Chronic constipation is a prevalent disorder representing a significant public health problem. The management of chronic constipation remains challenging, with people reporting dissatisfaction with available treatment options (1). Current clinical guidelines offer limited dietary recommendations only, and there is a lack of comprehensive evidence-based guidelines for the dietary management of chronic constipation. The aim of this project was to develop the first comprehensive evidence-based dietary guidelines for the management of chronic constipation in adults via a systematic literature review and a Delphi consensus process among an expert steering committee.

The scope of the guidelines included dietary supplements, foods and drinks, and whole diets in adults with chronic constipation. Four systematic reviews and meta-analyses were performed to identify eligible randomised controlled trials (RCTs)(2-5). The findings generated from the meta-analysis of RCTs were then used to develop guideline statements using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and a Delphi consensus survey among a multi-disciplinary expert steering committee. Recommendation statements were produced for treatment response, stool output, gut symptoms, adverse events, and quality of life. Statements were generated based on the findings only where ≥2 RCTs contributed to the meta-analysis (2-5). The “strength of recommendation” was assessed using the GRADE approach. Once statements were generated, they underwent consensus voting amongst the expert steering committee using a modified Delphi survey approach. Recommendation statements with ≥85% agreement were accepted.

The four systematic reviews included a total of 75 RCTs (2-5). Based upon these, 59 dietary recommendation statements were generated and accepted through the Delphi survey. In terms of dietary supplements, 15 recommendation statements related to fibre supplements (overall and specific types), 20 related to probiotics (overall and specific species or strains), 2 to synbiotics (overall), 5 to magnesium oxide, 2 to senna, and 3 to kiwifruit supplements. In terms of foods, 3 recommendation statements related to kiwifruits, 2 to prunes, and 2 to rye bread. In terms of drinks, 5 recommendation statements related to high mineral-containing water. No recommendations were made for whole diet approaches due to lack of evidence. Ten statements had a very low level of evidence, 41 had low level of evidence, and 8 had moderate evidence. Twenty-seven statements were strong recommendations and 32 were qualified recommendations.

These are the first ever comprehensive evidence-based dietary guidelines for the management of constipation. Recommendations were made for several dietary supplements, foods and drinks that have never been previously included in clinical guidelines. These guidelines offer new evidence-based dietary recommendations that can be rapidly implemented into clinical practice, thereby improving clinical care and patient outcomes.

Background: Telemedicine evaluation for treatment of acute stroke patients with IV thrombolysis has been shown to be beneficial. Its usefulness for the evaluation of patients transferred from a primary stroke centre (PSC) to a comprehensive stroke centre (CSC) for endovascular thrombectomy (EVT) is less well defined. Methods: We retrospectively analyzed the Canadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022 to compare treatment metrics and early outcomes between two groups: patients evaluated by telemedicine (TM) and patients evaluated in person (non-TM) at the PSC prior to CSC transfer. Results: We included 3317 patients who were transferred from a PSC to a CSC for: 888 TM and 2429 non-TM. There were no major differences in baseline characteristics, including intravenous thrombolysis administration, though the TM group included more men. TM patients had longer onset-to-puncture times (441 vs 403 minutes, p<0.001) and higher symptomatic intracerebral hemorrhage (sICH) rates (7.4% vs 3.7%, p<0.001), but CSC door-to-puncture times and successful recanalization rates did not differ. Conclusions: Patients transferred to a CSC for EVT first evaluated by TM had similar characteristics to those evaluated in person at the PSC, but longer onset-to-puncture times and higher sICH rates.

Background: Accessible ambulatory neurology care can reduce the need for inpatient evaluation. Aligning patient demand (service requests) with provider and space resources can optimize ambulatory clinic flow. In response to increasing referral volumes and wait times for neurologist access, a quality improvement initiative was undertaken to address demand. Methods: Process mapping and root cause analysis demonstrated access challenges and referral processing errors. Audit of 968 accepted referrals revealed variation in triage processes and decisions for referral questions. Neurologists defined inclusion criteria to specialty programs, based on referral questions. Referral management transitioned to a central intake model, reducing intra- and inter-clinic triage variability. Guidelines were established to prevent triage duplication and standardize appointment management. The primary outcome was accepted referrals per month. Secondary outcomes were referral rejection rate and neurology wait times. Results: Significantly more referrals were received per month post intervention (987 vs. 859, p<0.000). The number of accepted referrals did not change (p=0.147). Referral rejection rate increased from 21% to 31 % (p<0.000). Wait times increased by 16% (p=0.003). Conclusions: Referral management helped respond to increased referral requests. Despite no change in accepted referrals, wait times increased, suggesting a significant capacity problem and focus for further work.

Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

Here we analyse the archival data for a set of 27 Transiting Exoplanet Survey Satellite Targets of Interest in search for artificially generated radio signals, or ‘technosignatures’, interrupted by occultation. Exoplanetary eclipses are notable events to observe in the search for technosignatures, as they mark the geometrical alignment of the target, its host star, and Earth. During an eclipse event, any signal emanating from the target of interest should cease for the duration of the eclipse and resume after the line-of-sight has been restored. Target observations were made by Breakthrough Listen using Murriyang, the CSIRO Parkes 64-m radio telescope, coupled with the ultra-wide low frequency receiver covering a continuous range of frequencies spanning 704–4 032 MHz inclusive. Each target was observed in a pattern consisting of six back-to-back 5-min source and reference sky positions for comparison during data analysis. We performed a Doppler search for narrowband signals with a minimum signal-to-noise ratio of 10, a minimum drift rate of $\pm\,0.1$ Hz/s, and a maximum drift rate of $\pm\,4.0$ Hz/s using the turboseti pipeline. In the analysis of 1 954 880 signals, 14 639 passed automated radio interference filters where each event was presented as a set of stacked dynamic spectra. Despite manually inspecting each diagram for a signal of interest, all events were attributed to terrestrial radio frequency interference.

Using US quarterly data (1967–2023), including inflation’s post-pandemic surge and decline alongside monetary policies characterized by quantitative easing before refocusing on the 2% target, we utilize traditional and novel econometric tools to assess the stability of key macroeconomic variables’ responses to monetary shocks. Our findings confirm the relevance of a broad Divisia aggregate in understanding monetary policy transmission and highlight its empirical importance in explaining output and price dynamics across decades. Time-varying impulse response functions (IRFs) reveal consistent and puzzle-free price responses to Divisia-based monetary shocks throughout the sample, aligning with theory. Time-varying IRFs indicate that pandemic-related outliers in GDP (2020Q2) do not disrupt results. In contrast, Fed Funds rate or shadow policy interest rate shocks often yield puzzling outcomes across earlier and extended periods.

Primary production is fundamental to ecosystems, and in many extreme environments production is facilitated by microbial mats. Microbial mats are complex assemblages of photo- and heterotrophic microorganisms colonizing sediment and soil surfaces. These communities are the dominant producers of the McMurdo Dry Valleys, Antarctica, where they occupy lentic and lotic environments as well as intermittently wet soils. While the influence of microbial mats on stream nutrient dynamics and lake organic matter cycling is well documented, the influence of microbial mats on underlying soil is less well understood, particularly the effects of microbial mat nitrogen and carbon fixation. Taylor Valley soils occur across variable levels of inorganic phosphorus availability, with the Ross Sea drift containing four times that of the Taylor drifts, providing opportunities to examine how soil geochemistry influences microbial mats and the ecological functions they regulate. We found that inorganic phosphorus availability is positively correlated with microbial mat biomass, pigment concentration and nitrogen fixation potential. Additionally, our results demonstrate that dense microbial mats influence the ecological functioning of underlying soils by enriching organic carbon and total nitrogen stocks (two times higher). This work contributes to ongoing questions regarding the sources of energy fuelling soil food webs and the regional carbon balance in the McMurdo Dry Valleys.

