A double-blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with type 2 diabetes

Aims: To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed-dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy. Methods: In this 24-week double-blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice-daily premix insulin therapy (target pre-breakfast and pre-evening meal glucose ≤ 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo. Results: Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 ± 1.5 U/day, mean ± se) compared with placebo [59.0 ± 3.0 U/day; model-adjusted difference -26.6 (95% CI -37.7, -15,5) U/day, P < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA 1c rosiglitazone + metformin vs. placebo 6.8 ± 0.1 vs. 7.5 ± 0.1%; difference -0.7 (-0.8, -0.5)%, P < 0.001] and more individuals achieved glycaemic targets (HbA1c < 7.0% 70 vs. 34%, P < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P = 0.02] with rosiglitazone + metformin. Conclusions: Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated. © 2007 The Authors.

Logics of marginalisation in health and social care reform:integration, choice, and provider-blind provision

The period 2010–2013 was a time of far-reaching structural reforms of the National Health Service in England. Of particular interest in this paper is the way in which radical critiques of the reform process were marginalised by pragmatic concerns about how to maintain the market-competition thrust of the reforms while avoiding potential fragmentation. We draw on the Essex school of political discourse theory and develop a ‘nodal’ analytical framework to argue that widespread and repeated appeals to a narrative of choice-based integrated care served to take the fragmentation ‘sting’ out of radical critiques of the pro-competition reform process. This served to marginalise alternative visions of health and social care, and to pre-empt the contestation of a key norm in the provision of health care that is closely associated with the notions of ‘any willing provider’ and ‘any qualified provider’: provider-blind provision.

Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes:a randomized double-blind placebo-controlled 102-week trial

Aims: To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin. Methods: This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18-77 years and inadequate glycaemic control on diet and exercise [HbA1c 53-86 mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy 2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After 24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo group regimen (placebo+low-dose metformin group). Changes in HbA1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. Results: Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c (-5.8 mmol/mol [-0.53%], P = 0.018; and -4.8 mmol/mol [-0.44%], P = 0.048), respectively); and for FPG (-0.69 mmol/L, P = 0.044; and -1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant (-2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group. Conclusions: Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.

Mode-division-multiplexed 3x112-Gb/s DP-QPSK transmission over 80 km few-mode fiber with inline MM-EDFA and blind DSP

We show transmission of a 3x112-Gb/s DP-QPSK mode-division-multiplexed signal up to 80km, with and without multi-mode EDFA, using blind 6x6 MIMO digital signal processing. We show that the OSNR-penalty induced by mode-mixing in the multi-mode EDFA is negligible.

On the Quotient Function Employed in the Blind Source Separation Problem

MSC 2010: 42C40, 94A12

Decision-directed-free blind phase noise estimation for COOFDM

We demonstrate an effective decision-directed-free blind phase noise compensation method for CO-OFDM transmission. By applying this technique, the common phase error can be accurately estimated using as few as three test phases.

Multiplier-free blind phase noise estimation for CO-OFDM transmission

We experimentally demonstrate an effective multiplier-free blind phase noise estimation technique for CO-OFDM systems for the first time based on the statistical properties of the received symbols' phases. Our technique operates in polar coordinates, providing very low implementation complexity.

Improving the scientific reliability of biological detection of explosives by Canis familiaris: Active odour signatures and their implications

The use of canines as a method of detection of explosives is well established worldwide and those applying this technology range from police forces and law enforcement to humanitarian agencies in the developing world. Despite the recent surge in publication of novel instrumental sensors for explosives detection, canines are still regarded by many to be the most effective real-time field method of explosives detection. However, unlike instrumental methods, currently it is difficult to determine detection levels, perform calibration of the canines' ability or produce scientifically valid quality control checks. Accordingly, amongst increasingly strict requirements regarding forensic evidence admission such as Frye and Daubert, there is a need for better scientific understanding of the process of canine detection. ^ When translated to the field of canine detection, just like any instrumental technique, peer reviewed publication of the reliability, success and error rates, is required for admissibility. Commonly training is focussed towards high explosives such as TNT and Composition 4, and the low explosives such as Black and Smokeless Powders are added often only for completeness. ^ Headspace analyses of explosive samples, performed by Solid Phase Microextraction (SPME) paired with Gas Chromatography - Mass Spectrometry (GC-MS), and Gas Chromatography - Electron Capture Detection (GC-ECD) was conducted, highlighting common odour chemicals. The odour chemicals detected were then presented to previously trained and certified explosives detection canines, and the activity/inactivity of the odour determined through field trials and experiments. ^ It was demonstrated that TNT and cast explosives share a common odour signature, and the same may be said for plasticized explosives such as Composition C-4 and Deta Sheet. Conversely, smokeless powders were demonstrated not to share common odours. An evaluation of the effectiveness of commercially available pseudo aids reported limited success. The implications of the explosive odour studies upon canine training then led to the development of novel inert training aids based upon the active odours determined. ^

