Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study.

BACKGROUND: In about 30% of young stroke patients, no cause can be identified. In elderly patients, kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke. There are hypotheses that novel non-traditional risk factors, like chronic inflammation and oxidative stress, are involved in chronic kidney disease, affecting the cerebral microvasculature that would in turn lead to stroke. Our objective is to investigate the influence of kidney dysfunction on long-term mortality and incident vascular events after stroke in young adults aged 18 through 50 and if this relationship would be independent of other cardiovascular risk factors. METHODS: We prospectively included 460 young stroke patients with an ischemic stroke or transient ischemic attack admitted to our department between January 1, 1980 and November 1, 2010. Follow-up was done between 2014 and 2015. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine levels and was divided in 3 subgroups: eGFR 120 ml/min/1.73 m2. Cox proportional hazard models were used to determine the effect of kidney dysfunction on mortality and incident vascular events, adjusting for cardiovascular risk factors. RESULTS: An eGFR <60 (HR 4.6; 95% CI 2.6-8.2) was associated with an increased risk of death and an increased risk of incident stroke (HR 4.1; 95% CI 1.9-9.0) independent of cardiovascular risk factors, but it was not associated with other vascular events. The point estimate for the 15-year cumulative mortality was 70% (95% CI 46-94) for patients with a low eGFR, 24% (95% CI 18-30) for patients with a normal eGFR and 30% (95% CI 12-48) for patients with a high eGFR. The point estimate for the 15-year cumulative risk of incident stroke was 45% (95% CI 16-74) for patients with a low eGFR, 13% (95% CI 9-17) for patients with a normal eGFR and 8% (95% CI 0-18) for patients with a high eGFR. CONCLUSIONS: Kidney dysfunction is related to long-term mortality and stroke recurrence, but not to incident cardiovascular disease, on average 11 years after young stroke. This warrants a more intensive follow-up of young stroke patients with signs of kidney dysfunction in the early phase. In addition, the clear association between kidney dysfunction and incident stroke seen in our young stroke population might be a first step in the recognition of kidney dysfunction as a new risk factor for the development of stroke at young age. Also, it can lead to new insights in the etiological differences between cardiovascular and cerebrovascular disease.This study was funded by the Dutch Epilepsy Fund (grant number 10-18)

Windbreaks in North American Agricultural Systems

Windbreaks are a major component of successful agricultural systems throughout the world. The focus of this chapter is on temperate-zone, commercial, agricultural systems in North America, where windbreaks contribute to both producer profitability and environmental quality by increasing crop production while simultaneously reducing the level of off-farm inputs. They help control erosion and blowing snow, improve animal health and survival under winter conditions, reduce energy consumption of the farmstead unit, and enhance habitat diversity, providing refuges for predatory birds and insects. On a larger landscape scale windbreaks provide habitat for various types of wildlife and have the potential to contribute significant benefits to the carbon balance equation, easing the economic burdens associated with climate change. For a windbreak to function properly, it must be designed with the needs of the landowner in mind. The ability of a windbreak to meet a specific need is determined by its structure: both external structure, width, height, shape, and orientation as well as the internal structure; the amount and arrangement of the branches, leaves, and stems of the trees or shrubs in the windbreak. In response to windbreak structure, wind flow in the vicinity of a windbreak is altered and the microclimate in sheltered areas is changed; temperatures tend to be slightly higher and evaporation is reduced. These types of changes in microclimate can be utilized to enhance agricultural sustainability and profitability. While specific mechanisms of the shelter response remain unclear and are topics for further research, the two biggest challenges we face are: developing a better understanding of why producers are reluctant to adopt windbreak technology and defining the role of woody plants in the agricultural landscape

Oxford Phase 3 unicompartmental knee arthroplasty: medium-term results of a minimally invasive surgical procedure

PURPOSE: In the last decade, a major increase in the use of and interest in unicompartmental knee arthroplasty (UKA) has developed. The Oxford Phase 3 UKA is implanted with a minimally invasive technique using newly developed instruments. The objective of this prospective study was to evaluate the outcome of UKA in patients with medial osteoarthritis of the knee in a high-volume unit. METHODS: Two-hundred and forty-four UKAs were performed with a minimally invasive approach. The median age was 72 (43-91) years. The median follow-up was 4.2 years (range 1-10.4 years). Fourteen patients died, and nine were considered to be lost to follow-up, but all had a well-functioning prosthesis in situ until their last follow-up. Pain, function and health-related quality of life were evaluated pre- and postoperatively using patient- and assessor-based outcome scores, as well as radiographic evidence. RESULTS: The mean Knee Society knee and function scores, WOMAC-scores, Oxford-score and VAS pain and satisfaction all improved. Nine knees required revision. Eleven patients required an additional arthroscopic procedure due to persisting pain secondary to intra-articular pathology, and four patients required manipulation under anaesthesia because of limited range of motion. The 7-year cumulative survival rate of the arthroplasty was 94.4%. A low incidence (21%) of a radiolucent line beneath the tibial component was observed at 5 years of follow-up. CONCLUSION: This study showed a high survival rate of the Oxford Phase 3 UKA. Patient satisfaction and functional performance were also very high. Major complication rate was low; in addition, the incidence of radiolucency under the tibial component, when compared to present literature, was low. When strict indication criteria are followed, excellent, durable, and in our opinion reliable, results can be expected for this procedur

Exploring the perspectives and preferences for HTA across German healthcare stakeholders using a multi-criteria assessment of a pulmonary heart sensor as a case study

