A review of published analyses of case-cohort studies and recommendations for future reporting.

The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%). The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.SJS was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1]. IRW was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number U105260558]. MP, SGT and AMW were supported by the British Heart Foundation www.bhf.org.uk [grant number CH/12/2/29428].This is the final published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's website at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.010117

Gambaran Jumlah Trombosit pada Pasien Kanker Serviks di RSU Dokter Soedarso Tahun 2011-2012

Latar Belakang: Rata Rata satu koma empat juta wanita di-seluruhdunia hidup dengan kanker serviks. Kanker serviks termasuk dari sepuluhbesar kanker penyebab kematian pada wanita di Indonesia. Hasilpenelitian terkini mengindikasikan adanya hubungan antara tingginyajumlah trombosit dengan prognosis yang buruk dari kanker sistemginekologi. Tujuan: Penelitian ini bertujuan mengetahui bagaimanagambaran jumlah trombosit pada pasien kanker serviks. Metodologi:Penelitian adalah penelitian deskriptif. Pengumpulan data dilakukan dibagian rekam medis RSU DOKTER SOEDARSO pada tanggal 25 Maretsampai 3 Mei 2013. Data dikumpulkan dari buku registrasi rawat inap danrawat jalan di poli obstetri dan ginekologi di RSU DOKTER SOEDARSO,sampel diambil secara consecutive sampling. Data dianalisis denganstatistik sederhana. Hasil: Ditemukan 39 sampel yang sesuai kriteriainklusi dan eksklusi dengan karakteristik sampel ; usia dengan 42 48tahun (35.9%), pekerjaan ibu rumah tangga (87.2%), dan stadium III/a(43.6%) adalah frekuensi yang tertinggi. Jumlah trombosit yang ditemukanpaling banyak adalah trombositosis (>400.000/ul) (64.1%). Rata-rata nilaitrombosit tertinggi yang ditemukan ada di stadium IV (592.000/ul).Kesimpulan: Distribusi jumlah trombosit terbanyak adalah trombositosis.Keadaan trombositosis mulai ditemukan pada stadium III/a. Nilai trombositmeningkat secara linier dengan stadium kanker serviks

Proteome phenotypes discriminate the growing location and malting traits in field-grown barley

Barley is one of the key cereal grains for malting and brewing industries. However, climate variability and unprecedented weather events can impact barley yield and end-product quality. The genetic background and environmental conditions are key factors in defining the barley proteome content and malting characteristics. Here, we measure the barley proteome and malting characteristics of three barley lines grown in Western Australia, differing in genetic background and growing location, by applying liquid chromatography-mass spectrometry (LC-MS). Using data-dependent acquisition LC-MS, 1571 proteins were detected with high confidence. Quantitative data acquired using sequential window acquisition of all theoretical (SWATH) MS on barley samples resulted in quantitation of 920 proteins. Multivariate analyses revealed that the barley lines\u27 genetics and their growing locations are strongly correlated between proteins and desired traits such as the malt yield. Linking meteorological data with proteomic measurements revealed how high-temperature stress in northern regions affects seed temperature tolerance during malting, resulting in a higher malt yield. Our results show the impact of environmental conditions on the barley proteome and malt characteristics; these findings have the potential to expedite breeding programs and malt quality prediction

Assessing risk prediction models using individual participant data from multiple studies.

Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous

The effects of velocity and nitrate on Phormidium accrual cycles: a stream mesocosm experiment

Proliferations of benthic cyanobacteria in the genus Phormidium are a global concern because of their increasing prevalence and ability to produce harmful toxins. Most studies have been observational and have linked physicochemical variables to Phormidium cover measured at the reach scale. Authors of these studies have alluded to nutrients and flow as key factors in accrual. Our goal was to use an experimental approach to examine how changes in velocity and NO₃⁻ concentrations influence Phormidium accrual. We hypothesized that: 1) Phormidium biomass accrual would be positively correlated with stream velocity; 2) biomass accrual would be positively related to NO₃⁻ concentration, which would have a stronger effect during early accrual; 3) an NO₃⁻ ✕ velocity interaction would arise from saturation of accrual at high NO₃⁻ and high velocity; and 4) the probability of detachment would increase with decreasing velocity. We assessed mat expansion, biomass (as phycoerythrin and chlorophyll a [Chl a] concentrations, and biovolume), and algal assemblage composition in flow-through channel mesocosms for 16 d. We crossed 2 velocity treatments (0.1 and 0.2 m/s, slow and fast, respectively) with 3 NO₃⁻ treatments (0.02, 0.1, and 0.4 mg/L, ambient, medium, and high, respectively). Velocity was positively correlated with all measures of Phormidium biomass, but patch expansion rates increased at similar rates across all treatments. NO₃⁻ had no effect during early accrual, but phycoerythrin concentrations increased with increasing NO₃⁻ in fast-velocity treatments. At the end of the experiment, patch size was greater in the high-velocity treatments because of a greater number of partial or full patch detachments in slow-velocity treatments. These results suggest that NO₃⁻ concentrations do not affect Phormidium expansion and detachment, but may be important during colonization (not investigated), and that mat expansion occurs at a similar rate regardless of velocity, but termination of accrual cycles occurs earlier in slow velocities

Development of a behaviour change intervention to encourage timely cancer symptom presentation among people living in deprived communities using the Behaviour Change Wheel

We are grateful to the National Awareness and Early Diagnosis Initiative (NAEDI) for funding this work. The NAEDI funding consortium, under the auspices of the National Cancer Research Institute (NCRI), consists of Cancer Research UK; Department of Health (England); Economic and Social Research Council; Health and Social Care R&D Division, Public Health Agency (Northern Ireland); National Institute for Social Care and Health Research (Wales); and the Scottish Government. We would like to thank ABACus project management team members Tim Banks and Maura Matthews from Tenovus Cancer Care for their ongoing support and involvement in the project. The authors would also like to acknowledge the support of the ABACus steering group (Danny Antebi, Tracey Deacon, Karen Gully, Jane Hanson, Sharon Hillier, Alex Murray, Richard Neal, Gill Richardson, Mark Rogers, and Sara Thomas). Compliance with Ethical StandardsPeer reviewedPublisher PD

The melting curve of Ni to 1 Mbar

International audienceThe melting curve of Ni has been determined to 125 GPa using laser-heated diamond anvil cell (LH-DAC) experiments in which two melting criteria were used: firstly, the appearance of liquid diffuse scattering (LDS) during in situ X-ray diffraction (XRD) and secondly, plateaux in temperature vs. laser power functions in both in situ and off-line experiments. Our new melting curve, defined by a Simon–Glatzel fit to the data where T M ( K ) = [ ( P M 18.78 ± 10.20 + 1 ) ] 1 / 2.42 ± 0.66 × 1726 , is in good agreement with the majority of the theoretical studies on Ni melting and matches closely the available shock wave melting data. It is however dramatically steeper than the previous off-line LH-DAC studies in which determination of melting was based on the visual observation of motion aided by the laser speckle method. We estimate the melting point ( T M ) of Ni at the inner-core boundary (ICB) pressure of 330 GPa to be T M = 5800 ± 700 K ( 2 σ ) , within error of the value for Fe of T M = 6230 ± 500 K determined in a recent in situ LH-DAC study by similar methods to those employed here. This similarity suggests that the alloying of 5–10 wt.% Ni with the Fe-rich core alloy is unlikely to have any significant effect on the temperature of the ICB, though this is dependent on the details of the topology of the Fe–Ni binary phase diagram at core pressures. Our melting temperature for Ni at 330 GPa is ∼2500 K higher than that found in previous experimental studies employing the laser speckle method. We find that those earlier melting curves coincide with the onset of rapid sub-solidus recrystallization, suggesting that visual observations of motion may have misinterpreted dynamic recrystallization as convective motion of a melt. This finding has significant implications for our understanding of the high-pressure melting behaviour of a number of other transition metals

Management of Acute COPD Exacerbations in Australia: Do we Follow the Guidelines?