Design of an automated book reader as an assistive technology tool for blind persons

This dissertation introduces a novel automated book reader as an assistive technology tool for persons with blindness. The literature shows extensive work in the area of optical character recognition, but the current methodologies available for the automated reading of books or bound volumes remain inadequate and are severely constrained during document scanning or image acquisition processes. The goal of the book reader design is to automate and simplify the task of reading a book while providing a user-friendly environment with a realistic but affordable system design. This design responds to the main concerns of (a) providing a method of image acquisition that maintains the integrity of the source (b) overcoming optical character recognition errors created by inherent imaging issues such as curvature effects and barrel distortion, and (c) determining a suitable method for accurate recognition of characters that yields an interface with the ability to read from any open book with a high reading accuracy nearing 98%. This research endeavor focuses in its initial aim on the development of an assistive technology tool to help persons with blindness in the reading of books and other bound volumes. But its secondary and broader aim is to also find in this design the perfect platform for the digitization process of bound documentation in line with the mission of the Open Content Alliance (OCA), a nonprofit Alliance at making reading materials available in digital form. The theoretical perspective of this research relates to the mathematical developments that are made in order to resolve both the inherent distortions due to the properties of the camera lens and the anticipated distortions of the changing page curvature as one leafs through the book. This is evidenced by the significant increase of the recognition rate of characters and a high accuracy read-out through text to speech processing. This reasonably priced interface with its high performance results and its compatibility to any computer or laptop through universal serial bus connectors extends greatly the prospects for universal accessibility to documentation.

Improved sampling, pre-concentration, and detection of hidden explosives and illicit drugs by a novel solid phase microextraction geometry coupled to ion mobility spectrometry

The 9/11 Act mandates the inspection of 100% of cargo shipments entering the U.S. by 2012 and 100% inspection of air cargo by March 2010. So far, only 5% of inbound shipping containers are inspected thoroughly while air cargo inspections have fared better at 50%. Government officials have admitted that these milestones cannot be met since the appropriate technology does not exist. This research presents a novel planar solid phase microextraction (PSPME) device with enhanced surface area and capacity for collection of the volatile chemical signatures in air that are emitted from illicit compounds for direct introduction into ion mobility spectrometers (IMS) for detection. These IMS detectors are widely used to detect particles of illicit substances and do not have to be adapted specifically to this technology. For static extractions, PDMS and sol-gel PDMS PSPME devices provide significant increases in sensitivity over conventional fiber SPME. Results show a 50–400 times increase in mass detected of piperonal and a 2–4 times increase for TNT. In a blind study of 6 cases suspected to contain varying amounts of MDMA, PSPME-IMS correctly detected 5 positive cases with no false positives or negatives. One of these cases had minimal amounts of MDMA resulting in a false negative response for fiber SPME-IMS. A La (dihed) phase chemistry has shown an increase in the extraction efficiency of TNT and 2,4-DNT and enhanced retention over time. An alternative PSPME device was also developed for the rapid (seconds) dynamic sampling and preconcentration of large volumes of air for direct thermal desorption into an IMS. This device affords high extraction efficiencies due to strong retention properties under ambient conditions resulting in ppt detection limits when 3.5 L of air are sampled over the course of 10 seconds. Dynamic PSPME was used to sample the headspace over the following: MDMA tablets (12–40 ng detected of piperonal), high explosives (Pentolite) (0.6 ng detected of TNT), and several smokeless powders (26–35 ng of 2,4-DNT and 11–74 ng DPA detected). PSPME-IMS technology is flexible to end-user needs, is low-cost, rapid, sensitive, easy to use, easy to implement, and effective. ^

