The Diffusion of the Internet in a Pro-IT Cultural Environment: A Content Analysis of the Singapore Experience

Despite the magnitude of the Internet phenomenon, relatively few studies investigate the factors influencing its diffusion. This paper seeks to provide a better understanding of the forces that influence the diffusion of the Internet in Singapore. A push-pull framework that incorporates the political, technological, economic, and social factors is developed as the basis for examining this phenomenon. Based on this framework, a content-analytic approach is used to analyze the messages conveyed in Singapore\u27s two local English-medium newspapers. The results show that both push and pull forces predominated in the early stages of Internet diffusion. However, as time went by, the pull forces predominated over the push forces. The results also show that factors such as building telecommunication infrastructure, having on-line information and services, and creating business opportunities were important in the diffusion of the Internet in Singapore

Eradication of hepatitis C infection: the importance of targeting people who inject drugs

Hepatitis C virus (HCV) affects ~170 million people worldwide and causes significant morbidity and mortality.1 In high-income countries, people who inject drugs (PWID) are at greatest risk of HCV infection.2 Until recently HCV eradication seemed unlikely, but recent advances in HCV treatment and improved understanding of the effectiveness of harm-reduction intervention effectiveness give reason for optimism. Current HCV treatments can cure ~75% of patients and new drugs will further improve effectiveness (over 90% cure) and improve tolerability.3 If HCV treatment can be delivered effectively to those at highest risk of onward transmission, significant reductions in future HCV cases are possible. The feasibility of disease eradication must be assessed on both scientific criteria (e.g., epidemiological susceptibility, effective and practical intervention available, and demonstrated feasibility of elimination) and political criteria (e.g., burden of disease, cost of intervention).4 With effective, curative treatment now available, HCV meets these criteria

NMFS / Interagency Working Group Evaluation of CITES Criteria and Guidelines.

EXECUTIVE SUMMARY: At present, the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) criteria used to assess whether a population qualifies for inclusion in the CITES Appendices relate to (A) size of the population, (B) area of distribution of the population, and (C) declines in the size of the population. Numeric guidelines are provided as indicators of a small population (less than 5,000 individuals), a small subpopulation (less than 500 individuals), a restricted area of distribution for a population (less than 10,000 km2), a restricted area of distribution for a subpopula-tion (less than 500 km2), a high rate of decline (a decrease of 50% or more in total within 5 years or two generations whichever is longer or, for a small wild population, a decline of 20% or more in total within ten years or three generations whichever is longer), large fluctuations (population size or area of distribution varies widely, rapidly and frequently, with a variation greater than one order of magnitude), and a short-term fluctuation (one of two years or less). The Working Group discussed several broad issues of relevance to the CITES criteria and guidelines. These included the importance of the historical extent of decline versus the recent rate of decline; the utility and validity of incorporating relative population productivity into decline criteria; the utility of absolute numbers for defining small populations or small areas; the appropriateness of generation times as time frames for examining declines; the importance of the magnitude and frequency of fluctuations as factors affecting risk of extinction; and the overall utility of numeric thresh-olds or guidelines

Pressuring and restrictive feeding styles influence infant feeding and size among a low-income African-American sample

The prevalence of overweight among infants and toddlers has increased dramatically in the past three decades, highlighting the importance of identifying factors contributing to early excess weight gain, particularly in high-risk groups. Parental feeding styles, the attitudes and behaviors that characterize parental approaches to maintaining or modifying children’s eating behavior, are an important behavioral component shaping early obesity risk. Using longitudinal data from the Infant Care and Risk of Obesity Study, a cohort study of 217 African-American mother-infant pairs with feeding styles, dietary recalls and anthropometry collected from 3-18 months of infant age, we examined the relationship between feeding styles, infant diet and weight–for-age and sum of skinfolds. Longitudinal mixed models indicated that higher pressuring and indulgent feeding style scores were positively associated with greater infant energy intake, reduced odds of breastfeeding and higher levels of age-inappropriate feeding of liquids and solids while restrictive feeding styles were associated with lower energy intake, higher odds of breastfeeding and reduced odds of inappropriate feeding. Pressuring and restriction were also oppositely related to infant size with pressuring associated with lower infant weight-for-age and restriction with higher weight-for-age and sum of skinfolds. Infant size also predicted maternal feeding styles in subsequent visits indicating that the relationship between size and feeding styles is likely bidirectional. Our results suggest that the degree to which parents are pressuring or restrictive during feeding shapes the early feeding environment and, consequently, may be an important environmental factor in the development of obesity

Multicenter observational study on factors and outcomes associated with various methicillin-resistant Staphylococcus aureus types in children with cystic fibrosis

