Palaeoecological investigation of the past biological structure and function of the Trinity Broads

This is the final report to the Trinity Broads Partnership on the ‘Palaeoecological investigation of the past biological structure and function in the Trinity Broads’. The Trinity Broads are deeper and discrete from much of the rest of the Norfolk Broads and there has therefore been much speculation that their biology was different from the Broads in other river basins. The aim of the project was to employ palaeoecological techniques to investigate the past biological structure and function of the Broads, in particular the past aquatic flora

Palaeoecological study of Rockland Broad

The decline in ecological quality and conservation value of European fresh waters is an all too common phenomenon. In lowland Britain the main anthropogenic impact on aquatic systems is that associated with elevated nutrient loading. The Broads are internationally important wetlands spanning a number of river basins in East Anglia. The Broads have suffered, along with other wetlands, and it is chiefly eutrophication that has had a deleterious effect on the system (Mason & Bryant 1975, Moss 1977) with a resultant decline in their ecological quality and conservation value. One of the changes in the ecological structure and functioning of shallow lakes in response to enrichment is an alteration in their macrophyte flora (Ris & Sand-Jensen 2001) and in extreme cases there may be the complete loss of submerged plants (Scheffer et al. 1993). The loss of the diversity of the macrophyte flora in the Broads is perhaps the main factor in the decline in their conservation value

Practical approaches to Bayesian sample size determination in non-inferiority trials with binary outcomes.

Bayesian analysis of a non-inferiority trial is advantageous in allowing direct probability statements to be made about the relative treatment difference rather than relying on an arbitrary and often poorly justified non-inferiority margin. When the primary analysis will be Bayesian, a Bayesian approach to sample size determination will often be appropriate for consistency with the analysis. We demonstrate three Bayesian approaches to choosing sample size for non-inferiority trials with binary outcomes and review their advantages and disadvantages. First, we present a predictive power approach for determining sample size using the probability that the trial will produce a convincing result in the final analysis. Next, we determine sample size by considering the expected posterior probability of non-inferiority in the trial. Finally, we demonstrate a precision-based approach. We apply these methods to a non-inferiority trial in antiretroviral therapy for treatment of HIV-infected children. A predictive power approach would be most accessible in practical settings, because it is analogous to the standard frequentist approach. Sample sizes are larger than with frequentist calculations unless an informative analysis prior is specified, because appropriate allowance is made for uncertainty in the assumed design parameters, ignored in frequentist calculations. An expected posterior probability approach will lead to a smaller sample size and is appropriate when the focus is on estimating posterior probability rather than on testing. A precision-based approach would be useful when sample size is restricted by limits on recruitment or costs, but it would be difficult to decide on sample size using this approach alone

Islands of conformational stability for Filopodia

Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of . We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work

Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis

Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis. Following induction of EAV on day 0, a sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies to glomerular basement membrane was administered on day 14. This resulted in a significant increase in disease severity at day 28 compared to MPO immunisation alone - with more urinary abnormalities, infiltrating glomerular leucocytes, and crescent formation that progressed to glomerular and tubulointerstitial scarring by day 56, recapitulating important features of human disease. Importantly, the glomerulonephritis remained pauci-immune, and was strictly dependent on the presence of autoimmunity to MPO, as there was no evidence of renal disease following administration of sub-nephritogenic NTS alone or after immunisation with a control protein in place of MPO. Detailed phenotyping of glomerular leucocytes identified an early infiltrate of non-classical monocytes following NTS administration that, in the presence of autoimmunity to MPO, may initiate the subsequent influx of classical monocytes which augment glomerular injury. We also showed that this model can be used to test novel therapeutics by using a small molecule kinase inhibitor (fostamatinib) that rapidly attenuated both glomerular and pulmonary injury over a four-day treatment period. We believe that this enhanced model of MPO-AAV will prove useful for the study of glomerular leucocyte behaviour and novel therapeutics in AAV in the future. This article is protected by copyright. All rights reserved

Medical causes of admissions to hospital among adults in Africa: a systematic review.

BACKGROUND: Despite the publication of several studies on the subject, there is significant uncertainty regarding the burden of disease among adults in sub-Saharan Africa (sSA). OBJECTIVES: To describe the breadth of available data regarding causes of admission to hospital, to systematically analyze the methodological quality of these studies, and to provide recommendations for future research. DESIGN: We performed a systematic online and hand-based search for articles describing patterns of medical illnesses in patients admitted to hospitals in sSA between 1950 and 2010. Diseases were grouped into bodily systems using International Classification of Disease (ICD) guidelines. We compared the proportions of admissions and deaths by diagnostic category using χ2. RESULTS: Thirty articles, describing 86,307 admissions and 9,695 deaths, met the inclusion criteria. The leading causes of admission were infectious and parasitic diseases (19.8%, 95% confidence interval [CI] 19.6-20.1), respiratory (16.2%, 95% CI 16.0-16.5) and circulatory (11.3%, 95% CI 11.1-11.5) illnesses. The leading causes of death were infectious and parasitic (17.1%, 95% CI 16.4-17.9), circulatory (16%, 95% CI 15.3-16.8) and digestive (16.2%, 95% CI 15.4-16.9). Circulatory diseases increased from 3.9% of all admissions in 1950-59 to 19.9% in 2000-2010 (RR 5.1, 95% CI 4.5-5.8, test for trend p<0.00005). The most prevalent methodological deficiencies, present in two-thirds of studies, were failures to use standardized case definitions and ICD guidelines for classifying illnesses. CONCLUSIONS: Cardiovascular and infectious diseases are currently the leading causes of admissions and in-hospital deaths in sSA. Methodological deficiencies have limited the usefulness of previous studies in defining national patterns of disease in adults. As African countries pass through demographic and health transition, they need to significantly invest in clinical research capacity to provide an accurate description of the disease burden among adults for public health policy

