Lysophosphatidic acid cooperates with 1alpha,25(OH)2D3 in stimulating human MG63 osteoblast maturation.

Osteoblast maturation is partly controlled by the interaction of 1alpha,25(OH)(2)D(3) (D3), an active metabolite of Vitamin D, with other growth factors. The first reports describing the in vitro effect of D3 on human osteoblast differentiation performed experiments in the presence of serum. One potentially exciting candidate that might help explain the D3 responses observed for osteoblasts cultured with serum is lysophosphatidic acid (LPA). Drawn to the possibility that D3 and serum borne LPA might interact to induce osteoblast maturation we co-treated human cells with D3 and serum in the presence of Ki16425, an LPA receptor antagonist. Ki16425 inhibited osteoblast maturation as determined by markedly reduced alkaline phosphatase (ALP) expression. We subsequently found that LPA and D3 acted synergistically in generating mature osteoblasts and that this differentiation response could be inhibited using pertussis toxin, implying an important role of Galphai signal transduction. Furthermore, we found evidence for a dependency on both mitogen activated protein kinase kinase (MEK) and Rho associated coiled kinase (ROCK) for LPA and D3 stimulated maturation.

Effect of acupuncture on nausea of pregnancy: a randomized, controlled trial.

OBJECTIVE: To compare acupuncture with sham (placebo) acupuncture for treatment of nausea of pregnancy. METHODS: In a subject- and observer-masked, randomized, controlled trial in the maternity unit at Exeter Hospital, we gave 55 women between 6 and 10 weeks' gestation genuine, traditional-style acupuncture or sham treatment with a cocktail stick on three or four occasions over 3 weeks. The main outcome measure was nausea score, as determined by subject report on a visual analogue scale in a daily diary. Anxiety and depression also were assessed. RESULTS: Nausea scores decreased from a median of 85.5 (interquartile range 71.25-89.75) to 47.5 (interquartile range 29.25-69.5) in the acupuncture group and from 87.0 (interquartile range 73.0-90.0) to 48.0 (interquartile range 14.0-80.0) in the sham treatment group. There was strong evidence of a time effect (P <.001) but no evidence of a group effect (P =.9) or a group-time interaction (P =.8). Similarly, there was evidence of time effects in scores for anxiety and depression but no group differences. The study had a power of 95% to detect significant differences in nausea scores. CONCLUSION: Acupuncture was as effective in treating nausea of pregnancy as a sham procedure.

Efficient marker-based recurrent selection for multiple quantitative trait loci.

We studied the efficiency of recurrent selection based solely on marker genotypes (marker-based selection), in order to increase favourable allele frequency at 50 previously detected quantitative trait loci (QTLs). Two selection procedures were investigated, using computer simulations: (1) Truncation Selection (MTS), in which individuals are ranked based on marker score, and best individuals are selected for recombination; and (2) QTL Complementation Selection (QCS), in which individuals are selected such that their QTL composition complements those individuals already selected. Provided QTL locations are accurate, marker-based selection with a population size of 200 was very effective in rapidly increasing frequencies of favourable QTL alleles. QCS methods were more effective than MTS for improving the mean frequency and fixation of favourable QTL alleles. Marker-based selection was not very sensitive to a reduction in population size, and appears valuable to optimize the use of molecular markers in recurrent selection programmes.

Teaching biomedical applications to secondary students.

Certain aspects of biomedical engineering applications lend themselves well to experimentation that can be done by high school students. This paper describes two experiments done during a six-week summer internship program in which two high school students used electrodes, circuit boards, and computers to mimic a sophisticated heart monitor and also to control a robotic car. Our experience suggests that simple illustrations of complex instrumentation can be effective in introducing adolescents to the biomedical engineering field.

Nitric oxide production during adjuvant-induced and collagen-induced arthritis.

