bluuebunny/crossref_metadata_2025 huggingface dataset:
An informatics model for guiding assembly of telemicrobiology workstations for malaria collaborative diagnostics using commodity products and open-source software
Authors: Suhanic West , Crandall Ian , Pennefather Peter
Published: July 2009

Background

Deficits in clinical microbiology infrastructure exacerbate global infectious disease burdens. This paper examines how commodity computation, communication, and measurement products combined with open-source analysis and communication applications can be incorporated into laboratory medicine microbiology protocols. Those commodity components are all now sourceable globally. An informatics model is presented for guiding the use of low-cost commodity components and free software in the assembly of clinically useful and usable telemicrobiology workstations.

Methods

The model incorporates two general principles: 1) collaborative diagnostics, where free and open communication and networking applications are used to link distributed collaborators for reciprocal assistance in organizing and interpreting digital diagnostic data; and 2) commodity engineering, which leverages globally available consumer electronics and open-source informatics applications, to build generic open systems that measure needed information in ways substantially equivalent to more complex proprietary systems. Routine microscopic examination of Giemsa and fluorescently stained blood smears for diagnosing malaria is used as an example to validate the model.

Results

The model is used as a constraint-based guide for the design, assembly, and testing of a functioning, open, and commoditized telemicroscopy system that supports distributed acquisition, exploration, analysis, interpretation, and reporting of digital microscopy images of stained malarial blood smears while also supporting remote diagnostic tracking, quality assessment and diagnostic process development.

Conclusion

The open telemicroscopy workstation design and use-process described here can address clinical microbiology infrastructure deficits in an economically sound and sustainable manner. It can boost capacity to deal with comprehensive measurement of disease and care outcomes in individuals and groups in a distributed and collaborative fashion. The workstation enables local control over the creation and use of diagnostic data, while allowing for remote collaborative support of diagnostic data interpretation and tracking. It can enable global pooling of malaria disease information and the development of open, participatory, and adaptable laboratory medicine practices. The informatic model highlights how the larger issue of access to generic commoditized measurement, information processing, and communication technology in both high- and low-income countries can enable diagnostic services that are much less expensive, but substantially equivalent to those currently in use in high-income countries.
Plasmodium falciparum enolase: stage-specific expression and sub-cellular localization
Authors: Pal Bhowmick Ipsita , Kumar Nirbhay , Sharma Shobhona , Coppens Isabelle , Jarori Gotam K
Published: July 2009

Background

In an earlier study, it was observed that the vaccination with Plasmodium falciparum enolase can confer partial protection against malaria in mice. Evidence has also build up to indicate that enolases may perform several non-glycolytic functions in pathogens. Investigating the stage-specific expression and sub-cellular localization of a protein may provide insights into its moonlighting functions.

Methods

Sub-cellular localization of P. falciparum enolase was examined using immunofluorescence assay, immuno-gold electron microscopy and western blotting.

Results

Enolase protein was detected at every stage in parasite life cycle examined. In asexual stages, enolase was predominantly (≥85–90%) present in soluble fraction, while in sexual stages it was mostly associated with particulate fraction. Apart from cytosol, enolase was found to be associated with nucleus, food vacuole, cytoskeleton and plasma membrane.

Conclusion

Diverse localization of enolase suggests that apart from catalyzing the conversion of 2-phosphoglycericacid into phosphoenolpyruvate in glycolysis, enolase may be involved in a host of other biological functions. For instance, enolase localized on the merozoite surface may be involved in red blood cell invasion; vacuolar enolase may be involved in food vacuole formation and/or development; nuclear enolase may play a role in transcription.
CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway
Authors: Catusse Julie , Clark David J , Gompels Ursula A
Published: July 2009

Background

Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A) infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked.

Methods

Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation.

Results

U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4.

Conclusion

U83A diverts human chemokines from signalling, but not regulatory or scavenger, receptors facilitating their clearance, while occupying signalling receptors at the cell surface. This can enhance virus specific inflammation, facilitating dissemination to replication sensitive leukocytes while evading clearance; this has implications for linked neuro-inflammatory pathologies.
Proteomic profiling of glucocorticoid-exposed myogenic cells: Time series assessment of protein translocation and transcription of inactive mRNAs
Authors: Reeves Erica KM , Gordish-Dressman Heather , Hoffman Eric P , Hathout Yetrib
Published: July 2009

Background

Prednisone, one of the most highly prescribed drugs, has well characterized effects on gene transcription mediated by the glucocorticoid receptor. These effects are typically occurring on the scale of hours. Prednisone also has a number of non-transcriptional effects (occurring on minutes scale) on protein signaling, yet these are less well studied. We sought to expand the understanding of acute effects of prednisone action on cell signaling using a combination of SILAC strategy and subcellular fractionations from C2C12 myotubes.

