Open Access to essential health care information

Open Access publishing is a valuable resource for the synthesis and distribution of essential health care information. This article discusses the potential benefits of Open Access, specifically in terms of Low and Middle Income (LAMI) countries in which there is currently a lack of informed health care providers – mainly a consequence of poor availability to information. We propose that without copyright restrictions, Open Access facilitates distribution of the most relevant research and health care information. Furthermore, we suggest that the technology and infrastructure that has been put in place for Open Access could be used to publish download-able manuals, guides or basic handbooks created by healthcare providers in LAMI countries

Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays

The short ACTH stimulation test (250 μg) is the dynamic test most frequently used to assess adrenal function. It is possible that a single basal cortisol could be used to predict the dynamic response, but research has been hampered by the use of different assays and thresholds. OBJECTIVE: To propose a morning baseline cortisol criterion of three of the most commonly used modern cortisol immunoassays - Advia Centaur (Siemens), Architect (Abbott) and the Roche Modular System (Roche) - that could predict adrenal sufficiency. DESIGN: Observational, retrospective cross-sectional study at two centres. PATIENTS AND MEASUREMENTS: Retrospective analysis of the results of 1019 Short Synacthen tests (SSTs) with the Advia Centaur, 449 SSTs with the Architect and 2050 SSTs with the Roche Modular System assay. Serum cortisol levels were measured prior to injection of 250 μg Synacthen and after 30 min. Overall, we were able to collate data from a total of 3518 SSTs in 3571 patients. RESULTS: Using receiver-operator curve analysis, baseline cortisol levels for predicting passing the SST with 100% specificity were 358 nmol/l for Siemens, 336 nmol/l for Abbott and 506 nmol/l for Roche. Utilizing these criteria, 589, 158 and 578 SSTs, respectively, for Siemens, Abbott and Roche immunoassays could have been avoided. CONCLUSIONS: We have defined assay-specific morning cortisol levels that are able to predict the integrity of the hypothalamo-pituitary-adrenal axis. We propose that this represents a valid tool for the initial assessment of adrenal function and has the potential to obviate the need for dynamic testing in a significant number of patients

(Not) Keeping the stem straight: a proteomic analysis of maritime pine seedlings undergoing phototropism and gravitropism

<p>Abstract</p> <p>Background</p> <p>Plants are subjected to continuous stimuli from the environment and have evolved an ability to respond through various growth and development processes. Phototropism and gravitropism responses enable the plant to reorient with regard to light and gravity.</p> <p>Results</p> <p>We quantified the speed of maritime pine seedlings to reorient with regard to light and gravity over 22 days. Seedlings were inclined at 15, 30 and 45 degrees with vertical plants as controls. A lateral light source illuminated the plants and stem movement over time was recorded. Depending on the initial angle of stem lean, the apical response to the lateral light source differed. In control and 15° inclined plants, the apex turned directly towards the light source after only 2 h. In plants inclined at 30° and 45°, the apex first reoriented in the vertical plane after 2 h, then turned towards the light source after 24 h. Two-dimensional gel electrophoresis coupled with mass spectrometry was then used to describe the molecular response of stem bending involved in photo- and gravi-tropism after 22 hr and 8 days of treatment. A total of 486 spots were quantitatively analyzed using image analysis software. Significant changes were determined in the protein accumulation of 68 protein spots. Early response gravitropic associated proteins were identified, which are known to function in energy related and primary metabolism. A group of thirty eight proteins were found to be involved in primary metabolism and energy related metabolic pathways. Degradation of Rubisco was implicated in some protein shifts.</p> <p>Conclusions</p> <p>Our study demonstrates a rapid gravitropic response in apices of maritime pine seedlings inclined >30°. Little or no response was observed at the stem bases of the same plants. The primary gravitropic response is concomitant with a modification of the proteome, consisting of an over accumulation of energy and metabolism associated proteins, which may allow the stem to reorient rapidly after bending.</p

