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Until recently, the massive development of industrial and smallholder oil palm (Elaeis guineensis Jacq.) plantations has generally been conducted according to the monocrop model. However, alternative cropping systems have emerged, based on more diversified systems that combine various crops within the oil palm plots. By giving this plant a status equivalent to that of a tree, these practices correspond to agroforestry systems. In the present study, 39 agroforestry systems were identified worldwide through a preliminary literature review, a review of NGO websites and expert surveys. Our results reveal five different types of oil palm agroforestry systems: (i) associations with livestock during the production phase of the oil palm; (ii) traditional African palm and food crop systems sustained over time; (iii) associations with food crops during the juvenile phase of the oil palm; (iv) systems developed by family farms that permanently associate other plants; and (v) prototype designs developed by research institutions, often at the request of local agricultural enterprises. The spatiotemporal description of these systems enabled us to identify associated ecosystem services. Building on various proposals of biodiversity insertion in a monoculture to convert it into an agroforestry system, the present study offers new perspectives for the sustainable development of palm oil production.

Assessing the sustainability of socio-ecological systems requires understanding the interactions between numerous ecological, economic and social components. Models are often used to investigate how interactions shape system feedbacks and drive the complex dynamics at play in such systems. However, building these models is a non-trivial exercise, which often neglects stakeholder knowledge and perceptions. We adopted a participatory approach that relies on conducting workshops to engage stakeholders into the development of qualitative models of system feedback. This type of participatory qualitative modeling is well suited to address the complexity of socio-ecological systems in a holistic manner, identify key stakes and feedbacks, and predict responses to perturbations. We use this approach to investigate the factors that condition sustainability of the socio-ecological system associated with shellfish aquaculture in the Normand-Breton Gulf in France. Six region-specific workshops were organized with shellfish producers, managers and other stakeholders to identify and describe key components, interactions and pressures that contribute to overall socio-ecological dynamics. Differences and commonalities in system perceptions were identified across the different regions and focus groups. We reconciled stakeholder-specific discrepancies in model structure into a synthetic representation that conciliates alternative views of the system. Next, we predicted how the system might respond to alternative scenarios of change. Overall, our participatory qualitative modeling exercise identified key drivers of the system under study that constitute effective management levers to maintain system sustainability. For instance, low social acceptability of the aquaculture industry generally appears to be a major constraint on the sustainability of shellfish aquaculture in the Normand-Breton Gulf, while reducing rearing density appears to be a key driver of sustainability.

Le développement massif des palmeraies industrielles et villageoises s’est réalisé en suivant un dispositif de plantation en culture pure du palmier à huile (Elaeis guineensis Jacq.). Cependant, divers systèmes de culture alternatifs ont émergé, dans lesquels sont associés des cultures et des animaux à diverses phases du cycle de culture du palmier. En attribuant à cette plante un statut équivalent à celui d’un arbre, ces systèmes correspondent à des systèmes agroforestiers. Dans cette étude, trente-neuf systèmes agroforestiers à base de palmier à huile ont été identifiés dans le monde à partir de la littérature, de la consultation de sites internet et d’enquêtes. Cinq types de systèmes agroforestiers ont émergé : i) l’agropastoralisme, correspondant à l’introduction d’élevage pendant la phase productive du cycle de culture du palmier ; ii) l’agroforesterie traditionnelle africaine à base de palmiers et de cultures vivrières ; iii) l’agroforesterie temporaire avec des cultures vivrières en palmeraie juvénile ; iv) l’agroforesterie permanente avec des cultures pérennes ; et enfin v) des prototypes de systèmes agroforestiers à base de palmiers sélectionnés, conçus par des institutions de recherche et développement, souvent à la demande d’entreprises agricoles ou d’agro-industries. La description spatio-temporelle de ces systèmes a permis de mettre en évidence les services écosystémiques rendus par les espèces associées. Diverses perspectives de développement de l’agroforesterie sont discutées en tant qu’alternative aux palmeraies monospécifiques, pour introduire de la biodiversité dans des territoires historiquement spécialisés en élaeiculture, pour initier du développement élaeicole en zones suboptimales, ou encore pour s’adapter au changement climatique.

Les modes de production des connaissances scientifiques dans le domaine agricole sont questionnés par l'écologisation des pratiques ou l'essor des sciences participatives. Les pratiques de recherche, tant en sciences biotechniques qu'en sciences humaines, et leur relation aux connaissances autres que scientifiques, en ressortent interpellées. Comment articuler ces différents types de connaissances dans l'activité scientifique ? Quelles interactions avec nos propres connaissances de chercheurs ? Comment accéder aux connaissances des agriculteurs, et qu'en faire ? Que faire dans des situations où les connaissances deviennent source de tension ? Cet article rend compte des réflexions qui ont émergé lors de la conception et de l'animation de l'école-chercheurs organisée par l'Inra et le Cirad en juin 2016. Son objectif était d'outiller les participants pour analyser et agir avec réflexivité dans ces situations. Nous analysons les étapes de sa conception et les échanges interdisciplinaires qu'elle a nécessités dans l'équipe organisatrice, les cadrages et modalités pédagogiques choisis, et enfin leurs impacts sur le déroulement de l'école.

Widespread use of topology optimisation as a design tool for additive manufacturing faces major inhibiting obstacles, such as high computational costs and complexity, concern for other failure modes, and manufacturability. Interactive infill topology optimisation presents an alternative approach to circumvent some of these barriers. The novel contribution of the present work prompts the user to draw a tailored infill pattern, specify regions of interest to locate the infill, and control how strictly the pattern is replicated in the material layout of the design using appearance constraints. This approach improves engineering metrics not directly included in the optimisation formulation by incorporating the user’s engineering experience, thereby avoiding increased computational costs, parameter tuning, and numerical artifacts associated with complex objective functions and constraints. Two 2D benchmark examples increase the linear buckling resistance and energy absorption, respectively, and a 2.5D example minimises compliance while reducing the quantity of overhang supports for additive manufacturing.

The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations.

Abstract Background Experimentally, erythropoietin (EPO) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury. We tested the hypothesis that different doses of recombinant human EPO administered to patients after cardiac surgery would minimize kidney lesions and the systemic inflammatory response, thereby decreasing acute kidney injury (AKI) incidence. Methods In this double-blinded randomized control study, 80 patients admitted to the ICU post-cardiac surgery were randomized by computer to receive intravenously isotonic saline (n = 40) versus α-Epoetin (n = 40): either 40000 IU (n = 20) or 20000 IU (n = 20). The study lasted one year. The primary outcome was the change in urinary NGAL concentration from baseline and 48 h after EPO injection. Creatinine, cystatine C and urinary NGAL levels were measured on the day of randomization and 2–4 days after EPO injection. To assess acute inflammatory response, serum cytokines (IL6 and IL8) were measured at randomization and four days after r-HuEPO injection. Patients and care-takers were blinded for the assignment. Results No patient was excluded after randomization. Patient groups did not differ in terms of age, gender, comorbidities and renal function at randomization. The rate of AKI assessed by AKIN criteria was 22.5% in our population. EPO treatment did not significantly modify the difference in uNGAl between 48 hours and randomization compared to placebo [2.5 ng/ml (−17.3; 22.5) vs 0.7 ng/ml (−31.77; 25.15), p = 0.77] and the incidence of AKI was similar. Inflammatory cytokines levels were not influenced by EPO treatment. Mortality and hospital stays were similar between the groups and no adverse event was recorded. Conclusion In this randomized-controlled trial, α-Epoetin administrated after cardiac surgery, although safe, demonstrated neither nephroprotective nor anti-inflammatory properties. Trial registration number NCT00676234

Abstract Introduction Oxalate nephropathy has various etiologies and remains a rare cause of renal failure. To the best of our knowledge, we report the first case of oxalate nephropathy following octreotide therapy. Case presentation We report the case of a 78-year-old Caucasian man taking chronic octreotide treatment for acromegaly who presented with acute oxalate nephropathy after antibiotic therapy. The diagnosis was confirmed by urinary analysis and a kidney biopsy. The recovery of renal function was favorable after hydration and withdrawal of octreotide therapy. Conclusions Oxalate nephropathy should be suspected in patients at risk who present with acute kidney injury after prolonged antibiotic treatment. This diagnosis should be distinguished from immuno-allergic interstitial nephritis and requires specific care. The evolution of this condition may be favorable if the pathology is identified correctly. Octreotide therapy should be considered a risk factor for enteric oxaluria.

