Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals.

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 ( Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement

Using the Sustainability Monitoring and Assessment Routine (SMART) for the Systematic Analysis of Trade-Offs and Synergies between Sustainability Dimensions and Themes at Farm Level

When trying to optimize the sustainability performance of farms and farming systems, a consideration of trade-offs and synergies between different themes and dimensions is required. The aim of this paper is to perform a systematic analysis of trade-offs and synergies across all dimensions and themes. To achieve this aim we used the Sustainability Monitoring and Assessment Routine (SMART)-Farm Tool which operationalizes the Sustainability Assessment of Food and Agriculture Systems (SAFA) Guidelines by defining science-based indicator sets and assessment procedures. It identifies the degree of goal achievement with respect to the 58 themes defined in the SAFA Guidelines using an impact matrix that defines 327 indicators and 1769 relations between sustainability themes and indicators. We illustrate how the SMART-Farm Tool can be successfully applied to assess the sustainability performance of farms of different types and in different geographic regions. Our analysis revealed important synergies between themes within a sustainability dimension and across dimensions. We found major trade-offs within the environmental dimension and between the environmental and economic dimension. The trade-offs within the environmental dimension were even larger than the trade-offs with other dimensions. The study also underlines the importance of the governance dimension with regard to achieving a good level of performance in the other dimensions

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Group membership and certification effects on incomes of coffee farmers in Uganda

Discrepancies in certification effects on smallholder incomes have been found in scientific literature. Unobserved farmer-group heterogeneity is a likely reason. For the long-standing Robusta coffee farmer-groups in Uganda, we find no significant effect of certification on net-farm income. But, we find 20 percentage point differences in net-farm income between certified and non-certified farmers explained by membership duration. In contrast, the recently founded certified Arabica coffee farmer-groups have positive net-farm income effects of 151 per cent, partly explained by a higher degree of vertical integration. With or without certification, long-standing group membership is found to have positive income effects

LC-MS/MS Detection of Increased Androstenedione Levels in Patients Receiving Danazol Therapy

exterior, detail of eave with woodcarving details on a house representing an Aceh, Northern Sumatra domestic form at the park, 198

Stakeholder engagement in prioritizing sustainability assessment themes for smallholder coffee production in Uganda

Many sustainability assessment frameworks have been developed in recent years, but translating them into practical tools to guide decision making remains challenging. By engaging coffee stakeholders in Uganda, we demonstrate a process of translating the widely-accepted framework for Sustainability Assessments of Food and Agriculture Systems (SAFA), developed by the Food and Agriculture Organisation of the United Nations (FAO), to smallholder production systems. Stakeholders prioritized the sustainability themes in terms of relevance and feasibility, and subsequently identified relevant sub-themes. We find that the structure and scope of some generally accepted themes need appropriate modifications in order to address the social and structural heterogeneity of smallholder production systems. Although importance and feasibility rankings significantly vary within and between stakeholder groups, governance and economic themes are commonly perceived as very important though equally the least feasible for smallholders. Thus, the inclusion of the ‘farmer-group’ structure as part of the sustainability assessment criteria is perceived as necessary especially toward achieving governance-related goals. These findings emphasize the need of engaging stakeholders in defining locally adapted sustainability assessment criteria

Sustainability Performance of Certified and Non-certified Smallholder Coffee Farms in Uganda

The transition toward sustainable agricultural production can be supported with improved insight into the performance of existing farming systems. The Sustainability Assessments of Food and Agriculture Systems (SAFA) framework published by the Food and Agriculture Organization (FAO) provides a comprehensive and harmonised framework to assess and compare farming systems. We used the indicator-based SAFA consistent Sustainability Monitoring and Assessment RouTine (SMART) Farm Tool to analyze and compare the sustainability performance of certified organic and fair trade as well as non-certified smallholder farms in Uganda. Using the respective sustainability scores, we analyzed the synergies and trade-offs between sustainability themes using the non-parametric Spearman correlation test. We find that certification is associated with improved sustainability performance of smallholder coffee farms. It enhances the achievement of governance goals through its influences on group organization and collective capacities - this results in positive effects on other sustainability dimensions. Major synergies were observed between social and governance themes, and between economic and environmental themes. Although, the extent and distribution of the synergies and trade-offs varied among farms, they were consistent between the production systems. These results show that the production systems can potentially have more influence on the sustainability performance than certification per se

Accounting for uncertainty in multi-criteria sustainability assessments at the farm level: Improving the robustness of the SMART-Farm Tool

