Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Real-world hepatitis C prevalence and treatment uptake at opioid agonist therapy clinics in Ontario, Canada.

Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.

Associations of changes in physical activity and sedentary time with weight recurrence after bariatric surgery: a 5-year prospective study.

BACKGROUND: Increasing physical activity and limiting sedentary time may minimize weight recurrence after bariatric surgery. However, few studies have evaluated potential associations of objectively-measured physical activity and sedentary time with post-surgical weight recurrence over time. AIMS: To evaluate associations of change in physical activity and sedentary time with weight recurrence after bariatric surgery. METHODS: Participants from the Oslo Bariatric Surgery Study, a prospective cohort study, wore an ActiGraph monitor for seven days at 1- and 5 years after surgery to assess daily physical activity and sedentary time. Participants' weight was measured at in-person clinic visits. Chi-square Test and Paired-samples T-test evaluated group differences and change over time, while Pearson's Correlation, multiple logistic and linear regression investigated associations between variables. RESULTS: Five years after surgery 79 participants (70.5% response rate, 81% female) (mean (sd) age: 54.0 (±9.3), BMI: 32.1 (±4.7)) had valid monitor data. Participants increased their sedentary time (71.4 minutes/day (95% CI: 54.2-88.6, p = <0.001)) and reduced daily steps (-1411.1 (95% CI: 737.8-208.4), p = <0.001), light physical activity (-54.1 min/day (95% CI: 40.9-67.2, p = <0.001)), and total physical activity (-48.2 (95% CI: 34.6-63.3), p = <0.001) from 1- to 5 years after surgery. No change was found for moderate-to-vigorous intensity physical activity. No associations were found between changes in steps, physical activity or sedentary time and weight recurrence. CONCLUSION: Participants increased sedentary time and decreased light- and total physical activity between 1- and 5 years post-surgery. Overall, changes in physical activity and sedentary time were not associated with weight recurrence. Interventions to help patients increase physical activity and limit sedentary time after bariatric surgery are needed.

Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

The cause of death in bacterial meningitis.

BACKGROUND: Death from bacterial meningitis is rarely attributed to the actual event causing death. The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis. METHODS: In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown. RESULTS: We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%). CONCLUSION: Fatal complications due to the primary infection - meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.

Effect of Calcipotriene/Betamethasone Dipropionate 0.005%/0.064% Foam on Target Lesions in Plaque Psoriasis: A Post-Hoc Analysis

Objective: Investigate the effect of fixed-combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam on target lesion severity in plaque psoriasis. Design: Post-hoc analysis was conducted on data from a Phase 3, randomized, double-blind, multicenter clinical study of Cal/BD foam in the treatment of psoriasis vulgaris for 4 weeks (PSO-FAST; NCT01866163). Participants: In PSO-FAST, 426 patients (≥18 years) with psoriasis vulgaris (≥mild severity) were randomized 3:1 to Cal/BD foam (n=323) or vehicle foam (n=103), applied once daily. Measurements: Assessments included (1) target lesion severity (redness, scaliness, and thickness) at baseline and weeks 1, 2, and 4; and (2) the proportion of patients with ≥50% reduction in total sign score (TSS-50) from baseline at weeks 1, 2, and 4. Results: A greater proportion of patients achieved considerable improvement (a score of 0 or 1) in the severity of target lesions after 4 weeks of treatment with Cal/BD foam vs vehicle foam at week 4 (redness: 76.2% vs 21.4%; P<.001; scaliness: 91.3% vs 61.2%; P<.001; and thickness: 83.3% vs 35.0%; P<.001, respectively). Rapid onset of efficacy was observed as early as week 1. Significantly more patients also achieved TSS-50 at week 4 with Cal/BD foam vs vehicle foam for their target lesions regardless of treatment area, including the elbows and knees (P<.05 for all). Conclusions: Significant improvements in target lesion severity were achieved with up to 4 weeks of treatment with once-daily Cal/BD foam for adults with plaque psoriasis versus vehicle foam, with rapid onset of efficacy observed at week 1. J Drugs Dermatol. 2020;19(2)121-126. doi:10.36849/JDD.2020.4750

An age difference of two billion years between a metal-rich and a metal-poor globular cluster.

Globular clusters trace the formation history of the spheroidal components of our Galaxy and other galaxies, which represent the bulk of star formation over the history of the Universe. The clusters exhibit a range of metallicities (abundances of elements heavier than helium), with metal-poor clusters dominating the stellar halo of the Galaxy, and higher-metallicity clusters found within the inner Galaxy, associated with the stellar bulge, or the thick disk. Age differences between these clusters can indicate the sequence in which the components of the Galaxy formed, and in particular which clusters were formed outside the Galaxy and were later engulfed along with their original host galaxies, and which were formed within it. Here we report an absolute age of 9.9 ± 0.7 billion years (at 95 per cent confidence) for the metal-rich globular cluster 47 Tucanae, determined by modelling the properties of the cluster's white-dwarf cooling sequence. This is about two billion years younger than has been inferred for the metal-poor cluster NGC 6397 from the same models, and provides quantitative evidence that metal-rich clusters like 47 Tucanae formed later than metal-poor halo clusters like NGC 6397.