Abstract Background Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. Methods/Design The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE100C*6 versus FE100C*3 followed by Docetaxel100*3). Discussion In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE100C-Docetaxel100, and 1,327 received French FE100C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. Trial Registration clinical Trials.gov NCT01222052.

Abstract Background Current research on quantitative genetics has provided efficient guidelines for the sustainable management of selected populations: genetic gain is maximized while the loss of genetic diversity is maintained at a reasonable rate. However, actual selection schemes are complex, especially for large domestic species, and they have to take into account many operational constraints. This paper deals with the actual selection of dairy goats where the challenge is to optimize diffusion of buck semen on the field. Three objectives are considered simultaneously: i) natural service buck replacement (NSR); ii) goat replacement (GR); iii) semen distribution of young bucks to be progeny-tested. An appropriate optimization method is developed, which involves five analytical steps. Solutions are obtained by simulated annealing and the corresponding algorithms are presented in detail. Results The whole procedure was tested on two French goat populations (Alpine and Saanen breeds) and the results presented in the abstract were based on the average of the two breeds. The procedure induced an immediate acceleration of genetic gain in comparison with the current annual genetic gain (0.15 genetic standard deviation unit), as shown by two facts. First, the genetic level of replacement natural service (NS) bucks was predicted, 1.5 years ahead at the moment of reproduction, to be equivalent to that of the progeny-tested bucks in service, born from the current breeding scheme. Second, the genetic level of replacement goats was much higher than that of their dams (0.86 unit), which represented 6 years of selection, although dams were only 3 years older than their replacement daughters. This improved genetic gain could be achieved while decreasing inbreeding coefficients substantially. Inbreeding coefficients (%) of NS bucks was lower than that of the progeny-tested bucks (-0.17). Goats were also less inbred than their dams (-0.67). Conclusions It was possible to account for complex operational constraints while developing goat selection schemes, both efficient and sustainable. Therefore, the recommended selection and mating decisions might receive attention from goat breeders using both AI and NS.

Abstract Background Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. Methods A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. Results Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 ± 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb ≥ 11 g/dL. Mean EPO dose was 155 ± 118 IU/kg/week, being delivered mostly by subcutaneous route (64–71%). Mean serum ferritin and transferrin saturation were 435 ± 253 μg/L and 30 ± 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 ± 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb ≥ 11 g/dL than in those with Hb Conclusion In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.

Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma (MAC), but despite progress in identifying novel causative genes, many patients remain without a genetic diagnosis. We studied a cohort of 19 patients with MAC who were ascertained from a population with high rates of consanguinity. Using single nucleotide polymorphism (SNP) arrays and whole exome sequencing (WES), we identified one pathogenic variant in TENM3 in a patient with cataracts in addition to MAC. We also detected novel variants of unknown significance in genes that have previously been associated with MAC, including KIF26B, MICU1 and CDON, and identified variants in candidate genes for MAC from the Wnt signaling pathway, comprising LRP6, WNT2B and IQGAP1, but our findings do not prove causality. Plausible variants were not found for many of the cases, indicating that our current understanding of the pathogenesis of MAC, a highly heterogeneous group of ocular defects, remains incomplete.

We describe an 11-year old boy with severe global developmental delays, failure to thrive and growth retardation, refractory seizures with recurrent status epilepticus, hypogammaglobulinemia, hypergonadotropic hypogonadism, and duodenal strictures. He had facial and skin findings compatible with trichothiodystrophy, including sparse and brittle hair, thin eyebrows, and dry skin. Exome sequencing showed a hemizygous, truncating variant in RNF113A, c.903_910delGCAGACCA, predicting p.(Gln302fs*12), that was inherited from his mother. Although his clinical features overlap closely with features described in the two previously reported male first cousins with RNF113A loss of function mutations, the duodenal strictures seen in this patient have not been reported. Interestingly, the patient's mother had short stature and 100% skewed X-inactivation as seen in other obligate female carriers. A second male with developmental delays, microcephaly, seizures, ambiguous genitalia, and facial anomalies that included sparse and brittle hair, thin eyebrows and dry skin was recently reported to have c.897_898delTG, predicting p.(Cys299*) in RNF113A and we provide additional clinical details for this patient. This report further supports deleterious variants in RNF113A as a cause of a novel trichothiodystrophy syndrome.