Viral dynamics of acute HIV-1 infection.

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R(0)), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (alpha) was highly variable among individuals. The phase 1 viral decay rate (delta(I) = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R(0)) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection

The coastal marine mollusc fauna of King Island, Tasmania

The findings of a week-long survey of coastal marine molluscs around King Island are documented. In total, 408 species were recorded, 78 for the first time. King Island appears to be the only Tasmanian outpost for 44 species. Only two non-native species were found. A number of usually distinct species-pairs or groups appear to form intergrades around King Island. Along the island’s east coast, beached shells belonging to Quaternary-era sub-fossils were found, not all of which are represented in the contemporary local fauna. Following critical examination of published sources and museum specimens, a checklist of King Island’s coastal marine mollusc fauna is presented, comprising 619 species. It is likely that many more local species await discovery and documentation

Photoreflectance/scattering measurements of spider silks informed by standard optics.

The silks of certain orb weaving spiders are emerging as high-quality optical materials. This motivates study of the optical properties of such silk and particularly the comparative optical properties of the silks of different species. Any differences in optical properties may impart biological advantage for a spider species and make the silks interesting for biomimetic prospecting as optical materials. A prior study of the reflectance of spider silks from 18 species reported results for three species of modern orb weaving spiders (Nephila clavipes, Argiope argentata and Micrathena Schreibersi) as having reduced reflectance in the UV range. (Modern in the context used here means more recently derived.) The reduced UV reflectance was interpreted as an adaptive advantage in making the silks less visible to insects. Herein, a standard, experimental technique for measuring the reflectance spectrum of diffuse surfaces, using commercially available equipment, has been applied to samples of the silks of four modern species of orb weaving spiders: Phonognatha graeffei, Eriophora transmarina, Nephila plumipes and Argiope keyserlingi. This is a different technique than used in the previous study. Three of the four silks measured have a reduced signal in the UV. By taking the form of the silks as optical elements into account, it is shown that this is attributable to a combination of wavelength-dependent absorption and scattering by the silks rather than differences in reflectance for the different silks. Phonognatha graeffei dragline silk emerges as a very interesting spider silk with a flat 'reflectance'/scattering spectrum which may indicate it is a low UV absorbing dielectric micro-fibre. Overall the measurement emerges as having the potential to compare the large numbers of silks from different species to prospect for those which have desirable optical properties

Thallium concentration and thallium isotope composition of lateritic terrains

Continental weathering plays a key role in modifying the geochemical budget of terrestrial reservoirs. Laterites are the products of extreme sub-aerial continental weathering. This study presents the first investigation of thallium (Tl) abundances and stable isotopic compositions of lateritic terrains. Two laterite profiles from India of differing protolith and age are studied. Thallium concentrations range between 7 and 244 ng/g for a basalt-based lateritic profile and 37–652 ng/g within a greywacke lateritic profile. The average Tl stable isotope composition of the two profiles is similar to many typical igneous materials, however, the intense tropical weathering causes a small but resolvable fractionation of Tl stable isotopes towards heavy values in the residual soils. The profiles are dominated by significant positive isotope excursions (reported as ε205Tl relative to standard NBS997) of +3.5 ± 0.5 2sd and +6.2 ± 0.5 2sd at the inferred palaeowater tables within both laterite profiles. These signatures likely reflect combined changes in redox state and mineralogy. Extensive mineral dissolution under through-flowing fluids alongside the formation of new phases such as phyllosilicates and Mn- and Fe-oxides and hydroxides likely account for some of the Tl mobilisation, sorption and coprecipitation. In the case of laterites, the formation of the new phases and role of surface sorption likely contribute to stable Tl isotope fractionation. The identification of strong isotope excursions at inferred palaeowater tables encourages future research to determine specific mineral phases that may drive significant fractionation of Tl stable isotopes. This study showcases the magnitude of natural variation possible in terrestrial soils. Such information is key to the nascent application of Tl isotope compositions as tracers of anthropogenic pollution

Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey

Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates

The Extended Dawid-Skene Model:Fusing Information from Multiple Data Schemas

While label fusion from multiple noisy annotations is a well understood concept in data wrangling (tackled for example by the Dawid-Skene (DS) model), we consider the extended problem of carrying out learning when the labels themselves are not consistently annotated with the same schema. We show that even if annotators use disparate, albeit related, label-sets, we can still draw inferences for the underlying full label-set. We propose the Inter-Schema AdapteR (ISAR) to translate the fully-specified label-set to the one used by each annotator, enabling learning under such heterogeneous schemas, without the need to re-annotate the data. We apply our method to a mouse behavioural dataset, achieving significant gains (compared with DS) in out-of-sample log-likelihood (-3.40 to -2.39) and F1-score (0.785 to 0.864).Comment: Updated with Author-Preprint version following Publication in P. Cellier and K. Driessens (Eds.): ECML PKDD 2019 Workshops, CCIS 1167, pp. 121 - 136, 202

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Comparison of methods for handling missing data on immunohistochemical markers in survival analysis of breast cancer

Background:Tissue micro-arrays (TMAs) are increasingly used to generate data of the molecular phenotype of tumours in clinical epidemiology studies, such as studies of disease prognosis. However, TMA data are particularly prone to missingness. A variety of methods to deal with missing data are available. However, the validity of the various approaches is dependent on the structure of the missing data and there are few empirical studies dealing with missing data from molecular pathology. The purpose of this study was to investigate the results of four commonly used approaches to handling missing data from a large, multi-centre study of the molecular pathological determinants of prognosis in breast cancer.Patients and Methods:We pooled data from over 11 000 cases of invasive breast cancer from five studies that collected information on seven prognostic indicators together with survival time data. We compared the results of a multi-variate Cox regression using four approaches to handling missing data-complete case analysis (CCA), mean substitution (MS) and multiple imputation without inclusion of the outcome (MI) and multiple imputation with inclusion of the outcome (MI). We also performed an analysis in which missing data were simulated under different assumptions and the results of the four methods were compared.Results:Over half the cases had missing data on at least one of the seven variables and 11 percent had missing data on 4 or more. The multi-variate hazard ratio estimates based on multiple imputation models were very similar to those derived after using MS, with similar standard errors. Hazard ratio estimates based on the CCA were only slightly different, but the estimates were less precise as the standard errors were large. However, in data simulated to be missing completely at random (MCAR) or missing at random (MAR), estimates for MI were least biased and most accurate, whereas estimates for CCA were most biased and least accurate.Conclusion:In this study, empirical results from analyses using CCA, MS, MI and MI were similar, although results from CCA were less precise. The results from simulations suggest that in general MI is likely to be the best. Given the ease of implementing MI in standard statistical software, the results of MI and CCA should be compared in any multi-variate analysis where missing data are a problem. © 2011 Cancer Research UK. All rights reserved

Novel Role of Y1 Receptors in the Coordinated Regulation of Bone and Energy Homeostasis

The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y recep- tors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1/ mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1/ mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, con- ditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Further- more, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by non- hypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors