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Biomedical subjects

R Carr

Publications and source records attributed to R Carr.

At least 19 recordsLinked to original sources
PubMed2006

Preparative deracemization of unnatural amino acids.

Unnatural amino acids are a growing class of intermediates required for pharmaceuticals, agrochemicals and other industrial products. However, no single method has proven sufficiently versatile to prepare these compounds broadly at scale. To address this need, we have developed a general chemoenzymatic process to prepare enantiomerically pure L- and D-amino acids in high yield by deracemization of racemic starting materials. This method involves the concerted action of an enantioselective oxidase biocatalyst and a non-selective chemical reducing agent to effect the stereoinversion of one enantiomer and can result in an enantiomeric excess of >99% from the starting racemate, and product yields of over 90%. This approach compares very favourably with resolution processes, which have a maximum single-pass yield of 50%. We have developed efficient methods to adapt the process towards new target compounds and to optimize key factors that influence process efficiency and offer competitive economics at scale.

Amino Acids↗
PubMed2006

The role of sympathy on avoidance intention toward persons living with HIV/AIDS in Jamaica.

As the number of persons living with HIV/AIDS (PLWHA) continues to increase in Jamaica, concerns of attitudes become more important. As such, the objective of the present study is to examine the attitudes of university students in Jamaica toward PLWHA including sympathy and avoidance intentions. A large sample of university students (N=1,252) was surveyed between June 2001 and February 2002 using a 193-item questionnaire that measured HIV-related knowledge, attitudes and behaviors. Results revealed that less than half of the students reported sympathetic attitudes toward homosexual males or female prostitutes living with HIV/AIDS (41% and 44%, respectively) while the majority reported sympathetic attitudes toward heterosexual males and non-prostitute females living with the disease (67% and 81%, respectively). Most students (80%) reported no avoidance intentions toward family members or friends living with the disease. Sympathy, HIV knowledge, education and awareness were associated with no avoidance intention of HIV-positive family members and friends. These findings suggest that sympathy could be important in improving prosocial intentions toward PLWHA and warrants further research.

Adult↗
PubMed2005

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Journal Article↗
PubMed2005

Precision measurement of the weak mixing angle in Møller scattering.

We report on a precision measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV) = [-131 +/- 14(stat) +/- 10(syst)] x 10(-9), leading to the determination of the weak mixing angle sin2(thetaW(eff) = 0.2397 +/- 0.0010(stat) +/- 0.0008(syst), evaluated at Q2 = 0.026 GeV2. Combining this result with the measurements of sin2(thetaW(eff) at the Z0 pole, the running of the weak mixing angle is observed with over 6sigma significance. The measurement sets constraints on new physics effects at the TeV scale.

Journal Article↗
PubMed2005

Vanishing magnetic interactions in ferromagnetic thin films.

We have used element-specific hysteresis measurements, based on the x-ray magnetic circular dichroism technique, to investigate magnetic trilayer structures composed of Fe and Ni layers. Within a critical regime we have discovered a class of structures in which the exchange interaction, the mechanism responsible for the macroscopic magnetism, can become vanishingly small. The experimental observations are supported by first principles theory and are explained as arising from a cancellation of several competing magnetic interactions. Hence, we have discovered a system with a novel exchange interaction between magnetic layers in direct contact that replaces the conventional exchange interaction in ferromagnets.

Journal Article↗
PubMed2005

Hemolysis during percutaneous mechanical thrombectomy can mimic a hemolytic transfusion reaction.

BACKGROUND: Interventional radiologists have developed percutaneous mechanical thrombectomy (PMT) devices to remove intravascular thrombi. Hemolysis, secondary to thrombus destruction from these devices, has been described in radiology journals, but similar reports appear to be lacking in the transfusion medicine literature. Two cases of hemolysis after PMT are described that involved the transfusion service, one of which was reported as a hemolytic transfusion reaction. CASE REPORTS: The first patient received 4 units of red cells (RBCs) during a thrombectomy and subsequent placement of a transjugular intrahepatic portosystemic shunt. The patient developed hemoglobinuria, and it was reported to the blood bank as a possible hemolytic transfusion reaction. After RBC mismatch and bacterial contamination were excluded, the hemolysis was attributed to thrombectomy-related mechanical hemolysis. In the second case, a hemolyzed sample was sent to the blood bank for a type and cross-match. Upon requesting that the sample be redrawn, it was learned that the sample was obtained after PMT. CONCLUSION: Patients who have undergone PMT can have clinical and laboratory findings suggestive of hemolytic transfusion reactions. Although interventional radiologists are familiar with these side effects, the blood bank profession needs to be aware that these procedures cause nonimmune hemolysis and must consider this possibility when evaluating transfusion reactions in these patients.

