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Biomedical subjects

R Milner

Publications and source records attributed to R Milner.

At least 19 recordsLinked to original sources
PubMed2006

Measurements of the generalized electric and magnetic polarizabilities of the proton at low Q2 using the virtual-compton-scattering reaction.

The mean square polarizability radii of the proton have been measured for the first time in a virtual-Compton-scattering experiment performed at the MIT-Bates out-of-plane scattering facility. Response functions and polarizabilities obtained from a dispersion analysis of the data at Q2 = 0.057 GeV2/c2 are in agreement with O(p3) heavy baryon chiral perturbation theory. The data support the dominance of mesonic effects in the polarizabilities.

Journal Article↗
PubMed2006

Coherent THz synchrotron radiation from a storage ring with high-frequency RF system.

The generation of brilliant, stable, and broadband coherent synchrotron radiation (CSR) in electron storage rings depends strongly on ring rf system properties such as frequency and gap voltage. We have observed intense coherent radiation at frequencies approaching the THz regime produced by the MIT-Bates South Hall Ring, which employs a high-frequency S-band rf system. The measured CSR spectral intensity enhancement with 2 mA stored current was up to 10,000 times above background for wave numbers near 3 cm(-1). The measurements also uncovered strong beam instabilities that must be suppressed if such a very high rf frequency electron storage ring is to become a viable coherent THz source.

Journal Article↗
PubMed2006

Vascular matrix adhesion and the blood-brain barrier.

The integrity of the cerebral microvasculature depends on the interaction between its component cells and the extracellular matrix, as well as reorganized cell-cell interactions. In the central nervous system, matrix adhesion receptors are expressed in the microvasculature and by neurons and their supporting glial cells. Cells within cerebral microvessels express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Endothelial cells and astrocytes within cerebral capillaries co-operate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells and oligodendroglia. Significant alterations in both cellular adhesion receptors and their matrix ligands occur during focal cerebral ischaemia, which support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood-brain permeability barrier and that modulation of these receptors contributes to alterations in the barrier during brain injury.

Animals↗
PubMed2005

Investigation of the conjectured nucleon deformation at low momentum transfer.

We report new precise H(e,e(')p)pi(0) measurements at the Delta(1232) resonance at Q(2)=0.127 (GeV/c)(2) obtained at the MIT-Bates out-of-plane scattering facility which are particularly sensitive to the transverse electric amplitude (E2) of the gamma(*)N-->Delta transition. The new data have been analyzed together with those of earlier measurements to yield precise quadrupole to dipole amplitude ratios: Re(E(3/2)(1+)/M(3/2)(1+))=(-2.3+/-0.3(stat+syst)+/-0.6(model))% and Re(S(3/2)(1+)/M(3/2)(1+))=(-6.1+/-0.2(stat+syst)+/-0.5(model))% for M(3/2)(1+)=(41.4+/-0.3(stat+syst)+/-0.4(model))(10(-3)/m(pi(+))). The derived amplitudes give credence to the conjecture of deformation in hadrons favoring, at low Q2, the dominance of mesonic effects.

Journal Article↗
PubMed2005

Predicting return to work after low back injury using the Psychosocial Risk for Occupational Disability Instrument: a validation study.

INTRODUCTION: This paper reports on the predictive validity of a Psychosocial Risk for Occupational Disability Scale in the workers' compensation environment using a paper and pencil version of a previously validated multimethod instrument on a new, subacute sample of workers with low back pain. METHODS: A cohort longitudinal study design with a randomly selected cohort off work for 4-6 weeks was applied. The questionnaire was completed by 111 eligible workers at 4-6 weeks following injury. Return to work status data at three months was obtained from 100 workers. Sixty-four workers had returned to work (RTW) and 36 had not (NRTW). RESULTS: Stepwise backward elimination resulted in a model with these predictors: Expectations of Recovery, SF-36 Vitality, SF-36 Mental Health, and Waddell Symptoms. The correct classification of RTW/NRTW was 79%, with sensitivity (NRTW) of 61% and specificity (RTW) of 89%. The area under the ROC curve was 84%. CONCLUSIONS: New evidence for predictive validity for the Psychosocial Risk-for-Disability Instrument was provided. IMPLICATIONS: The instrument can be useful and practical for prediction of return to work outcomes in the subacute stage after low back injury in the workers' compensation context.

