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Biomedical subjects

R Morse

Publications and source records attributed to R Morse.

At least 19 recordsLinked to original sources

Search for extraterrestrial point sources of neutrinos with AMANDA-II.

We present the results of a search for point sources of high-energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.

Journal Article↗

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector.

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

Journal Article↗

Neuropsychological functioning following systemic treatment in women treated for breast cancer: a review.

The aim of this review was to evaluate the effect of treatment and illness-related factors on neuropsychological functioning in women treated for breast cancer. Eight studies were identified examining neuropsychological test performance following systemic treatment. Six of the eight studies suggest that neuropsychological functioning may be impaired following treatment. However, there are a number of important methodological issues which limit interpretation of these results. Therefore, it is unclear whether neuropsychological outcome differs according to a range of treatment, biomedical and psychological factors. Larger samples with longitudinal follow-up are required in order to examine the treatment-related factors that best predict cognitive deficits.

Antineoplastic Combined Chemotherapy Protocols↗

TrialDB: A web-based Clinical Study Data Management System.

Clinical Study Data Management Systems (CSDMSs) are a class of software that support centralized management of data generated during the conduct of clinical studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such systems, which are typically deployed at an institutional or organizational level, must accommodate diverse types of data from different clinical domains that is generated by different groups of clinical investigators. Large-scale CSDMSs typically employ a high-end database engine that is usually accessed over an intranet or the Internet using Web-based technologies. CSDMSs in institution-wide use for a variety of clinical domains are best served by entity-attribute-value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are aware of use EAV design. However, de novo development of EAV databases for data management is a challenging task. A large body of generic metadata-driven code must be developed before a basic EAV application can be written. Clearly, the availability of pre-existing software with the requisite functionality would be very valuable. We will discuss the benefits of such software being in open-source form.

Clinical Trials as Topic↗

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice.

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.

Journal Article↗

Can parents rate their child's health-related quality of life? Results of a systematic review.

A systematic review was conducted to determine the relationship between ratings of children's health-related quality of life (HRQoL) made by parents and children. This was investigated in relation to four questions: is agreement greater for some domains (e.g. physical HRQoL) than others?; do parents perceive illness to have a greater impact than their child?; how is agreement affected by child age, gender and illness status?; and is the relationship between proxy ratings affected by the method of data collection? Fourteen studies were identified. Consistent with previous research, there was greater agreement for observable functioning (e.g. physical HRQoL), and less for non-observable functioning (e.g. emotional or social HRQoL). Three studies assessed whether parents perceive the illness to have a greater impact than their child, but no clear conclusions could be drawn given differences in measures used. Agreement is better between parents and chronically sick children compared with parents and their healthy children, but no effects were found for age or gender. All of these results may be dependent on the specific measure of HRQoL employed. There remain strong arguments for obtaining information from both parents and children whenever possible.

Adolescent↗

The measurement of quality of life in children: past and future perspectives.

Quality of life (QoL) is central to pediatric practice. Where it is possible to manage but not cure a disease, it is important to determine how far treatment and disease compromise the child's QoL. In this way, informed judgments can be made about whether or not treatment is appropriate, and, where there is a choice, which choice might be the best option for the child. In this review, we consider different approaches to measuring child QoL, report a methodological review of measures currently available, evaluate the quality of these measures, and finally consider the implications for the future development and use of QoL measures. Computer searches identified 269 potentially relevant articles, of which 137 were included in the review. Of these, 43 were primarily concerned with the development of a new measure of QoL, 79 reported subsequent development of these same measures, and 15 used a battery approach to measure QoL. All currently available measures have limitations (e.g., limited psychometric data, lack of parallel forms for children and proxy raters, and insufficient attention to children's ability to complete paper-and-pencil measures). However, recommendations are made on the basis of those considered to be most satisfactory. It is essential that attempts be made to use QoL measures in research (e.g., evaluation of clinical trials and alternative treatments) to gain experience that will guide development of a second generation of more sophisticated measures. Despite the practical difficulties identified, measurement of QoL remains of central interest to all those concerned with the well-being of children.

Child↗

A review of measures of quality of life for children with chronic illness.

