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Biomedical subjects

M A McLaughlin

Publications and source records attributed to M A McLaughlin.

At least 19 recordsLinked to original sources
PubMed2006

Tests of general relativity from timing the double pulsar.

The double pulsar system PSR J0737-3039A/B is unique in that both neutron stars are detectable as radio pulsars. They are also known to have much higher mean orbital velocities and accelerations than those of other binary pulsars. The system is therefore a good candidate for testing Einstein's theory of general relativity and alternative theories of gravity in the strong-field regime. We report on precision timing observations taken over the 2.5 years since its discovery and present four independent strong-field tests of general relativity. These tests use the theory-independent mass ratio of the two stars. By measuring relativistic corrections to the Keplerian description of the orbital motion, we find that the "post-Keplerian" parameter s agrees with the value predicted by general relativity within an uncertainty of 0.05%, the most precise test yet obtained. We also show that the transverse velocity of the system's center of mass is extremely small. Combined with the system's location near the Sun, this result suggests that future tests of gravitational theories with the double pulsar will supersede the best current solar system tests. It also implies that the second-born pulsar may not have formed through the core collapse of a helium star, as is usually assumed.

Journal Article↗
PubMed2006

Transient radio bursts from rotating neutron stars.

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.

Journal Article↗
PubMed2005

An expanding radio nebula produced by a giant flare from the magnetar SGR 1806-20.

Soft gamma-ray repeaters (SGRs) are 'magnetars', a small class of slowly spinning neutron stars with extreme surface magnetic fields, B approximately 10(15) gauss (refs 1 , 2 -3). On 27 December 2004, a giant flare was detected from the magnetar SGR 1806-20 (ref. 2), only the third such event recorded. This burst of energy was detected by a variety of instruments and even caused an ionospheric disturbance in the Earth's upper atmosphere that was recorded around the globe. Here we report the detection of a fading radio afterglow produced by this outburst, with a luminosity 500 times larger than the only other detection of a similar source. From day 6 to day 19 after the flare from SGR 1806-20, a resolved, linearly polarized, radio nebula was seen, expanding at approximately a quarter of the speed of light. To create this nebula, at least 4 x 10(43) ergs of energy must have been emitted by the giant flare in the form of magnetic fields and relativistic particles.

Journal Article↗
PubMed2004

A double-pulsar system: a rare laboratory for relativistic gravity and plasma physics.

The clocklike properties of pulsars moving in the gravitational fields of their unseen neutron-star companions have allowed unique tests of general relativity and provided evidence for gravitational radiation. We report here the detection of the 2.8-second pulsar J0737-3039B as the companion to the 23-millisecond pulsar J0737-3039A in a highly relativistic double neutron star system, allowing unprecedented tests of fundamental gravitational physics. We observed a short eclipse of J0737-3039A by J0737-3039B and orbital modulation of the flux density and the pulse shape of J0737-3039B, probably because of the influence of J0737-3039A's energy flux on its magnetosphere. These effects will allow us to probe magneto-ionic properties of a pulsar magnetosphere.

Journal Article↗
PubMed2003

An increased estimate of the merger rate of double neutron stars from observations of a highly relativistic system.

The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe).

Journal Article↗
PubMed2001

Rapid analysis of sugars in fruit juices by FT-NIR spectroscopy.

A simple analytical procedure using FT-NIR and multivariate techniques for the rapid determination of individual sugars in fruit juices was evaluated. Different NIR detection devices and sample preparation methods were tested by using model solutions to determine their analytical performance. Aqueous solutions of sugar mixtures (glucose, fructose, and sucrose; 0-8% w/v) were used to develop a calibration model. Direct measurements were made by transflection using a reflectance accessory, by transmittance using a 0.5-mm cell, and by reflectance using a fiberglass paper filter. FT-NIR spectral data were transformed to the second derivative. Partial least-squares regression (PLSR) was used to create calibration models that were cross-validated (leave-one-out approach). The prediction ability of the models was evaluated on fruit juices and compared with HPLC and standard enzymatic techniques. The PLSR loading spectra showed characteristic absorption bands for the different sugars. Models generated from transmittance spectra gave the best performance with standard error of prediction (SEP) <0.10% and R(2) of 99.9% that accurately and precisely predicted the sugar levels in juices, whereas lower precision was obtained with models generated from reflectance spectra. FT-NIR spectroscopy allowed for the rapid ( approximately 3 min analysis time), accurate and non-destructive analysis of sugars in juices and could be applied in quality control of beverages or to monitor for adulteration or contamination.