Results

De novo translation of proteins was inhibited in both SILAC labeled and unlabeled C2C12 myotubes. Unlabeled cells were exposed to prednisone while SILAC labeled cells remained untreated. After 0, 5, 15, and 30 minutes of prednisone exposure, labeled and unlabeled cells were mixed at 1:1 ratios and fractionated into cytosolic and nuclear fractions. A total of 534 proteins in the cytosol and 626 proteins in the nucleus were identified and quantitated, using 3 or more peptides per protein with peptide based probability ≤ 0.001. We identified significant increases (1.7- to 3.1- fold) in cytoplasmic abundance of 11 ribosomal proteins within 5 minutes of exposure, all of which returned to baseline by 30 min. We hypothesized that these drug-induced acute changes in the subcellular localization of the cell's protein translational machinery could lead to altered translation of quiescent RNAs. To test this, de novo protein synthesis was assayed after 15 minutes of drug exposure. Quantitative fluorography identified 16 2D gel spots showing rapid changes in translation; five of these were identified by MS/MS (pyruvate kinase, annexin A6 isoform A and isoform B, nasopharyngeal epithelium specific protein 1, and isoform 2 of Replication factor C subunit 1), and all showed the 5' terminal oligopyrimidine motifs associated with mRNA sequestration to and from inactive mRNA pools.

Conclusion

We describe novel approaches of subcellular proteomic profiling and assessment of acute changes on a minute-based time scale. These data expand the current knowledge of acute, non-transcriptional activities of glucocorticoids, including changes in protein subcellular localization, altered translation of quiescent RNA pools, and PKC-mediated cytoskeleton remodeling.
Age and gender differences in seven tests of functional mobility
Authors: Butler Annie A , Menant Jasmine C , Tiedemann Anne C , Lord Stephen R
Published: July 2009

Background

The objective of this study was to examine age and gender differences in seven tests of functional mobility.

Methods

The study included 50 young participants aged 20 to 39 years, and 684 older participants aged 75 to 98 years. Functional mobility measures included the coordinated stability test, the near tandem balance test, the six metre walk test, the sit to stand test with five repetitions, the alternate step test and the stair ascent and descent tests.

Results

Older participants performed significantly worse than the younger participants in all of the functional mobility tests (p < 0.001), with the older women performing worse than the older men in all of the tests (p < 0.05). Significant correlations were found within the older group among all the functional mobility tests scores (r = 0.24–0.87, p < 0.001), and between functional mobility performance and age (r = 0.14–0.35, p < 0.001). People with arthritis and stroke performed worse than people without these conditions in these tests.

Conclusion

This study provides a normative database for performance of young and older community-dwelling people in a battery of validated and reliable functional mobility tests. The results confirm age-related differences in functional mobility between young and older adults.
The prM-independent packaging of pseudotyped Japanese encephalitis virus
Authors: Lee Hee Jung , Min Kyung-Il , Lee Jungeun , Kang Sin-Hyung , Jeon Wonkyung , Nam Jae Hwan , Ju Young Ran , Kim Young Bong
Published: July 2009

As noted in other flaviviruses, the envelope (E) protein of Japanese encephalitis virus (JEV) interacts with a cellular receptor and mediates membrane fusion to allow viral entry into target cells, thus eliciting neutralizing antibody response. The formation of the flavivirus prM/E complex is followed by the cleavage of precursor membrane (prM) and membrane (M) protein by a cellular signalase. To test the effect of prM in JEV biology, we constucted JEV-MuLV pseudotyped viruses that express the prM/E protein or E only. The infectivity and titers of JEV pseudotyped viruses were examined in several cell lines. We also analyzed the neutralizing capacities with anti-JEV sera from JEV-immunized mice. Even though prM is crucial for multiple stages of JEV biology, the JEV-pseudotyped viruses produced with prM/E or with E only showed similar infectivity and titers in several cell lines and similar neutralizing sensitivity. These results showed that JEV-MuLV pseudotyped viruses did not require prM for production of infectious pseudotyped viruses.
Superior dislocation of the patella: a case report
Authors: Cusco Xavier , Seijas Roberto , Ares Oscar , Cugat Jose R , Garcia-Balletbo Montserrat , Cugat Ramon
Published: July 2009

Background

Superior dislocation of the patella is an uncommon condition that mainly occurs in knees with a high patella and medial femorotibial degenerative arthritis. There are no previous reports of this condition occurring in association with tibial valgus osteotomy. Case report: We report the case of a patient in whom vertical dislocation recurred twice at 4 months after tibial valgus osteotomy. To avert additional recurrence or new dislocations, the patient was treated surgically to remove the existing osteophytes. Conclusions: An arthroscopic approach was decided because of the lower associated morbidity and good results with this technique compared to open surgery.
ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside
Authors: Zhou Jianbiao , Goh Boon-Cher , Albert Daniel H , Chen Chien-Shing
Published: July 2009

Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents.