OBJECTIVE: To investigate the role of nitric oxide (NO) production and NO synthase (NOS) induction during adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) in Dark Agouti rats. METHODS: Urinary nitrate excretion and immune NOS (INOS) messenger RNA (mRNA) expression were measured in the joint, lymph node, spleen, and liver tissues following the induction of either AIA or CIA. RESULTS: Urinary nitrate excretion and iNOS mRNA expression increased substantially during joint inflammation in both models of arthritis. However, the increases in urinary nitrate excretion and iNOS mRNA expression observed in the joint, liver, and spleen tissues during AIA were greater than those observed during CIA, although iNOS induction in the lymph nodes was similar for both models. A prior injection with Mycobacterium bovis heat-shock protein resulted in suppression of arthritis and NO production in AIA, but not in CIA. CONCLUSION: Differences in NO production during AIA versus CIA are a reflection of the fundamental pathophysiologic differences between these 2 models of arthritis. Thus, NO production in these 2 models could not be merely a nonspecific reaction to the adjuvant injection, nor simply a byproduct of local inflammation in the joint.

Geodemographic segmentation systems for screening health data.

AIM: To describe how geodemographic segmentation systems might be useful as a quick and easy way of exploring postcoded health databases for potential interesting patterns related to deprivation and other socioeconomic characteristics. DESIGN AND SETTING: This is demonstrated using GB Profiles, a freely available geodemographic classification system developed at Leeds University. It is used here to screen a database of colorectal cancer registrations as a first step in the analysis of that data. RESULTS AND CONCLUSION: Conventional geodemographics is a fairly simple technology and a number of outstanding methodological problems are identified. A solution to some problems is illustrated by using neural net based classifiers and then by reference to a more sophisticated geodemographic approach via a data optimal segmentation technique.

Putting the 1991 census sample of anonymised records on your Unix workstation.

"The authors describe the development of a customised computer software package for easing the analysis of the U.K. 1991 Sample of Anonymised Records. The resulting USAR [Unix Sample of Anonymised Records] package is designed to be portable within the Unix environment. It offers a number of features such as interactive table design, intelligent data interpretation, and fuzzy query. An example of SAR analysis is provided."

Algorithms for reengineering 1991 census geography.

"The availability of GIS [geographic information systems] technology and digital boundaries of census output areas now makes it possible for users to design their own census geography. Three algorithms are described that can be used for this purpose. An Arc/Info implementation is briefly outlined and case studies presented to demonstrate some of the results of explicitly designing zoning systems for use with 1991 [U.K.] census data."

Do interventions that improve immunisation uptake also reduce social inequalities in uptake?

OBJECTIVE: To investigate whether an intervention designed to improve overall immunisation uptake affected social inequalities in uptake. DESIGN: Cross-sectional small area analyses measuring immunisation uptake in cohorts of children before and after intervention. Small areas classified into five groups, from most deprived to most affluent, with Townsend deprivation score of census enumeration districts. SETTING: County of Northumberland. SUBJECTS: All children born in country in four birth cohorts (1981-2, 1985-6, 1987-8, and 1990-1) and still resident at time of analysis. MAIN OUTCOME MEASURES: Overall uptake in each cohort of pertussis, diphtheria, and measles immunisation, difference in uptake between most deprived and most affluent areas, and odds ratio of uptake between deprived and affluent areas. RESULTS: Coverage for pertussis immunisation rose from 53.4% in first cohort to 91.1% in final cohort. Coverage in the most deprived areas was lower than in the most affluent areas by 4.7%, 8.7%, 10.2%, and 7.0% respectively in successive cohorts, corresponding to an increase in odds ratio of uptake between deprived and affluent areas from 1.2 to 1.6 to 1.9 to 2.3. Coverage for diphtheria immunisation rose from 70.0% to 93.8%; differences between deprived and affluent areas changed from 8.6% to 8.3% to 9.0% to 5.5%, corresponding to odds ratios of 1.5, 2.0, 2.5, and 2.6. Coverage for measles immunisation rose from 52.5% to 91.4%; differences between deprived and affluent areas changed from 9.1% to 5.7% to 8.2% to 3.6%, corresponding to odds ratios of 1.4, 1.4, 1.7, and 1.5. CONCLUSION: Despite substantial increase in immunisation uptake, inequalities between deprived and affluent areas persisted or became wider. Any reduction in inequality occurred only after uptake in affluent areas approached 95%. Interventions that improve overall uptake of preventive measures are unlikely to reduce social inequalities in uptake.

Are multidimensional social classifications of areas useful in UK health service research?

