Cosmogenic nuclides indicate that boulder fields are dynamic, ancient, multigenerational features

Boulder fields are found throughout the world; yet, the history of these features, as well as the processes that form them, remain poorly understood. In high and mid-latitudes, boulder fields are thought to form and be active during glacial periods; however, few quantitative data support this assertion. Here, we use in situ cosmogenic 10Be and 26Al to quantify the near-surface history of 52 samples in and around the largest boulder field in North America, Hickory Run, in central Pennsylvania, USA. Boulder surface 10Be concentrations (n = 43) increase downslope, indicate minimum near-surface histories of 70-600 k.y., and are not correlated with lithology or boulder size. Measurements of samples from the top and bottom of one boulder and three underlying clasts as well as 26Al/10Be ratios (n = 25) suggest that at least some boulders have complex exposure histories caused by flipping and/or cover by other rocks, soil, or ice. Cosmogenic nuclide data demonstrate that Hickory Run, and likely other boulder fields, are dynamic features that persist through multiple glacial-interglacial cycles because of boulder resistance to weathering and erosion. Long and complex boulder histories suggest that climatic interpretations based on the presence of these rocky landforms are likely over simplifications

Low-temperature thermochronometry along the Kunlun and Haiyuan Faults, NE Tibetan Plateau: Evidence for kinematic change during late-stage orogenesis

The Tibetan Plateau is a prime example of a collisional orogen with widespread strike-slip faults whose age and tectonic significance remain controversial. We present new low-temperature thermochronometry to date periods of exhumation associated with Kunlun and Haiyuan faulting, two major strike-slip faults within the northeastern margin of Tibet. Apatite and zircon (U-Th)/He and apatite fission-track ages, which record exhumation from ∼2 to 6 km crustal depths, provide minimum bounds on fault timing. Results from Kunlun samples show increased exhumation rates along the western fault segment at circa 12-8 Ma with a possible earlier phase of motion from ∼30-20 Ma, along the central fault segment at circa 20-15 Ma, and along the eastern fault segment at circa 8-5 Ma. Combined with previous studies, our results suggest that motion along the Haiyuan fault may have occurred as early as ∼15 Ma along the western/central fault segment before initiating at least by 10-8 Ma along the eastern fault tip. We relate an ∼250 km wide zone of transpressional shear to synchronous Kunlun and Haiyuan fault motion and suggest that the present-day configuration of active faults along the northeastern margin of Tibet was likely established since middle Miocene time. We interpret the onset of transpression to relate to the progressive confinement of Tibet against rigid crustal blocks to the north and expansion of crustal thickening to the east during the later stages of orogen development. Key Points Low-T thermochronometry dates periods of exhumation along NE Tibet faults Left-lateral faulting by mid-to-late Miocene along the Kunlun and Haiyuan Faults Shift to widespread lateral faulting in late stage of Tibet collisional histor

Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis

Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA Bank and all samples available underwent whole genome sequencing. A replication set from the Netherlands was used for validation. Sequences of candidate survival genes were extracted and variants passing quality control with a minor allele frequency ≤0.05 were selected for association testing. Analysis was by burden testing using SKAT. Candidate survival genes UNC13A, KIFAP3, and EPHA4 were tested for association in a UK sample comprising 25 short survivors and 25 long survivors. Results showed that only SNVs in UNC13A were associated with survival (p = 6.57 × 10−3). SNV rs10419420:G > A was found exclusively in long survivors (3/25) and rs4808092:G > A exclusively in short survivors (4/25). These findings were not replicated in a Dutch sample. In conclusion, population specific rare variants of UNC13A may modulate survival in ALS

The Tug1 locus is essential for male fertility

Background: Several long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge. Results: We previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities - two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential. Conclusions: Our results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci

Shape programming for narrow ribbons of nematic elastomers

Using the theory of Γ-convergence, we derive from three-dimensional elasticity new one-dimensional models for non-Euclidean elastic ribbons, i.e., ribbons exhibiting spontaneous curvature and twist. We apply the models to shape-selection problems for thin films of nematic elastomers with twist and splay-bend texture of the nematic director. For the former, we discuss the possibility of helicoid-like shapes as an alternative to spiral ribbons

Existence of a continental-scale river system in eastern Tibet during the late Cretaceous–early Palaeogene

The establishment of continental-scale drainage systems on Earth is largely controlled by topography related to plate boundary deformation and buoyant mantle. Drainage patterns of the great rivers in Asia are thought to be highly dynamic during the Cenozoic collision of India and Eurasia, but the drainage pattern and landscape evolution prior to the development of high topography in eastern Tibet remain largely unknown. Here we report the results of petro-stratigraphy, heavy-mineral analysis, and detrital zircon U-Pb dating from late Cretaceous–early Palaeogene sedimentary basin strata along the present-day eastern margin of the Tibetan Plateau. Similarities in the provenance signatures among basins indicate that a continental-scale fluvial system once drained southward into the Neo-Tethyan Ocean. These results challenge existing models of drainage networks that flowed toward the East Asian marginal seas and require revisions to inference of palaeo-topography during the Late Cretaceous. The presence of a continent-scale river may have provided a stable long-term base level which, in turn, facilitated the development of an extensive low-relief landscape that is preserved atop interfluves above the deeply incised canyons of eastern Tibet

