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Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls. In this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls. Over an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17-1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk. All males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls.

Background Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk. Methods A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality. Results Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality. Conclusion Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.

Objectives Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases. Methods This consensus paper was discussed by an expert panel at The Interventional Oncology Sans Frontières 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented. Results Specific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable. Conclusions In the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology. Key Points • Best results require due consideration of tumour size, number, volume and location. • Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. • Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. • Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. • Future applications may include resectable disease, e.g. for small solitary tumours.

The weathering rate of carbonate minerals is several orders of magnitude higher than for silicate minerals. Therefore, small amounts of carbonate minerals have the potential to control the dissolved weathering loads in silicate-dominated catchments. Both weathering processes produce alkalinity under the consumption of CO2. Given that only alkalinity generation from silicate weathering is thought to be a long-term sink for CO2, a misattributed weathering source could lead to incorrect conclusions about long- and short-term CO2 fixation. In this study, we aimed to identify the weathering sources responsible for alkalinity generation and CO2 fixation across watershed scales in a degrading permafrost landscape in northern Norway, 68.7–70.5∘ N, and on a temporal scale, in a subarctic headwater catchment on the mountainside of Iskorasfjellet, characterized by sporadic permafrost and underlain mainly by silicates as the alkalinity-bearing lithology. By analyzing total alkalinity (AT) and dissolved inorganic carbon (DIC) concentrations, as well as the stable isotope signature of the latter (δ13C-DIC), in conjunction with dissolved cation and anion loads, we found that AT was almost entirely derived from weathering of the sparse carbonate minerals. We propose that in the headwater catchment the riparian zone is a hotspot area of AT generation and release due to its enhanced hydrological connectivity and that the weathering load contribution from the uphill catchment is limited by insufficient contact time of weathering agents and weatherable materials. By using stable water isotopes, it was possible to explain temporal variations in AT concentrations following a precipitation event due to surface runoff. In addition to carbonic acid, sulfuric acid, probably originating from oxidation of pyrite or reduced sulfur in wetlands or from acid deposition, is shown to be a potential corrosive reactant. An increased proportion of sulfuric acid as a potential weathering agent may have resulted in a decrease in AT. Therefore, carbonate weathering in the studied area should be considered not only as a short-term CO2 sink but also as a potential CO2 source. Finally, we found that AT increased with decreasing permafrost probability, and attributed this relation to an increased water storage capacity associated with increasing contact of weathering agent and rock surfaces and enhanced microbial activity. As both soil respiration and permafrost thaw are expected to increase with climate change, increasing the availability of weathering agents in the form of CO2 and water storage capacity, respectively, we suggest that future weathering rates and alkalinity generation will increase concomitantly in the study area.

The use of permutation methods for exact inference dates back to Fisher in 1935. Since then, the practicality of such methods has increased steadily with computing power. They can now easily be employed in many situations without concern for computing difficulties. We discuss the reasoning behind these methods and describe situations when they are exact and distribution-free. We illustrate their use in several examples.

Background: The aim was to improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance multiparametric ultrasound examination techniques. Methods: Multiparametric ultrasound consists of B-mode, shear-wave elastography and contrast enhanced ultrasound (CEUS) including Time-Intensity-Curve (TIC) analysis. A bolus of 1–2.4 mL Sulfur Hexafluorid microbubbles was injected for CEUS. Postoperative histopathology was the diagnostic gold standard. Results: 116 patients were included in this study. 102 benign thyroid nodules were diagnosed as well as 20 carcinomas. Suspicious B-mode findings like microcalcifications, a blurry edge and no homogeneous sonomorphological structure were detected in 60, 75 and 80% of all carcinomas but only in 13.7, 36.3 and 46.1% of all benign lesions. The average shear-wave elastography measurements of malignant lesions (4.6 m/s or 69.8 kPa centrally and 4.2 m/s or 60.1 kPa marginally) exceed the values of benign nodules. Suspicious CEUS findings like a not-homogeneous wash-in and a wash-out were detected almost twice as often in carcinomas. Conclusion: Multiparametric ultrasound offers new possibilities for the preoperative distinction between benign and malignant thyroid nodules. A score based system of B-mode, shear-wave and CEUS malignancy criteria shows promising results in the detection of thyroid carcinomas. It reaches a sensitivity of 95% and specificity of 75.49%.

The Chicxulub asteroid impact event at the Cretaceous-Paleogene (K-Pg) boundary ~66 Myr ago is widely considered responsible for the mass extinction event leading to the demise of the non-avian dinosaurs. Short-term cooling due to massive release of climate-active agents is hypothesized to have been crucial, with S-bearing gases originating from the target rock vaporization considered an important driving force. Yet, the magnitude of the S release remains poorly constrained. Here we empirically estimate the amount of impact-released S relying on the concentration of S and its isotopic composition within the impact structure and a set of terrestrial K-Pg boundary ejecta sites. The average value of 67 ± 39 Gt obtained is ~5-fold lower than previous numerical estimates. The lower mass of S-released may indicate a less prominent role for S emission leading to a milder impact winter with key implications for species survival during the first years following the impact. The amount of S released by the Chicxulub impact event is empirically determined to be 5 times lower than previously estimated, with important consequences for our understanding of the climate cooling that ultimately led to the K-Pg mass extinction.

The Drewer quarry located in the Rhenish Massif is a well-studied outcrop that comprises Upper Devonian (Famennian) to Lower Carboniferous (Viséan) strata. Within the Drewer deposits two black shale intervals have been described that are linked to two global oceanic anoxic events, the Hangenberg Event and the Lower Alum Shale Event. The black shales associated with the Middle Tournaisian Lower Alum Shale Event contain abundant phosphatic concretions, which were investigated using thin section petrography, powder X-ray diffraction, Fourier-transform infrared spectrometry and scanning electron microscopy. The concretions formed during several growth phases under anoxic and at least episodically sulphidic conditions within the sediment and served as a substrate for subsurface microbial mats that formed phosphatic microstromatolites. The microstromatolites occur either as partially branched columns of up to 600 µm in length attached to the phosphatic concretions or as smaller, bulbous aggregates surrounding the concretions. Element mapping identified the presence of pyrite and other metal sulphides within the phosphatic microstromatolites. The carbon and oxygen stable isotopic composition of phosphate-associated carbonate within the phosphatic microstromatolites suggests that the mat-forming microorganisms were probably anaerobic, chemotrophic microbial communities dwelling in the anoxic environment during the Lower Alum Shale Event. Such interpretation agrees with the deeper-water depositional setting of the Lower Alum Black Shale and its high content of organic matter, suggesting that chemotrophic microbial mats are potent agents of phosphogenesis in general, and of the formation of phosphatic stromatolites in particular.