Assessing children’s diets is currently challenging and burdensome. Abbreviated FFQ have the potential to assess dietary patterns in a rapid and standardised manner. Using nationally representative UK dietary intake and biomarker data, we developed an abbreviated FFQ to calculate dietary quality scores for pre-school and primary school-aged children. UK National Diet and Nutrition Survey (2008–2016) weekly consumption frequencies of 129 food groups from 4-d diaries were cross-sectionally analysed using principal component analysis. A 129-item score was derived, alongside a 12-item score based on foods with the six highest and six lowest coefficients. Participants included 1069 pre-schoolers and 2565 primary schoolchildren. The first principal component explained 3·4 and 3·0 % of the variation in the original diet variables for pre-school and primary school groups, respectively, and described a prudent diet pattern. Prudent diet scores were characterised by greater consumption of fruit, vegetables and tap water and lower consumption of crisps, manufactured coated chicken/turkey products, purchased chips and soft drinks for both age groups. Correlations between the 129-item and 12-item scores were 0·86 and 0·84 for pre-school and primary school-aged children, respectively. Bland–Altman mean differences between the scores were 0·00 sd; 95 % limits of agreement were −1·05 to 1·05 and −1·10 to 1·10 sd for pre-school and primary school-aged children, respectively. Correlations between dietary scores and nutritional biomarkers showed only minor attenuation for the 12-item compared with the 129-item scores, illustrating acceptable congruence between prudent diet scores. The two 12-item FFQ offer user-friendly tools to measure dietary quality among UK children.

It is widely accepted that we ought to avoid taking excessive risks of causing gratuitous suffering. The practical implications of this truism, however, depend on how we understand what counts as an excessive risk. Precautionary frameworks help us decide when a risk exceeds the threshold for action, with the recent Birch et al. (2021) framework for assessing invertebrate sentience being one such example. The Birch et al. framework uses four neurobiological and four behavioural criteria to provide an evidence-based standard that can be used in determining when precautionary action to promote invertebrate welfare may be warranted. Our aim in this discussion paper is to provide a new motivation for the threshold approach that the Birch et al. framework represents while simultaneously identifying some possible revisions to the framework that can reduce false positives without abandoning the framework’s precautionary objectives.

Objectives/Goals: Clinical trial success requires recruiting and retaining diverse participants. The ER&R Certificate Program trains clinical research professionals (CRPs) in equity, diversity, and inclusion (EDI), addressing biases, and integrating regulatory knowledge with practical skills to foster inclusive research practices. Methods/Study Population: An interdisciplinary Steering Committee, supported by Duke CTSI and DOCR, developed and implemented an engagement, recruitment, and retention certificate program (ER&R) for CRPs. With expert-led instruction, including e-learning, group sessions, and hands-on activities, ER&R integrates EDI into participant engagement practices. Participants complete 7 core courses and at least 3 elective courses, reflecting their unique responsibilities. Program evaluation uses the Kirkpatrick model to assess participant learning, competency, and EDI integration into clinical research. Since launch, the program has expanded to include clinical research trainees from Durham Technical Community College. All elements of the program were designed to allow for sharing across academic medical institutions. Results/Anticipated Results: A total of 202 CRPs and trainees have participated since launch (2020), including 17 trainee participants from Durham Technical Community College (2022–2024). Post-program evaluations showed significant growth in recruitment and retention self-efficacy. An early evaluation of the first 2 cohorts (n = 59) included a self-assessment across defined competencies showing marked increases in comfort across all learning objectives, with notable gains in: Community and Stakeholder Engagement, Recruitment on a Shoestring Budget, Community-Engaged Research Initiatives, and Social Marketing. Participants valued the program’s focus on EDI and sought more practical strategies and peer collaboration. 50 additional institutions have engaged with our implementation consultations and program repository. Discussion/Significance of Impact: Barriers to equitable ER&R exist at the individual, study, and system levels. Addressing these requires more intentional engagement practices. The ER&R certificate program is an innovative model for integrating equity principles with practical and required knowledge and skills training for participant-facing research professionals.

This re-evaluation of the work of Karlheinz Stockhausen is presented as a dialogue between its authors, conducted by email between July and October 2024. The dialogue takes as its starting point a consideration of the continuing relevance of Stockhausen’s music to music today, but begins by tracing the authors’ engagement with this music over the last five decades. The dialogue moves on to the discussion of a series of key aspects of Stockhausen’s work across his creative life, from Kreuzspiel to KLANG: the relationship between his electronic music and his compositional practice for acoustic instruments; form-schemes in his music and, in particular, the development of moment form; and his use of synthesisers. In conclusion, the authors assess Stockhausen’s influence on their own work and the extent of his significance for younger generations of musicians.