The analysis of collective orientation and process feedback in relation to coordination and performance in interdependently working teams.

Effective teamwork is not only essential for teams themselves, but also for organizations and our society. To facilitate team processes and enhance team performance, feedback interventions are a widely used means. However, different types of feedback (i.e., individual vs. team-level feedback, performance vs. process feedback) can have various effects leaving the question of their effectiveness unanswered. This is especially important when team members' attitudes (namely collective orientation) are considered. Thus, understanding the interplay between types of feedback and team members' attitudes would reveal new opportunities for fostering reliable teamwork. The methodology of the present study is based on a laboratory approach. Teams (N = 142) of two worked together over four scenarios to extinguish forest fires in a microworld. We examined the effects of collective orientation on team coordination and team performance. To understand the interplay between feedback and attitudes we examined the effect of different feedback interventions on team performance and on a change in collective orientation. For analyzing multilevel mediation and changes over time, Bayesian multilevel models were applied. Results show a positive relationship between collective orientation and team performance mediated by coordination. Additionally, team-level process and performance feedback seem to be slightly more beneficial for maintaining performance over time with increasing difficulty of the task compared to individual-level process feedback. Feedback can lead to an increase in collective orientation if these values are low at the beginning. Our research highlights the importance of collective orientation and feedback interventions on team processes and performance for interdependently working teams.

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. METHODS: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. RESULTS: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. CONCLUSIONS: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Vibrio-Sequins - dPCR-traceable DNA standards for quantitative genomics of Vibrio spp.

BACKGROUND: Vibrio spp. are a diverse group of ecologically important marine bacteria responsible for several foodborne outbreaks of gastroenteritis around the world. Their detection and characterization are moving away from conventional culture-based methods towards next generation sequencing (NGS)-based approaches. However, genomic methods are relative in nature and suffer from technical biases arising from library preparation and sequencing. Here, we introduce a quantitative NGS-based method that enables the quantitation of Vibrio spp. at the limit of quantification (LOQ) through artificial DNA standards and their absolute quantification via digital PCR (dPCR). RESULTS: We developed six DNA standards, called Vibrio-Sequins, together with optimized TaqMan assays for their quantification in individually sequenced DNA libraries via dPCR. To enable Vibrio-Sequin quantification, we validated three duplex dPCR methods to quantify the six targets. LOQs were ranging from 20 to 120 cp/µl for the six standards, whereas the limit of detection (LOD) was ~ 10 cp/µl for all six assays. Subsequently, a quantitative genomics approach was applied to quantify Vibrio-DNA in a pooled DNA mixture derived from several Vibrio species in a proof-of-concept study, demonstrating the increased power of our quantitative genomic pipeline through the coupling of NGS and dPCR. CONCLUSIONS: We significantly advance existing quantitative (meta)genomic methods by ensuring metrological traceability of NGS-based DNA quantification. Our method represents a useful tool for future metagenomic studies aiming at quantifying microbial DNA in an absolute manner. The inclusion of dPCR into sequencing-based methods supports the development of statistical approaches for the estimation of measurement uncertainties (MU) for NGS, which is still in its infancy.

New global indicator for workers' health: mortality rate from diseases attributable to selected occupational risk factors.

Through sustainable development goals 3 and 8 and other policies, countries have committed to protect and promote workers' health by reducing the work-related burden of disease. To monitor progress on these commitments, indicators that capture the work-related burden of disease should be available for monitoring workers' health and sustainable development. The World Health Organization and the International Labour Organization estimate that only 363 283 (19%) of 1 879 890 work-related deaths globally in 2016 were due to injuries, whereas 1 516 607 (81%) deaths were due to diseases. Most monitoring systems focusing on workers' health or sustainable development, such as the global indicator framework for the sustainable development goals, include an indicator on the burden of occupational injuries. Few such systems, however, have an indicator on the burden of work-related diseases. To address this gap, we present a new global indicator: mortality rate from diseases attributable to selected occupational risk factors, by disease, risk factor, sex and age group. We outline the policy rationale of the indicator, describe its data sources and methods of calculation, and report and analyse the official indicator for 183 countries. We also provide examples of the use of the indicator in national workers' health monitoring systems and highlight the indicator's strengths and limitations. We conclude that integrating the new indicator into monitoring systems will provide more comprehensive and accurate surveillance of workers' health, and allow harmonization across global, regional and national monitoring systems. Inequalities in workers' health can be analysed and the evidence base can be improved towards more effective policy and systems on workers' health.