The Impact of Self-Monitoring Blood Glucose Adherence On Glycemic Goal Attainment in an Indigent Population, With Pharmacy Assistance.

Self-monitoring of bood glucose alone is not a good predictor of HbA1c goal attainment. Health plans might benefit from formulary restrictions to provide more cost-effective care, without negatively impacting glycemic control. And by using targeted inteventions, healthcare providers could help maximize SMBG's clinical benefit for patients who receive test strips. Self-monitoring of blood glucose (SMBG) can be an important tool in diabetes treatment, both for patient self-management and for guiding clinicians regarding medication adjustments. Evidence supports the association of SMBG with clinical outcomes in patients with type-1 diabetes mellitus (T1DM) although it is mixed for patients with type-2 diabetes mellitus (T2DM). The cost of SMBG comprises a substantial portion of the total cost for patients with diabetes, and test strips are one of the main expenditures of the University of North Carolina Medical Center Pharmacy Assistance Program (PAP), which provides medication coverage, including test strips, to indigent patients who have no pharmacy insurance. The objective of this study is to evaluate the utility of SMBG based on the impact of test-strip adherence on glycemic goal attainment in an indigent population that is provided with low-copay test strips. This retrospective cohort study included patients with T1DM or T2DM who were enrolled in PAP in 2016 and who received a prescription for test strips during the 90 days prior to hemoglobin A1c (HbA1c) measurement. Adherence was defined as the proportion of days covered (PDC) > 0.8. Of the 498 patients encountered, 20% of the adherent group (n = 245) and 25% of the nonadherent group (n = 253) had a goal of HbA1c < 7% (P = 0.24). There were no differences in mean HbA1c between the groups, except in the multiple daily injections (MDI) of the insulin subgroup (8.9% vs. 9.6%, P = 0.009). The adherent group was 80% less likely to have a diabetes-related hospitalization (odds ratio [OR], 0.2; 95% CI, 0.04-0.92). The total test-strip cost to PAP was more than $200,000. In conclusion, in an indigent population, adherence to SMBG does not correlate with glycemic goal attainment and imposes a substantial cost burden on the healthcare system.

Eutrophication causes speciation reversal in whitefish adaptive radiations.

Species diversity can be lost through two different but potentially interacting extinction processes: demographic decline and speciation reversal through introgressive hybridization. To investigate the relative contribution of these processes, we analysed historical and contemporary data of replicate whitefish radiations from 17 pre-alpine European lakes and reconstructed changes in genetic species differentiation through time using historical samples. Here we provide evidence that species diversity evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline. Across the radiations, the magnitude of eutrophication explains the pattern of species loss and levels of genetic and functional distinctiveness among remaining species. We argue that extinction by speciation reversal may be more widespread than currently appreciated. Preventing such extinctions will require that conservation efforts not only target existing species but identify and protect the ecological and evolutionary processes that generate and maintain species.

Secular and longitudinal physical activity changes in population-based samples of children and adolescents.

The aims of this study were to investigate whether physical activity (PA) and sedentary time (ST) in 9- and 15-year-olds differed between 2005-2006 and 2011-2012 (secular change), and to investigate changes in PA and ST from age 9 to 15 (longitudinal change). In 2005-2006, we invited nationally representative samples of Norwegian 9- (n=1470) and 15-year-olds (n=1348) to participate. In 2011-2012, we invited a new nationally representative sample of 9-year-olds (n=1945), whereas 15-year-olds (n=1759) were invited to participate either based on previous participation in 2005-2006 or from a random sample of schools. We assessed PA and ST objectively using accelerometers. In 2011-2012, both 9- and 15-year-olds spent more time sedentary (≥35.7 min/d, P<.001) and less time in light PA (≥35.2 min/d, P<.001) compared to their peers in 2005-2006. Nine-year-old girls also spent less time in moderate-to-vigorous PA (MVPA) (4.2 min/d, P=.041). In both age groups, the proportion accumulating an average of 60 min/d of MVPA did not differ between the two cohorts. From age 9 to 15, girls and boys decreased their time spent in LPA (≥106.7 min/d, P<.001) and in MVPA (≥20.8 min/d, P<.001). During the same period, ST increased by a mean of >2 h/d (P<.011). We observed an adverse secular change in PA from 2005-2006 to 2011-2012 among 9- and 15-year-olds, and a large decline in PA in the participants followed longitudinally from age 9 to 15 years.

Extremely prematurely born adolescents self-report of anxiety symptoms, and the mothers' reports on their offspring.

