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Biomedical subjects

M West

Publications and source records attributed to M West.

At least 37 records · Page 2Linked to original sources

Return to work for persons with traumatic brain injury.

Individuals with traumatic brain injuries experience an array of physical, cognitive, and emotional changes that often make return to preinjury employment unlikely and locating new employment difficult. The authors review the literature related to the return to work for persons with traumatic brain injuries. This includes return to work outcomes, factors influencing return to work, and vocational programs that enhance employment, including a supported employment approach. Guidelines for professionals engaged in supported employment practices are also provided.

Brain Injuries↗

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗

Functional mapping of the DNA binding domain of bovine papillomavirus E1 protein.

Bovine papillomavirus type 1 (BPV-1) requires viral proteins E1 and E2 for efficient DNA replication in host cells. E1 functions at the BPV origin as an ATP-dependent helicase during replication initiation. Previously, we used alanine mutagenesis to identify two hydrophilic regions of the E1 DNA binding domain (E1DBD), HR1 (E1(179-191)) and HR3 (E1(241-252)), which are critical for sequence-specific recognition of the papillomavirus origin. Based on sequence and structure, these regions are similar in spacing and location to DNA binding regions A and B2 of T antigen, the DNA replication initiator of simian virus 40 (SV40). HR1 and A are both part of extended loops which are supported by residues from the HR3 and B2 alpha-helices. Both elements contain basic residues which may contact DNA, although lack of cocrystal structures for both E1 and T antigen make this uncertain. To better understand how E1 interacts with origin DNA, we used random mutagenesis and a yeast one-hybrid screen to select mutations of the E1DBD which disrupt sequence-specific DNA interactions. From the screen we selected seven single point mutants and one double point mutant (F175S, N184Y/K288R, D185G, V193M, F237L, K241E, R243K, and V246D) for in vitro analysis. All mutants tested in electrophoretic mobility shift assays displayed reduced sequence-specific DNA binding compared to the wild-type E1DBD. Mutants D185G, F237L, and R243K were rescued in vitro for DNA binding by the replication enhancer protein E2. We also tested the eight mutations in full-length E1 for the ability to support DNA replication in Chinese hamster ovary cells. Only mutants D185G, F237L, and R243K supported significant DNA replication in vivo which highlights the importance of E1DBD-E2 interactions for papillomavirus DNA replication. Based on the specific point mutations examined, we also assigned putative roles to individual residues in DNA binding. Finally, we discuss sequence and spacing similarities between E1 HR1 and HR3 and short regions of two other DNA tumor virus origin-binding proteins, SV40 T antigen and Epstein-Barr virus nuclear antigen 1 (EBNA1). We propose that all three proteins use a similar DNA recognition mechanism consisting of a loop structure which makes base-specific contacts (HR1) and a helix which primarily contacts the DNA backbone (HR3).

Amino Acid Sequence↗

Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis.

We have used high-density DNA microarrays to provide an analysis of gene regulation during the mammalian cell cycle and the role of E2F in this process. Cell cycle analysis was facilitated by a combined examination of gene control in serum-stimulated fibroblasts and cells synchronized at G(1)/S by hydroxyurea block that were then released to proceed through the cell cycle. The latter approach (G(1)/S synchronization) is critical for rigorously maintaining cell synchrony for unambiguous analysis of gene regulation in later stages of the cell cycle. Analysis of these samples identified seven distinct clusters of genes that exhibit unique patterns of expression. Genes tend to cluster within these groups based on common function and the time during the cell cycle that the activity is required. Placed in this context, the analysis of genes induced by E2F proteins identified genes or expressed sequence tags not previously described as regulated by E2F proteins; surprisingly, many of these encode proteins known to function during mitosis. A comparison of the E2F-induced genes with the patterns of cell growth-regulated gene expression revealed that virtually all of the E2F-induced genes are found in only two of the cell cycle clusters; one group was regulated at G(1)/S, and the second group, which included the mitotic activities, was regulated at G(2). The activation of the G(2) genes suggests a broader role for E2F in the control of both DNA replication and mitotic activities.

Animals↗

Attachment disorganization and dissociative symptoms in clinically treated adolescents.