Orbital Elements and Stellar Parameters of the Active Binary UX Arietis

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.Stellar activity observed as large surface spots, radio flares, or emission lines is often found in binary systems. UX Arietis exhibits these signs of activity, originating on the K0 subgiant primary component. Our aim is to resolve the binary, measure the orbital motion, and provide accurate stellar parameters such as masses and luminosities to aid in the interpretation of the observed phenomena. Using the CHARA six-telescope optical long-baseline array on Mount Wilson, California, we obtained amplitudes and phases of the interferometric visibility on baselines up to 330 m in length, resolving the two components of the binary. We reanalyzed archival Center for Astrophysics spectra to disentangle the binary component spectra and the spectrum of the third component, which was resolved by speckle interferometry. We also obtained new spectra with the Nordic Optical Telescope, and we present new photometric data that we use to model stellar surface spot locations. Both interferometric visibilities and spectroscopic radial velocities are modeled with a spotted primary stellar surface using the Wilson–Devinney code. We fit the orbital elements to the apparent orbit and radial velocity data to derive the distance (52.1 ± 0.8 pc) and stellar masses (MP = 1.30 0.06 M, MS = 1.14 0.06 M). The radius of the primary can be determined to be RP = 5.6 0.1 R and that of the secondary to be RS = 1.6 0.2 R. The equivalent spot coverage of the primary component was found to be 62% with an effective temperature 20% below that of the unspotted surface.We thank Robert Wilson (University of Florida) for providing a custom version of his code to compute images of spotted stellar surfaces and for his help with using it. This work is based upon observations obtained with the Georgia State University (GSU) Center for High Angular Resolution Astronomy (CHARA) array at Mount Wilson Observatory. The CHARA array is supported by the National Science Foundation under grant numbers AST-1211929 and AST-1411654. Institutional support has been provided by the GSU College of Arts and Sciences and the GSU Office of the Vice President for Research and Economic Development. The MIRC instrument at the CHARA array was funded by the University of Michigan. F.B., R.R., and J.D.M. acknowledge support from NSF-AST 1210972 and 1108963. G.T. acknowledges partial support from NSF grant AST-1509375. S.K. acknowledges support from an STFC Rutherford Fellowship (ST/J004030/1) and ERC Starting Grant (grant agreement no. 639889). This work is also based on observations made with the Nordic Optical Telescope (NOT), operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This research has made use of the SIMBAD database, operated at the CDS, Strasbourg, France. This research has made use of the Jean-Marie Mariotti Center SearchCal service13 codeveloped by FIZEAU and LAOG/IPAG and of the CDS astronomical databases SIMBAD and VIZIER.14 This research has made use of the Washington Double Star Catalog, maintained at the U.S. Naval Observatory. We thank Nicholas Elias II for discussions. We thank Dimitri Pourbaix for maintaining and providing access to the SB9 database of RV measurements of spectroscopic binaries

Prevalence and phase variable expression status of two autotransporters, NalP and MspA, in carriage and disease isolates of Neisseria meningitidis.

Neisseria meningitidis is a human nasopharyngeal commensal capable of causing life-threatening septicemia and meningitis. Many meningococcal surface structures, including the autotransporter proteins NalP and MspA, are subject to phase variation (PV) due to the presence of homopolymeric tracts within their coding sequences. The functions of MspA are unknown. NalP proteolytically cleaves several surface-located virulence factors including the 4CMenB antigen NhbA. Therefore, NalP is a phase-variable regulator of the meningococcal outer membrane and secretome whose expression may reduce isolate susceptibility to 4CMenB-induced immune responses. To improve our understanding of the contributions of MspA and NalP to meningococcal-host interactions, their distribution and phase-variable expression status was studied in epidemiologically relevant samples, including 127 carriage and 514 invasive isolates representative of multiple clonal complexes and serogroups. Prevalence estimates of >98% and >88% were obtained for mspA and nalP, respectively, with no significant differences in their frequencies in disease versus carriage isolates. 16% of serogroup B (MenB) invasive isolates, predominately from clonal complexes ST-269 and ST-461, lacked nalP. Deletion of nalP often resulted from recombination events between flanking repetitive elements. PolyC tract lengths ranged from 6-15 bp in nalP and 6-14 bp in mspA. In an examination of PV status, 58.8% of carriage, and 40.1% of invasive nalP-positive MenB isolates were nalP phase ON. The frequency of this phenotype was not significantly different in serogroup Y (MenY) carriage strains, but was significantly higher in invasive MenY strains (86.3%; p<0.0001). Approximately 90% of MenB carriage and invasive isolates were mspA phase ON; significantly more than MenY carriage (32.7%) or invasive (13.7%) isolates. This differential expression resulted from different mode mspA tract lengths between the serogroups. Our data indicates a differential requirement for NalP and MspA expression in MenB and MenY strains and is a step towards understanding the contributions of phase-variable loci to meningococcal biology

The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig