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Biomedical subjects

P Joyce

Publications and source records attributed to P Joyce.

At least 19 recordsLinked to original sources

Phylogeography and mitochondrial diversity of extirpated brown bear (Ursus arctos) populations in the contiguous United States and Mexico.

The fossil record indicates that the brown bear (Ursus arctos) colonized North America from Asia over 50 000 years ago. The species historically occupied the western United States and northern Mexico but has been extirpated from over 99% of this range in the last two centuries. To evaluate colonization hypotheses, subspecific classifications, and historical patterns and levels of genetic diversity in this region, we sequenced 229 nucleotides of the mitochondrial DNA control region in 108 museum specimens. The work was set in a global context by synthesizing all previous brown bear control region sequences from around the world. In mid-latitude North America a single moderately diverse clade is observed, represented by 23 haplotypes with up to 3.5% divergence. Only eight of 23 haplotypes (35%) are observed in the extensively sampled extant populations suggesting a substantial loss of genetic variability. The restriction of all haplotypes from mid-latitude North America to a single clade suggests that this region was founded by bears with a similar maternal ancestry. However, the levels and distributions of diversity also suggest that the colonizing population was not a small founder event, and that expansion occurred long enough ago for local mutations to accrue. Our data are consistent with recent genetic evidence that brown bears were south of the ice prior to the last glacial maximum. There is no support for previous subspecies designations, although bears of the southwestern United States may have had a distinctive, but recent, pattern of ancestry.

Animals↗

Testing population genetic structure using parametric bootstrapping and MIGRATE-N.

We present a method for investigating genetic population structure using sequence data. Our hypothesis states that the parameters most responsible for the formation of genetic structure among different populations are the relative rates of mutation (micro) and migration (M). The evolution of genetic structure among different populations requires rates of M << p because this allows population-specific mutation to accumulate. Rates of micro << M will result in populations that are effectively panmictic because genetic differentiation will not develop among demes. Our test is implemented by using a parametric bootstrap to create the null distribution of the likelihood of the data having been produced under an appropriate model of sequence evolution and a migration rate sufficient to approximate panmixia. We describe this test, then apply it to mtDNA data from 243 plethodontid salamanders. We are able to reject the null hypothesis of no population structure on all but smallest geographic scales, a result consistent with the apparent lack of migration in Plethodon idahoensis. This approach represents a new method of investigating population structure with haploid DNA, and as such may be particularly useful for preliminary investigation of non-model organisms in which multi-locus nuclear data are not available.

Animals↗

Cardiovascular toxicity is increased, but manageable, during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for patients aged 60 years and older.

High-dose therapy (HDT) for non-Hodgkins lymphoma (NHL) and multiple myeloma (MM) is considered a feasible option for patients aged 60 years. This study compared the outcomes for all patients aged 60 years treated with HDT at the center to a matched cohort group aged <60 years. Results for patients who were 60 years at HDT between 1997--2002 were retrospectively analysed to assess efficacy and safety. Event-free (EFS) and overall survival (OS) rates were compared with a cohort group, matched by disease type, chemotherapy sensitivity, year of treatment and conditioning regimen. Patients with NHL were also matched by International Prognostic Index score. Forty patients aged 60 years were identified. Median age was 65 (range 60--76) with 22 MM and 18 NHL; 50% had 1 or more co-morbidity; 35% had cardiovascular co-morbidity vs. 18% of controls (p=0.075). Response rates (RR) following HDT for MM were: 4 (18%) complete responses (CR) and 18 (82%) partial responses (PR), giving an overall response rate (ORR) of 100%, vs. 77% for controls (p=0.02). For NHL patients there were: 8 CR (44%) and 4 PR (22%), giving an ORR of 67%, vs. 83% for controls (p=0.3). Transplant-related mortality was 8% compared to 5% in controls (p=0.6). Toxicities were similar with the exception of cardiac toxicity, which was significantly higher in patients aged 60 years vs. controls (50% grade 3 vs. 10%: p<0.0001). Atrial fibrillation was the most frequent cardiovascular toxicity (9 patients). At a median follow-up of 33 months, there is no significant difference between older vs. younger patients in median EFS (24 vs. 38 months: p=0.78) or OS (40 months vs. not reached: p=0.23). HDT is feasible and effective in selected patients 60 years with MM and NHL. Patients 60 years are more susceptible to cardiovascular toxicities, particularly atrial fibrillation, but have similar or better response rates following HDT and similar long-term outcomes to younger patients.