Accidents, Occupational↗
PubMed2004

Short-term sleep deficits do not adversely affect acquisition of laparoscopic skills in a laboratory setting.

BACKGROUND: Residents often are sleep deprived after being on call. This study evaluated the effects of these sleep deficits on the acquisition of laparoscopic skills in the laboratory setting. METHODS: The amount of sleep on the preceding night was recorded for 40 residents undergoing surgical skills training. The residents underwent a pretest, training, practice, and a posttest using basic (pegboard, cup drop, rope pass) and task-specific (pattern cutting, clip application, loop application) drills. Time to completion, penalty score, and total score were assessed. RESULTS: Significant improvements were seen in the time and total score for all six drills, with a significant decrease in penalty scores noted for the pegboard and rope pass drills. No significant differences in skill acquisition were attributable to amount of sleep. CONCLUSION: Training in the laboratory results in significant improvement of basic laparoscopic skills. Because short-term sleep deficits do not appear to hinder the acquisition of these skills, this model can be effectively applied, even after residents correct have been on call.

Adult↗
PubMed2004

Psychosocial factors predictive of occupational low back disability: towards development of a return-to-work model.

This paper focuses on the identification and testing of potential psychosocial factors contributing to an integrated multivariate predictive model of occupational low back disability. Psychosocial predictors originate from five traditions of psychosocial research: psychopathological, cognitive, diathesis-stress, human adaptation and organizational psychology. The psychosocial variables chosen for this study reflect a full range of research findings. They were investigated using 253 subacute and chronic pain injured workers. Three outcome measures were utilized: return-to-work status, duration of disability and disability costs. The key psychosocial predictors identified were expectations of recovery and perception of health change. Also implicated, but to a lesser degree, were occupational stability, skill discretion at work, co-worker support, and the response of the workers' compensation system and employer to the disability. All psychosocial models were better at predicting who will return than who will not return to work.

Adolescent↗
PubMed2001

Developmental regulation of alphav integrins produces functional changes in astrocyte behavior.

To examine the role of the extracellular matrix in regulating astrocyte behavior we previously characterized alphav integrin expression on postnatal astrocytes in vitro and found that they express alphavbeta5 and alphavbeta8. Here we show that differentiation of immature cells into astrocytes is accompanied by developmental regulation of alphav integrins, downregulation of alphavbeta1 and alphavbeta8, and upregulation of alphavbeta5. In addition, using two previously described astrocyte cell lines, we found that the neurite-permissive A7 cell line expressed high levels of alphavbeta1 in addition to alphavbeta5 and alphavbeta8, while the neurite-inhibitory Neu7 cell line expressed only alphavbeta5. To examine integrin function we generated clones of the Neu7 cell line expressing alphavbeta1 or alphavbeta3 in addition to alphavbeta5. This showed that the parent Neu7 cells migrated more slowly than the A7 cells on fibronectin and vitronectin, but that Neu7 cells expressing alphavbeta1 or alphavbeta3 integrins showed enhanced migration on fibronectin and vitronectin, respectively. These results show that alphav integrin expression is regulated during astrocyte development and confirm an instructive role in cell migration for alphavbeta1 in embryonic cells and alphavbeta3 in astroglial tumors.

Animals↗
PubMed2001

Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males.

A potential consequence of systemic administration of viral vectors is the inadvertent introduction of foreign DNA into recipient germ cells. To evaluate the safety of in vivo recombinant adeno-associated virus (rAAV) mediated gene transfer approaches for hemophilia B, we explored the risk of germline transmission of vector sequences following intramuscular (IM) injection of rAAV in four species of male animals (mouse, rat, rabbit and dog). In vector biodistribution studies in mice and rats, there is a dose-dependent increase in the likelihood that vector sequences can be detected in gonadal DNA using a sensitive PCR technique. However, in dogs DNA extracted from semen is negative for vector sequences. To address this discrepancy, studies were done in rabbits, and both semen and testicular DNAs were analyzed for the presence of vector sequences. These studies showed that no AAV vector sequences were detected in DNA extracted from rabbit semen samples collected at time points ranging from 7 to 90 days following IM injection of 1 x 10(13) vector genomes rAAV (vg) per kg. In contrast, DNA extracted from gonadal tissue was positive for vector sequences, but the positive signals diminished in number and strength with time. By FISH analysis, AAV signals were localized to the testis basement membrane and the interstitial space; no intracellular signal was observed. We observed similar findings following hepatic artery administration of rAAV in rats and dogs, suggesting that our findings are independent of the route of administration of vector. Attempts to transduce isolated murine spermatogonia directly with AAV-lacZ were unsuccessful. In clinical studies human subjects injected IM with an AAV vector at doses up to 2 x 10(12) vg/kg have shown no evidence of vector sequences in semen. Together, these studies suggest that rAAV introduced into skeletal muscle or the hepatic artery does not transduce male germ cells efficiently. We conclude that the risk of inadvertent germline transmission of vector sequences following IM or hepatic artery injection of AAV-2 vectors is extremely low.

