Thawing Yedoma permafrost is a neglected nitrous oxide source.

In contrast to the well-recognized permafrost carbon (C) feedback to climate change, the fate of permafrost nitrogen (N) after thaw is poorly understood. According to mounting evidence, part of the N liberated from permafrost may be released to the atmosphere as the strong greenhouse gas (GHG) nitrous oxide (N2O). Here, we report post-thaw N2O release from late Pleistocene permafrost deposits called Yedoma, which store a substantial part of permafrost C and N and are highly vulnerable to thaw. While freshly thawed, unvegetated Yedoma in disturbed areas emit little N2O, emissions increase within few years after stabilization, drying and revegetation with grasses to high rates (548 (133-6286) µg N m-2 day-1; median with (range)), exceeding by 1-2 orders of magnitude the typical rates from permafrost-affected soils. Using targeted metagenomics of key N cycling genes, we link the increase in in situ N2O emissions with structural changes of the microbial community responsible for N cycling. Our results highlight the importance of extra N availability from thawing Yedoma permafrost, causing a positive climate feedback from the Arctic in the form of N2O emissions.

A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. METHODS: Based on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. KEY RESULTS: Suggestive GWAS signals (P ≤ 5.0 × 10-6 ) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P = 3.1 × 10-10 ) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. CONCLUSION & INFERENCES: Our results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population.

BACKGROUND: Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. METHODS: We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). KEY RESULTS: We identified 30 GERD suggestive risk loci (P≤5×10-5 ), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. CONCLUSIONS: We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.

Functional dyspepsia impairs quality of life in the adult population.

BACKGROUND: Data on the impact of functional dyspepsia on health-related quality of life in the general adult population are scarce. AIM: To explore the impact of functional dyspepsia applying the Rome III definition on health-related quality of life in the general population. METHOD: A random sample of an adult Swedish population (n=1001, The Kalixanda study) was invited to undergo an oesophagogastroduodenoscopy. An extended abdominal symptom questionnaire and Short Form-36 (SF-36) questionnaire, which includes eight domains measuring physical, mental and social aspects of quality of life, were completed at the clinic visit just before oesophagogastroduodenoscopy. RESULTS: Two hundred and two (20%) individuals reported uninvestigated dyspepsia (UID), 157 (16%) functional dyspepsia (FD), 52 (5%) epigastric pain syndrome (EPS) and 122 (12%) postprandial distress syndrome (PDS). UID, FD and PDS had a clinically meaningful (a ≥ 5 point) and statistically significant impact (P<0.05) on health-related quality of life in all SF-36 domains except for Role Emotional. EPS had a significant impact on Bodily Pain and Vitality. Overlap of FD with irritable bowel syndrome (IBS) had a significant impact on Bodily Pain (P=0.002) and General Health (P=0.02) while FD overlap with gastro-oesophageal reflux symptoms (GERS) had a significant impact on Bodily Pain (P=0.02) compared with FD without any overlap with IBS or GERS. CONCLUSION: Functional dyspepsia impacts all main domains describing physical, mental and social aspects of health-related quality of life in the general population. Overlap of functional dyspepsia with irritable bowel syndrome or gastro-oesophageal reflux symptoms impacts the domain related to bodily pain.

Reactor decay heat in 239Pu: solving the γ discrepancy in the 4-3000-s cooling period.

The ß feeding probability of (102,104,105,106,107)Tc, 105Mo, and 101Nb nuclei, which are important contributors to the decay heat in nuclear reactors, has been measured using the total absorption technique. We have coupled for the first time a total absorption spectrometer to a Penning trap in order to obtain sources of very high isobaric purity. Our results solve a significant part of a long-standing discrepancy in the γ component of the decay heat for 239Pu in the 4-3000 s range.

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. AIM: To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. METHODS: A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. RESULTS: Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). CONCLUSION: Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders.

Do gastrointestinal symptoms fluctuate in the short-term perspective? The Kalixanda study.

BACKGROUND/AIM: Short-term fluctuation of gastrointestinal symptoms in the general population is largely unknown. We aimed to determine gastrointestinal symptom fluctuation in an random adult population using a validated questionnaire assessing gastrointestinal symptoms. METHODS: A representative sample (n = 2,860) of the population (n = 21,610, 20-81 years of age; mean age 50.4 years) in Northern Sweden was studied. The subjects were asked to complete the questionnaire on two occasions [mean 2.5 months (range 1-6)], firstly via mail and secondly at a visit to the clinic. An upper endoscopy was performed after the last assessment of symptoms. RESULTS: 2,122 individuals (74.2%) completed the initial questionnaire; 1,001 of these (mean age 54.1 years, 48.8 males) completed the second questionnaire. On the first occasion, 40% of the subjects were symptom-free (20.2%) or could not be classified according to their symptom pattern, of those with symptoms 39% reported troublesome reflux symptoms, 40% dyspeptic symptoms and 30% irritable bowel symptoms. Symptom overlap occurred in more than two thirds of the subjects. At the second visit 75% of the subjects who had reported dyspeptic complaints still reported such complaints. CONCLUSIONS: In this population-based study, gastrointestinal symptoms were common. Some symptom fluctuation occurred in the shorter term, but troublesome gastrointestinal complaints remained in approximately 90% of subjects over a 1-6-month period.

Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study.

BACKGROUND: The impact of gastro-oesophageal reflux symptoms on health-related quality of life in the general population is poorly characterized. AIM: To identify the frequency of troublesome reflux symptoms associated with impaired health-related quality of life in the general population. METHODS: A representative random sample of 3000 adult inhabitants of northern Sweden was surveyed using the validated Abdominal Symptom Questionnaire (response rate 74%). In total, 1001 random responders were endoscoped and assessed using the Short Form-36 Health Survey. RESULTS: Complete data were obtained for 999 subjects: 6% reported reflux symptoms (heartburn and/or regurgitation) daily, 14% weekly and 20% less than weekly during the previous 3 months. Compared with no reflux symptoms, a clinically relevant impairment of health-related quality of life (>or=5 points and P < 0.05) was seen in all eight Short Form-36 dimensions for daily symptoms, in five dimensions for weekly symptoms and in one dimension for less than weekly symptoms. There were no meaningful differences in Short Form-36 scores between subjects with and without oesophagitis. CONCLUSIONS: Most aspects of health-related quality of life were impaired in individuals with daily or weekly reflux symptoms. Troublesome reflux symptoms at least weekly may identify gastro-oesophageal reflux disease.

Cost analysis of an open low-field (0.23T) MRI unit: effect of procedure shares in combined imaging, interventional, and neurosurgical use.

PURPOSE: To analyze the cost structure of procedures performed in a multipurpose interventional magnetic resonance imaging (IMRI) unit and to analyze the effect of procedure shares on cost structure. MATERIAL AND METHODS: During a 1-year period, 691 procedures were performed in the IMRI unit, of which 563 were diagnostic MRI examinations, 89 MRI-guided interventions, and 39 MRI-guided neurosurgical operations. Three alternative utilization models of IMRI were created to simulate different local institutions by adjusting the proportions of different procedures. The costs of procedures were calculated by activity-based cost analysis. RESULTS: The cost of the main procedure (imaging, biopsy, injection, or operation) was the most significant item in all procedures, accounting for 66-89% of the total costs. The volume of imaging has a major effect on unit costs. Volume is not such a deterministic factor in interventions due to the high material costs. The volume of neurosurgical use of IMRI has a major effect on the costs of radiological procedures due to the long operation times. CONCLUSION: The volumes of different procedures done on an IMRI unit have significant effects on the unit costs of the procedures.

Cost comparison of low-field (0.23 T) MRI-guided laser ablation and surgery in the treatment of osteoid osteoma.

The purpose of this study was to analyze the costs of magnetic resonance imaging (MRI)-guided laser ablation and to compare them with the costs of surgery in the treatment of osteoid osteoma. Seven patients with osteoid osteoma were treated with MRI-guided interstitial laser ablation during 1 year. The reference material consisted of six patients whose osteoid osteoma was treated surgically by either superficial or deep excision with metallic fixation. The costs were analyzed by using activity-based cost accounting. The mean cost of the MRI-guided laser ablation was 2,392 euros and of the excision of superficially located osteoid osteoma 1,807 euros. The cost of excision of deeply located osteoma with metallic fixation was considerably higher (4,996 euros). This was due to the higher material, personnel, and ward costs. The cost of MRI-guided laser ablation of osteoid osteoma was higher than the cost of surgical excision of a superficial osteoma but considerably lower than the cost of excision of a deeply located osteoma where metallic fixation was needed. When the number and mean cost of sick days or days of restricted weight bearing were also included, the cost of MRI-guided laser ablation was lower than the costs of either superficial or deep excision.

Body mass index and chronic unexplained gastrointestinal symptoms: an adult endoscopic population based study.

BACKGROUND: We aimed to determine whether obese subjects experience more gastro-oesophageal reflux (GORS) symptoms than normal subjects, and further to determine if this association was explained by oesophagitis or medications that lower oesophageal sphincter pressure. METHODS: In a representative Swedish population, a random sample (n = 1001, mean age 53.5 years, 51% women) had upper endoscopy. GORS was defined as any bothersome heartburn or acid regurgitation. RESULTS: The prevalence of obesity (body mass index > or =30) was 16%; oesophagitis was significantly more prevalent in obesity (26.5%) than in normal subjects (9.3%). There were associations between obesity and GORS (odds ratio (OR) 2.05 (95% confidence interval (CI) 1.39, 3.01)), epigastric pain (OR 1.63 (95% CI 1.05, 2.55)), irritable bowel symptoms (OR 1.58 (95% CI 1.05, 2.38)), any abdominal pain (OR 1.59 (95% CI 1.08, 2.35)), vomiting (OR 3.11 (95% CI 1.18, 8.20)), retching (OR 1.74 (95% CI 1.1.3, 2.67)), diarrhoea (OR 2.2 (95% CI 1.38, 3.46)), any stool urgency (OR 1.60 (95% CI 1.04, 2.47)), nocturnal urgency (OR 2.57 (95% CI 1.33, 4.98)), and incomplete rectal evacuation (OR 1.64 (95% CI 1.09, 2.47)), adjusting for age, sex, and education. When subjects with oesophagitis and peptic ulcer were excluded, only diarrhoea, incomplete evacuation, and vomiting were significantly associated with obesity. The association between GORS and obesity remained significant adjusting for medication use (OR 1.9 (95% CI 1.3, 3.0)). CONCLUSIONS: GORS is associated with obesity; this appears to be explained by increased upper endoscopy findings in obesity.

