The Value of Support: STEM Intervention Programs Impact Student Persistence and Belonging.

In response to unwaveringly high attrition from STEM pathways, STEM Intervention Programs (SIPs) support STEM students in effort to increase retention. Using mixed methods (survey and focus groups), we studied students at one university who were either supported or unsupported by SIPs to understand how students may differ in experiences believed to contribute to STEM persistence. We evaluated: sense of belonging, scientific self-efficacy, scientific community values, scientific identity, and STEM involvement. The enrollment status of students two and a half years postsurvey was also tracked. SIP students reported significantly higher science identity and sense of belonging and were more involved in STEM-related activities than counterparts unsupported by SIPs. Differences in these measures were correlated with race/ethnicity, college generation status, and age. Notably, SIP students had higher odds of persisting in STEM than students not supported by SIPs. Focus group data provide additional meaning to the measured survey constructs and revealed nuanced qualitative differences between SIP and non-SIP student experiences. Overall, being involved in a SIP at our institution trends positively with theoretical models that explain STEM student persistence. SIPs have the potential to provide and/or facilitate meaningful and critical support, and students without those intentional supports may be left behind

Multivariate association analysis of the components of metabolic syndrome from the Framingham Heart Study

Metabolic syndrome, by definition, is the manifestation of multiple, correlated metabolic impairments. It is known to have both strong environmental and genetic contributions. However, isolating genetic variants predisposing to such a complex trait has limitations. Using pedigree data, when available, may well lead to increased ability to detect variants associated with such complex traits. The ability to incorporate multiple correlated traits into a joint analysis may also allow increased detection of associated genes. Therefore, to demonstrate the utility of both univariate and multivariate family-based association analysis and to identify possible genetic variants associated with metabolic syndrome, we performed a scan of the Affymetrix 50 k Human Gene Panel data using 1) each of the traits comprising metabolic syndrome: triglycerides, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, blood glucose, and body mass index, and 2) a composite trait including all of the above, jointly. Two single-nucleotide polymorphisms within the cholesterol ester transfer protein (CETP) gene remained significant even after correcting for multiple testing in both the univariate (p < 5 × 10-7) and multivariate (p < 5 × 10-9) association analysis. Three genes met significance for multiple traits after correction for multiple testing in the univariate analysis, while five genes remained significant in the multivariate association. We conclude that while both univariate and multivariate family-based association analysis can identify genes of interest, our multivariate approach is less affected by multiple testing correction and yields more significant results

An update on oral cavity cancer:epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput ‘omics’ technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease. Keywords: Epidemiology, Oral Cancer, Survival, Risk Factors, Squamous Cell Carcinoma, Mouth Neoplasm

Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses

beta-hexosaminidase is an enzyme responsible for the degradation of gangliosides, glycans, and other glycoconjugates containing beta-linked hexosamines that enter the lysosome. GM2 gangliosidoses, such as Tay-Sachs and Sandhoff, are lysosomal storage disorders characterized by beta-hexosaminidase deficiency and subsequent lysosomal accumulation of its substrate metabolites. These two diseases result in neurodegeneration and early mortality in children. A significant difference between these two disorders is the accumulation in Sandhoff disease of soluble oligosaccharide metabolites that derive from N- and O-linked glycans. In this paper we describe our results from a longitudinal biochemical study of a feline model of Sandhoff disease and an ovine model of Tay-Sachs disease to investigate the accumulation of GM2/GA2 gangliosides, a secondary biomarker for phospholipidosis, bis-(monoacylglycero)-phosphate, and soluble glycan metabolites in both tissue and fluid samples from both animal models. While both Sandhoff cats and Tay-Sachs sheep accumulated significant amounts of GM2 and GA2 gangliosides compared to age-matched unaffected controls, the Sandhoff cats having the more severe disease, accumulated larger amounts of gangliosides compared to Tay-Sachs sheep in their occipital lobes. For monitoring glycan metabolites, we developed a quantitative LC/MS assay for one of these free glycans in order to perform longitudinal analysis. The Sandhoff cats showed significant disease-related increases in this glycan in brain and in other matrices including urine which may provide a useful clinical tool for measuring disease severity and therapeutic efficacy. Finally, we observed age-dependent increasing accumulation for a number of analytes, especially in Sandhoff cats where glycosphingolipid, phospholipid, and glycan levels showed incremental increases at later time points without signs of peaking. This large animal natural history study for Sandhoff and Tay-Sachs is the first of its kind, providing insight into disease progression at the biochemical level. This report may help in the development and testing of new therapies to treat these disorders

