Multi-proxy record of ocean-climate variability during the last two millennia on the Mackenzie Shelf, Beaufort Sea

A 2,000 year-long oceanographic history, in sub-centennial resolution, from a Canadian Beaufort Sea continental shelf site (60 meters water depth) near the Mackenzie River outlet is reconstructed from ostracode and foraminifera faunal assemblages, shell stable isotopes (δ18O, δ13C) and sediment biogenic silica. The chronology of three sediment cores making up the composite section was established using 137Cs and 210Pb dating for the most recent 150 years and combined with linear interpolation of radiocarbon dates from bivalve shells and foraminifera tests. Continuous centimeter-sampling of the multicore and high-resolution sampling of a gravity and piston core yielded a time-averaged faunal record of every ~40 years from 0 to 1850 CE and every ~24 years from 1850 to 2013 CE. Proxy records were consistent with temperature oscillations and related changes in organic carbon cycling associated with the Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA). Abundance changes in dominant microfossil species, such as the ostracode Paracyprideis pseudopunctillata and agglutinated foraminifers Spiroplectammina biformis and S. earlandi, are used as indicators of less saline, and possibly corrosive/turbid bottom conditions associated with the MCA (~800-1200 CE) and the most recent ~60 years (1950-2013). During these periods, pronounced fluctuations in these species suggest that prolonged seasonal sea-ice melting, changes in riverine inputs and sediment dynamics affected the benthic environment. Taxa analyzed for stable oxygen isotope composition of carbonates show the lowest δ18O values during intervals within the MCA and the highest during the late LIA, which is consistent with a 1° to 2°C cooling of bottom waters. Faunal and isotopic changes during the cooler LIA (1300-1850 CE) are most apparent at ~1500-1850 CE and are particularly pronounced during 1850 to ~1900 CE, with a ~0.5 per mil increase in δ18O values of carbonates from median values in the analyzed taxa. This very cold 50-year period suggests that enhanced summer sea ice suppressed productivity, which is indicated by low sediment biogenic silica values and lower δ13C values in analyzed species. From 1900 CE to present, declines in calcareous faunal assemblages and changes in dominant species (Cassidulina reniforme and P. pseudopunctillata) are associated with less hospitable bottom waters, indicated by a peak in agglutinated foraminifera from 1950-1990 CE

Conflict and Livelihood Decisions in the Chittagong Hill Tracts of Bangladesh

__Abstract__ We analyse rural household livelihood and child school enrolment decisions in the post-conflict setting of the Chittagong Hill Tracts (CHT) region of Bangladesh. What makes this paper innovative is the use of current subjective perceptions regarding the possibility of violence in the future and past actual experiences of violence in explaining household economic decision-making. Preferences are endogenous in line with behavioural economics. Regression results show that heightened subjective perceptions of future violence and past actual experiences of conflict influence current consumption and child enrolment and could encourage risky mixed crop cultivation. The trauma emanating from past experiences combined with current high perceptions of risk of violence may induce bolder and riskier behaviour in line with prospect theories of risk. Furthermore, a postconflic

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

First measurement of the cross-correlation of CMB lensing and galaxy lensing

We measure the cross-correlation of cosmic microwave background (CMB) lensing convergence maps derived from Atacama Cosmology Telescope data with galaxy lensing convergence maps as measured by the Canada-France-Hawaii Telescope Stripe 82 Survey. The CMB-galaxy lensing cross power spectrum is measured for the first time with a significance of 4.2σ, which corresponds to a 12% constraint on the amplitude of density fluctuations at redshifts ∼0.9. With upcoming improved lensing data, this novel type of measurement will become a powerful cosmological probe, providing a precise measurement of the mass distribution at intermediate redshifts and serving as a calibrator for systematic biases in weak lensing measurements

Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.

