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Biomedical subjects

John Taylor

Publications and source records attributed to John Taylor.

At least 37 records · Page 2Linked to original sources

The anatomy of complications workshop: an educational strategy to improve the training and performance of fellows in gynecologic oncology.

OBJECTIVES: In Australasia, the USA, and Canada, certified gynecologic oncologists (CGO) are expected to be competent in performing intestinal, urological, and vascular procedures relevant to gynecologic oncology. This competency may be difficult to achieve and experience with simulation rather than human patients may be preferable during initial training. We present the structure, objectives, rationale, and outcomes for a surgical skill workshop aimed to improve the performance of fellows in gynecologic oncology. WORKSHOP STRUCTURE: The overall objective of the workshop is the prevention and management of complications in gynecologic oncology surgery. Preworkshop preparation includes anatomical illustrations to guide reading and a training video describing surgical procedures and the relevant aspects of ovine and porcine anatomy. There are four modules: (i) Anatomy includes an interactive lecture, cadaveric dissection, and examination of prosections. (ii) Porcine surgery involves the demonstration, practice, and learning of techniques needed to deal with unexpected or deliberate operative injury to bowel, bladder, ureter, and major blood vessels and performance of less common operations. (iii) Live ovine surgery allows further supervised practice of these procedures plus the repair of vascular injury. (iv) Case presentations allow each participant to present a complicated case in a facilitated group session with discussion and feedback from their peers. This session is controlled, nonthreatening, and interactive. CONCLUSION: Participant feedback and evaluation suggests that this workshop format and the opportunity to practice less common procedures are helpful to clinical practice. This educational model is presented in the hope that it may act as a template for the development of similar programs for fellows in other countries.

Animals↗

Birth order in sex-offending and aggressive-offending men.

The relation between birth order and number of sexual and violent convictions was investigated retrospectively in a sample of 113 men, to determine whether the established fraternal birth order effect in male homosexual preference and deviant sexual preference (e.g., for rape and pedophilia) may be extended to sexual behavior. Participants were mentally disordered offenders detained in a medium secure psychiatric unit in the United Kingdom and comprised 64 men with sexual convictions and 49 men with nonsexual violent convictions. Sibling data from psychiatric notes were used to calculate Berglin's birth order index for each participant and conviction data were obtained from the Home Office Offenders' Index. Fraternal birth order was significantly correlated with number of sexual convictions (p < or = .05). No association was found between fraternal or sororal birth order and violent convictions in either the sex offender or violent offender group. Results suggest that the fraternal birth order effect previously found for deviant sexual preference in sex offenders (K. Côté, C. M. Earls, & M. L. Lalumière, 2002; M. L. Lalumière, G. T. Harris, V. L. Quinsey, & M. E. Rice, 1998) also applies to sexually deviant behavior and is specific to sexual rather than general offending. Results are discussed in terms of the maternal immunosensitization hypothesis.

Adult↗

Relative efficacy of criminological, clinical, and personality measures of future risk of offending in mentally disordered offenders: a comparative study of HCR-20, PCL:SV, and OGRS.

The authors compared the ability of 3 commonly used measures of risk of future offending in a sample of 315 mentally disordered offenders discharged from a medium-secure unit in the United Kingdom. The authors explored whether the same criminogenic factors that predict recidivism in the general population also predict recidivism in mentally disordered offenders. The actuarial measure, using mainly criminological variables, provided the best prediction of recidivism compared with measures based on personality or clinical information, which provided no incremental validity over the actuarial measure. The authors suggest that for maximum efficacy clinical risk should be rated at a time of active symptoms rather than at discharge when symptoms are minimal.

Adult↗

Systolic blood pressure diurnal variation is not a predictor of renal target organ damage in kidney transplant recipients.

Elevated blood pressure and diurnal blood pressure variation detected by ambulatory blood pressure monitoring has been shown to be predictive of worse outcome in end-stage renal disease patients in small studies. What has been lacking is a large study to determine whether these ambulatory blood pressure monitoring (ABPM)-derived variables are predictors of worse outcome in renal transplant recipients. All the patients that underwent renal transplantation and follow up at this institution from January 1998 till October 2002 were involved in this study (n=177). All patients were followed up for at least 48 weeks. Last creatinine correlated positively with duration of dialysis (p=0.035, r=0.158), kidney-donor age (p<0.0001, r=0.377), early kidney function (p<0.0001, r=0.610, r=0.683), 24-h systolic blood pressure (SBP) load (p=0.002, r=0.228), and ABPM-derived pulse pressure (p<0.0001, r=0.269). However neither office blood pressure nor SBP diurnal variation were predictors of kidney outcome. Regression analysis showed that early kidney function was the only independent predictor of transplant outcome (p<0.0001). Systolic blood pressure diurnal variation, though an important predictor of target organ damage in chronic kidney disease patients, was not a predictor of renal transplant function in renal transplant recipients. Only early kidney function was an independent predictor of later serum creatinine.

