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Biomedical subjects

M Gibbs

Publications and source records attributed to M Gibbs.

At least 19 recordsLinked to original sources

Egg size-number trade-off and a decline in oviposition site choice quality: female Pararge aegeria butterflies pay a cost of having males present at oviposition.

Once mated, the optimal strategy for females of the monandrous butterfly, Pararge aegeria, is to avoid male contact and devote as much time as possible to ovipositing, as there is little advantage for females to engage in multiple matings. In other butterfly species the presence of males during egg laying has been shown to affect aspects of oviposition behavior and it has been suggested that repeated interference from males has the potential to reduce reproductive output. The aim of this study was to assess the effects of male presence during oviposition on reproductive output and behavior of a population of P. aegeria obtained from Madeira Island, Portugal, and maintained in the laboratory. Two experiments were performed where females were housed individually in small cages. Experiment 1 examined how social factors influenced the egg laying behavior of females. To do this the presence or absence of males was manipulated and egg size and number was measured over the first 14 days of oviposition. It was observed that when males were present during oviposition females made a trade-off between egg size and number. Experiment 2 examined how social factors affected oviposition site choice. Again, male presence/absence was manipulated, but in this experiment where the female laid her egg in relation to host quality was scored, and the size of the egg laid was measured. In the absence of males females selectively positioned their larger eggs on good quality host plants. However, selective oviposition was no longer observed when females were in the presence of males. We suggest that P. aegeria females from the Madeira Island population are adapted for a flexible oviposition strategy, governed by external cues, allowing a trade-off between egg size and number when the time available for egg laying is limiting.

Animals↗

The impact of the 2003 heat wave on daily mortality in England and Wales and the use of rapid weekly mortality estimates.

This paper describes a retrospective analysis of the impact of the 2003 heat wave on mortality in England and Wales, and compares this with rapid estimates based on the Office for National Statistics routine weekly deaths reporting system. Daily mortality data for 4 to 13 August 2003, when temperatures were much hotter than normally seen in England, were compared with averages for the same period in years 1998 to 2002. The August 2003 heat wave was associated with a large short-term increase in mortality, particularly in London. Ozone and particulate matter concentrations were also elevated during the heat wave. Overall, there were 2139 (16%) excess deaths in England and Wales. Worst affected were people over the age of 75 years. The impact was greatest in the London region where deaths in those over the age of 75 increased by 59%. Estimated excess mortality was greater than for other recent heat waves in the United Kingdom. The estimated number of deaths registered each week is reported by the Office for National Statistics. The first clear indication of a substantial increase in deaths was published on 21 August 2003. This provided a quick first estimate of the number of deaths attributable to the heat wave and reflected the pattern of daily deaths in relation to the hottest days, but underestimated the excess when compared with the later analysis.

Aged↗

Probabilistic methods in BCI research.

This paper suggests a probabilistic treatment of the signal processing part of a brain-computer interface (BCI). We suggest two improvements for BCIs that cannot be obtained easily with other data driven approaches. Simply by using one large joint distribution as a model of the entire signal processing part of the BCI, we can obtain predictions that implicitly weight information according to its certainty. Offline experiments reveal that this results in statistically significant higher bit rates. Probabilistic methods are also very useful to obtain adaptive learning algorithms that can cope with nonstationary problems. An experimental evaluation shows that an adaptive BCI outperforms the equivalent static implementations, even when using only a moderate number of trials. This suggests that adaptive translation algorithms might help in cases where brain dynamics change due to learning effects or fatigue.

Algorithms↗

Adaptation of the circadian rhythm of 6-sulphatoxymelatonin to a shift schedule of seven nights followed by seven days in offshore oil installation workers.

This study evaluated circadian adaptation in a 'swing shift' schedule (seven nights, 18:00-06:00 h; then 7 days, 06:00-18:00 h) on North Sea oil installations. Eleven healthy men provided sequential urine collections for the study period offshore. The urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) was used as an index of circadian phase. A significant difference (P=0.0004) was found between the mean aMT6s acrophase (calculated peak time) at the start (+/-SD: 05:34+/-2.42 h) and end (+/-SD: 10.95+/-3.34 h) of the night shift week, but not between the start (+/-SD: 11:04+/-4.03 h) and end (+/-SD: 12:59+/-8.83 h) of the day shift week. As a group, the subjects adapted to the night shift but very large individual variations were seen during the day shift. These individual differences clearly require further study.

Adaptation, Physiological↗

A joint analysis of asthma affection status and IgE levels in multiple data sets collected for asthma.

