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Biomedical subjects

C Field

Publications and source records attributed to C Field.

At least 19 recordsLinked to original sources

Longitudinal variable selection by cross-validation in the case of many covariates.

Longitudinal models are commonly used for studying data collected on individuals repeatedly through time. While there are now a variety of such models available (marginal models, mixed effects models, etc.), far fewer options exist for the closely related issue of variable selection. In addition, longitudinal data typically derive from medical or other large-scale studies where often large numbers of potential explanatory variables and hence even larger numbers of candidate models must be considered. Cross-validation is a popular method for variable selection based on the predictive ability of the model. Here, we propose a cross-validation Markov chain Monte Carlo procedure as a general variable selection tool which avoids the need to visit all candidate models. Inclusion of a 'one-standard error' rule provides users with a collection of good models as is often desired. We demonstrate the effectiveness of our procedure both in a simulation setting and in a real application.

Cohort Studies↗

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Deltaproteobacteria↗

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↗

Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is a newer method of delivering highly conformal, salivary gland sparing radiation treatment that is finding increasing applications in head and neck malignancies. However, the radiation dose distribution to the mandible is rarely considered with IMRT, and the potential risks of osteoradionecrosis or osseointegrated implant failure are not well characterized for this modality. In a series of 10 patients with oral cavity and nasopharyngeal cancers who previously underwent IMRT, examination of the three-dimensional mandibular dose distribution was undertaken. The findings indicate a modest potential risk of osteoradionecrosis and osseointegrated implant failure in cases where IMRT optimization constraints are not specifically aimed at sparing the mandibular bone. Significantly higher mandibular doses (P < 0.04) were received in cases of oral cavity as opposed to nasopharyngeal cancers with IMRT. Efforts to optimize IMRT to further reduce doses to the mandible should be considered, and development of software tools to integrate three-dimensional dose distributions into planning of post-radiotherapy osseointegration would be beneficial.

Carcinoma↗

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↗

Accuracy, efficiency and robustness of four algorithms allowing full sibship reconstruction from DNA marker data.

In the problem of reconstructing full sib pedigrees from DNA marker data, three existing algorithms and one new algorithm are compared in terms of accuracy, efficiency and robustness using real and simulated data sets. An algorithm based on the exclusion principle and another based on a maximization of the Simpson index were very accurate at reconstructing data sets comprising a few large families but had problems with data sets with limited family structure, while a Markov Chain Monte Carlo (MCMC) algorithm based on the maximization of a partition score had the opposite behaviour. An MCMC algorithm based on maximizing the full joint likelihood performed best in small data sets comprising several medium-sized families but did not work well under most other conditions. It appears that the likelihood surface may be rough and presents challenges for the MCMC algorithm to find the global maximum. This likelihood algorithm also exhibited problems in reconstructing large family groups, due possibly to limits in computational precision. The accuracy of each algorithm improved with an increasing amount of information in the data set, and was very high with eight loci with eight alleles each. All four algorithms were quite robust to deviation from an idealized uniform allelic distribution, to departures from idealized Mendelian inheritance in simulated data sets and to the presence of null alleles. In contrast, none of the algorithms were very robust to the probable presence of error/mutation in the data. Depending upon the type of mutation or errors and the algorithm used, between 70 and 98% of the affected individuals were classified improperly on average.

Algorithms↗

Observation of plasma focusing of a 28.5 GeV positron beam.

The observation of plasma focusing of a 28.5 GeV positron beam is reported. The plasma was formed by ionizing a nitrogen jet only 3 mm thick. Simultaneous focusing in both transverse dimensions was observed with effective focusing strengths of order tesla per micron. The minimum area of the beam spot was reduced by a factor of 2.0+/-0.3 by the plasma. The longitudinal beam envelope was measured and compared with numerical calculations.

Journal Article↗

Observation of the Askaryan effect: coherent microwave Cherenkov emission from charge asymmetry in high-energy particle cascades.

We present the first direct experimental evidence for the charge excess in high-energy particle showers and corresponding radio emission predicted nearly 40 years ago by Askaryan. We directed picosecond pulses of GeV bremsstrahlung photons at the SLAC Final Focus Test Beam into a 3.5 ton silica sand target, producing electromagnetic showers several meters long. A series of antennas spanning 0.3 to 6 GHz detected strong, subnanosecond radio-frequency pulses produced by the showers. Measurements of the polarization, coherence, timing, field strength vs shower depth, and field strength vs frequency are completely consistent with predictions. These measurements thus provide strong support for experiments designed to detect high-energy cosmic rays such as neutrinos via coherent radio emission from their cascades.