Aged↗
PubMed2004

Observation of parity nonconservation in møller scattering.

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV)=[-175+/-30(stat)+/-20(syst)] x 10(-9). This first direct observation of parity nonconservation in Møller scattering leads to a measurement of the electron's weak charge at low energy Q(e)(W)=-0.053+/-0.011. This is consistent with the standard model expectation at the current level of precision: sin((2)theta(W)(M(Z))((-)MS)=0.2293+/-0.0024(stat)+/-0.0016(syst)+/-0.0006(theory).

Journal Article↗
PubMed2004

Future possibilities of the Linac Coherent Light Source.

A study of the potential for the development of the Linac Coherent Light Source (LCLS) beyond the specifications of the baseline design is presented. These future developments include delivery of X-ray pulses in the 1 fs regime, extension of the spectral range, increase of the FEL power, exploitation of the spontaneous emission, and a more flexible time structure. As this potential is exploited, the LCLS can maintain its role as a world-leading instrument for many years beyond its commissioning in 2008 and initial operation as the world's first X-ray free-electron laser.

Journal Article↗
PubMed2004

Parity-violating electron deuteron scattering and the proton's neutral weak axial vector form factor.

We report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at backward angles at Q2=0.038 (GeV/c)2. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon, which can potentially receive large electroweak corrections. The measured asymmetry A=-3.51+/-0.57 (stat)+/-0.58 (syst) ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at Q2=0.091 (GeV/c)2, which are also consistent with theoretical predictions.

Journal Article↗
PubMed2004

A risk-based methodology for deriving quality standards for organic contaminants in sewage sludge for use in agriculture--Conceptual Framework.

This paper describes a systematic methodology (Conceptual Framework) to derive quality standards for organic (anthropogenic) contaminants in sewage sludge added to agricultural land, in the context of revision of EU Sludge Directive 86/278/EEC and the broader Soil Thematic Strategy. The overall objective is to ensure, based on a risk assessment approach, a sustainable use of sludge over a long time horizon. ILSI-Europe's Conceptual Framework is in essence consistent with the EU Technical Guidance Document (TGD) for Environmental Risk Assessment of Chemicals in the soil compartment, or US-EPA's Sewage Sludge Use and Disposal Regulations, Part 503 Standards. A 'checklist' of different exposure pathways and transfer processes for organic contaminants needs to be considered, and the most sensitive relevant toxicological endpoint and its PNEC need to be identified. The additional complexity specific to deriving Sludge Quality Standards (SQS) is that the toxicity results may need-e.g., for (indirect) human toxicity-to be related back to maximum acceptable soil exposure levels (PEC(soil)). In turn, the latter need to be back-calculated to the maximum acceptable levels in sewage sludge (PEC(sludge)) at the time of application. Finally, for a sustainable sludge use, the exposure from repeated addition and potential chemical build-up over time (e.g., 100 years) needs to be assessed. The SQS may therefore vary with the (local) sludge application regime, and/or sludge pretreatment processes.

Agriculture↗
PubMed2004

Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma.

We describe a patient with non-Hodgkin's lymphoma who developed a lupus anticoagulant (LA) detectable by activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT) and kaolin clotting time (KCT). IgM anticardiolipin antibodies (ACA) were elevated. At a later admission, and following treatment for the lymphoma, routine coagulation screening showed an elevated prothrombin time (PT) without correction in mixing tests using a recombinant thromboplastin. Routine APTT was below the reference range and ACA levels were normal. Raw data for one-stage factor assays demonstrated the presence of an inhibitor. Analysis for LA was undertaken by DRVVT, KCT, activated seven lupus anticoagulant assay, Taipan snake venom time, platelet neutralisation procedures (PNP), Ecarin time and PT using rabbit brain thromboplastin. The results revealed a LA capable of prolonging the clotting times of the PNPs and PT using recombinant thromboplastin, but that was corrected using Ecarin venom, modified PNP and brain thromboplastin. The antibody also demonstrated the lupus anticoagulant co-factor effect. The factor VIII: C was markedly raised which may have masked the LA in the APTT. The changing laboratory profile over time demonstrates the effects of LA heterogeneity and variations in sensitivity and specificity of assays for the detection of antiphospholipid antibodies.

