Prevalent low-grade dysplasia: the strongest predictor of malignant progression in Barrett's columnar-lined oesophagus

No abstract

A primary health-care intervention on pre- and postnatal risk factor behavior to prevent childhood allergy. The Prevention of Allergy among Children in Trondheim (PACT) study

Background: This study aimed to evaluate the impact of a primary prevention intervention program on risk behavior for allergic diseases among children up to 2 years of age. The setting was in ordinary pre- and postnatal primary health care in Trondheim, Norway. Methods: The Prevention of Allergy among Children in Trondheim, Norway (PACT) study invited all pregnant women and parents to children up to 2 years of age in the community to participate in a non-randomized, controlled, multiple life-style intervention study. Interventional topics was increased dietary intake of cod liver oil and oily fish for women during pregnancy and for infants during the first 2 years of life, reduced parental smoking and reduced indoor dampness. A control cohort was established prior to the intervention cohort with “follow up as usual”. Questionnaires were completed in pregnancy, 6 weeks after birth and at 1 and 2 years of age. Trends in exposure and behavior are described. Results: Intake of oily fish and cod liver oil increased statistically significantly among women and infants in the intervention cohort compared to the control cohort. There was a low postnatal smoking prevalence in both cohorts, with a trend towards a decreasing smoking prevalence in the control cohort. There was no change in indoor dampness or in behavior related to non- intervened life-style factors. Conclusions: The dietary intervention seemed to be successful. The observed reduced smoking behavior could not be attributed to the intervention program, and the latter had no effect on indoor dampness

Decomposing the spatial and temporal effects of climate on bird populations in northern European mountains

The relationships between species abundance or occurrence versus spatial variation in climate are commonly used in species distribution models to forecast future distributions. Under "space-for-time substitution", the effects of climate variation on species are assumed to be equivalent in both space and time. Two unresolved issues of space-for-time substitution are the time period for species' responses and also the relative contributions of rapid- versus slow reactions in shaping spatial and temporal responses to climate change. To test the assumption of equivalence, we used a new approach of climate decomposition to separate variation in temperature and precipitation in Fennoscandia into spatial, temporal, and spatiotemporal components over a 23-year period (1996-2018). We compiled information on land cover, topography, and six components of climate for 1756 fixed route surveys, and we modeled annual counts of 39 bird species breeding in the mountains of Fennoscandia. Local abundance of breeding birds was associated with the spatial components of climate as expected, but the temporal and spatiotemporal climatic variation from the current and previous breeding seasons were also important. The directions of the effects of the three climate components differed within and among species, suggesting that species can respond both rapidly and slowly to climate variation and that the responses represent different ecological processes. Thus, the assumption of equivalent species' response to spatial and temporal variation in climate was seldom met in our study system. Consequently, for the majority of our species, space-for-time substitution may only be applicable once the slow species' responses to a changing climate have occurred, whereas forecasts for the near future need to accommodate the temporal components of climate variation. However, appropriate forecast horizons for space-for-time substitution are rarely considered and may be difficult to reliably identify. Accurately predicting change is challenging because multiple ecological processes affect species distributions at different temporal scales.Peer reviewe

60 million years of glaciation in the Transantarctic Mountains

The Antarctic continent reached its current polar location ~83 Ma and became shrouded by ice sheets ~34 Ma, coincident with dramatic global cooling at the Eocene-Oligocene boundary. However, it is not known whether the first Antarctic glaciers formed immediately prior to this or were present significantly earlier. Here we show that mountain glaciers were likely present in the Transantarctic Mountains during the Late Palaeocene (~60–56 Ma) and middle Eocene (~48–40 Ma). Temperate (warm-based) glaciers were prevalent during the Late Eocene (~40–34 Ma) and, in reduced numbers, during the Oligocene (~34–23 Ma), before larger, likely cold-based, ice masses (including ice sheets) dominated. Some temperate mountain glaciers were present during the Miocene Climatic Optimum (~15 Ma), before a widespread switch to cold-based glaciation. Our findings highlight the longevity of glaciation in Antarctica and suggest that glaciers were present even during the Early-Cenozoic greenhouse world

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Family eczema-history in 2-year olds with eczema; a prospective, population-based study. The PACT-study, Norway

<p>Abstract</p> <p>Background</p> <p>A maternal line of inheritance regarding eczema has been described in several studies, whereas others find associations to both a maternal as well as a paternal line of inheritance. When studying family history of eczema symptoms, cohort studies including siblings are rare. Time point for assessing family eczema-history could be of importance when studying the associations between family eczema-history and children with eczema, as parents with unaffected children may not recall mild symptoms in other siblings or their own disease history. We therefore aimed to study the associations between reported eczema in mother, father and siblings and reported eczema in index child where information on family history was collected at two different ages of index child.</p> <p>Methods</p> <p>Parents/children participating in The Prevention of Allergy among Children in Trondheim (PACT) study were given questionnaires on reported eczema symptoms in mother, father and siblings at 6 weeks and 1 year. When index child was 2 years of age, a detailed questionnaire on different health issues with emphasize on different allergy related disorders were filled in.</p> <p>Results</p> <p>Both maternal and paternal reports on eczema were significantly associated with eczema in index child. Reporting family eczema-history at 1 year (N = 3087), "eczema sibling only" [adjusted odds ratio (aOR) = 3.13 (2.27-4.33)] as well as all other family-groups containing siblings with eczema were strongly associated with eczema 2 years. When family eczema-history was reported at 6 weeks (N = 2657), reporting of "eczema sibling only" was not associated to reported eczema at 2 years in index child [aOR = 1.31 (0.77-2.23)].</p> <p>Conclusions</p> <p>Having sibling(s) with eczema strengthened the associations between maternal and paternal reports on eczema with eczema in index child only when exposure was reported at 1 year. These findings indicate that results from questionnaires-based studies of family eczema-history depend on whether or not index child has yet developed eczema.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN28090297">ISRCTN28090297</a></p

Decomposing the spatial and temporal effects of climate on bird populations in northern European mountains

The relationships between species abundance or occurrence versus spatial variation in climate are commonly used in species distribution models to forecast future distributions. Under "space-for-time substitution", the effects of climate variation on species are assumed to be equivalent in both space and time. Two unresolved issues of space-for-time substitution are the time period for species' responses and also the relative contributions of rapid- versus slow reactions in shaping spatial and temporal responses to climate change. To test the assumption of equivalence, we used a new approach of climate decomposition to separate variation in temperature and precipitation in Fennoscandia into spatial, temporal, and spatiotemporal components over a 23-year period (1996-2018). We compiled information on land cover, topography, and six components of climate for 1756 fixed route surveys, and we modeled annual counts of 39 bird species breeding in the mountains of Fennoscandia. Local abundance of breeding birds was associated with the spatial components of climate as expected, but the temporal and spatiotemporal climatic variation from the current and previous breeding seasons were also important. The directions of the effects of the three climate components differed within and among species, suggesting that species can respond both rapidly and slowly to climate variation and that the responses represent different ecological processes. Thus, the assumption of equivalent species' response to spatial and temporal variation in climate was seldom met in our study system. Consequently, for the majority of our species, space-for-time substitution may only be applicable once the slow species' responses to a changing climate have occurred, whereas forecasts for the near future need to accommodate the temporal components of climate variation. However, appropriate forecast horizons for space-for-time substitution are rarely considered and may be difficult to reliably identify. Accurately predicting change is challenging because multiple ecological processes affect species distributions at different temporal scales