Treatment intensification with insulin glargine in patients with inadequately controlled type 2 diabetes improves glycaemic control with a high treatment satisfaction and no weight gain

PRINCIPLES We aimed to evaluate the efficacy of, and treatment satisfaction with, insulin glargine administered with SoloSTAR® or ClikSTAR® pens in patients with type 2 diabetes mellitus managed by primary care physicians in Switzerland. METHODS A total of 327 patients with inadequately controlled type 2 diabetes were enrolled by 72 physicians in this prospective observational study, which aimed to evaluate the efficacy of a 6-month course of insulin glargine therapy measured as development of glycaemic control (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]) and weight change. We also assessed preference for reusable or disposable pens, and treatment satisfaction. RESULTS After 6 months, the mean daily dose of insulin glargine was 27.7±14.3 U, and dose titration was completed in 228 (72.4%) patients. Mean HbA1c decreased from 8.9%±1.6% (n=327) to 7.3%±1.0% (n=315) (p<0.0001), and 138 (43.8%) patients achieved an HbA1c≤7.0%. Mean FPG decreased from 10.9±4.5 to 7.3±1.8 mmol/l (p<0.0001). Mean body weight did not change (85.4±17.2 kg vs 85.0±16.5 kg; p=0.11). Patients' preference was in favour of the disposable SoloStar® pen (80%), as compared with the reusable ClickStar® pen (20%). Overall, 92.6% of physicians and 96.3% of patients were satisfied or very satisfied with the insulin glargine therapy. CONCLUSIONS In patients with type 2 diabetes insulin glargine administered by SoloSTAR® or ClikSTAR® pens, education on insulin injection and on self-management of diabetes was associated with clinically meaningful improvements in HbA1c and FPG without a mean collective weight gain. The vast majority of both patients and primary care physicians were satisfied with the treatment intensification.

A review of effective weight loss and/or weight gain prevention for disadvantaged populations

Introduction. The prevalence of overweight and obesity has increased sharply for both adults and children, particularity in disadvantaged populations. Changes in dietary habits are small; however applying behavior-change principles has been associated with weight loss and preventing weight gain. This article will review studies targeting economically disadvantaged and/or communities of color incorporating the Transtheoretical Model of Change (TTM).^ Methods. Inclusion criteria were established. Descriptions of characteristics of the reviewed study interventions are included.^ Results. The search yielded a total of 23 articles identified through the electronic database PubMed that included Transtheoretical Model of Change (TTM) interventions regarding diet and/or nutrition, physical activity and/or exercise in disadvantaged populations. Thirteen study interventions centered solely on diet modification, five focused only on physical activity, and five concentrated on a combination of both. The preponderance of studies targeted WIC and urban recipients.^ Discussion/Conclusion. Although the majority of intervention studies supported the use of the Transtheoretical Model of Change (TTM) for weight loss and preventing weight gain, researchers noted that challenges still exist and further interventions are needed.^

