Biomedical subjects
Publications and source records attributed to William Nelson.
A new high-affinity thyroid hormone antagonist 6 with druglike properties was designed and synthesized. The compound behaved as an antagonist in a cell transactivation assay, and in a first in vivo experiment in rats.
Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.
Previous approaches to comparing gene and chromosome organization between two genomes have been based on genetic maps or genomic sequences. We have developed a system to align an FPC-based physical map to a genomic sequence based on BAC end sequences and sequence-tagged hybridization markers and to align two FPC maps to one another based on shared markers and fingerprints. The system, called SyMAP (Synteny Mapping and Analysis Program), consists of an algorithm to compute synteny blocks and Web-based graphics to visualize the results. The approach to calculating the anchors (corresponding elements on the respective maps) maximizes the inclusion of anchors with different rates of divergence. Chains (putative syntenic sets of anchors) are computed using a dynamic programming algorithm, which includes off-diagonal anchors that result from map coordinate errors and small inversions. As the gap parameters (the distances allowed between anchors in a chain) can vary over different data sets and be difficult to set manually, they are automatically computed per data set. The criterion for a chain to be acceptable is based on the number of anchors and the Pearson correlation coefficient. Neighboring chains are merged into synteny blocks for display. This algorithm has been tested with three data sets that vary in the number of BACs, BAC end sequences, hybridization markers, distance between anchors, and number and antiquity of genome duplication events. The Web-based graphics uses Java for a highly interactive display that allows the user to interrogate the evidence of synteny.
Explore the source record for details and available documents.
OBJECTIVE: To determine whether bioethicists are distributed along a rural-to-urban continuum in a way that reflects potential need of those resources as determined by the general population, hospital facilities and hospital beds. METHODS: US members of a large, multidisciplinary professional society, the American Society of Bioethics and Humanities (ASBH), the US population, hospital facilities and hospital beds were classified across a four-tier rural-to-urban continuum. The proportion of each group in rural settings was compared with that in urban settings, and odds ratios were calculated with 95% confidence intervals. RESULTS: Although 91% of ASBH members live or work in urban settings, only 66% of the US population did so. In contrast, 2% of ASBH members live or work in rural settings compared with 13% of the population. ASBH members were 10.7 times (95% CI 6.6 to 17.3) as likely to be represented in urban than in rural settings when compared with the general population, 25.6 times (95% CI 15.8 to 41.5) and 6.9 times (95% CI 4.3 to 11.1) as likely with regard to hospital facilities and hospital beds, respectively. CONCLUSIONS: Using various comparisons it was found that ASBH members are under-represented in rural as compared with urban settings. Although not all bioethicists are ASBH members, these findings suggest that the availability of professional bioethical resources may be inadequate in rural America. The disparities that were found may have considerable effect on ethics scholarship, research, ethical committees and education, and adds to the argument that rural American communities are under-served.
Using a multiply matched, concurrent cohort analysis, with 568 subjects matched from data obtained by our laboratory over the past 7 yr, we examined whether parental presence during induction of anesthesia (PPIA) reduces children's anxiety depending on the interaction between child and parent's baseline anxiety. Children's and parents' baseline anxiety was assessed preoperatively; children's anxiety was again assessed during induction of anesthesia. We found that anxious children who received PPIA from a calm parent were significantly less anxious during induction of anesthesia as compared with anxious children who did not receive PPIA (P = 0.03). In contrast, calm children who received PPIA from an overly anxious parent were significantly more anxious as compared with calm children who were not accompanied by a parent (P = 0.002). We found no effect of PPIA on children's anxiety during induction of anesthesia when calm parents accompanied calm children into the operating room (P = 0.15) or when overly anxious parents accompanied anxious children (P = 0.49). We conclude that the presence of a calm parent does benefit an anxious child during induction of anesthesia and the presence of an overly anxious parent has no benefit.
Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.
We have applied "whole-genome shotgun sequencing" to microbial populations collected en masse on tangential flow and impact filters from seawater samples collected from the Sargasso Sea near Bermuda. A total of 1.045 billion base pairs of nonredundant sequence was generated, annotated, and analyzed to elucidate the gene content, diversity, and relative abundance of the organisms within these environmental samples. These data are estimated to derive from at least 1800 genomic species based on sequence relatedness, including 148 previously unknown bacterial phylotypes. We have identified over 1.2 million previously unknown genes represented in these samples, including more than 782 new rhodopsin-like photoreceptors. Variation in species present and stoichiometry suggests substantial oceanic microbial diversity.