Psychological therapies for people with intellectual disabilities : an updated systematic review and meta-analysis

Objective The aim of this systematic review and meta-analysis (PROSPERO 2020 CRD42020169323) was to evaluate the efficacy of psychological therapy for people with intellectual disabilities. Method A comprehensive literature search yielded 22,444 studies which were screened for eligibility. Studies were eligible for inclusion if a psychological therapy was delivered to people with intellectual disabilities compared to a group who did not receive the therapy. Thirty-three controlled trials were eligible for inclusion in the review, with 19 included within a DerSimonian-Laird random effects meta-analysis. Subgroup analysis was completed by clinical presentation, and by comparing randomised trials to non-randomised trials, and group-based to individually delivered psychotherapy. Results Following the removal of outliers, psychological therapy for a range of mental health problems was associated with a small and significant effect size, g = 0.43, 95% CI [0.20, 0.67], N = 698. There was evidence of heterogeneity and bias due to studies with small sample sizes and a lack of randomisation. Non-randomised studies were associated with a large effect size, g = 0.90, 95% CI [0.47, 1.32], N = 174, while randomised studies were associated with a small effect size, g = 0.36, 95% CI [0.17, 0.55], N = 438, excluding outliers. Individually delivered psychological therapy was associated with a small and non-significant effect size, g = 0.32, 95% CI [−0.01, 0.65], N = 146, while group-based interventions were associated with a small and significant effect size, g = 0.37, 95% CI [0.05, 0.68], N = 361, again, excluding outliers. Psychological therapy for anger was associated with a moderate effect size, g = 0.60, 95% CI [0.26, 0.93], N = 324, while treatment for depression and anxiety was associated with a small and non-significant effect size, g = 0.38, 95% CI [−0.10, 0.85], N = 216, after outliers were removed. Conclusions Studies are fraught with methodological weaknesses limiting the ability to make firm conclusions about the effectiveness of psychological therapy for people with intellectual disabilities. Improved reporting standards, appropriately powered and well-designed trials, and greater consideration of the nature and degree of adaptations to therapy are needed to minimise bias and increase the certainty of conclusions

Therapists’ experiences of remotely delivering cognitive-behavioural or graded-exercise interventions for fatigue: a qualitative evaluation