Par le biais des objectifs de développement durable 3 et 8 ainsi que d'autres mesures, plusieurs pays se sont engagés à protéger et promouvoir la santé des travailleurs en réduisant l'impact des maladies liées au travail. Mais pour évaluer leurs progrès en la matière, il convient de mettre en place des indicateurs estimant l'impact des maladies liées au travail afin de placer le développement durable et la santé des travailleurs sous surveillance. D'après l'Organisation mondiale de la Santé et l'Organisation internationale du Travail, seulement 363 283 (19%) des 1 879 890 décès liés au travail dans le monde en 2016 découlaient de blessures, tandis que 1 516 607 (81%) d'entre eux étaient causés par des maladies. La plupart des systèmes de surveillance qui s'intéressent à la santé des travailleurs ou au développement durable, comme le cadre mondial d'indicateurs pour les objectifs de développement durable, comportent un indicateur relatif à l'impact des accidents de travail. Cependant, rares sont ceux qui possèdent un indicateur concernant l'impact des maladies professionnelles. Pour combler cette lacune, nous dévoilons un nouvel indicateur mondial: le taux de mortalité dû aux maladies attribuables à certains facteurs de risque professionnels classé par maladie, facteur de risque, sexe et catégorie d'âge. Nous exposons le motif politique de l'indicateur, décrivons l'origine des données et les méthodes de calcul, et communiquons et analysons l'indicateur officiel pour 183 pays. Nous fournissons également des exemples de la façon dont l'indicateur peut être utilisé dans des systèmes nationaux de surveillance de la santé des travailleurs et soulignons ses forces et faiblesses. Nous concluons en affirmant que l'intégration de ce nouvel indicateur dans les systèmes de surveillance offrira un suivi plus complet et précis de la santé des travailleurs et ouvrira la voie à une harmonisation des systèmes mondiaux, nationaux et régionaux. Il est possible d'analyser les inégalités en matière de santé des travailleurs et d'en améliorer les bases factuelles afin d'établir des politiques et systèmes plus efficaces dans ce domaine.

A través de los objetivos de desarrollo sostenible 3 y 8 y de otras políticas, los países se han comprometido a proteger y promover la salud de los trabajadores reduciendo la carga de morbilidad relacionada con el trabajo. Para supervisar los avances en el cumplimiento de estos compromisos, debería disponerse de indicadores que reflejen la carga de morbilidad relacionada con el trabajo, a fin de controlar la salud de los trabajadores y el desarrollo sostenible. La Organización Mundial de la Salud y la Organización Internacional del Trabajo estiman que solo 363 283 (19%) de las 1 879 890 muertes relacionadas con el trabajo a nivel mundial en 2016 se debieron a lesiones, mientras que 1 516 607 (81%) muertes se debieron a enfermedades. La mayoría de los sistemas de vigilancia centrados en la salud de los trabajadores o el desarrollo sostenible, como el marco de indicadores mundiales para los objetivos de desarrollo sostenible, incluyen un indicador sobre la carga de las lesiones laborales. No obstante, pocos de estos sistemas cuentan con un indicador sobre la carga de las enfermedades relacionadas con el trabajo. Para subsanar esta carencia, presentamos un nuevo indicador mundial: la tasa de mortalidad por enfermedades atribuibles a factores de riesgo laborales seleccionados, por enfermedad, factor de riesgo, sexo y grupo de edad. Describimos la justificación política del indicador, describimos sus fuentes de datos y métodos de cálculo, e informamos y analizamos el indicador oficial para 183 países. También proporcionamos ejemplos del uso del indicador en los sistemas nacionales de vigilancia de la salud de los trabajadores y destacamos las ventajas y las limitaciones del indicador. Concluimos que la integración del nuevo indicador en los sistemas de vigilancia proporcionará una vigilancia más exhaustiva y precisa de la salud de los trabajadores, y permitirá la armonización entre los sistemas de vigilancia mundiales, regionales y nacionales. Se podrán analizar las desigualdades en la salud de los trabajadores y se podrá mejorar la base de evidencias para lograr políticas y sistemas más eficaces en materia de salud de los trabajadores.