ABT-869, a novel ATP-competitive receptor tyrosine kinase inhibitor is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families. ABT-869 showed potent antiproliferative and apoptotic properties in vitro and in animal cancer xenograft models using tumor cell lines that were "addicted" to signaling of kinases targeted by ABT-869. When given together with chemotherapy or mTOR inhibitors, ABT-869 showed at least additive therapeutic effects. The phase I trial for ABT-869 was recently completed and it demonstrated respectable efficacy in solid tumors including lung and hepatocellular carcinoma with manageable side effects. Tumor cavitation and reduction of contrast enhancement after ABT-869 treatment supported the antiangiogenic activity. The correlative laboratory studies conducted with the trial also highlight potential biomarkers for future patient selection and treatment outcome.

Parallel to the clinical development, in vitro studies on ABT-869 resistance phenotype identified novel resistance mechanism that may be applicable to other TKIs. The future therapeutic roles of ABT-869 are currently been tested in phase II trials.
Medial patellofemoral ligament injury patterns and associated pathology in lateral patella dislocation: an MRI study
Authors: Guerrero Patrick , Li Xinning , Patel Ketan , Brown Michael , Busconi Brian
Published: July 2009

Background

Lateral Patella dislocations are common injuries seen in the active and young adult populations. Our study focus was to evaluate medial patellofemoral ligament (MPFL) injury patterns and associated knee pathology using Magnetic Resonance Imaging studies.

Methods

MRI studies taken at one imaging site between January, 2007 to January, 2008 with the final diagnosis of patella dislocation were screened for this study. Of the 324 cases that were found, 195 patients with lateral patellar dislocation traumatic enough to cause bone bruises on the lateral femoral trochlea and the medial facet of the patella were selected for this study. The MRI images were reviewed by three independent observers for location and type of MPFL injury, osteochondral defects, loose bodies, MCL and meniscus tears. The data was analyzed as a single cohort and by gender.

Results

This study consisted of 127 males and 68 females; mean age of 23 yrs. Tear of the MPFL at the patellar attachment occurred in 93/195 knees (47%), at the femoral attachment in 50/195 knees (26%), and at both the femoral and patella attachment sites in 26/195 knees (13%). Attenuation of the MPFL without rupture occurred in 26/195 knees (13%). Associated findings included loose bodies in 23/195 (13%), meniscus tears 41/195 (21%), patella avulsion/fracture in 14/195 (7%), medial collateral ligament sprains/tears in 37/195 (19%) and osteochondral lesions in 96/195 knees (49%). Statistical analysis showed females had significantly more associated meniscus tears than the males (27% vs. 17%, p = 0.04). Although not statistically significant, osteochondral lesions were seen more in male patients with acute patella dislocation (52% vs. 42%, p = 0.08).

Conclusion

Patients who present with lateral patella dislocation with the classic bone bruise pattern seen on MRI will likely rupture the MPFL at the patellar side. Females are more likely to have an associated meniscal tear than males; however, more males have underlying osteochondral lesions. Given the high percentage of associated pathology, we recommend a MRI of the knee in all patients who present with acute patella dislocation.
Using Medical Emergency Teams to detect preventable adverse events
Authors: Iyengar Akshai , Baxter Alan , Forster Alan J
Published: July 2009

Introduction

Medical Emergency Teams (METs), also known as Rapid Response Teams, are recommended as a patient safety measure. A potential benefit of implementing an MET is the capacity to systematically assess preventable adverse events, which are defined as poor outcomes caused by errors or system design flaws. We describe how we used MET calls to systematically identify preventable adverse events in an academic tertiary care hospital, and describe our surveillance results.

Methods

For four weeks we collected standard information on consecutive MET calls. Within a week of the MET call, a multi-disciplinary team reviewed the information and rated the cause of the outcome using a previously developed rating scale. We classified the type and severity of the preventable adverse event.

Results

We captured information on all 65 MET calls occurring during the study period. Of these, 16 (24%, 95% confidence interval [CI] 16%–36%) were felt to be preventable adverse events. The most common cause of the preventable adverse events was error in providing appropriate therapy despite an accurate diagnosis. One service accounted for a disproportionate number of preventable adverse events (n = 5, [31%, 95% CI 14%–56%]).

Conclusions

Our method of reviewing MET calls was easy to implement and yielded important results. Hospitals maintaining an MET can use our method as a preventable adverse event detection system at little additional cost.
MotifAdjuster: a tool for computational reassessment of transcription factor binding site annotations
Authors: Keilwagen Jens , Baumbach Jan , Kohl Thomas A , Grosse Ivo
Published: July 2009

Valuable binding-site annotation data are stored in databases. However, several types of errors can, and do, occur in the process of manually incorporating annotation data from the scientific literature into these databases. Here, we introduce MotifAdjuster http://dig.ipk-gatersleben.de/MotifAdjuster.html, a tool that helps to detect these errors, and we demonstrate its efficacy on public data sets.
Kinin B1 receptor activation turns on exocytosis of matrix metalloprotease-9 and myeloperoxidase in human neutrophils: involvement of mitogen-activated protein kinase family
Authors: Ehrenfeld Pamela , Matus Carola E , Pavicic Francisca , Toledo Cesar , Nualart Francisco , Gonzalez Carlos B , Burgos Rafael A , Bhoola Kanti D , Figueroa Carlos D
Published: July 2009

Proinflammatory peptides known as kinins activate the human neutrophil and induce the release of its primary and tertiary granules.

