Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2–p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2–p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2–p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2–p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2–p12 of importance in osteosarcoma tumourigenesis

Environmental sustainability and gynaecological surgery:Which factors influence behaviour? An interview study

OBJECTIVE: To assess the various factors that influence environmentally sustainable behaviour in gynaecological surgery and examine the differences between gynaecologists and residents.DESIGN: An interview study.SETTING: Academic and non-academic hospitals in the Netherlands.POPULATION: Gynaecologists (n = 10) and residents (n = 6).METHODS: Thematic analysis of semi-structured interviews to determine the various factors that influence environmentally sustainable behaviour in gynaecological surgery and to examine the differences between gynaecologists and residents. By using the Desmond framework and the COM-B BCW, both organisational and individual factors related to behaviour were considered.MAIN OUTCOME MEASURES: Factors that influence environmentally sustainable behaviour.RESULTS: Awareness is increasing but practical knowledge is insufficient. It is crucial to integrate education on the environmental impact of everyday decisions for residents and gynaecologists. Gynaecologists make their own choices but residents' autonomy is limited. There is the necessity to provide environmentally sustainable surgical equipment without compromising other standards. There is a need for a societal change that encourages safe and open communication about environmental sustainability. To transition to environmentally sustainable practices, leadership, time, collaboration with the industry and supportive regulatory changes are essential.CONCLUSION: This study lays the groundwork for promoting more environmentally sustainable behaviour in gynaecological surgery. The key recommendations, addressing hospital regulations, leadership, policy revisions, collaboration with the industry, guideline development and education, offer practical steps towards a more sustainable healthcare system. Encouraging environmentally sustainable practices should be embraced to enhance the well-being of both our planet and our population, driving us closer to a more environmentally sustainable future in healthcare.</p

Modellentwicklung eines ganzheitlichen Projektmanagementsystems für kerntechnische Rückbauprojekte (MogaMaR) : Schlussbericht des Forschungsvorhabens

Die Entwicklung eines ganzheitlichen und integrierten Projektplanungssystems ist dringend notwendig, um Abweichungen von der Planung kerntechnischer Rückbauprojekte zu vermeiden und bestehende Unsicherheiten in die Planung zu integrieren. Im Rahmen des Forschungsprojekts MogaMaR wurden Besonderheiten kerntechnischer Rückbauprojekte und Schwachstellen im Projektmanagement identifiziert. Darauf aufbauend wurde ein ganzheitliches Projektplanungssystem für kerntechnische Rückbauprojekte entwickelt

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Maternal one-carbon (1-C) metabolism provides methylgroups for fetal development and programing by DNA methylation as one of the underlying epigenetic mechanisms. We aimed to investigate maternal 1-C biomarkers, folic acid supplement use, and MTHFR C677T genotype as determinants of 1-C metabolism in early pregnancy in association with newborn DNA methylation levels of fetal growth and neurodevelopment candidate genes. The participants were 463 mother-child pairs of Dutch national origin from a large populationbased birth cohort in Rotterdam, The Netherlands. In early pregnancy (median 13.0 weeks, 90% range 10.4-17.1), we assessed the maternal folate and homocysteine blood concentrations, folic acid supplement use, and the MTHFR C677T genotype in mothers and newborns. In newborns, DNA methylation was measured in umbilical cord blood white blood cells at 11 regions of the seven genes: NR3C1, DRD4, 5-HTT, IGF2DMR, H19, KCNQ1OT1, and MTHFR. The associations between the 1-C determinants and DNA methylation were examined using linear mixed models. An association was observed between maternal folate deficiency and lower newborn DNA methylation, which attenuated after adjustment for potential confounders. The maternal MTHFR TT genotype was significantly associated with lower DNA methylation. However, maternal homocysteine and folate concentrations, folic acid supplement use, and the MTHFR genotype in the newborn were not associated with newborn DNA methylation. The maternal MTHFR C677T genotype, as a determinant of folate status and 1-C metabolism, is associated with variations in the epigenome of a selection of genes in newborns. Research on the implications of these variations in methylation on gene expression and health is recommended

DNA methylation profiles at birth and child ADHD symptoms

Attention deficit/hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder. In addition, early life environmental factors contribute to the occurrence of ADHD. Recently, DNA methylation has emerged as a mechanism potentially mediating genetic and environmental effects.Here, we investigated whether newborn DNA methylation patterns of selected candidate genes involved in psychiatric disorders or fetal growth are associated with ADHD symptoms in childhood. Participants were 426 children from a large population based cohort of Dutch national origin. Behavio