Adult weight gain and risk of colon cancer in men

Previous research supports the hypothesis that a "rich" diet (i.e., high in fat and low in fiber) increases the risk of colon cancer. Previous research also supports the hypothesis that physical inactivity increases the risk of colon cancer, perhaps because physical inactivity decreases gut motility, thereby increasing tee time that carcinogens are in contact with the intestinal mucosa. Habitual physical inactivity, combined with rich diet, ordinarily results in chronic energy imbalance and gain in weight, except when energy balance is modified by disease or factors such as cigarette smoking. Cigarette smokers typically stay lean because of effects of smoking on the resting metabolic rate as well as on efficiency of caloric intake and storage. Therefore, if physical inactivity and rich diet do increase the risk of colon cancer, then weight gain during young adulthood should be positively associated with incidence of colon cancer during later life, especially in nonsmokers.^ This hypothesis was investigated in a cohort of 2,059 randomly selected middle-aged men who were employed at the Western Electric Company in Chicago and were free of clinically diagnosed cancer at initial examination in 1958. Body mass index (BMI) in middle age was calculated from measured height and weight at the initial examination. BMI at age 20 was estimated from weight at age 20 as recalled at the initial examination and height as measured at the initial examination. Change in BMI between age 20 and middle age was estimated by subtracting the BMI at 20 from the BMI in middle age. Forty-nine incident cases of colon cancer were detected during 25 years (43,326 person-years) at risk. When stratified by level of change in BMI from age 20 to middle age ($\le$1.9, 2.0-3.9, 4.0-5.9, $\ge$6.0 kg/m$\sp2$), age-adjusted relative hazards of colon cancer in never-smokers were 1.00, 1.22, 2.31, and 5.01, respectively (p for trend = 0.008); corresponding values in ever-smokers were 1.00, 0.95, 0.77, and 0.87, These associations did not change appreciably after further adjustment for BMI at age 20, subscapular-triceps skinfold ratio, cigarette smoking, consumption of alcohol, energy, fat, and calcium.^ We also investigated the hypothesis that the risk of colon cancer was higher in men who were lean at age 20 and became fat by middle age (lean-to-fat) than in men who were fat at age 20 and stayed fat in middle-age (fat-to-fat). "Lean" was defined as BMI $<$24 kg/m$\sp2$ at age 20 and as BMI $<$27.0 kg/m$\sp2$ in middle age. Among never-smokers, in comparison to men who were lean at age 20 and in middle age (lean-to-lean), the age-adjusted relative hazard of colon cancer was 1.43 in the fat-to-fat group (95% confidence interval (CI) 0.37-5.52) and 3.36 in the lean-to-fat group (95% CI 1.21-9.37). This investigation provides new results on the magnitude of risk of colon cancer associated with weight gain during adulthood (from age 20 to middle age). This relation was obscured or underestimated in previous studies due to effect-modification by cigarette smoking. Finally, the result supports the idea that a life-style characterized by chronic energy imbalance during young adulthood increases risk of colon cancer. ^

SOCIAL AND BIOLOGICAL DETERMINANTS OF SHORT-TERM GROWTH VELOCITY AMONG PRESCHOOLERS OF RURAL GUATEMALA: A PATH ANALYSIS APPROACH (WEIGHT-GAIN, IRON DEFICIENCY, GASTROINTESTINAL SYMPTOMS)

This dissertation develops and tests through path analysis a theoretical model to explain how socioeconomic, socioenvironmental, and biologic risk factors simultaneously influence each other to further produce short-term, depressed growth in preschoolers. Three areas of risk factors were identified: child's proximal environment, maturational stage, and biological vulnerability. The theoretical model represented both the conceptual framework and the nature and direction of the hypotheses. Original research completed in 1978-80 and in 1982 provided the background data. It was analyzed first by nested-analysis of variance, followed by path analysis. The study provided evidence of mild iron deficiency and gastrointestinal symptomatology in the etiology of depressed, short-term weight gain. Also, there was evidence suggesting that family resources for material and social survival significantly contribute to the variability of short-term, age-adjusted growth velocity. These results challenge current views of unifocal intervention, whether for prevention or control. For policy formulations, though, the mechanisms underlying any set of interlaced relationships must be decoded. Theoretical formulations here proposed should be reassessed under a more extensive research design. It is suggested that studies should be undertaken where social changes are actually in progress; otherwise, nutritional epidemiology in developing countries operates somewhere between social reality and research concepts, with little grasp of its real potential. The study stresses that there is a connection between substantive theory, empirical observation, and policy issues. ^

Role of obesity, weight gain, physical activity, and polymorphisms in the mTOR pathway and the risk of renal cell carcinoma

