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Since profiling of circulating tumor DNA (ctDNA) has shown utility in non-Hodgkin lymphoma genotyping and risk stratification, we employed a noninvasive approach in cHL to overcome challenges imposed by low tumor fractions. B Methods: b We profiled baseline plasma samples from 366 patients diagnosed with cHL, 99% of whom were enrolled prior to anti-lymphoma therapy. B Introduction: b The scarcity of malignant Reed-Sternberg cells has hampered comprehensive genomic profiling of classic Hodgkin lymphoma (cHL) as might inform personalized therapeutic strategies. [Extracted from the article]

B Conclusions: b Detection of ctDNA MRD using PhasED-Seq is prognostic for outcomes in rrLBCL patients undergoing CAR19 therapy, and has superior performance compared to CAPP-Seq and PET/CT. B Introduction: b Over half of relapsed/refractory large B-cell lymphoma (rrLBCL) patients receiving anti-CD19 chimeric antigen receptor (CAR19) T-cells experience subsequent relapse. [Extracted from the article]

The effects of strong ground shaking on hillslope stability can persist for many years after a large earthquake, leading to an increase in the rates of post earthquake land sliding. The factors that control the rate of post‐earthquake land sliding are poorly constrained, hindering our ability to reliably forecast how landscapes and landslide hazards and risk evolve. To address this, we use a unique data set comprising high‐resolution terrestrial laser scans and airborne lidar captured during and after the 2010–2011 Canterbury Earthquake Sequence, New Zealand. This earthquake sequence triggered thousands of rock falls, and rock and debris avalanches (collectively referred to as "rockfall"), resulting in loss‐of‐life and damage to residential dwellings, commercial buildings and other infrastructure in the Port Hills of Christchurch, New Zealand. This unique data set spans 5 years and includes five significant earthquakes. We used these data to (a) quantify the regional‐scale "rockfall" rates in response to these earthquakes and the postearthquake decay in rockfall rates with time; and (b) investigate the site‐specific factors controlling the location of seismic and nonseismic rockfalls using frequency ratios and logistic regression techniques. We found that rockfall rates increased significantly in response to the initial earthquake that generated the strongest shaking in the sequence—The MW 6.2 22 February 2011 event—Compared to the long‐term background rates derived from the dating of pre‐2010 talus piles at the toe of the slopes. Non seismic rockfall rates also increased immediately after the 22 February 2011 earthquake and decayed with time following a power‐law trend. About 50% of the decay back to the pre‐earthquake rockfall rates occurred within 1–5 years after the 22 February 2011 earthquake. Our results show that the short‐term decay in rockfall rates over time, after the initial earthquake, was attributed to the subsequent erosion of seismically damaged rock mass materials caused by environmental processes such as rain. For earthquake‐induced rockfall at the regional‐scale, the peak ground accelerations is the most significant variable in forecasting rockfall volume, followed by the relative height above the base of the slope. For both earthquake and non‐seismic conditions at the site‐specific scale, the probability of rockfall increases when the adjacent areas have failed previously, indicating that accrued damage preconditions localized areas of the slope for subsequent failure. Such preconditioning is a crucial factor driving subsequent rockfalls; that is, future rockfalls are likely to cluster near areas that failed in the past. Plain Language Summary: Evidence from previous earthquakes suggests that the frequency of land sliding after a large earthquake is significantly higher than before it. Strong earthquakes cause slope cracking and generate landslide debris, which can be more readily remobilized post earthquake, creating new hazards, including further landslides and landslide dams. These hazards may persist for years and decades and represent a prolonged risk that the impacted communities must consider. Currently, the relative increase in land sliding and rate of decay during and after a major earthquake is rarely quantified, thus posing a knowledge gap for those rebuilding after a major earthquake. This paper explores high‐resolution terrestrial laser scan models of slope surfaces and how these surfaces changed during and after strong earthquake shaking during the 2010–2011 Canterbury Earthquake Sequence (CES) in New Zealand. These surface "change" models were used to quantify the volumes of debris–rock and soil–that fell from these slopes during and after the CES. These data were used to establish a regional‐scale, physical relationship between the volume of debris falling from the cliffs per earthquake or unit of time, per unit area of slope. Using the change models, we investigated the factors that control the temporal and spatial distribution of the rockfalls at the regional‐ and site‐specific scales. At the regional scale, we found that the size of the slope and the relative increase in rockfall rates above pre‐CES rates controlled the subsequent non‐seismic rockfall decay time. At the site‐specific scale, the main conclusions from this study are: (a) for earthquake triggers, the peak ground acceleration (a measure of earthquake ground shaking) was the most important variable in forecasting the probability of failure, followed by the relative elevation or height above the base of the slope; and (b) for both earthquake and nonseismic triggers, the probability of failure increases when the adjacent areas have failed previously, indicating that preconditioning of the slope to failure is a key factor driving subsequent rockfalls. Key Points: We quantify rock slope changes during and after a major earthquake sequence through repeat high‐resolution terrestrial laser scan surveysWe analyze landslide rates over 5 years, during and after the earthquakes at the regional‐ and site‐specific scalesNon seismic landslide rates are heightened immediately after the initial earthquake and decayed with time (1–5 years) following a power‐law trend [ABSTRACT FROM AUTHOR]