AIMS: To identify currently available generic and disease specific measures of quality of life (QoL) for work with children; and make recommendations about the future development and application of QoL measures. METHODS: Systematic searches were conducted to identify measures of QoL. Primary research papers were coded by the authors on the basis of predefined inclusion and exclusion criteria. RESULTS: Of the 137 papers included in the review, 43 involved the development of a new measure. These included 19 generic and 24 disease specific measures. Almost half the measures were developed in the USA. Measures were identified which were appropriate for children across a broad age range, and included provision for completion by different respondents (child only, parent only, or both). There were no clear distinctions between measures of QoL, health, or functional status. CONCLUSIONS: We have identified a small number of measures which fulfil basic requirements and could be used to assess QoL in clinical trials or following interventions. However, there remain a number of problems in measuring QoL in children. These include limited availability of disease specific measures; discrepancies between child and parent ratings; limited availability of measures for self completion by children; lack of precision regarding the content of domains of QoL; and the cultural appropriateness of measures developed elsewhere for children in the UK.

Activities of Daily Living↗

Quality-of-life measures in chronic diseases of childhood.

SCOPE OF THE REPORT: This report is concerned with the evaluation of measures broadly designed to measure quality of life (QoL) in children and adolescents, either by self-report or proxy raters. Four research questions were identified: (1) To what extent are adult measures used in the evaluation of healthcare interventions in children? (2) How appropriate are adult measures for use with children? (3) To what extent do child self-reports correspond with assessments made by parents and carers? (4) How feasible and reliable are proxy measures of QoL in different disease contexts? OBJECTIVES: (1) To review the state of the art with regard to measurement of QoL for children. (2) To make recommendations regarding the value of currently available measures for different purposes. (3) To identify further research needs. METHOD: Electronic databases were searched for the period 1980-July 1999 for articles relating to measures of QoL, health status or well-being in children (under 18 years) with chronic disease. Handsearching of relevant journals and cross-referencing with reference lists in identified articles was also carried out. Key workers in the field were contacted for additional information, and the Internet was searched for relevant websites. RESULTS: Forty-three measures were identified (19 generic and 24 disease-specific). Sixteen measures allowed for completion by children and parent/caregiver; seven only allowed for completion by a proxy, and the remainder (n = 17) allowed only for child completion. The measures were described as QoL (n = 30), health status, (n = 2), perception of illness (n = 1), life satisfaction (n = 1) and quality of well-being (n = 1). RESULTS - TO WHAT EXTENT ARE ADULT MEASURES USED IN THE EVALUATION OF HEALTHCARE INTERVENTIONS IN CHILDREN?: Three studies were identified where adult measures were used with very few changes made for children. In 11 studies involving nine separate measures of QoL, adult measures were used as a model for work with children. RESULTS - HOW APPROPRIATE ARE ADULT MEASURES FOR USE WITH CHILDREN?: Adult measures may fail to tap the specific aspects of QoL that are important to the child. Measures based on adult work impose considerable response burden for children, in terms of length, reading skills and response scale. Wording and format of adult measures may need to be modified to account for children's cognitive and language skills. More basic research is needed to determine the level of response burden that children of different ages can manage. Assessments of difficulty (e.g. reading age) need to be routinely included with information about new measures. RESULTS - TO WHAT EXTENT DO CHILD SELF-REPORTS CORRESPOND WITH ASSESSMENTS MADE BY PARENTS AND CARERS?: Fourteen studies were identified in which concor-dance between child and parent was investigated, often as part of the development of a new measure. There was some evidence for greater concordance between child and parent for physical functioning compared with social and emotional domains, but greater heterogeneity in the latter measures may contribute to inconsistent results. There was no simple relationship between concordance and moderating variables such as age, gender and illness, but this conclusion was addressed only very rarely. RESULTS - HOW FEASIBLE AND RELIABLE ARE PROXY MEASURES OF QOL IN DIFFERENT DISEASE CONTEXTS?: Only five papers fulfilled the review criteria. Evaluation is difficult because authors fail to justify their choice of measures, and do not report critical information such as completion rates or missing data. Use of existing measures can potentially eliminate the time and expense required to develop a comprehensive measure of QoL, but a full battery of standardised tests may be expensive in terms of time for administration and scoring. In addition, battery measures tend to be lengthy and therefore demanding for sick patients. They are not recommended for work with children. RECOMMENDATIONS FOR RESEARCH - MINIMUM CRITERIA FOR NEW MEASURES: A set of procedures needs to be established for the development of new measures. These need to draw on the experience gained in development of child and adult measures to date. Basic research to enhance understanding of how children interpret questions in QoL measures is recommended. We need to understand the differences in meaning of items between children and adults, and between children of different ages. Some attempt to develop measures for children of 6 years or more have been reported, and these should be further developed. (ABSTRACT TRUNCATED)

Adolescent↗

Human hearing enhanced by noise.

