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While it's known that the dysregulation of splicing contributes to disease, identifying specific splicing alterations is a bottleneck for current research. On an individual scale, mutations in signaling cues disrupt canonical splicing and force the production of an aberrant splicing event. On a global scale, splicing factor mutations result in widespread splicing dysregulation and create a subset of isoforms that contribute to disease progression. In both cases, identifying specific splicing aberrations that drive disease is important in developing targeted therapies, and can greatly improve the lives of patients bearing these mutations. To study novel deleterious splicing events, scientists need the appropriate tools to identify and functionally characterize these isoforms. In chapter 2 of this dissertation, I found that using CRISPR/Cas9 to express aberrant exon skipping events from their endogenous promoter did not produce enough aberrant isoform to confirm the oncogenic potential in two functional assays. Because exon skipping events, alone, were not sufficient to confer an oncogenic phenotype, I investigated the level of a known oncogenic isoform, MET exon 14 skipping (METΔ14), expressed in lung adenocarcinoma primary samples in chapter 3. I found that METΔ14 is overexpressed in an allele-specific manner, and METΔ14 overexpression is required to activate the receptor. In chapter 4, through a collaboration with Dr. Esther Obeng’s lab, I performed long read sequencing in cell lines expressing mutant SF3B1, a common splicing factor mutation in Myelodysplastic Syndrome (MDS). This collaboration uncovered previously unannotated isoforms with potential implication in MDS. Overall, the work in this dissertation outlines the trials and tribulations of using the correct tools to functionally characterize aberrant splicing events, and describes triumphs of discovering how METΔ14 is expressed in lung cancer tumors and isoforms implicated in MDS-associated anemia requiring further characterization.

On June 17, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) amendments for the mRNA-1273 (Moderna) COVID-19 vaccine for use in children aged 6 months-5 years, administered as 2 doses (25 µg [0.25 mL] each), 4 weeks apart, and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine for use in children aged 6 months-4 years, administered as 3 doses (3 µg [0.2 mL] each), at intervals of 3 weeks between doses 1 and 2 and ≥8 weeks between doses 2 and 3. On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued separate interim recommendations for use of the Moderna COVID-19 vaccine in children aged 6 months-5 years and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-4 years for the prevention of COVID-19.* Both the Moderna and Pfizer-BioNTech COVID-19 vaccines met the criteria for immunobridging, which is the comparison of neutralizing antibody levels postvaccination in young children with those in young adults in whom efficacy had been demonstrated. Descriptive efficacy analyses were also conducted for both Moderna and Pfizer-BioNTech COVID-19 vaccines during the period when the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) predominated. No specific safety concerns were identified among recipients of either vaccine. ACIP recommendations for the use of the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-5 years and 6 months-4 years, respectively, are interim and will be updated as additional information becomes available. Vaccination is important for protecting children aged 6 months-5 years against COVID-19.

This study aimed to evaluate the feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet (MD) in established community groups where existing social support may assist the behaviour change process. Four established community groups with members at increased Cardiovascular Disease (CVD) risk and homogenous in gender were recruited and randomised to receive either a 12-month Peer Support (PS) intervention (PSG) (n 2) or a Minimal Support intervention (educational materials only) (MSG) (n 2). The feasibility of the intervention was assessed using recruitment and retention rates, assessing the variability of outcome measures (primary outcome: adoption of an MD at 6 months (using a Mediterranean Diet Score (MDS)) and process evaluation measures including qualitative interviews. Recruitment rates for community groups (n 4/8), participants (n 31/51) and peer supporters (n 6/14) were 50 %, 61 % and 43 %, respectively. The recruitment strategy faced several challenges with recruitment and retention of participants, leading to a smaller sample than intended. At 12 months, a 65 % and 76·5 % retention rate for PSG and MSG participants was observed, respectively. A > 2-point increase in MDS was observed in both the PSG and the MSG at 6 months, maintained at 12 months. An increase in MD adherence was evident in both groups during follow-up; however, the challenges faced in recruitment and retention suggest a definitive study of the peer support intervention using current methods is not feasible and refinement based on the current feasibility study should be incorporated. Lessons learned during the implementation of this intervention will help inform future interventions in this area.

