Distributions of flux vacua

We give results for the distribution and number of flux vacua of various types, supersymmetric and nonsupersymmetric, in IIb string theory compactified on Calabi-Yau manifolds. We compare this with related problems such as counting attractor points.Comment: 43 pages, 7 figures. v2: improved discussion of finding vacua with discrete flux, references adde

Autoradiography of diffusible substances : localization of steroids in the testis

The testis contains two cell compartments respectively having an endocrine and an exocrine function. The seminiferous tubules contain a cell renewal system concerned with the production of spermatozoa, and are the exocrine part of the organ. In the other compartment, the interstitial tissue, Leydig cells are found having an endocrine function in the biosynthesis of androgenic steroids. The studies presented in this thesis are mainly concerned with two questions regarding the role of steroids in the testis: -Firstly, which (sub) cellular structures are involved in the synthesis and secretion of androgen in the Leydig cells. -Secondly, which testicular cells or cell organelles are targets for androgen and estrogen action and what" is the route by which these steroids reach their targets. To answer these questions tritiated steroids have been administered to the rat testis under various experimental conditions. The incorporated radioactivity was subsequently localized in tissue sections by autoradiography both at the level of the light and of the electron microscope. Before discussing the merits and the technical problems of this experimental approach an outline of the role of steroids (among other factors) in testis in general and for spermatogenesis in particular will be given

New Vesicle-polymer Hybrids: the parachute architecture

The influence of organized media on polymerization reactions results in many cases in interesting morphologies of the polymeric material. In the present study, vesicle bilayers were used as ordered medium for the free radical polymerization of styrene. Cryo-electron microscopy gives evidence that the polymerization induces phase-separation phenomena leading to parachute-like morphologies. On the basis of general knowledge about vesicles and polymerizations in heterogeneous media, explanations for the observed phenomena are given. Bearing in mind that vesicles are outstanding models for membrane mimetic chemistry, it becomes evident that these findings can be relevant to the investigation of, for example, membrane−protein interactions

Protocol for the development of a global core outcome set for the surgical treatment of differentiated thyroid cancer:a literature review and international Delphi survey

Introduction:There is a lack of consensus on the optimal surgical strategy for differentiated thyroid cancer (DTC), partly due to inconsistent reporting of outcomes. This limits the ability to compare study results, hindering the ability to draw conclusions regarding novel treatment strategies. The development of a core outcome set (COS) reduces heterogeneity in the selection and reporting of clinical trial outcomes. Currently, there is no COS for the surgical treatment of DTC. We aim to reach a global consensus among patients and physicians on the COS for the surgical treatment for patients with DTC of all ages. Methods and analysis: The DTC-COS development will consist of three phases: first, an extensive literature review will be performed to identify reported outcomes in studies regarding surgical treatment for DTC in patients of all ages. Second, a 2-step or 3-step Delphi procedure will be performed to identify a final set of core outcomes out of the selected outcomes from the literature review. For this Delphi survey, both healthcare professionals and patients will be invited. Third, an (online) expert meeting with participants from every stakeholder group is organised to ratify the final core outcome set. The final COS will be reported in accordance with the COS-Standards for Reporting statement. Ethics and dissemination: The medical research ethics committee of the Amsterdam UMC confirmed that the Dutch Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that full approval by the committee is not required. The study is registered in the COMET initiative database (registration number 2597). Results will be presented in peer-reviewed academic journals and at (international) conferences.</p

The Definition of Recurrence of Differentiated Thyroid Cancer:A Systematic Review of the Literature

Background: Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories.Methods: This study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In December 2023, a systematic literature search in MEDLINE and EMBASE was performed for studies reporting on the recurrence of DTC, from January 2018 to December 2023. Studies that did not provide a definition were excluded. Primary outcome was the definition of recurrence of DTC. Secondary outcome was whether studies differentiated between recurrence and persistent disease. Two independent investigators screened the titles and abstracts, followed by full-text assessment and data extraction. The study protocol was registered in PROSPERO, CRD42021291753.Results: In total, 1450 studies were identified. Seventy studies met the inclusion criteria, including 69 retrospective studies and 1 randomised controlled trial (RCT). Median number of patients in the included studies was 438 (range 25-2297). In total, 17 studies (24.3%) reported on lobectomy, 4 studies (5.7%) on total thyroidectomy without RAI, and 49 studies (70.0%) with RAI. All studies defined recurrence using one or a combination of four diagnostic modalities cytology/pathology, imaging studies, thyroglobulin (-antibodies), and a predetermined minimum tumor-free time span. The most common definition of recurrence following lobectomy was cytology/pathology-proven recurrence (47.1% of this subgroup), following total thyroidectomy with RAI was cytology/pathology-proven recurrence and/or anomalies detected on imaging studies (22.4% of this subgroup). No consistent definition was found following total thyroidectomy without RAI. Nine studies (12.9%) differentiated between recurrence and persistent disease.Conclusion: Our main finding is that there is no universally accepted definition for recurrence of DTC in the current studies across any of the treatment categories. The findings of this study will provide the basis for a future, international Delphi-based proposal to establish a universally accepted definition of recurrence of DTC. A uniform definition could facilitate global discussion and enhance the assessment of treatment outcomes regarding recurrence of DTC.</p

Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis

Objective: The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC. Methods: The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database. Results: We included 3902 patients with a median follow-up of 7.8 (4.1-12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2-4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively. Conclusion: The absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors