Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case-control study.

This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVES: To estimate data loss and bias in studies of Clinical Practice Research Datalink (CPRD) data that restrict analyses to Read codes, omitting anything recorded as text. DESIGN: Matched case-control study. SETTING: Patients contributing data to the CPRD. PARTICIPANTS: 4915 bladder and 3635 pancreatic, cancer cases diagnosed between 1 January 2000 and 31 December 2009, matched on age, sex and general practitioner practice to up to 5 controls (bladder: n=21 718; pancreas: n=16 459). The analysis period was the year before cancer diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of haematuria, jaundice and abdominal pain, grouped by recording style: Read code or text-only (ie, hidden text). The association between recording style and case-control status (χ(2) test). For each feature, the odds ratio (OR; conditional logistic regression) and positive predictive value (PPV; Bayes' theorem) for cancer, before and after addition of hidden text records. RESULTS: Of the 20 958 total records of the features, 7951 (38%) were recorded in hidden text. Hidden text recording was more strongly associated with controls than with cases for haematuria (140/336=42% vs 556/3147=18%) in bladder cancer (χ(2) test, p<0.001), and for jaundice (21/31=67% vs 463/1565=30%, p<0.0001) and abdominal pain (323/1126=29% vs 397/1789=22%, p<0.001) in pancreatic cancer. Adding hidden text records corrected PPVs of haematuria for bladder cancer from 4.0% (95% CI 3.5% to 4.6%) to 2.9% (2.6% to 3.2%), and of jaundice for pancreatic cancer from 12.8% (7.3% to 21.6%) to 6.3% (4.5% to 8.7%). Adding hidden text records did not alter the PPV of abdominal pain for bladder (codes: 0.14%, 0.13% to 0.16% vs codes plus hidden text: 0.14%, 0.13% to 0.15%) or pancreatic (0.23%, 0.21% to 0.25% vs 0.21%, 0.20% to 0.22%) cancer. CONCLUSIONS: Omission of text records from CPRD studies introduces bias that inflates outcome measures for recognised alarm symptoms. This potentially reinforces clinicians' views of the known importance of these symptoms, marginalising the significance of 'low-risk but not no-risk' symptoms.SJP is funded by a University of Exeter PhD studentship. This report presents independent research part funded by the National Institute for Health Research Programme Grants for Applied Research programme (RP-PG-0608- 10045). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the Department of Health

BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression

The incidence of BK virus infection in kidney transplant recipients has increased over recent decades, coincident with the use of more potent immunosuppression. More importantly, posttransplant BK virus replication has emerged as an important cause of graft damage and subsequent graft loss. Immunosuppression has been accepted as a major risk for BK virus replication. However, the specific contribution of individual immunosuppressive medications to this risk has not been well established. The purpose of this paper is to provide an overview of the recent literature on the influence of the various immunosuppressant drugs and drug combinations on posttransplant BK virus replication. Evidence supporting the various immunosuppression reduction strategies utilised in the management of BK virus will also be briefly discussed

Integration of visual and auditory information by superior temporal sulcus neurons responsive to the sight of actions

&amp; Processing of complex visual stimuli comprising facial movements, hand actions, and body movements is known to occur in the superior temporal sulcus (STS) of humans and nonhuman primates. The STS is also thought to play a role in the integration of multimodal sensory input. We investigated whether STS neurons coding the sight of actions also integrated the sound of those actions. For 23 % of neurons responsive to the sight of an action, the sound of that action significantly modulated the visual response. The sound of the action increased or decreased the visually evoked response for an equal number of neurons. In the neurons whose visual response was increased by the addition of sound (but not those neurons whose responses were decreased), the audiovisual integration was dependent upon the sound of the action matching the sight of the action. These results suggest that neurons in the STS form multisensory representations of observed actions. &amp

Do Global Diversity Patterns of Vertebrates Reflect Those of Monocots?

Few studies of global diversity gradients in plants exist, largely because the data are not available for all species involved. Instead, most global studies have focussed on vertebrates, as these taxa have historically been associated with the most complete data. Here, we address this shortfall by first investigating global diversity gradients in monocots, a morphologically and functionally diverse clade representing a quarter of flowering plant diversity, and then assessing congruence between monocot and vertebrate diversity patterns. To do this, we create a new dataset that merges biome-level associations for all monocot genera with country-level associations for almost all &sim;70,000 species. We then assess the evidence for direct versus indirect effects of this plant diversity on vertebrate diversity using a combination of linear regression and structural equation modelling (SEM). Finally, we also calculate overlap of diversity hotspots for monocots and each vertebrate taxon. Monocots follow a latitudinal gradient although with pockets of extra-tropical diversity, mirroring patterns in vertebrates. Monocot diversity is positively associated with vertebrate diversity, but the strength of correlation varies depending on the clades being compared. Monocot diversity explains marginal amounts of variance (&lt;10%) after environmental factors have been accounted for. However, correlations remain among model residuals, and SEMs apparently reveal some direct effects of monocot richness. Our results suggest that collinear responses to environmental gradients are behind much of the congruence observed, but that there is some evidence for direct effects of producer diversity on consumer diversity. Much remains to be done before broad-scale diversity gradients among taxa are fully explained. Our dataset of monocot distributions will aid in this endeavour