Four COVID-19 vaccines are currently approved for primary series vaccination in the United States under a Biologics License Application or authorized under an emergency use authorization (EUA) by the Food and Drug Administration (FDA), and recommended for primary series vaccination by the Advisory Committee on Immunization Practices (ACIP): 1) the 2- or 3-dose monovalent mRNA BNT162b2 (Pfizer-BioNTech, Comirnaty) COVID-19 vaccine; 2) the 2- or 3-dose monovalent mRNA mRNA-1273 (Moderna, Spikevax) COVID-19 vaccine; 3) the single-dose adenovirus vector-based Ad26.COV.S (Janssen [JohnsonJohnson]) COVID-19 vaccine; and 4) the 2-dose adjuvanted, protein subunit-based NVX-CoV2373 (Novavax) COVID-19 vaccine. The number of doses recommended is based on recipient age and immunocompromise status (1). For additional protection, FDA has amended EUAs to allow for COVID-19 booster doses in eligible persons (1). Because COVID-19 vaccines have demonstrated decreased effectiveness during the period when the Omicron variant (B.1.1.529) of SARS-CoV-2 predominated, bivalent booster doses (i.e., vaccine with equal components from the ancestral and Omicron strains) were considered for the express purpose of improving protection conferred by COVID-19 vaccine booster doses (2). During September-October 2022, FDA authorized bivalent mRNA vaccines for use as a booster dose in persons aged ≥5 years who completed any FDA-approved or FDA-authorized primary series and removed EUAs for monovalent COVID-19 booster doses (1). Pfizer-BioNTech and Moderna bivalent booster vaccines each contain equal amounts of spike mRNA from the ancestral and Omicron BA.4/BA.5 strains. After the EUA amendments, ACIP and CDC recommended that all persons aged ≥5 years receive 1 bivalent mRNA booster dose ≥2 months after completion of any FDA-approved or FDA-authorized monovalent primary series or monovalent booster doses.

The NVX-CoV2373 (Novavax) COVID-19 vaccine is a recombinant spike (rS) protein nanoparticle vaccine with Matrix-M adjuvant to protect against infection with SARS-CoV-2, the virus that causes COVID-19. On July 13, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Novavax vaccine for primary COVID-19 immunization of unvaccinated adults aged ≥18 years, administered as 2 doses (5 μg rS and 50 μg Matrix-M adjuvant in each dose) 3 weeks apart (1). On July 19, 2022, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the Novavax vaccine in persons aged ≥18 years for the prevention of COVID-19.* In the per-protocol

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged

The mRNA-1273 (Moderna) COVID-19 vaccine is a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. During December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA), and the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use among persons aged ≥18 years (1), which was adopted by CDC. During December 19, 2020-January 30, 2022, approximately 204 million doses of Moderna COVID-19 vaccine were administered in the United States (2) as a primary series of 2 intramuscular doses (100 μg [0.5 mL] each) 4 weeks apart. On January 31, 2022, FDA approved a Biologics License Application (BLA) for use of the Moderna COVID-19 vaccine (Spikevax, ModernaTX, Inc.) in persons aged ≥18 years (3). On February 4, 2022, the ACIP COVID-19 Vaccines Work Group conclusions regarding recommendations for the use of the Moderna COVID-19 vaccine were presented to ACIP at a public meeting. The Work Group's deliberations were based on the Evidence to Recommendation (EtR) Framework,* which incorporates the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach

Drosophila obscura is a common fruit fly that inhabits the temperate forests of Europe. While it is abundant in the north compared to other Drosophila, its density decreases southwards, where it is gradually replaced by other Drosophila species. This study describes variation in the mitochondrial Cyt b gene of D. obscura from several European populations. We observed a large number of haplotypes, together with the structuring of genetic variation. Genetic variation is higher in the west where O1 and related divergent haplotypes dominate. In the east, the O2 haplotype is most frequent, together with haplotypes that recently arose from it. In the central part of the species range, both O1 and O2 are equally present, along with many others. These data reveal signs of population expansions that probably happened earlier in the west, and more recently in the east. Though our conclusions are based on only one genetic marker, limiting the power of the analysis, the results imply either postglacial expansion from two unique sources or, more likely, eastwards stepping-stone expansion. This study adds important information on genetic variation and phylogeography to the obscure biology of D. obscura, a species that has the potential to become an interesting model in evolutionary biology and conservation genetics. peerReviewed

Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.

The cross-species transmission (CST) of pathogens can have dramatic consequences, as highlighted by recent disease emergence events affecting human, animal and plant health. Understanding the ecological and evolutionary factors that increase the likelihood of disease agents infecting and establishing in a novel host is therefore an important research area. Previous work across different pathogens, including rabies virus (RABV), found that increased evolutionary distance between hosts reduces the frequency of cross-species transmission and of permanent host shifts. However, whether this effect of host relatedness still holds for transmission among recently diverged hosts is not well understood. We aimed to ask if high host relatedness can still increase the probability of a host shift between more recently diverged hosts, and the importance of this effect relative to ecological predictors. We first addressed this question by quantifying the CST frequency of RABV between North American bat species within the genus Myotis, using a multi-decade data set containing 128 nucleoprotein (N) RABV sequences from ten host species. We compared RABV CST frequency within Myotis to the rates of CST between nine genera of North American bat species. We then examined whether host relatedness or host range overlap better explains the frequency of CST seen between Myotis species. We found that at the within genus scale, host range overlap, rather than host relatedness best explains the frequency of CST events. Moreover, we found evidence of CST occurring among a higher proportion of species, and CST more frequently resulting in sustained transmission in the novel host in the Myotis dataset compared to the multi-genus dataset. Our results suggest that among recently diverged species, the ability to infect a novel host is no longer restricted by physiological barriers but instead is limited by physical contact. Our results improve predictions of where future CST events for RABV might occur and clarify the relationship between host divergence and pathogen emergence.

Objectives: Despite a push for increased local public health capacity, no clear baseline for performance of local health departments (LHDs) exists. The objectives of this study were to quantify the self-reported performance of LHDs on the 10 Essential Public Health Services (EPHSs) and describe the relationships between performance and characteristics of LHDs. Methods: We used data on 2000 LHDs from the 2013 National Profile of Local Health Departments survey to develop principal components analysis–based scores to evaluate each LHD on the performance of EPHSs. Scores ranged from 0 to 100. LHDs that performed no activities within an EPHS had a score of 0, and LHDs that performed all activities within an EPHS had a score of 100. We explored the relationships between EPHS scores and LHD characteristics by using multivariate linear regression and cluster analysis. Results: Performance scores varied greatly by LHDs and EPHSs; however, LHDs typically scored Conclusions: Our results suggest weaknesses in many LHDs’ fulfillment of the EPHSs, particularly in low-population and low-funding settings. LHDs should be given the resources to increase capacity and ensure the EPHSs are met in communities.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, JohnsonJohnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged50 years, as well as the availability of alternative COVID-19 vaccines, is required to guide vaccine decision-making and ensure early recognition and clinical management of TTS.