Background: Adults with intellectual disability (ID) have poorer physical and perceived health than the general population. Knowledge of perceived health predictors is both limited and important for guiding the development of preventive actions. The aims of this study were to investigate (1) the associations between perceived health and demographics, degree of ID, physical health conditions, and weight and physical activity level and (2) lifestyle factors and multimorbidity as predictors for perceived health adjusted for age, gender, and level of ID. Method: The North Health in Intellectual Disability study is a community based cross‐sectional survey. The POMONA‐15 health indicators were used. Univariate and multivariate logistic regression analyses with poor versus good health as the dependent variable were applied. Results: The sample included 214 adults with a mean age 36.1 (SD 13.8) years; 56% were men, and 27% reported perceiving their health as poor. In univariate analyses, there were significant associations between poor health ratings and female gender, lower motor function, number of physical health conditions and several indicators of levels of physical activity. In the final adjusted model, female gender [odds ratio (OR) 2.4, P < 0.05], level of ID (OR 0.65, P < 0.05), numbers of physical health conditions (OR 1.6, P < 0.001) and lower motor function (OR 1.5 P < 0.05) were significant explanatory variables for poor perceived health, with a tendency to independently impact failure to achieve 30 min of physical activity daily (OR 2.0, P = 0.07). Conclusion: Adults with ID with female gender, reduced motor function and more physical health conditions are at increased risk of lower perceived health and should be given attention in health promoting interventions. A lack of physical activity tends to negatively influence perceived health. [ABSTRACT FROM AUTHOR]

The European Spallation Source (ESS) is intended to become the most powerful spallation neutron source in the world and the flagship of neutron science in upcoming decades. The exceptionally high neutron flux will provide unique opportunities for scientific experiments but also set high requirements for the detectors. One of the most challenging aspects is the rate capability and in particular the peak instantaneous rate capability, i.e. the number of neutrons hitting the detector per channel or cm2 at the peak of the neutron pulse. The primary purpose of this paper is to estimate the incident rates that are anticipated for the BIFROST instrument planned for ESS, and also to demonstrate the use of powerful simulation tools for the correct interpretation of neutron transport in crystalline materials. A full simulation model of the instrument from source to detector position, implemented with the use of multiple simulation software packages, is presented. For a single detector tube, instantaneous incident rates with a maximum of 1.7 GHz for a Bragg peak from a single crystal and 0.3 MHz for a vanadium sample are found. This paper also includes the first application of a new pyrolytic graphite model and a comparison of different simulation tools to highlight their strengths and weaknesses. [ABSTRACT FROM AUTHOR]

Noncontact measurements of spatially varied ground surface deformation during landslide motion can provide important constraints on landslide mechanics. Here, we present and test a new method for extracting measurements of rapid landslide surface displacement and velocity (accelerations of approximately 1 m/s2) using sequences of stereo images obtained from a pair of inexpensive, stationary 4K video cameras with nominal frame rates of 29.97 Hz. The method combines elements of Structure from Motion with those of optical flow to extract data on 3‐D evolution of the ground surface during slope failure. We apply the method to an experiment at the U.S. Geological Survey debris‐flow flume in which a high‐speed, liquefying landslide was triggered by gradually adding water to a 6‐m3 prism of loosely packed sediment on a 31° slope. Strip‐scanning lidar measurements made during the experiment corroborate our video‐based measurements, but the latter encompassed the entire landslide surface and were much lower in cost. Our video‐based measurements enabled computation of depth‐integrated landslide dilation/contraction rates. The range of computed rates was within the ranges inferred from independent measurements of evolving pore water pressures and reasonable estimates of the hydraulic permeability of the sediment. Dilation and contraction rates play a crucial role in landslide mechanics. The dilation and contraction we observe contradict the incompressible flow assumption used in many studies that have employed noncontact methods to infer landslide properties. Key Points: Rapidly evolving landslide geometry can be quantified using two uncalibrated video camerasVideo‐based geometry agrees with independently derived lidar‐based geometry within a few centimetersDepth‐integrated landslide dilation/contraction rates inferred from video compare well with rates inferred from pore‐pressure measurements [ABSTRACT FROM AUTHOR]

We use a mapped landslide inventory coupled with a 2‐m resolution vertical difference model covering an area of 6,875 km2 to accurately constrain landslide volume‐area relationships. We use the difference model to calculate the source volumes for landslides triggered by the MW 7.8 Kaikōura, New Zealand, earthquake of 14 November 2016. Of the 29,519 mapped landslides in the inventory, 28,394 are within the analysis area, and of these, we have calculated the volume of 17,256 source areas that are ≥90% free of debris. Of the 28,394 landslides, about 80% are classified as soil or rock avalanches and the remainder as mainly translational slides. Our results show that both the soil avalanches and the rock avalanches, ignoring their source geology, have area to volume power‐law scaling exponents (γ) of 0.921 to 1.060 and 1.040 to 1.138, respectively. These are lower than the γ values of 1.1–1.3 (for soil) and 1.3–1.6 (for rock) reported in the literature for undifferentiated landslide types. They are, however, similar to those γ values estimated from other coseismic landslide inventories. In contrast, for 50 selected rotational, translational (planar slide surfaces), or compound slides, where much of the debris remains in the source area, we found γ values range between 1.46 and 1.47, indicating that their slide surfaces were considerably deeper than those landslides classified as avalanches. This study, like previous studies on coseismic landslides, shows that soil and rock avalanches (disrupted landslides) are the dominant landslide type triggered by earthquakes and that they tend to be shallow. Key Points: We use a 2‐m resolution vertical difference model to estimate source volumes for 17,256 landslides with sources ≥90% free of debris triggered by the MW7.8 2016 Kaikōura EarthquakeThe model was derived by subtracting a tectonically adjusted pre‐EQ surface model from a post‐EQ model, covering an area of 6,875 km2Landslide trigger mechanism, type/failure mode, and source material are critical for accurate estimation of landslide volumes from source‐area geometries [ABSTRACT FROM AUTHOR]

