High Dimensional Classification with combined Adaptive Sparse PLS and Logistic Regression

Motivation: The high dimensionality of genomic data calls for the development of specific classification methodologies, especially to prevent over-optimistic predictions. This challenge can be tackled by compression and variable selection, which combined constitute a powerful framework for classification, as well as data visualization and interpretation. However, current proposed combinations lead to instable and non convergent methods due to inappropriate computational frameworks. We hereby propose a stable and convergent approach for classification in high dimensional based on sparse Partial Least Squares (sparse PLS). Results: We start by proposing a new solution for the sparse PLS problem that is based on proximal operators for the case of univariate responses. Then we develop an adaptive version of the sparse PLS for classification, which combines iterative optimization of logistic regression and sparse PLS to ensure convergence and stability. Our results are confirmed on synthetic and experimental data. In particular we show how crucial convergence and stability can be when cross-validation is involved for calibration purposes. Using gene expression data we explore the prediction of breast cancer relapse. We also propose a multicategorial version of our method on the prediction of cell-types based on single-cell expression data. Availability: Our approach is implemented in the plsgenomics R-package.Comment: 9 pages, 3 figures, 4 tables + Supplementary Materials 8 pages, 3 figures, 10 table

Addiction in Europe, 1860s-1960s: Concepts and Responses in Italy, Poland, Austria, and the United Kingdom

Concepts play a central part in the formulation of problems and proposed solutions to the use of substances. This article reports the initial results from a cross European historical study, carried out to a common methodology, of the language of addiction and policy responses in two key periods, 1860–1930 and the 1950s and 1960s. It concludes that the language of addiction was varied and nonstandard in the first period. The Anglo-American model of inebriety did not apply across Europe but there was a common focus on theories of heredity and national degeneration. After World War II, there was a more homogenous language but still distinct national differences in emphasis and national interests and policy responses to different substances. More research will be needed to deepen understanding of the conditions under which these changes took place and the social and policy appeal of disease theories

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Research activity and the association with mortality.

INTRODUCTION: The aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes. METHODS: National Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated. RESULTS: Low mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855-2,843], 5.9 patients/bed [2.7-9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864-1,357] p<0.0001, 2.6 patients/bed [1.7-3.5] p<0.0169) or, high (n = 42, 930 £/bed [683-1,177] p = 0.0001, 1.8 patients/bed [1.4-2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033-1.068] p<0.0001, recruitment 1.069 [1.052-1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024-1.055] p<0.0001, recruitment 1.085 [1.070-1.100] p<0.0001). CONCLUSIONS: Research active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors

The impact of foreign direct investment, foreign aid and trade on poverty reduction : evidence from Sub-Saharan African countries

Abstract:Despite postulations on the effects of foreign direct investment (FDI), foreign aid, and trade on growth, empirical evidence from extant research has been mixed. The focus of recent research has shifted from the growth effects of these international flows to their poverty reduction effects. However, results have also been mixed. Most studies have examined the empirical evidence of these flows separately and have mostly conducted single country studies. In this study, we use data from twenty-nine countries in Sub-Saharan Africa between the period 1990–2017 to analyze the effects of FDI, trade, and foreign aid on poverty reduction in a single model using the Feasible Generalized Least Square (FGLS) technique. Our results show that FDI and foreign aid have a negative effect on poverty reduction in the countries studied. These results suggest that the level of FDI required to alleviate poverty has not been reached, and foreign aid have not been properly channeled. However, the results show that trade has a positive and significant impact on poverty reduction, especially in low-income countries. We conclude with policy recommendations

Primary care obesity management in Hungary: evaluation of the knowledge, practice and attitudes of family physicians

BACKGROUND: Obesity, a threatening pandemic, has an important public health implication. Before proper medication is available, primary care providers will have a distinguished role in prevention and management. Their performance may be influenced by many factors but their personal motivation is still an under-researched area. METHOD: The knowledge, attitudes and practice were reviewed in this questionnaire study involving a representative sample of 10% of all Hungarian family physicians. In different settings, 521 practitioners (448 GPs and 73 residents/vocational trainees) were questioned using a validated questionnaire. RESULTS: The knowledge about multimorbidity, a main consequence of obesity, was balanced.Only 51% of the GPs were aware of the diagnostic threshold for obesity; awareness being higher in cities (60%) and the highest among residents (90%). They also considered obesity an illness rather than an aesthetic issue.There were wider differences regarding attitudes and practice, influenced by the the doctors' age, gender, known BMI, previous qualification, less by working location.GPs with qualification in family medicine alone considered obesity management as higher professional satisfaction, compared to physicians who had previously other board qualification (77%vs68%). They measured their patients' waist circumference and waist/hip ratio (72%vs62%) more frequently, provided the obese with dietary advice more often, while this service was less frequent among capital-based doctors who accepted the self-reported body weight dates by patients more frequently / commonly. Similar reduced activity and weight-measurement in outdoor clothing were more typical among older doctors.Diagnosis based on BMI alone was the highest in cities (85%). Consultations were significantly shorter in practices with a higher number of enrolled patients and were longer by female providers who consulted longer with patients about the suspected causes of developing obesity (65%vs44%) and offered dietary records for patients significantly more frequently (65%vs52%). Most of the younger doctors agreed that obesity management was a primary care issue.Doctors in the normal BMI range were unanimous that they should be a model for their patients (94%vs81%). CONCLUSION: More education of primary care physicians, available practical guidelines and higher community involvement are needed to improve the obesity management in Hungary