BACKGROUND: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. METHODS: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. RESULTS: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. CONCLUSION: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development

Two-season Atacama Cosmology Telescope polarimeter lensing power spectrum

© 2017 American Physical Society. We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck ΛCDM model over a range of multipoles L=80-2100, with an amplitude of lensing Alens=1.06±0.15(stat)±0.06(sys) relative to Planck. Our measurement of the CMB lensing power spectrum gives σ8Ωm0.25=0.643±0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be σ8=0.831±0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol data set.This work was supported by the U.S. National Science Foundation (NSF) through Grants. No. AST-1440226, No. AST-0965625 and No. AST-0408698 for the ACT project, as well as Grants No. PHY-1214379 and No. PHY-0855887. Funding was also provided by Princeton University, the University of Pennsylvania, and a Canada Foundation for Innovation (CFI) grant to U. B. C. A. C. T. operates in the Parque Astronómico Atacama in northern Chile under the auspices of the Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT). Computations were performed on the GPC supercomputer at the SciNet HPC Consortium. SciNetis funded bytheCFI under the auspices of Compute Canada, the Government of Ontario, the Ontario Research Fund Research Excellence, and the University of Toronto. The development of multichroic detectors and lenses was supported by NASA Grants No. NNX13AE56G and No. NNX14AB58G. N. S. acknowledges support from NSF Grant No. 1513618. A. K. has been supported by NSF Grant No. AST-1312380. R. D. and L. M. thank CONICYT for Grants No. ALMA-CONICYT 31140004, No. FONDECYT 1141113, No. Anillo ACT-1417 and BASAL CATA. We also thank the Mishrahi Fund and the Wilkinson Fund for their generous support of the project

Generation of Covalently Closed Circular DNA of Hepatitis B Viruses via Intracellular Recycling Is Regulated in a Virus Specific Manner

Persistence of hepatitis B virus (HBV) infection requires covalently closed circular (ccc)DNA formation and amplification, which can occur via intracellular recycling of the viral polymerase-linked relaxed circular (rc) DNA genomes present in virions. Here we reveal a fundamental difference between HBV and the related duck hepatitis B virus (DHBV) in the recycling mechanism. Direct comparison of HBV and DHBV cccDNA amplification in cross-species transfection experiments showed that, in the same human cell background, DHBV but not HBV rcDNA converts efficiently into cccDNA. By characterizing the distinct forms of HBV and DHBV rcDNA accumulating in the cells we find that nuclear import, complete versus partial release from the capsid and complete versus partial removal of the covalently bound polymerase contribute to limiting HBV cccDNA formation; particularly, we identify genome region-selectively opened nuclear capsids as a putative novel HBV uncoating intermediate. However, the presence in the nucleus of around 40% of completely uncoated rcDNA that lacks most if not all of the covalently bound protein strongly suggests a major block further downstream that operates in the HBV but not DHBV recycling pathway. In summary, our results uncover an unexpected contribution of the virus to cccDNA formation that might help to better understand the persistence of HBV infection. Moreover, efficient DHBV cccDNA formation in human hepatoma cells should greatly facilitate experimental identification, and possibly inhibition, of the human cell factors involved in the process

The establishment of the Standard Cosmological Model through observations

Over the last decades, observations with increasing quality have revolutionized our understanding of the general properties of the Universe. Questions posed for millenia by mankind about the origin, evolution and structure of the cosmos have found an answer. This has been possible mainly thanks to observations of the Cosmic Microwave Background, of the large-scale distribution of matter structure in the local Universe, and of type Ia supernovae that have revealed the accelerated expansion of the Universe. All these observations have successfully converged into the so-called "concordance model". In spite of all these observational successes, there are still some important open problems, the most obvious of which are what generated the initial matter inhomogeneities that led to the structure observable in today's Universe, and what is the nature of dark matter, and of the dark energy that drives the accelerated expansion. In this chapter I will expand on the previous aspects. I will present a general description of the Standard Cosmological Model of the Universe, with special emphasis on the most recent observations that have us allowed to consolidate this model. I will also discuss the shortfalls of this model, its most pressing open questions, and will briefly describe the observational programmes that are being planned to tackle these issues.Comment: Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p