Background and purpose: Visual snow syndrome is a recently described condition of unknown prevalence. We investigated the prevalence in a representative population sample from the UK and tested the hypothesis that visual snow syndrome is associated with young age, headache, tinnitus and mood impairment. Methods: Using a crowdsourcing platform, we recruited a representative sample of 1015 adult laypeople from the UK, matched for age, gender and ethnicity according to national census data. Participants were unprimed, i.e. were inquired about the 'frequency of certain medical conditions' but not 'visual snow syndrome'. Results: A total of 38 of 1015 participants reported symptoms compatible with visual snow [3.7%; 95% confidence interval (CI), 2.7–5.2] and 22/1015 met criteria for visual snow syndrome (2.2%; 95% CI, 1.4–3.3). The female‐to–male ratio for visual snow syndrome was 1.6:1. Subjects with visual snow syndrome were older (50.6 ± 14 years) than the population mean (44.8 ± 15 years), although this was not statistically different (P = 0.06). Of 22 participants with visual snow syndrome, 16 had mood symptoms (72.7%; P = 0.01), 12 had headache (54.5%; P = 0.06), including five with visual migraine aura (22.7%; P = 0.15) and 13 had tinnitus (59.1%; P < 0.001). No participant had diabetes or a cleft lip (control questions). Following a multivariable regression analysis to adjust for age and gender, only the association between visual snow syndrome and tinnitus remained significant (odds ratio, 3.93; 95% CI, 1.63–9.9; P = 0.003). Conclusions: The UK prevalence of visual snow syndrome is around 2%. We confirmed an association with tinnitus, but unprimed laypeople with visual snow syndrome are on average older than those seeking medical attention. [ABSTRACT FROM AUTHOR]

Distinct molecular determinants of treatment-failure in elderly Hodgkin lymphoma identified by cell-free DNA profiling: A LYSA Study Interestingly, pre-treatment ctDNA levels did not differ between EBV+ and EBV- tumors ( I p i = 0.92), while specific genetic aberrations were significantly associated with respective EBV status (Figure C). Older HL pts, especially those with high baseline ctDNA levels and/or EBV+ tumors, have an exceedingly high risk of treatment failure with conventional chemotherapy, and likely require future risk-adapted strategies. [Extracted from the article]

Background: Attention towards cardiovascular disease prevention in patients with moderate to severe psoriasis increased with the introduction of biological therapy. Objective: To determine the risk of myocardial infarction (MI) following hospital‐diagnosed psoriasis compared with the general population, in eras before and following the introduction of biological therapy. Methods: We conducted a cohort study in Denmark utilising nationwide prospectively collected data from population‐based registries. For the early era cohort, we identified subjects with first time hospital‐diagnosed psoriasis between 1995 and 2002, and, for the late era cohort, those diagnosed between 2006 and 2013. Comparison cohorts from the general population were matched (10:1) on sex and birth year. All individuals were followed from date of psoriasis diagnosis (index date for matched controls) until incidence of MI, death, emigration or end of study (1 January 2002 for the early era cohort; 1 January 2013 for the late era cohort). We computed the cumulative MI incidence at 5 years of follow‐up, and used Cox regression to compute HRs of MI comparing psoriasis subjects with general population subjects. Results: For the early era, we identified 4302 psoriatic subjects and 43 791 general population subjects; and for the late era, 4577 psoriatic subjects (4% received biologic therapy) and 46 376 general population subjects. The cumulative incidence of MI among psoriatic subjects in the early era was 2.5% and it was 2.2% in the late era. The HRs comparing MI risk in the psoriasis and general population cohorts were 1.40 (95% CI: 1.09–1.80), for the early era, and 1.39 (95% CI: 1.10–1.75) for the late era, adjusting for educational level and use of cardiovascular drugs. Conclusion: The increased risk of MI among patients with hospital‐diagnosed psoriasis, relative to the general population, remained unchanged during the initial years of increased attention towards cardiovascular disease prevention and availability of biologic therapy. [ABSTRACT FROM AUTHOR]

