Historical ‘signposts’ and other temporal indicators in the Czech lexicon

This article posits that the Czechs employ a great many historical markers, previously applied to other events of national importance, which help to shape collective memory and right the ‘wrongs’ of the past. It is argued that these temporal indicators share a number of clearly defined characteristics, and that their use is too systematic and calculated to be merely a function of the constraints of the lexicon. The first part of the study considers in detail questions of semantics (especially the distinction between denotation and connotation), the lexicographical sources available to the researcher, and the lexical ‘signpost’ in context, while the second part focuses on practical examples of lexical re-appropriation since 1918, with particular reference to dictionaries and the Czech National Corpus.University of Wolverhampto

Common European Sales Law (CESL) and Private International Law: Some Critical Remarks

This article is an updated and revised version of the contribution published by the author in XI Anuario Español de Derecho Internacional Privado, 2011, 25-61, under the title: “La Propuesta de Reglamento relativo a una normativa común de compraventa europea y el Derecho internacional privado”.La Propuesta de Reglamento del Parlamento Europeo y del Consejo relativo a una normativa común de compraventa europea de 11 de octubre de 2011 (PCESL) introduce una reglamentación material para algunas compraventas transfronterizas que no desplaza la aplicación de las normas de conflicto (en particular de las contenidas de los Reglamentos “Roma I” y “Roma II”). Al contrario, el instrumento opcional contenido en la Propuesta de Reglamento (CESL) presupone la aplicación de la ley de un Estado miembro, como lex contractus. Una vez escogida por las partes, la CESL desplaza a las normas internas cobre compraventa de la ley del Estado miembro. Esta opción del legislador comunitario plantea numerosos problemas e interrogantes acerca de las relaciones entre la CESL y las normas de Derecho internacional privado y en torno a su coexistencia con otros convenios internacionales y el propio acervo comunitario. El análisis de estas relaciones es el objeto del presente estudio, que permite concluir con una valoración negativa de la competitividad internacional de este nuevo instrumento comunitario.The Proposal for a Regulation of the European Parliament and of the Council on a Common European Sales Law of 11 October 2011 (PCESL) introduces a substantive regulation for some cross-border sales contracts that does not displace the application of conflict-of-laws rules (especially those included in “Rome I” and “Rome II” Regulations). On the contrary, the optional instrument included in the Proposal (CESL) presupposes the application of the law of a Member State as lex contractus. Once the parties have chosen the CESL, this regime prevails over the internal rules on sales contracts of the law of that Member State. The formula used by the European legislator gives rise to many concerns and questions about the relationships between the CESL and the conflict-of-laws rules and about its cohabitation with other international conventions and the European acquis itself. The analysis of these relationships is the subject of this article, which concludes with a negative assessment on the international competitiveness of the new European instrument

Familial aggregation and heritability of schizophrenia and co-aggregation of psychiatric illnesses in affected families

Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55-46.92), 6.30 (6.09-6.53), 2.44 (1.91-3.12), and 1.88 (1.64-2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79-6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00-16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34-3.64) for mood disorders and 3.91 (3.35-4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia

Development and validation of Prediction models for Risks of complications in Early-onset Pre-eclampsia (PREP):a prospective cohort study

Background: The prognosis of early-onset pre-eclampsia (before 34 weeks’ gestation) is variable. Accurate prediction of complications is required to plan appropriate management in high-risk women. Objective: To develop and validate prediction models for outcomes in early-onset pre-eclampsia. Design: Prospective cohort for model development, with validation in two external data sets. Setting: Model development: 53 obstetric units in the UK. Model transportability: PIERS (Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia TRial Amsterdam) studies. Participants: Pregnant women with early-onset pre-eclampsia. Sample size: Nine hundred and forty-six women in the model development data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability (external validation) data sets. Predictors: The predictors were identified from systematic reviews of tests to predict complications in pre-eclampsia and were prioritised by Delphi survey. Main outcome measures: The primary outcome was the composite of adverse maternal outcomes established using Delphi surveys. The secondary outcome was the composite of fetal and neonatal complications. Analysis: We developed two prediction models: a logistic regression model (PREP-L) to assess the overall risk of any maternal outcome until postnatal discharge and a survival analysis model (PREP-S) to obtain individual risk estimates at daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) and external validation (of the reduced models in the transportability data), we computed the ability of the models to discriminate between those with and without poor outcomes (c-statistic), and the agreement between predicted and observed risk (calibration slope). Results: The PREP-L model included maternal age, gestational age at diagnosis, medical history, systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum urea concentration, oxygen saturation, baseline treatment with antihypertensive drugs and administration of magnesium sulphate. The PREP-S model additionally included exaggerated tendon reflexes and serum alanine aminotransaminase and creatinine concentration. Both models showed good discrimination for maternal complications, with an optimism-adjusted c-statistic of 0.82 [95% confidence interval (CI) 0.80 to 0.84] for PREP-L and 0.75 (95% CI 0.73 to 0.78) for the PREP-S model in the internal validation. External validation of the reduced PREP-L model showed good performance with a c-statistic of 0.81 (95% CI 0.77 to 0.85) in PIERS and 0.75 (95% CI 0.64 to 0.86) in PETRA cohorts for maternal complications, and calibrated well with slopes of 0.93 (95% CI 0.72 to 1.10) and 0.90 (95% CI 0.48 to 1.32), respectively. In the PIERS data set, the reduced PREP-S model had a c-statistic of 0.71 (95% CI 0.67 to 0.75) and a calibration slope of 0.67 (95% CI 0.56 to 0.79). Low gestational age at diagnosis, high urine protein-to-creatinine ratio, increased serum urea concentration, treatment with antihypertensive drugs, magnesium sulphate, abnormal uterine artery Doppler scan findings and estimated fetal weight below the 10th centile were associated with fetal complications. Conclusions: The PREP-L model provided individualised risk estimates in early-onset pre-eclampsia to plan management of high-or low-risk individuals. The PREP-S model has the potential to be used as a triage tool for risk assessment. The impacts of the model use on outcomes need further evaluation

