Prevalence and causes of prescribing errors: the prescribing outcomes for trainee doctors engaged in clinical training (PROTECT) study

Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p&#60;0.001), surgical (p = &#60;0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p&#60;0.001), a greater number of prescribed medicines (p&#60;0.001) and the months December and June (p&#60;0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.</p

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: constraints on the time variation of fundamental constants from the large-scale two-point correlation function

We obtain constraints on the variation of the fundamental constants from the full shape of the redshift-space correlation function of a sample of luminous galaxies drawn from the Data Release 9 of the Baryonic Oscillations Spectroscopic Survey. We combine this information with data from recent CMB, BAO and H_0 measurements. We focus on possible variations of the fine structure constant \alpha and the electron mass m_e in the early universe, and study the degeneracies between these constants and other cosmological parameters, such as the dark energy equation of state parameter w_DE, the massive neutrinos fraction f_\nu, the effective number of relativistic species N_eff, and the primordial helium abundance Y_He. When only one of the fundamental constants is varied, our final bounds are \alpha / \alpha_0 = 0.9957_{-0.0042}^{+0.0041} and m_e /(m_e)_0 = 1.006_{-0.013}^{+0.014}. For their joint variation, our results are \alpha / \alpha_0 = 0.9901_{-0.0054}^{+0.0055} and m_e /(m_e)_0 = 1.028 +/- 0.019. Although when m_e is allowed to vary our constraints on w_DE are consistent with a cosmological constant, when \alpha is treated as a free parameter we find w_DE = -1.20 +/- 0.13; more than 1 \sigma away from its standard value. When f_\nu and \alpha are allowed to vary simultaneously, we find f_\nu < 0.043 (95% CL), implying a limit of \sum m_\nu < 0.46 eV (95% CL), while for m_e variation, we obtain f_nu < 0.086 (95% CL), which implies \sum m_\nu < 1.1 eV (95% CL). When N_eff or Y_He are considered as free parameters, their simultaneous variation with \alpha provides constraints close to their standard values (when the H_0 prior is not included in the analysis), while when m_e is allowed to vary, their preferred values are significantly higher. In all cases, our results are consistent with no variations of \alpha or m_e at the 1 or 2 \sigma level.Comment: 18 pages, 16 figures. Submitted to MNRA

Discovery of an Ultrasoft X-ray Transient Source in the 2XMM Catalog: a Tidal Disruption Event Candidate

We have discovered an ultrasoft X-ray transient source, 2XMMi J184725.1-631724, which was detected serendipitously in two XMM-Newton observations in the direction of the center of the galaxy IC 4765-f01-1504 at a redshift of 0.0353. These two observations were separated by 211 days, with the 0.2-10 keV absorbed flux increasing by a factor of about 9. Their spectra are best described by a model dominated by a thermal disk or a single-temperature blackbody component (contributing >80% of the flux) plus a weak power-law component. The thermal emission has a temperature of a few tens of eV, and the weak power-law component has a photon index of ~3.5. Similar to the black hole X-ray binaries in the thermal state, our source exhibits an accretion disk whose luminosity appears to follow the $L\propto T^4$ relation. This would indicate that the black hole mass is about 10^5-10^6 M_sun using the best-fitting inner disk radius. Both XMM-Newton observations show variability of about 21% on timescales of hours, which can be explained as due to fast variations in the mass accretion rate. The source was not detected by ROSAT in an observation in 1992, indicating a variability factor of >64 over longer timescales. The source was not detected again in X-rays in a Swift observation in 2011 February, implying a flux decrease by a factor of >12 since the last XMM-Newton observation. The transient nature, in addition to the extreme softness of the X-ray spectra and the inactivity of the galaxy implied by the lack of strong optical emission lines, makes it a candidate tidal disruption event. If this is the case, the first XMM-Newton observation would have been in the rising phase, and the second one in the decay phase.Comment: 12 pages, 6 figures. Accepted for publication in Ap

Glycogene Expression Alterations Associated with Pancreatic Cancer Epithelial-Mesenchymal Transition in Complementary Model Systems