Aim: To determine differences in coronary plaque composition and inflammatory biomarkers between men and women with newly diagnosed Type 2 diabetes without known cardiovascular disease. Methods: A total of 88 people with newly diagnosed (<1 year) Type 2 diabetes underwent contrast‐enhanced coronary computed tomography angiography. Advanced coronary plaque analysis was performed using semi‐automated software. Plasma concentrations of inflammatory biomarkers were determined. Results: There were no significant differences between men (n=60) and women (n=28) regarding age or cardiovascular risk factors (all P>0.05). The median (quartiles) serum levels of fibrinogen [10.9 (9.8–12.6) μmol/l vs 9.7 (8.8–10.9) μmol/l], fibrin d‐dimer [0.3 (0.2–0.4) mg/l vs 0.27 (0.2–0.4) mg/l] and C‐reactive protein [3.1 (1.1–5.2) mg/l vs (0.8–2.6) 1.6 mg/l] were significantly higher in women (all P<0.05). Overall, men more often had multi‐vessel involvement [28 men (47%) vs 4 women (14%)], and higher total plaque burden [median (quartiles) 11.6 (2.3–36.0)% vs 2.0 (0.4–5.4)%; both P<0.05]. The median (quartiles) total plaque volume [269.9 (62.6–641.9) mm3 vs 61.1 (7.6–239.9) mm3] and absolute calcified plaque volume [33.5 (8.3–148.3) mm3 vs 4.7 (0.9–17.3) mm3] were higher in men (both P<0.05). Women had a lower relative proportion of the calcified plaque component [median (quartiles) 7.8 (4.7–15.4)% vs 23.7 (8.4–31.1)%] and a higher relative proportion (median [quartiles]) of the non‐low‐density non‐calfied plaque component [77.6 (66.0–86.0)% vs 63.6 (54.0–72.9)%; both P<0.05]. Conclusions: In people with newly diagnosed Type 2 diabetes, women had lower absolute coronary plaque volumes but a more unfavourable plaque composition and enhanced systemic inflammation compared with men. What's new?: It is known that Type 2 diabetes increases the risk of developing coronary artery disease more markedly in women than in men, but differences in coronary plaque composition between the sexes are poorly elucidated.This study found that women have smaller absolute volumes of coronary plaque components but a more unfavourable coronary plaque structure and enhanced systemic inflammation.The reported difference in plaque composition between men and women with a new diagnosis of Type 2 diabetes might be the basis for larger studies evaluating the impact of sex‐differentiated therapeutic strategies at an early stage of Type 2 diabetes to prevent the development and progression of cardiovascular disease. [ABSTRACT FROM AUTHOR]

We evaluated effects of the school‐based intervention “FIFA 11 for Health” for Europe on health and fitness profile in 10‐ to 12‐year‐old Faroese schoolchildren. 392 fifth‐grade children were randomized into a control group (CG: n = 100, 11.1 ± 0.3 years, 149.0 ± 6.7 cm, 42.4 ± 10.2 kg) and an intervention group (IG: n = 292, 11.1 ± 0.3 years, 150.6 ± 6.9 cm, 44.2 ± 9.4 kg). IG underwent an 11‐week intervention in which 2 weekly sessions of 45 minutes were included in the school curriculum focusing on health aspects, football skills, and 3v3 small‐sided games. CG continued with their regular activities. Body composition, blood pressure, and resting heart rate, as well as Yo‐Yo intermittent recovery children’s test (YYIR1C) performance, horizontal jumping ability and postural balance were assessed pre and post intervention. Systolic blood pressure decreased more (−2.8 ± 9.9 vs 2.9 ± 8.4 mm Hg, P < .05) in IG than in CG. Lean body mass (1.0 ± 1.7 vs 0.7 ± 1.6 kg), postural balance (0.3 ± 3.9 vs −1.2 ± 5.9 seconds) and horizontal jump performance (5 ± 9 vs ‐5 ± 10 cm) increased more (P < .05) in IG than in CG. YYIR1C performance improved in CG (17%, 625 ± 423 to 730 ± 565 m) and IG (18%, 689 ± 412 vs 813 ± 391 m), but without between‐group differences. A within‐group decrease from 23.1 ± 8.4 to 22.5 ± 8.3% (P < .05) was observed in body fat percentage in IG only. In conclusion, the “FIFA 11 for Health” for Europe program had beneficial effects on SBP, body composition, jump performance and postural balance in 10‐ to 12‐year‐old Faroese schoolchildren, supporting the notion that school‐based football interventions can facilitate health of children in a small‐scale society and serve as an early step in the prevention of non‐communicable diseases. [ABSTRACT FROM AUTHOR]

Abstract: Background: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. Methods: We performed a prospective, multicenter study of CDI within 365 days post‐allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post‐transplant and while hospitalized and contacted monthly up to 18 months post‐transplantation. Results: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post‐index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post‐index date (HR = 4.7, P = .09). Conclusions: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post‐transplant period. [ABSTRACT FROM AUTHOR]

Detecting similarity between texts is a frequently encountered text mining task. Because the measurement of similarity is typically composed of a number of metrics, and some measures are sensitive to subjective interpretation, a generic detector obtained using machine learning often has difficulties balancing the roles of different metrics according to the semantic context exhibited in a specific collection of texts. In order to facilitate human interaction in a visual analytics process for text similarity detection, we first map the problem of pairwise sequence comparison to that of image processing, allowing patterns of similarity to be visualized as a 2D pixelmap.We then devise a visual interface to enable users to construct and experiment with different detectors using primitive metrics, in a way similar to constructing an image processing pipeline. We deployed this new approach for the identification of commonplaces in 18th-century literary and print culture. Domain experts were then able to make use of the prototype system to derive new scholarly discoveries and generate new hypotheses. [ABSTRACT FROM AUTHOR]