The interplay between obesity, physical activity, weight gain and genetic variants in mTOR pathway have not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association. Incident renal cell carcinoma cases and healthy controls were recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas. Cases and controls were frequency-matched by age (±5 years), ethnicity, sex, and county of residence. Epidemiologic data were collected via in-person interview. A total of 577 cases and 593 healthy controls (all white) were included. One hundred ninety-two (192) SNPs from 22 genes were available and their genotyping data were extracted from previous genome-wide association studies. Logistic regression and regression spline were performed to obtain odds ratios. Obesity at age 20, 40, and 3 years prior to diagnosis/recruitment, and moderate and large weight gain from age 20 to 40 were each significantly associated with increased RCC risk. Low physical activity was associated with a 4.08-fold (95% CI: 2.92-5.70) increased risk. Five single nucleotide polymorphisms (SNPs) were significantly associated with RCC risk and their cumulative effect increased the risk by up to 72% (95% CI: 1.20-2.46). Strata specific effects for weight change and genotyping cumulative groups were observed. However, no interaction was suggested by our study. In conclusion, energy balance related risk factors and genetic variants in the mTOR pathway may jointly influence susceptibility to RCC. ^

Association between sugar-sweetened beverages and both gestational weight gain and gestational diabetes

This cross-sectional study aimed at evaluating the association between sugar sweetened beverage (SSB) consumption and both excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM). The study was conducted in the postpartum units of Memorial Hermann Hospital, Lyndon Baines Johnson General Hospital, the University of Texas Medical Branch at Galveston General Hospital, and the University of Texas at Brownsville Hospital. Between June 2009 and September 2010, women between the ages of 18 and 49 years with singleton pregnancies who delivered an infant born at 37 weeks of gestation or later were approached. Descriptive, univariate and multivariate analysis were employed in our study using the Statistical Analysis System (SAS) software version 9.1 (SAS Institute Inc. Cary, North Carolina). Our investigation did not find statistically significant associations between SSBs and EGWG. Our study reported no evidence of an association between SSBs and GDM except for sports drinks. However, the estimate of this association was deemed very imprecise. In conclusion, our study did not find strong provide strong support for the hypothesis that high consumption of SSBs increases the risk of EGWG or GDM. ^

Gain-of-function of the p53R172H mutation in a mouse model of Li -Fraumeni syndrome

Missense mutations in the p53 tumor-suppressor gene are the most common alterations of p53 in somatic tumors and in patients with Li-Fraumeni syndrome. p53 missense mutations occur in the DNA binding region and disrupt the ability of p53 to activate transcription. In vitro studies have shown that some p53 missense mutants have a gain-of-function or dominant-negative activity. ^ The p53 175 Arg-to-His (p53 R175H) mutation in humans has been shown to have dominant-negative and gain-of-function properties in vitro. This mutation is observed in the germline of individuals with Li-Fraumeni syndrome. To accurately model Li-Fraumeni syndrome and to examine the mechanistic nature of a gain-of-function missense mutation on in vivo tumorigenesis, we generated and characterized a mouse with the corresponding mutation, p53 R172H. p53R172H homozygous and heterozygous mice developed similar tumor spectra and survival curves as p53 −/− and p53+/− mice, respectively. However, tumors in p53+/R172H mice metastasized to various organs with high frequency, suggesting a gain-of-function phenotype by p53R172H in vivo. Mouse embryonic fibroblasts (MEFs) from p53R172H mice also showed gain-of-function phenotypes in cell proliferation, DNA synthesis, and transformation potential, while cells from p53+/− and p53−/− mice did not. ^ To mechanistically characterize the gain-of-function phenotype of the p53R172H mutant, the role of p53 family members, p63 and p73, was analyzed. Disruption of p63 and p73 by siRNAs in p53 −/− MEFs increased transformation potential and reinitiated DNA synthesis to levels observed in p53R172H/R172H cells. Additionally, p63 and p73 were bound and functionally inactivated by p53R172H in metastatic p53 R172H tumor-derived cell lines, indicating a role for the p53 family members in the gain-of-function phenotype. This study provides in vivo evidence for the gain-of-function effect of p53 missense mutations and more accurately models the Li-Fraumeni syndrome. ^

Environmental consciousness, economic gain and consumer choice of energy efficient appliances in Thailand, China and India

In developing economies, consumption of electricity in residential and commercial sectors increased with economic development. In order to identify the factors for effective facilitation of standard and labeling programs, this article explores factors that affect consumer choice to energy-efficient products. Main findings are as follows: (1)Consumers in Thailand shows the highest awareness to environmental friendly concepts, followed by India and China.(2) Chosen labeled products include air-conditioners, TVs, refrigerators and washing machines, but not some popular products such as ceiling fans, electric fans or mobile phones. (3) Consumer who has higher energy conservation perception will buy energy efficient products.(4) Consumers in China, India and Thailand are sensitive to energy efficiency of products, primarily because they lead to less expenditure on electricity. (5) Labeling works to make levels of the energy efficiency of products more visible and thus helped consumers to choose the products.

Non-linear gain - look-up table based approach for modeling a family of DC to DC converters based on transient response analysis

The purpose of this work is to propose a structure for simulating power systems using behavioral models of nonlinear DC to DC converters implemented through a look-up table of gains. This structure is specially designed for converters whose output impedance depends on the load current level, e.g. quasi-resonant converters. The proposed model is a generic one whose parameters can be obtained by direct measuring the transient response at different operating points. It also includes optional functionalities for modeling converters with current limitation and current sharing in paralleling characteristics. The pusposed structured also allows including aditional characteristics of the DC to DC converter as the efficency as a function of the input voltage and the output current or overvoltage and undervoltage protections. In addition, this proposed model is valid for overdamped and underdamped situations.

Independent AND-parallel implementation of narrowing

We present a parallel graph narrowing machine, which is used to implement a functional logic language on a shared memory multiprocessor. It is an extensión of an abstract machine for a purely functional language. The result is a programmed graph reduction machine which integrates the mechanisms of unification, backtracking, and independent and-parallelism. In the machine, the subexpressions of an expression can run in parallel. In the case of backtracking, the structure of an expression is used to avoid the reevaluation of subexpressions as far as possible. Deterministic computations are detected. Their results are maintained and need not be reevaluated after backtracking.

Pulse shortening of gain switched single mode semiconductor lasers using a variable delay interferometer

We propose a pulse shaping and shortening technique for pulses generated from gain switched single mode semiconductor lasers, based on a Mach Zehnder interferometer with variable delay. The spectral and temporal characteristics of the pulses obtained with the proposed technique are investigated with numerical simulations. Experiments are performed with a Distributed Feedback laser and a Vertical Cavity Surface Emitting Laser, emitting at 1.5 µm, obtaining pulse duration reduction of 25-30%. The main asset of the proposed technique is that it can be applied to different devices and pulses, taking advantage of the flexibility of the gain switching technique.

Comments and remarks over classic linear loop-gain method for oscillator design and analysis. New proposed method based on NDF/RRT

Abstract. This paper describes a new and original method for designing oscillators based on the Normalized Determinant Function (NDF) and Return Relations (RRT)- Firstly, a review of the loop-gain method will be performed. The loop-gain method pros, cons and some examples for exploring wrong solutions provided by this method will be shown. This method produces in some cases wrong solutions because some necessary conditions have not been fulfilled. The required necessary conditions to assure a right solution will be described. The necessity of using the NDF or the Transpose Return Relations (RRT), which are related with the True Loop-Gain, to test the additional conditions will be demonstrated. To conclude this paper, the steps for oscillator design and analysis, using the proposed NDF/RRj method, will be presented. The loop-gain wrong solutions will be compared with the NDF/RRj and the accuracy of this method to estimate the oscillation frequency and QL will be demonstrated. Some additional examples of plane reference oscillators (Z/Y/T), will be added and they will be analyzed with the new NDF/RRj proposed method, even these oscillators cannot be analyzed using the classic loop gain method.

Dispersive optical bistability in quantum wells with logarithmic gain

We present an analytical model for studying optical bistability in semiconductor lasers that exhibit a logarithmic dependence of the optical gain on carrier concentration. Model results are shown for a Fabry–Pérot quantum-well laser and compared with the predictions of a commercial computer-aided design (CAD) software tool.

Analysis of gain-switching in two-section tapered lasers

We analyze the gain-switching dynamics of two-section tapered lasers by means of a simplified three-rate-equation model. The goal is to improve the understanding of the underlying physics and to optimize the device geometry to achieve high power short duration optical pulses.