Effect of homeopathic treatment used in commercial boar semen diluent on sperm viability

Background: It has been speculated that the homeopathic treatment of sperm cells in order to improve semen quality could be promising. However, few data is available and its use in spermatozoa requires investigation. It is well established that mitochondrial membrane potential is an important viability parameter of spermatozoa and it is intimately related to reproductive efficiency. In this manner, new technologies in order to improve the activity of sperm cells and, finally, the fecundity of swine herds are of extremely importance. Due to the lack of knowledge of homeopathic treatment effect on spermatozoa, the aim of the present study was to verify the effect of three different homeopathic treatments on viability of boar sperm cells. Methods: semen samples were obtained from two sexually mature boars (18 mo of age). The boars were cross bred, with similar genetics of Pietrain versus Duroc, BP 450 progeny from a supplier company of similar reproductive performance animals. The animals were maintained in individual stalls, study conducted in Sao Paulo - Brazil. Three homeopathic treatments: Pulsatilla 6CH, Avena 6 CH or both, compared to placebo treatment (sucrose), the homeopathic medicaments or the control were administrated as globules manipulated according Brazilian Homeopathic Pharmacology. Each globule weighted 30 mg and contained sucrose as vehicle. One dose of two globules was added per 100 mL of diluted boar semen, which were chilled for 24 or 48 hours. All samples were labeled in codes in order to allow all laboratory analysis and evaluations being performed as a blind test. Data were tested for normality of residues and homogeneity of variances using the Guided Data Analysis software. Variables and interactions were analyzed by the PROC MIXED of the SAS package (SAS Institute Ins. Cary, NC). Adjusted least squares means (LSMEANS) of treatments were compared using the Tukey Test. Results: The different treatments contributed to maintain acrossome integrity for prolonged periods of cooling over 48 hours. The use of Pulsatilla was effective in maintaining high sperm mitochondria activity up to 24 hours from harvesting. Conclusion: Homeopathic medications can be used in artificial insemination in order to improve the quality of cooled and stored pig semen [1]. Keywords: homeopathy, swine semen, sperm viability. Reference [1] Soto, F. R. M.; Vuaden, E. R.; Coelho, C. P.; Bonamin, L. V.; Azevedo, S. S. A.; Benites, N. R.; Barros, F. R. O.; Goissis, M. D.; Assumpção, M. E. O. D.; Visintin, J. A.; Marques, M. G. Effects of the utilization of homeopathic elements in commercial diluent on swine sperm viability. In Vitro Cell.Dev.Biol.—Animal. 47:205–209, 2011.

The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study

Background We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO). Methods In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores. Results Of 1130 patients enrolled, 587 (51.9%) had baseline MO. Fremanezumab reduced placebo-adjusted least-squares mean (95% confidence interval) monthly HDs (− 2.2 [− 3.1 to − 1.2] and − 2.7 [− 3.7 to − 1.8]; P < 0.0001) in patients with MO and without MO (quarterly − 1.4 [− 2.3 to − 0.5], P = 0.0026; monthly − 1.4 [− 2.3 to − 0.6], P = 0.0017). Significantly more fremanezumab-treated patients had ≥ 50% reduction in HDs versus placebo, regardless of baseline MO (with: quarterly 70/201 [34.8%], monthly 78/198 [39.4%] vs placebo 26/188 [13.8%]; without: quarterly 71/174 [40.8%], monthly 75/177 [42.4%] vs placebo 41/183 [22.4%]). Fremanezumab improved HIT-6 and MSQoL scores. Significantly more fremanezumab-treated patients reverted to no MO (quarterly 111/201 [55.2%], monthly 120/198 [60.6%]) versus placebo (87/188 [46.3%]). Conclusions Fremanezumab is effective for prevention of migraine in patients with CM, regardless of MO, and demonstrated a benefit over placebo in reducing MO. Trial registration ClinicalTrials.gov NCT02621931 (HALO CM), registered December 12, 2012.

Efficacy and safety over 2 years of exenatide plus dapagliflozin in the DURATION-8 study: a multicenter, double-blind, phase 3, randomized controlled trial