A key public health issue is the health of the increasing global ageing population. Such a population shift will necessitate changes and improvements to healthcare systems and individual lifestyle behaviours to ensure that adults who are living longer are doing so in good health. Just as in any other age group, adequate nutrition is paramount to ensure optimal physical and mental functioning for older adults. However, the ability to achieve adequate nutritional status will be affected by a range of factors; for example chronic illnesses can have a direct impact on nutritional status, while suffering from poor mental health can affect appetite. This chapter aims to describe the ageing population and nutritional requirements of older adults, present the evidence linking nutrition and chronic disease risk and then summarise the factors that affect dietary intake, nutritional status and malnutrition risk of older adults, including medical, physical, psychological, social and economic factors, which can have both direct and indirect impact on dietary intake.

Background Dietary-based primary prevention guidelines for chronic kidney disease (CKD) treatment are lacking due to limited evidence. Single nutrient intake studies do not account for complex dietary interactions. We assessed associations between dietary patterns and renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). Design A cross-sectional observational study used NICOLA baseline dietary data collected between February 2014 and March 2016 via a food frequency questionnaire for 2590 participants aged ≥ 50 years. Principal component analysis identified a posteriori dietary patterns. Renal function was characterised by estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin-C. Associations were assessed according to quintiles of dietary pattern adherence and multivariable regression analysis examined associations with eGFR. Results Variation in three dietary patterns was significantly associated with eGFR. After adjustment for potential confounders, participants with least adherence to the ‘healthy’ dietary pattern 1 had a mean eGFR 3.4 ml/min/1.73m2 (95% confidence interval, [CI] − 5.0, − 1.7, p 2 (CI 0.2, 3.5, p = 0.03) higher than those with highest adherence. Participants with lowest adherence to dietary pattern 3, characterised by a high consumption of alcohol and coffee, had a mean eGFR 1.8 ml/min/1.73m2 (− 3.5, − 0.01, p = 0.05) lower than those with greatest adherence. Conclusions Our findings identify independent associations between dietary patterns and eGFR. These findings can inform the development of diet-related primary prevention advice for CKD.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. Methods Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. Findings Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. Interpretation Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. Funding None.

Introduction:Full nutritional assessments are currently complex and invasive. There is a need for a non-invasive, timely and cost-effective method to assess nutritional status. Evidence indicates the usefulness of saliva in diagnosing oral or systemic disorders. Saliva is suggested to be a reliable and non-invasive matrix in which to measure nutritional biomarkers. The aim of this work was to systematically review the evidence for salivary biomarkers as indicators of nutritional status.Materials and Methods:Studies identifying salivary biomarkers in relation to nutritional status or dietary intake outcomes were included. A search strategy combined terms “saliva” AND “biomarkers” AND “nutrition”. Four databases were searched, MEDLINE, EMBASE, Web of Science and Scopus. All study designs conducted in humans of all ages, from all countries and settings were included. Non-English and animal studies were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool where applicable. (PROSPERO Registration Number:CRD42018107667)Results:6585 papers were identified, 4836 papers remained after removing duplicates, 4715 were irrelevant, 134 full-texts were assessed for eligibility and 64 papers included in the final analysis. A number of potential salivary biomarkers related to nutritional status were identified including: total protein, albumin, prealbumin, transferrin, ferritin and iron. Total protein levels in saliva in malnourished individuals were significantly different to controls in 7/10 studies (70%). In one study conducted in individuals with iron deficiency anaemia (IDA), total protein was significantly different to controls. Albumin levels in malnourished individuals were significantly different to controls in 5/8 studies (62.5%). Prealbumin and transferrin levels in malnourished individuals were significantly different to controls in 3/3 studies (100%). In one study conducted in malnourished individuals, salivary ferritin levels was significantly different to controls. Ferritin levels in individuals with IDA were significantly different to controls in 3/3 studies (100%). Iron levels in individuals with IDA were significantly different in 2/2 studies (100%). However, even within the studies above where significant differences existed, the direction of salivary biomarker differences was sometimes inconsistent. For example, total protein in malnourished individuals was significantly lower than controls in three studies, higher in three studies and one showed mixed findings. In addition, overall the quality of evidence available was very poor.Discussion:Despite conflicting evidence in salivary nutritional biomarkers in individuals with malnutrition or IDA, saliva may be a useful non-invasive matrix to assess nutritional status. Further high quality research exploring the utility of these biomarkers is required.

