Contaminant mass discharge estimation of a sulfonamide plume by use of hydraulic profiling tool (HPT) and fluorescence techniques.

The contaminant mass discharge is a relevant metric to evaluate the risk that a groundwater plume poses to water resources. However, this assessment is often vitiated by a high uncertainty inherent to the assessment method and often limited number of measurement points to carry out the assessment. Direct-Push techniques in combination with profiling tools and dedicated sampling can be an interesting alternative to increase the measurement point density and hence reduce the mass discharge uncertainty. The main objective of our study was to assess if DP logging and sampling could be employed to get a reasonable estimate of contaminant mass discharge in a large sulfonamide contaminant plume (> 1500 m wide), compared to a more traditional approach based on monitoring wells. To do so, an Hydraulic Profiling Tool (HPT) logging with a dedicated site calibration was used to estimate the hydraulic conductivity field. The sulfonamide concentrations were inferred from the compound fluorescence properties measured by laboratory spectrofluorometry (λEx / λEm = 255/340 nm) and a dedicated log-log linear regression model. Our results show that HPT-derived hydraulic conductivity values are in good agreement with the monitoring well results, and within the order of magnitude reported in similar studies or indirect geophysical techniques. Fluorescence appears as a powerful proxy for the sulfonamide concentration levels. Ultimately, the contaminant mass discharge estimate from HPT and fluorescence techniques lies within a factor 2 from the estimate by monitoring wells, with 549 [274-668] and 776 [695-879] kg/yr respectively. Overall, this study highlights that DP logging tools combined with indirect methods (correlation with fluorescence) could provide a relevant contaminant mass discharge estimate for some optically active substances, given that a proper calibration phase is carried out.

Burden of Illness in People with Alzheimer's Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, and an updated quantification of its impact on morbidity, disability, and mortality is warranted. We conducted a systematic literature review, focusing on the past decade, to characterize AD and assess its impact on affected individuals. METHODS: Searches of Embase, MEDLINE, and the Cochrane Library were conducted on August 7, 2020 and updated on November 10, 2021. Observational studies from any country reporting incidence, prevalence, comorbidities, and/or outcomes related to disability and mortality/life expectancy, in people with mild cognitive impairment (MCI) due to AD, or mild, moderate, or severe AD dementia, were considered relevant. RESULTS: Data were extracted from 88 studies (46 incidence/prevalence; 44 comorbidities; 25 mortality-/disability-related outcomes), mostly from Europe, the USA, and Asia. AD dementia diagnosis was confirmed using biomarkers in only 6 studies. Estimated 5-year mortality in AD was 35%, and comorbidity prevalence estimates varied widely (hypertension: 30.2-73.9%; diabetes: 6.0-24.3%; stroke: 2.7-13.7%). Overall, people with AD dementia were more likely to have cardiovascular disease or diabetes than controls, and 5-year mortality in people with AD dementia was double that in the age- and year-matched general population (115.0 vs 60.6 per 1,000 person-years). CONCLUSIONS: AD is associated with excess morbidity and mortality. Future longitudinal studies of population aging, incorporating biomarker assessment to confirm AD diagnoses, are needed to better characterize the course of MCI due to AD and AD dementia.

The evolving landscape of publishing in the field of pain: An automated bibliometric analysis from 1975 to 2020.

