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Online prompt selection for program synthesis
Get PDFLarge Language Models (LLMs) demonstrate impressive capabilities in the domain of program synthesis. This level of performance is not, however, universal across all tasks, all LLMs and all prompting styles. There are many areas where one LLM dominates, one prompting style dominates, or where calling a symbolic solver is a better choice than an LLM. A key challenge for the user then, is to identify not only when an LLM is the right choice of solver, and the appropriate LLM to call for a given synthesis task, but also the right way to call it. A non-expert user who makes the wrong choice, incurs a cost both in terms of results (number of tasks solved, and the time it takes to solve them) and financial cost, if using a closed-source language model via a commercial API. We frame this choice as an online learning problem. We use a multi-armed bandit algorithm to select which symbolic solver, or LLM and prompt combination to deploy in order to maximize a given reward function (which may prioritize solving time, number of synthesis tasks solved, or financial cost of solving). We implement an instance of this approach, called CYANEA, and evaluate it on synthesis queries from the literature in ranking function synthesis, from the syntax-guided synthesis competition, and fresh, unseen queries generated from SMT problems. CYANEA solves 37.2% more queries than the best single solver and achieves results within 4% of the virtual best solver
The Role of Preoperative Weight Loss Interventions on Long-Term Bariatric Surgery Outcomes: A Systematic Review
Get PDFThe percentage of the world’s population with Class II obesity (body mass index (BMI) ≥ 35) and above is increasing annually. Bariatric (elective weight-loss) surgery is performed for less than one percent of eligible patients. A recent Delphi was unable to reach a consensus recommendation for or against mandated weight loss targets prior to bariatric surgery. This systematic review, performed according to the PRISMA 2020 guidelines, looks at the literature to determine whether there is evidence that pre-operative weight loss affects long-term (≥ 5 year) outcomes of bariatric surgery (weight loss, co-morbidity resolution). Methods: MEDLINE, EMBASE, CABI digital library and Cochrane Central Register of Controlled Trials (Central) were searched 1st January 2000 - 1st March 2025. Twenty-one full papers were then assessed and only three papers met the eligibility criteria for inclusion in this review. Results: 1072 patients were included (age range 26-73 years, sleeve: bypass 60.3%:49.7%, F:M 70.2%:29.8%). The studies differed in their pre-operative prepara-tion and selection criteria for surgery: one paper used an intensive pre-operative information course and mandated 5% weight-loss. This study reported a significant association with pre-operative weight loss and long-term outcomes. Two papers had no mandated pre-operative weight-loss target and found there was no association between pre-operative weight loss and long term outcomes. Conclusions: There is limited and conflicting evidence that pre-operative weight loss percentage affects long-term outcomes of bariatric surgery. Further research looking at five-, ten- and twenty-year outcomes for bariatric patients is required, particularly randomised controlled trials or tier one evidence. Keywords: Bariatric surgery, Pre-operative weight loss, Pre-operative optimisation, Pre-operative lifestyle interventions, Long-term outcomes<br/
Pricing event risk:Evidence from concave implied volatility curves
Get PDFWe document that implied volatility (IV) curves of short-term equity options frequently become concave prior to earnings announcements day (EAD), typically reflecting a bimodal risk-neutral distribution for the underlying stock price. Firms with concave IV curves exhibit significantly higher absolute stock returns on EAD and higher realized volatility after the announcement, rendering concavity an ex-ante signal for event risk. Returns on delta-neutral straddles, delta-neutral strangles, and delta- and vega-neutral calendar straddles are negative and significantly lower in the presence of concave IV curves, showing that investors pay a substantial premium to hedge against the gamma risk arising from this event
Cell-Free Protein Synthesis as a Method to Rapidly Screen Machine Learning-Generated Protease Variants
Get PDFMachine learning (ML) tools have revolutionized protein structure prediction, engineering, and design, but the best ML tool is only as good as the training data it learns from. To obtain high-quality structural or functional data, protein purification is typically required, which is both time and resource consuming, especially at the scale required to train ML tools. Here, we showcase cell-free protein synthesis as a straightforward and fast tool for screening and scoring the activity of protein variants in ML workflows. We demonstrate the utility of the system by improving the kinetic qualities of a protease. By rapidly screening just 48 random variants to initially sample the fitness landscape, followed by 32 more targeted variants, we identified several protease variants with improved kinetic properties
