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Biomedical subjects

J L O'Brien

Publications and source records attributed to J L O'Brien.

At least 19 recordsLinked to original sources

Progress in silicon-based quantum computing.

We review progress at the Australian Centre for Quantum Computer Technology towards the fabrication and demonstration of spin qubits and charge qubits based on phosphorus donor atoms embedded in intrinsic silicon. Fabrication is being pursued via two complementary pathways: a 'top-down' approach for near-term production of few-qubit demonstration devices and a 'bottom-up' approach for large-scale qubit arrays with sub-nanometre precision. The 'top-down' approach employs a low-energy (keV) ion beam to implant the phosphorus atoms. Single-atom control during implantation is achieved by monitoring on-chip detector electrodes, integrated within the device structure. In contrast, the 'bottom-up' approach uses scanning tunnelling microscope lithography and epitaxial silicon overgrowth to construct devices at an atomic scale. In both cases, surface electrodes control the qubit using voltage pulses, and dual single-electron transistors operating near the quantum limit provide fast read-out with spurious-signal rejection.

Journal Article↗

Ancilla-assisted quantum process tomography.

Complete and precise characterization of a quantum dynamical process can be achieved via the method of quantum process tomography. Using a source of correlated photons, we have implemented several methods, each investigating a wide range of processes, e.g., unitary, decohering, and polarizing. One of these methods, ancilla-assisted process tomography (AAPT), makes use of an additional "ancilla system," and we have theoretically determined the conditions when AAPT is possible. Surprisingly, entanglement is not required. We present data obtained using both separable and entangled input states. The use of entanglement yields superior results, however.

Journal Article↗

Density-dependent spin polarization in ultra-low-disorder quantum wires.

There is controversy as to whether a one-dimensional (1D) electron gas can spin polarize in the absence of a magnetic field. Together with a simple model, we present conductance measurements on ultra-low-disorder quantum wires supportive of a spin polarization at B=0. A spin energy gap is indicated by the presence of a feature in the range (0.5-0.7)x2e(2)/h in conductance data. Importantly, it appears that the spin gap is not constant but a function of the electron density. Data obtained using a bias spectroscopy technique are consistent with the spin gap widening further as the Fermi level is increased.

Journal Article↗

Novel synthesis of the glycosidase inhibitor deoxymannojirimycin and of a synthetic precursor D-lyxo-hexos-5-ulose.

[reaction: see text]. The synthesis of D-lyxo-hexos-5-ulose (5-ketomannose, 1,5-dicarbonyl sugar), a synthetic precursor to the glycoprocessing inhibitor deoxymannojirimycin, was carried out by an in situ epoxidation and hydrolysis of a trimethylsilyl-protected 6-deoxyhex-5-enopyranoside followed by facile removal of the protecting groups. A novel nine-step synthesis of deoxymannojirimycin has also been achieved from methyl alpha-D-mannopyranoside; this involved methanolysis of epoxides derived from an acetylated 1-azido-6-deoxyhex-5-enopyranoside followed by deprotection and catalytic hydrogenation.

1-Deoxynojirimycin↗

Neuropsychologic testing within 18 hours after cardiac surgery.

OBJECTIVE: To undertake neuropsychologic testing within 18 hours of cardiac surgery after fast-track anesthesia. DESIGN: Prospective study. SETTING: University hospital, single center. PARTICIPANTS: Fifty patients undergoing first-time elective coronary artery surgery. INTERVENTIONS: A neuropsychologic test battery was administered preoperatively and 18 hours and 5 days after surgery. MAIN RESULTS: Seven patients were withdrawn, and 9 patients did not attempt the postoperative tests (on both occasions) because of medical complications. Thirty patients completed > or =4 tests at both postoperative occasions. Of these, 9 patients (30%) showed a deficit in > or =2 tests at 18 hours postoperatively, and 3 (10%) showed a deficit at 5 days postoperatively. CONCLUSION: In the absence of medical complications and despite the difficulties, early postoperative neuropsychologic testing is possible after fast-track anesthesia. Such testing has the potential to more clearly define the course of cognitive decline after cardiac surgery.

Aged↗

Comparison of anxiety assessments between clinicians and patients with acute myocardial infarction in cardiac critical care units.