BACKGROUND: The aims of this bibliometric analysis were (1) a longitudinal analysis of the publication landscape in the field of pain (1975-2020) and (2) to characterize the overall publication profiles for two selected journals: European Journal of Pain and PAIN® utilizing an automated approach. METHODS: Database searches in Scopus extracted all journals with 'pain' in their title. For the two specific journals, papers were manually/automatically profiled into preclinical, human and translational studies. RESULTS: A gross list of 64 journals in the field of pain consisting of both active and ceased journals in Scopus were included in this analysis which identified 62,565 papers with approximately 4000 papers published/year. These papers include 2759 and 9156 papers in Eur. J. Pain and PAIN®, respectively. Currently, there are 24 active 'pain' journals. Authors/paper increase from 2 to 7 indicating a development from mono-disciplinary to multi-disciplinary studies. The overall publication profiles assessing preclinical, human (experimental/clinical) and translational papers in Eur. J. Pain and PAIN® were almost similar (14%, 75% and 10% versus 26%, 63% and 10%). Papers have changed over the years from mono-disciplinary studies (e.g. behavioural studies) to multi-disciplinary studies (e.g. combined behavioural and cell studies). After optimization, the search model matched the manual screening by 100%, 98% and 96% for the preclinical, clinical and healthy volunteer categories. CONCLUSIONS: Over the last 45 years, more than 60,000 pain-related papers have been published. Papers develop over the years from mono-disciplinary to multi-disciplinary studies. The overall publication profile including preclinical, human (experimental/clinical) and translational papers was almost similar in Eur. J. Pain and PAIN®. SIGNIFICANCE: The bibliometric analysis of a pain journal provides information on which specific areas of research are published, how this may have changed over the years and how a journal is positioned compared with other journals in the field.

NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice.

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.

Ticks harbor and excrete chronic wasting disease prions.

Chronic wasting disease (CWD) is a fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting cervids. Circulating PrPCWD in blood may pose a risk for indirect transmission by way of hematophagous ectoparasites acting as mechanical vectors. Cervids can carry high tick infestations and exhibit allogrooming, a common tick defense strategy between conspecifics. Ingestion of ticks during allogrooming may expose naïve animals to CWD, if ticks harbor PrPCWD. This study investigates whether ticks can harbor transmission-relevant quantities of PrPCWD by combining experimental tick feeding trials and evaluation of ticks from free-ranging white-tailed deer (Odocoileus virginianus). Using the real-time quaking-induced conversion (RT-QuIC) assay, we show that black-legged ticks (Ixodes scapularis) fed PrPCWD-spiked blood using artificial membranes ingest and excrete PrPCWD. Combining results of RT-QuIC and protein misfolding cyclic amplification, we detected seeding activity from 6 of 15 (40%) pooled tick samples collected from wild CWD-infected white-tailed deer. Seeding activities in ticks were analogous to 10-1000 ng of CWD-positive retropharyngeal lymph node collected from deer upon which they were feeding. Estimates revealed a median infectious dose range of 0.3-42.4 per tick, suggesting that ticks can take up transmission-relevant amounts of PrPCWD and may pose a CWD risk to cervids.

Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life.

BACKGROUND: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner. METHODS: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients' cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education. RESULTS: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life. LIMITATIONS: The study was cross-sectional, which precludes causality inferences. CONCLUSIONS: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.

Using multi-event hydrologic and hydraulic signatures from water level sensors to diagnose locations of uncertainty in integrated urban drainage models used in living digital twins.

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.

Rhinopharynx irrigations and mouthwash with dissolved mupirocin in treatment of MRSA throat colonization - proof-of-concept study.

BACKGROUND: To prevent transmission of, and infection with, meticillin-resistant Staphylococcus aureus (MRSA), eradication treatment of colonized individuals is recommended. Throat colonization is a well-known risk factor for eradication failure. Staphylococcus aureus throat colonization is associated with colonization of the rhinopharynx, but in the currently recommended Danish MRSA eradication strategies, rhinopharynx colonization is not directly targeted. Rhinopharynx colonization could therefore be an important risk factor for prolonged MRSA throat carriage. AIM: To determine whether irrigation and wash of the rhinopharynx and mouth with dissolved mupirocin is a feasible and potentially efficacious supplementary strategy against treatment-resistant MRSA throat carriage. METHODS: The patient study was an open, non-blinded, trial including 20 treatment-resistant MRSA throat carriers. In the study, the patients received a supplementary treatment besides the standard treatment according to the Danish MRSA eradication strategy. The supplementary treatment consisted of rhinopharyngeal irrigation and mouth-gurgling twice a day for 14 days with a mupirocin ointment (22 g 2% ointment per litre of isotonic sterile saline solution) in a 37°C solution. FINDINGS: Eighteen patients (90%) complied with the treatment protocol and none ex-perienced any major adverse events. Out of the 18 patients who finished the study per protocol, 15 (83%) and seven (39%) patients had negative MRSA sampling results one and six months after end of treatment, respectively. CONCLUSION: This study demonstrates the feasibility and clinical potential of also targeting the rhinopharynx and oropharynx in non-systemic throat MRSA eradication strategies.