IntroductionChewing a greater number of chews per bite has been shown to increase fullness, lower hunger levels and lead to a lower energy intake, when compared to chewing each bite fewer times. Increased levels of fullness and decreased levels of hunger have also been observed after consuming harder textured foods which require more chewing activity and have a longer oro-sensory exposure time. The aim of this study was to investigate whether consumption of foods differing in texture, classified as ‘fast’ or ‘slow’ foods, combined with differences in oral processing behaviours (chewing normally or more slowly), has an impact on self-reported hunger, fullness and satiety outcomes.Materials and MethodsThis is an interim analysis of a randomised crossover experiment designed to test the impact of both oral processing behaviours and food texture on self-reported hunger, fullness and satiety. Participants consumed two breakfasts of different texture (a ‘fast’ yoghurt and fruit compote option, and a ‘slow’ granola option) twice; once at their normal rate of eating and once after being instructed to eat slowly. Measures of self-reported appetite (hunger, fullness, satiety, desire to eat and prospective food consumption) were assessed using a visual analogue scale at three time points; baseline (minimum 20 minutes before consumption), immediately pre-consumption and post-consumption. Statistical analysis was conducted in SPSS; paired sample t tests and one-way analysis of variance was conducted to measure whether change in appetite ratings between the time points differed between the four breakfast options.ResultsData were collected from 16 healthy volunteers (study aiming to recruit n = 21; mean age 32.1 y, female n = 13, 81.3%). For all four breakfast options, levels of hunger, desire to eat and prospective food consumption significantly decreased, and levels of fullness and satiety significantly increased between both baseline and post-consumption, (p < 0.05) and between pre-consumption and post-consumption (p < 0.05). However, amongst the four breakfast options, no significant differences were observed in change in these appetite measures between baseline and post-consumption and pre- and post-consumption (p > 0.05).DiscussionThis interim analysis demonstrates no differences in mean change in appetite measures for breakfast options of different texture chewed normally or more slowly. Analysis of the full study will determine the effect of oral processing behaviours and food texture on self-reported hunger, fullness and satiety outcomes.

This study examined the relationship between maternal social stability and household residency among youth in vulnerable families. Data on the household residency of biological children (under 18 years of age) was collected from 259 mothers in Baltimore, Maryland. Only half (50%) of the mothers lived with at least one of their biological children. Multivariate logistic regression analyses were conducted to determine which maternal characteristics and stability factors predicting the likelihood of a child not living with their biological mother. A history of mental health diagnoses as well as economic and housing instability were the strongest predictors of children not living with their biological mothers. Social stability factors such as incarceration history, and receipt of food stamps were not associated with an increased likelihood that children were not living with their biological mother. Maternal economic and housing instability may be the basis on which vulnerability begins for youth. These findings serve as the foundation for future researchers interested in identifying factors that may moderate or mediate the complex relationship between maternal stability and childhood outcomes.

ObjectiveDoctors play an important role in the identification of nutritional disorders and as advocates for a healthy diet, and although the key tenets of good nutrition education for medical students have been discussed, reports on implementation are sparse. The present commentary responds to a gap in UK medical students’ understanding of nutrition and public health and suggests ways to improve it.DesignWe review literature about nutrition education in medical schools and discuss a 6-week elective in public health nutrition for medical students. We discuss suggested competencies in nutrition and compare means of students’ confidence and knowledge before and after.SettingA nutrition and public health elective in a UK medical school, discussing advocacy, motivational interviewing, supplements, nutritional deficits, parenteral nutrition, obesity services. We utilised multidisciplinary teaching approaches including dietitians, managers and pharmacists, and students implemented a public health activity in a local school.SubjectsFifteen final-year medical students were enrolled; sixty school pupils participated in the public health activity.ResultsThe students were not confident in nutrition competencies before and were taught less than European counterparts. Students enjoyed the course, had improved knowledge, and felt more confident in interviewing and prescribing supplements. Feedback from the local school was positive.ConclusionsStudents in our UK medical school were not confident in their required competencies within the confines of the current educational programme. An elective course can improve medical students’ knowledge. Similar courses could be implemented in other medical schools to improve nutrition and public health knowledge and practice in future doctors.