AIM: To compare anxiety symptoms in adolescents born extremely prematurely to term-born controls. METHODS: We had 96 preterm-born adolescents and 40 term-born controls from Denmark, and their mothers score the adolescents on the Revised Children Anxiety and Depression scale. We analysed group differences, cross-informant correlations and relative risks for elevated anxiety symptoms. RESULTS: Self-reported anxiety symptoms did not significantly differ, although the upper confidence limit (95% CI: -3.3 to 5.1) supported an odds ratio of 2 for the preterm-born participants. Mothers of the preterm-born participants reported higher social anxiety symptoms than did mothers of controls (51.7 versus 46.8, p = 0.001). The relative risk for being above a threshold indicating distressing anxiety was small from self-reports (1.39; p = 0.60). From mother-reports, the relative risk was noticeable but not significant (4.58; p = 0.14). Cross-informant scores correlated significant for total anxiety and social anxiety for the preterm-born (rτ = 0.2, p = 0.001; rτ = 0.3, p ≤ 0.001). CONCLUSIONS: Self-reports did not clearly indicate more anxiety in the preterm group, although confidence intervals supported a possible twofold increase. Mother- and self-reports correlated only for the preterm group, which may indicate increased sensitivity for their children's symptoms.

Objectively measured sedentary time and physical activity and associations with body weight gain: does body weight determine a decline in moderate and vigorous intensity physical activity?

OBJECTIVES: High levels of physical activity (PA) may prevent the development of obesity. However, the magnitude and direction of the association between PA of various intensities, sedentary time and weight status remain unclear. Thus, we examined whether objectively measured sedentary time and PA independently predict gain in body weight, change in body weight and to examine the possibility of reverse causation. METHODS: We examined the prospective associations between sedentary time, PA and body weight (BW). Baseline measurements were conducted in 2008/2009 and follow-up measurements in 2014/2015 in a random sample of the adult Norwegian population (N=1710, 45.1% men). Moderate and vigorous intensity PA (MVPA) and sedentary time were measured by accelerometry and BW and height self-reported. We first modelled the associations between baseline sedentary time and PA with BW at follow-up. We then modelled the reverse associations (BW as the exposure) and sedentary time and PA (as outcomes) in separate models. All models were adjusted for age, sex, baseline value of the outcome, socio-economic status, alcohol consumption, smoking, monitor wear time and follow-up time. RESULTS: Body mass index (BMI) increased by 0.2 units (P=0.003) between baseline and follow-up, and 46.5% of participants were either overweight (36.4%) or obese (10.1%) at baseline increasing to 49.6% (11.7% obese) at follow-up. Baseline sedentary time, MVPA and vigorous PA were not associated with BW at follow-up after adjustment for covariates. In contrast, baseline BW was inversely associated with MVPA (ß=-0.11; 95% confidence interval (CI); -0.21, -0.009) and VPA (ß=-0.035; 95% CI; -0.059, -0.011) in adjusted models. These associations were unchanged when BW was substituted by BMI. CONCLUSIONS: Baseline BW seems to determine a decrease in MVPA in healthy adult Norwegian men and women, more so than the reverse.

Prediction of long-term clinical outcome in a diverse chronic hepatitis B population: Role of the PAGE-B score.

An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic .91) and reduced transplant-free survival (C-statistic .83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were .70 (0.59-0.81), .82 (0.75-0.89), .73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic .87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement.

The effects of intra-articular glucocorticoids and exercise on pain and synovitis assessed on static and dynamic magnetic resonance imaging in knee osteoarthritis: exploratory outcomes from a randomized controlled trial.

OBJECTIVE: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis. DESIGN: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26. RESULTS: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs. CONCLUSIONS: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

Reference values for and cross-validation of time to exhaustion on a modified Balke protocol in Norwegian men and women.

The aims of the present study were to provide reference values for time to exhaustion (TTE) on a modified Balke treadmill protocol, and to perform a cross-validation of TTE as a measure of maximal oxygen consumption (VO2max ), in Norwegian men and women 20-85 years of age. Reference values for TTE were derived from a national sample of 765 subjects. An additional sample of 119 subjects was included in the cross-validation (total n = 884), where prediction equations for VO2max was established. A decline in TTE was seen with increased age. Prediction of VO2max in an independent dataset (n = 319) resulted in a R2  = 0.78 and standard error of the estimate = 4.55 mL/kg/min. The observed-predicted bias was small (mean difference <1.24 mL/kg/min), whereas random error was considerable (95% limits of agreement ± 7.11-9.70 mL/kg/min) across age in both men and women. Despite limitations concerning the prediction of VO2max on an individual level, TTE from the Balke protocol is a good measure of aerobic fitness in adults across a range of settings, and could be evaluated according to the suggested reference values.

