Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

Multicenter Comparison of Molecular Tumor Boards in The Netherlands: Definition, Composition, Methods, and Targeted Therapy Recommendations

Background: Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods: MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results: Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type–specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion: MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a “Dutch MTB model” for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice: Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing

Technology and Structural Change in Alberta Cereal Agriculture

Structural change and technology within the agriculture and food system in Alberta are becoming more complex as agriculture industrializes. This relationship is neither simultaneous nor unique according to work done on commercial cereal farms in central Alberta. The nature of the relationship appears to be one of periodic reversal of causality. Technology, characterised mainly as mechanical and chemical, shaped structure during the period represented by the 1971 census. Biotechnology is beginning now to have its own effect on fixed factor proportions distinct from that of mechanical technology. Mechanical technology change is having a greater effect on capital/labor ratios in 1986 than in 1971. Fixed factor proportions, as observed in 1986, appear to be becoming limiting to technology. Disturbances to the economic structure of agriculture by technological change normally bring reaction to preserve the status quo. The reaction, taking the form of subsidies and credit policies, may be counter productive to technological change required for competition in world markets during periods when structure determines technology. Perhaps the most important of these structural changes has been the declining rural equity in farm businesses which is slowly changing the self employed nature of agriculture to that of the owner/employee organisation of urban economies. This change makes farm family income increasingly dependent on off farm employment in rural and periurban areas. The results from this study lead to the conclusion that government policies to limit the consolidation of farms are more inhibiting now to technological change than they used to be. With the emergence of interest in agricultural free trade, it is more essential than ever before to distinguish between subsidies which compensate for hurt from hostile weather or foreign domestic policies, from those subsidies which address structural hurt from technological progress

Design of free stalls for dairy herds: A review.

Lying is an important behavior of dairy cattle. Cows should spend more than 50% of a day lying as it has a high impact on their milk yield and animal welfare. The design, size, and flooring properties of the free stalls influence the time cows spend lying, the way they lie down, and their rising movements. The purpose of this review is to provide an overview of the currently available information with the aim to assist farmers and advisors to come to an optimal design of the free stalls. The design of the free stalls should enable the cows to move and lie in positions as natural as possible. Cows should rest, with all parts of the body, on a clean, dry and soft bed, be able to stretch their front legs forward, lie on their sides with unobstructed space for their neck and head, and rest with their heads against their flanks without hindrance from a partition. When they stand, they should not be hindered by neck rails, partitions, or supports. A comfortable place for cows to lie down helps cows to stay healthy, improve welfare, and increase milk yield. Hence, the probability of a longer productive life for the cows increases and the number of replacements per year decreases

Design of free stalls for dairy herds: A review.

Lying is an important behavior of dairy cattle. Cows should spend more than 50% of a day lying as it has a high impact on their milk yield and animal welfare. The design, size, and flooring properties of the free stalls influence the time cows spend lying, the way they lie down, and their rising movements. The purpose of this review is to provide an overview of the currently available information with the aim to assist farmers and advisors to come to an optimal design of the free stalls. The design of the free stalls should enable the cows to move and lie in positions as natural as possible. Cows should rest, with all parts of the body, on a clean, dry and soft bed, be able to stretch their front legs forward, lie on their sides with unobstructed space for their neck and head, and rest with their heads against their flanks without hindrance from a partition. When they stand, they should not be hindered by neck rails, partitions, or supports. A comfortable place for cows to lie down helps cows to stay healthy, improve welfare, and increase milk yield. Hence, the probability of a longer productive life for the cows increases and the number of replacements per year decreases