No difference in antidepressant prescription in rheumatoid arthritis and controls. Results from a population-based, matched inception cohort.

OBJECTIVE: Depression occurs at least two times more often in rheumatoid arthritis (RA) patients than in controls, but little is known about the treatment of depression in RA. The primary objective of this study was to compare the 1 year period prevalence of antidepressant prescription in patients with RA versus controls. METHOD: We included a retrospective inception cohort of 509 patients with incident RA and 2545 frequency-matched population controls ascertained from 1995 to 2002. The cohort was followed until 31 December 2017 and linked with nationwide Danish registers. From the Danish National Prescription Register, we obtained information on redeemed prescriptions of antidepressants (Anatomical Therapeutic Chemical code N06A). RESULTS: We did not demonstrate significant differences in the 1 year period prevalence ratios and the incidence rate ratios for either antidepressant prescription or the frequency of hospital admissions with depressive episode. The most frequent indication for antidepressant prescription in patients with RA was depression. Cox regression analyses showed no association between RA and antidepressant prescription. CONCLUSION: We found no significant differences in the occurrence of antidepressant prescription in patients with RA versus matched controls. The main indication for antidepressant prescription in RA was depression.

Beta Decay of Molecular Tritium.

The beta decay of tritium in the form of molecular T_{2} is the basis of sensitive experiments to measure neutrino mass. The final-state electronic, vibrational, and rotational excitations modify the beta spectrum significantly and are obtained from theory. We report measurements of the branching ratios to specific ionization states for the isotopolog HT. Two earlier, concordant measurements gave branching ratios of HT to the bound HHe^{+} ion of 89.5% and 93.2%, in sharp disagreement with the theoretical prediction of 55%-57%, raising concerns about the theory's reliability in neutrino mass experiments. Our result, 56.5(6)%, is compatible with the theoretical expectation and disagrees strongly with the previous measurements.

Increased risk of long-term sickness absence, lower rate of return to work and higher risk of disability pension among people with type 1 and type 2 diabetes mellitus: a Danish retrospective cohort study with up to 17 years' follow-up.

AIM: To evaluate labour market outcomes in type 1 or type 2 diabetes. METHODS: Individuals with type 1 (n = 431) and type 2 diabetes (n = 4047) were identified in Danish national registers from 1994 to 2011 and compared with individuals without diabetes (n = 101 295). Multi-state Cox proportional hazards analyses estimated hazard ratios (HR) with 95% confidence intervals (CI) for transitions between work, sickness absence, unemployment and disability pension. RESULTS: We observed significantly higher HR of sickness absence in type 1 diabetes (women: 1.34, 95% CI 1.12-1.62; men: 1.43, 1.01-2.03) and type 2 diabetes (women: 1.46, 95% CI 1.35-1.58; men: 1.64, 1.46-1.85) compared with people without diabetes. HR of unemployment was higher for men with type 1 diabetes (1.25, 95% CI 1.01-1.53) and women with type 2 diabetes (1.09, 95% CI 1.03-1.16) and men with type 2 diabetes (1.17, 95% CI 1.08-1.27). HR of disability pension was higher in type 1 diabetes (women: 1.90, 95% CI 1.46-2.46; men: 2.09, 1.38-3.18) and type 2 diabetes (women: 1.78, 95% CI 1.62-1.96; men: 2.11, 1.86-2.40). Only women with type 2 diabetes were less likely to return to work from sickness absence (HR 0.91, 95% CI 0.86-0.98) or unemployment (0.89, 95% CI 0.85-0.94). We found no significant difference between the two types of diabetes. Hazard ratios for diabetes regarding unemployment, sickness absence while unemployed and disability pension were significantly higher for men than for women. CONCLUSIONS: Both type 1 and type 2 diabetes affect labour market outcomes, but future studies should also consider comorbidity and social gradient.

