Priority sites for wildfowl conservation in Mexico

A set of priority sites for wildfowl conservation in Mexico was determined using contemporary count data (1991–2000) from the U.S. Fish & Wildlife Service mid-winter surveys. We used a complementarity approach implemented through linear integer programming that addresses particular conservation concerns for every species included in the analysis and large fluctuations in numbers through time. A set of 31 priority sites was identified, which held more than 69% of the mid-winter count total in Mexico during all surveyed years. Six sites were in the northern highlands, 12 in the central highlands, six on the Gulf of Mexico coast and seven on the upper Pacific coast. Twenty-two sites from the priority set have previously been identified as qualifying for designation as wetlands of international importance under the Ramsar Convention and 20 sites are classified as Important Areas for Bird Conservation in Mexico. The information presented here provides an accountable, spatially-explicit, numerical basis for ongoing conservation planning efforts in Mexico, which can be used to improve existing wildfowl conservation networks in the country and can also be useful for conservation planning exercises elsewhere

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from two randomized, placebo-controlled clinical trials

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 (KP54) can induce oocyte maturation during in vitro fertilization treatment, including in women at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. Objective To determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (Phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (Phase-2a trial). Design Two randomized, placebo-controlled, parallel group, dose-finding trials. Setting Clinical trials unit, Netherlands. Participants Healthy women aged 18-35 years, either without (Phase-1; n=24), or with ovarian stimulation (Phase-2a; n=75). Interventions Phase-1: Single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n=6 per dose). Phase-2a: Single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n=16-17 per dose), triptorelin 0.2 mg (n=5; active comparator), or placebo (n=5). Main Objectives and Outcome Measures Phase-1: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones). Phase-2a: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); time to ovulation assessed by transvaginal ultrasound. Results In both trials, MVT-602 was safe and well-tolerated across the entire dose-range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours. In the Phase-2a trial, LH concentrations increased dose-dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3μg MVT-602 and remained above 15 IU/L for 33 hours. Time to ovulation following drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1μg), 82% (0.3μg), and 75% (0.1μg), of women after MVT-602, 100% after triptorelin, and 60% after placebo. Conclusions MVT-602 induces LH concentrations of similar amplitude and duration as the physiological mid-cycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR

Large-eddy simulation of spectral coherence in a wind turbine wake

This work is mainly dedicated to the study of the characteristics of spectral coherence of turbulence fluctuations in wind turbine wakes. A computational fluid dynamics (CFD) code has been implemented using a large-eddy simulation (LES) approach, which is thought to be conceptually more suitable for studying the turbulence evolution in a wind turbine wake. Comparisons with experimental data from the Nørrekær Enge II Windfarm, in Denmark, and with an analytical model proposed by Panofsky and Dutton have been performed, and the results are found to be in reasonable agreement with both

Revisión taxonómica del género Gamochaeta Wedd. (Gnaphalieae, Asteraceae) en Chile

Twenty four species of Gamochaeta (Gnaphalieae, Asteraceae), G. aliena, G. alpina, G. americana, G. andina, G. axillaris, G. chamissonis, G. depilata, G. deserticola, G. falcata, G. filaginea, G. humilis, G. longipedicellata, G. neuquensis, G. nivalis, G. oligantha, G. procumbens, G. ramosa, G. serpyllifolia, G. simplicicaulis, G. spiciformis, G. stachydifolia, G. subfalcata, G. valparadisea, and G. villarroelii, are formally monographed with morphological descriptions, illustrations, geographic distribution and habitat, distribution maps, phenology, lists of representative specimens examined, and a comprehensive identification key for every species. A new name Gamochaeta ramosa S.E. Freire, N. Bayón & C.M. Baeza for Gnaphalium ramosum Phil. (1864) non Lam. (1779) nec Sch. Bip. (1845), is proposed. The following taxa are newly synonymized: Gamochaeta foliosa with G. spiciformis; G. monticola with G. oligantha; Gnaphalium petraeumwith Gamochaeta andina; G. suffruticosa with G. chamissonis; Gnaphalium bellidifolium, Gamochaeta berteroana with G. filaginea; and Gnaphalium agreste with Gamochaeta stachydifolia. Lectotypes are newly designated for Gnaphalium andinum, G. berteroanum, G. suffruticosum, and G. villarroelii.Este trabajo comprende la revisión de 24 especies de Gamochaeta para Chile, G. aliena, G. alpina, G. americana, G. andina, G. axillaris, G. chamissonis, G. depilata, G. deserticola, G. falcata, G. filaginea, G. humilis, G. longipedicellata, G. neuquensis, G. nivalis, G. oligantha, G. procumbens, G. ramosa, G. serpyllifolia, G. simplicicaulis, G. spiciformis, G. stachydifolia, G. subfalcata, G. valparadisea y G. villarroelii. Se incluye una clave para identificarlas y para cada una de las especies se brinda descripción, ilustración, fenología, distribución geográfica y hábitat, mapa de distribución, material adicional examinado y afinidades taxonómicas. Sobre la base del estudio de los materiales tipo, se establecen los siguientes nuevos sinónimos: Gamochaeta foliosa con G. spiciformis; G. monticola con G. oligantha; Gnaphalium petraeum con Gamochaeta andina; G. suffruticosa con G. chamissonis; Gnaphalium bellidifolium, Gamochaeta berteroana con G. filaginea; Gnaphalium agreste con Gamochaeta stachydifolia; y se propone el nuevo nombre Gamochaeta ramosa S.E. Freire, N. Bayón & C.M. Baeza parar Gnaphalium ramosum Phil. (1864) non Lam. (1779) nec Sch. Bip. (1845). Se designan lectotipos para las siguientes especies: Gnaphalium andinum, G. berteroanum, G. suffruticosum y G. villarroelii