Chemistry Related to the Catalytic Cycle of the Antioxidant Ebselen.

The antioxidant drug ebselen has been widely studied in both laboratories and in clinical trials. The catalytic mechanism by which it destroys hydrogen peroxide via reduction with glutathione or other thiols is complex and has been the subject of considerable debate. During reinvestigations of several key steps, we found that the seleninamide that comprises the first oxidation product of ebselen underwent facile reversible methanolysis to an unstable seleninate ester and two dimeric products. In its reaction with benzyl alcohol, the seleninamide produced a benzyl ester that reacted readily by selenoxide elimination, with formation of benzaldehyde. Oxidation of ebselen seleninic acid did not afford a selenonium seleninate salt as previously observed with benzene seleninic acid, but instead generated a mixture of the seleninic and selenonic acids. Thiolysis of ebselen with benzyl thiol was faster than oxidation by ca. an order of magnitude and produced a stable selenenyl sulfide. When glutathione was employed, the product rapidly disproportionated to glutathione disulfide and ebselen diselenide. Oxidation of the S-benzyl selenenyl sulfide, or thiolysis of the seleninamide with benzyl thiol, afforded a transient thiolseleninate that also readily underwent selenoxide elimination. The S-benzyl derivative disproportionated readily when catalyzed by the simultaneous presence of both the thiol and triethylamine. The phenylthio analogue disproportionated when exposed to ambient or UV (360 nm) light by a proposed radical mechanism. These observations provide additional insight into several reactions and intermediates related to ebselen.

Natural Cycle Frozen Embryo Transfer: Evaluating Optimal Protocols for Preparation and Timing.

Background: While natural cycle frozen embryo transfer (NC-FET) is becoming increasingly common, significant practice variation exists in the use of ovulation induction medications, administration of ovulation trigger, and timing of embryo transfer without consensus as to the optimal protocol. Aims: The objective of this study is to evaluate the association of key aspects of the NC-FET protocol with implantation, pregnancy and live birth. Settings and Design: This was a retrospective cohort study of blastocyst stage NC-FET cycles from October 2019 to July 2021 at a single academic fertility centre. Materials and Methods: Protocols varied between cycles across three key parameters which were evaluated as primary predictors of cycle outcomes: (1) use of letrozole for mild ovarian stimulation/ovulation induction, (2) administration of exogenous ovulation trigger versus spontaneous luteinising hormone surge and (3) transfer timing based on ovulation trigger versus sequential progesterone monitoring. Primary outcomes included implantation rate, clinical pregnancy and ongoing pregnancy. Statistical Analysis Used: Generalised estimating equations were fitted to obtain adjusted odds ratios or rate ratios as appropriate with 95% confidence intervals for each outcome across the three primary predictors. Results: A total of 183 cycles from 170 unique patients were eligible for inclusion. The average implantation rate was 0.58, resulting in an overall clinical pregnancy and ongoing pregnancy rate of 59.0% and 51.4%, respectively. After adjusting for age at embryo freeze and history of a failed embryo transfer, there were no significant associations between any predictor and implantation rate, clinical pregnancy, ongoing pregnancy, or live birth. Conclusion: In NC-FET, a variety of preparation and timing protocols may lead to comparable cycle outcomes, potentially allowing for flexibility on the basis of patient and physician preference. These findings warrant validation in a larger, randomised trial.

