Justifying the Special Theory of Relativity with Unconceived Methods

Many realists argue that present scientific theories will not follow the fate of past scientific theories because the former are more successful than the latter. Critics object that realists need to show that present theories have reached the level of success that warrants their truth. I reply that the special theory of relativity has been repeatedly reinforced by unconceived scientific methods, so it will be reinforced by infinitely many unconceived scientific methods. This argument for the special theory of relativity overcomes the critics’ objection, and has advantages over the no-miracle argument and the selective induction for it

An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention

Background Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. Methods A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. Results All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-η2 = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12-PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD-RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). Conclusions Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted

Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed through Private Drug Shops in Rural Tanzania

BACKGROUND: WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. METHODS/PRINCIPAL FINDINGS: Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). CONCLUSIONS: A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39125414

Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings

<p>Abstract</p> <p>Background</p> <p>To examine the agreement between depression symptoms using an assessment tool (PHQ-9), and physician documentation of the same symptoms during a clinic visit, and then to examine how the presence of these symptoms affects depression diagnosis in primary care settings.</p> <p>Methods</p> <p>Interviewer administered surveys and medical record reviews. A total of 304 participants were recruited from 2321 participants screened for depression at two large urban primary care community settings.</p> <p>Results</p> <p>Of the 2321 participants screened for depression 304 were positive for depression and of these 75.3% (n = 229) were significantly depressed (PHQ-9 score ≥ 10). Of these, 31.0% were diagnosed by a physician with a depressive disorder. A total of 57.6% (n = 175) of study participants had both significant depression symptoms and functional impairment. Of these 37.7% were diagnosed by physicians as depressed. Cohen's Kappa analysis, used to determine the agreement between depression symptoms elicited using the PHQ-9 and physician documentation of these symptoms showed only slight agreement (0.001–0.101) for all depression symptoms using standard agreement rating scales. Further analysis showed that only suicidal ideation and hypersomnia or insomnia were associated with an increased likelihood of physician depression diagnosis (OR 5.41 P sig < .01 and (OR 2.02 P sig < .05 respectively). Other depression symptoms and chronic medical conditions had no affect on physician depression diagnosis.</p> <p>Conclusion</p> <p>Two-thirds of individuals with depression are undiagnosed in primary care settings. While functional impairment increases the rate of physician diagnosis of depression, the agreement between a structured assessment and physician elicited and or documented symptoms during a clinical encounter is very low. Suicidality, hypersomnia and insomnia are associated with an increase in the rate of depression diagnosis even when physician and self report of the symptom differ. Interventions that emphasize the use of routine structured screening of primary care patients might also improve the rate of diagnosis of depression in these settings. Further studies are needed to explore depression symptom assessment during physician patient encounter in primary care settings.</p

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

<p>Abstract</p> <p>Background</p> <p>Intensive anti-malaria campaigns targeting the <it>Anopheles </it>population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of <it>Anopheles </it>mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions.</p> <p>Methods</p> <p>An ecological model of <it>Anopheles gambiae sensu lato </it>populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density.</p> <p>Results</p> <p>A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density.</p> <p>Conclusions</p> <p>Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density.</p