Case-Study: An Industry-Academic Engagement Study of the Brewing and Distilling Sector in Ireland

Industry-academic (I-A) engagement models refer to the collaboration between academic institutions and industry partners to co-create and develop educational programmes that are relevant and responsive to industry needs. This study consists of research conducted as part of a 5 month Convene fellowship. It examines aspects such as industry demand, training, competency, knowledge, research projects, and modes of delivery for a proposed Postgraduate Diploma (PgDip, 60 ETS) and Master of Science (MSc, 90 ECTS) in Brewing and Distilling (B&D). This study used an I-A model to capture and collate sector specific feedback and priorities. This was achieved through 40 industry surveys and 28 stakeholder interviews, conducted between February and June 2022. Notably, this engagement model was found to effectively inform curriculum development, clarify industry skill-set expectations, and elucidate sector demands, challenges, knowledge gaps, and opportunities

Right Here Right Now (RHRN) pilot study: testing a method of near-real-time data collection on the social determinants of health

Background: Informing policy and practice with up-to-date evidence on the social determinants of health is an ongoing challenge. One limitation of traditional approaches is the time-lag between identification of a policy or practice need and availability of results. The Right Here Right Now (RHRN) study piloted a near-real-time data-collection process to investigate whether this gap could be bridged. Methods: A website was developed to facilitate the issue of questions, data capture and presentation of findings. Respondents were recruited using two distinct methods – a clustered random probability sample, and a quota sample from street stalls. Weekly four-part questions were issued by email, Short Messaging Service (SMS or text) or post. Quantitative data were descriptively summarised, qualitative data thematically analysed, and a summary report circulated two weeks after each question was issued. The pilot spanned 26 weeks. Results: It proved possible to recruit and retain a panel of respondents providing quantitative and qualitative data on a range of issues. The samples were subject to similar recruitment and response biases as more traditional data-collection approaches. Participants valued the potential to influence change, and stakeholders were enthusiastic about the findings generated, despite reservations about the lack of sample representativeness. Stakeholders acknowledged that decision-making processes are not flexible enough to respond to weekly evidence. Conclusion: RHRN produced a process for collecting near-real-time data for policy-relevant topics, although obtaining and maintaining representative samples was problematic. Adaptations were identified to inform a more sustainable model of near-real-time data collection and dissemination in the future

Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 μM). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes

Female sex but not oestrogen receptor expression predicts survival in advanced gastroesophageal adenocarcinoma—a post-hoc analysis of the go2 trial

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52–90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERβ expression. There was no survival impact according to ERβ expression level. Female sex and younger age were associated with lower ERβ expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .)

Experiences of Self-Management Support Following a Stroke: A Meta-Review of Qualitative Systematic Reviews

Supporting self-management in stroke patients improves psychological and functional outcomes but evidence on how to achieve this is sparse. We aimed to synthesise evidence from systematic reviews of qualitative studies in an overarching meta-review to inform the delivery and development of self-management support interventions.We systematically searched eight electronic databases including MEDLINE, EMBASE and CINAHL for qualitative systematic reviews (published January 1993 to June 2012). We included studies exploring patients', carers' or health care professionals' experiences relevant to self-management support following a stroke, including studies describing the lived experience of surviving a stroke. We meta-synthesised the included review findings using a meta-ethnographic framework.Seven reviews, reporting 130 unique studies, were included. Themes emerging from the reviews were pertinent, consistent and showed data saturation; though explicit mention of self-management support was rare. Our meta-review highlighted the devastating impact of stroke on patients' self-image; the varying needs for self-management support across the trajectory of recovery; the need for psychological and emotional support throughout recovery particularly when physical recovery plateaus; the considerable information needs of patients and carers which also vary across the trajectory of recovery; the importance of good patient-professional communication; the potential benefits of goal-setting and action-planning; and the need for social support which might be met by groups for stroke survivors.The observed data saturation suggests that, currently, no further qualitative research simply describing the lived experience of stroke is needed; we propose that it would be more useful to focus on qualitative research informing self-management support interventions and their implementation. Our findings demonstrate both the on-going importance of self-management support and the evolving priorities throughout the stages of recovery following a stroke. The challenge now is to ensure these findings inform routine practice and the development of interventions to support self-management amongst stroke survivors

The implications of state-dependent tDCS effects in aging:Behavioural response is determined by baseline performance

Young adults typically display a processing advantage towards the left side of space (“pseudoneglect”), possibly as a result of right parietal dominance for spatial attention. This bias is ameliorated with age, with older adults displaying either no strongly lateralised bias, or a slight bias towards the right. This may represent an age-related reduction of right hemispheric dominance and/or increased left hemispheric involvement. Here, we applied anodal transcranial direct current stimulation (atDCS) to the right posterior parietal cortex (PPC; R-atDCS), the left PPC (L-atDCS) and a Sham protocol in young and older adults during a titrated lateralised visual detection task. We aimed to facilitate visual detection sensitivity in the contralateral visual field with both R-atDCS and L-atDCS relative to Sham. We found no differences in the effects of stimulation between young and older adults. Instead the effects of atDCS were state-dependent (i.e. related to task performance at baseline). Relative to Sham, poor task performers were impaired in both visual fields by anodal stimulation of the left posterior parietal cortex (PPC). Conversely, good performers maintained sensitivity in both visual fields in response to R-atDCS, although this effect was small. We highlight the importance of considering baseline task ability when designing tDCS experiments, particularly in older adults