Identifying Host Genetic Risk Factors in the Context of Public Health Surveillance for Invasive Pneumococcal Disease

Host genetic factors that modify risk of pneumococcal disease may help target future public health interventions to individuals at highest risk of disease. We linked data from population-based surveillance for invasive pneumococcal disease (IPD) with state-based newborn dried bloodspot repositories to identify biological samples from individuals who developed invasive pneumococcal disease. Genomic DNA was extracted from 366 case and 732 anonymous control samples. TagSNPs were selected in 34 candidate genes thought to be associated with host response to invasive pneumococcal disease, and a total of 326 variants were successfully genotyped. Among 543 European Americans (EA) (182 cases and 361 controls), and 166 African Americans (AA) (53 cases and 113 controls), common variants in surfactant protein D (SFTPD) are consistently underrepresented in IPD. SFTPD variants with the strongest association for IPD are intronic rs17886286 (allelic OR 0.45, 95% confidence interval (CI) [0.25, 0.82], with p = 0.007) in EA and 5′ flanking rs12219080 (allelic OR 0.32, 95%CI [0.13, 0.78], with p = 0.009) in AA. Variants in CD46 and IL1R1 are also associated with IPD in both EA and AA, but with effects in different directions; FAS, IL1B, IL4, IL10, IL12B, SFTPA1, SFTPB, and PTAFR variants are associated (p≤0.05) with IPD in EA or AA. We conclude that variants in SFTPD may protect against IPD in EA and AA and genetic variation in other host response pathways may also contribute to risk of IPD. While our associations are not corrected for multiple comparisons and therefore must be replicated in additional cohorts, this pilot study underscores the feasibility of integrating public health surveillance with existing, prospectively collected, newborn dried blood spot repositories to identify host genetic factors associated with infectious diseases

Long-term management of GERD in the elderly with pantoprazole

The prevalence of gastroesophageal reflux disease (GERD) increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs) are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD

Infected Dendritic Cells Facilitate Systemic Dissemination and Transplacental Passage of the Obligate Intracellular Parasite Neospora caninum in Mice

The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites

A qualitative investigation of lived experiences of long-term health condition management with people who are food insecure.

Background: As more people are living with one or more chronic health conditions, supporting patients to become activated, self-managers of their conditions has become a key health policy focus both in the UK and internationally. There is also growing evidence in the UK that those with long term health conditions have an increased risk of being food insecure. While international evidence indicates that food insecurity adversely affects individual's health condition management capability, little is known about how those so affected manage their condition(s) in this context. An investigation of lived experience of health condition management was undertaken with food insecure people living in north east Scotland. The study aimed to explore the challenges facing food insecure people in terms of, i. their self-care condition management practices, and ii. disclosing and discussing the experience of managing their condition with a health care professional, and iii. Notions of the support they might wish to receive from them. Methods: Twenty in-depth interviews were conducted with individuals attending a food bank and food pantry in north east Scotland. Interview audio recordings were fully transcribed and thematically analysed. Results: Individuals reporting multiple physical and mental health conditions, took part in the study. Four main themes were identified i.e.: 1. food practices, trade-offs and compromises, that relate to economic constraints and lack of choice; 2. illness experiences and food as they relate to physical and mental ill-health; 3. (in) visibility of participants' economic vulnerability within health care consultations; and 4. perceptions and expectations of the health care system. Conclusions: This study, the first of its kind in the UK, indicated that participants' health condition management aspirations were undermined by the experience of food insecurity, and that their health care consultations in were, on the whole, devoid of discussions of those challenges. As such, the study indicated practical and ethical implications for health care policy, practice and research associated with the risk of intervention-generated health inequalities that were suggested by this study. Better understanding is needed about the impact of household food insecurity on existing ill health, wellbeing and health care use across the UK