Partial type constructors: Or, making ad hoc datatypes less ad hoc

This work is licensed under a Creative Commons Attribution 4.0 International License.Functional programming languages assume that type constructors are total. Yet functional programmers know better: counterexamples range from container types that make limiting assumptions about their contents (e.g., requiring computable equality or ordering functions) to type families with defining equations only over certain choices of arguments. We present a language design and formal theory of partial type constructors, capturing the domains of type constructors using qualified types. Our design is both simple and expressive: we support partial datatypes as first-class citizens (including as instances of parametric abstractions, such as the Haskell Functor and Monad classes), and show a simple type elaboration algorithm that avoids placing undue annotation burden on programmers. We show that our type system rejects ill-defined types and can be compiled to a semantic model based on System F. Finally, we have conducted an experimental analysis of a body of Haskell code, using a proof-of-concept implementation of our system; while there are cases where our system requires additional annotations, these cases are rarely encountered in practical Haskell code

Revue systématique d’essais comparatifs randomisés d’interventions d’abandon du tabac chez les jeunes

Contexte : Bien que l’usage de la cigarette demeure courant parmi les jeunes, on en sait encore bien peu sur la façon de les aider à cesser de fumer. Seulement quelques revues systématiques d’essais comparatifs randomisés (ECR) ont évalué l’efficacité des interventions d’abandon du tabac chez les jeunes.Objectif : Résumer les connaissances sur l’efficacité des interventions visant à aider les jeunes à cesser de fumer en se basant sur des données probantes provenant d’ECR.Sélection des études et extraction des données : Nous avons retenu tous les ECR publiés qui évaluaient les interventions d’abandon du tabac ciblant les jeunes âgés de 20 ans et moins et qui rapportaient l’abstinence au tabac selon une analyse en intention de traiter. Nous avons relevé les études pertinentes provenant de huit revues de synthèse décrivant des études portant sur des interventions d’abandon du tabac publiées entre 2002 et 2006, ainsi qu’une recherche menée dans les bases de données PubMed et PsycINFO entre 2001 et novembre  2006. Nous rapportons l’abstinence au tabagisme au moment du suivi le plus prolongé. Les auteurs ont sélectionné d’un commun accord les données retenues pour cette revue.Résultats : Nous avons identifié 16 ECR auxquels ont participé 6 623 jeunes ; 11 études évaluant des interventions comportementales qui comprenaient 5 764 participants; quatre examinant des interventions pharmacologiques qui comptaient 529 participants ; et une se penchant sur l’acupuncture au laser qui comportait 330 participants. Trois interventions comportementales menées en milieu scolaire sur quatre et une intervention réalisée en milieu de soins de santé sur quatre ont fait augmenter de façon significative l’abstinence au tabac, quatre semaines à 24 mois suivant les interventions. Parmi les quatre ERC qui évaluaient les interventions pharmacologiques réalisées à l’aide soit de bupropion, de timbres ou de gommes à la nicotine, une étude, où le timbre à la nicotine a été utilisé en combinaison avec un counseling cognitivo-comportemental, a montré une hausse marquée, quoique non significative, de l’abstinence six mois après la date d’abandon.Conclusion : Il existe encore peu de preuves démontrant l’efficacité des interventions d’abandon du tabac chez les jeunes. Quatre programmes en milieu scolaire et une intervention dans un établissement de santé ont mis en évidence une certaine efficacité, tandis que pour la thérapie pharmacologique, les résultats ne sont pas encore concluants.Background: Cigarette use remains common among young people but little is known about how to help adolescent smokers quit. There are few systematic reviews of randomized controlled trials (RCTs) that evaluate the effectiveness of cessation interventions for youth.Objective: To synthesize knowledge on the effectiveness of cessation interventions targeted to youth based on evidence from RCTs.Selection of studies and data extraction: We retained all published RCTs with intention to treat analyses that evaluated cessation interventions targeted to youth aged ≤ 20 years. Relevant studies were identified from eight review articles of smoking cessation intervention studies published between 2002 and 2006, and from a search conducted in PubMed and PsycINFO databases from 2001 to November 2006. The outcome of primary interest was abstinence at the longest reported follow-up. Extraction of data was by consensus of the authors. Results: We identified 16 RCTs with a total of 6623 participants; 11 studies that included 5764 participants evaluated behavioural interventions, four with 529 participants evaluated pharmacological interventions, and one with 330 participants evaluated a laser acupuncture intervention. Three of four behavioural interventions conducted in school settings, and one of four conducted in a health care setting significantly increased abstinence four weeks to 24 months after the interventions. Of four RCTs that evaluated pharmacological interventions using either bupropion or nicotine patch or gum, one study using the nicotine patch coupled with cognitive-behavioural counselling showed a marked albeit non-significant increase in abstinence six months after quit date.Conclusion: There is still limited evidence demonstrating the efficacy of smoking cessation interventions in youth. Four school-based programs and one intervention in a health care setting have shown efficacy, while results for pharmacological therapy are inconsistent across studies.Contexto: si bien el tabaco sigue siendo de uso corriente entre los jóvenes, todavía no se sabe mucho sobre cómo ayudarlos a dejar de fumar. Solamente algunas revisiones sistemáticas de ensayos comparativos aleatorizados han evaluado la eficacia de las intervenciones dirigidas a lograr el abandono del tabaco entre los jóvenes.Objetivo: resumir los conocimientos sobre la eficacia de las intervenciones destinadas a ayudar a jóvenes a dejar de fumar sobre la base de los datos probados de los ensayos comparativos aleatorizados.Selección de estudios y extracción de datos: hemos retenido todos los ensayos comparativos aleatorizados publicados, que evalúan las intervenciones de abandono del tabaco en los jóvenes de 20 años y menos, y que informan sobre la abstinencia de tabaco, según un análisis que tiene la intención de tratar. Hemos seleccionado los trabajos pertinentes provenientes de ocho revistas de síntesis, que describen estudios referidos a intervenciones de abandono del tabaco publicados entre 2002 y 2006, así como una investigación llevada a cabo en las bases de datos PubMed et PsycINFO, realizada entre 2001 y noviembre de 2006. Informamos sobre la abstinencia del tabaquismo en el momento de seguimiento más prolongado. Los autores han seleccionado de común acuerdo los datos retenidos por esta revista.Resultados: hemos identificado dieciséis estudios comparativos aleatorizados en los que participaron 6.623 jóvenes; once estudios que evalúan las intervenciones comportamentales, con 5.764 participantes; cuatro que examinan las intervenciones farmacológicas en las que intervienen 529 participantes y uno que se centra en la acupuntura al láser, con 330 participantes. Tres intervenciones comportamentales realizadas en medio escolar de cada cuatro y una intervención realizada en el medio de la atención sanitaria de cada cuatro, aumentaron de manera significativa la abstinencia al tabaco, cuatro semanas a 24 meses después de las intervenciones. Entre los cuatro estudios comparativos aleatorizados que evaluaban las intervenciones farmacológicas, realizadas ya sea con ayuda de bupropion, de parches o de gomas de mascar a la nicotina, uno de ellos, en el que se utilizó un parche de nicotina en combinación con orientación psicológica cognitivo-comportamental, indicó un aumento marcado, aunque no significativo, de la abstinencia, seis meses después de la fecha de abandono.Conclusión: existen todavía pocas pruebas que demuestren la eficacia de las intervenciones de abandono del tabaco entre los jóvenes. Cuatro programas en medio escolar y una intervención en un establecimiento de salud evidenciaron una cierta eficacia, mientras que los resultados no son todavía concluyentes en lo que se refiere a la terapia farmacológica

