The Development of an Instrument for Client Based Principal Evaluation

Given the shortcomings of existing administrator evaluation instruments and in particular of those of a diagnostic nature, it is desirable to design a sound measurement instrument that can be used with confidence by practitioners. (Program Approaches to Administrative Training and Development.

Specialty choice in UK junior doctors: Is psychiatry the least popular specialty for UK and international medical graduates?

<p>Abstract</p> <p>Background</p> <p>In the UK and many other countries, many specialties have had longstanding problems with recruitment and have increasingly relied on international medical graduates to fill junior and senior posts. We aimed to determine what specialties were the most popular and desirable among candidates for training posts, and whether this differed by country of undergraduate training.</p> <p>Methods</p> <p>We conducted a database analysis of applications to Modernising Medical Careers for all training posts in England in 2008. Total number of applications (as an index of popularity) and applications per vacancy (as an index of desirability) were analysed for ten different specialties. We tested whether mean consultant incomes correlated with specialty choice.</p> <p>Results</p> <p>In, 2008, there were 80,949 applications for specialty training in England, of which 31,434 were UK graduates (39%). Among UK medical graduates, psychiatry was the sixth most popular specialty (999 applicants) out of 10 specialty groups, while it was fourth for international graduates (5,953 applicants). Among UK graduates, surgery (9.4 applicants per vacancy) and radiology (8.0) had the highest number of applicants per vacancy and paediatrics (1.2) and psychiatry (1.1) the lowest. Among international medical graduates, psychiatry had the fourth highest number of applicants per place (6.3). Specialty popularity for UK graduates was correlated with predicted income (p = 0.006).</p> <p>Conclusion</p> <p>Based on the number of applicants per place, there was some consistency in the most popular specialties for both UK and international medical graduates, but there were differences in the popularity of psychiatry. With anticipated decreases in the number of new international medical graduates training in the UK, university departments and professional associations may need to review strategies to attract more UK medical graduates into certain specialties, particularly psychiatry and paediatrics.</p

Dome growth, collapse, and valley fill at Soufrière Hills Volcano, Montserrat, from 1995 to 2013: Contributions from satellite radar measurements of topographic change

Frequent high-resolution measurements of topography at active volcanoes can provide important information for assessing the distribution and rate of emplacement of volcanic deposits and their influence on hazard. At dome-building volcanoes, monitoring techniques such as LiDAR and photogrammetry often provide a limited view of the area affected by the eruption. Here, we show the ability of satellite radar observations to image the lava dome and pyroclastic density current deposits that resulted from 15 years of eruptive activity at Soufrière Hills Volcano, Montserrat, from 1995 to 2010. We present the first geodetic measurements of the complete subaerial deposition field on Montserrat, including the lava dome. Synthetic aperture radar observations from the Advanced Land Observation Satellite (ALOS) and TanDEM-X mission are used to map the distribution and magnitude of elevation changes. We estimate a net dense-rock equivalent volume increase of 108 ± 15M m3 of the lava dome and 300 ± 220M m3 of talus and subaerial pyroclastic density current deposits. We also show variations in deposit distribution during different phases of the eruption, with greatest on-land deposition to the south and west, from 1995 to 2005, and the thickest deposits to the west and north after 2005. We conclude by assessing the potential of using radar-derived topographic measurements as a tool for monitoring and hazard assessment during eruptions at dome-building volcanoes

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=-0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression

Targeted Proteomics and Molecular Mechanisms of Gene Activation

Mass spectrometry-based proteomics is a powerful tool when combined with hypothesis driven protein purification. Regulation of protein-protein interactions is a major molecular mechanism for gene activation. Protein purification, functional assays, and antibody-based western blots have traditionally been used to elucidate many of the most critical and perhaps universal protein-protein interactions required for gene expression, such as the assembly of the general transcription machinery. The Mediator complex is an essential part of the general transcription machinery that integrates signals from DNA-binding transcriptional activators through protein-protein interactions to regulate RNA Pol II activity. Gene activation is ultimately determined by incoming stimuli and subsequent inter-cellular signaling. How these signals are integrated in a spatial and temporal fashion for the regulation of distinct genes by activator-Mediator interactions is unclear. One proposed molecular mechanism of gene activation by the Mediator complex is through a structural shift in the complex. Mediator structural shifts may trigger new protein-protein interactions required for transcription of select genes in response to a specific stimulus. To test this, Mediator complexes were purified with and without transcriptional activators. The activation domains of the transcriptional activators SREBP-1a and VP16, which generate distinct structures upon binding Mediator, were used to affinity purify activator-bound Mediator complexes. For comparison, antibodies for the Mediator subunits MED1 and CDK8 were used to affinity purify activator-free Mediator complexes. A mass spectrometry-based proteomics platform was established to characterize the protein compositions of each Mediator complex purification. The results showed additional cofactors in the activator-bound Mediator complexes, many of which had known function related to gene expression. Selected cofactors were validated for binding Mediator with an orthogonal purification that combined the activator and antibody purifications and western blotting. Together the proteomics data predicted and the western blotting confirmed new protein-protein interactions relevant for regulation of gene expression that were activator-specific. Collectively, these targeted proteomics approaches have generated many new hypotheses and have fundamentally altered our understanding of how gene expression is regulated

Evaluation of the Escherichia coli threonine deaminase gene as a selectable marker for plant transformation