Ethnicity and the association between anthropometric indices of obesity and cardiovascular risk in women: a cross-sectional study

Objectives: The objectives of this study were to determine whether the cross-sectional associations between anthropometric obesity measures, body mass index (BMI), waist circumference (WC) and waist-to hip ratio (WHR), and calculated 10-year cardiovascular disease (CVD) risk using the Framingham and general CVD risk score models, are the same for women of Australian, UK and Ireland, North European, South European and Asian descent. This study would investigate which anthropometric obesity measure is most predictive at identifying women at increased CVD risk in each ethnic group. Design: Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study. Setting: Population-based survey in Australia. Participants: 4354 women aged 20–69 years with no history of heart disease, diabetes or stroke. Most participants were of Australian, UK and Ireland, North European, South European or Asian descent (97%).Outcome measures: Anthropometric obesity measures that demonstrated stronger predictive ability of identifying women at increased CVD risk and likelihood of being above the promulgated treatment thresholds of various risk score models. Results: Central obesity measures, WC and WHR, were better predictors of cardiovascular risk. WHR reported a stronger predictive ability than WC and BMI in Caucasian women. In Northern European women, BMI was a better indicator of risk using the general CVD (10% threshold) and Framingham (20% threshold) risk score models. WC was the most predictive of cardiovascular risk among Asian women. Conclusions: Ethnicity should be incorporated into CVD assessment. The same anthropometric obesity measure cannot be used across all ethnic groups. Ethnic-specific CVD prevention and treatment strategies need to be further developed

'Linkage' pharmaceutical evergreening in Canada and Australia

'Evergreening' is not a formal concept of patent law. It is best understood as a social idea used to refer to the myriad ways in which pharmaceutical patent owners utilise the law and related regulatory processes to extend their high rent-earning intellectual monopoly privileges, particularly over highly profitable (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while the courts are an instrument frequently used by pharmaceutical brand name manufacturers to prolong their patent royalties, 'evergreening' is rarely mentioned explicitly by judges in patent protection cases. The term usually refers to threats made to competitors about a brand-name manufacturer's tactical use of pharmaceutical patents (including over uses, delivery systems and even packaging), not to extension of any particular patent over an active product ingredient. This article focuses in particular on the 'evergreening' potential of so-called 'linkage' provisions, imposed on the regulatory (safety, quality and efficacy) approval systems for generic pharmaceuticals of Canada and Australia, by specific articles in trade agreements with the US. These 'linkage' provisions have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They require such drug regulators to facilitate notification of, or even prevent, any potential patent infringement by a generic pharmaceutical manufacturer. This article explores the regulatory lessons to be learnt from Canada's and Australia's shared experience in terms of minimizing potential adverse impacts of such 'linkage evergreening' provisions on drug costs and thereby potentially on citizen's access to affordable, essential medicines

Invited Commentary: Treatment Drop-in-Making the Case for Causal Prediction.

Clinical prediction models (CPMs) are often used to guide treatment initiation, with individuals at high risk offered treatment. This implicitly assumes that the probability quoted from a CPM represents the risk to an individual of an adverse outcome in absence of treatment. However, for a CPM to correctly target this estimand requires careful causal thinking. One problem that needs to be overcome is treatment drop-in: where individuals in the development data commence treatment after the time of prediction but before the outcome occurs. In this issue of the Journal, Xu et al. (Am J Epidemiol. 2021;190(10):2000-2014) use causal estimates from external data sources, such as clinical trials, to adjust CPMs for treatment drop-in. This represents a pragmatic and promising approach to address this issue, and it illustrates the value of utilizing causal inference in prediction. Building causality into the prediction pipeline can also bring other benefits. These include the ability to make and compare hypothetical predictions under different interventions, to make CPMs more explainable and transparent, and to improve model generalizability. Enriching CPMs with causal inference therefore has the potential to add considerable value to the role of prediction in healthcare

Alcohol dependence in public policy: towards its (re)inclusion

Public policy on alcohol in the UK relies on health promotion campaigns that encourage individuals who misuse alcohol to make healthier choices about their drinking. Individuals with alcohol-dependence syndrome have an impaired capacity to choose health. As a result, individuals with the worst alcohol misuse problems lie largely outside the reach of choice-based policy. However, such policy has been widely criticized and efforts to reform it are underway. This paper argues that the British Medical Association’s recent attempt to improve policy on alcohol in the UK by introducing strategies which have been shown to control drinking within populations still gives insufficient attention to alcohol dependence. This is because it fails accurately and consistently to characterize alcohol dependence and gives insufficient attention to the social challenges it presents