OBJECTIVE: To examine the association of unresolved and unclassifiable attachment with dissociative symptomatology in a sample of 133 adolescents in psychiatric treatment. METHOD: The study compared 69 adolescents who were unresolved and unclassifiable with 64 adolescents who were not unresolved and unclassifiable. Attachment organization was assessed using the Adult Attachment Interview (AAI). Dissociative symptomatology was assessed using a scale derived from the Youth Self Report (YSR) behaviour checklist. RESULTS: A continuing unresolved and unclassifiable response to attachment-related trauma was correlated with dissociative symptomatology for both male and female adolescents. CONCLUSIONS: Cognitive disorganization may be an important variable mediating between the effects of earlier traumatic caregiving experiences and later dissociative symptoms.

Adolescent↗

Lipid-lowering efficacy, safety, and costs of a large-scale therapeutic statin formulary conversion program.

STUDY OBJECTIVE: To assess the lipid-lowering efficacy, safety, and costs of a large-scale statin formulary conversion program. DESIGN: Prospective, observational study. SETTING: Tertiary academic medical center. PATIENTS: A total of 980 patients consented to participate; 942 patients completed the study. INTERVENTION: Patients were converted from their current statin therapy to either cerivastatin 0.4 or 0.8 mg/day, or simvastatin 80 mg/day, using a conversion algorithm. MEASUREMENTS AND MAIN RESULTS: Efficacy and safety were evaluated at baseline and after 6 weeks of therapy; costs were also measured. Overall attainment of the National Cholesterol Education Program (NCEP) goal for low-density lipoprotein cholesterol (LDL) increased from 64.8% to 74.5% of patients (p<0.001); mean LDL decreased from 115+/-30 mg/dl to 106+/-25 mg/dl (p<0.001). Adverse events occurred in 3% of patients, and included myositis (0.6%) and increased hepatic transaminases (0.1%). Overall costs were reduced by $115/patient treatment-year. CONCLUSION: Statin therapeutic interchange can improve lipid control at reduced costs. The possibility of uncommon but potentially serious adverse effects suggests that these programs require appropriate monitoring.

Aged↗

Doctoral students' responses to writing critique: messages for teachers.

Writing is a major part of learning scholarship in a discipline. Therefore, it is important to understand what promotes and what hinders this learning. In transcribed interviews, 15 doctoral students in nursing at a large university described to us what they saw as helpful or not helpful about responses to their writing. The themes take the form of messages for teachers that, when reported in the context of the composition literature, provide helpful suggestions for teachers.

Authorship↗

A data mart for operations analysis.

In this article we describe the evolution and architecture of a data mart developed to address the modeling and analysis needs of healthcare operations analysts. More specifically, the data mart is used in projects relating to demand analysis, forecasting, capacity planning, and service system design for a healthcare system consisting of a large tertiary care hospital and a smaller community hospital. The primary focus of the mart is on the detailed movement of inpatients through each hospital, although most component data tables include outpatient information such as emergency center visits, surgical cases, cardiac catheterization cases, and short-stay visits. We show that the data mart goes well beyond consolidating data from different sources by including a number of complex, precalculated fields, data structures, and function libraries that are specific to the needs of operations analysts. We discuss several outstanding and challenging design issues that should be of interest to the data warehouse vendor community.

Bed Occupancy↗

Using data mining to find fraud in HCFA health care claims.

Data mining can be/used to detect health care fraud and abuse through visualization of very large data sets to isolate new and unusual patterns of activity. Data mining has allowed better direction and use of health care fraud detection and investigative resources by recognizing and quantifying the underlying indicators of fraudulent claims, fraudulent providers, and fraudulent beneficiaries. A large amount of work must be performed prior to the actual data mining. These precursory tasks include: customer discussions, data extraction and cleaning, transformation of the database, and auditing (basic statistics and visualization of the information) of the data. This paper describes the tasks performed in support of a project for HCFA (Health Care Financing Administration).

Centers for Medicare and Medicaid Services, U.S.↗

A consensus sequence for long-chain fatty-acid alcohol oxidases from Candida identifies a family of genes involved in lipid omega-oxidation in yeast with homologues in plants and bacteria.