Adult↗

Efficient use of animal manure on cropland--economic analysis.

Manure contains all the macro- and microelements needed for plant growth; however, it represents one of the most underutilized resources in the US. The major problem with the use of manure on cropland is the direct effect of its composition on application cost. This cost is a function of the mineralization process of organic matter. The mineralization process is influenced by the properties of the manure, properties of the soil, moisture, and temperature. This study evaluates the simultaneous effect of these variables on the optimal use of manure on cropland. The results show that the properties of manure and soil significantly affect the mineralization of organic nitrogen and thus the optimal quantity of manure required to satisfy the nutrient requirement of crops in a given rotation system. Manure application costs range from a low of 18% of the cost of commercial fertilizer for chicken manure applied to one type of soil, to a high of 125% of the cost of commercial fertilizer for cow manure applied to another type of soil. The maximum distance to transfer manure to the field, that will equate its application cost to the cost of commercial fertilizer, ranges from a high of 35 km (22 miles) for chicken manure applied to one type of soil, to a low of 1 km (0.62 miles) for cow manure applied to another type of soil. For rotation system 2, manure application costs range from a low of 37% of the cost of commercial fertilizer for chicken manure applied to one type of soil, to a high of 136% of the cost of commercial fertilizer for cow manure applied to another type of soil. The maximum distance to transfer manure to the field, that will equate its cost to the cost of commercial fertilizer, ranges from a high of 20 km (12.5 miles) for chicken manure applied to one type of soil, to a low of 0 km (0 miles) for cow manure applied to another type of soil.

Agriculture↗

Likelihoods and simulation methods for a class of nonneutral population genetics models.

Methods for simulating samples and sample statistics, under mutation-selection-drift equilibrium for a class of nonneutral population genetics models, and for evaluating the likelihood surface, in selection and mutation parameters, are developed and applied for observed data. The methods apply to large populations in settings in which selection is weak, in the sense that selection intensities, like mutation rates, are of the order of the inverse of the population size. General diploid selection is allowed, but the approach is currently restricted to models, such as the infinite alleles model and certain K-models, in which the type of a mutant allele does not depend on the type of its progenitor allele. The simulation methods have considerable advantages over available alternatives. No other methods currently seem practicable for approximating likelihood surfaces.

Alleles↗

Rapid and comprehensive determination of cytochrome P450 CYP2D6 poor metabolizer genotypes by multiplex polymerase chain reaction.

The liver enzyme cytochrome P450 CYP2D6 (debrisoquine 4-hydroxylase) metabolizes numerous drugs, including many antidepressants, neuroleptics, antiarrhythmics, and antihypertensive agents. Variability in the gene that encodes this enzyme is an important factor underlying variable drug treatment responses. Some 5-10% of Caucasians lack functional CYP2D6, and the genetic basis of most of these "poor metabolizer" alleles is now well defined. As the CYP2D6 status of a patient can have profound effects on response to drug treatment, it is important to devise methods that permit rapid and economical determination of CYP2D6 genotype. We have developed a robust polymerase chain reaction method that simultaneously identifies the variants CYP2D6 *3, *4, *6, *8, *11, *12, *14, *15, *19, and *20. This constitutes most of the poor metabolizer alleles described in Caucasian and Asian populations. Separate PCR reactions or Southern blots are required for *7, the *5 deletion, and the hybrid alleles *13 and *16. The multiplex assay was validated on 100 individuals previously genotyped by specific polymerase chain reaction-restriction fragment length polymorphism analysis, and proved 100% accurate in this sample. The assay performed consistently with Taq DNA polymerases from various suppliers, within a broad range of temperatures and MgCl(2) concentrations, and using genomic DNA prepared by a range of methods including extraction from dried blood spots on card. This multiplexed, amplification refractory mutation system (ARMS) method is reliable, rapid, relatively cheap, amenable to automation, and offers the advantages of minimal sample handling with no requirement for restriction enzymes as in earlier CYP2D6 assays.