Journal Article↗

Lava lamp, a novel peripheral golgi protein, is required for Drosophila melanogaster cellularization.

Drosophila cellularization and animal cell cytokinesis rely on the coordinated functions of the microfilament and microtubule cytoskeletal systems. To identify new proteins involved in cellularization and cytokinesis, we have conducted a biochemical screen for microfilament/microtubule-associated proteins (MMAPs). 17 MMAPs were identified; seven have been previously implicated in cellularization and/or cytokinesis, including KLP3A, Anillin, Septins, and Dynamin. We now show that a novel MMAP, Lava Lamp (Lva), is also required for cellularization. Lva is a coiled-coil protein and, unlike other proteins previously implicated in cellularization or cytokinesis, it is Golgi associated. Our functional analysis shows that cellularization is dramatically inhibited upon injecting anti-Lva antibodies (IgG and Fab) into embryos. In addition, we show that brefeldin A, a potent inhibitor of membrane trafficking, also inhibits cellularization. Biochemical analysis demonstrates that Lva physically interacts with the MMAPs Spectrin and CLIP190. We suggest that Lva and Spectrin may form a Golgi-based scaffold that mediates the interaction of Golgi bodies with microtubules and facilitates Golgi-derived membrane secretion required for the formation of furrows during cellularization. Our results are consistent with the idea that animal cell cytokinesis depends on both actomyosin-based contraction and Golgi-derived membrane secretion.

Actins↗

Progression of consequences among heavy-drinking college students.

Among a sample of 180 male and 226 female undergraduates, 84.2% reported a heavy drinking episode (5+ drinks for men, 4+ for women) within the previous 90 days. Principal-components analysis revealed 3 alcohol-related problem factors among the heavy drinkers (Careless Behavior, Risky/Reckless Behavior, and Authority Problems). Nearly all heavy drinkers experienced a careless behavior that was due to drinking (92.7%), and many reported a risky/reckless behavior (60.2%), yet only one third (33.9%) experienced an authority problem. Guttman scaling procedures revealed a progression from Careless Behavior to Reckless/Risky Behavior to an Authority Problem. Heavy drinkers with an authority problem drank more frequently, consumed more when drinking, endorsed more alcohol expectancies, and reported earlier ages of initial and regular drinking than other groups.

Adult↗

Assessing coronary artery disease with thallium-201 rest and technetium-99m-sestamibi stress testing at two centers.

OBJECTIVE: In this study we assessed the specific location(s) of cardiac wall abnormalities in a population of patients referred for coronary artery disease and compared gender differences in the interpretation of nuclear medicine rest/stress results. METHODS: The study group consisted of 846 patients referred to 2 nuclear medicine outpatient cardiology centers for assessment between November 1998 and April 1999. All patients received dual-isotope perfusion 201Tl rest/99mTc-sestamibi stress tests. A retrospective analysis of patient results was performed. RESULTS: In both facilities the largest percentage of defects was identified in the inferior wall (35.5%), followed by the anterior wall (26.5%). Cardiac defects identified in 3 other walls were much lower: lateral wall (14.2%), septal (13.8%), and apical (9.5%). In both outpatient clinics the normalcy rate was much higher for women than men. The normalcy rate in men was 40%, whereas women demonstrated a normalcy rate of 60%. An analysis of treadmill stress versus pharmacologic stress did not illuminate the cause of this difference. CONCLUSION: The most common site of myocardial wall abnormalities occurred in the inferior wall followed by the anterior wall. A large disparity was identified between the results for men compared with those for women. Men had nearly twice the number of defects as women in this study.

Coronary Disease↗

Cytokinesis in eukaryotes: a mechanistic comparison.

Cytokinesis is a crucial but poorly understood process of cell proliferation. Recently, molecular genetic analyses of fungal cytokinesis have led to an appreciation of contractile mechanisms in simple eukaryotes, and studies in animal and plant cells have led to new insights into the role of microtubules in the cleavage process. These findings suggest that fundamental mechanisms of cytokinesis may be highly conserved among eukaryotic organisms.

Actomyosin↗

The economic burden of irritable bowel syndrome in Canada.

In the treatment of irritable bowel syndrome (IBS), medical practitioners and policymakers face the task of providing both high quality and cost effective medical care for a condition with no certain cure. To date, studies have examined only total medical costs to patients with symptoms consistent with an IBS diagnosis. However, these studies have not examined the direct and indirect costs incurred in the course of treatment for IBS, excluding the costs of unrelated medical conditions. Because patients with IBS have been shown to differ significantly from non-IBS patients in their desire to seek medical care, one cannot consider solely the cost differential in medical costs for IBS and non-IBS patients. The present study examines a set of patients who have been diagnosed with IBS and seek medical care for IBS.