OBJECTIVES: To show the advantages and disadvantages of a multi-dimensional small area classification in the analysis of child health data in order to measure social inequalities in health and to identify the types of area that have greater health needs. DESIGN: Health data on children from the district child health information system and a survey of primary school children's height were classified by the census enumeration district of residence using the Super profiles neighbourhood classification. SETTING: County of Northumberland, United Kingdom. SUBJECTS: One cohort comprised 21,702 preschool children age 0-5 years resident in Northumberland, and another cohort 9930 school children aged 5-8.5 years. MAIN OUTCOME MEASURES: Variations between types of area in the proportions of babies with birthweight less than 2.8 kg; births to mothers aged less than 20 years; pertussis immunisation uptake; child health screening uptake; and mean height of school children. RESULTS: Areas with the poorest child health measures were those which were most socially disadvantaged. The most affluent areas tended to have the best measures of health, although rural areas also had good measures. Problems in analysis included examples of the "ecological fallacy", misleading area descriptions, and the identification of the specific factors associated with poor health measures. Advantages included a wider view of social circumstances than simply "deprivation" and the ability to identify characteristic types of areas with increased child health needs. CONCLUSIONS: There is a limited place for multidimensional small area classifications in the analysis of health data for both research and health needs assessment provided the inherent drawbacks of these data are understood in interpreting the results.

Methods to evaluate populations for alleles to improve an elite hybrid.

Elite hybrids can be improved by the introgression of favorable alleles not already present in the hybrid. Our first objective was to evaluate several estimators derived from quantitative genetic theory that attempt to quantify the relative number of useful alleles in potential donor populations. Secondly, we wanted to evaluate two proposed ways of determining relatedness of donor populations to the parents of the elite hybrid. Two experiments, each consisting of 21 maize populations of known pedigree, were grown at three and four environments in Minnesota in 1991. Yield and plant height means were used to provide estimates of each of the following statistics: (1) LPLU, a minimally biased statistic, (2) UBND, the minimum estimate of an upper bound, (3) NI, the net improvement, (4) PTC, the predicted three-way cross, and (5) TCSC, the testcross of the populations. These statistics are biased estimators of the relative number of unique favorable alleles contained within a population compared to a reference elite hybrid. Based on rank correlations, all statistics except NI ranked populations similarly. The percent novel germplasm relative to the single cross to be improved was positively correlated with the estimates of favorable alleles except when NI was used as the estimator. The relationship estimators agreed with the genetic constitution of the donor populations. Strong positive correlations existed between diversity, based on the relationship rankings, and all the estimator rankings, except NI. Potential donor populations were effectively identified by LPLU, UBND, PTC, and TCSC. NI was not a good estimator of unique favorable alleles.

Do inaccuracies in small area deprivation analyses matter?

OBJECTIVE: To assess the accuracy of computerised matching of postcode to enumeration district (ED) and to determine whether any mismatching reduces the validity of methods to distinguish socioeconomic differences in "small area" deprivation studies. DESIGN: Computerised and manual matching of postcodes to EDs were compared and the census based Townsend deprivation score was compared with socioeconomic data on individual families. SETTING: County of Northumberland, England, 1989. SUBJECTS: Random sample of 301 families with a child aged less than 15 months. MAIN RESULTS: With computerised matching only 47% of postcodes were matched to the correct ED. Eighty per cent of the deprivation scores of the computer matched EDs, however, approximated (+/- 2) to the deprivation score of the actual ED. When EDs were divided into quintiles according to the deprivation score, accurate manual matching showed that 75% of families in the most deprived EDs were classed as deprived compared with 4% in the most affluent EDs. With the inaccuracies introduced by computer matching of postcodes, the corresponding figures were 56% and 12% respectively. CONCLUSIONS: Computerised matching of postcodes to EDs is highly inaccurate, but this has little effect on the allocation of deprivation scores. The socioeconomic inequalities shown by the deprivation score are blunted, but not eradicated, by this mismatching.

Measurement of social inequalities in health and use of health services among children in Northumberland.