Rationale: Methicillin-resistant Staphylococcus aureus (MRSA) prevalence continues to increase in patients with cystic fibrosis (CF) in the United States, reaching 26.5% in 2012. Approximately 30% of strains are SCCmec (staphylococcal cassette chromosome mec) IV type, frequently USA300, which in the general population have different genotypic and phenotypic features than SCCmec II type. Objectives: We hypothesized that risk factors for acquisition and outcomes in patients with CF differed for "health care-associated" (SCCmec II) versus "community-associated" (SCCmec IV)MRSAstrains. Methods: To determine the role of SCCmec type and Panton-Valentine leukocidin (PVL), MRSA isolates from patients not more than 18 years old at seven CF centers were typed and the association of potential risk factors and subsequent clinical course was assessed, using data provided by the CF Patient Registry. Measurements and Main Results: Participants with chronic MRSA (295) had typeable isolates and clinical data; 205 (69.5%) had SCCmec II PVL(-), 39 (13.2%) had SCCmec IV PVL(-), and 51 (17.3%) had SCCmec IVPVL(1) strains.SCCmec IV, comparedwith SCCmec II, increased during the study period, 1996-2010 (P = 0.03). SCCmec II was associated with Pseudomonas aeruginosa-positive cultures and three or more clinic visits in the 6 months preceding the first positive MRSA culture (adjusted odds ratio, 2.05; 95% confidence interval, 1.13-3.74; P = 0.019). Lung function and anthropometrics remained unchanged in the 6 months after initial MRSA detection compared with the 6 months prior. Although CF care increased for participants in both groups in the 6 months after MRSA detection, inhaled antibiotics were prescribed more frequently in those with SCCmec II strains and increased hospitalizations occurred in those with SCCmec IV PVL(-) strains compared with those with PVL(1) strains (adjusted difference, 34.10%; 95% confidence interval, 7.58-60.61; P = 0.012). Participants in both groups had an increase in CF care in the 2 years after MRSA detection compared with the 2 years prior. Conclusions: Increased exposure to CF clinics and P. aeruginosa may constitute risk factors for acquisition of SCCmec II MRSA strains. Clinical interventions increased 6 months and 2 years after initial MRSA detection regardless of SCCmec type

Retnla (Relmα/Fizz1) Suppresses Helminth-Induced Th2-Type Immunity

Retnla (Resistin-like molecule alpha/FIZZ1) is induced during Th2 cytokine immune responses. However, the role of Retnla in Th2-type immunity is unknown. Here, using Retnla−/− mice and three distinct helminth models, we show that Retnla functions as a negative regulator of Th2 responses. Pulmonary granuloma formation induced by the eggs of the helminth parasite Schistosoma mansoni is dependent on IL-4 and IL-13 and associated with marked increases in Retnla expression. We found that both primary and secondary pulmonary granuloma formation were exacerbated in the absence of Retlna. The number of granuloma-associated eosinophils and serum IgE titers were also enhanced. Moreover, when chronically infected with S. mansoni cercariae, Retnla−/− mice displayed significant increases in granulomatous inflammation in the liver and the development of fibrosis and progression to hepatosplenic disease was markedly augmented. Finally, Retnla−/− mice infected with the gastrointestinal (GI) parasite Nippostrongylus brasiliensis had intensified lung pathology to migrating larvae, reduced fecundity, and accelerated expulsion of adult worms from the intestine, suggesting Th2 immunity was enhanced. When their immune responses were compared, helminth infected Retnla−/− mice developed stronger Th2 responses, which could be reversed by exogenous rRelmα treatment. Studies with several cytokine knockout mice showed that expression of Retnla was dependent on IL-4 and IL-13 and inhibited by IFN-γ, while tissue localization and cell isolation experiments indicated that eosinophils and epithelial cells were the primary producers of Retnla in the liver and lung, respectively. Thus, the Th2-inducible gene Retnla suppresses resistance to GI nematode infection, pulmonary granulomatous inflammation, and fibrosis by negatively regulating Th2-dependent responses

Using a formative simulated patient exercise for curriculum evaluation

BACKGROUND: It is not clear that teaching specific history taking, physical examination and patient teaching techniques to medical students results in durable behavioural changes. We used a quasi-experimental design that approximated a randomized double blinded trial to examine whether a Participatory Decision-Making (PDM) educational module taught in a clerkship improves performance on a Simulated Patient Exercise (SPE) in another clerkship, and how this is influenced by the time between training and assessment. METHODS: Third year medical students in an internal medicine clerkship were assessed on their use of PDM skills in an SPE conducted in the second week of the clerkship. The rotational structure of the third year clerkships formed a pseudo-randomized design where students had 1) completed the family practice clerkship containing a training module on PDM skills approximately four weeks prior to the SPE, 2) completed the family medicine clerkship and the training module approximately 12 weeks prior to the SPE or 3) had not completed the family medicine clerkship and the PDM training module at the time they were assessed via the SPE. RESULTS: Based on limited pilot data there were statistically significant differences between students who received PDM training approximately four weeks prior to the SPE and students who received training approximately 12 weeks prior to the SPE. Students who received training 12 weeks prior to the SPE performed better than those who received training four weeks prior to the SPE. In a second comparison students who received training four weeks prior to the SPE performed better than those who did not receive training but the differences narrowly missed statistical significance (P < 0.05). CONCLUSION: This pilot study demonstrated the feasibility of a methodology for conducting rigorous curricular evaluations using natural experiments based on the structure of clinical rotations. In addition, it provided preliminary data suggesting targeted educational interventions can result in marked improvements in the clinical skills spontaneously exhibited by physician trainees in a setting different from which the skills were taught

