Handling polymorphic algebraic effects

Algebraic effects and handlers are a powerful abstraction mechanism to represent and implement control effects. In this work, we study their extension with parametric polymorphism that allows abstracting not only expressions but also effects and handlers. Although polymorphism makes it possible to reuse and reason about effect implementations more effectively, it has long been known that a naive combination of polymorphic effects and let-polymorphism breaks type safety. Although type safety can often be gained by restricting let-bound expressions---e.g., by adopting value restriction or weak polymorphism---we propose a complementary approach that restricts handlers instead of let-bound expressions. Our key observation is that, informally speaking, a handler is safe if resumptions from the handler do not interfere with each other. To formalize our idea, we define a call-by-value lambda calculus that supports let-polymorphism and polymorphic algebraic effects and handlers, design a type system that rejects interfering handlers, and prove type safety of our calculus.Comment: Added the errata for the ESOP'19 paper (page 28

Human Papilloma Virus vaccine and cervical cancer screening acceptability among adults in Quebec, Canada

<p>Abstract</p> <p>Background</p> <p>The Pap test has been used for cervical cancer screening for more than four decades. A human papillomavirus (HPV) vaccine has been approved for use in Canada and is commercially available now. These two preventive interventions should be considered simultaneously. General population support is an important factor for the successful combination of these interventions. The study had two objectives: 1) To assess practices, beliefs, and attitudes regarding Pap test screening and HPV immunization; 2) To identify socio-demographic factors for Pap screening and vaccine acceptability.</p> <p>Methods</p> <p>In 2006, 500 adults were invited to participate in a telephone survey in the region of Quebec City (urban and rural population, 600 000), Canada. Some neutral and standardized information on Pap test and HPV was provided before soliciting opinions.</p> <p>Results</p> <p>471 adults (18–69 year-olds) answered the questionnaire, the mean age was 45 years, 67% were female, and 65% had college or university degree. Eighty-six percent of women had undergone at least one Pap-test in their life, 55% in the last year, and 15% from 1 to 3 years ago. Among screened women, the test had been performed in the last three years in 100% of 18–30 year-olds, but only in 67% of 60–69 year-olds (P < 0.0001). Only 15% of respondents had heard of HPV. Eighty-seven percent agreed that HPV vaccines could prevent cervical cancer, 73% that the vaccine has to be administered before the onset of sexual activity, 89% would recommend vaccination to their daughters and nieces. Among respondents < 25 years, 91% would agree to receive the vaccine if it is publicly funded, but only 72% would agree to pay $100/dose.</p> <p>Conclusion</p> <p>There is an important heterogeneity in cervical cancer screening frequency and coverage. Despite low awareness of HPV infection, the majority of respondents would recommend or are ready to receive the HPV vaccine, but the cost could prevent its acceptability.</p

P2P Web service based system for supporting decision-making in cellular manufacturing scheduling

With the increase of the Internet and Virtual Enterprises (VEs), interfaces for web systems and automated services are becoming an emergent necessity. In this paper we propose a Peer-to-peer (P2P) web-based decision-support system for enabling access to different manufacturing scheduling methods, which can be remotely available and accessible from a distributed knowledge base. The XML-based modeling and communication is applied to manufacturing scheduling. Therefore, manufacturing scheduling problems and methods are modeled using XML. The proposed P2P web-based system works as web services, under the SOAP protocol. The system’s distributed knowledge base enables sharing information about scheduling problems and corresponding solving methods in a widened search space, through a scheduling community, integrating a VE. Running several methods enables different results for a given problem, consequently, contributing for a better decision-making. An important aspect is that this knowledge base can be easily and continuously updated by any contributor through the VE. Moreover, through this system once suitable available methods, for a given problem, are identified, it enables running one or more of them, for enabling a better manufacturing scheduling support, enhanced though incorporated fuzzy decision-making proceduresAichi Science and Technology Foundation(PTDC/EME-GIN/102143/2008)info:eu-repo/semantics/publishedVersio