Validation of the translation and cross-cultural adaptation into Finnish of the Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale and the Complaint Score Questionnaire.

BACKGROUND: Epidemiological surveys require questionnaires to be validated in the native language of the participants. The aim of this study was to validate the Finnish translations of the Abdominal Symptom Questionnaire (ASQ), the Hospital Anxiety and Depression Scale (HAD) and the Complaint Score Questionnaire (CSQ). METHODS: A random sample of adults (n = 3000) in a northern Swedish bilingual district was surveyed using a mailed ASQ offered in both SwedIsh and Finnish, and 2122 responded (239 in Finnish). A random subsample of the responders (n = 1001, 123 preferring Finish) was then surveyed once more using the ASQ, the HAD and the CSQ. The first 50 responders of the latter survey were then given the three questionnaires again within two weeks. The Finnish versions had been put through a comprehensive translation procedure RESULTS: A factor analysis comparison between the responders using either language in the mailed survey gave a comparable factor construction, and this was also comparable with an earlier analysis of the Swedish version. The Finnish responses to the second survey were further evaluated by testing internal consistency reliability, convergent validity towards previously validated relevant instruments (ShortForm-36 and the Gastrointestinal Symptom Rating Scale) and the test/re-test accuracy of the three questionnaires. These were found to be reliable, as was the correlation between the ASQ and the CSQ, for relevant domains. CONCLUSION: The Finnish translations of the ASQ, HAD and CSQ questionnaires all seem to be robust and usable for population-based surveys among Finnish adults.

Valid symptom reporting at upper endoscopy in a random sample of the Swedish adult general population: the Kalixanda study.

BACKGROUND: Upper oesophagogastroduodenoscopy is considered to be the gold standard for upper gastrointestinal disease assessment, but is currently seldom used in epidemiological studies. One concern is that the procedure may bias sampling among volunteers in a general adult population. The aim of this study was to explore whether the procedure affects symptom reporting. METHODS: A random sample of 3000 adults aged 20-81 years (mean age 50.4), from two Swedish municipalities (n=21,610) was surveyed using a validated postal questionnaire (the Abdominal Symptom Questionnaire) assessing gastrointestinal symptoms. A subsample of the responders was invited, in random order, to undergo an upper endoscopy and repeated symptom reporting using the same questionnaire, as well as a serology test for Helicobacter pylori. RESULTS: The response rate to the initial questionnaire was 74.2% and the participation rate for those eligible for the upper endoscopy was 73.3% (n = 1001, mean age 54.0 years, 48.8% male). No major social or symptom sampling error was encountered from the selection process, with the exception of an excess of symptom reporters among the youngest subjects. The prevalence of reflux symptoms, dyspeptic symptoms and irritable bowel symptoms was 40%, 37.6% and 29.6%, respectively, which is relatively high, but in no way extreme. CONCLUSIONS: The upper endoscopy survey strategy was successful. The response rate was high and there was no major selection bias of clinical relevance. The cohort selected for this study appears to be representative of the general Swedish adult population.

Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria.

PATIENTS AND METHODS: All children with Henoch-Schoenlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria (> 40 mg/h/m2), treated at 5 university hospitals and in 1 central hospital in Finland during in 1990-1997, were analyzed retrospectively. The mean age of these 19 patients (8 girls, 11 boys) at the time of diagnosis was 9.9 years (range 4.6-15.1 years). A renal biopsy had been performed in all cases, giving findings according to the classification used in the International Study of Kidney Diseases in Children (ISKDC) of grade II (4 patients), grade III (10), grade IV (4) and grade V (1). Six patients underwent a second biopsy. RESULTS: The yearly incidence of nephrotic-range HSP-GN in Finland was 2 per 1 million children under 15 years of age. After a mean follow-up of 4.6 years (range 9 months-9.1 years), 3 patients (15.7%) had no signs of nephritis, 11 (57.9%) had proteinuria < 1 g/day or microscopic hematuria, 2 (10.5%) had proteinuria > 1 g/day, and 3 (15.7%) had developed ESRD or uremia. 47% of the patients needed medication for proteinuria at the time of the latest follow-up. The first kidney biopsy did not predict the outcome of HSP-GN, since all the patients with the poorest outcome had only ISKDC II-III findings in their first biopsy. CONCLUSION: According to our series, the morbidity in cases of HSP-GN with nephrotic-range proteinuria is high and a close clinical follow-up is needed. The treatment of HSP-GN patients should be based on the clinical presentation rather than on the biopsy findings.