Objectives: With a decreased number of teeth, a reduction in chewing function can contribute to changes in food choices and ultimately impact on overall nutritional status. This study compared the impact of two tooth replacement strategies for partially dentate older patients on masticatory performance and nutritional status.Methods: Patients aged 65 years and older were randomly allocated to two different treatment groups. For the RPDP-group (removable partial dental prostheses) each participant was restored to complete dental arches with cobalt-chromium removable prostheses. For the SDA-group (shortened dental arch), participants were restored to 10 occluding pairs of natural and replacement teeth using adhesive bridgework. Masticatory performance was assessed with a colour-mixing ability test. Each patient provided haematological samples that were screened for biochemical markers of nutritional status. Patients were also assessed using the Mini Nutritional Assessment (MNA).Results: Eighty-nine patients completed the test for masticatory performance and provided blood samples and MNA scores at baseline (BL) and after 12 months (12 m). Masticatory performance (p < 0.001) and MNA (p < 0.05) increased significantly in both groups, but no significant between group differences were noted. A mixed picture was observed for nutrition biomarkers. Mixed-effect linear regression models did not demonstrate that nutritional status could be predicted from masticatory performance.Conclusions: These results indicate that prosthodontic rehabilitation according to the principles of the SDA is equivalent to RPDPs in terms of restoration of chewing capacity for partially dentate older patients. However, masticatory performance may only have minor associations with nutritional status for this patient group.Clinical significance: Replacing teeth with either RPDPs or SDA provides a prerequisite for efficient chewing. Further research is required to determine the impact of oral rehabilitation coupled with nutritional counselling for this patient population.

OBJECTIVES: Adults with poor oral health have been shown to consume poorer quality diets with lower intakes of fibre and protein; reporting difficulty consuming foods that are components of a Mediterranean Diet (MD) such as nuts and fruit(1,2,3). The aim of this analysis was to analyse data from a 12-month pilot cluster randomised study evaluating a peer support MD intervention in Northern Ireland, to investigate whether self-reported oral health status had an impact on change in Mediterranean Diet Score (MDS) and nutrient intakes between baseline and 6-months in response to advice to adopt a MD. METHODS: 4-day food diary data collected from participants (n = 31, mean age 59.5y) was entered into Nutritics and analysed using SPSS v22. General linear regression models were conducted to investigate whether self-reported oral health status, assessed via questionnaire, was a predictor of mean daily nutrient intakes and MDS at baseline and 6-months, as well as mean change in daily intake and MDS between baseline and 6-months. RESULTS: Significant increases in MDS were observed between baseline and 6-months for the three oral health groups (excellent or very good n = 12, good n = 8, fair or poor n = 11; P = 0.021, P = 0.001, P = 0.009 respectively), however there were no significant differences in change in MDS between the groups (P = 0.84). Results from fully adjusted regression models showed self-reported oral health status was not a predictor of MDS at baseline or 6-months or change in MDS from baseline to 6-months (P = 0.83, P = 0.12, P = 0.38 respectively). Change in mean daily intakes of monounsaturated fatty acids, carotene and fibre were, however, observed to be predicted by self-reported oral health status (P = 0.01, P = 0.04, P = 0.01 respectively adjusted for age, gender, years in full-time education and body mass index); with individuals in the excellent or very good oral health group having a significantly greater change in intake between baseline and 6-months compared to individuals in the fair or poor oral health group. CONCLUSIONS: These results highlight self-reported oral health status as a predictor of change in intakes of nutrients associated with MD, but not change in overall MDS, potentially due to small participant numbers. This information linking diet and oral health could be used to effectively develop future nutrition interventions. FUNDING SOURCES: Department for the Economy funded PhD.

