Relevance of eating pattern for selection of growing pigs

In this thesis investigations were directed at the consequences of testing future breeding pigs in group housing, with individual feed intake recording. Subjects to be addressed were: the effect of housing system on feed intake pattern and performance, relationships between feed intake pattern and performance and genetic aspects of the feed intake pattern. Housing system significantly influenced feed intake pattern, digestibility of feed, growth rate and feed conversion. Through effects on level of activity and digestibility, frequency of eating and daily eating time were negatively related with efficiency of production. Meal size and rate of feed intake were positively related with growth rate and backfat thickness. Feed intake traits had moderate heritabilities

A coupled agent-based model for France for simulating adaptation and migration decisions under future coastal flood risk

In this study, we couple an integrated flood damage and agent-based model (ABM) with a gravity model of internal migration and a flood risk module (DYNAMO-M) to project household adaptation and migration decisions under increasing coastal flood risk in France. We ground the agent decision rules in a framework of subjective expected utility theory. This method addresses agent's bounded rationality related to risk perception and risk aversion and simulates the impact of push, pull, and mooring factors on migration and adaptation decisions. The agents are parameterized using subnational statistics, and the model is calibrated using a household survey on adaptation uptake. Subsequently, the model simulates household adaptation and migration based on increasing coastal flood damage from 2015 until 2080. A medium population growth scenario is used to simulate future population development, and sea level rise (SLR) is assessed for different climate scenarios. The results indicate that SLR can drive migration exceeding 8000 and 10,000 coastal inhabitants for 2080 under the Representative Concentration Pathways 4.5 and 8.5, respectively. Although household adaptation to flood risk strongly impacts projected annual flood damage, its impact on migration decisions is small and falls within the 90% confidence interval of model runs. Projections of coastal migration under SLR are most sensitive to migration costs and coastal flood protection standards, highlighting the need for better characterization of both in modeling exercises. The modeling framework demonstrated in this study can be upscaled to the global scale and function as a platform for a more integrated assessment of SLR-induced migration

Making Birmingham a Flood Resilient City: Challenges and Opportunities

The city of Birmingham has experienced a number of significant flooding events in the past two decades. The impacts of these flood events include physical damage to critical infrastructure, as well as significant losses caused by business interruption and general disruption to communities. Human losses and impacts can be life changing. This study identifies the current challenges and opportunities of managing flood risk in the city of Birmingham, drawing on a desk-based account of current flood risk management (FRM) practice and diagnostic evidence. This interrogation adopts the use of a ‘flood resilience circle model’ to consider ways to address the challenges in a methodological manner aligned to an integrated approach to flood risk management. Solutions aligned to the key FRM stages of prevention, preparation, response and recovery are provided. The findings will be of interest to policy makers and decision makers on how to address current weaknesses in FRM practices towards the prospect of a sustainable approach that improves the resilience of the city and delivers multiple benefits. Recommendations made include the adoption of a blue-green systems approach, the development of a new communication strategy aligned to motivating behaviour change, and improved flood forecasting especially for surface water flooding

A coupled agent-based model to analyse human-drought feedbacks for agropastoralists in dryland regions

Drought is a persistent hazard that impacts the environment, people's livelihoods, access to education and food security. Adaptation choices made by people can influence the propagation of this drought hazard. However, few drought models incorporate adaptive behavior and feedbacks between adaptations and drought. In this research, we present a dynamic drought adaptation modeling framework, ADOPT-AP, which combines socio-hydrological and agent-based modeling approaches. This approach is applied to agropastoral communities in dryland regions in Kenya. We couple the spatially explicit hydrological Dryland Water Partitioning (DRYP) model with a behavioral model capable of simulating different bounded rational behavioral theories (ADOPT). The results demonstrate that agropastoralists respond differently to drought due to differences in (perceptions of) their hydrological environment. Downstream communities are impacted more heavily and implement more short-term adaptation measures than upstream communities in the same catchment. Additional drivers of drought adaptation concern socio-economic factors such as wealth and distance to wells. We show that the uptake of drought adaptation influences soil moisture (positively through irrigation) and groundwater (negatively through abstraction) and, thus, the drought propagation through the hydrological cycle

The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement

BACKGROUND: Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. MAIN BODY: Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. SHORT CONCLUSION: Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED

Hypoxia potentiates monocyte-derived dendritic cells for release of tumor necrosis factor alpha via MAP3K8

Dendritic cells (DCs) constantly sample peripheral tissues for antigens, which are subsequently ingested to derive peptides for presentation to T cells in lymph nodes. To do so, DCs have to traverse many different tissues with varying oxygen tensions. Additionally, DCs are often exposed to low oxygen tensions in tumors, where vascularization is lacking, as well as in inflammatory foci, where oxygen is rapidly consumed by inflammatory cells during the respiratory burst. DCs respond to oxygen levels to tailor immune responses to such low-oxygen environments. In the present study, we identified a mechanism of hypoxia-mediated potentiation of release of tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine with important roles in both anti-cancer immunity and autoimmune disease. We show in human monocyte-derived DCs (moDCs) that this potentiation is controlled exclusively via the p38/mitogen-activated protein kinase (MAPK) pathway. We identified MAPK kinase kinase 8 (MAP3K8) as a target gene of hypoxia-induced factor (HIF), a transcription factor controlled by oxygen tension, upstream of the p38/MAPK pathway. Hypoxia increased expression of MAP3K8 concomitant with the potentiation of TNF-alpha secretion. This potentiation was no longer observed upon siRNA silencing of MAP3K8 or with a small molecule inhibitor of this kinase, and this also decreased p38/MAPK phosphorylation. However, expression of DC maturation markers CD83, CD86, and HLA-DR were not changed by hypoxia. Since DCs play an important role in controlling T-cell activation and differentiation, our results provide novel insight in understanding T-cell responses in inflammation, cancer, autoimmune disease and other diseases where hypoxia is involved

The need for widely available genomic testing in rare eye diseases: an ERN-EYE position statement.

BACKGROUND: Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN-EYE) is to facilitate improvement in diagnosis of RED in European member states. MAIN BODY: Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. SHORT CONCLUSION: Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED

The natural history and genotype–phenotype correlations of TMPRSS3 hearing loss:an international, multi-center, cohort analysis

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype–phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.</p