Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM.

Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.

Central glucose sensing and the control of energy homeostasis

Glucose is an important signal that regulates glucose and energy homeostasis but its precise physiological role and signaling mechanism in the brain are still uncompletely understood. Over the recent years we have investigated the possibility that central glucose sensing may share functional similarities with glucose sensing by pancreatic beta-cells, in particular a requirement for the expression of the glucose transporter Glut2. Using mice with genetic inactivation of Glut2, but rescued pancreatic beta-cell function by transgenic expression of a glucose transporter, we have established that extrapancreatic glucose sensors are involved: i) in the control of glucagon secretion in response to hypoglycemia, ii) in the control of feeding and iii) of energy expenditure. We have more recently shown that central Glut2-dependent glucose sensors are involved in the regulation of NPY and POMC expression by arcuate nucleus neurons and that the sensitivity to leptin of these neurons is enhanced by Glut2-dependent glucose sensors. Using mice with genetic tagging of Glut2-expressing cells, we determined that the NPY and POMC neurons did not express Glut2 but were connected to Glut2 expressing neurons located most probably outside of the arcuate nucleus. We are now defining the electrophysiological behavior of these Glut2 expressing neurons. Our data provide an initial map of glucose sensing neurons expressing Glut2 and link these neurons with the control of specific physiological function.

Optimization and Management of Materials in Earthwork Construction, TR-501, 2010

As a result of forensic investigations of problems across Iowa, a research study was developed aimed at providing solutions to identified problems through better management and optimization of the available pavement geotechnical materials and through ground improvement, soil reinforcement, and other soil treatment techniques. The overall goal was worked out through simple laboratory experiments, such as particle size analysis, plasticity tests, compaction tests, permeability tests, and strength tests. A review of the problems suggested three areas of study: pavement cracking due to improper management of pavement geotechnical materials, permeability of mixed-subgrade soils, and settlement of soil above the pipe due to improper compaction of the backfill. This resulted in the following three areas of study: (1) The optimization and management of earthwork materials through general soil mixing of various select and unsuitable soils and a specific example of optimization of materials in earthwork construction by soil mixing; (2) An investigation of the saturated permeability of compacted glacial till in relation to validation and prediction with the Enhanced Integrated Climatic Model (EICM); and (3) A field investigation and numerical modeling of culvert settlement. For each area of study, a literature review was conducted, research data were collected and analyzed, and important findings and conclusions were drawn. It was found that optimum mixtures of select and unsuitable soils can be defined that allow the use of unsuitable materials in embankment and subgrade locations. An improved model of saturated hydraulic conductivity was proposed for use with glacial soils from Iowa. The use of proper trench backfill compaction or the use of flowable mortar will reduce the potential for developing a bump above culverts.

Postharvest quality of peaches harvested from integrated and conventional production systems

Over three years the postharvest quality of 'Marli' peaches harvested from the integrated (IFP) and conventional production (CFP) systems was evaluated. The peaches were harvested from commercial orchards of Prunus persica at two locations close to the city of São Jerônimo, RS, Brazil, and stored at 0.5°C for 10, 20 or 30 days. The peaches were evaluated at harvest, at retrieval from storage and after ripening periods at 20°C. No differences in fruit weight losses were determined. Decay incidence was low, and no differences were detected amongst systems in both 2001 and 2002 seasons, but in the 2000 season CFP peaches were more decayed. Flesh firmness of peaches from the IFP system were greater than CFP fruits in the years 2000 and 2001. In 2002, firmness changed little during storage and ripening. Peaches from the IFP in 2000 had higher titratable acidity and lower soluble solids. In the 2000 season, flesh browning was observed in decayed fruits, always at ripening after 20 or 30 days of cold storage Chilling injuries such as browning, woolliness and leatheriness ocurred in 2002. There were no differences amongst systems related to peach quality.