The initial step in the synthesis of isoleucine (Ile) is the conversion of threonine to α-ketobutyrate. This reaction is carried out by threonine deaminase (TD), which is feedback-regulated by Ile. Mutations in TD that manifest insensitivity to Ile feedback inhibition result in intracellular accumulation of Ile. Previous reports have shown that in planta expression of the wild-type Escherichia coli TD, ilvA, or an Ile-insensitive mutant designated ilvA-466, increased cellular concentrations of Ile. A structural analog of Ile, L-O-methylthreonine (OMT), is able to compete effectively with Ile during translation and induce cell death. It has been postulated that OMT could therefore be utilized as an effective selective agent in plant engineering studies. To test this concept, we designed two binary plasmids that harbored an nptII cassette and either the wild-type ilvA or mutant ilvA-466. The ilvA coding sequences were fused to a plastid transit peptide down stream of a modified 35S CaMV promoter. Tobacco transformations were set up implementing a selection protocol based on either kanamycin or OMT. The ilvA gene was effectively utilized as a selectable marker gene to identify tobacco transformants when coupled with OMT as the selection agent. However, the transformation efficiency was substantially lower than that observed with nptII using kanamycin as the selection agent. Moreover, in a subset of the ilvA transformants and in a majority of the ilvA-466 transgenic lines, a severe off-type was observed under greenhouse conditions that correlated with increased levels of expression of the ilvA transgene

Thin-skinned mass-wasting responsible for widespread deformation at Arenal volcano

The shape and stability of a volcano’s edifice depends on the relationship between eruption rate and the loss or redistribution of material due to erosion, mass-wasting or deformation. This work provides measurements of deformation and shallow mass-wasting at a stratovolcano immediately after an extended period of growth, and demonstrates that high rates of deformation can be associated with shallow edifice processes. We measure displacements and surface property changes on the upper flanks of Arenal, Costa Rica, after a ~40 year period of edifice growth. We present high-resolution satellite radar imagery of the 2011-2013 period that provides evidence of frequent rockfalls and of at least 16 slow-moving, shallow landslides (estimated to be 5-11 m thick, total volume = 2.4×107 m3 DRE). The 2012 Nicoya Earthquake (Mw 7.4) had no measurable impact on the velocities of sliding units at Arenal, but did result in an increase in the area affected by rockfall

Transient deformation associated with explosive eruption measured at Masaya volcano (Nicaragua) using Interferometric Synthetic Aperture Radar

Deformation caused by processes within a volcanic conduit are localised, transient, and therefore challenging to measure. However, observations of such deformation are important because they provide insight into conditions preceding explosive activity, and are important for hazard assessment. Here, we present measurements of low magnitude, transient deformation covering an area of ∼4 km2 at Masaya volcano spanning a period of explosive eruptions (30th April - 17th May 2012). Radial uplift of duration 24 days and peak displacements of a few millimetres occurred in the month before the eruption, but switched to subsidence ∼27 days before the onset of the explosive eruption on 30th of April. Uplift resumed during, and continued for ∼16 days after the end of the explosive eruption period. We use a finite element modelling approach to investigate a range of possible source geometries for this deformation, and find that the changes in pressurisation of a conduit 450 m below the surface vent (radius 160 m and length 700 m), surrounded by a halo of brecciated material with a Young’s modulus of 15 GPa, gave a good fit to the InSAR displacements. We propose that the pre-eruptive deformation sequence at Masaya is likely to have been caused by the movement of magma through a constriction within the shallow conduit system. Although measuring displacements associated with conduit processes remains challenging, new high resolution InSAR datasets will increasingly allow the measurement of transient and lower magnitude deformation signals, improving the method’s applicability for observing transitions between volcanic activity characterised by an open and a closed conduit system

Cumulative meta-analysis of interleukins 6 and 1 beta, tumour necrosis factor alpha and C-reactive protein in patients with major depressive disorder

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and Psychlnfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p <0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p <0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-alpha levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1 beta levels and major depression (d = -0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-alpha, interleukin-1 beta and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression. (C) 2015 The Authors. Published by Elsevier Inc.Peer reviewe

The effect of adjusting LDL-cholesterol for Lp(a)-cholesterol on the diagnosis of familial hypercholesterolaemia

BACKGROUND: Familial hypercholesterolaemia (FH) diagnostic tools help prioritise patients for genetic testing and include LDL-C estimates commonly calculated using the Friedewald equation. However, cholesterol contributions from lipoprotein(a) (Lp(a)) can overestimate 'true' LDL-C, leading to potentially inappropriate clinical FH diagnosis. OBJECTIVE: To assess how adjusting LDL-C for Lp(a)-cholesterol affects FH diagnoses using Simon Broome (SB) and Dutch Lipid Clinic Network (DLCN) criteria. METHODS: Adults referred to a tertiary lipid clinic in London, UK were included if they had undergone FH genetic testing based on SB or DLCN criteria. LDL-C was adjusted for Lp(a)-cholesterol using estimated cholesterol contents of 17.3%, 30% and 45%, and the effects of these adjustments on reclassification to 'unlikely' FH and diagnostic accuracy were determined. RESULTS: Depending on the estimated cholesterol content applied, LDL-C adjustment reclassified 8-23% and 6-17% of patients to 'unlikely' FH using SB and DLCN criteria, respectively. The highest reclassification rates were observed following 45% adjustment in mutation-negative patients with higher Lp(a) levels. This led to an improvement in diagnostic accuracy (46% to 57% with SB, and 32% to 44% with DLCN following 45% adjustment) through increased specificity. However all adjustment factors led to erroneous reclassification of mutation-positive patients to 'unlikely' FH. CONCLUSION: LDL-C adjustment for Lp(a)-cholesterol improves the accuracy of clinical FH diagnostic tools. Adopting this approach would reduce unnecessary genetic testing but also incorrectly reclassify mutation-positive patients. Health economic analysis is needed to balance the risks of over- and under-diagnosis before LDL-C adjustments for Lp(a) can be recommended