In this study, 11 microsatellite markers were used to determine the structure of West Greenlandic lumpfish Cyclopterus lumpus populations across six spawning locations spanning >1500 km and compared with neighbouring populations in Canada and Iceland. To evaluate whether data allow for identification of origin of C. lumpus in Greenlandic waters, genetic assignment analysis was performed for 86 C. lumpus sampled on a feeding migration. Significant structuring with isolation by distance was observed in the West Greenland samples and two major subpopulations, north and south, were suggested. Based on FST values, closer relationships were observed between Greenland and Canada, than Greenland and Iceland. Surprisingly, the North Greenland population showed more similarities with Canadian samples, than did the geographically closer south-west Greenland population. Origin could be assigned for a high proportion of non-spawning fish and demonstrated a marked east-west spatial separation of fish of Greenlandic and Icelandic genotypes. [ABSTRACT FROM AUTHOR]

Background Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake. Methods Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet ( n = 71) or orlistat medication therapy plus a low-fat diet ( n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition. Results Participant's mean age was 53 years, baseline body mass index was 39.3 kg m-2 and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss ( P = 0.02) and less rapid weight regain ( P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain ( P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition. Conclusions Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss. [ABSTRACT FROM AUTHOR]

Although the grey seal Halichoerus grypus is one of the most familiar and intensively studied of all pinniped species, its global population structure remains to be elucidated. Little is also known about how the species as a whole may have historically responded to climate-driven changes in habitat availability and anthropogenic exploitation. We therefore analysed samples from over 1500 individuals collected from 22 colonies spanning the Western and Eastern Atlantic and the Baltic Sea regions, represented by 350 bp of the mitochondrial hypervariable region and up to nine microsatellites. Strong population structure was observed at both types of marker, and highly asymmetrical patterns of gene flow were also inferred, with the Orkney Islands being identified as a source of emigrants to other areas in the Eastern Atlantic. The Baltic and Eastern Atlantic regions were estimated to have diverged a little over 10 000 years ago, consistent with the last proposed isolation of the Baltic Sea. Approximate Bayesian computation also identified genetic signals consistent with postglacial population expansion across much of the species range, suggesting that grey seals are highly responsive to changes in habitat availability. [ABSTRACT FROM AUTHOR]

We analysed participants with type 2 diabetes (n = 46) within a larger weight loss trial (n = 146) who were randomized to 48 weeks of a low-carbohydrate diet ( LCD; n = 22) or a low-fat diet + orlistat ( LFD + O; n = 24). At baseline, mean body mass index ( BMI) was 39.5 kg/m2 (s.d. 6.5) and haemoglobin A1c ( HbA1c) 7.6% (s.d. 1.3). Although the interventions reduced BMI similarly ( LCD −2.4 kg/m2; LFD + O −2.7 kg/m2, p = 0.7), LCD led to a relative improvement in HbA1c: −0.7% in LCD versus +0.2% in LFD + O [difference −0.8%, 95% confidence interval ( CI) = −1.6, −0.02; p = 0.045]. LCD also led to a greater reduction in antiglycaemic medications using a novel medication effect score ( MES) based on medication potency and total daily dose; 70.6% of LCD versus 30.4% LFD + O decreased their MES by ≥50% (p = 0.01). Lowering dietary carbohydrate intake demonstrated benefits on glycaemic control beyond its weight loss effects, while at the same time lowering antiglycaemic medication requirements. [ABSTRACT FROM AUTHOR]

Aim Using mice deficient in the CaV3.1 T-type Ca2+ channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. Methods We used immunofluorescence microscopy to localize CaV3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca2+ currents, pressure myography and Ca2+ imaging to test diameter and Ca2+ responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca2+ handling proteins in wild-type and CaV3.1−/− mice. Results Our data indicated that CaV3.1 channels are important for the maintenance of myogenic tone at low pressures (40-80 mm Hg), whereas they are not involved in high-voltage-activated Ca2+ currents, Ca2+ entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55-0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca2+ currents in mouse mesenteric vascular smooth muscle cell. Conclusion Our data using mice deficient in the CaV3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV3.1 channels are not involved in Ca2+ entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55-0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca2+ channels. [ABSTRACT FROM AUTHOR]

Key points It is often assumed that automatic movements such as walking require little conscious attention and it has therefore been argued that these movements require little cortical control., In humans, however, the gait function is often heavily impaired or completely lost following cortical lesions such as stroke., In this study we investigated synchrony between cortical signals recorded with electroencephalography (EEG) and electromyographic signals (EMG activity) recorded from the tibialis anterior muscle (TA) during walking., We found evidence of synchrony in the frequency domain (coherence) between the primary motor cortex and the TA muscle indicating a cortical involvement in human gait function., This finding underpins the importance of restoration of the activity and connectivity between the motor cortex and the spinal cord in the recovery of gait function in patients with damage of the central nervous system. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 479-487 (2012) Abstract Aim To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort ( n = 2353 generally healthy individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new-onset diabetes ( P < 0.0001). Results New-onset diabetes ( n = 182) was associated with increased soluble urokinase plasminogen activator receptor levels ( P = 0.013). Among 699 middle-aged (41 and 51 years) and 564 older (61 and 71 years) non-smokers, participants in the upper soluble urokinase plasminogen activator receptor quartile had a sex- and age-adjusted relative risk of 6.01 (95% CI 2.17-16.6, P < 0.0006) and relative risk of 3.25 (95% CI 1.51-6.98, P = 0.0025), respectively, for new-onset diabetes compared with participants in the lowest quartile. This relationship remained significant after additional adjustments for C-reactive protein and leukocytes or fasting glucose and insulin or BMI ( P < 0.05). The soluble urokinase plasminogen activator receptor was not related to incident diabetes among smokers (P ≥ 0.85). Conclusions In these explorative analyses, the soluble urokinase plasminogen activator receptor associated independently with incident diabetes in non-smokers, supporting an immune origin of Type 2 diabetes. Competing disease risk may explain lack of association among smokers. [ABSTRACT FROM AUTHOR]

