An automated in vitro model for the evaluation of ultrasound modalities measuring myocardial deformation

<p>Abstract</p> <p>Background</p> <p>Echocardiography is the method of choice when one wishes to examine myocardial function. Qualitative assessment of the 2D grey scale images obtained is subjective, and objective methods are required. Speckle Tracking Ultrasound is an emerging technology, offering an objective mean of quantifying left ventricular wall motion. However, before a new ultrasound technology can be adopted in the clinic, accuracy and reproducibility needs to be investigated.</p> <p>Aim</p> <p>It was hypothesized that the collection of ultrasound sample data from an in vitro model could be automated. The aim was to optimize an in vitro model to allow for efficient collection of sample data.</p> <p>Material & Methods</p> <p>A tissue-mimicking phantom was made from water, gelatin powder, psyllium fibers and a preservative. Sonomicrometry crystals were molded into the phantom. The solid phantom was mounted in a stable stand and cyclically compressed. Peak strain was then measured by Speckle Tracking Ultrasound and sonomicrometry.</p> <p>Results</p> <p>We succeeded in automating the acquisition and analysis of sample data. Sample data was collected at a rate of 200 measurement pairs in 30 minutes. We found good agreement between Speckle Tracking Ultrasound and sonomicrometry in the in vitro model. Best agreement was 0.83 ± 0.70%. Worst agreement was -1.13 ± 6.46%.</p> <p>Conclusions</p> <p>It has been shown possible to automate a model that can be used for evaluating the in vitro accuracy and precision of ultrasound modalities measuring deformation. Sonomicrometry and Speckle Tracking Ultrasound had acceptable agreement.</p

Haematogenous Staphylococcus aureus meningitis. A 10-year nationwide study of 96 consecutive cases

BACKGROUND: Haematogenous Staphylococcus aureus meningitis is rare but associated with high mortality. Knowledge about the disease is still limited. The objective of this study was to evaluate demographic and clinical prognostic features of bacteraemic S. aureus meningitis. METHODS: Nationwide surveillance in Denmark from 1991 to 2000 with clinical and bacteriological data. Risks of death were estimated by Cox proportional hazards regression analysis. RESULTS: Among 12480 cases of S. aureus bacteraemia/sepsis, we identified 96 cases of non-surgical bacteraemic S. aureus meningitis (0.8%). Incidence rates were 0.24 (95% confidence interval [CI], 0.18 to 0.30)/100 000 population between 1991–1995 and 0.13 (CI, 0.08 to 0.17)/100 000 population between 1996–2000. Mortality was 56%. After adjustment, only co morbidity (hazard ratio [HR], 3.45; CI, 1.15 to 10.30) and critical illness (Pitt score ≥ 4) (HR, 2.14; CI, 1.09 to 4.19) remained independent predictors of mortality. CONCLUSION: The incidence, but not mortality of bacteraemic S. aureus meningitis decreased during the study period. Co morbidity and critical illness were independent predictors of a poor outcome

The quality of communication about older patients between hospital physicians and general practitioners: a panel study assessment

<p>Abstract</p> <p>Background</p> <p>Optimal care of patients is dependent on good professional interaction between general practitioners and general hospital physicians. In Norway this is mainly based upon referral and discharge letters. The main objectives of this study were to assess the quality of the written communication between physicians and to estimate the number of patients that could have been treated at primary care level instead of at a general hospital.</p> <p>Methods</p> <p>This study comprised referral and discharge letters for 100 patients above 75 years of age admitted to orthopaedic, pulmonary and cardiological departments at the city general hospital in Trondheim, Norway. The assessments were done using a Delphi technique with two expert panels, each with one general hospital specialist, one general practitioner and one public health nurse using a standardised evaluation protocol with a visual analogue scale (VAS). The panels assessed the quality of the description of the patient's actual medical condition, former medical history, signs, medication, Activity of Daily Living (ADL), social network, need of home care and the benefit of general hospital care.</p> <p>Results</p> <p>While information in the referral letters on actual medical situation, medical history, symptoms, signs and medications was assessed to be of high quality in 84%, 39%, 56%, 56% and 39%, respectively, the corresponding information assessed to be of high quality in discharge letters was for actual medical situation 96%, medical history 92%, symptoms 60%, signs 55% and medications 82%. Only half of the discharge letters had satisfactory information on ADL. Some two-thirds of the patients were assessed to have had large health benefits from the general hospital care in question. One of six patients could have been treated without a general hospital admission. The specialists assessed that 77% of the patients had had a large benefit from the general hospital care; however, the general practitioners assessment was only 59%. One of four of the discharge letters did not describe who was responsible for follow-up care.</p> <p>Conclusion</p> <p>In this study from one general hospital both referral and discharge letters were missing vital medical information, and referral letters to such an extent that it might represent a health hazard for older patients. There was also low consensus between health professionals at primary and secondary level of what was high benefit of care for older patients at a general hospital.</p