Aged↗
PubMed2004

Haemopoietic growth factors for neonates: assessing risks and benefits.

This review summarises the rationale, clinical trial evidence for benefit and potential toxicities of Erythropoietin, Thrombopoietin, Granulocyte Colony Stimulating Factor and Granulocyte-Macrophage Colony Stimulating Factor. Erythropoietin has failed to have a clinical impact on red cell transfusion requirement in very low birth weight infants; it is uncertain whether Thrombopoietin will find a significant clinical role in neonatal thrombocytopenia and there is, as yet, insufficient evidence for the routine use of Granulocyte- or Granulocyte-Macrophage Colony Stimulating Factor to prevent or treat bacterial infection. A number of theoretical risks of haemopoietic growth factor use in neonates have been suggested, but no toxicities have been observed during their clinical use. Exploring the potential for benefit in selected groups of infants should be encouraged.

Erythropoietin↗
PubMed2003

Properties of the ultrashort gain length, self-amplified spontaneous emission free-electron laser in the linear regime and saturation.

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission (SASE) free-electron laser (FEL), which achieved saturation at 840 nm within a single-pass 4-m undulator. The experiment was performed at the Accelerator Test Facility at BNL, using a high brightness 70-MeV electron beam. A gain length shorter than 18 cm has been obtained, yielding a total gain of 2 x 10(8) at saturation. The FEL performance, including the spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. Results are compared to the three-dimensional SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL systems. An agreement between simulations and experimental results has been obtained at an unprecedented level of detail.

Journal Article↗
PubMed2003

G-CSF and GM-CSF for treating or preventing neonatal infections.

BACKGROUND: The colony stimulating factors (CSFs), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF), are naturally occurring cytokines that stimulate the production and antibacterial function of neutrophils and monocytes. Two strategies have been adopted for exploring whether CSFs can provide clinical benefit for preterm infants. The first has investigated their use as a treatment to improve outcome in established systemic infection, especially when complicated by a low neutrophil count. The alternative strategy has been to use CSFs prophylactically, to prevent sepsis prospectively through stimulation of neutrophil production and bactericidal function. OBJECTIVES: To determine the efficacy and safety of the haemopoietic colony stimulating factors (G-CSF or GM-CSF) in newborn infants, when used for:a) treatment of suspected or proven systemic infection to reduce mortality, orb) prophylaxis, to prevent systemic infection in infants at high risk of nosocomial infection. To determine, in subgroup analysis, the influence of pre-existing or high risk of neutropenia on the outcome of therapy. SEARCH STRATEGY: PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) were searched in April 2003 using the keywords: G-CSF, GM-CSF, infant newborn, with and without the limit Clinical Trial. In addition, reference lists of identified RCTs, meta-analyses and personal files were searched. SELECTION CRITERIA: The criteria used to select studies for inclusion were: DESIGN: RCT. SUBJECTS: Newborn infants in intensive care. INTERVENTIONS: G-CSF or GM-CSF given as treatment in conjunction with antibiotics for suspected or microbiologically proven systemic infection. G-CSF or GM-CSF given as prophylaxis with the aim of reducing the incidence of systemic infection. OUTCOMES: Treatment studies reporting all cause mortality. Prophylaxis studies reporting subsequent incidence of sepsis and / or mortality. DATA COLLECTION AND ANALYSIS: Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) using the fixed effect model are reported. Number needed to treat (NNT) was calculated for the outcomes that showed a statistically significant reduction in RR. MAIN RESULTS: Seven treatment studies of 257 infants with suspected systemic bacterial infection and three prophylaxis studies comprising 359 neonates are analysed. Treatment studies: There is no evidence that the addition of G-CSF or GM-CSF to antibiotic therapy in preterm infants with suspected systemic infection reduces immediate all cause mortality. No significant survival advantage was seen at 14 days from the start of therapy [typical RR 0.71 (95% CI 0.38,1.33); typical RD -0.05 (95% CI -0.14, 0.04)]. However all seven of the treatment studies were small, the largest recruiting only 60 infants. The subgroup analysis of 97 infants from three treatment studies who, in addition to systemic infection, had clinically significant neutropenia (< 1.7 x 10(9)/l) at trial entry, does show a significant reduction in mortality by day 14 [RR 0.34 (95% CI 0.12, 0.92); RD -0.18 (95% CI -0.33, -0.03); NNT 6 (95% CI 3-33)]. Prophylaxis studies have not demonstrated a significant reduction in mortality in neonates receiving GM-CSF [RR 0.59 (95% CI 0.24,1.44); RD -0.03 (95% CI -0.08,0.02)]. The identification of sepsis as the primary outcome of prophylaxis studies has been hampered by inadequately stringent definitions of systemic infection. However, data from one study suggest that prophylactic GM-CSF may provide protection against infection when given to preterm infants who are neutropenic or at high risk of developing postnatal neutropenia. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to support the introduction of either G-CSF or GM-CSF into neonatal practice, either as treatment of established systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates. No toxicity of CSF use was reported in any systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates. No toxicity of CSF use was reported in any study included in this review. The limited data suggesting that CSF treatment may reduce mortality when systemic infection is accompanied by severe neutropenia should be investigated further in adequately powered trials which recruit sufficient infants infected with organisms associated with a significant mortality risk.