During neutrophil activation and degranulation, MMP-9 and MPO are released into the extracellular space to propagate inflammatory disorders. As kinin peptides are major participants in acute inflammatory responses, and the G-protein-coupled B1R mediates the chemotaxis of human neutrophils, we examined the release of the neutrophil enzymes MMP-9 and MPO by the B1R agonist LDBK and determined the signaling pathways that may regulate this cellular effect. Cytochalasin-treated and -untreated neutrophils were suspended in HBSS and stimulated with a range concentration of LDBK for 5 min. Zymography and Western blotting revealed that LDBK induced the release of MMP-9 and MPO. The use of specific signaling transduction inhibitors showed that release of MMP-9 depended on ERK1/2 and p38 MAPKs, whereas release of MPO involved only the p38 cascade. Inhibition of the key steps in these pathways showed that the release of both enzymes depended on PKC and PI3K. Stimulation of neutrophils with LDBK produced phosphorylation of ERK1/2 and p38 MAPK, which was inhibited by B1R antagonists. The phosphorylated ERK1/2 MAPK translocated to the neutrophil nucleus, suggesting that transcription of new genes may follow activation of B1R. Our results demonstrate that in human neutrophils, activation of kinin B1R by LDBK initiates separate signaling cascades that trigger the release of MMP-9 and MPO from tertiary and primary granules, respectively, suggesting that the B1R plays a pivotal role in inflammatory disorders.
Graded Egfr activity patterns theDrosophilaeggshell independently of autocrine feedback
Authors: Lachance Jean-François Boisclair , Lomas Mariana Fregoso , Eleiche Aliaa , Kerr Phoenix Bouchard , Nilson Laura A.
Published: July 2009

The pattern of the Drosophila eggshell is determined by the establishment of a complex and stereotyped pattern of cell fates in the follicular epithelium of the ovary. Localized activation of the Epidermal growth factor receptor (Egfr) is essential for this patterning. Modulation of Egfr pathway activity in time and space determines distinct fates at their appropriate locations, but the details of how Egfr signaling is regulated and how the profile of Egfr activity corresponds to cell fate remain unclear. Here we analyze the effect of loss of various Egfr regulators and targets on follicle cell patterning, using a marker for follicle cell fate, and on the mature eggshell phenotype, using a novel eggshell marker. We show, contrary to current patterning models, that feedback regulation of Egfr activity by the autocrine ligand Spitz and the inhibitor Argos is not necessary for patterning. Given the cell-autonomous nature of the mutant phenotypes we observed, we propose instead that the pattern of cell fates is generated by spatial information derived directly from the germline ligand Gurken, without a requirement for subsequent patterning by diffusible Egfr regulators in the follicular epithelium.
Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling
Authors: Jülich Dörthe , Mould A. Paul , Koper Ewa , Holley Scott A.
Published: July 2009

Extracellular matrixes (ECMs) coat and subdivide animal tissues, but it is unclear how ECM formation is restricted to tissue surfaces and specific cell interfaces. During zebrafish somite morphogenesis, segmental assembly of an ECM composed of Fibronectin (FN) depends on the FN receptor Integrinα5β1. Using in vivo imaging and genetic mosaics, our studies suggest that incipient Itgα5 clustering along the nascent border precedes matrix formation and is independent of FN binding. Integrin clustering can be initiated by Eph/Ephrin signaling, with Ephrin reverse signaling being sufficient for clustering. Prior to activation, Itgα5 expressed on adjacent cells reciprocally and non-cell-autonomously inhibits spontaneous Integrin clustering and assembly of an ECM. Surface derepression of this inhibition provides a self-organizing mechanism for the formation and maintenance of ECM along the tissue surface. Within the tissue, interplay between Eph/Ephrin signaling, ligand-independent Integrin clustering and reciprocal Integrin inhibition restricts de novo ECM production to somite boundaries.
Feedback control of the EGFR signaling gradient: superposition of domain-splitting events inDrosophilaoogenesis
Authors: Zartman Jeremiah J. , Kanodia Jitendra S. , Cheung Lily S. , Shvartsman Stanislav Y.
Published: July 2009