We present a joint linkage analysis of eight data sets collected for asthma. Three of the data sets are full genome scans, while the remaining five concentrate on a 40-cM region on chromosome 5. We perform the analysis using one qualitative and one quantitative phenotype: asthma status and IgE level. Considering all data sets simultaneously, we do not find evidence for linkage to asthma affection status beyond the level expected to occur by chance twice per genome scan. In contrast, we observe significant linkage to IgE level on chromosome 6.

Adult↗

Terrigenous clay deposition on estuarine sandflats: using stable isotopes to determine the role of the mud crab, Helice crassa Dana, in the recovery process.

Clay slurries, mixed in seawater, were deposited on intertidal mudflats in two contrasting estuaries in an experiment designed to evaluate the potential impact of soil erosion from adjacent urban developments on the biodiversity of the benthic communities, and the subsequent recovery mechanisms. Profiles of the natural abundance of stable isotopes from sediment cores where examined to determine immediate and longer-term impacts of the clay on the ambient sediments. The source clays with delta13C values of about -26 per thousand were easily distinguished from natural sediments with delta13C values of -19.7 +/- 1.1 per thousand at site OK and -14.2 +/- 0.9 per thousand at site WP, and bioturbation was seen to generate a gradient between these values. Physical processes of burial, or erosion and dispersal by estuarine flows initiated the recovery process. Repeated drying cycles left the clay surface cracked and able to trap natural sediments and food on the otherwise barren surface. Colonisation of the clay plots by the mud crab, Helice crassa, was important to the recovery process and depended on proximity to adjacent crab colonies. Burrowing activity by larger crabs enhanced the erosion of the clay surface while the resultant bioturbation blended the clay into the underlying sediments. Smaller crabs had less effect on erosion and bioturbation from their burrowing was mostly confined within the clay layer. Where the clay was more than 3 cm thick, they did not break through the bottom of the clay and the interface between clay and sediment was still sharp after 12 months. 13C variations also indicated that crab burrows and cracking of the clay surface moved natural sediment deep into the plots where it could be worked into the clay by subsequent crab burrowing activities thus enhancing recovery from the clay impact.

Aluminum Silicates↗

Genetic linkage analysis of prostate cancer families to Xq27-28.

OBJECTIVES: A recent linkage analysis of 360 families at high risk for prostate cancer identified the q27-28 region on chromosome X as the potential location of a gene involved in prostate cancer susceptibility. Here we report on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic Research Study (PROGRESS). METHODS: DNA samples from these families were genotyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region. RESULTS: Two-point parametric analysis of the total data set resulted in positive lod scores at only two markers, DXS984 and DXS1193, with scores of 0.628 at a recombination fraction (theta) of 0.36 and 0.012 at theta = 0.48, respectively. The stratification of pedigrees according to the assumed mode of transmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at theta = 0.28). CONCLUSIONS: Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-28, the results are consistent with a small percentage of families being linked to this region. The analysis further highlights difficulties in replicating linkage results in an etiologically heterogeneous, complexly inherited disease.

Age Factors↗

Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci.

PURPOSE: Hereditary prostate cancer is an etiologically heterogeneous disease with six susceptibility loci mapped to date. We aimed to describe a collection of high-risk prostate cancer families and assess linkage to multiple markers at four loci: HPC1 (1q24-25), PCaP (1q42.2-43), HPCX (Xq27-28), and CAPB (1p36). EXPERIMENTAL DESIGN: Medical record data on 505 affected men in 149 multiply-affected prostate cancer families were reviewed, and correlations of clinical traits within each family were calculated. Logarithm of odds (LOD) score and nonparametric (NPL) linkage analyses were performed; white families were stratified by age of diagnosis, grade and stage of disease, and evidence of linkage to the other loci to increase genetic homogeneity. RESULTS: Age at diagnosis was the most correlated clinical trait within families. A maximum NPL score of 2.61 (P = 0.007) appeared to confirm HPC1 linkage for families that had a prevalence of high-grade or advanced-stage prostate cancer and which were not likely to be linked to PCaP, HPCX, or CAPB. Because the NPL scores improved when families more likely to be linked to the other loci were excluded, HPC1 may act independently of the other loci. The relationship of HPC1 and aggressive disease was strongest in families with median age at diagnosis > or =65 years (NPL, 3.48; P = 0.0008). CONCLUSIONS: The current results suggest that HPC1 linkage may be most common among families with more severe prostate cancer. Stratification by clinical characteristics may be a useful tool in prostate cancer linkage analyses and may increase our understanding of hereditary prostate cancer.