The ability to selectively detect and target cancer cells that have undergone an epithelial-mesenchymal transition (EMT) may lead to improved methods to treat cancers such as pancreatic cancer. The remodeling of cellular glycosylation previously has been associated with cell differentiation and may represent a valuable class of molecular targets for EMT.As a first step toward investigating the nature of glycosylation alterations in EMT, we characterized the expression of glycan-related genes in three in-vitro model systems that each represented a complementary aspect of pancreatic cancer EMT. These models included: 1) TGFβ-induced EMT, which provided a look at the active transition between states; 2) a panel of 22 pancreatic cancer cell lines, which represented terminal differentiation states of either epithelial-like or mesenchymal-like; and 3) actively-migrating and stationary cells, which provided a look at the mechanism of migration. We analyzed expression data from a list of 587 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc.) or EMT. Glycogenes were altered at a higher prevalence than all other genes in the first two models (p<0.05 and <0.005, respectively) but not in the migration model. Several functional themes were shared between the induced-EMT model and the cell line panel, including alterations to matrix components and proteoglycans, the sulfation of glycosaminoglycans; mannose receptor family members; initiation of O-glycosylation; and certain forms of sialylation. Protein-level changes were confirmed by Western blot for the mannose receptor MRC2 and the O-glycosylation enzyme GALNT3, and cell-surface sulfation changes were confirmed using Alcian Blue staining.Alterations to glycogenes are a major component of cancer EMT and are characterized by changes to matrix components, the sulfation of GAGs, mannose receptors, O-glycosylation, and specific sialylated structures. These results provide leads for targeting aggressive and drug resistant forms of pancreatic cancer cells

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

Inflation and Kahler Stabilization of the Dilaton

The problems of attempting inflationary model-building in a theory containing a dilaton are explained. In particular, I study the shape of the dilaton potential today and during inflation, based on a weakly-coupled heterotic string model where corrections to the Kahler potential are assumed to be responsible for dilaton stabilization. Although no specific model-building is attempted, if the inflationary energy density is related to the scale of gaugino condensation, then the dilaton may be stabilized close enough to today's value that there is no significant change in the GUT scale coupling. This can occur in a very wide range of models, and helps to provide some justification for the standard predictions of the spectral index. I explain how this result can ultimately be traced to the supersymmetry structure of the theory.Comment: 12 pages, submitted to PR

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite heligmosomoides polygyrus

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4+ cells. In addition, MyD88-/- mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-β adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1-/- mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1-/- and MyD88-/- mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1-/-) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice

Satellite Tracking Reveals Long Distance Coastal Travel and Homing by Translocated Estuarine Crocodiles, Crocodylus porosus

Crocodilians have a wide distribution, often in remote areas, are cryptic, secretive and are easily disturbed by human presence. Their capacity for large scale movements is poorly known. Here, we report the first study of post-release movement patterns in translocated adult crocodiles, and the first application of satellite telemetry to a crocodilian. Three large male Crocodylus porosus (3.1–4.5 m) were captured in northern Australia and translocated by helicopter for 56, 99 and 411 km of coastline, the last across Cape York Peninsula from the west coast to the east coast. All crocodiles spent time around their release site before returning rapidly and apparently purposefully to their capture locations. The animal that circumnavigated Cape York Peninsula to return to its capture site, travelled more than 400 km in 20 days, which is the longest homeward travel yet reported for a crocodilian. Such impressive homing ability is significant because translocation has sometimes been used to manage potentially dangerous C. porosus close to human settlement. It is clear that large male estuarine crocodiles can exhibit strong site fidelity, have remarkable navigational skills, and may move long distances following a coastline. These long journeys included impressive daily movements of 10–30 km, often consecutively

Sampling and Analysis of Impact Crater Residues Found on the Wide Field Planetary Camera-2 Radiator

After nearly 16 years in low Earth orbit (LEO), the Wide Field Planetary Camera-2 (WFPC2) was recovered from the Hubble Space Telescope (HST) in May 2009, during the 12 day shuttle mission designated STS-125. The WFPC-2 radiator had been struck by approximately 700 impactors producing crater features 300 microns and larger in size. Following optical inspection in 2009, agreement was reached for joint NASA-ESA study of crater residues, in 2011. Over 480 impact features were extracted at NASA Johnson Space Center's (JSC) Space Exposed Hardware clean-room and curation facility during 2012, and were shared between NASA and ESA. We describe analyses conducted using scanning electron microscopy (SEM) - energy dispersive X-ray spectrometry (EDX): by NASA at JSC's Astromaterials Research and Exploration Science (ARES) Division; and for ESA at the Natural History Museum (NHM), with Ion beam analysis (IBA) using a scanned proton microbeam at the University of Surrey Ion Beam Centre (IBC)

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391