Adult↗

Postpartum maternal moods and infant size predict performance on a national high school entrance examination.

BACKGROUND: In an earlier series of studies, we documented the effects of feeding practices and postnatal maternal mood on the growth and development of 226 Barbadian children during the first few months of life. In this report, we extend our earlier studies by examining predictive relationships between infant size, feeding practices and postpartum maternal moods and scores on a national high school examination, the Common Entrance Examination (CEE), at 11 to 12 years of age. METHODS: Feeding practices, anthropometry, and maternal moods, using Zung depression and anxiety scales and a morale scale, were assessed at 7 weeks (n = 158), 3 months (n = 168), and 6 months (n = 209) postpartum. Background variables including sociodemographic and home environmental factors were also assessed during infancy. CEE scores on 169 of the children in the original study were obtained from the Ministry of Education of Barbados. RESULTS: In our sample of 86 boys and 83 girls, we found that reduced infant lengths and weights at 3 and 6 months of age were predictive of lower CEE, especially math scores. Children who were smaller at these early ages had significantly lower scores on the examination than did larger children. Postpartum maternal moods, including reports of despair and anxiety, were also found to be significant predictors of lower CEE scores, especially English scores. However, breast-feeding and other feeding practices were not directly associated with the CEE scores. Background variables, which significantly predicted lower CEE scores, included young maternal age at the time of her first pregnancy, more children in the home, less maternal education, and fewer home conveniences. Significant associations between infant anthropometry, maternal moods and CEE scores were all significant even when these background variables were controlled for. CONCLUSIONS: These findings have important implications for developing interventions early in life to improve academic test scores and future opportunities available to children in this setting.

Achievement↗

Personal resources and depression in the transition to adulthood: ethnic comparisons.

Based on a representative sample of 1,803 South Florida young adults, we examine the extent to which personal attributes mediate or moderate the ethnicity-depression relationship and condition the effects of social stress on depression. Our sample contains nearly equal proportions of African American, Cuban American, "other" Hispanic, and non-Hispanic white respondents. Findings suggest that there are ethnic variations in four of the five personal resources considered. Additionally, when accounting for ethnic differences in response tendencies and in the confounding of personal resources with depression, there is strong evidence for both direct and stress-buffering effects of personal resources. Although naïve comparisons of within group findings imply a number of ethnic variations in those effects, few statistically significant differences are observed. It is suggested that ethnic similarities outweigh differences, at least with respect to the mental health significance of the personal resources considered. Overall, the results highlight some of the complexities inherent in making multi-ethnic comparisons.

Adult↗

The human serum proteome: display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins.

Plasma, the soluble component of the human blood, is believed to harbor thousands of distinct proteins, which originate from a variety of cells and tissues through either active secretion or leakage from blood cells or tissues. The dynamic range of plasma protein concentrations comprises at least nine orders of magnitude. Proteins involved in coagulation, immune defense, small molecule transport, and protease inhibition, many of them present in high abundance in this body fluid, have been functionally characterized and associated with disease processes. For example, protein sequence mutations in coagulation factors cause various serious disease states. Diagnosing and monitoring such diseases in blood plasma of affected individuals has typically been conducted by use of enzyme-linked immunosorbent assays, which using a specific antibody quantitatively measure only the affected protein in the tested plasma samples. The discovery of protein biomarkers in plasma for diseases with no known correlations to genetic mutations is challenging. It requires a highly parallel display and quantitation strategy for proteins. We fractionated blood serum proteins prior to display on two-dimensional electrophoresis (2-DE) gels using immunoaffinity chromatography to remove the most abundant serum proteins, followed by sequential anion-exchange and size-exclusion chromatography. Serum proteins from 74 fractions were displayed on 2-DE gels. This approach succeeded in resolving approximately 3700 distinct protein spots, many of them post-translationally modified variants of plasma proteins. About 1800 distinct serum protein spots were identified by mass spectrometry. They collapsed into 325 distinct proteins, after sequence homology and similarity searches were carried out to eliminate redundant protein annotations. Although a relatively insensitive dye, Coomassie Brilliant Blue G-250, was used to visualize protein spots, several proteins known to be present in serum in < 10 ng/mL concentrations were identified such as interleukin-6, cathepsins, and peptide hormones. Considering that our strategy allows highly parallel protein quantitation on 2-DE gels, it holds promise to accelerate the discovery of novel serum protein biomarkers.