Noise was traditionally regarded as a nuisance, which should be minimized if possible. However, recent research has shown that addition of an appropriate amount of noise can actually improve signal detection in a nonlinear system, an effect called stochastic resonance. While stochastic resonance has been described in a variety of physical and biological systems, its functional significance in human sensory systems remains mostly unexplored. Here we report psychophysical data showing that signal detection and discrimination can be enhanced by noise in human subjects whose hearing is evoked by either normal acoustic stimulation or electric stimulation of the auditory nerve or the brainstem. Our results suggest that noise is an integral part of the normal sensory process and should be added to auditory prostheses.

Adult↗

The measurement of quality of life in young children.

The purpose of this paper is to argue for a measure of quality of life (QoL) for children aged between 4 and 8 years, describe the obstacles in developing such a measure, and provide evidence that it is possible to elicit directly information from children. Finally we summarize and critique measures that are currently available for this purpose.

Child↗

Secondary structure analysis of the dissimilatory sulphite reductase in Desulfovibrio desulfuricans.

The complete sequences of the dsrA and dsrB genes coding for the alpha- and beta-subunits, respectively, of the sulphite reductase enzyme in Desulfovibrio desulfuricans were determined. Analyses of the amino acid sequences indicated a number of serohaem/Fe4S4 binding consensus sequences whilst predictive secondary structure analysis revealed a similar pattern of alpha-helix and beta-strand structures between the two subunits which was indicative of gene duplication.

Amino Acid Sequence↗

Ultrasound interaction with large unilamellar vesicles at the phospholipid phase transition: perturbation by phospholipid side chain substitution with deuterium.

The ultrasonic absorption, alpha lambda, as a function of temperature and frequency was determined in large unilamellar vesicles (LUVs) in which specific phospholipid side chains were deuterated. Deuteration significantly altered the temperature and frequency dependence of alpha lambda. The frequency change was especially marked, with decreased frequency and broadening of the ultrasound relaxation, even with only minor changes in the phase transition temperature. Deuteration decreased the Tm and enthalpy of the lipid phase transition, as shown by differential scanning calorimetry, whereas electron spin resonance showed that at and above the lipid phase transition, no differences in the mobility as a function of temperature were observed. These results show that the observed increase in ultrasonic absorption in LUVs at the phospholipid phase transition arises from the interaction of ultrasound with the hydrophobic side chains, probably coupling with structural reorganization of small domains of molecules, a process which is maximized at the phase transition temperature.

1,2-Dipalmitoylphosphatidylcholine↗

Isolation of rifampin-resistant mutants of Listeria monocytogenes and their characterization by rpoB gene sequencing, temperature sensitivity for growth, and interaction with an epithelial cell line.

The sequence of the rpoB gene from Listeria monocytogenes was determined. Rifampin-resistant (Rif(r)) mutants arising from L. monocytogenes cultures exposed to rifampin were isolated, and by partial sequencing of their rpoB genes, seven different point mutations affecting five different amino acids (473Asp-->Asn or Gly, 479Gly-->Asp, 483His-->Tyr or Leu, 528Ile-->Phe, and 530Ser-->Tyr), which led to MICs of 0.5 to 100 microg/ml for the organisms, were determined. These mutants showed various deficiencies for growth at 42 degrees C, with only one being comparable to the wild-type strain. The interaction of these Rif(r) mutants with human Caco-2 cells was examined by using an immunofluorescence technique. Three mutants failed to interact, while three showed a reduced interaction compared to that of the wild type. It is believed that these pleiotropic phenotypes have arisen as a result of mutations within the DNA-dependent RNA polymerase holoenzyme.

