Design and Implementation of the Andromeda Proof Assistant

Andromeda is an LCF-style proof assistant where the user builds derivable judgments by writing code in a meta-level programming language AML. The only trusted component of Andromeda is a minimalist nucleus (an implementation of the inference rules of an object-level type theory), which controls construction and decomposition of type-theoretic judgments. Since the nucleus does not perform complex tasks like equality checking beyond syntactic equality, this responsibility is delegated to the user, who implements one or more equality checking procedures in the meta-language. The AML interpreter requests witnesses of equality from user code using the mechanism of algebraic operations and handlers. Dynamic checks in the nucleus guarantee that no invalid object-level derivations can be constructed. To demonstrate the flexibility of this system structure, we implemented a nucleus consisting of dependent type theory with equality reflection. Equality reflection provides a very high level of expressiveness, as it allows the user to add new judgmental equalities, but it also destroys desirable meta-theoretic properties of type theory (such as decidability and strong normalization). The power of effects and handlers in AML is demonstrated by a standard library that provides default algorithms for equality checking, computation of normal forms, and implicit argument filling. Users can extend these new algorithms by providing local "hints" or by completely replacing these algorithms for particular developments. We demonstrate the resulting system by showing how to axiomatize and compute with natural numbers, by axiomatizing the untyped lambda-calculus, and by implementing a simple automated system for managing a universe of types

Democratized image analytics by visual programming through integration of deep models and small-scale machine learning

Analysis of biomedical images requires computational expertize that are uncommon among biomedical scientists. Deep learning approaches for image analysis provide an opportunity to develop user-friendly tools for exploratory data analysis. Here, we use the visual programming toolbox Orange (http://orange.biolab.si) to simplify image analysis by integrating deep-learning embedding, machine learning procedures, and data visualization. Orange supports the construction of data analysis workflows by assembling components for data preprocessing, visualization, and modeling. We equipped Orange with components that use pre-trained deep convolutional networks to profile images with vectors of features. These vectors are used in image clustering and classification in a framework that enables mining of image sets for both novel and experienced users. We demonstrate the utility of the tool in image analysis of progenitor cells in mouse bone healing, identification of developmental competence in mouse oocytes, subcellular protein localization in yeast, and developmental morphology of social amoebae

Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature

Background and Purpose: Idarucizumab achieves instant reversal of anticoagulation and enables intravenous thrombolysis (IVT) in dabigatran-treated acute ischemic stroke (AIS) patients. AIS in dabigatran-treated patients is a rare event, therefore the experience is limited. A review of all published cases was performed to evaluate the safety and effectiveness of this therapeutic strategy. Methods: We searched PubMed and Scopus for all published cases of IVT after reversal with idarucizumab in dabigatran-treated AIS patients. The outcomes were safety assessed by hemorhagic transformation (HT), symptomatic intracranial hemorrhage (SICH) and death, and efficacy assessed by National Institutes of Health Stroke Scale (NIHSS) reduction. Results: We identified 251 AIS patients (39,9% females) with an average age of 74 years. HT, SICH, and death were reported in 19 (7.6%), 9 (3.6%), and 21 (8.4%) patients, respectively. Patients experiencing HT presented with more severe strokes (median NIHSS on admission: 21 vs. 8, p < 0.001; OR: 1.12, 95% CI: 1.05-1.20). After IVT there was a significant NIHSS reduction of 6 points (IQR:3-10, p < 0.001) post-stroke and linear regression revealed a correlation of admission NIHSS to NIHSS reduction (p < 0.001). Conclusions: In this systematic review of all published cases of IVT in dabigatran-treated AIS patients after reversal with idarucizumab the rates of HT, SICH and mortality, as well as NIHSS reduction, were comparable with previous studies in non-anticoagulated patients. This provides reassuring evidence about the safety and efficacy of this therapeutic strategy. © Copyright © 2021 Frol, Sagris, Pretnar Oblak, Šabovič and Ntaios

WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy

10.1016/S1470-0328(03)02430-3BJOG: An International Journal of Obstetrics and Gynaecology1109808-818BIOG