Adult↗

Anatomy of Complications workshop: an educational strategy to improve performance in obstetricians and gynaecologists.

Many specialist obstetricians and gynaecologists feel inadequately trained to deal with certain situations such as injury to bowel, bladder, ureter and major vessels, and value further training to prevent and manage these problems. We present the structure, objectives and rationale for a surgical skills workshop, which is an intensive practical learning experience aimed to improve the performance of obstetricians and gynaecologists. The overall objective of the workshop is improvement in the prevention and management of complications in obstetric and gynaecological surgery. Over 100 participants have completed the workshop so far. Pre-workshop preparation includes anatomical illustrations to guide reading and a training video describing surgical skills, ewe anatomy and hysterectomy in the ewe. There are four modules: anatomy includes an interactive lecture, cadaveric dissection and examination of prosections with specific learning tasks. Surgical skills involves the demonstration, practice and learning of techniques needed to deal with unexpected operative injury to bowel, bladder, ureter and major blood vessels. Live animal surgery on a ewe allows further supervised practice of the previously learned skills plus the repair of serious vascular injury. Case presentations allow each participant to present a complicated case in a facilitated group session with discussion and feedback from their peers. This session is controlled, non-threatening and a valuable interactive learning experience. Participant feedback suggests that this workshop format is useful and appears to improve the confidence, competence and performance of the participants. This workshop is presented as a template on which other educational activities can be developed.

Clinical Competence↗

Value of a structured participant evaluation questionnaire in the development of a surgical education program.

OBJECTIVE: To describe how the summative evaluation of attitudes and perceptions of participants at a surgical skills workshop influences and contributes to the development of the workshop. MATERIALS AND METHODS: One hundred participants from 11 workshops were invited to complete a structured scored anonymous questionnaire with 18 statements, at the end of each workshop. Space was provided for free comment next to each statement. The questionnaire covered all aspects of the workshop including the practical modules, learning materials, organisation, facilitators and the relevance of the workshop to their needs. Ninety-eight of the 100 participants returned the questionnaire and this analysis is based on their responses. RESULTS: All respondents considered the workshop content, structure and facilities enabled the educational objectives to be achieved. The scored responses to the structured statements helped to determine the degree of satisfaction with the workshop domains, but did not give direction for change. The informal 'free' comments gave insight as to how improvements could be achieved in specific domains. Numerous changes suggested by participants have been included in subsequent workshops. CONCLUSION: Summative evaluation of an educational program is important to determine participant satisfaction and to determine areas needing improvement. Structured scored questionnaires are helpful in determining levels of satisfaction with the various domains of the program. Informal written comments allow insight into specific areas requiring improvement and may provide guidance as to how improvement can be achieved. Space for such comment should be encouraged in any program evaluation questionnaire.

Clinical Competence↗

Drug interaction in a renal transplant patient: cyclosporin-Neoral and orlistat.

An overweight 56-year-old type II diabetic on peritoneal dialysis (body mass index 35 kg/m(2)) was taking Orlistat for some months up until live-unrelated renal transplantation. Despite oral cyclosporin A (CyA) for 48 hours pretransplantation, it was very difficult to achieve adequate CyA blood levels for the first week postengraftment despite the use of much larger oral CyA doses. After opening his bowels on day 7, and the use of 3 days intravenous CyA, good CyA blood levels were achieved then maintained with conventional oral doses. The authors believe that this case shows important interactions between CyA and Orlistat.

Administration, Oral↗

Suppression of rat and human growth hormone and prolactin secretion by a novel somatostatin/dopaminergic chimeric ligand.

