A main-group analogue of housene: the subtle influence of the inert-pair effect in group 15 clusters.
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Journal Article↗
Biomedical subjects
Michael Green
Publications and source records attributed to Michael Green.
Comparison between neural networks and multiple logistic regression to predict acute coronary syndrome in the emergency room.
OBJECTIVE: Patients with suspicion of acute coronary syndrome (ACS) are difficult to diagnose and they represent a very heterogeneous group. Some require immediate treatment while others, with only minor disorders, may be sent home. Detecting ACS patients using a machine learning approach would be advantageous in many situations. METHODS AND MATERIALS: Artificial neural network (ANN) ensembles and logistic regression models were trained on data from 634 patients presenting an emergency department with chest pain. Only data immediately available at patient presentation were used, including electrocardiogram (ECG) data. The models were analyzed using receiver operating characteristics (ROC) curve analysis, calibration assessments, inter- and intra-method variations. Effective odds ratios for the ANN ensembles were compared with the odds ratios obtained from the logistic model. RESULTS: The ANN ensemble approach together with ECG data preprocessed using principal component analysis resulted in an area under the ROC curve of 80%. At the sensitivity of 95% the specificity was 41%, corresponding to a negative predictive value of 97%, given the ACS prevalence of 21%. Adding clinical data available at presentation did not improve the ANN ensemble performance. Using the area under the ROC curve and model calibration as measures of performance we found an advantage using the ANN ensemble models compared to the logistic regression models. CONCLUSION: Clinically, a prediction model of the present type, combined with the judgment of trained emergency department personnel, could be useful for the early discharge of chest pain patients in populations with a low prevalence of ACS.
Acute Disease↗
Instruments for evaluating education in evidence-based practice: a systematic review.
CONTEXT: Evidence-based practice (EBP) is the integration of the best research evidence with patients' values and clinical circumstances in clinical decision making. Teaching of EBP should be evaluated and guided by evidence of its own effectiveness. OBJECTIVE: To appraise, summarize, and describe currently available EBP teaching evaluation instruments. DATA SOURCES AND STUDY SELECTION: We searched the MEDLINE, EMBASE, CINAHL, HAPI, and ERIC databases; reference lists of retrieved articles; EBP Internet sites; and 8 education journals from 1980 through April 2006. For inclusion, studies had to report an instrument evaluating EBP, contain sufficient description to permit analysis, and present quantitative results of administering the instrument. DATA EXTRACTION: Two raters independently abstracted information on the development, format, learner levels, evaluation domains, feasibility, reliability, and validity of the EBP evaluation instruments from each article. We defined 3 levels of instruments based on the type, extent, methods, and results of psychometric testing and suitability for different evaluation purposes. DATA SYNTHESIS: Of 347 articles identified, 115 were included, representing 104 unique instruments. The instruments were most commonly administered to medical students and postgraduate trainees and evaluated EBP skills. Among EBP skills, acquiring evidence and appraising evidence were most commonly evaluated, but newer instruments evaluated asking answerable questions and applying evidence to individual patients. Most behavior instruments measured the performance of EBP steps in practice but newer instruments documented the performance of evidence-based clinical maneuvers or patient-level outcomes. At least 1 type of validity evidence was demonstrated for 53% of instruments, but 3 or more types of validity evidence were established for only 10%. High-quality instruments were identified for evaluating the EBP competence of individual trainees, determining the effectiveness of EBP curricula, and assessing EBP behaviors with objective outcome measures. CONCLUSIONS: Instruments with reasonable validity are available for evaluating some domains of EBP and may be targeted to different evaluation needs. Further development and testing is required to evaluate EBP attitudes, behaviors, and more recently articulated EBP skills.
Educational Measurement↗
A comparison of quantitative-competitive and realtime PCR assays using an identical target sequence to detect Epstein-Barr virus viral load in the peripheral blood.
