Modified two-part strategy to rapidly improve target traits

OBJECTIVE Propose a modified two-part strategy by combining the benefits of population improvement and the conventional pipeline to rapidly improve target traits while reducing the risks of a full two-part transition

Multiple factors affect socioeconomics and wellbeing of artisanal sea cucumber fishers

Small-scale fisheries are important to livelihoods and subsistence seafood consumption of millions of fishers. Sea cucumbers are fished worldwide for export to Asia, yet few studies have assessed factors affecting socioeconomics and wellbeing among fishers. We interviewed 476 men and women sea cucumber fishers at multiple villages within multiple locations in Fiji, Kiribati, Tonga and New Caledonia using structured questionnaires. Low rates of subsistence consumption confirmed a primary role of sea cucumbers in income security. Prices of sea cucumbers sold by fishers varied greatly among countries, depending on the species. Gender variation in landing prices could be due to women catching smaller sea cucumbers or because some traders take advantage of them. Dissatisfaction with fishery income was common (44% of fishers), especially for i-Kiribati fishers, male fishers, and fishers experiencing difficulty selling their catch, but was uncorrelated with sale prices. Income dissatisfaction worsened with age. The number of livelihood activities averaged 2.2-2.5 across countries, and varied significantly among locations. Sea cucumbers were often a primary source of income to fishers, especially in Tonga. Other common livelihood activities were fishing other marine resources, copra production in Kiribati, agriculture in Fiji, and salaried jobs in New Caledonia. Fishing other coastal and coral reef resources was the most common fall-back livelihood option if fishers were forced to exit the fishery. Our data highlight large disparities in subsistence consumption, gender-related price equity, and livelihood diversity among parallel artisanal fisheries. Improvement of supply chains in dispersed small-scale fisheries appears as a critical need for enhancing income and wellbeing of fishers. Strong evidence for co-dependence among small-scale fisheries, through fall-back livelihood preferences of fishers, suggests that resource managers must mitigate concomitant effects on other fisheries when considering fishery closures. That is likely to depend on livelihood diversification programs to take pressure off co-dependent fisheries

Stochastic or deterministic:Duality of fatigue behaviour of 3D-printed meta-biomaterials

The two deformation modes of meta-biomaterials during cyclic loading have been revealed: stochastic and deterministic strut failure processes. Biomimetic Voronoi structures with a range of strut thicknesses and number of cells per unit volume are printed. We show that when the strut thickness is 200 μm or above, the fatigue fracture process of the lattice is deterministic and the fatigue scatters are below 15%. As the strut is thinned to 150 μm, the local failures occur randomly within the structure, which may lead to a high fatigue scatter (>30%). The two distinct behaviours result from the processing limit of the laser powder bed fusion technique. We demonstrate that the fatigue scatter and the location of the failure process within the lattice are related to the probability that a cluster of unconnected struts larger than a critical value can exist within the lattice. Unlike solid parts, porosity hardly triggers any damage in metallic lattices during cyclic deformation. The discovery of the Janus-like failure process opens up our understanding of meta-biomaterials and defines the pathway towards the design of mechanically durable intricate implants

Cognitive reserve, executive function, and memory in parkinson’s disease

Cognitive impairment is acknowledged as a feature of Parkinson’s disease (PD), and the most common cognitive declines are in executive function (EF) and memory. Cognitive reserve (CR) may offer some protection against cognitive dysfunction in PD. The present study used two proxies of CR (years of education, premorbid IQ) to examine the relationship between CR and (i) EF (ii) memory in a large PD sample (n = 334). Two aspects of EF were examined, including verbal fluency and planning skills. Two aspects of verbal memory were examined, including immediate recall and delayed recall. For EF, both CR proxies significantly predicted verbal fluency, but only years of education predicted planning skills. Years of education significantly predicted immediate recall, but premorbid IQ did not. Neither CR proxy predicted delayed recall. These findings suggest that CR, in particular years of education, may contribute to EF and memory function in those with PD. A key finding of this study is the varying contribution of CR proxies to different aspects of the same cognitive domain. The findings indicate that using only one proxy has the potential to be misleading and suggest that when testing the relationship between CR and cognition, studies should include tasks that measure different aspects of the cognitive domain(s) of interest

Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop

Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles.Fil: Russell, Ashley E.. University Johns Hopkins; Estados UnidosFil: Sneider, Alexandra. University Johns Hopkins; Estados UnidosFil: Witwer, Kenneth W.. University Johns Hopkins; Estados UnidosFil: Bergese, Paolo. Università Degli Studi Di Brescia; ItaliaFil: Bhattacharyya, Suvendra N.. Indian Institute of Chemical Biology; IndiaFil: Cocks, Alexander. Cardiff University; Reino UnidoFil: Cocucci, Emanuele. Ohio State University; Estados UnidosFil: Erdbrügger, Uta. University of Virginia; Estados UnidosFil: Falcon Perez, Juan M.. Ikerbasque Basque Foundation for Science; EspañaFil: Freeman, David W.. National Institute On Aging National Institute for Helth ; Estados UnidosFil: Gallagher, Thomas M.. Loyola University Of Chicago; Estados UnidosFil: Hu, Shuaishuai. Technological University Dublin; IrlandaFil: Huang, Yiyao. University Johns Hopkins; Estados Unidos. Southern Medical University; ChinaFil: Jay, Steven M.. University of Maryland; Estados UnidosFil: Kano, Shin-ichi. The University of Alabama at Birmingham School of Medicine; Estados UnidosFil: Lavieu, Gregory. Institut Curie; FranciaFil: Leszczynska, Aleksandra. University of California at San Diego; Estados UnidosFil: Llorente, Alicia M.. Oslo University Hospital; NoruegaFil: Lu, Quan. Harvard University. Harvard School of Public Health; Estados UnidosFil: Mahairaki, Vasiliki. University Johns Hopkins; Estados UnidosFil: Muth, Dillon C.. University Johns Hopkins; Estados UnidosFil: Noren Hooten, Nicole. National Institute On Aging National Institute for Helth ; Estados UnidosFil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Prada, Ilaria. Consiglio Nazionale delle Ricerche; ItaliaFil: Sahoo, Susmita. Icahn School of Medicine at Mount Sinai ; Estados UnidosFil: Schøyen, Tine Hiorth. Uit The Arctic University Of Norway; Noruega. University Johns Hopkins; Estados UnidosFil: Sheng, Lifuy. University of Washington. School of Medicine; Estados UnidosFil: Tesch, Deanna. Shaw University; Estados UnidosFil: Van Niel, Guillaume. No especifíca;Fil: Vandenbroucke, Roosmarijn E.. University of Ghent; BélgicaFil: Verweij, Frederik J.. No especifíca;Fil: Villar, Ana V.. Universidad de Cantabria; EspañaFil: Wauben, Marca. University of Utrecht; Países BajosFil: Wehman, Ann M.. Universität Würzburg; AlemaniaFil: Ardavan, Arzhang. Peking University; ; ChinaFil: Carter, David Raul Francisco. Oxford Brookes University; Reino UnidoFil: Vader, Pieter. University Medical Center Utrecht; Países Bajo

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The Design of Early-Stage Plant Breeding Trials Using Genetic Relatedness

© 2020, The Author(s). The use of appropriate statistical methods has a key role in improving the accuracy of selection decisions in a plant breeding program. This is particularly important in the early stages of testing in which selections are based on data from a limited number of field trials that include large numbers of breeding lines with minimal replication. The method of analysis currently recommended for early-stage trials in Australia involves a linear mixed model that includes genetic relatedness via ancestral information: non-genetic effects that reflect the experimental design and a residual model that accommodates spatial dependence. Such analyses have been widely accepted as they have been found to produce accurate predictions of both additive and total genetic effects, the latter providing the basis for selection decisions. In this paper, we present the results of a case study of 34 early-stage trials to demonstrate this type of analysis and to reinforce the importance of including information on genetic relatedness. In addition to the application of a superior method of analysis, it is also critical to ensure the use of sound experimental designs. Recently, model-based designs have become popular in Australian plant breeding programs. Within this paradigm, the design search would ideally be based on a linear mixed model that matches, as closely as possible, the model used for analysis. Therefore, in this paper, we propose the use of models for design generation that include information on genetic relatedness and also include non-genetic and residual models based on the analysis of historic data for individual breeding programs. At present, the most commonly used design generation model omits genetic relatedness information and uses non-genetic and residual models that are supplied as default models in the associated software packages. The major reasons for this are that preexisting software is unacceptably slow for designs incorporating genetic relatedness and the accuracy gains resulting from the use of genetic relatedness have not been quantified. Both of these issues are addressed in the current paper. An updating scheme for calculating the optimality criterion in the design search is presented and is shown to afford prodigious computational savings. An in silico study that compares three types of design function across a range of ancillary treatments shows the gains in accuracy for the prediction of total genetic effects (and thence selection) achieved from model-based designs using genetic relatedness and program specific non-genetic and residual models. Supplementary materials accompanying this paper appear online

Small-scale fishing income and fuel consumption: Fiji’s artisanal sea cucumber fishery

Understanding the income and costs of fishing is fundamental to managing fisheries and planning interventions to improve efficiency and gender equity. Few studies offer data on fisher incomes and fuel use in small-scale fisheries (SSFs), and fewer have assessed factors influencing variation among fishers and between genders. We interviewed 235 artisanal fishers among 34 island villages in an artisanal sea cucumber fishery in Fiji. Linear mixed models were used to determine the effect of geographic and socioeconomic variables on incomes and fuel use from fishing sea cucumbers. Net income of sea cucumbers to fishers, averaging FJ$8, 171 year−1 (US$4, 494 year−1) (range: FJ$0–52,008 year−1), varied among villages and was 47% lower for women than men. On an average, 60% of fishers’ gross annual income came from fishing and selling sea cucumbers, although this proportion varied greatly even within villages. Fishers who practised gleaning, fished less often, or possessing numerous livelihood income streams, were less economically dependent on sea cucumbers. Men tended to estimate higher incomes for an average day of fishing than women when compared with their recall of last sale. Fuel use varied greatly among regions in Fiji but, overall, averaged 428 L fisher−1 year−1, and represented 28% of gross income. More economical fishing strategies by women resulted in lower fuel use than men per fishing day. Breath-hold divers used less fuel (compared to fishers using scuba) and fishers targeting deep-water species used more fuel than other fishers. A best approximation of 8000 t CO2 year−1 for the carbon footprint of the whole fishery suggests that some SSFs, such as the one studied here, can be significant contributors to greenhouse gas emissions, even compared to many large-scale fisheries globally. Reforms to the management of SSFs should consider regulations that minimize carbon emissions and reduce economic dependency on vulnerable marine resources