Size-based variation in intertissue comparisons of stable carbon and nitrogen isotopic signatures of bull sharks (Carcharhinus leucas) and tiger sharks (Galeocerdo cuvier)

Stable isotopes are important tools for understanding the trophic roles of elasmobranchs. However, whether different tissues provide consistent stable isotope values within an individual are largely unknown. To address this, the relationships among carbon and nitrogen isotope values were quantified for blood, muscle, and fin from juvenile bull sharks (Carcharhinus leucas) and blood and fin from large tiger sharks (Galeocerdo cuvier) collected in two different ecosystems. We also investigated the relationship between shark size and the magnitude of differences in isotopic values between tissues. Isotope values were significantly positively correlated for all paired tissue comparisons, but R2 values were much higher for δ13C than for δ15N. Paired differences between isotopic values of tissues were relatively small but varied significantly with shark total length, suggesting that shark size can be an important factor influencing the magnitude of differences in isotope values of different tissues. For studies of juvenile sharks, care should be taken in using slow turnover tissues like muscle and fin, because they may retain a maternal signature for an extended time. Although correlations were relatively strong, results suggest that correction factors should be generated for the desired study species and may only allow coarse-scale comparisons between studies using different tissue types.

Validation of an Analytical Method for the Identification of SmartWater CSI Forensic Marking Technology

SmartWater is a chemical taggant used as a crime deterrent. The chemical taggant is a colorless liquid that fluoresces yellow under ultra-violet (UV) light and contains distinctive, identifiable and traceable elemental composition. For instance, upon a break and entry scenario, the burglar is sprayed with a solution that has an elemental signature custom-made to a specific location. The residues of this taggant persist on skin and other objects and can be easily recovered for further analysis. The product has been effectively used in Europe as a crime deterrent and has been recently introduced in South Florida. In 2014, Fourt Lauderdale Police Department reported the use of SmartWater products with a reduction in burglaries of 14% [1]. The International Forensic Research Institute (IFRI) at FIU validated the scientific foundation of the methods of recovery and analysis of these chemical tagging systems using LA-ICP-MS. Analytical figures of merit of the method such as precision, accuracy, limits of detection, linearity and selectivity are reported in this study. Moreover, blind samples were analyzed by LA-ICP-MS to compare the chemical signatures to the company’s database and evaluate error rates and the accuracy of the method. This study demonstrated that LA-ICP-MS could be used to effectively detect these traceable taggants to assist law enforcement agencies in the United States with cases involving transfer of these forensic coding systems.

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood : follow-up of a double-blind randomised controlled trial in Nepal

Date of Acceptance: 12/12/2014 Support statement: This study was funded by the Wellcome Trust (Ref 092121/Z/10/Z), who played no role in its conception, methods, analysis or interpretation. Funding information for this article has been deposited with FundRef.

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood : follow-up of a double-blind randomised controlled trial in Nepal

Date of Acceptance: 12/12/2014 Support statement: This study was funded by the Wellcome Trust (Ref 092121/Z/10/Z), who played no role in its conception, methods, analysis or interpretation. Funding information for this article has been deposited with FundRef.

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years : 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study

Acknowledgments The VIVIANE study was funded and coordinated by GlaxoSmithKline Biologicals SA, which also covered all costs associated with development and publication of this report. We thank all study participants and their families. We gratefully acknowledge the work of the central and local study coordinators, and staff members of the sites who participated in this study. Writing support services were provided by Mary Greenacre (An Sgriobhadair, Isle of Barra, UK), on behalf of GSK Vaccines; editing and publication coordination services were provided by Jérôme Leemans (Keyrus Biopharma, Lasne, Belgium), Stéphanie Delval (XPE Pharma and Science, Wavre, Belgium), and Matthieu Depuydt (Business Decision Life Sciences, Brussels, Belgium), on behalf of GSK Vaccines