Estimating the population exposed to a risk factor over a time window: A microsimulation modelling approach from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

OBJECTIVES: Burden of disease estimation commonly requires estimates of the population exposed to a risk factor over a time window (yeart to yeart+n). We present a microsimulation modelling approach for producing such estimates and apply it to calculate the population exposed to long working hours for one country (Italy). METHODS: We developed a three-model approach: Model 1, a multilevel model, estimates exposure to the risk factor at the first year of the time window (yeart). Model 2, a regression model, estimates transition probabilities between exposure categories during the time window (yeart to yeart+n). Model 3, a microsimulation model, estimates the exposed population over the time window, using the Monte Carlo method. The microsimulation is carried out in three steps: (a) a representative synthetic population is initiated in the first year of the time window using prevalence estimates from Model 1, (b) the exposed population is simulated over the time window using the transition probabilities from Model 2; and (c) the population is censored for deaths during the time window. RESULTS: We estimated the population exposed to long working hours (i.e. 41-48, 49-54 and ≥55 hours/week) over a 10-year time window (2002-11) in Italy. We populated all three models with official data from Labour Force Surveys, United Nations population estimates and World Health Organization life tables. Estimates were produced of populations exposed over the time window, disaggregated by sex and 5-year age group. CONCLUSIONS: Our modelling approach for estimating the population exposed to a risk factor over a time window is simple, versatile, and flexible. It however requires longitudinal exposure data and Model 3 (the microsimulation model) is stochastic. The approach can improve accuracy and transparency in exposure and burden of disease estimations. To improve the approach, a logical next step is changing Model 3 to a deterministic microsimulation method, such as modelling of microflows.

Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups.

During attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18- to 26-membered. The products showed potent GPx-like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

Assessor burden, inter-rater agreement and user experience of the RoB-SPEO tool for assessing risk of bias in studies estimating prevalence of exposure to occupational risk factors: An analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: As part of the development of the World Health Organization (WHO)/International Labour Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury, WHO and ILO carried out several systematic reviews to determine the prevalence of exposure to selected occupational risk factors. Risk of bias assessment for individual studies is a critical step of a systematic review. No tool existed for assessing the risk of bias in prevalence studies of exposure to occupational risk factors, so WHO and ILO developed and pilot tested the RoB-SPEO tool for this purpose. Here, we investigate the assessor burden, inter-rater agreement, and user experience of this new instrument, based on the abovementioned WHO/ILO systematic reviews. METHODS: Twenty-seven individual experts applied RoB-SPEO to assess risk of bias. Four systematic reviews provided a total of 283 individual assessments, carried out for 137 studies. For each study, two or more assessors independently assessed risk of bias across the eight RoB-SPEO domains selecting one of RoB-SPEO's six ratings (i.e., "low", "probably low", "probably high", "high", "unclear" or "cannot be determined"). Assessors were asked to report time taken (i.e. indicator of assessor burden) to complete each assessment and describe their user experience. To gauge assessor burden, we calculated the median and inter-quartile range of times taken per individual risk of bias assessment. To assess inter-rater reliability, we calculated a raw measure of inter-rater agreement (Pi) for each RoB-SPEO domain, between Pi = 0.00, indicating no agreement and Pi = 1.00, indicating perfect agreement. As subgroup analyses, Pi was also disaggregated by systematic review, assessor experience with RoB-SPEO (≤10 assessments versus > 10 assessments), and assessment time (tertiles: ≤25 min versus 26-66 min versus ≥ 67 min). To describe user experience, we synthesised the assessors' comments and recommendations. RESULTS: Assessors reported a median of 40 min to complete one assessment (interquartile range 21-120 min). For all domains, raw inter-rater agreement ranged from 0.54 to 0.82. Agreement varied by systematic review and assessor experience with RoB-SPEO between domains, and increased with increasing assessment time. A small number of users recommended further development of instructions for selected RoB-SPEO domains, especially bias in selection of participants into the study (domain 1) and bias due to differences in numerator and denominator (domain 7). DISCUSSION: Overall, our results indicated good agreement across the eight domains of the RoB-SPEO tool. The median assessment time was comparable to that of other risk of bias tools, indicating comparable assessor burden. However, there was considerable variation in time taken to complete assessments. Additional time spent on assessments may improve inter-rater agreement. Further development of the RoB-SPEO tool could focus on refining instructions for selected RoB-SPEO domains and additional testing to assess agreement for different topic areas and with a wider range of assessors from different research backgrounds.