Refinement of histologic subtypes and identification of biomarkers linked to unfavorable prognosis in cholangiocarcinoma: The ENSCCA registries’ framework for digital twin advancement
Get PDFBackground & Aims: Cholangiocarcinoma (CCA) displays remarkable anatomical and histological heterogeneity. Besides diagnosis confirmation, histology currently does not have a major role in the management of CCA. We aimed to study the clinical relevance of histological heterogeneity of CCA and putative tissue biomarkers by creating a multicentric digitalized European CCA Histology Registry. Approach & Results: Nine referral centers, participating in the International Cholangiocarcinoma clinical registry, shared samples and data from 293 patients. Histological and immunohistochemistry stains (n=10) were performed. Computed tomography (CT) scans (n=112 cases) were analyzed by morphological and radiomics techniques. A selection of cases (n=18) was processed for spatial transcriptomics analysis. No significant differences in 5-year overall survival (OS) were found in perihilar CCA vs intrahepatic (i) CCA, and in Small Bile Duct (SBD) vs Large Bile Duct (LBD) iCCA. When cases were classified by periodic acid of Schiff (PAS) positivity (mucin content), PAS HIGH LBD iCCA showed a significantly worse 5-year OS compared to PAS LOW iCCA. Multivariate Cox regression identified PAS HIGH LBD iCCA phenotype as an independent predictor of a worse OS. PAS HIGH LBD iCCA subtype showed specific molecular characteristics at spatial transcriptomics and immunohistochemistry; CT scans and serology could distinguish PAS HIGH LBD iCCA phenotype with excellent accuracy. Conclusion: Our data underline the importance of identifying morphological subclasses with a significant prevalence in CCA as a tool for risk stratification and prognosis. The European CCA Histology Registry represents a valuable platform for integrating digital pathology with clinical, radiological, and molecular information as a framework for digital twin advancement.</p
Characteristics associated with alterations in pruritus severity across gestation in intrahepatic cholestasis of pregnancy: a longitudinal cohort study
Get PDFBackground: Pruritus is a common symptom of intrahepatic cholestasis of pregnancy (ICP), yet its relationship with hypercholanaemia and progression across gestation remains unclear. Methods: 139 participants (1997–2020) recruited from nine UK hospitals and ICP Support. Maternal characteristics and serial serum measurements were collected. Pruritus severity was categorized into five levels. Multiple logistic regression was used to evaluate factors associated with pruritus deterioration. Results: Among 139 women, 53 % (61/115) experienced pruritus deterioration. ALT and bilirubin were not significantly associated with severity progression. However, bile acid concentration (OR 2.36, 95 % CI 1.22–4.56) and maternal BMI (OR 2.40, 95 % CI 1.20–4.81) were independent risk factors. A higher risk of pruritus severity deterioration was found in those with peak bile acid concentrations ≥ 100 µmol/L (OR 7.45, 95 %CI 1.43–38.86, p = 0.02). Conclusion: Higher peak bile acid concentrations and maternal BMI are associated with worsening pruritus severity in ICP.</p
A pragmatic double blind remote pilot feasibility randomised controlled trial of a self-management app for people with Sjögren disease
Get PDFObjectives: To pilot and assess the feasibility of a fully remote effectiveness evaluation of a novel smartphone self-management app for people living with Sjögren disease (SjD), including evaluating trial procedures and app engagement.Methods: We conducted a double-blind, randomised, fully-remote pilot feasibility of a self-management smartphone app (Sjogo) containing interactive components with an information-only control app. After completing onboarding procedures, participants were allocated to a trial arm following download from Apple App and Google Play stores. Participants completed symptoms and quality of life measures at baseline and (at two further timepoints (5–7 and 10–13 weeks) after download. Engagement with the app was measured with number and duration of logins.Results: 996 participants downloaded Sjogo to their smartphone. 871 (87.45%) consented to take part in the study and 617 (61.95%) completed the onboarding procedures and baseline measures and were randomised to the full-version of the app (n = 318) or control-version (n = 299). In-app randomisation produced balanced groups. In week 1 engagement was higher in the intervention group m = 4.76 logins (S.D. 8.06) than the control group m = 3.47 (S.D. 2.75). At week 2 engagement dropped in both groups (intervention group m = 1.17, SD 4.56, control m = 0.40, SD 0.93). Outcome completion rates at subsequent timepoints were 36.63% (weeks 5–7) and 27.39% (weeks 10–13).Conclusion: It is feasible to collect data fully remotely, automate trial procedures, and recruit participants to a randomised controlled trial of a self-management smartphone app for people with SjD through app stores. However, app engagement and outcome completion rates could be improved