Emerging role of insulin with incretin therapies for management of type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease warranting intensification of treatment, as beta-cell function declines over time. Current treatment algorithms recommend metformin as the first-line agent, while advocating the addition of either basal-bolus or premixed insulin as the final level of intervention. Incretin therapy, including incretin mimetics or enhancers, are the latest group of drugs available for treatment of T2DM. These agents act through the incretin axis, are currently recommended as add-on agents either as second-or third-line treatment, without concurrent use of insulin. Given the novel role of incretin therapy in terms of reducing postprandial hyperglycemia, and favorable effects on weight with reduced incidence of hypoglycemia, we explore alternative options for incretin therapy in T2DM management. Furthermore, as some evidence alludes to incretins potentially increasing betacell mass and altering disease progression, we propose introducing these agents earlier in the treatment algorithm. In addition, we suggest the concurrent use of incretins with insulin, given the favorable effects especially in relation to weight gain

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance

Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials

AIMS/HYPOTHESIS: Delayed-release metformin (Metformin DR) was developed to maximise gut-based mechanisms of metformin action by targeting the drug to the ileum. Metformin DR was evaluated in two studies. Study 1 compared the bioavailability and effects on circulating glucose and gut hormones (glucagon-like peptide-1, peptide YY) of Metformin DR dosed twice-daily to twice-daily immediate-release metformin (Metformin IR). Study 2 compared the bioavailability and glycaemic effects of Metformin DR dosages of 1,000 mg once-daily in the morning, 1,000 mg once-daily in the evening, and 500 mg twice-daily. METHODS: Study 1 was a blinded, randomised, crossover study (three × 5 day treatment periods) of twice-daily 500 mg or 1,000 mg Metformin DR vs twice-daily 1,000 mg Metformin IR in 24 participants with type 2 diabetes conducted at two study sites (Celerion Inc.; Tempe, AZ, and Lincoln, NE, USA). Plasma glucose and gut hormones were assessed over 10.25 h at the start and end of each treatment period; plasma metformin was measured over 11 h at the end of each treatment period. Study 2 was a non-blinded, randomised, crossover study (three × 7 day treatment periods) of 1,000 mg Metformin DR once-daily in the morning, 1,000 mg Metformin DR once-daily in the evening, or 500 mg Metformin DR twice-daily in 26 participants with type 2 diabetes performed at a single study site (Celerion, Tempe, AZ). Plasma glucose was assessed over 24 h at the start and end of each treatment period, and plasma metformin was measured over 30 h at the end of each treatment period. Both studies implemented centrally generated computer-based randomisation using a 1:1:1 allocation ratio. RESULTS: A total of 24 randomised participants were included in study 1; of these, 19 completed the study and were included in the evaluable population. In the evaluable population, all treatments produced similar significant reductions in fasting glucose (median reduction range, −0.67 to −0.81 mmol/l across treatments) and postprandial glucose (Day 5 to baseline AUC(0–t) ratio = 0.9 for all three treatments) and increases in gut hormones (Day 5 to baseline AUC(0–t) ratio range: 1.6–1.9 for GLP-1 and 1.4–1.5 for PYY) despite an almost 60% reduction in systemic metformin exposure for 500 mg Metformin DR compared with Metformin IR. A total of 26 randomised participants were included in study 2: 24 had at least one dose of study medication and at least one post-dose pharmacokinetic/pharmacodynamic assessment and were included in the pharmacokinetic/pharmacodynamic intent-to-treat analysis; and 12 completed all treatment periods and were included in the evaluable population. In the evaluable population, Metformin DR administered once-daily in the morning had 28% (90% CI −16%, −39%) lower bioavailability (least squares mean ratio of metformin AUC(0–24)) compared with either once-daily in the evening or twice-daily, although the glucose-lowering effects were maintained. In both studies, adverse events were primarily gastrointestinal in nature, and indicated similar or improved tolerability for Metformin DR vs Metformin IR; there were no clinically meaningful differences in vital signs, physical examinations or laboratory values. CONCLUSIONS/INTERPRETATION: Dissociation of gut hormone release and glucose lowering from plasma metformin exposure provides strong supportive evidence for a distal small intestine-mediated mechanism of action. Directly targeting the ileum with Metformin DR once-daily in the morning may provide maximal metformin efficacy with lower doses and substantially reduce plasma exposure. Metformin DR may minimise the risk of lactic acidosis in those at increased risk from metformin therapy, such as individuals with renal impairment. TRIAL REGISTRATION: Clinicaltrials.gov NCT01677299, NCT01804842 FUNDING: This study was funded by Elcelyx Therapeutics Inc. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-3992-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users