Rights and representation support justice across aquatic food systems.

Injustices are prevalent in food systems, where the accumulation of vast wealth is possible for a few, yet one in ten people remain hungry. Here, for 194 countries we combine aquatic food production, distribution and consumption data with corresponding national policy documents and, drawing on theories of social justice, explore whether barriers to participation explain unequal distributions of benefits. Using Bayesian models, we find economic and political barriers are associated with lower wealth-based benefits; countries produce and consume less when wealth, formal education and voice and accountability are lacking. In contrast, social barriers are associated with lower welfare-based benefits; aquatic foods are less affordable where gender inequality is greater. Our analyses of policy documents reveal a frequent failure to address political and gender-based barriers. However, policies linked to more just food system outcomes centre principles of human rights, specify inclusive decision-making processes and identify and challenge drivers of injustice.

One-Pot Synthesis of Aryl Selenonic Acids and Some Unexpected Byproducts.

The synthesis of aryl selenonic acids was achieved from diverse aryl bromides via a one-pot method involving metalation, selenation, and oxidation with hydrogen peroxide followed by ion exchange to afford the pure products in 77-90% yield. An o-hydroxymethyl derivative was found to dehydrate readily, affording the first example of a cyclic selenonic ester, while two minor byproducts were isolated and shown by X-ray crystallography to be mixed salts of aryl selenonic acids with either the corresponding aryl seleninic or selenious acid.

Global, regional, and national burdens of ischemic heart disease and stroke attributable to exposure to long working hours for 194 countries, 2000-2016: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: World Health Organization (WHO) and International Labour Organization (ILO) systematic reviews reported sufficient evidence for higher risks of ischemic heart disease and stroke amongst people working long hours (≥55 hours/week), compared with people working standard hours (35-40 hours/week). This article presents WHO/ILO Joint Estimates of global, regional, and national exposure to long working hours, for 194 countries, and the attributable burdens of ischemic heart disease and stroke, for 183 countries, by sex and age, for 2000, 2010, and 2016. METHODS AND FINDINGS: We calculated population-attributable fractions from estimates of the population exposed to long working hours and relative risks of exposure on the diseases from the systematic reviews. The exposed population was modelled using data from 2324 cross-sectional surveys and 1742 quarterly survey datasets. Attributable disease burdens were estimated by applying the population-attributable fractions to WHO's Global Health Estimates of total disease burdens. RESULTS: In 2016, 488 million people (95% uncertainty range: 472-503 million), or 8.9% (8.6-9.1) of the global population, were exposed to working long hours (≥55 hours/week). An estimated 745,194 deaths (705,786-784,601) and 23.3 million disability-adjusted life years (22.2-24.4) from ischemic heart disease and stroke combined were attributable to this exposure. The population-attributable fractions for deaths were 3.7% (3.4-4.0) for ischemic heart disease and 6.9% for stroke (6.4-7.5); for disability-adjusted life years they were 5.3% (4.9-5.6) for ischemic heart disease and 9.3% (8.7-9.9) for stroke. CONCLUSIONS: WHO and ILO estimate exposure to long working hours (≥55 hours/week) is common and causes large attributable burdens of ischemic heart disease and stroke. Protecting and promoting occupational and workers' safety and health requires interventions to reduce hazardous long working hours.