<b>OBJECTIVE: </b>In patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin produced greater reductions in glycemic parameters (glycated haemoglobin [HbA_1c], fasting plasma glucose [FPG], and 2-hour postprandial glucose [2-h PPG]), weight, and systolic blood pressure (SBP) than exenatide QW or dapagliflozin alone after 28 weeks of treatment in DURATION-8. Following a 24‑week extension period, improvements were sustained at 52 weeks. Here, we investigated efficacy and safety at 104 weeks after randomization. <p><b>RESEARCH DESIGN AND METHODS:</b> DURATION-8 was a 104-week, multicenter, double-blind, randomized, active‑controlled, phase 3 trial. In total, 695 adults (age ≥18 years) with type 2 diabetes and inadequate glycemic control (HbA_1c, 8.0%–12.0% [64–108 mmol/mol]) despite stable metformin monotherapy (≥1500 mg/day) were randomly assigned (1:1:1) to receive exenatide 2 mg QW plus once-daily dapagliflozin 10 mg, exenatide QW plus placebo, or dapagliflozin plus placebo. All 104-week evaluations were exploratory. </p> <p><b>RESULTS: </b>At week 104, 431 (62.0%) patients completed treatment. The adjusted least squares mean (LSM) change [standard error] from baseline to week 104 in HbA_1cwas greater with exenatide QW plus dapagliflozin (–1.70% [0.11]) versus exenatide QW plus placebo (–1.29% [0.12]; <i>P</i>=0.007) and dapagliflozin plus placebo (–1.06% [0.12]; <i>P</i><0.001). Clinically relevant changes in FPG, 2-h PPG, weight and SBP were also observed with exenatide QW plus dapagliflozin. There were no unexpected safety findings and exenatide QW plus dapagliflozin was well tolerated, with no episodes of major hypoglycemia. </p> <p><b>CONCLUSIONS: </b>In this exploratory analysis, among those individuals who completed the trial without rescue therapy, there was clinically relevant efficacy over 2 years with exenatide QW plus dapagliflozin, with no unexpected safety findings.<b></b></p>

Efficacy and safety over 2 years of exenatide plus dapagliflozin in the DURATION-8 study: a multicenter, double-blind, phase 3, randomized controlled trial

<b>OBJECTIVE: </b>In patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin produced greater reductions in glycemic parameters (glycated haemoglobin [HbA_1c], fasting plasma glucose [FPG], and 2-hour postprandial glucose [2-h PPG]), weight, and systolic blood pressure (SBP) than exenatide QW or dapagliflozin alone after 28 weeks of treatment in DURATION-8. Following a 24‑week extension period, improvements were sustained at 52 weeks. Here, we investigated efficacy and safety at 104 weeks after randomization. <p><b>RESEARCH DESIGN AND METHODS:</b> DURATION-8 was a 104-week, multicenter, double-blind, randomized, active‑controlled, phase 3 trial. In total, 695 adults (age ≥18 years) with type 2 diabetes and inadequate glycemic control (HbA_1c, 8.0%–12.0% [64–108 mmol/mol]) despite stable metformin monotherapy (≥1500 mg/day) were randomly assigned (1:1:1) to receive exenatide 2 mg QW plus once-daily dapagliflozin 10 mg, exenatide QW plus placebo, or dapagliflozin plus placebo. All 104-week evaluations were exploratory. </p> <p><b>RESULTS: </b>At week 104, 431 (62.0%) patients completed treatment. The adjusted least squares mean (LSM) change [standard error] from baseline to week 104 in HbA_1cwas greater with exenatide QW plus dapagliflozin (–1.70% [0.11]) versus exenatide QW plus placebo (–1.29% [0.12]; <i>P</i>=0.007) and dapagliflozin plus placebo (–1.06% [0.12]; <i>P</i><0.001). Clinically relevant changes in FPG, 2-h PPG, weight and SBP were also observed with exenatide QW plus dapagliflozin. There were no unexpected safety findings and exenatide QW plus dapagliflozin was well tolerated, with no episodes of major hypoglycemia. </p> <p><b>CONCLUSIONS: </b>In this exploratory analysis, among those individuals who completed the trial without rescue therapy, there was clinically relevant efficacy over 2 years with exenatide QW plus dapagliflozin, with no unexpected safety findings.<b></b></p>

EFFICIENCY OF ACTIVITIES OF TOURISM OPERATORS AND AGENTS ON THE MARKET OF TOURIST SERVICES OF UKRAINE

In the sections the research of efficiency of activity of tourist operators and agents in the market of tourist services of Ukraine proceeding from dependence of cost of permits on volume of their realization to the population and quantity of the served tourists is carried out. The necessity to use such methods as correlation-regression analysis and adjusted least squares to evaluate the efficiency of these legal entities in the market of tourist services is substantiated. The method of analysis of the operating environment was used in the study of the positions of the regions of Ukraine where legal entities operate in the market of tourist services, which allowed travel agents and tour operators) to attract tourists and sell tourist vouchers to the population. The direction of development of the modern market of tourist services and according to it the direction of effective development of the market of tourist services of Ukraine owing to activity of travel agents is revealed. The necessity of maximum coincidence of these directions is proved, while for travel agents in the regions of Ukraine there is no such coincidence. It is proposed to change the positions of the regions where these entities operate in the effective direction of the operating environment by reducing the cost of vouchers and increasing tourist activity, as the study identified a number of areas where tourists pay higher vouchers than the national average. As a result of the analysis of the environment of operation of tour operators in the regions of Ukraine, a special position in the Kharkiv region was revealed, as one that allows to assess the effectiveness of these entities in all other regions of the country. A much larger organization in the market of tourist services of tour operators is proved in comparison with travel agents, as the positions in the respective oblasts are currently in the direction of effective development with the exception of Ternopil, Khmelnytsky and Chernivtsi oblasts. Conclusions are made on the need to develop all business entities in the market of travel services, in particular to provide benefits from the activities of travel agents.