Animals↗
PubMed2001

Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytes in vivo and in vitro.

The CXC chemokine gamma interferon (IFN-gamma)-inducible protein CXCL10/IP-10 is markedly elevated in cerebrospinal fluid and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1) and is implicated in the pathogenesis of HIV-associated dementia (HAD). To explore the possible role of CXCL10/IP-10 in HAD, we examined the expression of this and other chemokines in the central nervous system (CNS) of transgenic mice with astrocyte-targeted expression of HIV gp120 under the control of the glial fibrillary acidic protein (GFAP) promoter, a murine model for HIV-1 encephalopathy. Compared with wild-type controls, CNS expression of the CC chemokine gene CCL2/MCP-1 and the CXC chemokine genes CXCL10/IP-10 and CXCL9/Mig was induced in the GFAP-HIV gp120 mice. CXCL10/IP-10 RNA expression was increased most and overlapped the expression of the transgene-encoded HIV gp120 gene. Astrocytes and to a lesser extent microglia were identified as the major cellular sites for CXCL10/IP-10 gene expression. There was no detectable expression of any class of IFN or their responsive genes. In astrocyte cultures, soluble recombinant HIV gp120 protein was capable of directly inducing CXCL10/IP-10 gene expression a process that was independent of STAT1. These findings highlight a novel IFN- and STAT1-independent mechanism for the regulation of CXCL10/IP-10 expression and directly link expression of HIV gp120 to the induction of CXCL10/IP-10 that is found in HIV infection of the CNS. Finally, one function of IP-10 expression may be the recruitment of leukocytes to the CNS, since the brain of GFAP-HIV gp120 mice had increased numbers of CD3(+) T cells that were found in close proximity to sites of CXCL10/IP-10 RNA expression.

Animals↗
PubMed2001

Prescribing practices and attitudes toward giving children antibiotics.

OBJECTIVE: To investigate whether overprescribing is common in treatment of pediatric upper respiratory infections and to examine factors that influence prescribing antibiotics for children. DESIGN: A random, stratified sample of practising family physicians was surveyed with a mailed questionnaire. Initial nonresponders were mailed a second questionnaire. SETTING: British Columbia. PARTICIPANTS: A total of 608 general and family physicians. Response rate was 64%; 392/612 surveys were completed. MAIN OUTCOME MEASURES: Physicians' self-reported prescribing practices and knowledge of and attitudes toward using antibiotics for children's upper respiratory tract infections. RESULTS: Relative to treatment guidelines developed for the study, most physicians responded appropriately to the cough (94%) and lobar pneumonia (99.1%) vignettes. More than half the physicians (56.5%) reported they would immediately prescribe antibiotics for tympanic membrane dysfunction, and 79.4% indicated they would prescribe antibiotics for pharyngitis without obtaining a laboratory culture. Approximately 25% of physicians in the study did not believe that prior antibiotic use increased personal risk for acquiring drug-resistant infection, and 23.1% did not believe that antibiotic use was an important factor in promoting resistance in their communities. CONCLUSION: Education in current treatment of pediatric upper respiratory tract illnesses and antimicrobial drug resistance is required. The high response to the questionnaire (64%) and the many requests from physicians to receive the project's educational materials (45%) indicate a high level of interest in this subject.

Age Factors↗
PubMed2000

Measurement of the spin asymmetry in the photoproduction of pairs of high- p(T) hadrons at HERMES

We present a measurement of the longitudinal spin asymmetry A(||) in photoproduction of pairs of hadrons with high transverse momentum p(T). Data were accumulated by the HERMES experiment using a 27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h(+)h(-) pairs with p(h(1))(T)>1.5 GeV/c and p(h(2))(T)>1.0 GeV/c, the measured asymmetry is A(||) = -0. 28+/-0.12(stat)+/-0.02(syst). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.