A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3 supplementation in adult patients with migraine.

BACKGROUND: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460). METHODS: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18-65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n = 24, 18 women and 6 men, 100 µg/day D3-Vitamin) or placebo (n = 24, 18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)2D were assessed from baseline to week 24. RESULTS: The number of headache days changed from 6.14 ± 3.60 in the treatment group and 5.72 ± 4.52 in the placebo group at baseline to 3.28 ± 3.24 and 4.93 ± 3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p < .001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)2D. No side-effects were reported or noted. CONCLUSIONS: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D3 might be one of the prophylactic options for adult patients with migraine.

Mortality and its predictors in patients with rheumatoid arthritis: a Danish population-based inception cohort study.

OBJECTIVES: To investigate mortality and its predictors in a retrospectively defined population-based rheumatoid arthritis (RA) inception cohort Method: We included patients ascertained with incident RA from a region in the southern part of Denmark from 1995 to 2002. All patients fulfilled the 1987 American College of Rheumatology criteria for RA. The patients were followed from RA classification until death, emigration, or end of follow-up on 31 December 2013. We used personal record linkage with national public registers to obtain information on education, employment, cohabitation, comorbidity, and vital status. RESULTS: The cohort comprised 509 patients, of whom 200 (39%) died during 6079 person-years. The most frequent underlying causes of death were cardiovascular disease (34%), neoplasms (26%), and respiratory disease (12%). In rheumatoid factor (RF)-positive males, the standardized mortality ratio (95% confidence interval) from all causes was 1.47 (1.15-1.88), from cardiovascular disease 1.63 (1.09-2.46), from respiratory disease 2.03 (1.06-3.90), and from neoplasms 2.26 (1.02-5.03) in the age group < 70 years, and 2.45 (1.23-4.90) in the age group > 79 years. On applying Cox models after multiple imputations by chained equations, we found that RF modified the effect of age. Employment status, comorbidity, and gender were independent baseline predictors of subsequent mortality. CONCLUSION: In this cohort, significant excess mortality was confined to RF-positive males. The effect of age was modified by RF, and employment status and comorbidity were independent predictors of mortality.

Interfacial electrostatics of poly(vinylamine hydrochloride), poly(diallyldimethylammonium chloride), poly-l-lysine, and poly-l-arginine interacting with lipid bilayers.

Charge densities of cationic polymers adsorbed to lipid bilayers are estimated from second harmonic generation (SHG) spectroscopy and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. The systems surveyed included poly(vinylamine hydrochloride) (PVAm), poly(diallyldimethylammonium chloride) (PDADMAC), poly-l-lysine (PLL), and poly-l-arginine (PLR), as well as polyalcohol controls. Upon accounting for the number of positive charges associated with each polyelectrolyte, the binding constants and apparent free energies of adsorption as estimated from SHG data are comparable despite differences in molecular masses and molecular structure, with ΔGads values of -61 ± 2, -58 ± 2, -57 ± 1, -52 ± 2, -52 ± 1 kJ mol-1 for PDADMAC400, PDADMAC100, PVAm, PLL, and PLR, respectively. Moreover, we find charge densities for polymer adlayers of approximately 0.3 C m-2 for poly(diallyldimethylammonium chloride) while those of poly(vinylamine) hydrochloride, poly-l-lysine, and poly-l-arginine are approximately 0.2 C m-2. Time-dependent studies indicate that polycation adsorption to supported lipid bilayers is only partially reversible for most of the polymers explored. Poly(diallyldimethylammonium chloride) does not demonstrate reversible binding even over long timescales (>8 hours).

Galectin-3 is Persistently Increased in Early Rheumatoid Arthritis (RA) and Associates with Anti-CCP Seropositivity and MRI Bone Lesions, While Early Fibrosis Markers Correlate with Disease Activity.

Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 µg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 µg/l [2.6;4.9], P = 0.05) and controls (3.8 µg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti-CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes.