Beverages↗
PubMed2001

Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes.

CONTEXT: Hip fracture is a common clinical problem that leads to considerable mortality and disability. A need exists for a practical means to monitor and improve outcomes, including function, for patients with hip fracture. OBJECTIVES: To identify and compare the importance of significant prefracture predictors of functional status and mortality at 6 months for patients hospitalized with hip fracture and to compare risk-adjusted outcomes for hospitals providing initial care. DESIGN: Prospective study with data obtained from medical records and through structured interviews with patients and proxies. SETTING AND PARTICIPANTS: A total of 571 adults aged 50 years or older with hip fracture who were admitted to 4 New York, NY, metropolitan hospitals between August 1997 and August 1998. MAIN OUTCOME MEASURES: In-hospital and 6-month mortality; locomotion at 6 months; and adverse outcomes at 6 months, defined as death or needing assistance to ambulate, compared by hospital, adjusting for patient risk factors. RESULTS: The in-hospital mortality rate was 1.6%. At 6 months, the mortality rate was 13.5%, and another 12.8% needed total assistance to ambulate. Laboratory values were strong predictors of mortality but were not significantly associated with locomotion. Age and prefracture residence at a nursing home were significant predictors of locomotion (P =.02 for both) but were not significantly associated with mortality. Adjustment for baseline characteristics either substantially augmented or diminished interhospital differences in outcomes. Two hospitals had 1 outcome (functional status or mortality) that was significantly worse than the overall mean while the other outcome was nonsignificantly better than average. CONCLUSIONS: Mortality and functional status ideally should be considered both together and individually to distinguish effects limited to one or the other outcome. Hospital performance for these 2 measures may differ substantially after adjustment, probably because different processes of care are important to each outcome.

Activities of Daily Living↗
PubMed2001

Ocular hypotensive and aqueous outflow-enhancing effects of AL-3037A (sodium ferri ethylenediaminetetraacetate).

AL-3037A (Sodium ferri ethylenediaminetetraacetate), a novel compound shown to stimulate the degradation of glycosaminoglycans, was evaluated for its effects on aqueous humor outflow and intraocular pressure (IOP) in four experimental models. Its effect on outflow facility was assessed in bovine and human ocular perfusion organ cultures. Its IOP effect was tested in normotensive and dexamethasone-induced ocular hypertensive rabbits. In bovine eyes, perfusion with AL-3037A (0.1% w/v, 2.3 m M) significantly increased the outflow facility well above the normal 'wash-out' effect. At 30 min after perfusion, the outflow facility of drug-treated eyes increased by 26.0+/-2.8% (mean +/- S.E.(M.), n = 8), significantly higher than the 12.1 +/- 2.8% increase in vehicle-treated eyes. This difference sustained throughout the study period (2 hr). The compound also enhanced aqueous outflow in perfused human anterior segments. In non-glaucomatous eyes, it produced a small decrease in IOP (15.4 +/- 4.6%, n = 17), but in tissues derived from glaucoma patients, bolus administration of 3 mg (7 micromol) of AL-3037A lowered the IOP by 52-68% (n = 2) lasting for at least 3 hr. This outflow-enhancing effect of AL-3037A in ex vivo studies was confirmed by in vivo results. In normotensive rabbits, oral (50 mg kg(-1)), intravenous (10 mg kg(-1)), or topical (2 mg; 50 microl of 4% w/v solution) administration of AL-3037A produced maximum reduction of IOP, when compared to vehicle-treated animals, by 34.7+/-3.5% (n = 10), 22.0 +/- 4.6% (n = 10), and 21.6 +/-4.5% (n = 10), respectively. In dexamethasone induced ocular hypertensive rabbits, topical application of the compound (0.5 mg; 25 microl of 2% w/v solution) reduced IOP significantly by 19.2+/- 0.4% (n = 7) at 3 hr after dosing. Importantly, the IOP lowering effect of AL-3037A did not diminish even after repeated treatments in consecutive days. Thus, in the four study models across three animal species, AL-3037A was demonstrated to be an efficacious ocular hypotensive compound whose effect is most likely mediated by augmentation of the aqueous outflow. Its proposed action on the metabolism of glycosaminoglycans may provide a new and unique mechanism for the treatment of glaucoma.