Tumor classification: molecular analysis meets Aristotle

BACKGROUND: Traditionally, tumors have been classified by their morphologic appearances. Unfortunately, tumors with similar histologic features often follow different clinical courses or respond differently to chemotherapy. Limitations in the clinical utility of morphology-based tumor classifications have prompted a search for a new tumor classification based on molecular analysis. Gene expression array data and proteomic data from tumor samples will provide complex data that is unobtainable from morphologic examination alone. The growing question facing cancer researchers is, "How can we successfully integrate the molecular, morphologic and clinical characteristics of human cancer to produce a helpful tumor classification?" DISCUSSION: Current efforts to classify cancers based on molecular features ignore lessons learned from millennia of experience in biological classification. A tumor classification must include every type of tumor and must provide a unique place for each tumor within the classification. Groups within a classification inherit the properties of their ancestors and impart properties to their descendants. A classification was prepared grouping tumors according to their histogenetic development. The classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. The clinical and research value of this historical approach to tumor classification is discussed. SUMMARY: This manuscript reviews tumor classification and provides a new and comprehensive classification for neoplasia that preserves traditional nomenclature while incorporating information derived from the molecular analysis of tumors. The classification is provided as an open access XML document that can be used by cancer researchers to relate tumor classes with heterogeneous experimental and clinical tumor databases

On Conduction in a Bacterial Sodium Channel

Voltage-gated Na+-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. Selective permeability of Na+ over Ca2+ or K+ ions is essential for the biological function of Na+-channels. After the emergence of the first high-resolution structure of a Na+-channel, an anionic coordination site was proposed to confer Na+ selectivity through partial dehydration of Na+ via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na+ ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K+-channels, the movements of the ions appear to be weakly coupled in Na+-channels. When the free-energy maps for Na+ and K+ ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydrated Na+ ion, and not a hydrated K+ ion, is energetically stable

Differentially expressed alternatively spliced genes in Malignant Pleural Mesothelioma identified using massively parallel transcriptome sequencing

<p>Abstract</p> <p>Background</p> <p>Analyses of Expressed Sequence Tags (ESTs) databases suggest that most human genes have multiple alternative splice variants. The alternative splicing of pre-mRNA is tightly regulated during development and in different tissue types. Changes in splicing patterns have been described in disease states. Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4 malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal lung. We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples.</p> <p>Methods</p> <p>We developed a software pipeline to map the transcriptome read sequences of the 4 MPM samples and 1 normal lung sample onto known exon junction sequences in the comprehensive AceView database of expressed sequences and to count how many reads map to each junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing platform for 5 samples were compared with 151,486 exon junctions from the AceView database. The exon junction expression index (EJEI) was calculated for each exon junction in each sample to measure the differential expression of alternative splicing events. Top ten exon junctions with the largest EJEI difference between the 4 mesothelioma and the normal lung sample were then examined for differential expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples. Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05) were further examined with qRT-PCR in additional 18 MPM and 18 normal lung specimens.</p> <p>Results</p> <p>We found 70,953 exon junctions covered by at least one sequence read in at least one of the 5 samples. All 10 identified most differentially expressed exon junctions were validated as present by RT-PCR, and 8 were differentially expressed exactly as predicted by the sequence analysis. The differential expression of the AceView exon junctions for the ACTG2 and CDK4 genes were also observed to be statistically significant in an additional 18 MPM and 18 normal lung samples examined using qRT-PCR. The differential expression of these two junctions was shown to successfully classify these mesothelioma and normal lung specimens with high sensitivity (89% and 78%, respectively).</p> <p>Conclusion</p> <p>Whole-transcriptome shotgun sequencing, combined with a downstream bioinformatics pipeline, provides powerful tools for the identification of differentially expressed exon junctions resulting from alternative splice variants. The alternatively spliced genes discovered in the study could serve as useful diagnostic markers as well as potential therapeutic targets for MPM.</p

Bill color, not badge size, indicates testosterone-related information in house sparrows

The honesty of ornamental signals of quality is often argued to be enforced via costs associated with testosterone. It is still poorly understood, however, how seasonal variation of testosterone within individuals is related to the timing and extent of ornament development. Here, we studied inter- and intra-individual variability of plasma testosterone levels in a population of 150 captive male house sparrows (Passer domesticus) through the course of a full year. We further analyzed the relationship between plasma testosterone levels and two sexually dimorphic ornaments: badge size and bill coloration. Also, because of a known negative relation between molt and circulating testosterone levels, we analyzed the relationship between ornamentation and molt status during the fall. We found that testosterone levels increased towards the breeding season and decreased before the onset of annual molt. However, within individuals, relative testosterone titers demonstrated low repeatability between seasons. Plasma testosterone levels were not correlated with badge size in any season but were correlated strongly with bill coloration during all periods, except the breeding season when variation in bill color was low. Finally, we found that bill coloration strongly correlated with molt status during fall. Our results indicate that bill coloration, not badge size, is the best ornamental indicator of a “running average” of male testosterone in house sparrows and therefore the best potential indicator of qualities and/or behavioral strategies associated with testosterone

The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans

The nematode, Caenorhabditis elegans, possesses the most extensive known superfamily of cys-loop ligand-gated ion channels (cys-loop LGICs) consisting of 102 subunit-encoding genes. Less than half of these genes have been functionally characterised which include cation-permeable channels gated by acetylcholine (ACh) and γ-aminobutyric acid (GABA) as well as anion-selective channels gated by ACh, GABA, glutamate and serotonin. Following the guidelines set for genetic nomenclature for C. elegans, we have designated unnamed subunits as lgc genes (ligand-gated ion channels of the cys-loop superfamily). Phylogenetic analysis shows that several of these lgc subunits form distinct groups which may represent novel cys-loop LGIC subtypes