The Changing Nature of Poverty

Since the beginning of the War on Poverty, the poverty rate has fluctuated widely, and at the same time the poverty population has undergone many changes, some mirroring the changing stereotypes of the poor and others less pronounced than the changing stereotypes would lead us to believe. A feminization of poverty has occurred, with many more of the poor now in households headed by women. Interestingly, aging of the poverty population has not occurred despite growth in the elderly segment of the overall population. Concerning turnover in the poverty population, we find that despite poverty theories emphasizing persistence, recurrent poverty is relatively rare and poverty is not generally passed from one generation to the next. Poverty prevention has come from both economic growth and government transfers; however, inequality in economic growth has contributed to poverty. With the proportion of elderly and female- headed households likely to continue at a high level into the future, poverty rates are also likely to remain high unless government transfers are increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66979/2/10.1177_000271628547900103.pd

A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies

Copyright © 2021 Nijman, Oostenbrink, Moll, Casals-Pascual, von Both, Cunnington, De, Eleftheriou, Emonts, Fink, van der Flier, de Groot, Kaforou, Kohlmaier, Kuijpers, Lim, Maconochie, Paulus, Martinon-Torres, Pokorn, Romaine, Calle, Schlapbach, Smit, Tsolia, Usuf, Wright, Yeung, Zavadska, Zenz, Levin, Herberg, Carrol and the PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union).Background: The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI. Methods: We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0– <16 years: the Alder Hey emergency department (n = 1,120), Alder Hey pediatric intensive care unit (n = 355), Erasmus emergency department (n = 1,993), Maasstad emergency department (n = 714) and St. Mary's hospital (n = 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) and resistin (2 cohorts) were compared for their ability to classify patients according to current standards (dichotomous classification of SBI vs. non-SBI), vs. a proposed PERFORM classification algorithm that assign patients to one of eleven categories. These categories were based on clinical phenotype, test outcomes and C-reactive protein level and accounted for the uncertainty of final diagnosis in many febrile children. The success of the biomarkers was measured by the Area under the receiver operating Curves (AUCs) when they were used individually or in combination. Results: Using the new PERFORM classification system, patients with clinically confident bacterial diagnosis (“definite bacterial” category) had significantly higher levels of PCT, NGAL and resistin compared with those with a clinically confident viral diagnosis (“definite viral” category). Patients with diagnostic uncertainty had biomarker concentrations that varied across the spectrum. AUCs were higher for classification of “definite bacterial” vs. “definite viral” following the PERFORM algorithm than using the “SBI” vs. “non-SBI” classification; summary AUC for PCT was 0.77 (95% CI 0.72–0.82) vs. 0.70 (95% CI 0.65–0.75); for NGAL this was 0.80 (95% CI 0.69–0.91) vs. 0.70 (95% CI 0.58–0.81); for resistin this was 0.68 (95% CI 0.61–0.75) vs. 0.64 (0.58–0.69) The three biomarkers combined had summary AUC of 0.83 (0.77–0.89) for “definite bacterial” vs. “definite viral” infections and 0.71 (0.67–0.74) for “SBI” vs. “non-SBI.” Conclusion: Biomarkers of bacterial infection were strongly associated with the diagnostic categories using the PERFORM classification system in five independent cohorts. Our proposed algorithm provides a novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies.publishersversionPeer reviewe

Predation Danger Can Explain Changes in Timing of Migration: The Case of the Barnacle Goose

Understanding stopover decisions of long-distance migratory birds is crucial for conservation and management of these species along their migratory flyway. Recently, an increasing number of Barnacle geese breeding in the Russian Arctic have delayed their departure from their wintering site in the Netherlands by approximately one month and have reduced their staging duration at stopover sites in the Baltic accordingly. Consequently, this extended stay increases agricultural damage in the Netherlands. Using a dynamic state variable approach we explored three hypotheses about the underlying causes of these changes in migratory behavior, possibly related to changes in (i) onset of spring, (ii) potential intake rates and (iii) predation danger at wintering and stopover sites. Our simulations showed that the observed advance in onset of spring contradicts the observed delay of departure, whereas both increased predation danger and decreased intake rates in the Baltic can explain the delay. Decreased intake rates are expected as a result of increased competition for food in the growing Barnacle goose population. However, the effect of predation danger in the model was particularly strong, and we hypothesize that Barnacle geese avoid Baltic stopover sites as a response to the rapidly increasing number of avian predators in the area. Therefore, danger should be considered as an important factor influencing Barnacle goose migratory behavior, and receive more attention in empirical studies

Viability of meta-populations of wetland birds in a fragmented landscape: Testing the key-patch approach

The key patch approach assumes that metapopulations in fragmented landscapes are likely to be viable with at least one "key" sub-population that is sufficiently large to ensure re-colonization of surrounding minor habitat patches. It is based on a minimum viable number of breeding pairs and within-breeding season dispersal distance, linked to size of the animal and longevity. It was tested using census data of 15 wetland bird species (bearded tit, bluethroat, great reed warbler, sedge warbler, Savi's warbler, grasshopper warbler, spotted crake, water rail, common snipe, common teal, garganey, little bittern, night heron, great bittern and marsh harrier) in 14 wetland complexes of variable size (3-55 k