Sitagliptin as combination therapy in the treatment of type 2 diabetes mellitus

The American Diabetes Association and The European Association for the Study of Diabetes recommend metformin as the initial agent of choice in the treatment of type 2 diabetes mellitus. Unfortunately, most patients require multiple medications to obtain glycemic control. One of the newest additions to the antidiabetic armamentarium is the class of drugs known as dipeptidyl-peptidase IV (DPP-IV) inhibitors. This novel approach focuses on harnessing the beneficial effects of GLP-1, an incretin hormone released from the gut postprandially. The first DPP-IV inhibitor approved in the United States was sitagliptin. It has been studied in both monotherapy and combination therapy. Combination studies with metformin realize a hemoglobin A1c reduction of 0.65%–1.1%. The combination of the two has a modest positive effect on body weight with the convenience of an oral route of administration. It has also been shown to be highly tolerable, efficacious and with little risk of hypoglycemia. This review will focus on combination therapy with sitagliptin with emphasis on combination with metformin

Universal nonlinear infection kernel from heterogeneous exposure on higher-order networks

The colocation of individuals in different environments is an important prerequisite for exposure to infectious diseases on a social network. Standard epidemic models fail to capture the potential complexity of this scenario by (1) neglecting the higher-order structure of contacts which typically occur through environments like workplaces, restaurants, and households; and by (2) assuming a linear relationship between the exposure to infected contacts and the risk of infection. Here, we leverage a hypergraph model to embrace the heterogeneity of environments and the heterogeneity of individual participation in these environments. We find that combining heterogeneous exposure with the concept of minimal infective dose induces a universal nonlinear relationship between infected contacts and infection risk. Under nonlinear infection kernels, conventional epidemic wisdom breaks down with the emergence of discontinuous transitions, super-exponential spread, and hysteresis

A Comparative Analysis of the Determinants of Executive Compensation between Canadian and U.S. Firms