As cotreatment of somatostatin (SRIF) and dopamine (DA) agonists reduces GH in acromegaly more effectively than either agonist alone, SRIF and DA receptors (SSTR and DAR) may interact with enhanced functional activity. The selective SSTR2 agonist, BIM-23023 (50% effective dose, 0.42), and the DAR2 agonist, BIM-53097 (50% effective dose, 22.1), dose- dependently inhibited GH secretion in cultured primary rat and human fetal as well as in human pituitary tumor cells derived from GH-secreting adenomas. The combination of individual SSTR2 and DAR2 agonists was additive for suppressing GH secretion in both rat and human pituitary cells. BIM-23A387 is a chimeric compound that contains structural elements of both SRIF and DA in a single molecule and retains potent, selective binding to DAR2 and SSTR2. BIM-23A387 (50% effective dose, 0.16 for SSTR2 and 24.5 for DAR2), displayed similar efficacy in suppressing GH secretion from rat pituitary cells as the combination of the two individual agonists. In contrast, the chimeric molecule was more potent than individual selective analogs in suppressing GH secretion by human fetal pituitary and GH-secreting adenoma cells (P < 0.05). Although the DAR2 antagonist, sulpiride, reversed BIM-23A387-induced GH suppression, blockade of SSTR2 by the selective SSTR antagonist, BIM-23454, did not block BIM-23A387-suppressed GH secretion. These results indicate that mechanisms by which the chimeric molecule suppresses pituitary GH secretion may not be mediated by individual SSTR2 or DAR2 signaling, respectively. Functional interaction of the two receptors may explain the clinical observation that more effective GH suppression is achieved when DAR2 and SSTR2 agonists are administered in combination. The SRIF/DA chimeric molecule, BIM-23A387, represents a novel tool for effective drug treatment of acromegaly and for prolactinomas otherwise resistant to dopaminergic therapy.

Animals↗

Functional association of somatostatin receptor subtypes 2 and 5 in inhibiting human growth hormone secretion.

We previously demonstrated that somatostatin (SRIF)-induced inhibition of GH secretion from human pituitary cells is mediated through both the SRIF receptor (SSTR) 2 and 5 subtypes. The interplay between these two SSTR subtypes in regulating GH was therefore tested in primary human fetal pituitary cultures (18-30 wk gestation). GHRH (10 nM)-stimulated GH secretion (51% increase, P < 0.05) was suppressed equally by either SSTR2 or SSTR5-selective agonists (10 nM). GH suppression correlated with agonist affinity for their respective receptor subtypes. Combined addition of SSTR2- and SSTR5-specific agonists was synergistic for GH suppression, achieving 73% (P < 0.05) inhibition as compared with inhibition attained with SSTR2 (32%) and SSTR5 (34%) agonists used alone (P < 0.05). The SSTR2 selective antagonist BIM-23454 dose-dependently blocked SSTR2 but not SSTR5-induced suppression of GH secretion. BIM-23454 also completely reversed GH suppression in response to the combined activation of SSTR2 and SSTR5. The IC(50) for BIM-23454 reversal of agonist-induced GH suppression was 55 nM and 33 nM for two SSTR2 agonists, 45 nM and 40 nM for the combination of SSTR2 and SSTR5 agonists, respectively, and 45 nM for the SSTR2/SSTR5 agonist BIM-23244, all of which were similar to the affinity of BIM-23454 for SSTR2 (32 nM). These results suggest the following: 1) activation of both SSTR2 and SSTR5 induces a functional association of receptor subtypes, resulting in synergistic GH suppression; 2) BIM-23454 is a potent SSTR2-selective antagonist capable of reversing SRIF-induced GH suppression; and 3) the ability of a selective SSTR2 antagonist to inhibit the GH suppressing action of SSTR2 agonist alone, SSTR2/SSTR5 biselective agonists, or SSTR2 and SSTR5 agonists in combination support the concept of a functional interaction between somatotroph SSTR2 and SSTR5 subtypes in primary human fetal pituitary cells.

Calcium↗

Dealing with saturation at the amino acid level: a case study based on anciently duplicated zebrafish genes.

