Effect of training on the response of plasma vascular endothelial growth factor to exercise in patients with peripheral arterial disease

Expansion of the capillary network, or angiogenesis, occurs following endurance training. This process, which is reliant on the presence of VEGF (vascular endothelial growth factor), is an adaptation to a chronic mismatch between oxygen demand and supply. Patients with IC (intermittent claudication) experience pain during exercise associated with an inadequate oxygen delivery to the muscles. Therefore the aims of the present study were to examine the plasma VEGF response to acute exercise, and to establish whether exercise training alters this response in patients with IC. In Part A, blood was collected from patients with IC (n = 18) before and after (+ 20 and + 60 min post-exercise) a maximal walking test to determine the plasma VEGF response to acute exercise. VEGF was present in the plasma of patients (45.11 +/- 29.96 pg/ml) and was unchanged in response to acute exercise. Part B was a training study to determine whether exercise training altered the VEGF response to acute exercise. Patients were randomly assigned to a treatment group (TMT; n = 7) that completed 6 weeks of high-intensity treadmill training, or to a control group (CON; n = 6). All patients completed a maximal walking test before and after the intervention, with blood samples drawn as for Part A. Training had no effect on plasma VEGF at rest or in response to acute exercise, despite a significant increase in maximal walking time in the TMT group (915 + 533 to 1206 + 500 s; P = 0.009) following the intervention. The absence of a change in plasma VEGF may reflect altered VEGF binding at the endothelium, although this cannot be confirmed by the present data.

The effect of inversion on the encoding of normal and “thatcherized” faces

In the "Thatcher illusion" a face, in which the eyes and mouth are inverted relative to the rest of the face, looks grotesque when shown upright but not when inverted. In four experiments we investigated the contribution of local and global processing to this illusion in normal observers. We examined inversion effects (i.e., better performance for upright than for inverted faces) in a task requiring discrimination of whether faces were or were not "thatcherized". Observers made same/different judgements to isolated face parts (Experiments 1-2) and to whole faces (Experiments 3-4). Face pairs had the same or different identity, allowing for different processing strategies using feature-based or configural information, respectively. In Experiment 1, feature-based matching of same-person face parts yielded only a small inversion effect for normal face parts. However, when feature-based matching was prevented by using the face parts of different people on all trials (Experiment 2) an inversion effect occurred for normal but not for thatcherized parts. In Experiments 3 and 4, inversion effects occurred with normal but not with thatcherized whole faces, on both same- and different-person matching tasks. This suggests that a common configural strategy was used with whole (normal) faces. Face context facilitated attention to misoriented parts in same-person but not in different-person matching. The results indicate that (1) face inversion disrupts local configural processing, but not the processing of image features, and (2) thatcherization disrupts local configural processing in upright faces.

Innovation in the pharmaceutical industry:a study of the effects of regulation on the U.K. pharmaceutical industry

A history of government drug regulation and the relationship between the pharmaceutical companies in the U.K. and the licensing authority is outlined. Phases of regulatory stringency are identified with the formation of the Committees on Safety of Drugs and Medicines viewed as watersheds. A study of the impact of government regulation on industrial R&D activities focuses on the effects on the rate and direction of new product innovation. A literature review examines the decline in new chemical entity innovation. Regulations are cited as a major but not singular cause of the decline. Previous research attempting to determine the causes of such a decline on an empirical basis is given and the methodological problems associated with such research are identified. The U.K. owned sector of the British pharmaceutical industry is selected for a study employing a bottom-up approach allowing disaggregation of data. A historical background to the industry is provided, with each company analysed or a case study basis. Variations between companies regarding the policies adopted for R&D are emphasised. The process of drug innovation is described in order to determine possible indicators of the rate and direction of inventive and innovative activity. All possible indicators are considered and their suitability assessed. R&D expenditure data for the period 1960-1983 is subsequently presented as an input indicator. Intermediate output indicators are treated in a similar way and patent data are identified as a readily-available and useful source. The advantages and disadvantages of using such data are considered. Using interview material, patenting policies for most of the U.K. companies are described providing a background for a patent-based study. Sources of patent data are examined with an emphasis on computerised systems. A number of searches using a variety of sources are presented. Patent family size is examined as a possible indicator of an invention's relative importance. The patenting activity of the companies over the period 1960-1983 is given and the variation between companies is noted. The relationship between patent data and other indicators used is analysed using statistical methods resulting in an apparent lack of correlation. An alternative approach taking into account variations in company policy and phases in research activity indicates a stronger relationship between patenting activity, R&D Expenditure and NCE output over the period. The relationship is not apparent at an aggregated company level. Some evidence is presented for a relationship between phases of regulatory stringency, inventive and innovative activity but the importance of other factors is emphasised.

