For the past 10 years or so, a number of so-called multiscale methods have been developed as an alternative approach to upscaling and to accelerate reservoir simulation. The key idea of all these ...methods is to construct a set of prolongation operators that map between unknowns associated with cells in a fine grid holding the petrophysical properties of the geological reservoir model and unknowns on a coarser grid used for dynamic simulation. The prolongation operators are computed numerically by solving localized flow problems, much in the same way as for flow-based upscaling methods, and can be used to construct a reduced coarse-scale system of flow equations that describe the macro-scale displacement driven by global forces. Unlike effective parameters, the multiscale basis functions have subscale resolution, which ensures that fine-scale heterogeneity is correctly accounted for in a systematic manner. Among all multiscale formulations discussed in the literature, the multiscale restriction-smoothed basis (MsRSB) method has proved to be particularly promising. This method has been implemented in a commercially available simulator and has three main advantages. First, the input grid and its coarse partition can have general polyhedral geometry and unstructured topology. Secondly, MsRSB is accurate and robust when used as an approximate solver and converges relatively fast when used as an iterative fine-scale solver. Finally, the method is formulated on top of a cell-centered, conservative, finite-volume method and is applicable to any flow model for which one can isolate a pressure equation. We discuss numerical challenges posed by contemporary geomodels and report a number of validation cases showing that the MsRSB method is an efficient, robust, and versatile method for simulating complex models of real reservoirs.
Calf mortality in Norwegian dairy herds Gulliksen, S.M.; Lie, K.I.; Løken, T. ...
Journal of dairy science,
06/2009, Letnik:
92, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The aims of this study were to estimate mortality rates in Norwegian dairy calves and young stock up to 1 yr of age, identify risk factors for calf mortality, and evaluate the etiology of calf ...mortality based on postmortem analyses. The material comprised 3 data sets. The first data set included information on 289,038 offspring in 14,474 dairy herds registered in the Norwegian Dairy Herd Recording System (NDHRS) in 2005. The second included recordings on 5,382 offspring in 125 Norwegian dairy herds participating in a survey on calf health, and the third included results from postmortem analyses of 65 calves from 37 of the survey herds. The calf mortality rate during the first year of life in all herds registered in the NDHRS was 7.8%, including abortion (0.7%) and stillbirth (3.4%). The overall calf mortality rate in liveborn calves in the survey herds was 4.6%. Cows with severe calving difficulties had an odds ratio (OR) of 38.7 of stillbirth compared with cows with no calving difficulties. Twins and triplets showed an increased risk of stillbirth compared with singletons (OR = 4.2 and 46.3, respectively), as did calves born in free stalls compared with tie stalls (OR = 1.9). Respiratory disease increased the risk of death in all age groups with hazard ratios (HR) of 6.4, 6.5, 7.4, and 5.6 during the first week of life, 8 to 30 d of age, 31 to 180 d of age, and 181 to 365 d of age, respectively. Diarrhea increased the risk of death among calves younger than 180 d of age, but the influence was only significant during the first week of life and between 8 to 31 d of age (HR = 2.4 and 2.9, respectively). Calves born during the winter were more likely to die during the first week of life than calves born during the summer (OR = 1.2), and were more likely to die during the first month of life than calves born during the autumn (OR = 1.2). Calf mortality rates in all age groups increased with increasing herd size. Calves housed in a group pen from 2 wk of age were more likely to die during the first month of life than calves housed individually (HR = 1.5). Bronchopneumonia and enteritis were the most frequent postmortem diagnoses, with proportional rates of 27.7 and 15.4%, respectively.
Prenatal fever and autism risk Hornig, M; Bresnahan, M A; Che, X ...
Molecular psychiatry,
03/2018, Letnik:
23, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence ...to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.
The objectives of the present study were to evaluate colostrum quality in Norwegian dairy cows based on IgG content, and to identify associations between possible risk factors and low colostral IgG. ...A longitudinal cross-sectional survey on calf health in Norway was performed between June 2004 and December 2006. The participating dairy herds were randomly selected among herds registered in the Norwegian Dairy Herd Recording System as having at least 15 cow years. The participating farmers were requested to sample 10mL of colostrum from the first milking after calving from 12 cows that had calved during the defined project period of 365 d. Colostrum samples from 1,250 cows from 119 herds were collected. The material consisted of 451, 337, 213, and 249 samples collected from cows in their first, second, third, and fourth parity or more, respectively. Analysis was performed on IgG content by using single radial immunodiffusion. Mixed models with herd as a cluster were fit by using grams of IgG per liter of colostrum as the dependent variable for the statistical analyses. The IgG content in the colostrum sampled ranged from 4 to 235g/L, with a median of 45.0g of IgG/L, with the 10th, 25th, 75th, and 90th percentiles being 23.1, 31.4, 63.6, and 91.6g of IgG/L, respectively. Altogether, 57.8% of the samples contained less than the desired 50g of IgG/L of colostrum. Cows in their fourth parity or more were found to have significantly higher levels of IgG per liter of colostrum than cows in their first or second parity. Colostrum from cows in their second parity had the lowest level of IgG. Cows calving during the winter months (December, January, and February) produced colostrum with a significantly lower IgG content compared with cows calving in any other season of the year. Somatic cell count, measured after calving, was significantly higher in cows producing colostrum of inferior quality compared with those producing high-quality colostrum. Of the total variation in colostrum quality, 13.7% could be explained by cluster effects within herd. The variation in IgG content in colostrum produced by Norwegian dairy cows indicates a need for improved colostrum quality control and subsequent adjustment of the colostrum feeding regimen to ensure a protective immunological status for newborn calves.
Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a ...safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function.
Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples.
Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.
Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.
Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving ...rituximab-containing chemotherapy have not been well described.
HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.
Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.
A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.
Questions have been raised over the acceptability of conducting human challenge studies in low and middle income countries (LMICs). Most of these concerns are based on theoretical considerations and ...there exists little data on the attitudes of stakeholders in these countries. This study examines the view of researchers and REC members in Thailand regarding the design and conduct of challenge studies in the country. A questionnaire was developed based on ethical frameworks for human challenge studies. The target respondents included those who had experience with health-related research at universities, non-university hospitals, and research institutes. A total of 240 respondents completed the on-line survey. In general, the respondents felt that the ethical issues raised by human challenge studies in LMICS do not differ significantly from those in high income countries, including: scientific rationale, safety, appropriate risks, and robust informed consent process. In contrast, issues that have been described as important for human challenge studies in LMICs were rated as having lower importance, including: a publicly available rationale, national priority, and community engagement. Responses did not vary significantly between researchers in different fields, nor between researchers and REC members. These findings provide an important perspective for assessing existing frameworks for human challenges studies in LMICs.
The ballan wrasse (Labrus bergylta) belongs to a large teleost family containing more than 600 species showing several unique evolutionary traits such as lack of stomach and hermaphroditism. Agastric ...fish are found throughout the teleost phylogeny, in quite diverse and unrelated lineages, indicating stomach loss has occurred independently multiple times in the course of evolution. By assembling the ballan wrasse genome and transcriptome we aimed to determine the genetic basis for its digestive system function and appetite regulation. Among other, this knowledge will aid the formulation of aquaculture diets that meet the nutritional needs of agastric species.
Long and short read sequencing technologies were combined to generate a ballan wrasse genome of 805 Mbp. Analysis of the genome and transcriptome assemblies confirmed the absence of genes that code for proteins involved in gastric function. The gene coding for the appetite stimulating protein ghrelin was also absent in wrasse. Gene synteny mapping identified several appetite-controlling genes and their paralogs previously undescribed in fish. Transcriptome profiling along the length of the intestine found a declining expression gradient from the anterior to the posterior, and a distinct expression profile in the hind gut.
We showed gene loss has occurred for all known genes related to stomach function in the ballan wrasse, while the remaining functions of the digestive tract appear intact. The results also show appetite control in ballan wrasse has undergone substantial changes. The loss of ghrelin suggests that other genes, such as motilin, may play a ghrelin like role. The wrasse genome offers novel insight in to the evolutionary traits of this large family. As the stomach plays a major role in protein digestion, the lack of genes related to stomach digestion in wrasse suggests it requires formulated diets with higher levels of readily digestible protein than those for gastric species.
The effects of nutrient and mechanical sensing on gut motility and intestinal metabolism in lower vertebrates remains largely unknown. Here we present the transcriptome response to luminal ...stimulation by nutrients and an inert bolus on nutrient response pathways and also the response on gut motility in a stomachless fish with a short digestive tract; the ballan wrasse (Labrus berggylta). Using an in vitro model, we differentiate how signals initiated by physical stretch (cellulose and plastic beads) and nutrients (lipid and protein) modulate the gut evacuation rate, motility patterns and the transcriptome. Intestinal stretch generated by inert cellulose initiated a faster evacuation of digesta out of the anterior intestine compared to digestible protein and lipid. Stretch on the intestine upregulated genes associated with increased muscle activity, whereas nutrients stimulated increased expression of several neuropeptides and receptors which are directly involved in gut motility regulation. Although administration of protein and lipid resulted in similar bulbous evacuation times, differences in intestinal motility, transit between the segments and gene expression between the two were observed. Lipid induced increased frequency of ripples and standing contraction in the middle section of the intestine compared to the protein group. We suggest that this difference in motility was modulated by factors prepronociceptin (pnoca), prodynorphin (pdyn) and neuromedin U (nmu), opioid neurotransmitters and peptides that are known to inhibit gastrointestinal motility and were upregulated by protein and not lipid. Our findings show that physical pressure in the intestine initiate contractions propelling the bolus distally, directly towards the exit, whereas the stimuli from nutrients modulates the motility to prolong the residence time of digesta in the digestive tract for optimal digestion.
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