Key Points Question Can effective comparison groups be created to assess county-level public health performance? Findings In this cross-sectional study including more than 300 million individuals in the United States, 8 groups of counties with similar sociodemographic characteristics were identified. Percentile ranks for outcome prevalence often differed when counties were considered within their cluster in comparison with a nationwide scale. Meaning Supplying counties with peer groups created using sociodemographic similarities may help local health departments to compare progress and share techniques in efforts to address leading public health challenges., Importance Health departments can be grouped together based on sociodemographic characteristics of the population served. Comparisons within these groups can then help with monitoring and improving the health of their populations. Objective To compare county-level percentile rankings on outcomes of smoking, motor vehicle crash deaths, and obesity within sociodemographic peer clusters vs nationwide rankings. Design, Setting, and Participants This cross-sectional, population-based study of demographic and health data from the 2014 Behavioral Risk Factor Surveillance System and the 2016 Robert Wood Johnson Foundation County Health Rankings data set was conducted at 3139 of 3143 US counties and county-equivalents. Four locations were excluded due to incomplete data. Data analysis was conducted between January and August 2017. Exposures Random forest algorithms were used to identify sociodemographic characteristics most associated with the outcomes of interest. These characteristics were race and ethnicity, educational attainment, age, marital status, employment status, sex, and health insurance status. k-means clustering was used to cluster counties based on these sociodemographic characteristics and the percentage of the county classified as rural. Main Outcomes and Measures County-level smoking prevalence, motor vehicle crash death rate, and obesity prevalence. County percentile rankings on the outcomes of interest were compared in the national context and the within-cluster context. Results A total of 318 856 967 individuals (mean [SD] individuals per county, 101 579.2 [326 315]; 161 911 910 women [50.8%]) were represented by the 3139 counties used in this analysis. Eight distinct sociodemographic clusters throughout the United States were found. Cluster-specific percentile rankings for both smoking prevalence and motor vehicle crash death rates improved more than 70 percentile points for several counties in the rural, American Indian cluster compared with the nationwide percentiles. Conversely, the young, urban, middle to high socioeconomic status cluster included counties with cluster-specific percentile rankings that declined by 60 percentile points or more compared with the nationwide rankings for all 3 outcomes of interest. Conclusions and Relevance Comparing county health outcomes on a nationwide or statewide basis fails to adequately account for sociodemographic context. Clustering counties by sociodemographic factors related to the outcome of interest allows a better understanding of other factors that may be shaping the prevalence of health outcomes. These groupings may also aid learning exchange., This cross-sectional study compares US county-level percentile rankings on outcomes of smoking, motor vehicle crash deaths, and obesity within sociodemographic peer clusters vs nationwide rankings.

Many of us think that ordinary objects – such as tables and chairs – exist. We also think that ordinary objects have parts: my chair has a seat and some legs as parts, for example. But once we are committed to the (seemingly innocuous) thesis that ordinary objects are composed of parts, we then open ourselves up to a whole host of philosophical problems, most of which center on what exactly this composition relation is. Composition as Identity (CI) is the view that the composition relation is the identity relation. While such a view has some advantages, there are many arguments against it. In this essay, I discuss several versions of the most common objection against CI, and show how the CI theorist can maintain that these arguments – contrary their initial intuitive appeal – are nonetheless unsound.