Monitoring the load of Epstein-Barr virus (EBV) in the peripheral blood by quantitative PCR has been accepted as a useful tool for predicting the onset of EBV related diseases, confirming an EBV disease diagnosis and following the response to treatment interventions. In the present study, the use of a realtime polymerase chain reaction (rt-PCR) assay developed for unpurified cell preparations was examined and the results of the realtime assay were compared to an EBV quantitative-competitive PCR assay (QC-PCR). Both assays use the same target sequence and the same method for determining the standard value for the copy number of EBV genomes present. A comparison of 572 PCR results reveals that the realtime assay gave 5-10-fold higher values than the QC-PCR. Fifty-one results (8.9%) were discordant between the two sets of data. The most commonly encountered discordant result was detection of low amounts of EBV DNA by the rt-PCR assay that were not detected in specimens by QC-PCR. The two assays had a high degree of correlation across the range of load detection allowing clinically relevant threshold values determined in the QC-PCR assay to be inferred for the rt-PCR assay. External normalization of the rt-PCR assay was determined to be an important tool for monitoring the quality and/or quantity of human DNA in the starting material. rt-PCR assays with unpurified cell lysates compare favorably with quantitative-competitive assays and when normalized offer real advantages in specimen preparation, assay manipulations and reproducibility over both quantitative-competitive assays and realtime assays that require purified nucleic acid inputs.
Blood↗
A new reaction pathway in organophosphorus chemistry: competing S(N)2 and AE' pathways for nucleophilic attack at a phosphorus-carbon cage compound.
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Journal Article↗
Structure and dynamics of the N-terminal loop of PsbQ from photosystem II of Spinacia oleracea.
Infrared and Raman spectroscopy were applied to identify restraints for the structure determination of the 20 amino acid loop between two beta-sheets of the N-terminal region of the PsbQ protein of the oxygen evolving complex of photosystem II from Spinacia oleracea by restraint-based homology modeling. One of the initial models has shown a stable fold of the loop in a 20 ns molecular dynamics simulation that is in accordance with spectroscopic data. Cleavage of the first 12 amino acids leads to a permanent drift in the root means square deviation of the protein backbone and induces major structural changes.
Amino Acid Sequence↗
Cationic phosphorus-carbon-pnictogen cages isolobal to [C5R5]+.
The cationic cages nido-[C2Bu(t)2P2E]+ (E = As, Sb), which are isolobal to the cyclopentadienyl cation, adopt square based pyramidal structures with the heavy pnictogen atom at the apex; NMR and computational methods have been used to probe the dynamic behaviour of the complexes.
Journal Article↗
Group A streptococcus.
Group A streptococci (GAS) are gram positive cocci that can be divided into more than 100 M-serotypes or emm types based on their M proteins. Their virulence is related directly to the M protein on the cell surface that inhibits phagocytosis. Although it is more commonly thought of in the context of causing clinical illness, Streptococcus pyogenes can colonize the pharynx and skin. Infections due to GAS include pharyngitis, impetigo, ecthyma, erysipelas, and cellulitis. These infections, as well as the manifestations of invasive disease including streptococcal toxic shock syndrome and necrotizing fasciitis, will be reviewed in this article. Also included will be the nonsuppurative complications of GAS infections, acute rheumatic fever and post streptococcal glomerular nephritis. GAS is an important cause of infections in children in both the ambulatory and hospital settings. Current efforts aimed at the development of a vaccine are warranted but remain in preliminary stages at this time.
Anti-Bacterial Agents↗
The tissue distribution of Evans blue dye in a sheep model of sentinel node biopsy.
BACKGROUND: Tc-Evans blue is a 'single dose' agent for lymphatic mapping combining radioactivity and blue dye for sentinel node identification. The mechanism and distribution of blue dye retention in the lymph node is not clearly understood. OBJECTIVE: To demonstrate the cellular distribution of Tc-Evans blue in sheep sentinel lymph nodes by measuring the radioactivity of different tissue components and correlating this with pathological examination. METHODS: Tc-Evans blue was used to identify sheep lymph nodes. Part of each node was sent for pathological examination including imprint cytology, and frozen and permanent section examination. Sections were examined without stains, with only red stains and conventional haematoxylin & eosin staining. The remaining nodal tissue was homogenized and components separated by enzymatic digestion and density gradient centrifugation. Fractions representing each tissue component were counted in a gamma counter and the distribution of Tc-Evans blue calculated. RESULTS: A dispersed population of blue staining cells was found. Their distribution, number and size indicated that they were histiocytes such as macrophages or antigen presenting cells. Radioactivity was distributed throughout the lymph node. Over 70% remained in the plasma, 19% in the leukocyte layer, and 10% was associated with erythrocytes and undigested tissue. CONCLUSION: The accumulation of radioactivity and blue colour in the lymph nodes indicates the mechanism of retention is a result of the binding interaction between Tc-Evans blue-protein and lymph node histiocytes including macrophages and antigen presenting cells.