Canada↗

Therapy of metabolic disorders with intravenous (IV) access ports and long term intravenous L-carnitine therapy.

With the expansion of newborn screening to include many organic acidurias and fatty acid oxidation defects, effective therapies of these disorders will be needed. Currently severe disorders such as methylmalonic and propionic aciduria. conventional therapy with diet and oral L-camitine often prove ineffective in preventing failure to thrive and recurrent metabolic decompensations. L-carnitine provides a natural pathway for removal of the toxic metabolites in these disorders and is life saving therapy but, with poor oral absorption (25%), it is difficult to supply adequate carnitine to meet the metabolic needs of these patients. Long term intravenous L-carnitine therapy, administered through a subcutaneous venous access port in 5 patients with organic acidurias [propionic aciduria (2), methylmalonic aciduria (2), 3 methylglutaconic aciduria(1)] resulted in improved growth, lower frequency of metabolic decompensations and increased tolerance of natural protein in the diet. An added benefit was the ability to initiate fluid. electrolytes, and antibiotics during metabolic decompensations at home thus averting hospitalizations.

Carnitine↗

Polymerization of purified yeast septins: evidence that organized filament arrays may not be required for septin function.

The septins are a family of proteins required for cytokinesis in a number of eukaryotic cell types. In budding yeast, these proteins are thought to be the structural components of a filament system present at the mother-bud neck, called the neck filaments. In this study, we report the isolation of a protein complex containing the yeast septins Cdc3p, Cdc10p, Cdc11p, and Cdc12p that is capable of forming long filaments in vitro. To investigate the relationship between these filaments and the neck filaments, we purified septin complexes from cells deleted for CDC10 or CDC11. These complexes were not capable of the polymerization exhibited by wild-type preparations, and analysis of the neck region by electron microscopy revealed that the cdc10Delta and cdc11Delta cells did not contain detectable neck filaments. These results strengthen the hypothesis that the septins are the major structural components of the neck filaments. Surprisingly, we found that septin dependent processes like cytokinesis and the localization of Bud4p to the neck still occurred in cdc10Delta cells. This suggests that the septins may be able to function in the absence of normal polymerization and the formation of a higher order filament structure.

Cell Cycle Proteins↗

Isolation of actin-associated proteins from Caenorhabditis elegans oocytes and their localization in the early embryo.

The actin cytoskeleton plays an important, but poorly understood, role in the development of multicellular organisms. To help illuminate this role, we used actin filament affinity chromatography to isolate actin binding proteins from large quantities of Caenorhabditis elegans oocytes. To examine how these proteins might be involved in early development, we prepared antibodies against some of them and determined their distribution in fixed embryos. Three of these proteins co-localize with different subsets of the embryonic actin cytoskeleton. One co-localizes with actin to all cell cortices. The second oscillates between the nucleus and cortex in a cell-cycle-dependent manner. The third is asymmetrically enriched at the anterior cortex of one-cell embryos, showing a temporal and spatial localization suggestive of a function in generating developmental asymmetry. We conclude that biochemistry is a feasible and useful approach in the study of early C. elegans development, and that the embryonic actin cytoskeleton is regulated in a complex fashion in order to carry out multiple, simultaneous functions.

Actins↗

Role and management of donkeys in Samburu and Turkana pastoralist societies in northern Kenya.

A survey was carried out in northern Kenya to obtain data on the role and management of donkeys in Samburu and Turkana pastoralist societies and to identify potential areas, if any, for interventions. Sixty-seven women owning or closely associated with 583 donkeys were surveyed during July/August 1994. The median donkey herd sizes in Samburu and Turkana societies were 4 and 10 respectively. Pack transport of water and domestic materials were the major reasons for keeping donkeys. Donkey milk, meat and blood were consumed widely by the Turkana but not by the Samburu. The major problems in donkey management were donkeys getting lost, being stolen, predation and being affected by diseases, in particular a disease condition involving unthriftiness, emaciation and slow growth. Traditional methods of treating donkey diseases were generally used. It was concluded that donkeys were an important component in the pastoralist societies surveyed although donkey numbers and transport capacity were not limiting factors in pastoralists activities. Potential areas for intervention were identified as disease investigation and stimulation of community based initiatives to tackle general management problems.

Animal Husbandry↗