BACKGROUND: Although anxiety is common after acute myocardial infarction and can adversely affect physical recovery, it is not part of the routine clinical assessment of patients with myocardial infarction. Furthermore, evidence suggests that patients and clinicians differ significantly in their assessments of patients' anxiety levels. OBJECTIVES: To determine the extent to which clinicians assess anxiety in patients with acute myocardial infarction and to compare patients' self-ratings with their clinicians' assessments. METHODS: In a prospective, descriptive study, 101 patients used the Spielberger State Anxiety Index to assess their anxiety during the first 48 hours after admission for acute myocardial infarction. Patients' scores were compared with nurses' and physicians' assessments of the patients' anxiety as reported in the medical record. RESULTS: Only 45 patients (45%) had anxiety assessments noted in the record. Of those 45, 26 patients (58%) were described simply as anxious without any further description of the level of anxiety. Eleven (24%) of those 45 patients had behaviors of anxiety recorded, again without any indication of the level of anxiety. No association between patients' self-assessments and their clinicians' assessments was apparent (lambda = .03; P > .05). CONCLUSIONS: Anxiety was not routinely assessed, despite nearly half the patients reporting moderate to extreme anxiety when asked. When clinicians assessed anxiety, their assessments did not match patients' self-ratings of anxiety. A simple, easy-to-use instrument for discriminating levels of anxiety is needed.

Aged↗

A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration.

OBJECTIVE: To compare the efficacy, safety, and cost of fixed-dose low-molecular-weight heparin (dalteparin) with adjusted-dose unfractionated heparin as anticoagulant for continuous hemofiltration. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: University-affiliated adult intensive care unit PATIENTS: All patients requiring continuous hemofiltration for acute renal failure or systemic inflammatory response syndrome (SIRS) were eligible. Fifty-seven patients were enrolled. Eleven were excluded, seven because of major protocol violations and four died before hemofiltration. INTERVENTIONS: Patients received continuous venovenous hemodialysis with filtration with prefilter replacement at 500 mL/hr and countercurrent dialysate at 1000 mL/hr. Filters were primed with normal saline containing anticoagulant. Dalteparin-treated patients received a commencement bolus of 20 units/kg and a maintenance infusion at 10 units/kg/hr. Heparin-treated patients received a commencement bolus of 2000-5000 units and a maintenance infusion at 10 units/kg/hr, titrated to achieve an activated partial thromboplastin time in the patient of 70-80 secs. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure--time to failure of the hemofilter--was compared using survival analysis. Twenty-two patients (13 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to heparin. Twenty-five patients (16 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to dalteparin. Mean (SE) activated partial thromboplastin time in the heparin group was 79 (4.3) secs. Mean (SE) anti-factor-Xa activity in the six patients given dalteparin who were assayed was 0.49 (0.07). Mean (SE) prehemofiltration platelet count was 225 (35.5) x 10(9) for heparin and 178 (18.1) x 10(9) for dalteparin (p = .24, unpaired Student's t-test). Mean (SE) prehemofiltration hemoglobin was 11.4 (0.61) g/dL for heparin and 10.6 (0.38) g/dL for dalteparin (p = .31, unpaired Student's t-test). PRIMARY OUTCOME: There was no significant difference in the time to failure between the two groups (p = .75, log rank test). For dalteparin, Kaplan-Meier (K-M) mean (SE) time to failure of the hemofilter was 46.8 (5.03) hrs. For heparin, K-M mean (SE) time to failure was 51.7 (7.51) hrs. The 95% CI for difference in mean time to failure was -13 to 23 hrs. The power of this study to detect a 50% change in filter life was >90%. SECONDARY OUTCOMES: Mean (SE) reduction in platelet count during hemofiltration was 63 (25.8) x 10(9) for heparin and 41.8 (26.6) x 10(9) for dalteparin (p = .57, unpaired Student's t-test). Eight patients given dalteparin and four patients given heparin had screening for heparin-induced thrombocytopenia; three of the dalteparin patients and one of the heparin patients were positive (p = 1.0, Fisher's exact test). There were three episodes of trivial bleeding and two episodes of significant bleeding for dalteparin, and there were three episodes of trivial bleeding and four episodes of significant bleeding for heparin (p = .53, chi-square test). The mean (SE) decrease in hemoglobin concentration during hemofiltration was 0.51 (0.54) g/dL for heparin and 0.28 (0.49) g/dL for dalteparin (p = .75, unpaired Student's t-test). The mean (SE) packed-cell transfusion volume during hemofiltration was 309 (128) mL for heparin and 290 (87) mL for dalteparin (p = .90, unpaired Student's t-test). Daily costs, including coagulation assays, of hemofiltration were approximately 10% higher using dalteparin than with heparin. CONCLUSIONS: Fixed-dose dalteparin provided identical filter life, comparable safety, but increased total daily cost compared with adjusted-dose heparin. Unfractionated heparin remains our anticoagulant of choice for continuous hemofiltration in intensive care.

Acute Kidney Injury↗

Evaluation of respiratory artifact correction techniques in multishot spiral functional MRI using receiver operator characteristic analyses.

Navigator corrections and low-spatial frequency (LSF) oversampling are investigated as methods for reducing respiration-related effects in multishot functional MRI. Both techniques take advantage of the smoothly varying or nearly constant phase variations linked to the respiration cycle. These techniques were tested in functional MRI studies with spiral k-space acquisitions. Receiver operator characteristic (ROC) analyses and the temporal variance averaged across the brain were used to evaluate their effectiveness. Both methods were found to increase the area under the ROC curve and to reduce the standard deviation, with the LSF oversampling method being more effective.

Artifacts↗

Only two of the Trichomonas vaginalis triplet AP51 adhesins are regulated by iron.

The sexually transmitted parasite Trichomonas vaginalis cytoadheres to the vaginal epithelium, and four candidate trichomonad adhesins have been identified. One such protein, termed AP51, was characterized further. To do this, we studied a 1 kb cDNA clone (AP51.2) isolated from a phagemid expression library, which encoded a fusion protein of approximately 38 kDa that was immuno-crossreactive with anti-AP51 serum and retained functional adhesive properties. We performed 5'-PCR amplification to recover the missing 5' end in order to provide the complete cDNA sequence for the gene encoded by AP51.2 (ap51-2). Other PCR products revealed almost complete sequences for two additional ap51 genes, making AP51 a member of a multigene family of at least three distinct proteins and genes. The ap51-1 and ap51-3 genes each encoded for 407 amino acids while ap51-2 encoded 408 amino acids, and not unexpectedly, these genes had a high percent identity at the DNA and amino acid levels. Mapping confirmed the sequence distinctions and uniqueness of the three ap51 genes. Southern analysis using gene-specific probes revealed the single copy nature of each of the ap51 genes, all of which were present among the numerous agar clones of single trichomonads of the isolates tested. Importantly, Northern analysis showed transcriptional regulation by iron of only the ap51-1 and ap51-3 genes but not ap51-2, perhaps indicating the presence of two bona fide isoforms of the ap51 genes. The 3'-untranslated region of ap51-3 had a short poly (A) tail as well as the sequence motif AUUUA, which may relate to differential degradation of ap51-3 transcripts, in comparison to ap51-1 and ap51-2. Finally, the ap51 genes had partial homology to the beta-subunit of succinyl-CoA synthetase, reinforcing the idea that molecular mimicry may play a role in host parasitism by T. vaginalis.

Adhesins, Bacterial↗

Early extubation following coronary artery bypass surgery: a prospective randomized controlled trial. The Fast Track Cardiac Care Team.

STUDY OBJECTIVES: To determine the safety of early extubation (EE) after coronary artery surgery. DESIGN: Prospective randomized controlled trial. SETTING: The cardiac surgery operating room and ICU of a university-affiliated teaching hospital. PATIENTS: One hundred eligible patients presenting for elective coronary artery surgery. INTERVENTIONS: Patients randomized to the EE group were administered a reduced dose of fentanyl (15 microg/kg) and an anesthetic compatible with EE, while patients randomized to the conventional extubation (CE) group were given fentanyl (50 microg/kg). MEASUREMENTS AND RESULTS: The time to extubation in the EE group (median, 240 min; range, 30 to 930 min) was significantly less than the CE group (median, 420 min; range, 125 to 1,140 min) (p<0.01). Twenty patients were withdrawn from the study according to protocol guidelines. There were no cases of reintubation or complications attributable to EE. CONCLUSIONS: By using an appropriate anesthetic technique and postoperative management, EE can be achieved following coronary artery bypass surgery without major complications.

Anesthesia↗

Molecular characterization of a third malic enzyme-like AP65 adhesin gene of Trichomonas vaginalis.