- We report on mineralogy, petrography, and whole-rock 26Al-26Mg systematics of eight amoeboid olivine aggregates (AOAs) from the oxidized CV chondrite Allende. The AOAs consist of forsteritic olivine, opaque nodules, and variable amounts of Ca,Al-rich inclusions (CAIs) of different types, and show evidence for alteration to varying degrees. Melilite and anorthite are replaced by nepheline, sodalite, and grossular; spinel is enriched in FeO; opaque nodules are replaced by Fe,Ni-sulfides, ferroan olivine and Ca,Fe-rich pyroxenes; forsteritic olivine is enriched in FeO and often overgrown by ferroan olivine. The AOAs are surrounded by fine-grained, matrix-like rims composed mainly of ferroan olivine and by a discontinuous layer of Ca,Fe-rich silicates. These observations indicate that AOAs experienced in situ elemental open-system iron-alkali-halogen metasomatic alteration during which Fe, Na, Cl, and Si were introduced, whereas Ca was removed from AOAs and used to form the Ca,Fe-rich silicate rims around AOAs. The whole-rock 26Al-26Mg systematics of the Allende AOAs plot above the isochron of the whole-rock Allende CAIs with a slope of (5.23 ± 0.13) × 10−5 reported by . In contrast, whole-rock 26Al-26Mg isotope systematics of CAIs and AOAs from the reduced CV chondrite Efremovka define a single isochron with a slope of (5.25± 0.01) × 10−5 (). We infer that the excesses in 26Mg* present in Allende AOAs are due to their late-stage open-system metasomatic alteration. Thus, the 26Al-26Mg isotope systematics of Allende CAIs and AOAs are disturbed by parent body alteration processes, and may not be suitable for high-precision chronology of the early solar system events and processes. [ABSTRACT FROM AUTHOR]

Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, Langkilde A, Petersen J, Pielak T, Møller LN, Jeppesen J, Lyngbæk S, Fenger M, Olsen MH, Hildebrandt PR, Borch-Johnsen K, Jørgensen T, Haugaard SB (Copenhagen University, Hvidovre Hospital, Hvidovre; Copenhagen University Hospital, Glostrup; Copenhagen University Hospital, Copenhagen; Copenhagen University Hospital, Glostrup; Copenhagen University, Hvidovre Hospital, Hvidovre; Steno Diabetes Center, Gentofte; University of Aarhus, Aarhus; University of Copenhagen, Copenhagen; Copenhagen University, Hvidovre Hospital, Hvidovre, Denmark). Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med 2010; 268: 296–308. Background. Low-grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type-2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease. Objective. The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population. Design. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting. General adult Caucasian population. Participants. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements. Blood samples were analysed for suPAR levels using a commercially available enzyme-linked immunosorbent assay. Risk of cancer ( n = 308), CVD ( n = 301), T2D ( n = 59) and mortality ( n = 411) was assessed with a multivariate proportional hazards model using Cox regression. Results. Elevated baseline suPAR level was associated with an increased risk of cancer, CVD, T2D and mortality during follow-up. suPAR was more strongly associated with cancer, CVD and mortality in men than in women, and in younger compared with older individuals. suPAR remained significantly associated with the risk of negative outcome after adjustment for a number of relevant risk factors including C-reactive protein levels. Limitation. Further validation in ethnic populations other than Caucasians is needed. Conclusion. The stable plasma protein suPAR may be a promising biomarker because of its independent association with incident cancer, CVD, T2D and mortality in the general population. [ABSTRACT FROM AUTHOR]

Objective To investigate whether acupuncture has a greater treatment effect than non-penetrating sham acupuncture in women with pelvic girdle pain (PGP) during pregnancy. Design Randomised double-blinded controlled trial. Setting East Hospital, Gothenburg, and 25 antenatal primary care units in the region of Västra Götaland, Sweden. Population A total of 115 pregnant women with a clinical diagnosis of PGP who scored ≥50 on a 100-mm visual analogue scale (VAS). Method Women were randomly allocated to standard treatment plus acupuncture or to standard treatment plus non-penetrating sham acupuncture for 8 weeks. Main outcome measures Main outcome measure was pain. Secondary outcomes were frequency of sick leave, functional status, discomfort of PGP, health-related quality of life and recovery of severity of PGP as assessed by the independent examiner. Results After treatment, median pain decreased from 66 to 36 in the acupuncture group and from 69 to 41 in the non-penetrating sham group ( P = 0.493) as assessed on a VAS. Women in the acupuncture group were in regular work to a higher extent than women in the sham group ( n = 28/57 versus 16/57, P = 0.041). The acupuncture group had superior ability to perform daily activities measured with the disability rating index (DRI) (44 versus 55, P = 0.001). There were no significant differences in quality of life, discomfort of PGP and recovery from severity of PGP between the groups. Conclusions Acupuncture had no significant effect on pain or on the degree of sick leave compared with non-penetrating sham acupuncture. There was some improvement in performing daily activities according to DRI. The data imply that needle penetration contributes to a limited extent to the previously reported beneficial effects of acupuncture. [ABSTRACT FROM AUTHOR]