Alleles↗

Identification of P gene mutations in individuals with oculocutaneous albinism in sub-saharan africa; robyn kerr, gwynneth stevens, prashiela manga, sarah salm, premila john, tabitha haw, and michele ramsay; (Article was originally published in human mutation 15:166-172, 2000)

The authors wish to correct a mistake which occurred in the reporting of one of the mutations. The mutation reported as 683insT is actually an insertion G mutation, and should thus be called 683insG.

Journal Article↗

Fasciola hepatica infection downregulates Th1 responses in mice.

Immune responses induced with helminth parasites have been extensively studied, but there is limited information on those to Fasciola hepatica, especially on the subtype of T cell induced with this parasite. We investigated the local and systemic T cell responses of different strains of mice following oral infection with doses of metacercariae from F. hepatica. Spleen cells from BALB/c and 129Sv/Ev mice given a low-dose (5 metacercariae) infection exhibited a Th2 response, producing high levels of the cytokines IL-4 and IL-5, and low levels of IFN-gamma and IL-2. In contrast, C57BL/6 mice showed a mixed Th1/Th2 response. A more marked polarization to a Th2 response was observed in BALB/c, 129Sv/Ev exposed to a high-dose (15 metacercariae) infection and the C57BL/6 mice also exhibited a clear Th2 response. IL-4 defective (IL-4-/-) C57BL/6 mice infected with 5 metacercariae produced less IFN-gamma and more IL-5 compared to their wild-type C57BL/6 counterparts, suggesting that IL-4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN-gamma and IL-2 was completely suppressed in the high-dose infection and this was also observed in IL-4-/- mice. Thus, liver flukes may secrete molecules that downregulate Th1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nodes (HLN) were also examined since newly excysted juveniles infect through the intestinal wall of their host before migrating to the hepatic tissue. Cells from both MLN and HLN secreted higher levels of IL-4 and IL-5 compared to spleen cells. We also observed a difference in cytokine profiles secreted by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.

Animals↗

Correlation between bovine milk somatic cell count and polymorphonuclear leukocyte level for samples of bulk milk and milk from individual cows.

The influence of various factors on the concentrations of polymorphonuclear neutrophilic leukocytes (PMN) in milk samples from bulk tanks and individual cows was investigated. While somatic cell counts (SCC) and PMN level were in both cases significantly correlated, lower correlation coefficients were found between SCC and PMN for samples of bulk tank milks than for milk samples from individual cows. Furthermore, plots of PMN concentrations versus SCC showed great variability in PMN in milk samples of similar total SCC. One factor that may lead to variability in bulk tank PMN levels was shown to be increased proportions of high SCC milk in the bulk tank mixture, which result in relatively high PMN levels without excessive elevation of total SCC. In milk samples from individual cows, it was found that there was also a significant seasonal influence on milk PMN content, with milk from cows calving in the spring having, at SCC > 160,000 cells/ ml, higher proportions of PMN in the total milk SCC than milk from autumn calving cows. The results of this study suggest that the concentration of PMN may be a useful indicator of herd status in bulk tank monitoring schemes.

Animals↗

No BLUE among phylogenetic estimators.

Multivariate analysis is a branch of statistics that successfully exploits the powerful tools of linear algebra to obtain a fairly comprehensive theory of estimation. The purpose of this paper is to explore to what extent a linear theory of estimation can be developed in the context of coalescent models used in the analysis of DNA polymorphism. We consider a large class of coalescent models, of which the neutral infinite sites model is one example. In the process, we discover several limitations of linear estimators that are quite distinct from those in the classical theory. In particular, we prove that there does not exist a uniformly BLUE (best linear unbiased estimator) for the scaled mutation parameter, under the assumptions of the neutral model of evolution. In fact, we show that no linear estimator performs uniformly better than the Watterson (1975) method based on the total number of segregating sites. For certain coalescent models, the segregating-sites estimator is actually optimal.The general conclusion is the following. If genealogical information is useful for estimating the rate of evolution, then there is no optimal linear method. If there is an optimal linear method, then no information other than the total number of segregating sites is needed.

Base Sequence↗

Effects of stocking density and concentrate supplementation of grazing dairy cows on milk production, composition and processing characteristics.