The functional effects of ceramide on the monocyte CD36 scavenger receptor and NADPH oxidase

Atherosclerosis is the principal cause of death in the United States, Europe and much of Asia. During the last decade, inflammation has been suggested to play a key role in the development of atherosclerosis. Reactive oxygen species (ROS) released during inflammation additionally oxidize LDL, which is subsequently taken up in an unregulated way through scavenger receptors on macrophages to form foam cells, the hallmark of atherosclerotic lesions. Previous work has shown that the lipid ceramide, which is found in aggregated LDL and in atherosclerotic plaques, decreases intracellular peroxide most likely through reducing NADPH oxidase activity. Ceramide is an important component of membrane microdomains called lipid rafts which are important for membrane protein function. Endogenous ceramide enhances lipid raft f'ormation and alters theirs composition. NADPH oxidase membrane subunits cytochrome b558 (which includes gp91) strongly associates with lipid rafts Therefore present study investigated whether short chain ceramides reduce NADPH oxidase in U937 monocytes by disrurting the membrane component of NADPH oxidase. Results showed that C2 ceramide alters the distribution of raft marker, flottillin and the raft environment. NADPH oxidase membrane component gp9J phox and cytosolic component p47 phox were identified in rafts. C2 ceramide reduces both gp91 and p47 phox in rafts, which leads to the decrease of peroxide production by NADPH oxidase. Ceramide is also an important second messenger involved in many different signaling pathways associated with atherogenesis from the activation of sphingomyelinase (SMase). It has been reported that SMase enhances LDL receptor mediated LDL endocytosis. However, no study has been done to investigate the effect of ceramide on scavenger receptors such as CD36 and oxidized LDL (OxLDL) uptake. CD36 is the major recertor far OxLDL. Reduced CD36 expression results in less foam cell formation and less atherosclerotic lesion without disrupting the clearance of OxLDL from plasma. This thesis shows that ceramides significantly reduce CD36 surface expression on U937 monocytes, macrophages and human primary monocytes. This effect is seen using both synthetic short chain ceramide and SMase catalysed long chain ceramide treatment. To investigate whether the effect of ceramide on CD36 is functional, OxLOL uptake was measured in ceramide treated cells. Ceramide reduces the uptake of OxLOL by both U937 monocytes and PMA-differentiated macrophages. The mechanism of ceramide reduction of CD36 expression was studied by measuring the surface antigen using flow cytometry and fluorescence microscopy, whole cellular CD36 expression and shedding of C036 by Western blotting of cell lysates and cell culture supernatants and mRNA level of CD36 using RT-PCR. Ceramide reduces shedding of CD36, activates mRNA expression of CD36 and induces intracellular CD36 accumulation probably through retaining the receptor inside cells. In summary, ceramides modulate several of the processes involved in LOL oxidation and uptake by CD36 receptors on monocytes/macrophages in a way which may protect against atherosclerosis.