Objective. An earlier publication showed that acupuncture and stabilising exercises as an adjunct to standard treatment was effective for pelvic girdle pain during pregnancy, but the post-pregnancy effects of these treatment modalities are unknown. The aim of this follow-up study was to describe regression of pelvic girdle pain after delivery in these women. Design. A randomised, single blind, controlled trial. Setting. East Hospital and 27 maternity care centres in Göteborg, Sweden. Population. Some 386 pregnant women with pelvic girdle pain. Methods. Participants were randomly assigned to standard treatment plus acupuncture (n=125), standard treatment plus specific stabilising exercises (n=131) or to standard treatment alone (n=130). Main outcome measures. Primary outcome measures: pain intensity (Visual Analogue Scale). Secondary outcome measure: assessment of the severity of pelvic girdle pain by an independent examiner 12 weeks after delivery. Results. Approximately three-quarters of all the women were free of pain 3 weeks after delivery. There were no differences in recovery between the 3 treatment groups. According to the detailed physical examination, pelvic girdle pain had resolved in 99% of the women 12 weeks after delivery. Conclusions. This study shows that irrespective of treatment modality, regression of pelvic girdle pain occurs in the great majority of women within 12 weeks after delivery. [ABSTRACT FROM AUTHOR]

Background. Use of antipsychotics has been linked with an adverse cardiovascular risk factor profile and an increased risk of dysrhythmia and sudden cardiac death. However, detailed data on the association between use of antipsychotics and development of atherosclerotic disease are limited. Objective. To examine risk of hospitalization for myocardial infarction (MI) amongst users of antipsychotics compared with non-users. Design and subjects. A population-based case–control study using data from hospital discharge registries in the counties of North Jutland, Viborg and Aarhus, Denmark, and the Danish Civil Registration System. We identified 21 377 cases of first-time hospitalization for MI and 106 885 sex- and age-matched non-MI population controls in the period 1992–2004. All prescriptions for antipsychotics filled prior to the date of admission for MI were retrieved from population-based prescription databases. We used conditional logistic regression to adjust for a wide range of covariates. Results. Current users of atypical [adjusted relative risk: 0.98, 95% confidence interval (CI): 0.88–1.09] and typical antipsychotics (adjusted relative risk: 0.99, 95% CI: 0.96–1.03) had no increased overall risk of being admitted to hospital for MI when compared with non-users of antipsychotics. These findings were consistent in all examined subgroups. Further, we found no association between the cumulative dose of antipsychotics and the risk of hospitalization for MI. Conclusion. These findings do not support the hypothesis that use of antipsychotics and in particular atypical antipsychotics is associated with increased risk of MI. [ABSTRACT FROM AUTHOR]

Type 2 diabetic patients with hypertension have an increased left ventricular (LV) mass and impaired cardiac function compared to hypertensive patients without diabetes. However, it is unknown if the impaired cardiac function can be explained solely by LV hypertrophy, or is independently related to diabetes. The aim of the present study was to compare LV function between diabetic and non-diabetic hypertensive patients with electrocardiographic LV hypertrophy. In 937 patients participating in the LIFE echocardiographic substudy, all echocardiograms were centrally evaluated by a core reading centre measuring LV mass, systolic and diastolic LV function. Known diabetes was present in 105 patients. Left ventricular mass was similar in diabetic and non-diabetic patients. Endocardial systolic LV function, estimated by LV ejection fraction, was reduced and indices of midwall systolic LV function were impaired in the diabetic patients. Diastolic LV filling pattern was impaired and arterial stiffness, measured by pulse pressure/stroke index, was increased in diabetic patients. Systolic and diastolic LV function in hypertensive patients with electrocardiographic LV hypertrophy and diabetes are impaired independent of LV mass, most likely reflecting the adverse effects of diabetes per se. Diabet. Med. (2005) [ABSTRACT FROM AUTHOR]

The development of pulmonary granulomatous lesions during mycobacterial infection is a complex phenomenon, in part caused by responses elicited towards the surface glycolipid trehalose 6,6′-dimycolate (TDM; cord factor). The molecular mechanisms underlying granuloma formation following challenge with TDM are not yet completely understood. The present study defines pathologic differences in acute response to Mycobacterium tuberculosis TDM in C57BL/6 mice and mice lacking the C5a receptor (C5aR–/–). Mice were intravenously injected with TDM prepared in water-in-oil-in-water emulsion and examined for histologic response and changes in proinflammatory cytokines and chemokines in lung tissue. Control C5a receptor-sufficient mice demonstrated a granulomatous response that peaked between days 4 and 7. Increased production of macrophage inflammatory protein-1 alpha (MIP-1α), interleukin-1β (IL-1β) and CXC chemokine KC (CXCL1) correlated with development of granulomas, along with modest change in tumor necrosis factor-alpha (TNF-α). In contrast, the C5aR–/– mice revealed markedly exacerbated inflammatory response. The receptor-deficient mice also demonstrated a lack of coherent granulomatous response, with severe oedema present and instances of lymphocytic cuffing around pulmonary vessels. Lung weight index was increased in the C5aR–/– mice, correlating with increased MIP-1α, KC, IL-1β and TNF-α over that identified in the congenic C5aR-sufficient controls. Correlate experiments performed in C5-deficient (B10.D2-H2d H2-T18c Hco/oSnJ) mice revealed similar results, leading to the conclusion that C5 plays a significant role in mediation of chemotactic and activation events that are the basis for maturation of granulomatous responses to TDM. [ABSTRACT FROM AUTHOR]

