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This chapter provides an up-to-date review of the literature on the phonetic and phonological patterns of Welsh and their development. While typically developing children’s acquisition constitutes a major component, it also discusses socio-phonetic variation and adult second language acquisition, thereby approaching Welsh speech development from a lifespan perspective. The chapter is structured in four major sections. The first section introduces the reader to the segmental and suprasegmental properties of the two main varieties of Welsh: Northern and Southern Welsh. Subsequently, the second section considers methodological aspects of studies on Welsh phonology, while the third section focuses on children’s development of Welsh speech patterns, starting with evidence from studies on early word productions before moving on to a discussion of consonant and consonant cluster acquisition in preschool and school-aged children. The section concludes with an account of developmental error patterns. The final major section then reviews the literature on the speech patterns of different groups of Welsh speakers and the role that extra-linguistic variables, such as sex/gender and language dominance, play in shaping these. Finally, studies on the Welsh accents of second language learners will be discussed. The chapter concludes with suggestions for future research.
This paper addresses the taxonomic status of the extinct large-bodied sea mink Neogale macrodon. Since the early twentieth century, bones of this mink have been found commingled with those of the extant mink, Neogale vison, in Maine’s prehistoric archaeological sites. These two size classes of mink have been described as separate species and as sexually dimorphic size variants of N. vison. A century later, researchers revisited this dispute using data from North American modern and archaeological mink skulls, along with limited postcranial bones, and decided in favor of two species. However, this conclusion was challenged.
We return to the discussion by focusing on postcranial bones, which have advantages over skulls for metric analyses. We considered historical evidence for mink morphology and behavior and determined that, although the two forms shared the same habitat, our large number of identified specimens (NISP) of mink (NISP > 1200) contained no detectable evidence for interbreeding. We conclude that the sea mink was an emerging marine fissiped, transitioning from an undetermined N. vison ancestor in a manner analogous to the polar bear (Ursus maritimus) and the sea otter (Enhydra lutris). Lastly, we suggest N. macrodon became extinct during the nineteenth century under heavy pressure from market hunting.
Fifty-three tests designed to measure aspects of creative thinking were administered to 410 air cadets and student officers. The scores were intercorrelated and 16 factors were extracted. Orthogonal rotations resulted in 14 identifiable factors, a doublet, and a residual. Nine previously identified factors were: verbal comprehension, numerical facility, perceptual speed, visualization, general reasoning, word fluency, associational fluency, ideational fluency, and a factor combining Thurstone's closure I and II. Five new factors were identified as originality, redefinition, adaptive flexibility, spontaneous flexibility, and sensitivity to problems.
The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient’s lesion for diagnostic testing.
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.
Aims
To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.
Method
We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.
Results
We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.
Conclusions
Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.
Objectives: Few reports have been published about the transmission of mpox in healthcare settings. During the 2022 multinational outbreak, the California Department of Public Health (CDPH) conducted a systematic review of healthcare personnel (HCP) with mpox, including their community and occupational exposures, to understand the transmission risk in healthcare settings. We also sought to inform return-to-work protocols by describing the frequency of HCP working while symptomatic for mpox and identifying occurrences of secondary transmission from infected HCP to patients. Methods: We analyzed surveillance data for laboratory-confirmed mpox cases in California with symptom onset from May 17 to September 30, 2022, collected by investigators at local health departments and reported to the CDPH. The reported data were supplemented by review of free-text variables, interview notes, and other files uploaded to state and county disease surveillance data registries. We identified HCP as all persons working in healthcare settings with potential for direct or indirect exposure to patients or infectious materials, including clinical and nonclinical staff but excluding remote workers. Results: The CDPH received reports of 3,176 mpox cases during the study period: 109 were HCP. Of the 109 HCP identified from 19 counties, 78 (72%) were aged 30–49 years, 102 (94%) were male, and 43 (39%) were Hispanic or Latino. Also, 29 HCP (27%) had received at least 1 dose of the JYNNEOS vaccine. Occupations requiring frequent physical interactions with patients were reported for 66 individuals (61%). During interviews with local health department investigators, nearly all HCP (n = 98, 90%) reported potential or confirmed sources of community exposure; 1 had confirmed occupational exposure with symptom onset 9 days after a sharps injury acquired during collection of an mpox specimen for testing. Of the 60 HCP who provided information about the days they worked, 35 (58%) worked while symptomatic, for a mean of 3.14 days (median, 2; IQR, 3). Also, 2 HCP worked for 12 days after symptom onset. No secondary cases of mpox were associated with HCP reported to the CDPH. Conclusions: This analysis suggests that HCP are more likely to be exposed to mpox in community settings than healthcare settings. The findings support recommendations against sharps use for mpox specimen collection. Although transmission between symptomatic HCP and patients was not reported, HCP can decrease opportunities for mpox transmission by closely monitoring themselves for symptoms after potential exposures and staying home from work if symptoms develop.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
National standards to ensure effective transition and smooth transfer of adolescents from paediatric to adult services are available but data on successful transition in CHD are limited. The aim of this study is to assess the effectiveness of our transition pathway.
Methods:
Adolescents with CHD, aged 15–19 years, who attended the joint cardiac transition clinic between 2009 and 2018 were identified from the Patient Administration Systems. Patient attendance at their first adult CHD service appointment at Royal Papworth Hospital was recorded.