The yeast Candida cloacae is capable of growing on alkanes and fatty acids as sole carbon sources. Transfer of cultures from a glucose medium to one containing oleic acid induced seven proteins of M(r) 102,000, 73,000, 61,000, 54,000, and 46,000 and two in the region of M(r) 45,000 and repressed a protein of M(r) 64,000. The induction of the M(r) 73,000 protein reached a 7-fold maximum 24 h after induction. The protein was confirmed by its enzyme activity to be a long-chain fatty-acid alcohol oxidase (LC-FAO) and purified to homogeneity from microsomes by a rapid procedure involving hydrophobic chromatography. An internal peptide of 30 amino acids was sequenced. A 1100-base pair cDNA fragment containing the LC-FAO peptide coding sequence was used to isolate a single exon genomic clone containing the full-length coding sequence of an LC-FAO (fao1). The fao1 gene product was expressed in Escherichia coli and was translated as a functional long-chain alcohol oxidase, which was present in the membrane fraction. In addition, full-length coding sequences for a Candida tropicalis LC-FAO (faoT) and a second C. cloacae LC-FAO (fao2) were isolated. The DNA sequences obtained had open reading frames of 2094 (fao1), 2091 (fao2), and 2112 (faoT) base pairs. The derived amino acid sequences of fao2 and faoT showed 89.4 and 76.2% similarities to fao1. The fao1 gene is much more highly induced on alkane than is fao2. Although this study describes the first known DNA sequences encoding LC-FAOs from any source, there are unassigned Arabidopsis sequences and an unassigned Mycobacterium sequence in the GenBank(TM) Data Bank that show strong homology to the described LC-FAO sequences. The conservation of sequence between yeast, plants, and bacteria suggests that an as yet undescribed family of long-chain fatty-acid oxidases exists in both eukaryotes and prokaryotes.

Alcohol Oxidoreductases↗

EEG effects of ECT: implications for rTMS.

Electroconvulsive therapy (ECT) involves the use of electrical stimulation to elicit a series of generalized tonic-clonic seizures for therapeutic purposes and is the most effective treatment known for major depression. These treatments have significant neurophysiologic effects, many of which are manifest in the electroencephalogram (EEG). The relationship between EEG data and the response to ECT has been studied since the 1940s, but for many years no consistent correlates were found. Recent studies indicate that a number of specific EEG features recorded during the induced seizures (ictal EEG) as well as before and after a course of treatment (interictal EEG) are related to both the therapeutic efficacy and cognitive side effects. Similar to ECT, repetitive transcranial magnetic stimulation (rTMS), which involves focal electromagnetic stimulation of cortical neurons, has also been studied as an antidepressant therapy and also appears to have neurophysiologic effects, although these have not been as fully investigated as is the case with ECT. Given the similarity of these treatments, it is natural to consider whether advances in understanding the electrophysiologic correlates of the ECT response might have implications for rTMS. The present article reviews the literature on the EEG effects of ECT and discusses the implications in terms of the likely efficacy and side effects associated with rTMS in specific anatomic locations, the potential for producing an antidepressant response with rTMS without eliciting seizure activity, eliciting focal seizures with rTMS, and the possibility of using rTMS to focally modulate seizure induction and spread with ECT to optimize treatment.

Brain Mapping↗

The genotypic landscape during in vitro evolution of a catalytic RNA: implications for phenotypic buffering.

The Tetrahymena group I ribozyme catalyzes the cleavage of a phosphodiester linkage in specific sequences of RNA. This phenotype can be used in an in vitro selection-amplification process to evolve variants that are capable of RNA catalysis in the presence of Ca(2+) as the sole available cation. With sufficient genotypic characterization of the population as it evolves, we have a rare opportunity of observing how the information stored in an evolving population responds to selective pressures, such as the requisite of catalyzing RNA cleavage in the absence of Mg(2+) or Mn(2+). In the present work, we examine the population dynamics of this system using sequence information from previous experimental work. We focus on two issues: How does the information content of the population evolve? and Is the system evolving as an adaptive walk on a rugged landscape? To investigate these questions, information theoretical parameters are examined. The evolution of the population is visualized by mapping the genotypic frequency distribution onto a two-dimensional projection of sequence space. The projection was generated using Hamming distances from the wild-type, starting sequence and a catalytically successful, evolved sequence. The evolution of the information content of the system was measured by calculating the grammar complexity of the observed sequences, which showed a very slight increase over 12 generations. This result is consistent with the system performing a search for a local optimum. The dynamics of the population in this sequence space is consistent with an adaptive walk on an uncorrelated, or "rugged," genotypic landscape, despite the observation that the phenotypic progress of the population appears smooth. The relative insensitivity of the phenotypic landscape to the variegation of the genotypic landscape suggests that the former is buffered against variation in the latter through various epigenetic-like mechanisms.

Evolution, Molecular↗

No loss of hippocampal neurons in AIDS patients.