Neuropathological criteria of anti-IgLON5-related tauopathy

We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell-adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem. The aim of the current study is to describe the neuropathological features of the anti-IgLON5 syndrome and to provide diagnostic levels of certainty based on the presence of associated clinical and immunological data. The brains of six patients were examined and the features required for the neuropathological diagnosis were established by consensus. Additional clinical and immunological criteria were used to define "definite", "probable" and "possible" diagnostic categories. The brains of all patients showed remarkably similar features consistent with a neurodegenerative disease with neuronal loss and gliosis and absence of inflammatory infiltrates. The most relevant finding was the neuronal accumulation of hyperphosphorylated tau composed of both three-repeat (3R) and four-repeat (4R) tau isoforms, preferentially involving the hypothalamus, and more severely the tegmental nuclei of the brainstem with a cranio-caudal gradient of severity until the upper cervical cord. A "definite" diagnosis of anti-IgLON5-related tauopathy is established when these neuropathological features are present along with the detection of serum or CSF IgLON5 antibodies. When the antibody status is unknown, a "probable" diagnosis requires neuropathological findings along with a compatible clinical history or confirmation of possession of HLA-DRB1*1001 and HLA-DQB1*0501 alleles. A "possible" diagnosis should be considered in cases with compatible neuropathology but without information about a relevant clinical presentation and immunological status. These criteria should help to identify undiagnosed cases among archival tissue, and will assist future clinicopathological studies of this novel disorder

Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation.

BackgroundA previous randomised study suggested that the progestagen, levonorgestrel, given alone in two separate doses each of 0.75 mg caused nausea and vomiting in fewer women and might be more effective than the Yuzpe regimen of combined oral contraceptives for emergency contraception, although the difference was not significant. We compared these two regimens when started within 72 h of unprotected coitus.MethodsWe enrolled in the double-blind, randomised trial 1998 women at 21 centres worldwide. Women with regular menses, not using hormonal contraception, and requesting emergency contraception after one unprotected coitus, received levonorgestrel (0.75 mg, repeated 12 h later) or the Yuzpe regimen (ethinyloestradiol 100 microg plus levonorgestrel 0.5 mg, repeated 12 h later).FindingsOutcome was unknown for 43 women (25 assigned levonorgestrel, 18 assigned Yuzpe regimen). Among the remaining 1955 women, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group compared with 3.2% (31/979) in the Yuzpe regimen group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI 0.18-0.70). The proportion of pregnancies prevented (compared with the expected number without treatment) was 85% (74-93) with the levonorgestrel regimen and 57% (39-71) with the Yuzpe regimen. Nausea (23.1 vs 50.5%) and vomiting (5.6 vs 18.8%) were significantly less frequent with the levonorgestrel regimen than with the Yuzpe regimen (p&lt;0.01). The efficacy of both treatments declined with increasing time since unprotected coitus (p=0.01).InterpretationThe levonorgestrel regimen was better tolerated and more effective than the current standard in hormonal emergency contraception. With either regimen, the earlier the treatment is given, the more effective it seems to be

Multinational comparative clinical trial of long-acting injectable contraceptives: norethisterone enanthate given in two dosage regimens and depot-medroxyprogesterone acetate. A preliminary report

A multicentre phase III clinical trial has been undertaken to compare norethisterone enantate (NET-EN) given by two different treatment regimens and depot-medroxyprogesterone acetate (DMPA). After 18 months of observation, preliminary findings are reported for 1,589 women who received DMPA 150mg every 90 days; 790 women who received NET-EN 200mg every 60 days; and 796 women who received NET-EN, 200mg every 60 days for 6 months, then 200mg every 84 days. The overall discontinuation rates per 100 women were similar for all three treatment groups over the 18 months observation (61.8-63.5 per 100 women). The discontinuation rates for bleeding problems and for personal reasons were also similar for all three treatment groups. However, terminations due to amenorrhoea were significantly higher among DMPA users (12.1 and 17.4 per 100 women at 12 and 18 months) as compared with both NET-EN groups (6.8-8.2 per 100 women at 12 months and 10.4-10.9 per 100 women at 18 months). The only significan