How to interprete subclinical thyroid dysfunction in the prevention and management of heart failure events? Individual participant data analysis from six prospective cohorts

Background: Guidelines of the Diagnosis and Management of Heart Failure (HF) recommend investigating exacerbating conditions, such as thyroid dysfunction, but without specifying impact of different TSH levels. Limited prospective data exist regarding the association between subclinical thyroid dysfunction and HF events. Methods: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of HF events. Individual data on 25,390 participants with 216,247 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH 4.5-19.9 mIU/L and subclinical hyperthyroidism as TSH <0.45 mIU/L, both with normal free thyroxine levels. HF events were defined as acute HF events, hospitalization or death related to HF events. Results: Among 25,390 participants, 2068 had subclinical hypothyroidism (8.1%) and 648 subclinical hyperthyroidism (2.6%). In age- and gender-adjusted analyses, risks of HF events were increased with both higher and lower TSH levels (P for quadratic pattern<0.01): hazard ratio (HR) was 1.01 (95% confidence interval [CI] 0.81-1.26) for TSH 4.5-6.9 mIU/L, 1.65 (CI 0.84-3.23) for TSH 7.0-9.9 mIU/L, 1.86 (CI 1.27-2.72) for TSH 10.0-19.9 mIUL/L (P for trend <0.01), and was 1.31 (CI 0.88-1.95) for TSH 0.10-0.44 mIU/L and 1.94 (CI 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. Conclusion: Risks of HF events were increased with both higher and lower TSH levels, particularly for TSH ≥10 mIU/L and for TSH <0.10 mIU/L. Our findings might help to interpret TSH levels in the prevention and investigation of HF.

Interactions of juvenile Lumbricus terrestris with adults and their burrow systems in a two-dimensional microcosm

The objective of this work was to evaluate interactions of Lumbricus terrestris juveniles with adults and with inherited burrow systems. An experiment was set up using a two dimensional Evans' boxes microcosm. Adult L. terrestris were added to 16 boxes (one individual per box) and kept in darkness at 17ºC along with eight unoccupied boxes for two months. The adult L. terrestris were removed from eight randomly selected boxes, and L. terrestris juveniles were added (one juvenile per box), composing three treatments with eight replicates: 1, with an adult in an inherited burrow (ABJ); 2, alone in an inherited burrow (BJ); and 3, alone in a previously uninhabited box (J). The proportion of juveniles occupying adult burrows observed was significantly different in treatments ABJ (48%) and BJ (75%). The mean mass of juveniles at experimental termination differed significantly among treatments and was greater in treatment J (4.04±0.39 g) in comparison to the BJ (3.09±0.93 g) and ABJ treatments (2.13±0.64 g). Results suggest a negative influence of both the presence of an adult and its burrow system on juvenile growth. Intraspecific competition partially explained this, but further investigation is required to examine how an inherited environment (i.e. burrow) could negatively affect the growth of juveniles.

Modulation of plant HMG-CoA reductase by protein phosphatase 2A: Positive and negative control at a key node of metabolism

The enzyme HMG-CoA reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis, critical not only for normal plant development, but also for the adaptation to demanding environmental conditions. Consistent with this notion, plant HMGR is modulated by many diverse endogenous signals and external stimuli. Protein phosphatase 2A (PP2A) is involved in auxin, abscisic acid, ethylene and brassinosteroid signaling and now emerges as a positive and negative multilevel regulator of plant HMGR, both during normal growth and in response to a variety of stress conditions. The interaction with HMGR is mediated by B" regulatory subunits of PP2A, which are also calcium binding proteins. The new discoveries uncover the potential of PP2A to integrate developmental and calcium-mediated environmental signals in the control of plant HMGR.

Regional differences in self-reported screening, prevalence and management of cardiovascular risk factors in Switzerland.

BACKGROUND: In Switzerland, health policies are decided at the local level, but little is known regarding their impact on the screening and management of cardiovascular risk factors (CVRFs). We thus aimed at assessing geographical levels of CVRFs in Switzerland.¦METHODS: Swiss Health Survey for 2007 (N = 17,879). Seven administrative regions were defined: West (Leman), West-Central (Mittelland), Zurich, South (Ticino), North-West, East and Central Switzerland. Obesity, smoking, hypertension, dyslipidemia and diabetes prevalence, treatment and screening within the last 12 months were assessed by interview.¦RESULTS: After multivariate adjustment for age, gender, educational level, marital status and Swiss citizenship, no significant differences were found between regions regarding prevalence of obesity or current smoking. Similarly, no differences were found regarding hypertension screening and prevalence. Two thirds of subjects who had been told they had high blood pressure were treated, the lowest treatment rates being found in East Switzerland: odds-ratio and [95% confidence interval] 0.65 [0.50-0.85]. Screening for hypercholesterolemia was more frequently reported in French (Leman) and Italian (Ticino) speaking regions. Four out of ten participants who had been told they had high cholesterol levels were treated and the lowest treatment rates were found in German-speaking regions. Screening for diabetes was higher in Ticino (1.24 [1.09 - 1.42]). Six out of ten participants who had been told they had diabetes were treated, the lowest treatment rates were found for German-speaking regions.¦CONCLUSIONS: In Switzerland, cardiovascular risk factor screening and management differ between regions and these differences cannot be accounted for by differences in populations' characteristics. Management of most cardiovascular risk factors could be improved.

Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control.

The Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21(WAF1/Cip1) gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-Jkappa protein to the p21 promoter. We show here that Notch 1 activation functions also through a second Calcineurin-dependent mechanism acting on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene, Calcineurin contributes significantly to the transcriptional response of keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype, associated with altered expression of Notch-responsive genes involved in hair follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth/differentiation control.

Evaluating teaching and management innovations in an online university: the case of the Universitat Oberta de Catalunya

The Universitat Oberta de Catalunya (UOC) is an online university that has innovation as a transversal feature in all its activities and processes. Therefore, innovation is present in the annual objectives of all the academic and management departments in order to increase student satisfaction. UOC stimulates innovation by funding strategic projects as well as organizing regular internal calls for small projects which brings about innovative academic and management proposals. In this paper we present the method for evaluating teaching and management innovations through internal calls (APLICA), by selecting which initiatives are suitable to become strategic innovative projects (INNOVA) or which features should compose any application available at the OpenApps platform. Besides, general indicators used by the Innovation Program to evaluate the activities carried out are also reported.

Prevention and management of potential adverse events during transapical aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Transapical transcatheter aortic valve replacement (TAVR) is a new minimally invasive technique with a known risk of unexpected intra-procedural complications. Nevertheless, the clinical results are good and the limited amount of procedural adverse events confirms the usefulness of a synergistic surgical/anesthesiological management in case of unexpected emergencies. METHODS: A review was made of the authors' four-year database and other available literature to identify major and minor intra-procedural complications occurring during transapical TAVR procedures. All implants were performed under general anesthesia with a balloon-expandable Edwards Sapien stent-valve, and followed international guidelines on indications and techniques. RESULTS: Procedural success rates ranged between 94% and 100%. Life-threatening apical bleeding occurred very rarely (0-5%), and its incidence decreased after the first series of implants. Stent-valve embolization was also rare, with a global incidence ranging from 0-2%, with evidence of improvement after the learning curve. Rates of valve malpositioning ranged from 0% to < 3%, whereas the risk of coronary obstruction ranged from 0% to 3.5%. Aortic root rupture and dissection were dramatic events reported in 0-2% of transapical cases. Stent-valve malfunction was rarely reported (1-2%), whereas the valve-in-valve bailout procedure for malpositioning, malfunctioning or severe paravalvular leak was reported in about 1.0-3.5% of cases. Sudden hemodynamic management and bailout procedures such as valve-in-valve rescue or cannulation for cardiopulmonary bypass were more effective when planned during the preoperative phase. CONCLUSION: Despite attempts to avoid pitfalls, complications during transapical aortic valve procedures still occur. Preoperative strategic planning, including hemodynamic status management, alternative cannulation sites and bailout procedures, are highly recommended, particularly during the learning curve of this technique.

Legal issues in promoting FOSS in R+D projects - Policy, Organisation and Management

Creating and using FLOSS in R+D projects raises several legal issues, which need to be managed as soon as possible - preferably during the project planning stage. Challenges in the areas of project structure and policy, licenses and licensing, exploitation strategies, community management, and FLOSS-friendliness in general all have their legal aspects, which are commented here. Some recommendations are made for assisting in the use of FLOSS in R+D projects, especially in multiple party consortiums.

Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.

The role of financial and accounting methods as estimators of intrinsic value: the Tubacex case

En aquest treball estudiem si el valor intrínsec de Tubacex entre 1994-2013 coincideix amb la seva tendència bursàtil a llarg termini, tenint en compte part de la teoria defensada per Shiller. També verifiquem la possible infravaloració de l’acció de Tubacex a 31/12/13. A la primera part expliquem els principals mètodes de valoració d’empreses y a la segona part fem una anàlisi del sector en el que opera Tubacex (acer inoxidable) i calculem el valor de l’acció de Tubacex per mitjà de tres mètodes de valoració (Free Cash Flow, Cash Flow i Valor en Llibres). Apliquem aquests tres mètodes de valoració per verificar si com a mínim algun d’ells coincideix amb la tendència bursàtil a llarg termini.