Structures of EccB\u3csub\u3e1\u3c/sub\u3e and EccD\u3csub\u3e1\u3c/sub\u3e from the Core Complex of the Mycobacterial ESX-1 Type VII Secretion System

Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD1has a ubiquitin-like fold and forms a dimer with a negatively charged groove. Conclusions: These structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies

Huntingtin Fragments and SOD1 Mutants Form Soluble Oligomers in the Cell

Diffusion coefficients of huntingtin (Htt) fragments and SOD1 mutants expressed in cells were measured using fluorescence correlation spectroscopy. The diffusion mobilities of both non-pathological Htt fragments (25 polyQs) and pathological Htt fragments (103 polyQs) were much slower than expected for monomers suggesting that they oligomerize. The mobility of these fragments was unaffected by duration of expression or by over-expression of Hsp70 and Hsp40. However in cells with HttQ103 inclusions, diffusion measurements showed that the residual cytosolic HttQ103 was monomeric. These results suggest that both non-pathological and pathological Htt fragments form soluble oligomers in the cytosol with the properties of the oligomers determining whether they cause pathology. SOD1 with point mutations (A4V, G37R, and G85R) also had slower diffusional mobility than the wild-type protein whose mobility was consistent with that of a dimer. However, the decrease in mobility of the different SOD1 mutantsdid not correlate with their known pathology. Therefore, while soluble oligomers always seem to be present under conditions where cell pathology occurs, the presence of the oligomers, in itself, does not determine the extent of neuropathology