Background Health technology assessment and healthcare decision-making are based on multiple criteria and evidence, and heterogeneous opinions of participating stakeholders. Multi-criteria decision analysis (MCDA) offers a potential framework to systematize this process and take different perspectives into account. The objectives of this study were to explore perspectives and preferences across German stakeholders when appraising healthcare interventions, using multi-criteria assessment of a heart pulmonary sensor as a case study. Methods An online survey of 100 German healthcare stakeholders was conducted using a comprehensive MCDA framework (EVIDEM V2.2). Participants were asked to provide i) relative weights for each criterion of the framework; ii) performance scores for a health pulmonary sensor, based on available data synthesized for each criterion; and iii) qualitative feedback on the consideration of contextual criteria. Normalized weights and scores were combined using a linear model to calculate a value estimate across different stakeholders. Differences across types of stakeholders were explored. Results The survey was completed by 54 participants. The most important criteria were efficacy, patient reported outcomes, disease severity, safety, and quality of evidence (relative weight >0.075 each). Compared to all participants, policymakers gave more weight to budget impact and quality of evidence. The quantitative appraisal of a pulmonary heart sensor revealed differences in scoring performance of this intervention at the criteria level between stakeholder groups. The highest value estimate of the sensor reached 0.68 (on a scale of 0 to 1, 1 representing maximum value) for industry representatives and the lowest value of 0.40 was reported for policymakers, compared to 0.48 for all participants. Participants indicated that most qualitative criteria should be considered and their impact on the quantitative appraisal was captured transparently. Conclusions The study identified important variations in perspectives across German stakeholders when appraising a healthcare intervention and revealed that MCDA can demonstrate the value of a specified technology for all participating stakeholders. Better understanding of these differences at the criteria level, in particular between policymakers and industry representatives, is important to focus innovation aligned with patient health and healthcare system values and constraints

Common garden experiments in the genomic era : new perspectives and opportunities

PdV was supported by a doctoral studentship from the French Ministère de la Recherche et de l’Enseignement Supérieur. OEG was supported by the Marine Alliance for Science and Technology for Scotland (MASTS)The study of local adaptation is rendered difficult by many evolutionary confounding phenomena (e.g. genetic drift and demographic history). When complex traits are involved in local adaptation, phenomena such as phenotypic plasticity further hamper evolutionary biologists to study the complex relationships between phenotype, genotype and environment. In this perspective paper, we suggest that the common garden experiment, specifically designed to deal with phenotypic plasticity has a clear role to play in the study of local adaptation, even (if not specifically) in the genomic era. After a quick review of some high-throughput genotyping protocols relevant in the context of a common garden, we explore how to improve common garden analyses with dense marker panel data and recent statistical methods. We then show how combining approaches from population genomics and genome-wide association studies with the settings of a common garden can yield to a very efficient, thorough and integrative study of local adaptation. Especially, evidence from genomic (e.g. genome scan) and phenotypic origins constitute independent insights into the possibility of local adaptation scenarios, and genome-wide association studies in the context of a common garden experiment allow to decipher the genetic bases of adaptive traits.PostprintPeer reviewe

How Distinctive are ADHD and RD? Results of a Double Dissociation Study

The nature of the comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and Reading Disability (RD) was examined using a double dissociation design. Children were between 8 and 12 years of age and entered into four groups: ADHD only (n = 24), ADHD+RD (n = 29), RD only (n = 41) and normal controls (n = 26). In total, 120 children participated in the study; 38 girls and 82 boys. Both ADHD and RD were associated with impairments in inhibition and lexical decision, although inhibition and lexical decision were more severely impaired in RD than in ADHD. Visuospatial working memory deficits were specific to children with only ADHD. It is concluded that there was overlap on lexical decision and to a lesser extent on inhibition between ADHD and RD. In ADHD, impairments were dependent on IQ, which suggest that the overlap in lexical decision and inhibition is different in origin for ADHD and RD. The ADHD only group was specifically characterized by deficits in visuospatial working memory. Hence, no double dissociation between ADHD and RD was found on executive functioning and lexical decision

Medium-size-vessel vasculitis

Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis

Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp(+/-) and cbp(+/+) littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.We are grateful to Begona Fernandez for her excellent technical assistance. We would like to thank S. Sawiak (Wolfson Imaging Centre, University of Cambridge, Cambridge, United Kingdom) for the mouse brain tissue probability maps and the SPMmouse plug-in, and to N. Kovacevic (Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada) for the atlas of the mouse brain. Supported by grants from the Spanish MINECO to S.C. (BFU 2012-39958) and MINECO and FEDER to D.M. (TEC 2012-33778) and from MINECO (SAF2011-22855) and Generalitat Valenciana (Prometeo/2012/005) to A.B. The Instituto de Neurociencias is "Centre of Excellence Severo Ochoa".Ateca Cabarga, JC.; Cosa, A.; Pallares, V.; Lopez-Atalaya, JP.; Barco, A.; Canals, S.; Moratal Pérez, D. (2015). Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry. Scientific Reports. 5. https://doi.org/10.1038/srep16256S5Rubinstein, J. H. & Taybi, H. Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child 105, 588–608 (1963).Van Belzen, M., Bartsch, O., Lacombe, D., Peters, D. J. & Hennekam, R. C. Rubinstein-Taybi syndrome (CREBBP, EP300). Eur J Hum Genet. 19, preceeding 118–120 (2011).Hennekam, R. C. 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