Acquired immunodeficiency syndrome (AIDS) is often accompanied by neurological disorders and neuropathological abnormalities. A loss of up to 30% of the neocortical neurons in brains from AIDS patients has been demonstrated in several studies. This neuron loss appeared to have no relationship with either the presence of clinical dementia or HIV encephalitis. The hippocampal region of the brain is an essential component of learning and memory processes and it is severely affected in a number of diseases, including temporal lobe epilepsy and Alzheimer's dementia. In view of the reports of a considerable loss of neocortical neurons, the aim of the present study was to investigate the degree to which neurons may be lost in hippocampus of AIDS patients. A stereological method, the optical fractionator, was used to estimate the total number of neurons in the five subregions of the hippocampus of nine AIDS patients and ten controls. There were no statistically significant differences in the group means of the number of neurons in any of the subdivisions. This result is discussed in the light of the large loss of neurons in the neocortex reported to take place in AIDS patients.

Acquired Immunodeficiency Syndrome↗

WESTCOP: a disease management approach to coronary artery disease.

Disease management is a systematic approach to improving care of populations of patients with specific clinical conditions. Critical to success are the formation of collaborative teams of health care stakeholders, development and promulgation of clinical practice guidelines, and performance measurement and feedback to providers as a process of continuous practice improvement. This article describes a disease management program for patients with coronary artery disease in a provincial health district with a population of 180,000. It discusses the rationale and methods behind the operationalisation of the main program elements, benefits achieved to date and challenges confronted.

Acute Disease↗

The Adolescent Unresolved Attachment Questionnaire: the assessment of perceptions of parental abdication of caregiving behavior.

This article reports on the Adolescent Unresolved Attachment Questionnaire (AUAQ), a brief questionnaire that assesses the caregiving experiences of unresolved adolescents (as recipients of caregiving). The AUAQ was developed and validated in a large normative sample (n = 691) and a sample of 133 adolescents in psychiatric treatment. It is a self-report questionnaire consisting of 3 scales with Likert-type responses ranging from strongly disagree to strongly agree. The Aloneness/Failed Protection Scale assesses the adolescent's perception of the care provided by the attachment figure. The Fear Scale taps the fear generated by the adolescent's appraisal of failed attachment figure care. The Anger/Dysregulation Scale assesses negative affective responses to the perceived lack of care from the attachment figure. All scales demonstrated satisfactory internal reliability and agreement between scores for adolescents (n = 91) from the normative sample who completed the AUAQ twice. Adolescents in the clinical sample also completed the Adult Attachment Interview (AAI; C. George, N. Kaplan, & M. Main, 1984/1985/1996); the AUAQ demonstrated high convergent validity with the AAI.

Adolescent↗

Identification of a short, hydrophilic amino acid sequence critical for origin recognition by the bovine papillomavirus E1 protein.

The E1 protein of bovine papillomavirus (BPV) is a site-specific DNA binding protein that recognizes an 18-bp inverted repeat element in the viral origin of replication. Sequence-specific DNA binding function maps to the region from approximately amino acids 140 to 300, and isolated polypeptides containing this region have been shown to retain origin binding in vitro. To investigate the sequence and structural characteristics which contribute to sequence-specific binding, the primary sequence of this region was examined for conserved features. The BPV E1 DNA binding domain (E1DBD) contains three major hydrophilic domains (HR1, amino acids 179-191; HR2, amino acids 218 to 230; and HR3, amino acids 241 to 252), of which only HR1 and HR3 are conserved among papillomavirus E1 proteins. E1DBD proteins with lysine-to-alanine mutations in HR1 and HR3 were severely impaired for DNA binding function in vitro, while a lysine-to-alanine mutation in HR2 had a minimal effect on DNA binding. Mutation of adjacent threonine residues in HR1 (T187 and T188) revealed that these two amino acids made drastically different contributions to DNA binding, with the T187 mutant being severely defective for origin binding whereas the T188 mutant was only mildly affected. Helical wheel projections of HR1 predict that T187 is on the same helical face as the critical lysine residues whereas T188 is on the opposing face, which is consistent with their respective contributions to DNA binding activity. To examine E1 binding in vivo, a yeast one-hybrid system was developed. Both full-length E1 and the E1DBD polypeptide were capable of specifically interacting with the E1 binding site in the context of the yeast genome, and HR1 was also critical for this in vivo interaction. Overall, our results indicate that HR1 is essential for origin binding by E1, and the features and properties of HR1 suggest that it may be part of a recognition sequence that mediates specific E1-nucleotide contacts.

Amino Acid Sequence↗