FreezeML:Complete and Easy Type Inference for First-Class Polymorphism

ML is remarkable in providing statically typed polymorphism without the programmer ever having to write any type annotations. The cost of this parsimony is that the programmer is limited to a form of polymorphism in which quantifiers can occur only at the outermost level of a type and type variables can be instantiated only with monomorphic types. Type inference for unrestricted System F-style polymorphism is undecidable in general. Nevertheless, the literature abounds with a range of proposals to bridge the gap between ML and System F. We put forth a new proposal, FreezeML, a conservative extension of ML with two new features. First, let- and lambda-binders may be annotated with arbitrary System F types. Second, variable occurrences may be frozen, explicitly disabling instantiation. FreezeML is equipped with type-preserving translations back and forth between System F and admits a type inference algorithm, an extension of algorithm W, that is sound and complete and which yields principal types.Comment: 48 pages, 23 Figures. Accepted for PLDI 202

Access to primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in Canada: a geographic analysis

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Cardiac magnetic resonance findings predict increased resource utilization in elective coronary artery bypass grafting

Morbidity following CABG (coronary artery bypass grafting) is difficult to predict and leads to increased healthcare costs. We hypothesized that pre-operative CMR (cardiac magnetic resonance) findings would predict resource utilization in elective CABG. Over a 12-month period, patients requiring elective CABG were invited to undergo CMR 1 day prior to CABG. Gadolinium-enhanced CMR was performed using a trueFISP inversion recovery sequence on a 1.5 tesla scanner (Sonata; Siemens). Clinical data were collected prospectively. Admission costs were quantified based on standardized actual cost/day. Admission cost greater than the median was defined as 'increased'. Of 458 elective CABG cases, 45 (10%) underwent pre-operative CMR. Pre-operative characteristics [mean (S.D.) age, 64 (9) years, mortality (1%) and median (interquartile range) admission duration, 7 (6–8) days] were similar in patients who did or did not undergo CMR. In the patients undergoing CMR, eight (18%) and 11 (24%) patients had reduced LV (left ventricular) systolic function by CMR [LVEF (LV ejection fraction) <55%] and echocardiography respectively. LE (late enhancement) with gadolinium was detected in 17 (38%) patients. The average cost/day was $2723. The median (interquartile range) admission cost was$19059 ($10891–157917). CMR LVEF {OR (odds ratio), 0.93 [95% CI (confidence interval), 0.87–0.99]; P=0.03} and SV (stroke volume) index [OR 1.07 (95% CI, 1.00–1.14); P=0.02] predicted increased admission cost. CMR LVEF (P=0.08) and EuroScore tended to predict actual admission cost (P=0.09), but SV by CMR (P=0.16) and LV function by echocardiography (P=0.95) did not. In conclusion, in this exploratory investigation, pre-operative CMR findings predicted admission duration and increased admission cost in elective CABG surgery. The cost-effectiveness of CMR in risk stratification in elective CABG surgery merits prospective assessment

Inferences Drawn from a Risk Assessment Compared Directly with a Randomized Trial of a Home Drinking Water Intervention

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk = −365 cases/year, sham minus active; 95% confidence interval (CI), −2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches

Determinants of Moral Judgments Regarding Budgetary Slack:An Experimental Examination of Pay Scheme and Personal Values

We study moral judgments regarding budgetary slack made by participants at the end of a participative budgeting experiment in which an expectation for a truthful budget was present. We find that participants who set budgets under a slackinducing pay scheme, and therefore built relatively high levels of budgetary slack, judged significant budgetary slack to be unethical on average, whereas participants who set budgets under a truth-inducing pay scheme did not. This suggests that the slack-inducing pay scheme generated a moral frame by setting economic self-interest against common social norms such as honesty or responsibility. We also find that participants who scored high in traditional values and empathy on a pre-experiment personality questionnaire (JPI-R) were more likely to judge significant budgetary slack to be unethical. These results suggest that financial incentives play a role in determining the moral frame of the budgeting setting and that personal values play a role in determining how individuals respond to that moral frame