Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana

Objective To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical (peripheral) settings that rely on clinical diagnosis

Classical BI: Its Semantics and Proof Theory

We present Classical BI (CBI), a new addition to the family of bunched logics which originates in O'Hearn and Pym's logic of bunched implications BI. CBI differs from existing bunched logics in that its multiplicative connectives behave classically rather than intuitionistically (including in particular a multiplicative version of classical negation). At the semantic level, CBI-formulas have the normal bunched logic reading as declarative statements about resources, but its resource models necessarily feature more structure than those for other bunched logics; principally, they satisfy the requirement that every resource has a unique dual. At the proof-theoretic level, a very natural formalism for CBI is provided by a display calculus \`a la Belnap, which can be seen as a generalisation of the bunched sequent calculus for BI. In this paper we formulate the aforementioned model theory and proof theory for CBI, and prove some fundamental results about the logic, most notably completeness of the proof theory with respect to the semantics.Comment: 42 pages, 8 figure

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

Histological Review of Skin cancers in African Albinos: A 10-year Retrospective Review.

Skin cancer is rare among Africans and albinism is an established risk for skin cancer in this population. Ultraviolet radiation is highest at the equator and African albinos living close to the equator have the highest risk of developing skin cancers. This was a retrospective study that involved histological review of all specimens with skin cancers from African albinos submitted to The Regional Dermatology Training Center in Moshi, Tanzania from 2002 to 2011. A total of 134 biopsies from 86 patients with a male to female ratio of 1:1 were reviewed. Head and neck was the commonest (n = 75, 56.0%) site affected by skin cancers. Squamous cell carcinoma (SCC) was more common than basal cell carcinoma (BCC) with a ratio of 1.2:1. Only one Acral lentiginous melanoma was reported. Majority (55.6%) of SCC were well differentiated while nodular BCC (75%) was the most common type of BCC. Squamous cell carcinoma is more common than basal cell carcinoma in African albinos

Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver

miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.This work was supported, in part, by NIH grants CA122694 (to K. Ghoshal), DK088076 (to K. Ghoshal), CA086978 (to K. Ghoshal and S.T. Jacob), Pelotonia Idea Grant (to J. Yu and K. Ghoshal), CA120185 (to J.T. Mendell), CA134292 (to J.T. Mendell), and the Cancer Prevention and Research Institute of Texas (to J.T. Men- dell). Bo Wang is supported by a Pelotonia graduate fellowship

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations

The Impact of a Filariasis Control Program on Lihir Island, Papua New Guinea

Large-scale intervention programmes to control filariasis are currently underway worldwide. However, a major unresolved question remains: what is the appropriate duration for these programmes? Recent theoretical work and clinical field experience has highlighted how the ecological diversity between different endemic regions hinders decision making processes of when to stop ongoing MDA programs. The goal of our study was to identify the factors determining success for a five year LF elimination program. We undertook different types of surveys together with a pre-existing MDA program in villages from two regions that had different infection prevalence rates. Our study shows that the five yearly cycles of MDA could neither eliminate the disease nor stop transmission in the high prevalence villages, such that low baseline lymphatic filariasis prevalence has a positive influence on the outcome of a program. Thus, the study provides data supporting the recommendation that in certain high prevalence and transmission environments more sustained efforts may be necessary

Environmental and Lifestyle Factors Associated with Perceived Facial Age in Chinese Women

Perceived facial age has been proposed as a biomarker of ageing with ‘looking young for one’s age' linked to physical and cognitive functioning and to increased survival for Caucasians. We have investigated the environmental and lifestyle factors associated with perceived facial ageing in Chinese women. Facial photographs were collected from 250 Chinese women, aged 25–70 years in Shanghai, China. Perceived facial age was determined and related to chronological age for each participant. Lifestyle and health information was collected by questionnaire. Bivariate analyses (controlling for chronological age) identified and quantified lifestyle variables associated with perceived facial age. Independent predictors of perceived age were identified by multivariate modelling. Factors which significantly associated with looking younger for one's chronological age included greater years of education (p<0.001), fewer household members (p = 0.027), menopausal status (p = 0.020), frequency of visiting one's doctor (p = 0.013), working indoors (p<0.001), spending less time in the sun (p = 0.015), moderate levels of physical activity (p = 0.004), higher frequency of teeth cleaning (p<0.001) and more frequent use of facial care products: cleanser (p<0.001); moisturiser (p = 0.016) or night cream (p = 0.016). Overall, 36.5% of the variation in the difference between perceived and chronological age could be explained by a combination of chronological age and 6 independent lifestyle variables. We have thus identified and quantified a number of factors associated with younger appearance in Chinese women. Presentation of these factors in the context of facial appearance could provide significant motivation for the adoption of a range of healthy behaviours at the level of both individuals and populations