Anti-Bacterial Agents↗
PubMed2003

Hypertriglyceridaemia and NK cell lymphoma.

This case report describes a patient who presented with pyrexia of unknown origin allied with hypertriglyceridaemia (16.2 mmol/l) but not hypercholesterolaemia (4.1 mmol/l). Investigations identified the cause of the pyrexia as an adult T-cell lymphoma of natural killer cell phenotype (CD3[+], CD7[+], anti-TCR alpha/beta[+], CD8[+], CD56[+]). Hypertriglyceridaemia has been reported with non-Hodgkin s lymphoma, and an animal model suggests that antilipoprotein lipase antibodies may be made as an immunological response to the tumour. Lymphomas should be considered as part of the differential diagnosis in type IV-V hyperlipidaemia.

Adult↗
PubMed2002

Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy.

Galantamine is a modest acetylcholinesterase inhibitor (AChEI) that is also an allosteric potentiating ligand (APL) of nicotinic acetylcholine receptors (nAChRs). In this report, these two effects are shown to be dependent upon each other using a realistic computer model of the cholinergic synaptic cleft. The model is based upon realistic estimates of the anatomy of a neuronal synapse, the kinetic states of pre- and postsynaptic nAChRs, and the acetylcholinesterase enzyme. The number of open postsynaptic nAChRs per action potential is a measure of cholinergic neurotransmission. Using mathematical equations and published data, the effect of the AChEI and APL actions of galantamine is quantitatively described and compared to the effects of pure AChEIs. The model shows that galantamine--compared to similar concentrations of pure AChEIs--is able to compensate for its somewhat modest effect on the cholinesterase enzyme with its allosteric modulatory effects that include the additional benefit of a lower degree of receptor desensitization.

Aged↗
PubMed2002

A new scale to assess radiographic success of secondary alveolar bone grafts.

OBJECTIVES: To propose a new scale for evaluating the position of the bone graft within the cleft and assess its inter- and intraobserver reliability. DESIGN: Sixty-six patients (70 cleft sites) over a 14-year period were assessed, 90% of patients retrospectively and 10% prospectively. The radiographs were reviewed by two clinicians in controlled conditions twice, with 1 week between assessments. Both clinicians were blind to patient identity. OUTCOME MEASURES: A new scale subdividing the position of the bone into one of six categories was used. The radiographs were also assessed using the Bergland scale. RESULTS: Using the Bergland scale, 62.9% of the cleft sites were type I, 21.4% type II, 4.3% type III, and 5.7% type IV. It was not possible to assess 5.7% of the clefts with this scale because the canine was unerupted. Using the Chelsea alveolar bone graft scale, 58% were category A, 20% B, 7% C, 3% D, 3% E, and 9% F. CONCLUSIONS: The above scale can be used to determine accurately the position of bone within the cleft site. It can be used in the mixed dentition prior to eruption of the canine. It demonstrated moderate to substantial inter- and intraobserver reliability and offers several advantages, compared with other scales.

Adolescent↗