Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

A bloodâ based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

IntroductionMultinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a bloodâ based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3â years.MethodsThe NRI included erythrocyte nâ 3 polyunsaturated fatty acids (nâ 3 PUFA 22:6nâ 3 and 20:5nâ 3), serum 25â hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0â 3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixedâ effects models.ResultsEighty percent had at lease one nutritional risk factor for cognitive decline (NRI â ¥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRIâ 1: β = â 0.04 SU/y, P = .03; NRIâ 2: β = â 0.08 SU/y, P < .0001; and NRIâ 3: β = â 0.11 SU/y, P = .0008).DiscussionIdentifying and addressing these wellâ established nutritional risk factors may reduce ageâ related cognitive decline in older adults; an observation that warrants further study.Highlightsâ ¢Multiâ nutrient approaches may produce more robust effects through interactive propertiesâ ¢Nutritional risk index can objectively quantify nutritionâ related cognitive changesâ ¢Optimum nutritional status associated with cognitive enhancement over 3â yearsâ ¢Suboptimum nutritional status associated with cognitive decline over 3â yearsâ ¢Optimizing this nutritional risk index may promote cognitive health in older adultsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152935/1/trc2jtrci201911004.pd

Development and evaluation of robust molecular markers linked to disease resistance in tomato for distinctness, uniformity and stability testing

Molecular markers linked to phenotypically important traits are of great interest especially when traits are difficult and/or costly to be observed. In tomato where a strong focus on resistance breeding has led to the introgression of several resistance genes, resistance traits have become important characteristics in distinctness, uniformity and stability (DUS) testing for Plant Breeders Rights (PBR) applications. Evaluation of disease traits in biological assays is not always straightforward because assays are often influenced by environmental factors, and difficulties in scoring exist. In this study, we describe the development and/or evaluation of molecular marker assays for the Verticillium genes Ve1 and Ve2, the tomato mosaic virusTm1 (linked marker), the tomato mosaic virus Tm2 and Tm22 genes, the Meloidogyne incognita Mi1-2 gene, the Fusarium I (linked marker) and I2 loci, which are obligatory traits in PBR testing. The marker assays were evaluated for their robustness in a ring test and then evaluated in a set of varieties. Although in general, results between biological assays and marker assays gave highly correlated results, marker assays showed an advantage over biological tests in that the results were clearer, i.e., homozygote/heterozygote presence of the resistance gene can be detected and heterogeneity in seed lots can be identified readily. Within the UPOV framework for granting of PBR, the markers have the potential to fulfil the requirements needed for implementation in DUS testing of candidate varieties and could complement or may be an alternative to the pathogenesis tests that are carried out at present

Training Genetic Counsellors to Deliver an Innovative Therapeutic Intervention: their views and experience of facilitating multi-family discussion groups

Innovations in clinical genetics have increased diagnosis, treatment and prognosis of inherited genetic conditions (IGCs). This has led to an increased number of families seeking genetic testing and / or genetic counselling and increased the clinical load for genetic counsellors (GCs). Keeping pace with biomedical discoveries, interventions are required to support families to understand, communicate and cope with their Inherited Genetic Condition. The Socio-Psychological Research in Genomics (SPRinG) collaborative have developed a new intervention, based on multi-family discussion groups (MFDGs), to support families affected by IGCs and train GCs in its delivery. A potential challenge to implementing the intervention was whether GCs were willing and able to undergo the training to deliver the MFDG. In analysing three multi-perspective interviews with GCs, this paper evaluates the training received. Findings suggests that MFDGs are a potential valuable resource in supporting families to communicate genetic risk information and can enhance family function and emotional well-being. Furthermore, we demonstrate that it is feasible to train GCs in the delivery of the intervention and that it has the potential to be integrated into clinical practice. Its longer term implementation into routine clinical practice however relies on changes in both organisation of clinical genetics services and genetic counsellors' professional development

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Style of Alpine tectonic deformation in the Castellane fold-and-thrust belt, (SW Alps, France): Insights from balanced cross-sections

International audienceThis study proposes a reappraisal of the role of the basement tectonics in the structuration of the Alpine foreland,across the Castellane fold-and-thrust belt located in southwestern Alps. We construct three 30 km length N–Sbalanced cross-sections across the entire fold-and-thrust belt, in order to quantify the amount of horizontalshortening due to the Pyrenean and Alpine deformations. We then assess the role of the basement inheritedstructures during the compressional phases which resulted in the exhumation of the Argentera–Mercantour Ex-ternal Crystalline Massif and the Barrot Dome. The construction of these balanced cross-sections suggests a dom-inant thick-skinned deformation style, which includes the reactivation of inherited Permian and Early Cretaceousbasement normal faults. We reconstructed three restoration stages: the oldest one highlights the geometry ofPermian and Early Cretaceous extensional structures; the intermediate one after the Late Cretaceous evidencesafirst compressional episode linked to the Pyrenean compression; and the latest one in the Oligocene showsthefirst Alpine folds resulting from the southward thrusting of the internal units over the external ones alongof the Penninic Frontal Thrust. Balanced cross-sections suggest very moderate crystalline basement–sedimentarycover decoupling.On the westernand central cross-sections, the estimatedamountof shorteningranges from 9.5to 10 km (21%) whereas on the easternmost one shows ~5 km of shortening (9%). These shortening values areconsistent with previously published estimates in the surrounding foreland subalpine chains. They highlight adecreasing value of Pyrenean shortening toward the east, while the Alpine shortening dominates and amplifiesthisfirst phase in a similar direction. We interpret this dominantly thick-skinned structural style as a possibleconsequenceofthe Neogenethermal weakening inthe European passivemarginabovethe Ligurian slab rollback

The deep structure and reactivation of the Kyrgyz Tien Shan: Modelling the past to better constrain the present

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How to interpret Cosmogenic Radionuclides Exposure (CRE) ages on river-incised gorges undergoing rock falls: application to Southern French Alps and Provence

International audienceRiver channels and hillslopes are shaped by the joint action of localized, vertical fluvial incision along the channel and of diffuse surface creep, landslides or rock falls on the adjacent slopes, the latter being often gathered under the generic term of hillslope processes. The interplay between river incision and hillslope processes is responsible for various landscape forms, from smooth, low-relief areas to sharp and deeply incised domains. In areas where river incision is the dominant erosive process, determining the gradual exposure of river gorge walls by cosmogenic radionuclide dating permits to estimate the long-term (several ka) local incision rate. However, strongly cohesive rocks like massive limestones or sandstones may be prone, from time to time, to abrupt and localized degradation by rock falls. On a gorge wall, besides resetting the exposure age signal on the area where a block has been detached, rock fall events also produce debris that transiently protect the bedrock from river incision and the bottom of the gorge wall from cosmic radiations. In some extreme cases, rock fall events can even lead to the formation of epigenetic gorges. Although gorge walls appear as good markers of river incision, the random occurrence of rock falls may therefore add complexity to the interpretation of exposure ages, to the point where the actual river incision imprint is barely discernable. In this presentation, we simulate the 1D evolution of topography and Cosmogenic Radionuclides Exposure (CRE) ages on a gorge wall progressively formed by river incision and randomly reshaped by rock falls, in order to evaluate the imprint of these events on the CRE signal. We then discuss the implications of these models on the sampling strategy and on the interpretation of previously dated river gorges in the Southern French Alps and Provence