The ray-finned fishes (Actinopterygii) seem to have two copies of many tetrapod (Sarcopterygii) genes. The origin of these duplicate fish genes is the subject of some controversy. One explanation for the existence of these extra fish genes could be an increase in the rate of independent gene duplications in fishes. Alternatively, gene duplicates in fish may have been formed in the ancestor of all or most Actinopterygii during a complete genome duplication event. A third possibility is that tetrapods have lost more genes than fish after gene or genome duplication events in the common ancestor of both lineages. These three hypotheses can be tested by phylogenetic reconstruction. Previously, we found that a large number of anciently duplicated genes of zebrafish are sister sequences in evolutionary trees suggesting that they were produced in Actinopterygii after the divergence of Sarcopterygii [Phil. Trans. R. Soc. Lond. B 356 (2001) 119]. On the other hand, several well-supported trees showed one of the two fish genes as the sister sequence to a monophyletic clade that included the second fish gene and genes from frog, chicken, mouse and human. These so-called outgroup topologies suggest that the origin of many fish duplicates predates the divergence of the Sarcopterygii and Actinopterygii and support the hypothesis that tetrapods have lost duplicates that have been retained in fish. Here we show that many of these 'outgroup' tree topologies are erroneous and can be corrected when mutational saturation is taken into account. To this end, a Java-based application has been developed to visualize the amount of saturation in amino acid sequences. The program graphically displays the number of observed frequent and rare amino acid replacements between pairs of sequences against their overall evolutionary distance. Discrimination between frequent and rare amino acid replacements is based on substitution probability matrices (e.g. PAM and BLOSUM). Evolutionary distances between sequences can be computed from the fraction of unsaturated sites only and evolutionary trees inferred by pairwise distance methods. When trees are computed by omitting the saturated fraction of sites, most fish duplicates are sister sequences.

Amino Acids↗

In vivo RNA-directed transcription, with template switching, by a mammalian RNA polymerase.

These studies support the interpretation that a host polymerase, most likely RNA polymerase II, can not only carry out transcription that is RNA directed, but also achieve template switching on a discontinuous RNA template, and even perform non-templated nucleotide incorporation. As part of an in vivo analysis of the initiation of replication of the RNA genome of human hepatitis delta virus (HDV), a series of linear RNAs containing HDV sequences was tested in order to explain the ability of this host polymerase to initiate RNA-directed RNA synthesis in vivo and produce replicating circular HDV species. The data support the hypothesis that the input linear template RNAs were not converted to circles before transcription but rather that in the process of transcription, the polymerase was able to make an intra-molecular template switch. Furthermore, in certain cases this switch produced small deletions of template sequences, and in some cases even insertion of non-templated sequences. Thus, in an in vivo situation, polymerase II has several important capabilities in addition to what is considered typical DNA-directed transcription.

Base Sequence↗

Health risk escalators and the rehabilitation of offenders with learning disabilities.

This paper presents a study of risk management in a hospital within the UK. National Health Service which attempts to rehabilitate offenders with learning disabilities. Analysis is based on the metaphor of a 'risk escalator'. Health and social care systems can be characterised as risk escalators if they possess three attributes. Firstly, risk managers should agree the rough ordering of the severity of a set of related risks. Secondly, a repertoire of responses which provide different trade-offs between autonomy and safety, and which can be calibrated against risk severity, should be available. Thirdly, the potential for positive and/or negative feedback, which give risk escalators their dynamic character, should be identified. Risk escalators may be deliberately designed, or may, like the hospital regime discussed in this paper, coalesce from pre-existing sub-systems offering different autonomy/safety balances. They may carry service users upwards towards greater safety if needed, as in health screening systems, or downward towards greater autonomy if justified, for instance in rehabilitation systems. Their therapeutic status is contestable. Upward risk escalators can be accused of generating positive feedback, with iatrogenic effect. Downward risk escalators may be criticised for pushing service users too strongly towards less intense interventions, causing neglect. The present case study brings out emergent properties of a downward risk escalator, including: organisational disruption to system functioning; preferencing of safety over autonomy; active and reflexive system management by clients; multiple, organisational risk rationalities; and the reification of riskiness as a generic attribute of individuals.

Crime↗

The fitness of filamentous fungi.

Fitness is a common currency in comparative biology. Without data on fitness, hypotheses about the adaptive significance of phenotypes or basic mechanisms of evolution, for example natural selection, remain speculative. Experiments with fungi can address questions specific to fungi or questions with a broader significance. Fungi can challenge the generality of fundamental evolutionary principles, yet there are no standard measures of fungal fitness. We argue that focusing on a single aspect of a complex life cycle, or a single measure of fitness (e.g. the number of asexual spores) is appropriate. Choosing which aspect of fitness to measure can be facilitated by an understanding of how fitness measures are correlated. Choices can also be based on the ecology of a species, for example whether a fungus is semelparous and reproduces once, or iteroparous and reproduces multiple times.

Biological Evolution↗