Spatio-temporal focal spot characterization and modeling of the NIF ARC kilojoule picosecond laser.

The advanced radiographic capability (ARC) laser system, part of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is a short-pulse laser capability integrated into the NIF. The ARC is designed to provide adjustable pulse lengths of ∼1-38ps in four independent beamlets, each with energies up to 1 kJ (depending on pulse duration). A detailed model of the ARC lasers has been developed that predicts the time- and space-resolved focal spots on target for each shot. Measurements made to characterize static and dynamic wavefront characteristics of the ARC are important inputs to the code. Modeling has been validated with measurements of the time-integrated focal spot at the target chamber center (TCC) at low power, and the space-integrated pulse duration at high power, using currently available diagnostics. These simulations indicate that each of the four ARC beamlets achieves a peak intensity on target of up to a few 1018W/cm2.

The Unexpected Role of SeVI Species in Epoxidations with Benzeneseleninic Acid and Hydrogen Peroxide.

Benzeneperoxyseleninic acid has been proposed as the key intermediate in the widely used epoxidation of alkenes with benzeneseleninic acid and hydrogen peroxide. However, it reacts sluggishly with cyclooctene and instead rapidly decomposes in solution to a mixed selenonium-selenonate salt that was identified by X-ray absorption and 77 Se NMR spectroscopy, as well as by single crystal X-ray diffraction. This process includes a selenoxide elimination of the peroxyseleninic acid with liberation of oxygen and additional redox steps. The salt is relatively stable in the solid state, but generates the corresponding selenonic acid in the presence of hydrogen peroxide. The selenonic acid is inert towards cyclooctene on its own; however, rapid epoxidation occurs when hydrogen peroxide is added. This shows that the selenonic acid must first be activated through further oxidation, presumably to the heretofore unknown benzeneperoxyselenonic acid. The latter is the principal oxidant in this epoxidation.

Cyclic Seleninate Esters, Spirodioxyselenuranes and Related Compounds: New Classes of Biological Antioxidants That Emulate Glutathione Peroxidase.

Selenium compounds play an important role in redox homeostasis in living organisms. One of their major functions is to suppress the harmful effects of hydrogen peroxide, hydroperoxides and downstream reactive oxygen species that lead to oxidative stress, which has in turn been implicated in many diseases and degenerative conditions. The glutathione peroxidase (GPx) family of selenoenzymes plays a key protective role by catalyzing the reduction of peroxides with glutathione. Considerable effort has been expended toward the discovery of small-molecule selenium compounds that mimic GPx. To date, ebselen has been the most widely studied such compound, including in several clinical trials. However, despite its proven lack of significant toxicity, it displays only moderate catalytic activity and very poor aqueous solubility. The cyclic seleninate esters and spirodioxyselenuranes have recently been investigated as potential next generation GPx mimetics, along with structurally related selenenate esters, diazaselenuranes and pincer selenuranes. Their catalytic activities, redox mechanisms and structure-activity relationships are described in this Review, along with a description and discussion of the relative merits of assays for measuring their activities.

Chemical properties of commercially available honey species and the functional properties of caramelization and Maillard reaction products derived from these honey species.