Efficacy of ertugliflozin in monotherapy or combination therapy in patients with type 2 diabetes: A pooled analysis of placebo-controlled studies

Background: This pooled analysis assessed the efficacy of ertugliflozin versus placebo as monotherapy or with other antihyperglycaemic agents across patient subgroups defined by demographic and disease characteristics. Methods: Data from three phase III randomised, placebo-controlled, double-blind studies (NCT01958671, NCT02033889 and NCT02036515) with similar designs and populations were pooled ( N = 1544). Results: At Week 26, placebo-adjusted least squares mean changes from baseline in glycated haemoglobin with ertugliflozin 5 and 15 mg were −0.8% (95% confidence interval: −0.9, −0.7) and −0.9% (–1.0, −0.8), respectively. Reductions were consistent across subgroups. Placebo-adjusted least squares mean changes in body weight were −1.8 kg (−2.2, −1.4) for both ertugliflozin doses; for systolic blood pressure, these were −3.4 mmHg (−4.8, −2.0) and −3.5 mmHg (−4.9, −2.0) for ertugliflozin 5 and 15 mg, respectively. Higher proportions of patients receiving ertugliflozin had glycated haemoglobin <7.0%, weight loss ⩾5% and systolic blood pressure <130 mmHg versus placebo. Ertugliflozin and placebo safety profiles were similar, including incidences of hypoglycaemia, urinary tract infection and hypovolaemia. Genital mycotic infection and adverse events related to osmotic diuresis were more common with ertugliflozin. Conclusion: Ertugliflozin demonstrated efficacy as monotherapy or with other antihyperglycaemic agents in patients with different demographic and disease characteristics and was generally well tolerated.

Longitudinal trajectories and prevalence of meeting dietary guidelines during the transition from adolescence to young adulthood

ABSTRACT Background Establishing healthy dietary habits during adolescence and young adulthood is critical for long-term health. Objectives This study assessed the prevalence of meeting US Dietary Guidelines and trajectories in dietary intake for 4 MyPlate food groups during the transition from adolescence to young adulthood. Methods Three waves of surveys and food frequency questionnaires were collected as part of Project EAT (Eating and Activity in Teens and Young Adults), a 15-y longitudinal study. Adolescents (n = 1177, 57% female, mean ± SD age 15.0 ± 1.5 y) were recruited in 1998–1999 in Minneapolis-St Paul, Minnesota public schools and were resurveyed twice in young adulthood at mean ± SD ages 25.3 ± 1.5 and 31.1 ± 1.5 y. The prevalence of meeting guidelines for each MyPlate food group was calculated at each time point. Mean daily servings were compared over 5 y in young adulthood through the use of paired t tests. Adjusted least-squares means were calculated to compare dietary intake in young adulthood across quartiles of adolescent intake. Results Adolescents had the highest prevalence of meeting dietary guidelines for fruit (37% for females and 30% for males) and dairy (53% for females and 61% for males); young adults >30 y had the highest prevalence of meeting dietary guidelines for vegetables (19% for females and 8% for males) and whole grains (23% for females and 17% for males). From the mid-twenties to early thirties, vegetable intake increased, whereas dairy intake decreased. Dietary intake generally tracked over time with individuals in the lower quartiles of intake at adolescence generally continuing to have low intake in young adulthood. Conclusions Although the prevalence of meeting dietary guidelines for whole grains and vegetables, and daily servings of vegetables increased with age, improving intake of whole fruit, whole grains, dairy, and vegetables remains key during the transition from adolescence to young adulthood.

PRECAUTIONARY LEARNING AND INFLATIONARY BIASES

In a canonical monetary policy model in which the central bank learns about underlying fundamentals by estimating the parameters of a Phillips curve, we show that the bank’s loss function is asymmetric such that parameter overestimates may be more or less costly than underestimates, creating a precautionary motive in estimation. This motive suggests the use of a more efficient variance-adjusted least-squares estimator for learning about fundamentals. Informed by this “precautionary learning” the central bank sets low inflation targets, and the economy can settle near a Ramsey equilibrium.

Polynomial regression with heteroscedastic measurement errors in both axes: Estimation and hypothesis testing

This article investigates point estimation and hypothesis testing in a polynomial regression model with heteroscedastic measurement errors present in both response and regressor variables. For point estimation, the adjusted least squares method and its modifications are developed. These methods can treat both functional and structural models, and models with or without an equation error. For hypothesis testing, the Wald-type and score-type tests are discussed. Their performance is investigated in a simulation study. Applications of these methods are also illustrated with real datasets.

Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis

ObjectiveTo compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR).MethodsEndpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates.ResultsAt 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: –0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was –0.22 (95% CI –0.38 to –0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: –1.9% versus 1.6% (adjusted difference for etanercept minus control: –4.7%,95% CI –9.9 to 0.5, p=0.07) for change in mNY criteria; –1.9% versus 7.8% (adjusted difference: –18.2%,95% CI –30.9 to –5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and –0.6% versus 6.7% (adjusted difference: –16.4%,95% CI –27.9 to –5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change.ConclusionDespite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy.Trial registration numbersNCT01258738, NCT01648907; Post-results.