Charcoal rot, caused by Macrophomina phaseolina, has become increasingly problematic for melon growers using subsurface drip irrigation in Arizona; but has rarely been observed in fields with furrow irrigation. Since the relationship between increasing incidence of charcoal rot on melon and irrigation type is unknown, studies were initiated to determine the effects of edaphic factors on inoculum density. Soil samples were collected once from fields irrigated by subsurface drip, with and without plastic mulch, and by furrow at 10, 20 and 30 cm depths. Samples were analysed for percentage soil moisture, pH, salinity and inoculum density. Percentage soil moisture was significantly higher at 20 and 30 cm depths in the furrow-irrigated field compared with the drip-irrigated field with plastic mulch, but not in the field without plastic mulch. Average minimum and maximum temperatures and inoculum density were significantly lower at all three depths in the furrow-irrigated field compared with both types of drip irrigation. pH was significantly higher in the furrow-irrigated field compared with both types of drip irrigation at 20 and 30 cm depths but not at 10 cm depth. Differences in inoculum densities of M. phaseolina suggest that drip irrigation may contribute to higher disease incidences. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between cumulative CS dose and risk of hip fracture.Design: Population-based case-control design.Subjects and Methods: A total of 6660 subjects with hip fracture and 33,272 age-matched population controls were identified using the County Hospital Discharge Registry in North Jutland County, Denmark and the Danish Central Personal Registry, respectively. Data on redeemed prescriptions for CS within the last 5 years before the index date were retrieved from a population-based prescription database, and recalculated to prednisolone equivalents. Cases and controls were categorized according to cumulative CS dose: (i) no use; (ii) <130 mg (e.g. equivalent to 30 mg of prednisolone for 4 days given for an acute exacerbation of asthma); (iii) 130-499 mg (e.g. equivalent to a short course of prednisolone of 450 mg for acute asthma); (iv) 500-1499 mg (e.g. equivalent to 7.5 mg prednisolone daily for 6 months or 800 microg day(-1) of inhaled budesonide for 1 year); and (v) > or =1500 mg (e.g. equivalent to >4.1 mg day(-1) for 1 year, a long-term high dose). Data were analysed using conditional logistic regression adjusted for potential confounders including gender, redeemed prescriptions for hormone replacement therapy, antiosteoporotic, anxiolytic, antipsychotic and antidepressant drugs.Results: Compared with never users, an increased risk of hip fracture was found for CS users, with increasing cumulative doses of any type of CS use during the preceding 5 years [adjusted odds ratio (OR)=0.96, 95% confidence interval (CI)=0.89-1.04] for <130 mg prednisolone; OR=1.17 (CI=1.01-1.35) for 130-499 mg; OR=1.36 (CI=1.19-1.56) for 500-1499 mg; and OR=1.65 (CI=1.43-1.92) for > or =1500 mg. An increased risk was also found when the study population was stratified according to gender, age and type of CS (systemic or topical).Conclusions: Even a limited daily dose of CS (more than an average dose of approximately 71 microg prednisolone per day) was associated with an increased risk of hip fracture. [ABSTRACT FROM AUTHOR]

Two sympatric subspecies of the xerohalophyte Atriplex canescens Pursh. (Nutt.) were compared for 84 d in out- door salinity trials in their native coastal desert environment in Sonora, Mexico. Subspecies linearis grows naturally on sea water in the high intertidal zone of estuaries while subspecies canescens grows on dunes. In lysimeter pot experiments, ssp. linearis exhibited 50% growth reduction when the mean root zone salinity reached 1160 mol m-3 NaCl compared to just 760 mol m-3 for ssp. canescens. When irrigated with sea water in a flood plot, ssp. linearis had 50% higher growth rates than ssp. canescens. The specialization of ssp. linearis for a saline environment was associated with greater net transport of Nat from root to shoot, greater Na+ accumulation in the leaves and a higher Na:K ratio in the leaves compared to ssp. canescens. On the other hand, the two subspecies achieved approximately the same degree of osmotic adjustment in the leaves, equal to two to three times the external salinity, and had similar water use efficiencies. Even at relatively low salinities, both subspecies accumulated larger quantities of Na+ for osmotic adjustment than K+. The results suggest that breeding for Na+ accumulation rather than exclusion might be the more effective strategy for improving salt tolerance of conventional crop plants. [ABSTRACT FROM AUTHOR]

Male Sprague-Dawley rats, 4 weeks old, were subjected to an ambient temperature of 4 C for periods up to 24 days and fed a synthetic diet containing one of the following oils: peanut oil (PO), rapeseed oil (RO), low erucic acid rapeseed oil (LO), and partially hydrogenated marine oil (HO), each at 20% w/w. A parallel experiment using the same oils was performed at room temperature (23 C). During cold stress, animals on the RO diet showed higher mortality than all other groups; all 20 animals in this group died within 5 days. At room temperature, however, all animals survived. The lipid accumulation in the heart reached its peak in all groups after 3 days and then gradually declined. The accumulation was most pronounced in the RO animals and coincided with the high mortality at 4 C. The fatty acid composition of the cardiac triglycerides reflected that of the diet, while the composition of the cardiac lecithin was only marginally modified. [ABSTRACT FROM AUTHOR]