Partout en Amérique du Nord, la rémunération des dirigeants de sociétés ouvertes fait de plus en plus l'objet d'un examen minutieux. Cette préoccupation se reflète dans la presse populaire {Globe and Mail, 10 avril 1993 ; Time, 9 janvier 1992) et dans les multiples revues de littérature sur la rémunération des dirigeants (Gomez-Mejia et Welbourne 1989 ; Lambert et Larcker 1991 ; Milkovich et Rabin 1991). Toutefois, la quasi-totalité de la recherche a été réalisée dans un contexte américain. En effet, alors qu'aux États-Unis la Securities and Exchange Commission (SEC) exige que les sociétés ouvertes divulguent la rémunération de leurs cinq dirigeants les mieux payés, les réglementations canadiennes n'obligeaient jusqu'à récemment les sociétés ouvertes à ne divulguer que la somme reçue par leurs dirigeants en tant que groupe.La présente étude vise à combler partiellement ce vide en utilisant les seules données fiables sur la rémunération des dirigeants canadiens, lesquelles sont publiées par des sociétés dont le siège social est au Canada et dont les actions sont négociées sur un marché boursier américain. Ces sociétés sont sujettes à la réglementation américaine de divulgation de la rémunération des dirigeants. La rémunération des dirigeants de ces sociétés canadiennes est d'abord analysée quant à l'étendue des quatre liens suivants (1) la relation entre la taille de l'organisation et la rémunération des dirigeants, (2) celui entre la performance organisationnelle et la rémunération des dirigeants, (3) l'effet direct du contrôle financier de la firme sur la rémunération des dirigeants et, (4) l'effet modérateur du contrôle financier d'une firme sur la relation entre la performance organisationnelle et la rémunération des dirigeants. Par la suite, la rémunération des dirigeants de ces sociétés canadiennes est comparée à celle des dirigeants de sociétés américaines similaires (taille, secteur) quant à l'étendue des quatre liens susmentionnés. L'ampleur des liens est inférée des coefficients obtenus d'analyses de régressions des moindres carrés.Les résultats obtenus indiquent que la taille d'une organisation est reliée positivement à la rémunération des dirigeants des sociétés canadiennes, et de façon plus étroite que pour les dirigeants de sociétés américaines. Les résultats sont cohérents avec ceux obtenus par les études antérieures tant britanniques qu'américaines. Les résultats de l'étude indiquent également que la performance organisationnelle, mesurée par le rendement de l'avoir des actionnaires, influence positivement la rémunération des dirigeants de sociétés canadiennes. Cette relation est toutefois plus forte dans le cas des dirigeants de sociétés américaines. Il ressort également de l'étude que la présence d'actionnaires importants dans une société (contrôle restreint) réduit le niveau de rémunération de ses dirigeants comparativement aux sociétés sans bloc de contrôle (propriété dispersée). Cet effet est plus marqué pour les sociétés américaines. La relation entre la performance organisationnelle et la rémunération des dirigeants de sociétés canadiennes et américaines est toutefois modifiée par l'introduction du contrôle financier comme variable modératrice. En effet, la performance organisationnelle — estimée à partir d'un indice de marché — a un effet positif sur la rémunération des dirigeants de sociétés canadiennes à propriété dispersée mais non sur la rémunération des dirigeants de sociétés canadiennes à contrôle restreint. Par contre, pour les dirigeants de sociétés américaines, la relation entre la performance organisationnelle — estimée par un indice de marché — et la rémunération des dirigeants est positive uniquement pour les sociétés à contrôle restreint mais non pour les sociétés à propriété dispersée. Les résultats obtenus pour les firmes américaines, mais non pour les firmes canadiennes, sont cohérents avec l'interprétation de la théorie des agences proposée par Tosi et Gomez-Mejia (1989). Selon ces auteurs, l'existence d'un bloc de contrôle dans l'actionnariat d'une firme devrait amener l'établissement d'un lien plus étroit entre la performance organisationnelle et la rémunération des dirigeants car les actionnaires ont la capacité d'imposer une formule de rémunération contingente à la performance.This study attempts to identify determinants of executive compensation in Canada while comparing how they differ between Canada and the United States. Results suggest that firm size, firm performance, and firm ownership structure all determine executive compensation in Canada. However, several differences between the determinants of executive compensation in Canada and the U.S. are identified

Influence of the n-p asymmetry on decay properties of palladium isotopes

The INDRA 4 π-array was coupled with the high acceptance spectrometer VAMOS to study the decay of palladium isotopes with a large range of N/Z = 1–1.26, produced in the 34,36,40Ar + 58,60,64Ni reactions at E/A = 13 .3MeV. The coupling of both apparatuses gives the opportunity to detect complete events with light charged particles identified in INDRA and the compound nucleus residue in VAMOS. The detailed studies of this experiment put constraints on the N/Z effects in the statistical models

Personal preferences for Personalised Trials among patients with chronic diseases: an empirical Bayesian analysis of a conjoint survey.

OBJECTIVE: To describe individual patient preferences for Personalised Trials and to identify factors and conditions associated with patient preferences. DESIGN: Each participant was presented with 18 conjoint questions via an online survey. Each question provided two choices of Personalised Trials that were defined by up to eight attributes, including treatment types, clinician involvement, study logistics and trial burden on a patient. SETTING: Online survey of adults with at least two common chronic conditions in the USA. PARTICIPANTS: A nationally representative sample of 501 individuals were recruited from the Chronic Illness Panel by Harris Poll Online. Participants were recruited from several sources, including emails, social media and telephone recruitment of the target population. MAIN OUTCOME MEASURES: The choice of Personalised Trial design that the participant preferred with each conjoint question. RESULTS: There was large variability in participants\u27 preferences for the design of Personalised Trials. On average, they preferred certain attributes, such as a short time commitment and no cost. Notably, a population-level analysis correctly predicted 62% of the conjoint responses. An empirical Bayesian analysis of the conjoint data, which supported the estimation of individual-level preferences, improved the accuracy to 86%. Based on estimates of individual-level preferences, patients with chronic pain preferred a long study duration (p≤0.001). Asthma patients were less averse to participation burden in terms of data-collection frequency than patients with other conditions (p=0.002). Patients with hypertension were more cost-sensitive (p\u3c0.001). CONCLUSION: These analyses provide a framework for elucidating individual-level preferences when implementing novel patient-centred interventions. The data showed that patient preference in Personalised Trials is highly variable, suggesting that individual differences must be accounted for when marketing Personalised Trials. These results have implications for advancing precise interventions in Personalised Trials by indicating when rigorous scientific principles, such as frequent monitoring, is feasible in a substantial subset of patients

Murmuration

Murmuration is an outcome of the EU Culture funded EMDL project (EMDL.eu), exhibited at Society for Arts and Technology’s (SAT) Satosphere. The artistic research initiative brought together an international interdisciplinary group to explore the fulldome environment as a platform for creative innovation. Murmuration consolidated research into networked navigation devices for virtual spaces, swarm algorithms for audience participation, 3D scanning (MRI volumetric modelling) and 3D sonification for game engines in performance

A study of physical activity comparing people with Charcot Marie Tooth disease to normal control subjects

PURPOSE: Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. METHODS: We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. RESULTS: Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. CONCLUSION: The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors • High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. • Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness

Age and anatomy of the Gongga Shan batholith, eastern Tibetan Plateau, and its relationship to the active Xianshui-he fault

The Gongga Shan batholith of eastern Tibet, previously documented as a ca. 32–12.8 Ma granite pluton, shows some of the youngest U-Pb granite crystallization ages recorded from the Tibetan Plateau, with major implications for the tectonothermal history of the region. Field observations indicate that the batholith is composite; some localities show at least seven crosscutting phases of granitoids that range in composition from diorite to leucocratic monzogranite. In this study we present U-Pb ages of zircon and allanite dated by laser ablation–inductively coupled plasma–mass spectrometry on seven samples, to further investigate the chronology of the batholith. The age data constrain two striking tectonic-plutonic events: a complex Triassic–Jurassic (ca. 215–159 Ma) record of biotite-hornblende granodiorite, K-feldspar megacrystic granite and leucogranitic plutonism, and a Miocene (ca. 14–5 Ma) record of monzonite-leucogranite emplacement. The former age range is attributed to widespread Indosinian tectonism, related to Paleo-Tethyan subduction zone magmatism along the western Yangtze block of south China. The younger component may be related to localized partial melting (muscovite dehydration) of thickened Triassic flysch-type sediments in the Songpan-Ganze terrane, and are among the youngest crustal melt granites exposed on the Tibetan Plateau. Zircon and allanite ages reflect multiple crustal remelting events; the youngest, ca. 5 Ma, resulted in dissolution and crystallization of zircons and growth and/or resetting of allanites. The young garnet, muscovite, and biotite leucogranites occur mainly in the central part of the batholith and adjacent to the eastern margin of the batholith at Kangding, where they are cut by the left-lateral Xianshui-he fault. The Xianshui-he fault is the most seismically active strike-slip fault in Tibet and is thought to record the eastward extrusion of the central part of the Tibetan Plateau. The fault obliquely cuts all granites of the Gongga Shan massif and has a major transpressional component in the Kangding-Moxi region. The course of the Xianshui Jiang river is offset by ∼62 km along the Xianshui-he fault and in the Kangding area granites as young as ca. 5 Ma are cut by the fault. Our new geochronological data show that only a part of the Gongga Shan granite batholith is composed of young (Miocene) melt, and we surmise that as most of eastern Tibet is composed of Precambrian–Triassic Indosinian rocks, there is no geological evidence to support regional Cenozoic internal thickening or metamorphism and no evidence for eastward-directed lower crustal flow away from Tibet. We suggest that underthrusting of Indian lower crust north as far as the Xianshui-he fault resulted in Cenozoic uplift of the eastern plateau