Post-IR IRSL Dating of the Nenana Dune Field in the Tanana Lowlands, central Alaska

Sand dunes record paleoclimatic change within their stratigraphy as they respond to climatic shifts through sequences of activation and stabilization. Developing chronologies documenting periods of dune activity and stabilization can thus provide information about past climatic conditions. Consequently, the need for accurate chronological determinations of aeolian features has stimulated the advancement of dating techniques. In Alaskan sand dune settings, radiocarbon dating of organic material and optical dating of quartz grains have proven to be problematic due to insufficient organic material and a weak optical signal, respectively. In such cases, feldspar grains can be dated using Infrared Stimulated Luminescence (IRSL) dating, but are often avoided due to inherent anomalous fading that results in age underestimation. The lack of a viable dating technique has resulted in a paucity of chronostratigraphic Alaskan dune studies, particularly within central Alaska. This research tests the use of a post-infrared (pIR) IRSL protocol, specifically designed to limit the effects of anomalous fading, on the Nenana dune field within the Tanana River Lowlands of central Alaska. Results indicate that dune activity occurred as far back as ~16 ka for the Nenana dunes, as deglaciation of the surrounding area provided an influx of sediment into glacial streams throughout the Tanana River Lowlands. IRSL ages indicate a switch from sand to silt accumulation between 11 ka and 10 ka and stabilization of the dune field that is likely tied to the spread of boreal forest throughout the region around this time. These IRSL ages align with regional proxy data indicating similar timing of activation and stabilization of aeolian features during the transition between the Late Pleistocene and early Holocene. This research represents one of the first IRSL sand dune studies of central Alaska and supports further use of a pIR IRSL protocol to expand aeolian research within Alaska

Encounters: Handling, Placing and Looking at Photographs in Relation to Migration

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Pediatric Plastic Bronchitis: Case Report and Retrospective Comparative Analysis of Epidemiology and Pathology

Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%

Physical activity promotion in physiotherapy practice: a systematic scoping review of a decade of literature

Background: The health benefits of physical activity (PA) have been extensively documented. Globally PA levels are low with only a small proportion of the population reaching recommended levels. Insufficient PA is seen as a major public health problem with high cost to society. Physiotherapists work with people to manage long-term conditions and are well-placed to deliver individual interventions to increase PA. Despite this little is known about the evidence that exists in this field. Methods: This scoping review comprises a comprehensive search of key databases using pre-determined search terms. This is supplemented with a parallel search that incorporated novel social media strands. In-line with current guidance, a robust screening process took place using agreed inclusion and exclusion criteria. Results: Thirty one studies met the inclusion criteria. The number of studies published annually increased over the decade. Ireland and USA yielded the largest number of publications with only one study from the UK. The target populations included physiotherapists and service users from a range of clinical populations. The studies were mainly quantitative and observational in design with a predominance of studies that scoped attitudes, perceptions, barriers and current practice. Conclusions: This reconnaissance has shown the state of the evidence to be sparse and disparate. However, the sharp rise in published work in recent years is encouraging. The predominance of scoping studies and the clear social, economic and political drivers for change in this area highlights a need for more pragmatic, interventional studies that can inform clinical practice

Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS)

Background: Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa). Methods: PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results: Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. Conclusion: This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®).This study was funded by Janssen, Pharmaceutical Companies of Johnson & Johnson

A case for the standardized letter of recommendation in otolaryngology residency selection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102208/1/lary24431.pd

Natural proteome diversity links aneuploidy tolerance to protein turnover

Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy—an imbalance in chromosome copy numbers—is frequent1, 2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory3–5. Here we generate a proteomic resource and merge it with genomic1 and transcriptomic6 data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins—especially subunits of protein complexes—show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes

DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon

Genetic variants in the DNA methyltransferase 3 A (DNMT3A) locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function. DNMT3A expression is downregulated in intestinal epithelial cells from IBD patients and upon tumor necrosis factor treatment in murine intestinal organoids. Ablation of DNMT3A in Caco-2 cells results in global DNA hypomethylation, which is linked to impaired regenerative capacity, transepithelial resistance and intercellular junction formation. Genetic deletion of Dnmt3a in intestinal epithelial cells (Dnmt3aΔIEC) in mice confirms the phenotype of an altered epithelial ultrastructure with shortened apical-junctional complexes, reduced Goblet cell numbers and increased intestinal permeability in the colon in vivo. Dnmt3aΔIEC mice suffer from increased susceptibility to experimental colitis, characterized by reduced epithelial regeneration. These data demonstrate a critical role for DNMT3A in orchestrating intestinal epithelial homeostasis and response to tissue damage and suggest an involvement of impaired epithelial DNMT3A function in the etiology of IBD