Adult↗

A genomic scan of families with prostate cancer identifies multiple regions of interest.

A 10-cM genomewide scan of 94 families with hereditary prostate cancer, including 432 affected men, was used to identify regions of putative prostate cancer-susceptibility loci. There was an average of 3.6 affected, genotyped men per family, and an overall mean age at diagnosis of 65.4 years. A total of 50 families were classified as early onset (mean age at diagnosis <66 years), and 44 families were classified as later onset (mean age at diagnosis > or =66 years). When the entire data set is considered, regions of interest (LOD score > or =1.5) were identified on chromosomes 10, 12, and 14, with a dominant model of inheritance. Under a recessive model LOD scores > or =1.5 were found on chromosomes 1, 8, 10, and 16. Stratification by age at diagnosis highlighted a putative susceptibility locus on chromosome 11, among the later-onset families, with a LOD score of 3. 02 (recombination fraction 0) at marker ATA34E08. Overall, this genomic scan suggests that there are multiple prostate cancer loci responsible for the hereditary form of this common and complex disease and that stratification by a variety of factors will be required for identification of all relevant genes.

Adult↗

Translocation of the Rac1 guanine nucleotide exchange factor Tiam1 induced by platelet-derived growth factor and lysophosphatidic acid.

Several guanine nucleotide exchange factors for the Rho family of GTPases that induce activation by exchanging GDP for GTP have been identified. One of these is the tumor invasion gene product Tiam1, which acts on Rac1. In this study, we demonstrate that platelet-derived growth factor (PDGF) and lysophosphatidic acid induce the translocation of Tiam1 to the membrane fraction of NIH 3T3 fibroblasts in a time-dependent manner. Previously, we have shown that Tiam1 is phosphorylated by protein kinase C (PKC) and calcium/calmodulin kinase II (CaMK II) after stimulation with agonists. Here we show, by pretreatment of cells with kinase inhibitors, that CaMK II, but not PKC, is involved in the membrane translocation of Tiam1. Addition of the calcium ionophore ionomycin alone induced the translocation of Tiam1. However, the cell-permeable diacylglycerol oleoylacetylglycerol was without effect and did not enhance the effect of ionomycin. These data further indicated a role for CaMK II and not PKC. Inhibition of phosphoinositide 3-kinase by wortmannin had little effect on the translocation of Tiam1. The role of phosphorylation was further studied by comparing the phosphorylation pattern of Tiam1 in the membranes versus whole cell Tiam1. PDGF-induced phosphorylation of membrane-associated Tiam1 occurred more rapidly than that of the total Tiam1 pool, and CaMK II, but not PKC, played a significant role in this process. Furthermore, by using the p21-binding domain of PAK-3, we show that PDGF, but not lysophosphatidic acid, activates Rac1 in vivo and that this activation involves CaMK II and PKC, but not 3-phosphoinositides. Our results indicate that Tiam1 is translocated to and phosphorylated at membranes after agonist stimulation and that CaMK II, but not PKC, is involved in this process. Also, these kinases are involved in the activation of Rac in vivo.

3T3 Cells↗

Linkage analysis of 150 high-risk prostate cancer families at 1q24-25.

Confirmation of linkage and estimation of the proportion of families who are linked in large independent datasets is essential to understanding the significance of cancer susceptibility genes. We report here on an analysis of 150 high-risk prostate cancer families (2,176 individuals) for potential linkage to the HPC1 prostate cancer susceptibility locus at 1q24-25. This dataset includes 640 affected men with an average age at prostate cancer diagnosis of 66. 8 years (range, 39-94), representing the largest collection of high-risk families analyzed for linkage in this region to date. Linkage to multiple 1q24-25 markers was strongly rejected for the sample as a whole (lod scores at theta = 0 ranged from -30.83 to -18. 42). Assuming heterogeneity, the estimated proportion of families linked (alpha) at HPC1 in the entire dataset was 2.6%, using multipoint analysis. Because locus heterogeneity may lead to false rejection of linkage, data were stratified based on homogeneous subsets. When restricted to 21 Caucasian families with five or more affected family members and mean age at diagnosis < = 65 years, the lod scores at theta = 0 remained less than -4.0. These results indicate that the overall portion of hereditary prostate cancer families whose disease is due to inherited variation in HPC1 may be less than originally estimated.

Adult↗

RT-PCR using redundant primers to detect the three viruses associated with carrot motley dwarf disease.

A method was developed for detecting and distinguishing the viruses associated with carrot motley dwarf (CMD) disease, i.e. Carrot mottle umbravirus (CMoV), Carrot red leaf virus (CRLV) and the virus known as carrot red leaf virus-associated RNA (CRLVaRNA). Redundant primers were made that targeted the RNA-dependent RNA polymerase (RdRp) gene in all available sequences of umbraviruses and in a subset of polerovirus genomes, and specific and redundant primers were made to target the same gene in CRLVaRNA. By using these primers in RT-PCR reactions, cDNAs were amplified from total RNA isolated from Belgian parsley with CMD disease. The cDNAs were sequenced and an analysis of this data showed that the plants contained all three viruses. RT-PCR assays were optimized for the simultaneous detection of the three viruses in infected parsley and chervil plants and in individual viruliferous aphids. This is the first report of a natural infection of CRLVaRNA in a plant other than carrot and the first report of this virus outside the USA. The study also confirmed that the umbravirus in parsley with CMD disease is CMoV, and that this virus is distinct from carrot mottle mimic umbravirus (CMoMV), which is also associated with CMD, but apparently not in Europe.

Animals↗

Wide-complex tachycardia: continued evaluation of diagnostic criteria.

OBJECTIVE: To evaluate the accuracy of the Brugada algorithm for analysis of wide-complex tachycardia (WCT) when applied by board-certified emergency physicians and board-certified cardiologists. METHODS: A database consisting of 157 electrocardiograms of WCTs were evaluated in a blinded fashion using the Brugada criteria to determine the presence of ventricular tachycardia (VT) or supraventricular tachycardia with aberrancy. These results were then compared with the electrophysiologically proven diagnosis for each tracing. Sensitivity and specificity of the Brugada criteria for diagnosis of VT were calculated. Two board-certified emergency physicians and two board-certified cardiologists analyzed each tracing, and interobserver agreement was determined using the kappa statistic. RESULTS: Sensitivity and specificity for the determination of VT using the Brugada algorithm were 85% [95% confidence interval (95% CI) = 79% to 91%] and 60% (95% CI = 43% to 78%) for cardiologist 1 (C 1) and 91% (95% CI = 86% to 96%) and 55% (95% CI = 37% to 72%) for C 2. Emergency physician (EP 1) achieved a sensitivity of 83% (95% CI = 78% to 91%) and a specificity of 43% (95% CI = 25% to 59%), while EP 2 attained 79% (95% CI = 73% to 87%) and 70% (95% CI = 51% to 84%), respectively. The original authors achieved a sensitivity of 98.7% and specificity of 96.5% when determining VT in their study population. Interobserver agreement for the emergency physicians and the cardiologists in determining VT was 82% and 81%, respectively. CONCLUSIONS: Neither the emergency physicians nor the cardiologists were able to achieve a sensitivity or specificity as high as that reported by the original investigators when using the Brugada algorithm to determine the presence of VT.

Adult↗

Designing and implementing a 'dual diagnosis' module: a review of the literature and some preliminary findings.

People with a learning disability experience the full range of mental health problems, with prevalence greater than in the general population. The literature suggests that the move to community care has highlighted their special needs, as they face a complexity of life experiences and risks. Nurses play a key role, and must be equipped with appropriate knowledge and expertise to respond to the mental health problems of people with a learning disability ('dual diagnosis'). Major national initiatives support research and propose access to appropriate education for care professionals. In order to respond to locally identified educational needs a 'dual diagnosis' module was developed for nurses working with people with a learning disability who experienced mental health difficulties. The aims were to increase knowledge, to consider implications for learning disability nursing, to increase awareness of research and policy issues, and ultimately to enhance practice. Preliminary findings suggest that participants have moved from an entry position of professional bias and lack of knowledge and skill, to a changed perspective and enhanced practice relating to the mental health needs of clients with a learning disability. These changes are, however, speculative and may be attributable to variables other than module completion. Implications for further research and development are suggested.

Attitude of Health Personnel↗

Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36.

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.

Aged↗

Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer.

One hundred fifty-two families with prostate cancer were analyzed for linkage to markers spanning a 20-cM region of 1q42.2-43, the location of a putative prostate cancer-susceptibility locus (PCAP). No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in our total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, pedigrees were stratified into homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although LOD scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least five affected men (nonparametric linkage score of 1.2; P=.1). If heterogeneity is assumed, an estimated 4%-9% of these 152 families may show linkage in this region. We conclude that the putative PCAP locus does not account for a large proportion of these families with prostate cancer, although the linkage of a small subset is compatible with these data.

Age Factors↗