Animals↗
GFP-tagged PrP supports compromised prion replication in transgenic mice.
The ability of green fluorescent protein (GFP)-prion protein (PrP) fusions to support prion propagation has not been demonstrated. Here, we show that while transgenic mice expressing PrP tagged at its amino terminus with enhanced GFP, referred to as EGFPrP-N, supported prion replication, disease onset was prolonged, the brains of diseased mice did not exhibit typical disease neuropathology and disease-associated EGFPrP-N lacked the full spectrum of biochemical properties normally associated with PrP(Sc). Co-expression of wild-type PrP and EGFPrP-N substantially reduced prion incubation times and resulted in accumulation of protease-resistant EGFPrP(Sc)-N in the brains of transgenic mice as well as chronically infected cultured cells, suggesting that wild-type PrP rescued a compromised amino terminal function in EGFPrP-N. While our results show that EGFPrP(C)-N adopts a conformation necessary for the production of infectious prions, the synergistic interaction of wild-type and EGFPrP-N underscores the importance of the amino terminus in modulating prion pathogenesis.
Animals↗
Ethnic differences in nicotine metabolic rate among New Zealanders.
AIMS: To estimate (a) the prevalence of gene variants associated with slow nicotine metabolism in the general Maori population and (b) nicotine intake and metabolic rate in Maori and European smokers. METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3'-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke's Bay Region (6 Maori and 6 European). RESULTS: (a) The frequencies of the slow nicotine metabolising variants, CYP2A6*9 and *4, were significantly higher in Maori compared to European (p<0.01). Indeed, the prevalence of the CYP2A6*9 variant in these Maori was among the highest in the world (approximately 20%). (b) In smokers, the Maori group had approximately 35% lower 3-HC:COT ratios indicating a reduced metabolic rate, as well as 2-fold lower cotinine levels per cigarette smoked, indicating reduced nicotine intake (p<0.05). The CYP2A6*9 allele was significantly more frequent in Maori smokers (70%) compared to Europeans (30%), p=0.03. CONCLUSIONS: The findings of this study provide evidence that Maori are genetically slower nicotine metabolisers compared to Europeans. Although more research is required, this study may help explain ethnic differences in smoking initiation and may also have important implications for smoking cessation programs - since metabolic differences between groups with varying ancestry implies that different optimal dosages of nicotine replacement therapy may be required for successful quitting.
Aryl Hydrocarbon Hydroxylases↗
Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.
PURPOSE: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients were randomly assigned to six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. RESULTS: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. CONCLUSION: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.
Adolescent↗
Efficacy of the live attenuated Francisella tularensis vaccine (LVS) in a murine model of disease.
A live attenuated vaccine Francisella tularensis live vaccine strain (LVS), that confers protection against tularemia infection in a number of animal models including man was developed during the 1960s in the US. In this study, we have established the median lethal dose (MLD) after intraperitoneal (i.p.) or intravenous (i.v.) delivery of NDBR Lot 4 F. tularensis LVS to be 4 cfu and 2.24 x 10(4) cfu, respectively, in BALB/c mice and less than 1 cfu and 1.29 x 10(4) cfu, respectively, in C57BL/6 mice. When delivered subcutaneously, the MLD for F. tularensis LVS was greater then 1 x 10(8) cfu in both strains of mouse. Using mouse models of systemic tularemia infection it was demonstrated that F. tularensis LVS immunised BALB/c mice were fully protected after challenge with approximately 1000 MLD of a strain of F. tularensis subsp. tularensis or a strain of F. tularensis subsp. holarctica. Under similar challenge conditions, protection in C57BL/6 mice was only evident against a subsp. holarctica strain. In BALB/c mice, protection against a subsp. holarctica strain was achieved 4 days after F. tularensis LVS immunisation whereas protection against a subsp. tularensis strain was only evident 14 days after F. tularensis LVS immunisation.