Many farm sustainability assessments use multi-criteria methods for aggregating indicators based on performance scores and importance weights. One of these is the SMART-Farm Tool, which measures the degree of goal achievement of farms across 327 indicators nested within 4 sustainability dimensions, 21 themes and 58 sub-themes of the FAO-SAFA Guidelines (Sustainability Assessment of Food and Agriculture). This study aims to improve the empirical foundation of the SMART-Farm Tool by (i) evaluating the uncertainty of indicator weights obtained via expert opinion and (ii) integrating this uncertainty into SMART assessment results. An adapted Delphi process was implemented, involving a group of 67 experts from 21 countries divided into thematic and regional sub-groups. Experts within each sub-group rated the importance of indicators of all 58 SAFA sub-themes, and self-assessed their own competence. Contrary to expectations, the uncertainty in expert opinions was relatively high for environmental indicator weights (although lowest for animal welfare), being comparable to social and governance indicators. Considerable uncertainty remained in indicator weights, even after two rounds of discussion and exchange of views. This is attributed to regional variation and inherent system complexity (i.e. experts having legitimate but diverging viewpoints based on contradictory evidence) rather than scientific ignorance (i.e. a lack of research evidence). Nevertheless, it is expected that the levels of uncertainty could be reduced by limiting the number of indicators to be evaluated and thus by allowing for more in-depth discussions among the experts. Monte Carlo Simulations were used to translate residual indicator weight uncertainty into SMART assessment results at the farm level for four example farms from both developed and developing countries. The resulting comparisons revealed several cases where substantial apparent differences between farms in sustainability scores for a specific sub-theme (up to 23%) were not statistically significant, while in other cases differences of 5% were significant. This emphasizes the general importance of considering uncertainty in multi-criteria assessment tools, with clear implications real-world applications, such as product certification, labelling and marketing. Finally, this study provides important methodological suggestions for implementing expert-based assessments in multi-criteria assessments efficiently

Assessment of Thyroid Function in Patients With Alkaptonuria

Importance: Alkaptonuria is an autosomal recessive disorder caused by pathogenic variants in the HGD gene. Deficiency of the HGD enzyme leads to tissue deposition of homogentisic acid (HGA), causing severe osteoarthropathies and cardiac valve degeneration. Although HGD is vital for the catabolism of tyrosine, which provides the basis for thyroid hormone synthesis, the prevalence of thyroid dysfunction in alkaptonuria is unknown. Objective: To assess thyroid structure and function in patients with alkaptonuria. Design, Setting, and Participants: A single-center cohort study was conducted in a tertiary referral center including patients with alkaptonuria followed up for a median of 93 (interquartile range, 48-150) months between February 1, 2000, and December 31, 2018. The alkaptonuria diagnosis was based on clinical presentation and elevated urine HGA levels. A total of 130 patients were considered for participation. Main Outcomes and Measures: Prevalence of thyroid dysfunction in adults with alkaptonuria compared with the general population. Thyrotropin and free thyroxine levels were measured by immunoassay and repeated in each patient a median of 3 (interquartile range, 2-22) times. Neck ultrasonographic scans were analyzed in a subset of participants. Logistic regression was used to test the association of thyroid dysfunction with age, sex, thyroid peroxidase (TPO) antibodies, serum tyrosine levels, and urine HGA levels. Results: Of the 130 patients, 5 were excluded owing to thyroidectomy as the cause of hypothyroidism. The study cohort consisted of 125 patients; the median age was 45 (interquartile range, 35-51) years. Most of the patients were men (72 [57.6%]). The prevalence of primary hyperthyroidism was 0.8% (1 of 125 patients), similar to 0.5% observed in the general population (difference, 0.003; 95% CI, -0.001 to 0.04; P = .88). The prevalence of primary hypothyroidism was 16.0% (20 of 125 patients), which is significantly higher than 3.7% reported in the general population (difference, 0.12; 95% CI, 0.10-0.24; P \u3c .001). Women were more likely to have primary hypothyroidism than men (odds ratio, 10.99; 95% CI, 3.13-38.66; P \u3c .001). Patients with TPO antibodies had a higher likelihood of primary hypothyroidism than those without TPO antibodies (odds ratio, 7.36; 95% CI, 1.89-28.62; P = .004). There was no significant difference in the prevalence of thyroid nodules between patients in this study (29 of 49 [59.2%]) vs the general population (68%) (difference, 0.088; 95% CI, -0.44 to 0.73; P = .20) or of cancer (7% vs 5%; difference, 0.01; 95% CI, -0.01 to 0.17; P = .86). Conclusions and Relevance: The high prevalence of primary hypothyroidism noted in patients with alkaptonuria in this study suggests that serial screening in this population should be considered and prioritized