High-Field Superconductivity at an Electronic Topological Transition in URhGe

The emergence of superconductivity at high magnetic fields in URhGe is regarded as a paradigm for new state formation approaching a quantum critical point. Until now, a divergence of the quasiparticle mass at the metamagnetic transition was considered essential for superconductivity to survive at magnetic fields above 30 tesla. Here we report the observation of quantum oscillations in URhGe revealing a tiny pocket of heavy quasiparticles that shrinks continuously with increasing magnetic field, and finally disappears at a topological Fermi surface transition close to or at the metamagnetic field. The quasiparticle mass decreases and remains finite, implying that the Fermi velocity vanishes due to the collapse of the Fermi wavevector. This offers a novel explanation for the re-emergence of superconductivity at extreme magnetic fields and makes URhGe the first proven example of a material where magnetic field-tuning of the Fermi surface, rather than quantum criticality alone, governs quantum phase formation.Comment: A revised version has been accepted for publication in Nature Physic

Cancer and renal insufficiency results of the BIRMA study

Background: Half of anticancer drugs are predominantly excreted in urine. Dosage adjustment in renal insufficiency (RI) is, therefore, a crucial issue. Moreover, patients with abnormal renal function are at high risk for drug-induced nephrotoxicity. The Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study investigated the prevalence of RI in cancer patients, and the profile/dosing of anticancer drugs prescribed. Methods:Primary end point: to estimate the prevalence of abnormal glomerular filtration rate (GFR; estimated with the abbreviated Modification of Diet in Renal Disease formula) and RI in cancer patient. Secondary end point: to describe the profile of anticancer drugs prescribed (dose reduction/nephrotoxicity). Data were collected for patients presenting at one of the seven Belgian BIRMA centres in March 2006. Results: A total of 1218 patients were included. The prevalence of elevated SCR (1.2 mg per 100 ml) was 14.9%, but 64.0% had a GFR90 ml min 1 per 1.73 m 2. In all, 78.6% of treated patients (n1087) were receiving at least one drug needing dosage adjustment and 78.1% received at least one nephrotoxic drug. In all, 56.5% of RI patients receiving chemotherapy requiring dose reduction in case of RI did not receive dose adjustment. Conclusions: The RI is highly frequent in cancer patients. In all, 80% of the patients receive potentially nephrotoxic drugs and/or for which dosage must be adjusted in RI. Oncologists should check the appropriate dose of chemotherapeutic drugs in relation to renal function before prescribing. © 2010 Cancer Research UK.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

S100A7 and the progression of breast cancer

The S100 gene family comprises more than 20 members whose protein sequences encompass at least one EF-hand Ca(2+ )binding motif. The expression of individual family members is not ubiquitous for all tissues and there appears to be an element of tissue-specific expression. Molecular analysis of breast tumors has revealed that several S100s, including S100A2, S100A4 and S100A7, exhibit altered expression levels during breast tumorigenesis and/or progression. Subsequent studies have started to describe a functional role for these S100 proteins as well as their mechanism of action and the biochemical pathways they modify. The present review outlines what is known about S100A7 in breast cancer and summarizes the need to better understand the importance of this protein in breast cancer

Reference Force Field and CDW Amplitude of Mixed-Valence Halogen-Bridged Pt Complexes

The spectroscopic effects of electron-phonon coupling in mixed-valence chlorine-bridged Pt chains complexes are investigated through a parallel infrared and Raman study of three compounds with decreasing Pt-Pt distance along the chain. The e-ph interaction is analyzed in terms of the Herzberg-Teller coupling scheme. We take into account the quadratic term and define a precise reference state. The force field relevant to this state is constructed, whereas the electronic structure is analyzed in terms of a simple phenomenological model, singling out a trimeric unit along the chain. In this way we are able to account for all the available optical data of the three compounds, and to estimate the relevant microscopic parameters, such as the e-ph coupling constants and the CDW amplitude.Comment: 10 pages, compressed postscript, 6 Tables and 5 Figures also in a compressed ps.Z file. Revision is in the submission format only (postscript instead of tex