sites favoured deposit feeders at the expense of suspension feeders and grazers. We discuss the significance of large rare species that contributed most to reference biomass estimates that appear under threat from multiple anthropogenic stressors.

Author Correction: Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sex offender treatment professional perceptions of Fetal Alcohol Spectrum Disorder (FASD) in the Midwest.

Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental condition that is precipitated by prenatal alcohol exposure. Typified by cognitive, social, and adaptive functioning impairments, FASD places impacted individuals at an elevated risk for involvement in the criminal justice system. In particular, it has been reported that some individuals diagnosed with FASD engage in inappropriate sexual behaviors. Because professionals working in the field of sexual offender treatment have the potential to strongly influence their clients, this study surveys professionals that provide treatment services to sexual offenders. Topics queried include knowledge of FASD, the role of FASD in criminal behavior, and training opportunities. The key findings from this study include that the respondents readily recognized symptoms, deficits, and consequences of FASD, but had very few opportunities to receive advanced training on FASD in the context of inappropriate sexual behavior. Findings suggest there is a strong need to develop educational and training programs that better equip professionals with the skills to assist clients with FASD in treatment settings for inappropriate sexual behavior.

Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana.

Arabidopsis thaliana NUDT1 (AtNUDT1) belongs to the Nudix family of proteins, which have a diverse range of substrates, including oxidized nucleotides such as 8-oxo-dGTP. The hydrolysis of oxidized dNTPs is highly important as it prevents their incorporation into DNA, thus preventing mutations and DNA damage. AtNUDT1 is the sole Nudix enzyme from A. thaliana shown to have activity against 8-oxo-dGTP. We present the structure of AtNUDT1 in complex with 8-oxo-dGTP. Structural comparison with bacterial and human homologues reveals a conserved overall fold. Analysis of the 8-oxo-dGTP binding mode shows that the residues Asn76 and Ser89 interact with the O8 atom of the substrate, a feature not observed in structures of protein homologues solved to date. Kinetic analysis of wild-type and mutant AtNUDT1 confirmed that these active site residues influence 8-oxo-dGTP hydrolysis. A recent study showed that AtNUDT1 is also able to hydrolyze terpene compounds. The diversity of reactions catalyzed by AtNUDT1 suggests that this Nudix enzyme from higher plants has evolved in a manner distinct to those from other organisms.

Considerations for incorporating real-time PCR assays into routine marine biosecurity surveillance programmes: a case study targeting the Mediterranean fanworm (Sabella spallanzanii) and club tunicate (Styela clava) 1.

Molecular techniques may provide effective tools to enhance marine biosecurity surveillance. Prior to routine implementation, evidence-based consideration of their benefits and limitations is needed. In this study, we assessed the efficiency and practicality of visual diver surveys and real-time PCR assays (targeting DNA and RNA) for detecting two marine invasive species whose infestation levels varied between species and location: Sabella spallanzanii and Styela clava. Filtered water samples (n = 171) were collected in parallel with dive surveys at two locations as part of the New Zealand Marine High Risk Site Surveillance programme: Nelson Harbour (27 sites) and Waitemata Harbour (30 sites). Diver surveys resulted in a greater number of detections compared to real-time PCR: S. clava - 21 versus 5 sites in Nelson, 6 versus 1 in Auckland; S. spallanzanii - 18 versus 10 in Auckland, no detections in Nelson. Occupancy modelling derived detection probabilities for the real-time PCR for S. clava were low (14%), compared to S. spallanzanii (66%). This could be related to abundances, or species-specific differences in DNA shedding. Only one RNA sample was positive, suggesting that most detections were from extracellular DNA or non-viable fragments. While molecular methods cannot yet replace visual observations, this study shows they provide useful complementary information.

Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold.

Human NUDT22 belongs to the diverse NUDIX family of proteins, but has, until now, remained uncharacterized. Here we show that human NUDT22 is a Mg2+-dependent UDP-glucose and UDP-galactose hydrolase, producing UMP and glucose 1-phosphate or galactose 1-phosphate. We present the structure of human NUDT22 alone and in a complex with the substrate UDP-glucose. These structures reveal a partially conserved NUDIX fold domain preceded by a unique N-terminal domain responsible for UDP moiety binding and recognition. The NUDIX domain of NUDT22 contains a modified NUDIX box identified using structural analysis and confirmed through functional analysis of mutants. Human NUDT22's distinct structure and function as a UDP-carbohydrate hydrolase establish a unique NUDIX protein subfamily.

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells. We confirm the involvement of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. We herein present TH5427 as a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism.

Knowledge translation in tri-sectoral collaborations: An exploration of perceptions of academia, industry and healthcare collaborations in innovation adoption.

With the aging population and increase in chronic disease conditions, innovation to transform treatment pathways and service delivery will be necessary. The innovation adoption process however, can take 15 years before widespread adoption occurs in most healthcare systems. Current UK government policies to increase the facilitation of innovation adoption are under way. The aim of this study is to explore perceptions of tri-sectoral collaborations in the healthcare sector. The data in the study are drawn from a cross-sectional survey conducted in 2015 of professionals in academia, industry and the healthcare sectors in England, focusing on Diabetes care. Academia and healthcare respondents had the least work experience outside of their sectors compared to the industry respondents. Healthcare and academia respondents rated the industry sector less trustworthy, unethical, having different goals and less understanding of the other sectors. Industry respondents had a more positive perspective towards potential collaborators. The results from the study demonstrate greater potential challenges to tri-sectoral collaborations and the government's knowledge translation policy, due to pre-conceived notions and lack of understanding of other sectors. The purely structural approach of establishing government mandated translational networks may be insufficient without active attempts to improve collaborative relationships. Mechanisms to facilitate trust building and collaboration are proposed.

A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family.

The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.

Utilizing a Human Factors Nursing Worksystem Improvement Framework to Increase Nurses' Time at the Bedside and Enhance Safety.

OBJECTIVE: The aim of this study is to increase nurses' time for direct patient care and improve safety via a novel human factors framework for nursing worksystem improvement. BACKGROUND: Time available for direct patient care influences outcomes, yet worksystem barriers prevent nurses adequate time at the bedside. METHODS: A novel human factors framework was developed for worksystem improvement in 3 units at 2 facilities. Objectives included improving nurse efficiency as measured by time-and-motion studies, reducing missing medications and subsequent trips to medication rooms and improving medication safety. RESULTS: Worksystem improvement resulted in time savings of 16% to 32% per nurse per 12-hour shift. Requests for missing medications dropped from 3.2 to 1.3 per day. Nurse medication room trips were reduced by 30% and nurse-reported medication errors fell from a range of 1.2 to 0.8 and 6.3 to 4.0 per month. CONCLUSIONS: An innovative human factors framework for nursing worksystem improvement provided practical and high priority targets for interventions that significantly improved the nursing worksystem.