Journal Article↗
PubMed2000

Radiofrequency thermal ablation: a potential treatment for hydropic fetuses with a large chest mass.

BACKGROUND/PURPOSE: Physiological changes secondary to a rapidly enlarging fetal chest mass can lead to nonimmune hydrops, which is a predictor of impending fetal demise. Currently, open fetal surgery is offered for specific patients with hydrops before 32 weeks' gestation. The authors asked if a less-invasive technique, radiofrequency thermal ablation (RTA), could be applied safely to the destruction of fetal lung tissue. METHODS: Time-dated pregnant ewes at 120 to 125 days' gestation (term, 140 to 145 days) underwent RTA through a hysterotomy (n = 3) or in a transuterine fashion under ultrasound guidance (n = 4). The probe is a 15-gauge needle with a maximal 2-cm deployment sphere at its tip. By varying the intensity and duration of treatment, the power settings were optimized to create a defined area of ablation with minimal surrounding tissue injury. Five of the 6 fetal lambs were killed acutely, and 1 was followed up for 1 week with frequent ultrasound examinations. RESULTS: Gross examination of the animals killed acutely showed a consistent area of ablation using 10 watts of applied power for 3 minutes. Direct coagulation necrosis lesions ranged from 1x1 cm to 2x2 cm in size depending on the extent of the probe deployment. One animal was followed up for 1 week and showed no major adverse physiological effects. CONCLUSION: Radiofrequency thermal ablation can be performed safely in this fetal sheep model to create a controlled area of lung tissue ablation.

Animals↗
PubMed2000

Long-term follow-up data from the Shunt Design Trial.

BACKGROUND: A previously reported multicenter randomized trial assessed whether 2 new shunt valve designs would reduce shunt failure rates compared to differential pressure valves. The study did not show a significant difference in the time to first shunt failure. Patients entered the trial between October 1, 1993, and October 31, 1995. The primary results were based on the patients' status as of October 31, 1996 (a minimum follow-up of 1 year). This report describes the late complications based on the patients' most recent follow-up. METHODS: Three hundred and forty-four hydrocephalic children at 12 North American and European centers were randomized to 1 of 3 valves: a standard differential pressure valve; a Delta valve (PS Medical-Medtronic) or a Sigma valve (NMT Cordis). Patients were followed until their first shunt failure. Shunt failure was defined as shunt surgery for obstruction, overdrainage, loculation or infection. If the shunt did not fail, follow-up was continued until August 31, 1999. RESULTS: One hundred and seventy-seven patients had shunt failure. Shunt obstruction occurred in 131, overdrainage in 13, loculated ventricles in 2 and infection in 29. The overall shunt survival was 62% at 1 year, 52% at 2 years, 46% at 3 years, 41% at 4 years. The survival curves for the 3 valves were similar to those from the original trial and did not show a survival advantage for any particular valve. CONCLUSIONS: Prolonged follow-up to date does not alter the primary conclusions of the trial: there does not appear to be one valve that is clearly the best for the initial treatment of pediatric hydrocephalus.

Adolescent↗
PubMed1999

Integrins mediate a neuronal survival signal for oligodendrocytes.

Target-dependent survival of newly differentiated cells is an important part of neural development. In the case of myelin-forming oligodendrocytes, it matches the number of oligodendrocytes to the available axons [1]. In addition to growth factors, an axonal signal regulates this survival: when axons are transected, oligodendrocytes die and, conversely, when the number of axons is increased by genetic manipulation, oligodendrocyte numbers increase [2] [3]. Newly formed oligodendrocytes that fail to contact axons undergo apoptosis, and co-culture experiments that model axon-glial interactions in vitro reveal a neuronal survival effect not present in neuron-conditioned medium [4] [5], suggesting that the signal is non-diffusible and present on the surface of axons. The nature of these neuronal signals is unknown, as are the mechanisms by which they interact with growth-factor-mediated survival signals. As integrins can regulate survival in other cell types [6] [7] [8], we determined whether integrins are involved in the neuronal survival effect. We found that the laminin receptor alpha6beta1 integrin, which is expressed on oligodendrocytes, enhances the sensitivity of oligodendrocytes to the survival effect of growth factors. On the basis of this interaction between integrin and growth-factor-mediated signalling, we propose a simple model by which signals from axons and other cell types might interact to regulate oligodendrocyte cell numbers.

Animals↗