Animals↗
PubMed2001

Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist.

Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.

Adenylyl Cyclases↗
PubMed2001

The aging heart. State-of-the-art prevention and management of cardiac disease.

The normal aging heart undergoes pathophysiologic changes that over time undermine cardiac structure and function. In older persons, declining cardiac function can be accelerated or exacerbated by chronic diseases such as hypertension or heart failure. The convergence of normal alterations and distinct cardiovascular conditions--disorders of rhythm, disorders of the organ itself, and vascular disease--compound the challenge of clinical management. This task is becoming somewhat less complex as new information emerges from clinical studies seeking more effective approaches to preventing and managing myocardial infarction, coronary artery disease, chronic heart failure, and systolic and diastolic dysfunction.

Aged↗
PubMed2000

Aqueous humor dynamics in monkeys with laser-induced glaucoma.

This study determines the effects of laser-induced glaucoma on aqueous humor dynamics of 18 cynomolgus monkeys. Baseline measurements of 12 monkeys included intraocular pressure (IOP) by pneumatonometry, aqueous flow by fluorophotometry and outflow facility by tonography. Beginning 4 to 14 days later, the trabecular meshwork of one eye was treated repeatedly with laser photocoagulation until elevated IOP was induced. Thirty-six to 75 days after the last laser treatment, all measurements were repeated. Between 1.7 and 11.4 years after laser treatment, the same 12 monkeys plus 6 additional monkeys underwent IOP and aqueous flow measurements. In addition, outflow facility was determined with fluorophotometry, and uveoscleral outflow was both calculated (n=18) and measured with an intracameral tracer (n=7). In glaucoma eyes compared to control eyes (n=12), IOP was increased (p<0.04) by at least 8 mmHg at Time 1 (1 to 3 months) or Time 2 (3 to 4 years) after laser treatment; aqueous flow was reduced (p=0.0007) by 46% at Time 1 but returned to baseline levels at Time 2; tonographic outflow facility was reduced (p=0.0008) by 71% at Time 1. In lasered eyes compared to control eyes, fluorophotometric outflow facility was reduced (p=0.0008; n=18) by 63%, and uveoscleral outflow was increased (p<0.05), whether calculated or measured with tracers at least 1 year after laser treatment. The increased IOP in monkeys with laser-induced glaucoma was caused by a sustained reduction in outflow facility. The uveoscleral outflow increase was not enough to prevent the rise in IOP.

Animals↗
PubMed1999

Annexin II and bleeding in acute promyelocytic leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid. METHODS: We studied a newly described receptor for fibrinolytic proteins, annexin II, in cells from patients with APL or other leukemias. We examined initial rates of in vitro generation of plasmin by tissue plasminogen activator (t-PA) in the presence of APL cells that did or did not have the characteristic translocation of APL, t(15;17). We also determined the effect of all-trans-retinoic acid on the expression of annexin II and the generation of cell-surface plasmin. RESULTS: The expression of annexin II, as detected by a fluorescein-tagged antibody, was greater on leukemic cells from patients with APL than on other types of leukemic cells (mean fluorescence intensity, 6.9 and 2.9, respectively; P<0.01). The t(15;17)-positive APL cells stimulated the generation of cell-surface, t-PA-dependent plasmin twice as efficiently as the t(15;17)-negative cells. This increase in plasmin was blocked by an anti-annexin II antibody and was induced by transfection of t(15;17)-negative cells with annexin II complementary DNA. The t(15;17)-positive APL cells contained abundant messenger RNA for annexin II, which disappeared through a transcriptional mechanism after treatment with all-trans-retinoic acid. CONCLUSIONS: Abnormally high levels of expression of annexin II on APL cells increase the production of plasmin, a fibrinolytic protein. Overexpression of annexin II may be a mechanism for the hemorrhagic complications of APL.

Adolescent↗
PubMed1999

H2O2 mediates O2 toxicity in cultured fetal rat distal lung epithelial cells.