Adherence to the vaginal epithelium by the sexually transmitted parasite Trichomonas vaginalis is mediated by four trichomonad surface proteins (AP65, AP51, AP33 and AP23). We recently showed that the 65-kDa adhesin is a member of a multigene family comprised of two similar but distinct proteins, AP65-1 and AP65-2, encoded by the genes ap65-1 and ap65-2, respectively. An additional immuno-crossreactive clone, the 1.2 kb F11.1 cDNA, was isolated from a phagemid expression library and encoded a fusion protein of approximately 46,000 daltons (46 kDa) that bound to HeLa cell surfaces. A significant portion of the 5' end was missing which, using the 5'-RACE method, was obtained and combined with the F11.1 clone to give a full-length cDNA. The ap65-3 gene encoded for a protein of 567 amino acids with a molecular mass of 63.1 kDa. The gene showed 88% and 96% identity at the DNA level with ap65-1 and ap65-2, respectively. Restriction mapping confirmed that the three AP65 genes are different. Southern analysis revealed that the ap65-3 gene is present in the T. vaginalis genome in multiple copies. Experiments with agar clones of trichomonads showed that each gene of the multigene family is present in all parasites, and Northern analysis showed that ap65-3 is expressed and transcriptionally regulated by iron. The ap65-3 gene had a leader sequence and, as with ap65-1 and ap65-2, showed significant homology to malic enzyme. Finally, analysis of the 3'-untranslated regions revealed that the transcript of ap65-3 had a long poly (A) tail in comparison to ap65-1 and ap65-2. Even more intriguing, sequences were found that may relate to differential degradation of select AP65 transcripts, such as the sequence motifs AUUUA for ap65-1 mRNA and UUAUUUAU for the ap65-2 mRNA, which were not found for ap65-3.

Amino Acid Sequence↗

Implementation of total quality management: conventional wisdom versus reality.

Hospitals nationwide are beginning to implement continuous quality improvement (CQI) (Barsness et al. 1993; Kosta 1992). In large part this is due to the belief that the implementation of CQI will lead to higher quality patient care, improved patient satisfaction, better employee morale, and lower cost service delivery. However, to date there have been few empirical studies of CQI implementation efforts in healthcare (Shortell et al. 1994).

Chief Executive Officers, Hospital↗

Keys for successful implementation of total quality management in hospitals.

This article reports the findings of an analysis of the implementation of continuous quality improvement (CQI) or total quality management (TQM) programs in 10 hospitals. This analysis is the result of a 2-year study designed to identify and assess the ingredients that lead to the successful implementation of CQI programs in acute care hospitals.

Hospital Administration↗

An integrative model for organization-wide quality improvement: lessons from the field.

This article describes a model of CQI that is designed to characterize the elements necessary for successfully improving quality at an organization-wide level; describe and understand the organizational dynamics in implementing an organization-wide effort; and aid in diagnosing and solving common implementation challenges. Three cases illustrate the model and how it can be used.

Health Services Research↗

Cloning and molecular characterization of two genes encoding adhesion proteins involved in Trichomonas vaginalis cytoadherence.

Cytoadherence to the vaginal epithelium is a critical step in infection by the eukaryotic flagellate Trichomonas vaginalis. Four trichomonad surface proteins (AP65, AP51, AP33 and AP23) mediate cytoadherence. The cDNA encoding the AP65 adhesin was isolated from a phagemid cDNA expression library by screening with antiserum and monoclonal antibody (mAb) raised against the purified trichomonad AP65 protein. Two clones, F11.2 and F11.5, coded for immuno-crossreactive recombinant proteins that possessed functional properties equal to the T. vaginalis AP65 adhesin. Analysis of full-length sequences corresponding to the F11.2 and F11.5 cDNAs revealed that both contained 1701-base open reading frames (ORFs) that encoded proteins of 63 281 daltons and 83 087 daltons, respectively. Comparison of the full-length sequences showed 87% identity at the nucleotide level and 91% identity at the protein level. Restriction-enzyme mapping and Southern analysis reaffirmed the distinctness of the F11.2 and F11.5 cDNAs, indicating that two different AP65 genes (now called ap65-1 and ap65-2) are present in the T. vaginalis genome in at least two copies each. Northern analysis detected high levels of transcript of approximately 1.8 kb for both ap65-1 and ap65-2 genes in trichomonads grown only in high-iron medium, confirming the transcriptional regulation of adhesin synthesis by iron. Homology searches revealed significant similarity (38% amino acid identity and 54% nucleotide identity) to malic enzymes. However, purified malic enzyme and mAb to AP65 crossreactive with malic enzyme neither inhibited cytoadherence of T. vaginalis to host cells nor prevented binding of the trichomonad AP65 to HeLa cells in a ligand assay.

Amino Acid Sequence↗

Assessing the evidence on CQI: is the glass half empty or half full?

Review of the literature on CQI/TQM in both health care and non-health care settings reveals some evidence of a positive impact for selected dimensions of CQI/TQM. There is little research, however, that examines CQI/TQM as a holistic integrated approach to quality improvement, nor are there many studies that go beyond single or small sample case studies. Using a conceptual framework involving cultural, technical, strategic, and structural dimensions, a number of barriers to CQI implementation are identified along with suggestions for high-priority areas of research.

Evaluation Studies as Topic↗