Relational logics of child maintenance and post-separation economic abuse in minoritized British South Asian Muslim post-divorce families
Get PDFThis paper furthers understandings of post-separation economic abuse in minoritised British South Asian Muslim post-divorce/separated families. We explore the relational logics of child maintenance payment, and propensities to post-separation economic abuse which are especially egregious for British South Asian Muslim women due interlinked factors: economic marginalisation, feminised poverty, gendered asymmetries in domestic finance, socioculturally distinct forms of economic restrictions, legal non-recognition of certain abuses, structural and institutional racialisation precipitating financial exclusion, and harmful immigration rules. We highlight the potential for child maintenance payment to become a means for perpetuating economic abuse post-separation, the state agency’s support to norms of male financial discretion enabling abuse, as well the necessity of the agency in checking economic exploitation where post-separation abuse remains inadequately addressed. We call for further intersectional research into the impact of recent legal developments in this area
Population density drives increased parasitism via greater exposure and reduced resource availability in wild red deer
Get PDFExposure to environmentally transmitted parasites should increase with population density due to accumulation of infective parasites in space. However, resource competition also increases with density, lowering immunity and increasing susceptibility, offering an alternative pathway for density-dependent infection. To test the relationships between these two processes and parasitism, we examined associations between host density, resource availability, immunity, and counts of 3 common helminth parasites using a long-term study of red deer. We found evidence that immunity increased with resource availability while parasite counts declined with immunity. We also found that greater density correlated with reduced resource availability, and while density was positively associated with both strongyle and tissue worm burdens, resource availability was independently and negatively associated with the same burdens. Our results support separate roles of density-dependent exposure and susceptibility in driving infection, providing evidence that resource competition is an important driver of infection, exacerbating effects of density-dependent increases in exposure.</p
Nurse educators' background, education, and experience in digital competence profiles:A descriptive comparative cross-sectional study in four countries
Get PDFAim: To identify and compare the digital competence profiles of nurse educators, the background variables associated with profiles, and the self-assessed level of digital competence in four European countries. Design: A descriptive comparative cross-sectional study. Methods: Data were collected from nurse educators (n = 263) in 36 nursing education organisations in Finland, Malta, Slovakia and Spain. Partitioning around medoids (PAM) clustering was used to identify competence groups, and descriptive and inferential statistics were used to examine the association of nurse educators' background variables. Results: The clustering analysis resulted in two nurse educator digital competence profile groups: high and moderate. The profiles differed based on completed pedagogical studies and teaching experience, with an emphasis on the high competence profile. Educators in the high competence profile group showed greater interest in using educational technology and self assessed their digital competence at a higher level compared to educators in the moderate competence profile group. Nurse educators' lowest digital competence was in the safe and responsible use of technology, such as knowing copyright laws. Conclusion: Despite the heterogeneous background of nurse educators, international continuing professional development needs in digital competence are identified. Nurse educators' continuing education should support the utilisation of technology through pedagogical approaches, and educators' competence in the safe and responsible use of technology (e.g., how to protect digital materials) must be enhanced in nursing education organisations. Implications for the Profession: This study highlights the need to further develop nurse educators' digital competence. Continuing professional development should target preparation in safe and responsible technology use and include pedagogical studies and mentoring from experienced peers. Reporting Method: The STROBE checklist was adhered to in reporting the results. Patient or Public Contribution: Each participating educational organisation assigned a contact person to distribute the survey to the nurse educators.</p
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