The morphogenesis of structures with repeated functional units, such as body segments and appendages, depends on multi-domain patterns of cell signaling and gene expression. We demonstrate that during Drosophilaoogenesis, the two-domain expression pattern of Broad, a transcription factor essential for the formation of the two respiratory eggshell appendages, is established by a single gradient of EGFR activation that induces both Broad and Pointed, which mediates repression of Broad. Two negative-feedback loops provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and Sprouty, control the number and position of Broad-expressing cells and in this way influence eggshell morphology. Later in oogenesis, the gradient of EGFR activation is split into two smaller domains in a process that depends on Argos, a secreted antagonist of EGFR signaling. In contrast to the previously proposed model of eggshell patterning, we show that the two-domain pattern of EGFR signaling is not essential for specifying the number of appendages. Thus,the processes that define the two-domain patterns of Broad and EGFR activation are distinct; their actions are separated in time and have different effects on eggshell morphology.
TheC. elegansTailless/TLX transcription factornhr-67controls neuronal identity and left/right asymmetric fate diversification
Authors: Sarin Sumeet , Antonio Celia , Tursun Baris , Hobert Oliver
Published: July 2009

An understanding of the molecular mechanisms of cell fate determination in the nervous system requires the elucidation of transcriptional regulatory programs that ultimately control neuron-type-specific gene expression profiles. We show here that the C. elegans Tailless/TLX-type, orphan nuclear receptor NHR-67 acts at several distinct steps to determine the identity and subsequent left/right (L/R) asymmetric subtype diversification of a class of gustatory neurons, the ASE neurons. nhr-67 controls several broad aspects of sensory neuron development and, in addition, triggers the expression of a sensory neuron-type-specific selector gene, che-1, which encodes a zinc-finger transcription factor. Subsequent to its induction of overall ASE fate, nhr-67 diversifies the fate of the two ASE neurons ASEL and ASER across the L/R axis by promoting ASER and inhibiting ASEL fate. This function is achieved through direct expression activation by nhr-67 of the Nkx6-type homeobox gene cog-1,an inducer of ASER fate, that is inhibited in ASEL through the miRNA lsy-6. Besides controlling bilateral and asymmetric aspects of ASE development, nhr-67 is also required for many other neurons of diverse lineage history and function to appropriately differentiate,illustrating the broad and diverse use of this type of transcription factor in neuronal development.
Seasonal variation in liver function tests: a time-series analysis of outpatient data
Authors: Miyake Kazunori , Miyake Noriko , Kondo Shigemi , Tabe Yoko , Ohsaka Akimichi , Miida Takashi
Published: July 2009

Background

Long-term physiological variations, such as seasonal variations, affect the screening efficiency at medical checkups. This study examined the seasonal variation in liver function tests using recently described data-mining methods.

Methods

The ‘latent reference values’ of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase ( γGT), cholinesterase (ChE) and total bilirubin (T-Bil) were extracted from a seven-year database of outpatients (aged 20–79 yr; comprising approximately 1,270,000 test results). After calculating the monthly means for each variable, the time-series data were separated into trend and seasonal components using a local regression model (Loess method). Then, a cosine function model (cosinor method) was applied to the seasonal component to determine the periodicity and fluctuation range. A two-year outpatient database (215,000 results) from another hospital was also analysed to confirm the reproducibility of these methods.

Results

The serum levels of test results tended to increase in the winter. The increase in AST and ALT was about 6% in men and women, and was greater than that in ChE, ALP (in men and women) and γGT (in men). In contrast, T-Bil increased by 3.6% (men) and 5.0% (women) in the summer. The total protein and albumin concentrations did not change significantly. AST and ALT showed similar seasonal variation in both institutions in the comparative analysis.

Conclusions

The liver function tests were observed to show seasonal variations. These seasonal variations should therefore be taken into consideration when establishing either reference intervals or cut-off values, which are especially important regarding aminotransferases.
Measurement of immunoglobulin A in saliva by particle-enhanced nephelometric immunoassay: sample collection, limits of quantitation, precision, stability and reference range
Authors: Booth Christine K , Dwyer Dan B , Pacque Paul F , Ball Madeleine J
Published: July 2009

Background

Total immunoglobulin A in saliva (s-IgA) is normally assayed using an enzyme-linked immunosorbent assay. We have investigated methodological issues relating to the use of particle-enhanced nephelometric immunoassay (PENIA) to measure s-IgA in whole unstimulated saliva and determine its reference range.

Methods

Whole unstimulated resting saliva was collected to determine sample stability (temperature, time, effect of a protease inhibitor), limit of quantitation (LOQ), assay precision and analytical variation. The reference range for 134 healthy adults was determined.

Results

Linearity was excellent (4–10.3 mg L−1, P < 0.001; R2 = 0.997) and without significant bias (mean of −0.7%). The lowest intra- and inter-analytical coefficients of variation were 1.8% and 7.5% and LOQ was 1.4 mg L−1. The concentration of s-IgA is stable at room temperature for up to 6 h, at 4°C for 48 h, at −4°C for two weeks and at −80°C for up to 1.3 yr. There is no evidence that a protease inhibitor increases the stability or that repeated freeze–thawing cycles degrade sample quality. The reference ranges for s-IgA concentration, s-IgA secretion, s-IgA:albumin and s-IgA:osmolality were 15.9–414.5 mg L−1, 7.2–234.9 μg min−1, 0.4–19 and 0.6–8.9, respectively.