Estimation of genetic parameters and heterosis for longevity in crossbred Danish dairy cattle.

Crossbreeding has been shown to improve the longevity of dairy cattle in countries across the world. The aim of this study was to estimate heterosis, breed effects, and genetic parameters for longevity in crossbred dairy cattle among Danish Holstein (DH), Danish Red (DR), and Danish Jersey (DJ) breeds. Data were provided from 119 Danish commercial herds that use systematic crossbreeding (i.e., rotational crossbreeding). Additional data from 11 mixed-breed herds with DH and DJ were included to estimate reliable breed effects for DJ. Survival information on 73,741 cows was analyzed with a linear animal model using the artificial insemination-REML algorithm in the DMU package. Five longevity (L) traits were defined: days from first calving until the end of first lactation or culling (L1), days from first calving until the end of second lactation or culling (L2), days from first calving until the end of third lactation or culling (L3), days from first calving until the end of fourth lactation or culling (L4), and days from first calving until the end of fifth lactation or culling (L5). Heritabilities ranged between 0.022 and 0.090. Additive breed effects in units of days were estimated relative to DH for DR as -0.5 (L1), +10.5 (L2), +18.5 (L3), +11.9 (L4), and +28.6 (L5), and corresponding figures for DJ were +2.0, +0.5, +14.2, +27.7, and +44.0. Heterosis effects in L1 were low (1.2%) but favorable in crosses between DH and DR, whereas negative heterosis effects were estimated for crosses between DH and DJ (-2.5%) and DR and DJ (-1.2%). The largest heterosis effects for L2, L3, L4, and L5 were found in DH × DR and were favorable (+3.3, +5.7, +7.7, and +8.5%, respectively). Corresponding figures for heterosis effects in DH × DJ and DR × DJ were favorable as well: +2.3, +4.1, +5.6, and +6.2% in DH × DJ and +3.1, +7.3, +6.9, and +7.2% in DR × DJ. The favorable heterosis effects show that crossbreeding is an efficient tool for improving longevity in Danish dairy cattle.

Total and beverage-specific alcohol intake and the risk of aggressive prostate cancer: a case-control study.

BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its association with aggressive prostate cancer (APC) is uncertain. Recent studies have shown a modest increase in risk of APC associated with heavy alcohol intake while association for beverage types remain inconsistent. METHODS: Using a case-control design and self-administered questionnaire, we examined the association between APC (high grade and/or advanced stage) and frequency and quantity of alcohol intake 2 years prior to enrolment. Furthermore, we delineated the relationships for beverage-specific intakes of beer, red wine, white wine and spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake frequency of ⩾5 days per week was associated with increased risk compared with no beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine was protective at all frequencies of consumption compared with those with no wine intake. For every 10 g per week ethanol intake from beer increase, the odds of advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was observed for red or white wine while a marginal dose-response relationship was found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and possibly spirits consumption is associated with increased risk while no dose-response relationship was found for red or white wine. Wine drinkers at all frequencies have a decreased risk of APC compared with those who did not drink wine.

Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study.

Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-ß-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.

Improving the energy balance of grass-based anaerobic digestion through combined harvesting and pretreatment.

An important challenge that has to be addressed to achieve sustainable anaerobic digestion of lignocellulosic substrates is the development of energy and cost efficient pretreatment methods. Technologies orientated to simultaneously harvest and mechanically pretreat the biomass at the field could meet these criteria as they can potentially reduce the energy losses. The objective of this study was to elucidate the effect of two full-scale harvesting machines to enhance the biogas production and subsequently, improve energy balance. The performances of Disc-mower and Excoriator were assessed on meadow and cultivated grass silages. The results showed that relatively high methane production can be achieved from meadow and cultivated grass harvested in different seasons. The findings indicated that the bioenergy production can be improved based on the selection of the appropriate harvesting technology. More specifically, Excoriator, which cuts and subsequently applies shearing forces on harvested biomass, enhanced the methane production up to 10% and the overall energy budget was improved proportionally to the driving speed increase.

Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA).

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.