The chemical parameters and the functionalities of six monofloral honeys of different botanical and geographical origins were investigated. Vitamins B1, B2, and C and the protein content of majority of honeys were distinguishable from general honey. Honeys not only were rich in a variety of functional components like flavonoids but also had strong anti-oxidant activities, scavenging activities against ROS, and anti-hypertensive and anti-allergic activities. Honeys were heated at 100 °C for 24 h and their browning intensity during heating process was observed to vary with botanical origin. The functional properties of caramelization and maillard reaction (MR) products derived from honeys during heating were evaluated. The browning of honeys progressed regardless of honey species. Anti-oxidant activities and scavenging activities against superoxide and DPPH radicals of products drastically increased, but ACE and hyaluronidase activities gradually decreased with passage of heating time. It concluded that the products, mainly melanoidins, produced simultaneously to browning process in caramelization and MR contributed to the expression of its useful function.

Adaptive evolution and segregating load contribute to the genomic landscape of divergence in two tree species connected by episodic gene flow.

Speciation often involves repeated episodes of genetic contact between divergent populations before reproductive isolation (RI) is complete. Whole-genome sequencing (WGS) holds great promise for unravelling the genomic bases of speciation. We have studied two ecologically divergent, hybridizing species of the 'model tree' genus Populus (poplars, aspens, cottonwoods), Populus alba and P. tremula, using >8.6 million single nucleotide polymorphisms (SNPs) from WGS of population pools. We used the genomic data to (i) scan these species' genomes for regions of elevated and reduced divergence, (ii) assess key aspects of their joint demographic history based on genomewide site frequency spectra (SFS) and (iii) infer the potential roles of adaptive and deleterious coding mutations in shaping the genomic landscape of divergence. We identified numerous small, unevenly distributed genome regions without fixed polymorphisms despite high overall genomic differentiation. The joint SFS was best explained by ancient and repeated gene flow and allowed pinpointing candidate interspecific migrant tracts. The direction of selection (DoS) differed between genes in putative migrant tracts and the remainder of the genome, thus indicating the potential roles of adaptive divergence and segregating deleterious mutations on the evolution and breakdown of RI. Genes affected by positive selection during divergence were enriched for several functionally interesting groups, including well-known candidate 'speciation genes' involved in plant innate immunity. Our results suggest that adaptive divergence affects RI in these hybridizing species mainly through intrinsic and demographic processes. Integrating genomic with molecular data holds great promise for revealing the effects of particular genetic pathways on speciation.

Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710.

BACKGROUND: Risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Multiple studies have reported the neutrophil-to-lymphocyte ratio (NLR) as a promising candidate; however, these analyses have methodological limitations. Therefore, the authors performed a category B biomarker study to test whether NLR is prognostic for overall survival (OS) after curative treatment or is predictive for the survival benefit from neoadjuvant chemotherapy (NAC). METHODS: This study is an unplanned secondary analysis of SWOG 8710, a randomized phase 3 trial that assessed cystectomy with or without NAC in 317 patients with muscle-invasive BC. NLR was calculated from prospectively collected complete blood counts. For the prognostic analysis, 230 patients were identified; for the predictive analysis, 263 were identified. NLR was evaluated with proportional hazards models including prespecified factors (age, sex, T-stage, lymphovascular invasion, and treatment arm). RESULTS: With a median follow-up of 18.6 years, there were 172 and 205 deaths in the prognostic and predictive cohorts, respectively. In a multivariable analysis, NLR was not prognostic for OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.98-1.11; P = .24). Furthermore, NLR did not predict for the OS benefit from NAC (HR, 1.01; 95% CI, 0.90-1.14; P = .86). Factors associated with worse OS were older age (HR, 1.05; 95% CI, 1.04-1.07; P < .001) and surgery without NAC (HR, 1.39; 95% CI, 1.03-1.88; P = .03). CONCLUSIONS: This is the first analysis of NLR in BC to use prospectively collected clinical trial data. In contrast to previous studies, it suggests that NLR is neither a prognostic nor predictive biomarker for OS in muscle-invasive BC. Cancer 2017;123:794-801. © 2016 American Cancer Society.

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer.

PURPOSE: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortly after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. METHODS AND MATERIALS: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. RESULTS: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. CONCLUSIONS: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.