A semi-parabolic wake model for large offshore wind farms based on the open source CFD solver OpenFOAM

Wake effect represents one of the main sources of energy loss and uncertainty when designing offshore wind farms. Traditionally analytical models have been used to optimize and estimate power deficits. However these models have shown to underestimate wake effect and consequently overestimate output power [1, 2]. This means that analytical models can be very helpful at optimizing preliminary layouts but not as accurate as needed for an ultimate fine design. Different techniques can be found in the literature to study wind turbine wakes that include simplified kinematic models and more advanced field models, that solve flow equations with different turbulence closure schemes. See the review papers of Crespo et al. [3], Vermeer et al. [4], and Sanderse et al. [5]. Purely elliptic Computational Fluid Dynamics (CFD) models based on the actuator disk technique have been developed during the last years [6–8]. They consider wind turbine rotor as a disk where a distribution of axial forces act over the incoming air. It is a fair approach but it can still be computationally expensive for big wind farms in an operative mode. With this technique still active, an alternative approach inspired on the parabolic wake models [9, 10] is proposed. Wind turbine rotors continue to be represented as actuator disks but now the domain is split into subdomains containing one or more wind turbines. The output of each subdomain is mapped onto the input boundary of the next one until the end of the domain is reached, getting a considerable decrease on computational time, by a factor of order 10. As the model is based on the open source CFD solver OpenFOAM, it can be parallelized to speed-up convergence. The near wake is calculated so no initial wind speed deficit profiles have to be supposed as in totally parabolic models and alternative turbulence models, such as the anisotropic Reynolds Stress Model (RSM) can be used. Traditional problems of elliptic models related to the estimation of the reference wind speed at each rotor position are mitigated due to the semi-parabolic algorithm. The model has been validated at the ECN test farm and at the offshore Horns Rev wind farm with significant results and also have been compared to other wake models

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation.

INTRODUCTION: The first-choice drug therapy in the management of type 2 diabetes is metformin . However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin. Linagliptin is the most recently launched gliptin, with a unique pharmacokinetic (PK) profile characterized by negligible renal excretion and is now also available as a fixed-dose combination (FDC) with metformin. AREAS COVERED: An extensive literature search was performed to analyze the potential PK and pharmacodynamic interactions between linagliptin and metformin. Linagliptin and metformin may be administered together, either separately or as FDC supported by bioequivalence studies. Linagliptin and metformin are not prone to PK drug-drug interactions. Their coadministration improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects. EXPERT OPINION: The combination linaglitpin plus metformin, if not contraindicated (renal failure), may be used as first-line or second-line therapy in the management of type 2 diabetes. That being said, the durability of the glucose-lowering effect of this combination needs to be further explored in long-term controlled trials