The growth of northeastern Tibet and its relevance to large-scale continental geodynamics: A review of recent studies

Recent studies of the northeastern part of the Tibetan Plateau have called attention to two emerging views of how the Tibetan Plateau has grown. First, deformation in northern Tibet began essentially at the time of collision with India, not 10-20 Myr later as might be expected if the locus of activity migrated northward as India penetrated the rest of Eurasia. Thus, the north-south dimensions of the Tibetan Plateau were set mainly by differences in lithospheric strength, with strong lithosphere beneath India and the Tarim and Qaidam basins steadily encroaching on one another as the region between them, the present-day Tibetan Plateau, deformed, and its north-south dimension became narrower. Second, abundant evidence calls for acceleration of deformation, including the formation of new faults, in northeastern Tibet since ~15 Ma and a less precisely dated change in orientation of crustal shortening since ~20 Ma. This reorientation of crustal shortening and roughly concurrent outward growth of high terrain, which swings from NNE-SSW in northern Tibet to more NE-SW and even ENE-WSW in the easternmost part of northeastern Tibet, are likely to be, in part, a consequence of crustal thickening within the high Tibetan Plateau reaching a limit, and the locus of continued shortening then migrating to the northeastern and eastern flanks. These changes in rates and orientation also could result from removal of some or all mantle lithosphere and increased gravitational potential energy per unit area and from a weakening of crustal material so that it could flow in response to pressure gradients set by evolving differences in elevation. Key Points The north-south limits of Tibet were set by lateral variations in strength Roughly 15 million years ago, deformation of NE Tibet accelerated Since 20-15 million years ago, the orientation of shortening rotated eastwar

The growth of northeastern Tibet and its relevance to large-scale continental geodynamics: A review of recent studies

Recent studies of the northeastern part of the Tibetan Plateau have called attention to two emerging views of how the Tibetan Plateau has grown. First, deformation in northern Tibet began essentially at the time of collision with India, not 10-20 Myr later as might be expected if the locus of activity migrated northward as India penetrated the rest of Eurasia. Thus, the north-south dimensions of the Tibetan Plateau were set mainly by differences in lithospheric strength, with strong lithosphere beneath India and the Tarim and Qaidam basins steadily encroaching on one another as the region between them, the present-day Tibetan Plateau, deformed, and its north-south dimension became narrower. Second, abundant evidence calls for acceleration of deformation, including the formation of new faults, in northeastern Tibet since ~15 Ma and a less precisely dated change in orientation of crustal shortening since ~20 Ma. This reorientation of crustal shortening and roughly concurrent outward growth of high terrain, which swings from NNE-SSW in northern Tibet to more NE-SW and even ENE-WSW in the easternmost part of northeastern Tibet, are likely to be, in part, a consequence of crustal thickening within the high Tibetan Plateau reaching a limit, and the locus of continued shortening then migrating to the northeastern and eastern flanks. These changes in rates and orientation also could result from removal of some or all mantle lithosphere and increased gravitational potential energy per unit area and from a weakening of crustal material so that it could flow in response to pressure gradients set by evolving differences in elevation. Key Points The north-south limits of Tibet were set by lateral variations in strength Roughly 15 million years ago, deformation of NE Tibet accelerated Since 20-15 million years ago, the orientation of shortening rotated eastwar

Exposure to potentially inappropriate medications in Brazilian elderly outpatients with metabolic diseases

ABSTRACT Management of pharmacotherapy in elderly with metabolic diseases is challenging and potentially inappropriate medications (PIMs) are risk factors for drug interactions and adverse events. The exposure to PIMs in elderly outpatients with metabolic diseases and its relationship with polypharmacy and other variables was investigated. PIMs prescribed to 207 elderly patients (aged 60 to 96 years) with metabolic diseases who attended a University Hospital of Sao Paulo city, Brazil, from April/2010 to January/2011, were evaluated. PIMs were detected using both 2003 Beers and 2008 STOPP criteria. The association between PIMs and age, gender and polypharmacy was also examined. 2008 STOPP criteria detected more PIMs (44.4 %) than 2003 Beers criteria (16.0%, p<0.001). Beers detected mainly PIMs antihypertensive (clonidine, 20.0%; doxazosin, 10.0%) and antidepressant (fluoxetine, 15.0%; amitriptyline, 10.0%) PIMs. Medicines used for cardiovascular (aspirin, 53.7%) and endocrine system (glibenclamide, 21.3%) were PIMs more frequently detected by 2008 STOPP. Unlike age and gender, polypharmacy increased the risk of PIMs by both 2003 Beers (OR: 4.0, CI95%: 1.2-13.8, p<0.031) and 2008 STOPP (OR: 6.8, CI95%: 3.0-15.3, p<0.001). Beers and STOPP criteria are important tools to evaluate the exposure to PIMs, which is strongly associated with polypharmacy in elderly outpatients with metabolic diseases

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

Background Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. Methods The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. Findings Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69–234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04–74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37–2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. Interpretation Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. Funding Bill & Melinda Gates Foundation