Objective: We aimed to assess adherence to the Australian national guideline (COPD-X) against audited practice, and to document the outcomes of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (COPD) at discharge and 28 days after. Methods: A prospective clinical audit of COPD hospital admission from five tertiary care hospitals in five states of Australia was conducted. Post-discharge follow-up was conducted via telephone to assess for readmission and health status. Results: There were 207 admissions for acute exacerbation (171 patients; mean 70.2 years old; 50.3%males). Readmission rates at 28 days were 25.4%, with one (0.6%) death during admission and eight(6.1%) post-discharge within 28 days. Concordance to the COPD-X guidance was variable; 22.7% performed spirometry, 81.1% had blood gases collected when forced expiratory volume in 1 s was \u3c1 \u3eL,99.5% had chest radiography performed, 95.1% were prescribed systemic corticosteroids and 95% were prescribed antibiotic therapy. There were 89.1% given oxygen therapy and 92.6% when arterial oxygen tension was \u3c80 \u3emmHg; 65.6% were given ventilatory assistance when pH was Conclusion: When compared against clinical practice guidelines, we found important gaps in management of patients admitted with COPD throughout tertiary care centres in Australia. Strategies to improve guideline uptake are needed to optimise care

Urban ponds as an aquatic biodiversity resource in modified landscapes

Urbanization is a global process contributing to the loss and fragmentation of natural habitats. Many studies have focused on the biological response of terrestrial taxa and habitats to urbanization. However, little is known regarding the consequences of urbanization on freshwater habitats, especially small lentic systems. In this study, we examined aquatic macro-invertebrate diversity (family and species level) and variation in community composition between 240 urban and 782 nonurban ponds distributed across the United Kingdom. Contrary to predictions, urban ponds supported similar numbers of invertebrate species and families compared to nonurban ponds. Similar gamma diversity was found between the two groups at both family and species taxonomic levels. The biological communities of urban ponds were markedly different to those of nonurban ponds, and the variability in urban pond community composition was greater than that in nonurban ponds, contrary to previous work showing homogenization of communities in urban areas. Positive spatial autocorrelation was recorded for urban and nonurban ponds at 0–50 km (distance between pond study sites) and negative spatial autocorrelation was observed at 100–150 km and was stronger in urban ponds in both cases. Ponds do not follow the same ecological patterns as terrestrial and lotic habitats (reduced taxonomic richness) in urban environments; in contrast, they support high taxonomic richness and contribute significantly to regional faunal diversity. Individual cities are complex structural mosaics which evolve over long periods of time and are managed in diverse ways. This facilitates the development of a wide range of environmental conditions and habitat niches in urban ponds which can promote greater heterogeneity between pond communities at larger scales. Ponds provide an opportunity for managers and environmental regulators to conserve and enhance freshwater biodiversity in urbanized landscapes whilst also facilitating key ecosystem services including storm water storage and water treatment

High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility

Transcriptional regulators lacking enzymatic activity or binding pockets with targetable molecular features have typically been considered “undruggable,” and a reductionist approach based on identification of their molecular targets has largely failed. We have demonstrated that the Ewing sarcoma chimeric transcription factor, EWSR1-FLI1, maintains accessible chromatin at disease-specific regions. We adapted formaldehyde-assisted isolation of regulatory elements (FAIRE), an assay for accessible chromatin, to screen an epigenetically targeted small molecule library for compounds that reverse the disease-associated signature. This approach can be applied broadly for discovery of chromatin-based developmental therapeutics and offers significant advantages because it does not require the selection of a single molecular target. Using this approach, we identified a specific class of compounds with therapeutic potential