Animals↗
Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule.
PURPOSE: This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal. RESULTS: In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments. CONCLUSION: Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.
Adult↗
Biosynthesis of the IFN-gamma binding protein of ectromelia virus, the causative agent of mousepox.
Ectromelia virus (ECTV), the causative agent of mousepox, expresses an extracellular interferon-gamma binding protein (IFN-gammaBP) with homology to the ligand binding domains of the IFN-gamma high affinity receptor (IFN-gammaR1). Unlike the cellular receptor, the IFN-gammaBP binds IFN-gamma from several species. The IFN-gammaBP is synthesized early after infection, accumulating in the extracellular milieu as dimers composed of two protein species with Mr of 34.6 or 33.0 kDa. Homodimers are covalently linked by an interchain disulphide bond at position 216. The IFN-gammaBP has complex N-linked oligosaccharides at positions 41 and 149 as determined by site-directed mutagenesis and glycosidase treatment. Glycosylation at position 41 is required for secretion from mammalian cells and may play a role in the activity of the IFN-gammaBP. Glycosylation at position 149 is not required for secretion, and the lack of glycosylation at this site does not diminish ligand binding as measured by surface plasmon resonance (SPR) and ELISA.
Animals↗
A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.
PURPOSE: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). EXPERIMENTAL DESIGN: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. RESULTS: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. CONCLUSIONS: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
Adult↗
Detection of geometric, but not topological, spatial transformations in 6- to 12-month-old infants in a visual exploration paradigm.
Several theories of spatial orientation propose that the geometry of an environment plays a privileged role in reorientation, relative to relations between individual landmarks. Infants (N = 90) in three age groups (6, 8 1/2, and 12 months) experienced three conditions: topological, geometric, and control. A round room contained four distinctive objects in a rectangular arrangement on the inside periphery. Infants were familiarized to the array prior to a 2-min test period. In the topological condition, two objects were switched. In the geometric condition, the objects were moved to form an irregular quadrilateral. In the control condition, the array remained unchanged. Infants of 8 1/2 months and over visually explored significantly more in the geometric condition only. An initial study with adults found greater visual exploration in both geometric and topological conditions. These results are discussed in the context of current theories of spatial orientation.
Adult↗
Adding another spectral dimension to 1H magnetic resonance spectroscopy of hepatic encephalopathy.
PURPOSE: To evaluate a localized two-dimensional correlated magnetic resonance spectroscopic (L-COSY) technique in patients with hepatic encephalopathy (HE) and healthy subjects, and to correlate the cerebral metabolite changes with neuropsychological (NP) test scores. MATERIALS AND METHODS: Eighteen minimal hepatic encephalopathy (MHE) patients and 21 healthy controls have been investigated. A GE 1.5-T magnetic resonance (MR) scanner was used in combination with a body MR coil for transmission and a 3-inch surface coil for reception. A 27-mL voxel was localized by three slice-selective radio frequency (RF) pulses (90 degrees-180 degrees-90 degrees) in the anterior cingulate region. The total duration of each two-dimensional L-COSY spectrum was approximately 25 minutes. The NP battery included a total of 15 tests, which were grouped into six domains. RESULTS: MR spectroscopic results showed a statistically significant decrease in myo-inositol (mI) and choline (Ch) and an increase in glutamate/glutamine (Glx) in patients when compared to healthy controls. There was also an increase in taurine (Tau) in patients. The NP results indicated a significant correlation between motor function assessed by NP tests and mI ratios recorded using two-dimensional L-COSY. CONCLUSION: The study demonstrated the feasibility of evaluating the two-dimensional L-COSY sequence in a clinical environment. The results showed additional cerebral metabolites that can be measured with the technique in comparison to one-dimensional study.
Brain↗