Fermion Masses in Emergent Electroweak Symmetry Breaking

We consider the generation of fermion masses in an emergent model of electroweak symmetry breaking with composite $W,Z$ gauge bosons. A universal bulk fermion profile in a warped extra dimension is used for all fermion flavors. Electroweak symmetry is broken at the UV (or Planck) scale where boundary mass terms are added to generate the fermion flavor structure. This leads to flavor-dependent nonuniversality in the gauge couplings. The effects are suppressed for the light fermion generations but are enhanced for the top quark where the $Zt{\bar t}$ and $Wt{\bar b}$ couplings can deviate at the $10-20$ level in the minimal setup. By the AdS/CFT correspondence our model implies that electroweak symmetry is not a fundamental gauge symmetry. Instead the Standard Model with massive fermions and $W,Z$ gauge bosons is an effective chiral Lagrangian for some underlying confining strong dynamics at the TeV scale, where mass is generated without a Higgs mechanism.Comment: modified discussion in Sec 3.1, version published in JHE

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Biomechanical evaluation of predictive parameters of progression in adolescent isthmic spondylolisthesis: a computer modeling and simulation study

<p>Abstract</p> <p>Background</p> <p>Pelvic incidence, sacral slope and slip percentage have been shown to be important predicting factors for assessing the risk of progression of low- and high-grade spondylolisthesis. Biomechanical factors, which affect the stress distribution and the mechanisms involved in the vertebral slippage, may also influence the risk of progression, but they are still not well known. The objective was to biomechanically evaluate how geometric sacral parameters influence shear and normal stress at the lumbosacral junction in spondylolisthesis.</p> <p>Methods</p> <p>A finite element model of a low-grade L5-S1 spondylolisthesis was constructed, including the morphology of the spine, pelvis and rib cage based on measurements from biplanar radiographs of a patient. Variations provided on this model aimed to study the effects on low grade spondylolisthesis as well as reproduce high grade spondylolisthesis. Normal and shear stresses at the lumbosacral junction were analyzed under various pelvic incidences, sacral slopes and slip percentages. Their influence on progression risk was statistically analyzed using a one-way analysis of variance.</p> <p>Results</p> <p>Stresses were mainly concentrated on the growth plate of S1, on the intervertebral disc of L5-S1, and ahead the sacral dome for low grade spondylolisthesis. For high grade spondylolisthesis, more important compression and shear stresses were seen in the anterior part of the growth plate and disc as compared to the lateral and posterior areas. Stress magnitudes over this area increased with slip percentage, sacral slope and pelvic incidence. Strong correlations were found between pelvic incidence and the resulting compression and shear stresses in the growth plate and intervertebral disc at the L5-S1 junction.</p> <p>Conclusions</p> <p>Progression of the slippage is mostly affected by a movement and an increase of stresses at the lumbosacral junction in accordance with spino-pelvic parameters. The statistical results provide evidence that pelvic incidence is a predictive parameter to determine progression in isthmic spondylolisthesis.</p

Marine integrons containing novel integrase genes, attachment sites, attI, and associated gene cassettes in polluted sediments from Suez and Tokyo Bays

In order to understand the structure and biological significance of integrons and associated gene cassettes in marine polluted sediments, metagenomic DNAs were extracted from sites at Suez and Tokyo Bays. PCR amplicons containing new integrase genes, intI, linked with novel gene cassettes, were recovered and had sizes from 1.8 to 2.5 kb. This approach uncovered, for the first time, the structure and diversity of both marine integron attachment site, attI, and the first gene cassette, the most efficiently expressed integron-associated gene cassette. The recovered 13 and 20 intI phylotypes, from Suez and Tokyo Bay samples, respectively, showed a highly divergence, suggesting a difference in integron composition between the sampling sites. Some intI phylotypes showed similarity with that from Geobacter metallireducens, belonging to Deltaproteobacteria, the dominant class in both sampling sites, as determined by 16S rRNA gene analysis. Thirty distinct families of putative attI site, as determined by the presence of an attI-like simple site, were recovered. A total of 146 and 68 gene cassettes represented Suez and Tokyo Bay unsaturated cassette pools, respectively. Gene cassettes, including a first cassette, from both sampling sites encoded two novel families of glyoxalase/bleomycin antibiotic-resistance protein. Gene cassettes from Suez Bay encoded proteins similar to haloacid dehalogenases, protein disulfide isomerases and death-on-curing and plasmid maintenance system killer proteins. First gene cassettes from Tokyo Bay encoded a xenobiotic-degrading protein, cardiolipin synthetase, esterase and WD40-like β propeller protein. Many of the first gene cassettes encoded proteins with no ascribable function but some of them were duplicated and possessed signal functional sites, suggesting efficient adaptive functions to their bacterial sources. Thus, each sampling site had a specific profile of integrons and cassette types consistent with the hypothesis that the environment shapes the genome