This study discusses three software tools, the first two aid in integrating sequence with an FPC physical map and the third automatically selects a minimal tiling path given genomic draft sequence and BAC end sequences. The first tool, FSD (FPC Simulated Digest), takes a sequenced clone and adds it back to the map based on a fingerprint generated by an in silico digest of the clone. This allows verification of sequenced clone positions and the integration of sequenced clones that were not originally part of the FPC map. The second tool, BSS (Blast Some Sequence), takes a query sequence and positions it on the map based on sequence associated with the clones in the map. BSS has multiple uses as follows: (1) When the query is a file of marker sequences, they can be added as electronic markers. (2) When the query is draft sequence, the results of BSS can be used to close gaps in a sequenced clone or the physical map. (3) When the query is a sequenced clone and the target is BAC end sequences, one may select the next clone for sequencing using both sequence comparison results and map location. (4) When the query is whole-genome draft sequence and the target is BAC end sequences, the results can be used to select many clones for a minimal tiling path at once. The third tool, pickMTP, automates the majority of this last usage of BSS. Results are presented using the rice FPC map, BAC end sequences, and whole-genome shotgun from Syngenta.
Explore the source record for details and available documents.
This report addresses the difficult situation in which a patient or surrogate decision maker wishes cardiopulmonary resuscitation to be attempted even though the physician believes that resuscitation efforts would be futile. It also reviews current controversies surrounding the subject of do-not-resuscitate (DNR) orders and medical futility, discusses the complex medical, legal, and ethical considerations involved, and then offers recommendations as a guide to clinicians and ethics committees in resolving these difficult issues. Conflicts over DNR orders and medical futility should not be resolved through a policy that attempts to define futility in the abstract, but rather through a predefined and fair process that addresses specific cases and includes multiple safeguards. As it examines these issues, the report focuses on the Veterans Health Administration (VHA). Current national VHA policy constrains physicians from entering a DNR order over the objection of a patient or surrogate even if the physician believes cardiopulmonary resuscitation to be futile. The VHA National Ethics Committee recommends that VHA policy be changed to reflect the opinions expressed in this report. The National Ethics Committee, which is composed of VHA clinicians and leaders, as well as veterans advocates, creates reports that analyze ethical issues affecting the health and care of veterans treated in the VHA, the largest integrated health care system in the United States. This report does not change or modify VHA policy.
A library of 6-phenylquinolin-2(1H)-ones with diversity at position 1 and the ortho, meta, and para positions of the pendant phenyl ring has been synthesized using solid-phase parallel synthetic techniques. A key step in the synthesis of the library is a tandem alkylation cleavage in which diversity can be introduced at position 1 simultaneously to the cleavage from the resin. The yields of this step were significantly improved over what has previously been reported by addition of cesium carbonate to scavenge the acid that is formed during the reaction. Furthermore, we have shown that the solid support linkage is tolerant to Suzuki coupling and etherification reaction conditions and that selective cleavage of the linkage can take place in the presence of esters. The resulting 6-phenylquinolin-2(1H)-one library was screened against a panel of nuclear hormone receptors (androgen, estrogen alpha and beta isoforms, glucocorticoid, mineralocorticoid, and progesterone). Certain members of this library display moderate affinity for several of these receptors, and consequently, the 6-phenylquinolin-2(1H)-one core of the library may be considered a privileged structure for nuclear hormone receptors. In contrast, other members of the library display high selectivity for a particular receptor. The highest affinity ligand (9{2,1,1}) possesses an affinity of 330 nM for the androgen receptor, whereas the most selective ligand (9{2,4,1}) displays an affinity of 900 nM for the androgen receptor and a selectivity of 140-fold over the next highest affinity receptor.
To better understand the available publications addressing ethical issues in rural health care we sought to identify the ethics literature that specifically focuses on rural America. We wanted to determine the extent to which the rural ethics literature was distributed between general commentaries, descriptive summaries of research, and original research publications. We identified 55 publications that specifically and substantively addressed rural health care ethics, published between 1966 and 2004. Only 7 (13%) of these publications were original research articles while (12) 22% were descriptive summaries of research and 36 (65%) were general commentaries. The majority of publications examined (55%) were clinically focused while 27% addressed organizational ethics and 18% addressed ethical ramifications of rural health care policy at a national or community level. Our findings indicate that there are a limited number of publications focusing on rural health care ethics, suggesting a need for scholars and researchers to more rigorously address rural ethics issues.
A total of 395 consultation-liaison psychiatrists, geriatricians, and geriatric psychologists responded to a survey that asked them to rate the frequency and importance to clinical care of 23 potential pitfalls and misunderstandings by clinicians who refer patients for assessment of decision-making capacity. Respondents also indicated which pitfalls were the most important to address in educating health care professionals. Overall, 22 of 23 pitfalls were rated as common by more than half of the respondents. Thirty-six percent of the respondents indicated that the most important pitfall to address in educating health care professionals was the tendency for health care practitioners to assume that a patient who lacks capacity for one type of medical decision also lacks capacity for all medical decisions. The results suggest that additional education is needed to improve clinicians' ability to evaluate patients' decision-making capacity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.