An analysis of research on the future of purchasing and supply management

Business organisations are going through rapid external environmental and internal organisational changes due to increasing globalisation, E-business, and outsourcing. As a result, the future of purchasing and supply management—as a function within organisations, as a process that spans organisation boundaries and as a profession—raises important concerns for both organisations and the purchasing professional. This paper considers a broad and rather fragmented body of empirical evidence and analyses 42 relevant empirical studies on the future of purchasing and supply management. The major findings are reported in terms of changes in business contexts, purchasing strategy, structure, role and responsibility, system development and skills. Cross-sectional comparative analyses were also conducted to examine variation by sector, firm type, people's roles in purchasing, and country. A number of major implications for the purchasing function, process and professional bodies are presented together with suggestions for future research to address significant gaps in the current body of knowledge.

The impact of coordination on the effectiveness of last mile relief distribution

Last mile relief distribution is the final stage of humanitarian logistics. It refers to the supply of relief items from local distribution centers to the disaster affected people (Balcik et al., 2008). In the last mile relief distribution literature, researchers have focused on the use of optimisation techniques for determining the exact optimal solution (Liberatore et al., 2014), but there is a need to include behavioural factors with those optimisation techniques in order to obtain better predictive results. This paper will explain how improving the coordination factor increases the effectiveness of the last mile relief distribution process. There are two stages of methodology used to achieve the goal: Interviews: The authors conducted interviews with the Indian Government and with South Asian NGOs to identify the critical factors for final relief distribution. After thematic and content analysis of the interviews and the reports, the authors found some behavioural factors which affect the final relief distribution. Model building: Last mile relief distribution in India follows a specific framework described in the Indian Government disaster management handbook. We modelled this framework using agent based simulation and investigated the impact of coordination on effectiveness. We define effectiveness as the speed and accuracy with which aid is delivered to affected people. We tested through simulation modelling whether coordination improves effectiveness.

The effect of instruction on the study behaviors and academic achievement of community college students

The purpose of this study was twofold. It was designed to determine (a) the efficacy of an intervention designed to increase the frequencies of appropriate study behaviors on the part of community college students who were preparing for academic mathematics activities and (b) whether any increase in appropriate study behavior frequency was accompanied by increased academic achievement in college preparatory mathematics classes. A total of 126 Miami Dade College students participated in this study. Two developmental (remedial) mathematics classes were randomly assigned as the experimental group, and two others were assigned as the control group. All students also took a College Survival (SLS) class. The Study Behavior Inventory (SBI) and the Computerized Placement Test (CPT) were administered to the four classes. The SBI was used as a pre- and post-test. The SLS curriculum and classroom time were the same for both groups. However, students in the treatment groups received instruction designed to increase the frequency of effective study behaviors associated with the three factors identified in the SBI, while the students in the control group participated in activities that did not emphasize study behaviors. A series of analysis of covariance procedures were used to analyze four hypotheses. The first three hypotheses proposed that students who were instructed in the use of appropriate study behaviors would score higher on the three factors of the Study Behavior Inventory than those who were not. The fourth hypothesis proposed that a greater proportion of mathematics students who were instructed in the use of appropriate study behaviors would receive a passing grade in their course than students who were in the control group. The four hypotheses were tested at the .05 level of significance. This study revealed that students who received instruction in appropriate study behaviors scored higher in the use of appropriate study behaviors and in mathematics achievement than students who did not. Additional research is needed to investigate whether these effects would persist over time, or be found in subjects other than mathematics.