Sarcolemma-localized nNOS is required to maintain activity after mild exercise

Many neuromuscular conditions are characterized by an exaggerated exercise- induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients(1), and some patients experience severe fatigue without any demonstrable somatic disease(2). Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown(2). With no treatment available, this form of inactivity is a major determinant of disability(3). Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase ( nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS- null mice do not have muscle pathology and have no loss of muscle- specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction- induced signalling from sarcolemma- localized nNOS, which decreases cGMP- mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise- induced signalling.Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant ; University of Iowa Cardiovascular Interdisciplinary Research ; National Research Service Award ; National Institute of Arthritis and Musculoskeletal and Skin Diseases ; National Institutes of Health ; Senator Paul D. Wellstone Fellowship ; Muscular Dystrophy Association Development Grant ; Howard Hughes Medical InstituteWe thank M. Anderson and M. Henry for comments, and M. M. Kilburg, K. Uppal, B. J. Steinmann and S. Watkins and members of the Campbell laboratory for scientific contributions. This work was supported in part by a Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant. Y.M.K. was supported by grants from the University of Iowa Cardiovascular Interdisciplinary Research/ National Research Service Award (NRSA) Fellowship, from an individual NRSA Fellowship from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, from the National Institutes of Health (NIH), and from a Senator Paul D. Wellstone Fellowship. E.P.R. was supported by a Muscular Dystrophy Association Development Grant. R.M.W. was supported by the NIH. K.P.C. is an investigator of the Howard Hughes Medical Institute.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62850/1/nature07414.pd

Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset

<p>Abstract</p> <p>Background</p> <p>The primary objective of this study was to determine if elevated antiphospholipid antibody titers were correlated with the presence of preeclampsia/eclampsia, systemic lupus erythematosus (SLE), placental insufficiency, and a prolonged length of stay (PLOS), in women who delivered throughout Florida, USA.</p> <p>Methods</p> <p>Cross-sectional analyses were conducted using a statewide hospital database. Prevalence odds ratios (OR) were calculated to quantify the association between elevated antiphospholipid antibody titers and four outcomes in 141,286 women who delivered in Florida in 2001. The possibility that the relationship between elevated antiphospholipid antibody titers and the outcomes of preeclampsia/eclampsia, placental insufficiency, and PLOS, may have been modified by the presence of SLE was evaluated in a multiple logistic regression model by creating a composite interaction term.</p> <p>Results</p> <p>Women with elevated antiphospholipid antibody titers (n = 88) were older, more likely to be of white race and not on Medicaid than women who did not have elevated antiphospholipid antibody titers. Women who had elevated antiphospholipid antibody titers had an increased adjusted odds ratio for preeclampsia and eclampsia, (OR = 2.93 p = 0.0015), SLE (OR = 61.24 p < 0.0001), placental insufficiency (OR = 4.58 p = 0.0003), and PLOS (OR = 3.93 p < 0.0001). Patients who had both an elevated antiphospholipid antibody titer and SLE were significantly more likely than the comparison group (women without an elevated titer who did not have SLE) to have the outcomes of preeclampsia, placental insufficiency and PLOS.</p> <p>Conclusion</p> <p>This exploratory epidemiologic investigation found moderate to very strong associations between elevated antiphospholipid antibody titers and four important outcomes in a large sample of women.</p

Health seeking behaviour, health system experience and tuberculosis case finding in Gambians with cough

BACKGROUND: Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis. METHODS: During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing ≥ 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray. RESULTS: 122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0 – 106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks. CONCLUSION: The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear

Reusable Components of Semantic Specifications

Semantic specifications of programming languages typically have poor modularity. This hinders reuse of parts of the semantics of one language when specifying a different language – even when the two languages have many constructs in common – and evolution of a language may require major reformulation of its semantics. Such drawbacks have discouraged language developers from using formal semantics to document their designs. In the PLanCompS project, we have developed a component-based approach to semantics. Here, we explain its modularity aspects, and present an illustrative case study: a component-based semantics for Caml Light. We have tested the correctness of the semantics by running programs on an interpreter generated from the semantics, comparing the output with that produced on the standard implementation of the language. Our approach provides good modularity, facilitates reuse, and should support co-evolution of languages and their formal semantics. It could be particularly useful in connection with domain-specific languages and language-driven software development

A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

<p>Abstract</p> <p>Background</p> <p>Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated.</p> <p>Methods</p> <p>A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3$18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination.</p> <p>Conclusion</p> <p>In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.</p

The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience

Peter Doshi and colleagues describe their experience trying and failing to access clinical study reports from the manufacturer of Tamiflu and challenge industry to defend their current position of RCT data secrecy

Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women

<p>Abstract</p> <p>Background</p> <p>Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions.</p> <p>Methods</p> <p>We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction.</p> <p>Results</p> <p>Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%).</p> <p>Conclusions</p> <p>Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and the value of vaccination to women in monogamous relationships.</p