Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice

Methods for determining cost-effectiveness of different treatments are well established, unlike appraisal of non-drug interventions, including novel diagnostics and biomarkers

The measurement of household consumption expenditures

Household-level data on consumer expenditures underpin a wide range of empirical research in modern economics, spanning micro-and macroeconomics. This research includes work on consumption and saving, on poverty and inequality, and on risk sharing and insurance. We review different ways in which such data can be collected or captured: traditional detailed budget surveys, less onerous survey procedures that might be included in more general surveys, and administrative or process data. We discuss the advantages and difficulties of each approach and suggest directions for future investigation. © 2014 by Annual Reviews. All rights reserved

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Effect of egg turning and incubation time on carbonic anhydrase gene expression in the blastoderm of the Japanese quail (Coturnix c. japonica)

(1) The gene expression of carbonic anhydrase, a key enzyme for the production sub-embryonic fluid (SEF), was assessed in turned and unturned eggs of the Japanese quail. The plasma membrane-associated isoforms CA IV, CAIX, CA XII, CA XIV, and the cytoplasmic isoform CA II, were investigated in the extra-embryonic tissue of the blastoderm and in embryonic blood. (2) Eggs were incubated at 37.6C, c. 60% R.H., and turned hourly (90 ) or left unturned. From 48 to 96 hours of incubation mRNA was extracted from blastoderm tissue, reverse-transcribed to cDNA and quantified by real-time qPCR using gene-specific primers. Blood collected at 96h was processed identically. (3) Blastoderm CAIV gene expression increased with the period of incubation only in turned eggs, with maxima at 84 and 96h of incubation. Only very low levels were found in blood. (4) Blastoderm CA II gene expression was greatest at 48 and 54h of incubation, subsequently declining to much lower levels and una ected by turning. Blood CA II gene expression was about 25-fold greater than that in the blastoderm. (5) The expression of CA IX in the blastoderm was the highest of all isoforms, yet unaffected by turning. CA XII did not amplify and CA XIV was present at unquantifiable low levels. (6) It is concluded that solely gene expression for CA IV is sensitive to egg turning, and that increased CA IV gene expression could account for the additional SEF mass found at 84-96h of incubation. in embryos of turned eggs

Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer

Fanconi anemia (FA) is a recessive disorder associated with progressive pancytopenia, multiple developmental defects, and marked predisposition to malignancies. FA is genetically heterogeneous, comprising at least 12 complementation groups (A–M). Activation of one of the FA proteins (FANCD2) by mono-ubiquitination is an essential step in DNA damage response. As FANCD2 interacts with BRCA1, is expressed in proliferating normal breast cells, and FANCD2 knockout mice develop breast tumors, we investigated the expression of FANCD2 in sporadic and hereditary invasive breast cancer patients to evaluate its possible role in breast carcinogenesis. Two tissue microarrays of 129 and 220 sporadic breast cancers and a tissue microarray containing 25 BRCA1 germline mutation-related invasive breast cancers were stained for FANCD2. Expression results were compared with several clinicopathological variables and tested for prognostic value. Eighteen of 96 (19%) sporadic breast cancers and two of 21 (10%) BRCA1-related breast cancers were completely FANCD2-negative, which, however, still showed proliferation. In the remaining cases, the percentage of FANCD2-expressing cells correlated strongly with mitotic index and percentage of cells positive for the proliferation markers Ki-67 and Cyclin A. In immunofluorescence double staining, coexpression of FANCD2 and Ki-67 was apparent. In survival analysis, high FANCD2 expression appeared to be prognostically unfavorable for overall survival (p = 0.03), independent from other major prognosticators (p = 0.026). In conclusion, FANCD2 expression is absent in 10–20% of sporadic and BRCA1-related breast cancers, indicating that somatic inactivating (epi)genetic events in FANCD2 may be important in both sporadic and hereditary breast carcinogenesis. FANCD2 is of independent prognostic value in sporadic breast cancer

Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

 This is the author accepted manuscript. The final version is available on open access from American Chemical Society via the DOI in this record The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10×) maximum foetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of micro-dissected heart tissues showed that both chemicals perturbed similar downstream molecular pathways and biological processes, including down-regulation of cartilage morphogenesis and filamentous protein synthesis. Collagen/keratin deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular- cardiovascular disease states.Biotechnology & Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC

Composite structural motifs of binding sites for delineating biological functions of proteins

