The politics of negotiation and implementation: A reciprocal water access agreement in the Himalayan foothills, India

In this paper, we examine the on-the-ground realities of upstream-downstream negotiations and transactions over ecosystem services. We explore the engagement, negotiation, implementation, and postimplementation phases of a “reciprocal water access” (RWA) agreement between village communities and municipal water users at Palampur, Himachal Pradesh, India. We aim to highlight how external actors drove the payments for ecosystem services agenda through a series of facilitation and research engagements, which were pivotal to the RWA’s adoption, and how the agreement fared once external agents withdrew. In the postimplementation period, the RWA agreement continues to be upheld by upstream communities amidst evolving, competing land-use changes and claims. The introduction of cash payments for environmental services for forest-water relationships has given rise to multifaceted difficulties for the upstream hamlets, which has impeded the functionality of their forest management committee. Upstream communities’ formal rights and abilities to control and manage their resources are dynamic and need strengthening and assurance; these developments result in fluctuating transaction and opportunity costs not originally envisaged by the RWA agreement. The paper demonstrates the importance of an explicit understanding of the local politics of negotiation and implementation to determine the effectiveness of compensation-based mechanisms for the supply of ecosystem services.Natural Environment Research CouncilThis is the final version of the article. It first appeared from Resilience Alliance via http://dx.doi.org/10.5751/ES-08462-21023

Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)

BACKGROUND: Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition. METHODS: We present a Canadian FPLD3 kindred with an affected mother who had loss of fat on arms and legs, but no increase in facial, neck, suprascapular or abdominal fat. She had profound insulin resistance, diabetes, severe hypertriglyceridemia and relapsing pancreatitis, while her pre-pubescent daughter had normal fat distribution but elevated plasma triglycerides and C-peptide and depressed high-density lipoprotein cholesterol. RESULTS: The mother and daughter were each heterozygous for PPARG nonsense mutation Y355X, whose protein product in vitro was transcriptionally inactive with no dominant-negative activity against the wild-type receptor. In addition the mutant protein appeared to be markedly unstable. CONCLUSION: Taken together with previous studies of human PPARG mutations, these findings suggest that PPAR-γ deficiency due either to haploinsufficiency or to substantial activity loss due to dominant negative interference of the normal allele product's function can each contribute to the FPLD3 phenotype

Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics

Understanding allostery in enzymes and tools to identify it, offer promising alternative strategies to inhibitor development. Through a combination of equilibrium and nonequilibrium molecular dynamics simulations, we identify allosteric effects and communication pathways in two prototypical class A β-lactamases, TEM-1 and KPC-2, which are important determinants of antibiotic resistance. The nonequilibrium simulations reveal pathways of communication operating over distances of 30 Å or more. Propagation of the signal occurs through cooperative coupling of loop dynamics. Notably, 50% or more of clinically relevant amino acid substitutions map onto the identified signal transduction pathways. This suggests that clinically important variation may affect, or be driven by, differences in allosteric behavior, providing a mechanism by which amino acid substitutions may affect the relationship between spectrum of activity, catalytic turnover and potential allosteric behavior in this clinically important enzyme family. Simulations of the type presented here will help in identifying and analyzing such differences

Probing ultrafast carrier dynamics and nonlinear absorption and refraction in core-shell silicon nanowires

We investigate the relaxation dynamics of photogenerated carriers in silicon nanowires consisting of a crystalline core and a surrounding amorphous shell, using femtosecond time-resolved differential reflectivity and transmission spectroscopy at photon energies of 3.15 eV and 1.57 eV. The complex behavior of the differential transmission and reflectivity transients is the mixed contributions from the crystalline core and the amorphous silicon on the nanowire surface and the substrate where competing effects of state filling and photoinduced absorption govern the carrier dynamics. Faster relaxation rates are observed on increasing the photo-generated carrier density. Independent experimental results on crystalline silicon-on-sapphire help us in separating the contributions from the carrier dynamics in crystalline core and the amorphous regions in the nanowire samples. Further, single beam z-scan nonlinear transmission experiments at 1.57 eV in both open and close aperture configurations yield two-photon absorption coefficient \$beta$ (~3 cm/GW) and nonlinear refraction coefficient \$gamma$ (-2.5x10^-4 cm2/GW).Comment: 6 pages, 6 figure

Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men

<p>Abstract</p> <p>Background</p> <p>Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.</p> <p>Methods</p> <p>Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.</p> <p>Results</p> <p>Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).</p> <p>Conclusions</p> <p>This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.</p

Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55–0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0–5.7), with a number needed to treat of 23 (95% CI, 18–33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event–free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1–4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4–4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0–6.7]), cardiovascular death (2.2 years [95% CI, 1.2–3.0]), and all-cause death (2.4 years [95% CI, 1.4–3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1–3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8–5.9]), and all-cause death (1.8 years [95% CI, 0.7–2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival

Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials

BACKGROUND: Sodium glucose cotransporter-2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. METHODS AND RESULTS: Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all-cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. CONCLUSIONS: In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit-to-visit SBP variability is independently associated with risks of hospitalization for heart failure and all-cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP-lowering effect. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791

The association between leukocytes and sperm quality is concentration dependent

<p>Abstract</p> <p>Background</p> <p>To evaluate the association between leukocytes (polymorphonuclear granulocytes -PMNL) and semen parameters at different leukocyte concentrations.</p> <p>Methods</p> <p>This was a retrospective clinical study at a university hospital andrology clinic. Semen samples from infertile men were analyzed for sperm morphology and motility according to seminal leukocytes (PMNL) concentration (category A: >0 to <0.25 × 10(6)/mL; category B: >0.25 to <0.5 × 10(6)/mL; category C: >0.5 to <0.75 × 10(6)/mL; category D: >0.75 to <1.0 × 10(6)/mL, category E: >1 × 10(6)/mL).</p> <p>Results</p> <p>The percentage of sperm with normal morphology increased significantly from category A (14%) to category D (19%) but decreased in category E to levels (14%) similar to those in category A. Motility grades a and a+b (combined) also increased from category A (12%, 20%) to category D (18.0%, 28.5%) and decreased in category E (11%, 20.5%) to levels similar to those in category A. Sperm deformities and motility grades c and d increased progressively in all categories.</p> <p>Summary</p> <p>Leukocytes had a positive association with normal morphology and progressive motility in semen samples at a concentration of 0-1 × 10(6)/mL. The findings suggest that the association between leukocytes (PMNL) and semen quality might be concentration dependent.</p

Study on the short-term effects of increased alcohol and cigarette consumption in healthy young men's seminal quality

Many studies have reported a negative impact of lifestyle factors on testicular function, spermatozoa parameters and pituitary-gonadal axis. However, conclusions are difficult to draw, since studies in the general population are rare. In this study we intended to address the early and late short-term impact of acute lifestyle alterations on young men's reproductive function. Thirty-six healthy male students, who attended the Portuguese academic festivities, provided semen samples and answered questionnaires at three time-points. The consumption of alcohol and cigarette increased more than 8 and 2 times, respectively, during the academic festivities and resulted in deleterious effects on semen quality: one week after the festivities, a decrease on semen volume, spermatozoa motility and normal morphology was observed, in parallel with an increase on immotile spermatozoa, head and midpiece defects and spermatozoa oxidative stress. Additionally, three months after the academic festivities, besides the detrimental effect on volume, motility and morphology, a negative impact on spermatozoa concentration was observed, along with a decrease on epididymal, seminal vesicles and prostate function. This study contributed to understanding the pathophysiology underlying semen quality degradation induced by acute lifestyle alterations, suggesting that high alcohol and cigarette consumption are associated with decreased semen quality in healthy young men.publishe