Many of us think that ordinary objects – such as tables and chairs – exist. We also think that ordinary objects have parts: my chair has a seat and some legs as parts, for example. But once we are committed to the (seemingly innocuous) thesis that ordinary objects are composed of parts, we then open ourselves up to a whole host of philosophical problems, most of which center on what exactly the composition relation is. Composition as Identity (CI) is the view that the composition relation is the identity relation. While such a view has some advantages, there are many arguments against it. In this essay, I will briefly canvass three different varieties of Composition as Identity, and suggest why one of them should be preferred over the others. Then I will outline several versions of the most common objection against CI. I will suggest how a CI theorist can respond to these charges by maintaining that some of the arguments are invalid. (In part 2, I show how a CI theorist can maintain that the remaining arguments, while valid, are unsound).

Atherosclerosis is a chronic condition that may begin prior to birth, particularly in the presence of factors that act through inflammatory pathways. Inflammation may alter epigenetic marks, and changes in methylation are observed in atherosclerotic lesions. We hypothesised that intrauterine inflammation (chorioamnionitis, which complicates 1-4% of all births in the US) would alter development of early atherosclerosis. We report preliminary findings from a novel mouse model of chorioamnionitis and atherosclerosis. We aim to investigate: 1. the effect of intrauterine inflammation on the development of early atherosclerosis in mice 2. molecular and epigenetic mechanisms Methods: Apolipoprotein E deficient pregnant mice (n=15-19 per group) received LPS (0.1 ng in 5 μl saline) or saline (5 μl) into each amniotic sac on gestational day 15. Offspring were weaned onto a high fat (21% v/v) diet at 4 weeks. Aortae, heart and plasma were collected from 6- and 12-week-old offspring. Aortae were analysed following Haematoxylin and Eosin (H&E) and Oil Red O staining. Heart and aortae cholesterol concentrations were quantified using colorimetric assay. Gene expression (Real-Time PCR) of candidate genes was measured. Results: Intra-amniotic LPS injection induced histological chorioamnionitis. In 6-week-old mice, intrauterine inflammation increased cholesterol concentrations in aorta and cardiac tissue (p Conclusions: Exposure to intrauterine inflammation has complex effects in this model. Contrary to our hypothesis, 12-week-old LPS-treated mice showed decreased intimal area with no other apparent histological differences, however early cholesterol and molecular biology changes exist. Differential epigenetic regulation may be an early underlying mechanism.

Fetal lung growth is critically dependent on the degree to which the lungs are expanded by liquid, although the mechanisms involved are unknown. As thrombospondin-1 (TSP-1) can regulate cell proliferation, attachment, spreading and angiogenesis, we investigated the effects of alterations in fetal lung expansion on TSP-1 expression in sheep. TSP-1 mRNA levels were investigated using Northern blot analysis and in situ hybridization, whereas the protein levels were determined by immunohistochemistry. Early growth response 1 (EGR1) mRNA levels were measured by quantitative real-time PCR. TSP-1 was expressed in type-II alveolar epithelial cells and fibroblasts and its mRNA levels increased from 100.0 +/- 14.0% in control fetuses to 347.5 +/- 73.6% at 36 h of increased lung expansion (P0.05), and were reduced to 39.4 +/- 6.1% of control levels (100.0 +/- 20.4%) at 20 days of decreased lung expansion (P0.05). The percentage of cells positive for TSP-1 mRNA increased from 1.9 +/- 0.4% to 5.2 +/- 0.8% at 36 h of increased fetal lung expansion (P0.01). The proportion of tissue stained positive for TSP-1 protein doubled at 36 h of increased lung expansion (23.3 +/- 2.2%) compared to controls (11.7 +/- 3.2%; P0.05). Conversely, at 20 days of decreased lung expansion, the percentage of tissue that stained positive for TSP-1 was halved (25.7 +/- 3.2%) compared to controls (39.8 +/- 3.3%; P0.05). The increase in TSP-1 expression may be due to increased mRNA levels of the transcription factor EGR1 at 36 h of increased lung expansion (2.7 +/- 0.7-fold of control levels (1.0 +/- 0.2); P0.05). Given the known functions of TSP-1 and its localization within the lung, we speculate that TSP-1 may have a significant role in regulating fetal lung growth.