Antibiotics, Antitubercular↗

Analysis of the beta' subunit of DNA-dependent RNA polymerase does not support the hypothesis inferred from 16S rRNA analysis that Oenococcus oeni (formerly Leuconostoc oenos) is a tachytelic (fast-evolving) bacterium.

rRNA sequencing has shown that leuconostocs comprise three distinct phylogenetic lineages which have been designated separate genera (viz., the genera Leuconostoc sensu stricto, Oenococcus, and Weissella). In addition, the 16S rRNA line formed by Oenococcus oeni (formerly Leuconostoc oenos) is exceptionally long; this fact, together with variations in the compositions of conserved positions in the 16S rRNA, has led to the hypothesis (D. Yang and C. R. Woese, Syst. Appl. Microbiol. 12:145-149, 1989) that this organism is a fast-evolving bacterium. Previous evidence that the leuconostocs should be divided into three genera and that O. oeni is an example of tachytelic evolution has come solely from rRNA analyses. In this study we seqenced the rpoC gene encoding the beta' subunit of DNA-dependent RNA polymerase of leuconostocs and performed a comparative phylogenetic analysis. The subdivision of the leuconostocs into three distinct lineages was confirmed by the rpoC gene data, but no evidence that indicated that O. oeni is evolving at an extraordinary rate was found. If O. oeni is truly tachytelic, then fast-evolving phenomena would be expected to occur throughout the whole genome, including this independent molecular chronometer.

Amino Acid Sequence↗

Evaluation of ambient asbestos concentrations in buildings following the Loma Prieta earthquake.

On October 17, 1989, an earthquake struck central, coastal California including San Francisco and the Bay Area, damaging many buildings. Because of concern over the possible exposure to asbestos in the damaged buildings, building owners/managers hired several Bay Area industrial hygiene firms to collect air samples in suspect buildings. RJ Lee Group analyzed a total of 419 air samples from 55 buildings (25 school, 3 university, 20 commercial, 5 public, and 2 residential buildings) using transmission electron microscopy and has compiled the results. The data from each building were averaged and grouped accordingly into three classifications: indoor buildings, buildings with asbestos abatement in progress at the time of the earthquake, and buildings where sampling was performed to monitor clean-up of debris. Several buildings were sampled on more than 1 day. The results indicate that asbestos levels differed little from outdoor levels, even immediately after the earthquake. Exceptions to this were samples collected in the vicinity of debris clean-up and in buildings undergoing abatement which were higher than the indoor or outdoor samples. However, these samples generally had concentrations below the AHERA clearance levels and all were well below the OSHA action limit.

Air Pollutants↗

HLA-A, B and DR antigens in renal transplantation. A further report on the Northwestern and MEDUNSA experience.

HLA histocompatibility antigens form part of the basis of immune reactions in transplant immunology. However, controversy surrounds their use in renal allograft organ sharing. Selected HLA-related studies in the transplant programmes of Northwestern Memorial Hospital (NWMH), Chicago, USA, and the Medical University of Southern Africa (MEDUNSA), Pretoria, are presented. In the Northwestern Memorial Hospital experience with 27 recipients of O-mismatches, 48% were mixed leucocyte culture (MLC) compatible (% relative response < 25). Actuarial graft survival rates at yearly intervals up to 5 years were 100%, 100%, 85%, 75%, 75%, compared with 75%, 65%, 65%, 55% and 55% in compatible and incompatible groups, respectively (Breslow P = 0.05 and Mantel-Cox P = 0.11). Creatinine values at yearly intervals up to 5 years were significantly better in the MLC-compatible group (Mann-Whitney U-test P < 0.05). In the MEDUNSA experience with 85 black recipients of poorly HLA-matched renal allografts of the same donor race, actuarial graft survival at yearly intervals up to 5 years was 73%, 68%, 61%, 61% and 57%. The commonest HLA-A, B and DR antigens at MEDUNSA are A30, A9, A2, A10, A28; B17, B12, B42, B8; DR3, DR5 and DR4 (in this order of frequency). The NWMH experience illustrates that HLA-matching improves renal allograft survival in O-mismatches. At MEDUNSA, however, satisfactory results are obtained using kidneys harvested from black donors.

Adult↗