Fractionated aliphatic alcohols as synthetic precursors of ultra long-chain monoacylglycerols for cosmetic applications.

BACKGROUND: Xerosis is an abnormally dry and flaky skin condition that is associated with a change in the packing behaviour of the lipid matrix in the stratum corneum (SC), the outermost layer of the skin. This skin condition can lead to an increase in transepidermal water loss (TEWL). As ultralong-chain fatty acids have a positive effect on maintaining the packing behaviour of the SC lipid matrix, a moisturizer which contains glycerides of ultralong-chain fatty acids could act as a semi-occlusive layer on the surface of the skin. This will lower the rate of water evaporation through the epidermis and consequently help prevent or improve skin xerosis. OBJECTIVE: To identify a novel source of ultralong-chain lipids and develop monoacylglycerols with mixed fatty acyl chain lengths that have occlusive properties superior to petrolatum. METHODS: Initially, Performacol 425, a mixture of very long-chain fatty alcohols, was fractionated using short path distillation to yield a fraction enriched with C22:0-C26:0 fatty alcohols. The fatty alcohol fraction was then oxidized using Jones reagent, and the resulting fatty acids were esterified with glycerol to yield the corresponding monoglycerides using Novozym 435. These were then evaluated using Fourier transform infrared spectroscopy, differential scanning calorimetry and water vapour transmission rate measurements. RESULTS: The monoacylglycerols enriched with C22:0-C26:0 displayed a melting point of 80°C and orthorhombic packing; packing behaviour mainly present in healthy SC. In addition, a phospholipid-structured emulsion containing 3% of the monoglycerides displayed occlusive properties superior to the vehicle containing 3% petrolatum jelly. CONCLUSIONS: Performacol 425 can be a potential source of fatty alcohols to synthesize monoacylglycerols that can improve the occlusive behaviour of phospholipid-structured emulsions.

Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.

It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.

Fast diffusion kurtosis imaging of fibrotic mouse kidneys.

Diffusion kurtosis imaging (DKI) is sensitive to tissue microstructure and may therefore be useful in the diagnosis and monitoring of disease in brain and body organs. Generally, diffusion magnetic resonance imaging (dMRI) in the body is challenging because of the heterogeneous body composition, which can cause image artefacts as a result of chemical shifts and susceptibility differences. In addition, the abdomen possesses physiological factors (e.g. breathing, heartbeat, blood flow) which may severely reduce image quality, especially when echo planar imaging is employed, as is typical in dMRI. Collectively, these challenging measurement conditions impede the use and exploration of DKI in the body. This impediment is further exacerbated by the traditionally large amount of data required for DKI and the low signal-to-noise ratio at the b-values needed to effectively probe the kurtosis regime. Recently introduced fast DKI techniques reduce the challenge of DKI in the body by decreasing the data requirement substantially, so that, for example, triggering and breath-hold techniques may be applied for the entire DKI acquisition without causing unfeasible scan times. One common pathological condition for which body DKI may be of immediate clinical value is kidney fibrosis, which causes progressive changes in organ microstructure. With its sensitivity to microstructure, DKI is an obvious candidate for a non-invasive evaluation method. We present preclinical evidence indicating that the rapidly obtainable tensor-derived mean kurtosis ( W̅) distinguishes moderately fibrotic kidneys from healthy controls. The presence and degree of fibrosis are confirmed by histology, which also indicates fibrosis as the main driver behind the DKI differences observed between groups. We therefore conclude that fast kurtosis is a likely candidate for an MRI-based method for the detection and monitoring of renal fibrosis. We provide protocol recommendations for fast renal DKI in humans based on a b-value optimisation performed using data acquired at 3 T in normal human kidney.

Cardiorespiratory fitness in groups with different physical activity levels.

The aim of the study was to determine how different categorizations of self-reported and objectively measured physical activity (PA) reflect variations in cardiorespiratory fitness (VO2max ). A total of 759 individuals (366 women) with a mean age of 48.5 years (SD 14.4) wore an accelerometer (ActiGraph GT1M) for seven consecutive days and answered the short International Physical Activity Questionnaire (IPAQ). VO2max was directly measured during a continuous graded exercise treadmill test until exhaustion. Men and women categorized as highly active by IPAQ had 9% and 13% higher VO2max , respectively, than those reporting a low PA level (P < 0.05). Men and women meeting the PA recommendation of 150 min/week of daily moderate intensity PA, measured by accelerometer, had 13% and 9% higher VO2max , respectively, than participants not meeting this recommendation (P < 0.01). No significant differences in average sedentary time, analyzed in total min/day and in bouts of 10 and 30 min, were found between participants with high or low cardiorespiratory fitness. However, women spent less time than men in bouts of sedentary behaviors. Self-reported PA by IPAQ and objectively measured PA by accelerometer were both useful instruments for detecting differences in VO2max .