Conclusion

Automated PENIA assay of s-IgA is precise and accurate. High stability of collected saliva samples and the ease and speed of the assay make this an ideal method for use in athletic and military training situations. The convenience of measuring albumin and IgA on the same analytical platform adds to the practicability of the test.
An audit of oral glucose tolerance tests at a large teaching hospital: indications, outcomes and confounding factors
Authors: Ryan Joshua , Siriwardhana Deepani , Vasikaran Samuel D
Published: July 2009

Background

Australian guidelines on the diagnosis of diabetes mellitus (DM) recommend performing an oral glucose tolerance test (OGTT) in people with fasting plasma glucose (FPG) values of 5.5–6.9 mmol/L.

Aim

To evaluate indications, outcomes and confounding factors of OGTTs performed at a large teaching hospital and to compare them with Australian DM guidelines.

Method

A retrospective audit of OGTTs performed over an 18-month period in a teaching hospital in a major Australian city. Information gathered included co-morbidities; medications; risk factors for type 2 DM; indication for OGTT; results of OGTT and previous glucose tests.

Results

All 129 OGTTs identified were included in the audit. Eighty-nine (69%) were male, with a median age of 57 years (range 19–86), and 3% were of Australian Aboriginal ethnicity. An indication for OGTT was identified in 93%, including FPG 5.5–6.9 mmol/L (36%) and random plasma glucose (RPG) 5.5–11.0 mmol/L (19%). Other indications for OGTT identified included polycystic ovary syndrome or metabolic syndrome (8%), peripheral neuropathy (3%) and as part of a research protocol (12%). Forty-two (35%) were inpatients at the time of OGTT, of which 35 (30%) were admitted for acute medical or surgical illnesses such as stroke. Nineteen percent were taking medications known to affect plasma glucose (e.g. oral corticosteroids).

Conclusion

Only 55% of OGTTs had a previous FPG or RPG value warranting OGTT using current Australian DM guidelines. Other valid indications for OGTT were identified in the majority of the remainder. In addition, 41% were performed in the presence of confounding factors (such as acute illness or medications known to affect plasma glucose). Many of the OGTTs that are currently being performed are in the presence of confounding factors that could cause misleading results.
Evaluation of redox statuses in patients with hepatitis B virus-associated hepatocellular carcinoma
Authors: Tsai Shih-Meng , Lin Shu-Kai , Lee King-The , Hsiao Jen-Kuei , Huang Jung-Chih , Wu Szu-Hsien , Ma Hsu , Wu Szu-Hwa , Tsai Li-Yu
Published: July 2009

Background

Excess reactive oxygen species related to neoplasia of liver has been established. Essentially, the human body has developed different antioxidant systems for defence against these attacks. To evaluate the redox status in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV), the most important aetiological factor in Taiwan, changes in O2. generation, lipid peroxidation as well as antioxidant status in the blood of HCC patients with HBV carriers for more than 20 years were measured.

Methods

Superoxide anion radical (O2.−) generation and the levels of malondialdehyde (MDA) served as an index of lipid peroxidation along with the analyses of activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx); also, glutathione status, including reduced glutathione (GSH) and oxidized glutathione (GSSG), and the levels of vitamins A, C and E were determined.

Results

In 54 patients, the levels of O2.−, MDA and GSSG, and the activities of SOD and GRx of blood were significantly higher than those of 57 controls. Conversely, the levels of GSH and total GSH, and GSH/GSSG ratio, and vitamins A and C were significantly decreased. Additionally, there were no significant changes in the activity of GPx and the levels of vitamin E.

Conclusions

Our data suggest that the redox statuses in patients with HBV-associated HCC were elevated or decreased in certain parameters. However, the increased activities of antioxidant enzymes may be a compensatory up-regulation and the decrease antioxidant statuses were responses to the enhanced oxidative stress in those patients.
Serum free light chain assay reduces the need for serum and urine immunofixation electrophoresis in the evaluation of monoclonal gammopathy
Authors: Fulton Richard B , Fernando Suran L
Published: July 2009

Background

The potential for serum free light chain (sFLC) assay measurements to replace urine electrophoresis (uEPG) and to also diminish the need for serum immunofixation (sIFE) in the screening for monoclonal gammopathy was assessed. A testing algorithm for monoclonal protein was developed based on our data and cost analysis.

Methods

Data from 890 consecutive sFLC requests were retrospectively analysed. These included 549 samples for serum electrophoresis (sEPG), 447 for sIFE, and 318 for uEPG and urine immunofixation (uIFE). A total of 219 samples had sFLC, sEPG, sIFE and uEPG + uIFE performed. The ability of different test combinations to detect the presence of monoclonal proteins was compared.

Results

The sFLC κ/ λ ratio (FLC ratio) indicated monoclonal light chains in 12% more samples than uEPG + uIFE. The combination of sEPG and FLC ratio detected monoclonal proteins in 49% more samples than the combination of sEPG and sIFE. Furthermore, the sEPG + FLC ratio combination detected monoclonal protein in 6% more samples than were detected by the combined performance of sEPG, sIFE, uEPG and uIFE. However, non-linearity of the assay, the expense of repeat determinations due to the narrow measuring ranges, and frequent antigen excess checks were found to be limitations of the sFLC assay in this study.

Conclusion

The FLC ratio is a more sensitive method than uIFE in the detection of monoclonal light chains and may substantially reduce the need for onerous 24 h urine collections. Our proposed algorithm for the evaluation of monoclonal gammopathy incorporates the sFLC assay, resulting in a reduction in the performance of labour intensive sIFE and uEPG + uIFE while still increasing the detection of monoclonal proteins.
Design, implementation and results of the quality control program for the Australian government's point of care testing in general practice trial
Authors: Shephard Mark , Shephard Anne , Watkinson Les , Mazzachi Beryl , Worley Paul
Published: July 2009

Background

From 2005 to 2007 the Australian Government funded a multicentre, clustered randomized controlled trial to determine the clinical effectiveness, cost-effectiveness, satisfaction and safety of point of care testing (PoCT) in general practice (GP). PoC tests measured (and devices used) in the trial were haemoglobin A1c and urine albumin:creatinine ratio (DCA 2000), lipids (Cholestech LDX) and international normalized ratio (CoaguChek S).

Methods

An internal quality control (QC) program was developed as part of a quality management framework for the trial. PoCT device operators were provided with a colour-coded QC Result Sheet and QC Action Sheet for on-site recording and interpreting of their results. Within-practice imprecision for QC testing was calculated and compared with the analytical goals for imprecision set prior to the trial.

Results

The average participation rate for QC testing was 91% or greater. Median within-practice imprecision met the analytical goals for all PoC tests, except for high-density lipoprotein-cholesterol (HDL-C) where observed performance was outside the minimum goal for one level and one lot number of QC. Most practices achieved the imprecision goals for all analytes, with the principal exception of HDL-C.

Conclusions

Results from QC testing indicate that PoCT in the GP trial met the analytical goals set for the trial, with the exception of HDL-C.
Convexity and Concavity Detection in Computational Graphs: Tree Walks for Convexity Assessment
Authors: Fourer Robert , Maheshwari Chandrakant , Neumaier Arnold , Orban Dominique , Schichl Hermann
Published: July 2009

We examine symbolic tools associated with two modeling systems for mathematical programming, which can be used to automatically detect the presence or absence of convexity and concavity in the objective and constraint functions, as well as convexity of the feasible set in some cases. The coconut solver system [Schichl, H. 2004a. COCONUT: COntinuous CONstraints—Updating the technology] focuses on nonlinear global continuous optimization and possesses its own modeling language and data structures. The Dr. Ampl meta-solver [Fourer, R., D. Orban. 2007. Dr. Ampl—A meta solver for optimization. Technical Report G-2007-10, GERAD, Montréal] aims to analyze nonlinear differentiable optimization models and hooks into the ampl Solver Library [Gay, D. M. 2002. Hooking your solver to AMPL]. Our symbolic convexity analysis may be supplemented, when it returns inconclusive results, with a numerical phase that may detect nonconvexity. We report numerical results using these tools on sets of test problems for both global and local optimization.
A Tree Search Algorithm for Solving the Container Loading Problem
Authors: Fanslau Tobias , Bortfeldt Andreas
Published: July 2009

This paper presents a tree search algorithm for the three-dimensional container loading problem (3D-CLP). The 3D-CLP is the problem of loading a subset of a given set of rectangular boxes into a rectangular container so that the packing volume is maximized. The method includes two variants: the full-support variant guarantees full support from below for all packed boxes, although this constraint is not taken into account by the nonsupport variant. The guillotine cut constraint is considered by both variants. The method is mainly based on two concepts. On the one hand, the block building approach is generalized. Not only are blocks of identical boxes in the same spatial orientation applied but also blocks of different boxes with small inner gaps. On the other hand, the tree search is carried out in a special fashion called a partition-controlled tree search. This makes the search both efficient and diverse, enabling a sufficient search width as well as a suitable degree of foresight. The approach achieves excellent results for the well-known 3D-CLP instances suggested by Bischoff and Ratcliff [Bischoff, E. E., M. S. W. Ratcliff. 1995. Issues in the development of approaches to container loading. Omega 23(4) 377–390] with reasonable computing time.
Worst-Case Conditional Value-at-Risk with Application to Robust Portfolio Management
Authors: Zhu Shushang , Fukushima Masao
Published: July 2009

This paper considers the worst-case Conditional Value-at-Risk (CVaR) in the situation where only partial information on the underlying probability distribution is available. The minimization of the worst-case CVaR under mixture distribution uncertainty, box uncertainty, and ellipsoidal uncertainty are investigated. The application of the worst-case CVaR to robust portfolio optimization is proposed, and the corresponding problems are cast as linear programs and second-order cone programs that can be solved efficiently. Market data simulation and Monte Carlo simulation examples are presented to illustrate the proposed approach.
Autism, “Recovery (to Normalcy),” and the Politics of Hope
Authors: Broderick Alicia A.
Published: July 2009

This article draws on the traditions of critical discourse analysis (N. Fairclough, 1995, 2001; M. Foucault, 1972, 1980; J. P. Gee, 1999) in critically examining the discursive formation of “recovery” from autism in applied behavioral analysis (ABA) discourse and its relationship to constructs of hope. Constituted principally in the work of O. I. Lovaas (1987) and C. Maurice (1993), and central to ABA discourse on recovery, has been the construction of a particular vision of hope that has at least 2 integral conceptual elements: (a) Hope for recovery within ABA discourse is constructed in binary opposition to hopelessness, and (b) recovery within ABA discourse is discursively constructed as “recovery (to normalcy).” The author analyzes these 2 pivotal ABA texts within the context of an analysis of other uses of the term recovery in broader bodies of literature: (a) within prior autism-related literature, particularly autobiography, and (b) within literature emanating from the psychiatric survivors' movement. If, indeed, visions of hope inform educational policy and decision making, this analysis addresses S. Danforth's (1997) cogent query, “On what basis hope?”, and asserts that moral and political commitments should be central sources of visions of hope and, therefore, inform educational policy and decision making for young children with labels of autism.
Implications of Increased C-Reactive Protein for Cardiovascular Risk Stratification in Black and White Men and Women in the US
Authors: Cushman Mary , McClure Leslie A , Howard Virginia J , Jenny Nancy S , Lakoski Susan G , Howard George
Published: July 2009

Background: We evaluated prevalence and correlates of increased high-sensitivity C-reactive protein (hsCRP) in a large population of blacks and whites, and the impact of hsCRP measurement on coronary heart disease risk reclassification.

Methods: We studied 19 080 participants of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study (age >45 years, without vascular diagnoses, and living dispersed across the US). A total of 8309 nondiabetic participants not using lipid-lowering medications were classified into 4 risk categories based on the Framingham vascular disease risk score. Participants with hsCRP <1 mg/L were reclassified to the next lower risk group, and those with hsCRP >3 mg/L to the next higher risk group. We also assessed reclassification of risk based on the Reynolds vascular risk score, incorporating hsCRP and family history.

Results: Overall, 40% of participants had hsCRP >3 mg/L. Blacks, women, and obese people were at highest risk for increased hsCRP. Among nondiabetic women at 5%–20% Framingham vascular predicted risk, hsCRP data led to reclassification of 48% to a higher risk group and 19% to a lower risk group. For men, these percentages were 24% and 40%. Blacks were more often reclassified to a higher risk group than whites. Reynolds vascular risk score data led to reclassification of 85% of women and 67% of men, almost exclusively to a lower risk group than the Framingham vascular score.

Conclusions: In this national study, a majority of participants, especially blacks and women, were reclassified to a different 10-year vascular risk category on the basis of hsCRP testing after risk assessment. With the inclusion of hsCRP testing data, the Reynolds risk score classified the population differently than the new Framingham vascular score. .
Reviews
Authors: MacDonald Claire
Published: July 2009

Playing with Words: The Spoken Word in Artistic Practice, ed. Cathy Lane (2008) Cromford, Derbyshire: RGAP/CRiSAP, 206 pp., ISBN 9780955827334, 12.99
The book objects: writing and performance
Authors: Webb Jen
Published: July 2009

It does not take many steps for book to transform from predicate to subject, or for object to change from noun to verb. In this article I discuss the book as concept and as object, drawing on the history of the book, and contemporary discourse and practice, to suggest how books engage
us as members of society and as individual practitioners. The article draws on Deleuze and Guattari's reconceptualization of the book as plateau, and as assemblages of strata, working rhizomatically rather than programmatically. It draws too on Foucault's reclamation of the book as experience
and experiment rather than knowledge-object to suggest ways of encountering the self and the world in the act of writing. Perhaps not surprisingly, I reject the death of the book scenario, and instead offer an expanded notion of the book as that which can lend itself to performative actualizations,
to the magic of the fetish object, and to the work of thought itself: the book as cognitive event; the book as ideas machine. To exemplify these notions, I discuss some recent moves in Australia to explore handmade books that operate not only as art objects, but as research products too, and
also suggest how digital books offer alternatives to the conventional performances of identity, for writers and readers.