Social inequalities in a variety of indicators of child health were measured using a 'small area' geographical method of social classification. Cross sectional analyses of routine child health information and of a population survey of the height of primary school children were used. Social classification was by census enumeration district of residence using the Townsend deprivation score. Over 21,000 children resident in Northumberland born between January 1985 and September 1990, and 9930 children aged 5-8.6 years in Northumberland schools were studied. The following differences between the most deprived 10% of areas and the most affluent 10% of areas were used as outcome measures: the proportion of birth weights less than 2800 g; the proportion of births to teenage mothers; the proportion of 15 month old children not immunised against pertussis; the proportion of infants not screened at 6 weeks of age; the proportion of children not screened at 18 months of age; and the mean height of children in SD scores. Between the most deprived and most affluent areas birth weights less than 2800 g varied from 18 to 11%, the percentage of teenage mothers from 18 to 3%, non-immunised children from 30 to 19%, children not screened at 18 months from 21 to 14%, and mean height from -0.2 SD scores to +0.1 SD scores. The area variation in screening at 6 weeks of age was less, but still poorer in deprived areas. It is concluded that small area methods are effective in showing inequalities in child health, even in a rural area where such methods might be expected to perform less well. Social inequalities in all the aspects of child health measured remain evident.

Cancer in young people in the north of England, 1968-85: analysis by census wards.

OBJECTIVE: To determine whether the seeming excess of childhood leukaemia and lymphoma identified in Seascale, Cumbria, UK, remains unusual when put into a wider context. DESIGN: Analysis of cancer incidence by geographical area. SETTING: The north of England including the Northern and North Western Regional Health Authority regions and the Southport and South Sefton districts of the Mersey Regional Health Authority. SUBJECTS: Altogether 6686 cases of malignant disease in people under 25 years old. MEASUREMENTS AND MAIN RESULTS: Cases of cancer diagnosed before their 25th birthday between January 1968 and December 1985 identified from three regional cancer registries were allocated to a census ward on the basis of 'usual place of residence'. Population data were derived from the 1971 and 1981 censuses, and the cancer incidence was calculated for each ward. Of the 6686 cases, there were 1035 cases of acute lymphoblastic leukaemia and 361 of non-Hodgkins lymphoma. Wards were ranked by cancer incidence and Poisson probability, using different population bases. Seascale ward is the most highly ranked ward for acute lymphoblastic leukaemia for the time periods 1968-85 or 1968-76. It is not the most highly ranked for non-Hodgkins lymphoma. However, combining acute lymphoblastic leukaemia and non-Hodgkins lymphoma incidence gives an even more extreme position for Seascale. The most extreme Poisson probability for any of the analyses was that for brain tumours in the electoral ward of Ashton St Michael, Tameside (p = 0.000009). CONCLUSION: The incidence of acute lymphoblastic leukaemia and non-Hodgkins lymphoma in the Seascale ward remains high when put into a wider context. For other cancers there are wards with even more extreme Poisson probability values.

The case for samples of anonymized records from the 1991 census.

"The census of population represents a rich source of social data. Other countries have released samples of anonymized records from their censuses to the research community for secondary analysis. So far this has not been done in Britain. The areas of research which might be expected to benefit from such microdata are outlined, and support is drawn from considering experience overseas. However, it is essential to protect the confidentiality of the data. The paper therefore considers the risks, both real and perceived, of identification of individuals from census microdata. The conclusion of the paper is that the potential benefits from census microdata are large and that the risks in terms of disclosure are very small. The authors therefore argue that the Office of Population Censuses and Surveys and the General Register Office of Scotland should release samples of anonymized records from the 1991 census for secondary analysis."

Measuring child health inequalities using aggregations of Enumeration Districts.

In demonstrating health variations between different areas in a district, it is conventional to use local authority ward-to-ward variations. In rural districts, because wards have small, heterogeneous populations, this method is less useful. We have investigated alternative ways of showing variations in child health by using different aggregations of Enumeration Districts (ED) in a small, sparsely populated rural area. EDs were aggregated first by a cluster analysis based classification (Super Profiles) and second according to a material deprivation score (the Townsend score). Both methods of aggregation showed similar variations between areas in the proportion of babies with low birthweight, the proportion of teenage mothers, immunization coverage and six-week screening examination coverage. Both methods discriminated better than a straightforward ward-based analysis. Neither method was clearly superior to the other. It is concluded that for both epidemiological research and for health service information purposes, either of these methods of ED aggregation has definite advantages over ward-based analyses in rural areas.