Assessment of the centre of pressure pattern and moments about S2 in scoliotic subjects during normal walking

Background Context: Research employing gait measurements indicate asymmetries in ground reaction forces and suggest relationships between these asymmetries, neurological dysfunction and spinal deformity. Although, studies have documented the use of centre of pressure (CoP) and net joint moments in gait assessment and have assessed centre of mass (CoM)-CoP distance relationships in clinical conditions, there is a paucity of information relating to the moments about CoM. It is commonly considered that CoM is situated around S2 vertebra in normal upright posture and hence this study uses S2 vertebral prominence as reference point relative to CoM. Purpose: To assess and establish asymmetry in the CoP pattern and moments about S2 vertebral prominence during level walking and its relationship to spinal deformity in adolescents with scoliosis. Patient sample: Nine Adolescent Idiopathic Scoliosis subjects (8 females and 1 male with varying curve magnitudes and laterality) scheduled for surgery within 2-3 days after data collection, took part in this study. Outcome measures: Kinetic and Kinematic Gait assessment was performed with an aim to estimate the CoP displacement and the moments generated by the ground reaction force about the S2 vertebral prominence during left and right stance during normal walking. Methods: The study employed a strain gauge force platform to estimate the medio-lateral and anterior-posterior displacement of COP and a six camera motion analysis system to track the reflective markers to assess the kinematics. The data were recorded simultaneously. Results: Results indicate wide variations in the medio lateral direction CoP, which could be related to the laterality of both the main and compensation curves. This variation is not evident in the anterior-posterior direction. Similar results were recorded for moments about S2 vertebral prominence. Subjects with higher left compensation curve had greater displacement to the left. Conclusion: Although further longitudinal studies are needed, results indicate that the variables identified in this study are applicable to initial screening and surgical evaluation of scoliosis. © 2008 Chockalingam et al; licensee BioMed Central Ltd

XRCC1 interacts with the p58 subunit of DNA Pol α-primase and may coordinate DNA repair and replication during S phase

Repair of single-stranded DNA breaks before DNA replication is critical in maintaining genomic stability; however, how cells deal with these lesions during S phase is not clear. Using combined approaches of proteomics and in vitro and in vivo protein–protein interaction, we identified the p58 subunit of DNA Pol α-primase as a new binding partner of XRCC1, a key protein of the single strand break repair (SSBR) complex. In vitro experiments reveal that the binding of poly(ADP-ribose) to p58 inhibits primase activity by competition with its DNA binding property. Overexpression of the XRCC1-BRCT1 domain in HeLa cells induces poly(ADP-ribose) synthesis, PARP-1 and XRCC1-BRCT1 poly(ADP-ribosyl)ation and a strong S phase delay in the presence of DNA damage. Addition of recombinant XRCC1-BRCT1 to Xenopus egg extracts slows down DNA synthesis and inhibits the binding of PCNA, but not MCM2 to alkylated chromatin, thus indicating interference with the assembly of functional replication forks. Altogether these results suggest a critical role for XRCC1 in connecting the SSBR machinery with the replication fork to halt DNA synthesis in response to DNA damage