Dapagliflozin: an evidence-based review of its potential in the treatment of type-2 diabetes

Dapagliflozin is a sodium-glucose co-transporter-2 inhibitor that lowers plasma glucose by decreasing its renal reabsorption. The resulting excretion of glucose in the urine (glucosuria) has transformed what was once solely regarded as an adverse facet of diabetes into a potential novel therapeutic strategy. Glucosuria leads to weight loss, due to a reduction in calories, which is thought to rehabilitate insulin sensitivity, at least partially. By acting independently of insulin action or secretion, dapagliflozin appears to avert or minimize two key barriers to optimal glycemic control: hypoglycemia and weight gain. From the clinical studies conducted thus far in patients with type 2 diabetes, dapagliflozin significantly decreases HbA1c (by ~0.5%–1%, from a baseline of 8%–9%), as well as body weight (~2–3 kg), without increased risk of hypoglycemia. Dapagliflozin thus represents a paradigm shift in the treatment of diabetes. While long-term data on safety and efficacy are forthcoming, the results published to date suggest that this agent has the potential to be another option in the treatment of diabetes treatments. This article examines the evidence currently available on the efficacy and safety of dapagliflozin

Identifying and Measuring the Effect of Firm Clusters Among Certified Organic Processors and Handlers

This paper investigates the certified organic handler sector, a specialized component of the middle part of the farm-to-table marketing chain, and documents the impacts of firm agglomeration (or firm clusters) on firm-level performance or firm-level decisions. After accounting for endogeneity in firm clustering, our findings confirm that firm clusters have significant impacts, though the estimate of the impact depends on how a firm cluster is defined. For example, significant impacts on sales per employee range from an additional $0.17 million to$1.47 million, depending on whether a small or large number of firms is used as the minimum number to define a firm cluster.firm clusters, organic, treatment effects, Agribusiness, Agricultural and Food Policy, Community/Rural/Urban Development,

Performance of Feature Selection Methods

High-throughput biological technologies offer the promise of finding feature sets to serve as biomarkers for medical applications; however, the sheer number of potential features (genes, proteins, etc.) means that there needs to be massive feature selection, far greater than that envisioned in the classical literature. This paper considers performance analysis for feature-selection algorithms from two fundamental perspectives: How does the classification accuracy achieved with a selected feature set compare to the accuracy when the best feature set is used and what is the optimal number of features that should be used? The criteria manifest themselves in several issues that need to be considered when examining the efficacy of a feature-selection algorithm: (1) the correlation between the classifier errors for the selected feature set and the theoretically best feature set; (2) the regressions of the aforementioned errors upon one another; (3) the peaking phenomenon, that is, the effect of sample size on feature selection; and (4) the analysis of feature selection in the framework of high-dimensional models corresponding to high-throughput data

Autonomous Driving: Mapping and Behavior Planning for Crosswalks

As autonomous driving integrates with every day traffic, early adopters are initially skeptical and designers are overly cautious. With safety as the top priority, current systems are sometimes too slow at executing maneuvers. Scenarios such as switching into a crowded lane or waiting for a left turn can result in the autonomous system to wait much longer than a human driver would. This behavior can be frustrating for passengers and confusing for other drivers around. Acceptable driving style also depends on other context like location and culture. A driver may be more forceful in a densely populated city compared to a calmer driver from the suburbs. This thesis explores the unsignalized pedestrian crosswalk scenario and methods that balance safety, assertiveness, caution, and obstruction of traffic flow when interacting with pedestrians. A configurable driving policy for the Autonomoose system is introduced with results. The work adopts the lanelet mapping format and introduces a method of mapping and representing the crosswalk regulation. The main contribution of the work is a tunable algorithmic approach for progressing through unsignalized crosswalks that exemplifies both conservative and assertive driving behavior. The algorithm described in this work is one of possibly infinitely many methods for handling unsignalized crosswalks. Reinforcement learning based solutions and other hand crafted algorithms can benefit from using the work proposed as a point of comparison. General concepts proposed in the algorithm may inspire more robust algorithms in future development

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Effect modification of the association between meteorological variables and mortality by urban climatic conditions in the tropical city of Kaohsiung, Taiwan

A deeper understanding of extreme hot weather are needed in cities sensitive to heat effects, an investigation was done in the tropical town of Kaohsiung in Taiwan. Its 11 districts were divided into three climatic classes varying from high urban heat, low levels of green space and lack of proximity to water bodies to low urban heat, adequate green space and proximity to water bodies. Daily data on natural mortality, meteorological variables, and pollutants from May-October 1999-2008 were analysed using generalised additive models for the time-series data. Subgroup analyses were conducted, stratifying decedents according to the level of planning activity required in order to mitigate adverse heat effects in their residential areas, classifying districts as “level 1” for those requiring a high level of mitigation action; “level 2” for those requiring some action; and “level 3” for those that need only preserve existing conditions. Stratified analyses showed that mortality increases per 1 °C rise on average, either on the same day or in the previous 4 days (lags 0-4), were associated with 2.8%, 2.3% and -1.3% for level 1, 2 and 3 districts, respectively. The slope describing the association between temperature and mortality was higher above 29.0 °C resulting in corresponding increases of 4.2%, 5.0% and 0.3% per per 1 °C rise in temperature, respectively. Other meteorological variables were not significantly associated with mortality. It is concluded that hot season mortality in Kaohsiung is only sensitive to heat effects in districts classified as having unfavourably climatic conditions and requiring mitigation efforts in city planning. Urban planning measures designed to improve climatic conditions could reduce excess mortality resulting from extreme hot weathe