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs which represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.Comment: 34 pages, 7 figure

Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK

Aims: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. Materials and methods: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. Results: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9–73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. Conclusion: The data suggest that international survival statistics are achieved in UK regional cancer centres

Juvenile idiopathic scoliosis treated with posterior arthrodesis and segmental pedicle screw instrumentation before the age of 9 years: a 5-year follow-up

<p>Abstract</p> <p>Study design</p> <p>Retrospective study.</p> <p>Objective</p> <p>To evaluate the radiological results of fusion with segmental pedicle screw fixation in juvenile idiopathic scoliosis with a minimum 5-year follow-up.</p> <p>Summary of background data</p> <p>Progression of spinal deformity after posterior instrumentation and fusion in immature patients has been reported by several authors. Segmental pedicle screw fixation has been shown to be effective in controlling both coronal and sagittal plane deformities. However, there is no long term study of fusion with segmental pedicle screw fixation in these group of patients.</p> <p>Methods</p> <p>Seven patients with juvenile idiopathic scoliosis treated by segmental pedicle screw fixation and fusion were analyzed. The average age of the patients was 7.4 years (range 5–9 years) at the time of the operation. All the patients were followed up 5 years or more (range 5–8 years) and were all Risser V at the most recent follow up. Three dimensional reconstruction of the radiographs was obtained and 3DStudio Max software was used for combining, evaluating and modifying the technical data derived from both 2d and 3d scan data.</p> <p>Results</p> <p>The preoperative thoracic curve of 56 ± 15° was corrected to 24 ± 17° (57% correction) at the latest follow-up. The lumbar curve of 43 ± 14° was corrected to 23 ± 6° (46% correction) at the latest follow-up. The preoperative thoracic kyphosis of 37 ± 13° and the lumbar lordosis of 33 ± 13° were changed to 27 ± 13° and 42 ± 21°, respectively at the latest follow-up. None of the patients showed coronal decompensation at the latest follow-up. Four patients had no evidence of crankshaft phenomenon. In two patients slight increase in Cobb angle at the instrumented segments with a significant increase in AVR suggesting crankshaft phenomenon was seen. One patient had a curve increase in both instrumented and non instrumented segments due to incorrect strategy.</p> <p>Conclusion</p> <p>In juvenile idiopathic curves of Risser 0 patients with open triradiate cartilages, routine combined anterior fusion to prevent crankshaft may not be warranted by posterior segmental pedicle screw instrumentation.</p

The effects of walking speed on minimum toe clearance and on the temporal relationship between minimum clearance and peak swing-foot velocity in unilateral trans-tibial amputees

yesBackground: Minimum toe clearance is a critical gait event because it coincides with peak forward velocity of the swing foot, and thus, there is an increased risk of tripping and falling. Trans-tibial amputees have increased risk of tripping compared to able-bodied individuals. Assessment of toe clearance during gait is thus clinically relevant. In able-bodied gait, minimum toe clearance increases with faster walking speeds, and it is widely reported that there is synchronicity between when peak swing-foot velocity and minimum toe clearance occur. There are no such studies involving lower-limb amputees. Objectives: To determine the effects of walking speed on minimum toe clearance and on the temporal relationship between clearance and peak swing-foot velocity in unilateral trans-tibial amputees. Study design: Cross-sectional. Methods: A total of 10 trans-tibial participants walked at slow, customary and fast speeds. Minimum toe clearance and the timings of minimum toe clearance and peak swing-foot velocity were determined and compared between intact and prosthetic sides. Results: Minimum toe clearance was reduced on the prosthetic side and, unlike on the intact side, did not increase with walking speed increase. Peak swing-foot velocity consistently occurred (~0.014 s) after point of minimum toe clearance on both limbs across all walking speeds, but there was no significant difference in the toe–ground clearance between the two events. Conclusion: The absence of speed related increases in minimum toe clearance on the prosthetic side suggests that speed related modulation of toe clearance for an intact limb typically occurs at the swing-limb ankle. The temporal consistency between peak foot velocity and minimum toe clearance on each limb suggests that swing-phase inter-segmental coordination is unaffected by trans-tibial amputation. Clinical relevance The lack of increase in minimum toe clearance on the prosthetic side at higher walking speeds may potentially increase risk of tripping. Findings indicate that determining the instant of peak swing-foot velocity will also consistently identify when/where minimum toe clearance occurs