The Influence of Vegetation on the Hydrodynamics and Geomorphology of a Tree Island in Everglades National Park (Florida, United States)

Transpiration-driven nutrient accumulation has been identified as a potential mechanism governing the creation and maintenance of wetland vegetation patterning. This process may contribute to the formation of nutrient-rich tree islands within the expansive oligotrophic marshes of the Everglades (Florida, United States). This study presents hydrogeochemical data indicating that tree root water uptake is a primary driver of groundwater ion accumulation across one of these islands. Sap flow, soil moisture, water level, water chemistry, and rainfall were measured to identify the relationships between climate, transpiration, and groundwater uptake by phreatophytes and to examine the effect this uptake has on groundwater chemistry and mineral formation in three woody plant communities of differing elevations. During the dry season, trees relied more on groundwater for transpiration, which led to a depressed water table and the advective movement of groundwater and dissolved ions, including phosphorus, from the surrounding marsh towards the centre of the island. Ion exclusion during root water uptake led to elevated concentrations of all major dissolved ions in the tree island groundwater compared with the adjacent marsh. Groundwater was predominately supersaturated with respect to aragonite and calcite in the lower-elevation woody communities, indicating the potential for soil formation. Elevated groundwater phosphorous concentrations detected in the highest-elevation woody community were associated with the leaching of inorganic sediments (i.e. hydroxyapatite) in the vadose zone. Understanding the complex feedback mechanisms regulating plant/groundwater/surface water interactions, nutrient dynamics, and potential soil formation is necessary to manage and restore patterned wetlands such as the Everglades.

Acculturation and Hispanic identity/ethnicity as a predictor of change on the brief situational confidence questionnaire

The purpose of this study was to investigate whether level of acculturation among Hispanic adolescent males (n = 174) influenced treatment outcome in a substance abuse program, specifically on the Brief Situational Confidence Questionnaire (BSCQ) which measures relapse confidence. It was hypothesized that lower levels of acculturation were likely to be predictive of positive change, whereas higher levels of acculturation were likely to be predictive of no change or negative change. It was found that adolescents changed over time in BSCQ scores regardless of which acculturation variable was measured. Contrary to expectations, for those adolescents placed in family treatment, place of birth was not significantly associated with treatment response. However, both, U.S. and non-U.S. born adolescents demonstrated a change over time when receiving family treatment, suggesting that the family substance abuse treatment utilized in this intervention effected change over time.

The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

[EN]GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway

Quantifying and Modeling the Influence of Forest on the Magnitude and Duration of Mountain Snow Storage in the Pacific Northwest, USA

Thesis (Ph.D.)--University of Washington, 2016-08

Marketing in SMEs: the sales process of SMEs on the food and drink industry.

There would appear to be varied approaches to the sales process practiced by SMEs in how they go about locating target customers, interfacing with prospects and new customers, presenting the benefits and features of their products and services, closing sales deals and building relationships, and an understanding of what the buyers needs are in the seller-buyer process. Recent research has revealed that while entrepreneurs and small business owners rely upon networking as an important source of sales, they lack marketing competencies, including personal selling skills and knowledge of what is involved in the sales process to close sales deals and build relationships. Small companies and start-ups with innovative products and services often find it difficult to persuade potential buyers of the merits of their offerings because, while the products and services may be excellent, they have not sufficiently well-developed selling skills necessary to persuade their target customers.

Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach

Background and Purpose: At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size. Methods: Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta meta-analysis to obtain a summary measure of the impact of the various design characteristics. Results: Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score. Conclusions: We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

Use of medications on the elderly

The elderly constitute a growing world population group, with more than 200 million people over 60 years of age. This fact has increased the detection of chronic-degenerative diseases, as well as the prescription and consumption of medicines. The elderly are particularly susceptible to adverse drug events or interactions with other drugs due to their physiological changes, genetic predisposition and environmental exposure. It becomes necessary to adapt the health systems with integral and multidisciplinary approaches suitable to this demographic change, as the knowledge about appropriate prescription, clinical pharmacology and medication use in the elderly has become essential. It has been shown that about two thirds of elderly patients receive inappropriate drug doses, and a substantial percentage of their hospital admissions are associated with potentially preventable toxic effects of drugs. To date, expert criteria, error detection tools and educational prescription plans have been developed by expert consensus for the safe use of drugs in the geriatric population. The objective of this study is a brief review of the principal physiological changes in an older adult, and summarize the contributions of the consensuses on prescription.