It is unknown which of the reactive oxygen species is primarily responsible for the cytotoxicity of 95% O2 for rat distal fetal lung epithelial cells in vitro. Incubation of cells with 25 U/ml polyethylene glycol (PEG)-conjugated SOD and 50 U/ml PEG-catalase, but not PEG-SOD or SOD mimics alone, significantly reduced 95% O2-mediated cytotoxicity. Liposome-entrapped catalase, without SOD, also significantly reduced 95% O2-mediated cytotoxicity. Increased formation of lipid hydroperoxides, as assessed by the formation of 8-isoprostane and aldehydes, was attenuated by both 100 microM Trolox, a vitamin E analogue, and by 5 microM U74389G, an amino steroid. Trolox, but not U74389G, prevented an increase in cell-derived H2O2, hydroxyl radical and 95% O2-mediated cytotoxicity. An increase in hydroxyl radical formation, but not cell death, observed in 95% O2, was prevented by 0.1 microM phenanthrolene, a cell permeant iron chelator. DNA extracts of rat distal fetal lung epithelial cells maintained under serum-free conditions had an electrophoretic pattern consistent with some degree of apoptosis. However, no increase in laddering was seen with exposure to 95% O2. These data are consistent with hydrogen peroxide, but not lipid hydroperoxides or hydroxyl radical, being a critical effector of O2-mediated necrotic cell death in distal lung epithelial cells.

Analysis of Variance↗
PubMed1999

The Patient Findings Questionnaire: one solution to an important standardized patient examination problem.

PURPOSE: To describe the Patient Findings Questionnaire (PFQ) and compare its scores and pass/fail decisions with those obtained from standardized patient (SP) examination checklists. METHOD: Checklists and PFQs were used to assess data acquisition by 790 second-year medical students. PFQs were composed of multiple-choice items designed to determine whether examines had acquired key historical patient information. RESULTS: At the item level, the two measurement methods yielded the same decisions about data acquisition on 88% of observed occasions. Most discrepancies (74%) involved SPs rating examinees as having elicited information when the examinee was unable to answer the associated PFQ item. At the test level, the two instruments yielded the same pass/fail decision on a large majority of occasions. CONCLUSIONS: The PFQ and checklist yielded similar data acquisition scores and decisions at the item and test levels. Replacement of the checklist with the PFQ should result in examinees' behaving in a way more consistent with recommended interviewing practices.

Chicago↗
PubMed1996

Effect of avian-human joint attention on allospecific vocal learning by grey parrots (Psittacus erithacus).

The authors studied whether grey parrots (Psittacus erithacus) would learn referential English vocalizations if training lacked full social interaction with humans. In previous studies, grey parrots learned human vocalizations most readily when training simultaneously demonstrated the meaning (full reference) and function (full contextual applicability) of the utterance and actively engaged the subject in learning (full interaction). Those studies, however, did not contrast effects of limited and full interaction or examine how interaction affects contextual applicability. Because an important factor in child language acquisition is joint attention-the social interaction between caretaker and human infant concerning objects and actions in their environment-the authors contrasted training in which joint attention was present or absent (i.e., full vs. limited interaction) and found that 2 parrots did not learn in the absence of joint attention but did learn English labels when full interaction was present.

Adult↗
PubMed1995

The three mechanisms for coronary artery disease progression: insights into future management.

The basic mechanisms of atherosclerotic progression have been well elucidated during the last few years. Basic experimental and clinical information has helped define the three stages of progression. In this review we outline the pathologic and clinical differences between slow, rapid, and intermediate progression. The eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in their various stages are defined. The relationship between specific type of lesion and chronic endothelial injury, cardiac risk factors, and increased vascular permeability to lipids is noteworthy. In regard to the acute coronary syndromes, the fate of plaque rupture and our understanding of "passive" vs. "active" rupture are defined. In addition to the phenomenon of plaque rupture, the thrombogenicity of atherosclerotic plaques in the genesis of coronary syndromes is described. The combination of plaque disruption and a high thrombogenic risk profile--including local and systemic factors--is vital to understanding the genesis of the acute coronary syndromes. In approaching the use of these new insights to arrest or reverse the atherosclerotic process, it is essential to remember that the disease process starts early in life and takes many years to progress to the symptomatic stage. The future holds promise for the development of preventive strategies to halt the progression of coronary disease--the number one killer in the United States.

Acute Disease↗