The effects on milk composition and processing characteristics of varying grass supply by changing stocking density and of offering a concentrate supplement were investigated. The experiment was conducted over 28 weeks of the lactation (April-October) using 48 spring-calved Friesian-Holstein cows. Three herds each of 16 cows were offered a restricted grass supply, a standard grass supply and a standard grass supply with a supplement of 3 kg concentrate/d. Treatment groups were grazed separately with a residence time of 3 d/paddock. Milk production, composition and processing characteristics such as renneting properties, ethanol stability and plasmin activity were measured weekly. Increasing stocking density above the standard system resulted in significant reductions in milk fat and protein yields, the concentrations of total protein, casein and whey proteins, and a deterioration in most processing characteristics. Imposing concentrate supplementation on the standard system increased total protein, casein and whey protein concentrations but generally did not improve processing characteristics except for ethanol stability. These results suggest that the standard grass supply in a rotational grazing paddock system can support efficient production of quality milk, and concentrate supplementation will not improve processing characteristics when an adequate supply of good quality herbage is available.

Animal Feed↗

Implementing supernumerary learning in a pre-registration diploma in nursing programme: an action research study.

The purpose of this study was to develop a framework for implementing supernumerary learning in a preregistration Diploma in Nursing programme in an Irish hospital. Experiences of student nurses (n = 31), clinical nursing staff (n = 8) and nurse teachers (n = 4) were explored, regarding the introduction of supernumerary status in this programme. An action research approach, employing phenomenological methods for gathering and analysing the data, was used to carry out the study. A framework for implementing supernumerary learning in a Diploma in Nursing programme was developed, based on the study. This framework reflects the level of knowledge, skills and attitudes of individuals partaking in supernumerary learning, and the role of the supervisor in the clinical area at each level. Possible implications of the changing role of the student nurse for nursing practice for education, management and research are suggested.

Attitude of Health Personnel↗

Growth hormone replacement does not improve psychological well-being in adult hypopituitarism: a randomized crossover trial.

In order to examine the effect of growth hormone (GH) on psychological parameters in adult hypopituitarism, 20 adults were studied, mean age 47 years (range 20-69) with hypopituitarism and confirmed GH deficiency (GH < 3 micrograms/l following clonidine 0.15 mg/m2). Subjects were randomly allocated to either GH-up to 0.25 U/kg per week in daily doses) or placebo for 3 months before crossover to the opposite treatment arm. Psychological parameters were assessed by self-reported questionnaires (Disease Specific Questionnaire (DSQ), the Symptom Checklist-90 (SCL-90), and the Social Adjustment Scale (SAS)) at baseline and monthly intervals to the end of the trial. Both SAS and SCL-90 total scores showed a significant decline with respect to time (p = .03 and .013 respectively), although this was not a function of active treatment. DSQ showed a trend to decline (p = .06), but no effect of active treatment. None of the subscale components of the SCL-90 showed any significant change on active treatment. Improvement in psychological parameters occurs as a function of enrolment to a clinical trial, rather than active GH replacement in adult hypopituitarism.

Adult↗

Effect of decreased milking frequency of cows in late lactation on milk somatic cell count, polymorphonuclear leucocyte numbers, composition and proteolytic activity.

The effects of reducing the frequency of milking of cows in late lactation on milk somatic cell count (SCC), polymorphonuclear leucocyte (PMN) content, chemical composition and proteolytic activity were investigated. Intermittent milking is frequently practised by Irish farmers in late lactation, and the objective of this study was to determine whether this procedure could be linked to altered quality of milk. Seventeen Holstein Friesian cows in late lactation (> 215 d in milk) were assigned to two treatment groups, and were either milked twice a day until drying-off (control group) or milked intermittently as the yield fell (test group). Milk composition and enzymic characteristics were measured on two occasions. At the first sampling, day 7, test cows were on once daily milking and at the second, day 15, the test cows were being milked every second day. Milk yields were significantly lower in test than control animals and decreased between days 7 and 15 in both groups. Milk SCC and PMN levels were increased on reducing milking frequency and, at day 15, the increase was not linked to decreased milk yield. Milk lactose levels were significantly decreased and pH, alpha-lactalbumin levels, plasmin activity and plasminogen activity significantly increased by reducing milking frequency. In conclusion, reduced frequency of milking in late lactation leads to the production of milk that is abnormal in character and this may be linked to reduced quality of dairy products manufactured from such milk.

Animals↗