Objectives: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) included remotely delivered personalised exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals (therapists’) perspectives of delivering the interventions in the LIFT trial. Methods: A subgroup of therapists who had delivered the PEP and CBA interventions took part in semi-structured telephone interviews. Results: Seventeen therapists (13 women, 4 men) who delivered PEP (n = 8) or CBA (n = 9) interventions participated. Five themes were identified: In ‘The benefits of informative, structured training’, therapists described how they were able to practice their skills, and the convenience of having the LIFT manual to refer to. When ‘Getting into the swing of it’, supporting patients gave therapists the confidence to tailor the content of the manual to each patient. Clinical supervision supported therapists to gain feedback and request assistance when required. In ‘Delivering the intervention’ therapists reported that patients valued the opportunity to address their fatigue and challenge their own beliefs. ‘Challenges in delivering the LIFT intervention’ therapists struggled to work collaboratively with patients who lacked motivation or stopped engaging. Finally, ‘Lift developing clinical skills’ therapists gained confidence and professional satisfaction seeing patients’ fatigue improve. Conclusion: Findings support the value of skills training for rheumatology health professionals to deliver a remote fatigue management intervention tested in the LIFT trial. These insights can inform service provision and clinical practice Lay summary What does this mean for patients ? Fatigue can be a challenge in inflammatory rheumatic diseases (IRDs). The LIFT study (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) explored interventions to support people with fatigue. These were: a cognitive-behavioural approach (CBA), a personalized exercise programme (PEP), or usual care. People with IRDs were chosen randomly to take part in seven sessions of CBA, seven sessions of PEP or usual care. All sessions (aside from the first PEP session) were delivered over the phone. The aim of this study was to explore therapists' experiences of delivering the intervention. Seventeen therapists (13 women and 4 men) took part; eight had delivered the PEP intervention, and 9 delivered the CBA intervention. Therapists who delivered LIFT told us they enjoyed the chance to practice their skills, and that the LIFT manual gave them the confidence to tailor the intervention to each patient. Clinical supervision was valued. Therapists also shared that LIFT improved their skills and they were happy to see patients' fatigue improve over time. These new results can inform clinical practice, and how services are provided

The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis

Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium) of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement.: University of Otago Research Grant (http://www.otago.ac.nz/research/otago004140.html); A grant-in-aid by the School of Medical Sciences, University of Otago (http://osms.otago.ac.nz/); The Mason Foundation (http://research-hub.griffith.edu.au/display/fosc_MASONG); Royal Society of New Zealand Marsden Fund (http://www.royalsociety.org.nz/programmes/funds/marsden/) grant number UOO0711. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Solutions trial: Solution focused brief therapy (SFBT) in 10–17-year-olds presenting at police custody: a randomised controlled trial

Background: Within England, children and young people (CYP) who come into police custody are referred to Liaison and Diversion (L&D) teams. L&D teams have responsibility for liaising with healthcare and other support services while working to divert CYP away from the criminal justice system but have traditionally not provided targeted psychological interventions to CYP. Considering evidence that Solution Focused Brief Therapy (SFBT) leads to a reduction in internalising and externalising behaviour problems in CYP, the aim of this randomised controlled trial (RCT) was to determine whether there is a difference between services as usual (SAU) plus SFBT offered by trained therapists working within a L&D team, and SAU alone, in reducing offending behaviours in 10–17-year-olds presenting at police custody. Methods: Design: two-arm individually RCT with internal pilot and process evaluation. Participants: N = approximately 448 CYP aged 10–17 years presenting at one of three police custody suites in the area served by Lancashire and South Cumbria NHS Foundation Trust (LSCFT) who are referred to the L&D team. Participants will be recruited and allocated to intervention:control on a 1:1 basis. Interviews will be performed with 30–40 CYP in the intervention arm, 15 CYP in the control arm, up to 20 parents/guardians across both arms, up to 15 practitioners, and up to 10 site staff responsible for screening CYP for the trial. Intervention and control: Those allocated to the intervention will be offered SAU plus SFBT, and control participants will receive SAU only. Primary outcome: CYP frequency of offending behaviours assessed through the Self-Report Delinquency Measure (SRDM) at 12 months post-randomisation. Secondary outcomes: criminal offence data (national police database); emotional and behavioural difficulties (self-report and parent/guardian reported); gang affiliation (self-report). Process evaluation: evaluation of acceptability and experiences of the CYP, parents/guardians, site staff and practitioners; fidelity of SFBT delivery. Discussion: This two-arm individually RCT will evaluate the effectiveness of SFBT in reducing offending behaviours in CYP presenting at police custody suites within the area served by LSCFT. Our process evaluation will assess the fidelity of delivery of SFBT, the factors affecting implementation, the acceptability of SFBT in CYP aged 10–17 years and recruitment and reach. We will also examine systems and structures for future delivery, therefore assessing overall scalability. Trial registration: ClinicalTrials.gov ISRCTN14195235. Registered on June 16, 2023