Results:
179 adolescents were seen in the joint cardiac transition clinic in the 9-year study period. The median age of the patients when seen was 16 (range 15–19) years. 145 patients were initially planned for transfer to the Royal Papworth Hospital adult CHD service. Three patients were subsequently excluded and the success of the transfer of care in 142 patients were analysed. 112 (78%) attended their first follow-up in the adult CHD clinic as planned, 28 (20%) attended after reminders were sent out with 5/28 requiring multiple reminders, and only 2 (1.4%) failed to attend. Overall, transfer of care was achieved in 140 (98.6%) patients.
Conclusion:
A dedicated joint cardiac transition clinic involving multi-professional medical and nursing teams from paediatric and adult cardiology services appears to achieve high engagement rates with the adult services. This approach allows a ‘face’ to be put on a named clinician delivering the adult service and should be encouraged.
OBJECTIVES/GOALS: The goal of this study is to examine the incidence, etiology, and outcomes of hepatocellular carcinoma (HCC) in a 27-county region in SE Minnesota and W Wisconsin between 2010 and 2021. A comparison of the first to second half of the period will be made to look for possible trends. METHODS/STUDY POPULATION: The Rochester Epidemiology Project (REP) is a database of patient records across SE Minnesota and W Wisconsin. Starting in 2010, the REP opened to a 27-county catchment area, which includes over 1.3 million patients with a population coverage of approximately 64%. This study will use the expanded REP data to collect data on patients 20 years of age and older with a new diagnosis of HCC between Jan 1, 2010 and Dec 31, 2021—an estimated 1000 cases. Patients with a record of less than one year of residence in the catchment area will be excluded. Data on etiology, comorbidities, and outcomes of HCC will be extracted from medical records and analyzed for risk factors and changes over time. RESULTS/ANTICIPATED RESULTS: We anticipate that the overall incidence of HCC in the REP geographic area has increased over the period of 2010 to 2021. We anticipate that the prevalence of hepatitis C virus infection in patients with HCC has between 2010 and 2021, due to the widespread use and accessibility of hepatitis C-specific antiviral treatment over the past decade. We anticipate that the prevalence of NAFLD in patients with HCC has increased between 2010 and 2021. We do not anticipate significant changes in treatment modality or survival outcomes over this period. DISCUSSION/SIGNIFICANCE: This study will provide a comprehensive update on the state, etiology, and outcomes of HCC in the area surrounding Rochester, MN. We will be able to track changes in risk factors over time and work to enhance screening protocols to target the most vulnerable populations.
A combination of morphological and molecular techniques were used to revise the genus Ellescus Dejean, 1821 (Coleoptera: Curculionidae: Ellescini) in North America. Four valid species of Ellescus are documented from the Nearctic Region. These are the widespread, hypervariable E. ephippiatus (Say, 1831), the Holarctic E. bipunctatus (Linnaeus, 1758) (of which E. borealis (Carr, 1920) new synonym is found to be a new junior synonym), the west coast endemic E. californicus (Casey, 1885) (resurrected from synonymy with E. ephippiatus (Say, 1831)), and the temperately distributed E. michaelinew species. A neotype is designated for E. bipunctatus. The European species, E. scanicus (Paykull, 1792), is determined to have been erroneously reported from North America. An illustrated identification key, distributional data, and DNA sequences (CO1, ITS2) are provided to facilitate identification of the Ellescus species in North America. Notably, CO1 failed to delineate E. ephippiatus and E. michaeli, but the faster-evolving ITS2 reliably separated these taxa, further supporting the use of multiple markers in taxonomic studies and the utility of ITS2 in weevil species delineation.
Until recently, the influence of basal liquid water on the evolution of buried glaciers in Mars' mid latitudes was assumed to be negligible because the latter stages of Mars' Amazonian period (3 Ga to present) have long been thought to have been similarly cold and dry to today. Recent identifications of several landforms interpreted as eskers associated with these young (100s Ma) glaciers calls this assumption into doubt. They indicate basal melting (at least locally and transiently) of their parent glaciers. Although rare, they demonstrate a more complex mid-to-late Amazonian environment than was previously understood. Here, we discuss several open questions posed by the existence of glacier-linked eskers on Mars, including on their global-scale abundance and distribution, the drivers and dynamics of melting and drainage, and the fate of meltwater upon reaching the ice margin. Such questions provide rich opportunities for collaboration between the Mars and Earth cryosphere research communities.
Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine and N-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.
To determine factors associated with increased response readiness to CBRN threats of paramedics in Ontario, Canada.
Methods:
An internet-based survey was distributed via email and delivered at the start of each shift presentation during October, 2019. The target population was active-duty paramedics in the Ontario region of Canada. The survey was comprised of 6 sections pertaining to demographics, attitudinal components of risk perception, self-efficacy, deployment concerns, and resilience. Survey mean, univariate, and multivariate regression analyses were used to find the individual effect of each variable.
Results:
The univariate analysis indicated that higher response readiness was associated with additional training, education, CBRN, and family concerns, and incident experience. However, some variables were non-significant in the multivariate analysis. Increased response readiness was associated with CBRN concerns and training.
Conclusion:
CBRN concerns and focused training regarding terrorism were both associated with increased response readiness. The information from the study can be used to build upon existing knowledge and support paramedics though training and preparation for CBRN specific disasters. The findings may also be used to improve current competency-based frameworks focused on response readiness.
The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown).
Aims
Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales.
Method
We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2–T5) using phenotypic and genetic longitudinal designs.
Results
The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3–T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2–T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later.
Conclusions
We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.
OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.
There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population.
Aims
To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness.
Method
Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health.
Results
A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses.
Conclusions
We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.