A reference relative time-scale as an alternative to chronological age for cohorts with long follow-up

Background: Epidemiologists have debated the appropriate time-scale for cohort survival studies; chronological age or time-on-study being two such time-scales. Importantly, assessment of risk factors may depend on the choice of time-scale. Recently, chronological or attained age has gained support but a case can be made for a ‘reference relative time-scale’ as an alternative which circumvents difficulties that arise with this and other scales. The reference relative time of an individual participant is the integral of a reference population hazard function between time of entry and time of exit of the individual. The objective here is to describe the reference relative time-scale, illustrate its use, make comparison with attained age by simulation and explain its relationship to modern and traditional epidemiologic methods. Results: A comparison was made between two models; a stratified Cox model with age as the time-scale versus an un-stratified Cox model using the reference relative time-scale. The illustrative comparison used a UK cohort of cotton workers, with differing ages at entry to the study, with accrual over a time period and with long follow-up. Additionally, exponential and Weibull models were fitted since the reference relative time-scale analysis need not be restricted to the Cox model. A simulation study showed that analysis using the reference relative time-scale and analysis using chronological age had very similar power to detect a significant risk factor and both were equally unbiased. Further, the analysis using the reference relative time-scale supported fully-parametric survival modelling and allowed percentile predictions and mortality curves to be constructed. Conclusions: The reference relative time-scale was a viable alternative to chronological age, led to simplification of the modelling process and possessed the defined features of a good time-scale as defined in reliability theory. The reference relative time-scale has several interpretations and provides a unifying concept that links contemporary approaches in survival and reliability analysis to the traditional epidemiologic methods of Poisson regression and standardised mortality ratios. The community of practitioners has not previously made this connection

Using Single loxP Sites to Enhance Homologous Recombination: ts Mutants in Sec1 of Dictyostelium discoideum

Dictyostelium discoideum amoebae are haploid and, as they share many features with animal cells, should be an ideal creature for studying basic processes such as cell locomotion. Isolation of mutants in this amoeba has largely been limited to non-essential genes: nsfA-the gene for NEM-sensitive factor-remains the only essential gene for which conditional (ts) mutants exist. These ts mutants were generated by gene replacement using a library of mutagenised nsfA containing a selectable marker: transformants were then screened for temperature sensitivity. The success of this approach depended on the high level of homologous recombination prevailing at this locus: approximately 95% of selected clones were homologous recombinants. This is unusually high for Dictyostelium: homologous recombination at other loci is usually much less, usually between 0-30%, making the isolation of ts mutants much more tedious.In trying to make ts mutants in sec1A, homologous recombination was found to be only approximately 25%. A new approach, involving single loxP sites, was investigated. LoxP sites are 34 bp sequences recognised by Cre recombinase and between which this enzyme catalyses recombination. A Dictyostelium line containing a single loxP site adjacent to the 3' end of the sec1A gene was engineered. A sec1A replacement DNA also containing a single loxP site in a homologous position was then introduced into this cell line. In the presence of CRE recombinase, homologous recombination increased to approximately 80% at this locus, presumably largely driven by intermolecular recombination between the two single loxP sites.A route to increase the rate of homologous recombination at a specific locus, sec1A, is described which enabled the isolation of 30 ts mutants in sec1A. One of these, sec1Ats1,has been studied and found to cease moving at the restrictive temperature. The approach described here may be valuable for enhancing homologous recombination at specified loci and thus for introducing mutations into specific genes in Dictyostelium and other creatures

Arginase-1–Expressing Macrophages Suppress Th2 Cytokine–Driven Inflammation and Fibrosis

Macrophage-specific expression of Arginase-1 is commonly believed to promote inflammation, fibrosis, and wound healing by enhancing L-proline, polyamine, and Th2 cytokine production. Here, however, we show that macrophage-specific Arg1 functions as an inhibitor of inflammation and fibrosis following infection with the Th2-inducing pathogen Schistosoma mansoni. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages, Arg1−/flox;LysMcre mice died at an accelerated rate. The mortality was not due to acute Th1/NOS2-mediated hepatotoxicity or endotoxemia. Instead, granulomatous inflammation, liver fibrosis, and portal hypertension increased in infected Arg1−/flox;LysMcre mice. Similar findings were obtained with Arg1flox/flox;Tie2cre mice, which delete Arg1 in all macrophage populations. Production of Th2 cytokines increased in the infected Arg1−/flox;LysMcre mice, and unlike alternatively activated wild-type macrophages, Arg1−/flox;LysMcre macrophages failed to inhibit T cell proliferation in vitro, providing an underlying mechanism for the exacerbated Th2 pathology. The suppressive activity of Arg1-expressing macrophages was independent of IL-10 and TGF-β1. However, when exogenous L-arginine was provided, T cell proliferation was restored, suggesting that Arg1-expressing macrophages deplete arginine, which is required to sustain CD4+ T cell responses. These data identify Arg1 as the essential suppressive mediator of alternatively activated macrophages (AAM) and demonstrate that Arg1-expressing macrophages function as suppressors rather than inducers of Th2-dependent inflammation and fibrosis