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Abstract Background In Singapore, research teams seek informed patient consent on an ad hoc basis for specific clinical studies and there is typically a role separation between operational and research staff. With the enactment of the Human Biomedical Research Act, there is increased emphasis on compliance with consent-taking processes and research documentation. To optimize resource use and facilitate long-term research sustainability at our institution, this study aimed to design and pilot an institution level informed consent workflow (the “intervention”) that is integrated with clinic operations. Methods We used the Consolidated Framework for Implementation Research (CFIR) as the underpinning theoretical framework and conducted the study in three stages: Stage 1, CFIR constructs were used to systematically identify barriers and facilitators of intervention implementation, and a simple time-and-motion study of the patient journey was used to inform the design of the intervention; Stage 2, implementation strategies were selected and mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy; Stage 3, we piloted and adapted the implementation process at two outpatient clinics and evaluated implementation effectiveness through patient participation rates. Results We identified 15 relevant CFIR constructs. Implementation strategies selected to address these constructs were targeted at three groups of stakeholders: institution leadership (develop relationships, involve executive boards, identify and prepare champions), clinic management team (develop relationships, identify and prepare champions, obtain support and commitment, educate stakeholders), and clinic operations staff (develop relationships, assess readiness, conduct training, cyclical tests of change, model and simulate change, capture and share local knowledge, obtain and use feedback). Time-and-motion study in clinics identified the pre-consultation timepoint as the most appropriate for the intervention. The implementation process was adapted according to clinic operations staff and service needs. At the conclusion of the pilot, 78.3% of eligible patients provided institution level informed consent via the integrated workflow implemented. Conclusions Our findings support the feasibility of implementing an institution level informed consent workflow that integrates with service operations at the outpatient setting to optimize healthcare resources for research. The CFIR provided a useful framework to identify barriers and facilitators in the design of the intervention and its implementation process.

In rainfed areas, precipitation variations directly impact wheat growth stages such as emergence, tillering, jointing and booting, and maturity. Evaluating the impact of climate change on precipitation patterns during these critical growth stages is crucial for adapting climate change and ensuring global food security. In this study, projections of five General Circulation models (GCMs) under two shared socioeconomic pathways (SSPs) were used to predict the changing characteristics of precipitation during four main growth stages of wheat in the rainfed region of the Pothwar Plateau, Pakistan. Historical datasets of daily precipitation at six weather stations were analyzed to check the past changes in the precipitation patterns. During the baseline period (1985–2014), the annual average precipitation decreased at a rate of −9.75 mm/decade, while the amount of precipitation during the rabi season (wheat-growing season) decreased at a rate of −20.47 mm/decade. An increase in the precipitation was found during the fourth (flowering) stage of crop growth, while the first three stages experienced a decrease in the precipitation amount. The multimodal ensembled data, under the SSP2-4.5 scenario, revealed a significant decline (at the rate of −16.63 mm/decade) in the future annual precipitation. However, it is projected that, under SSP2-4.5, there may be a slight increase (4.03 mm/decade) in the total precipitation amount during the future rabi season. Under the SSP5-8.5 scenario, average annual precipitation exhibited a slightly increasing trend, increasing by 1.0 mm/decade. However, during the rabi season, there was a possibility of a decrease in precipitation amount, with a rate of 11.64 mm/decade. It is also expected that the precipitation amount may vary significantly during the crown root initiation, jointing and booting, and flowering stages in the near future. These results provide a framework for the planning of wheat production in the Pothwar region of Pakistan, taking into account the potential impact of shifting weather patterns, particularly in terms of uneven precipitation. [ABSTRACT FROM AUTHOR]

We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.

This study aims to investigate the effect of bond issuance announcements and to determine the company characteristics that could influence this effect. The findings reveal positive cumulative average abnormal returns following bond issuances, indicating that the market considers bond offers to be favorable news. Nevertheless, cross-sectional regression analysis shows an insignificant relation of company profitability, growth opportunities, asset tangibility, size, and managerial ownership with cumulative abnormal returns. The results confirm that there is a signaling effect of bond issuance announcements and that this effect is not affected by company characteristics.