Miniature electrostatic electron energy analyzers and S-shaped deflector.

An instrument has been developed to avoid the rotation of large electron sources and detectors in quantum single particle scattering experiments. The rotation of an electron beam has been achieved by combining three small cylindrical electrostatic electron energy analyzers in series such that the first analyzer is fixed and the other two rotate together around the exit axis of the first; it is a development from an S-shaped deflector used by Hegemann et al. [J. Phys. B 26, 4607 (1993)]. Novel design and construction, using copper, aluminum, and stainless steel parts mounted on polyvinyl printed circuit board, enabled an efficient, small-sized high vacuum compatible instrument. The characteristics and versatility of the instrument have been shown by measurements of angular and spin asymmetries of electron scattering phenomena.

Patient reporting of suspected adverse drug reactions: a review of published literature and international experience.

AIMS: To synthesize data from published studies and international experience to identify evidence of potential benefits and drawbacks of direct patient reporting of suspected adverse drug reactions (ADRs) by patients. METHODS: Structured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts. RESULTS: Seven studies (eight papers) were included in the review. None of the studies concerned spontaneous reporting by patients. Information on patient reporting systems was obtained for six countries, with summary data reported by four. Patient reports identified possible new ADRs that had not previously been reported by health professionals. The quality of patient reports appears to be similar to that of health professional reports. There is some evidence that patients report an ADR when they consider their health professional has not paid attention to their concerns. Patient reports may, at least initially, be more time consuming to process. CONCLUSIONS: Overall, the evidence indicates that patient reporting of suspected ADRs has more potential benefits than drawbacks. Evaluation of patient reporting systems is needed to provide further evidence.

Interval mapping of carcass and meat quality traits in a divergent swine cross.

An autosomal scan of the swine genome with 119 polymorphic microsatellite (ms) markers and data from 116 F2 barrows of the University of Illinois Meishan x Yorkshire Swine Resource Families identified genomic regions with effects on variance in carcass composition and meat quality at nominal significance (p-value <0.05). Marker intervals on chromosomes 1, 6, 7, 8 and 12 (SSC1, SSC6, SSC7, SSC8, SSC12) with phenotypic effects on carcass length, 10th rib backfat thickness, average backfat thickness, leaf fat, loin eye area and intramuscular fat content confirm QTL effects identified previously based on genome wide significance (p-value <0.05). Several marker intervals included nominally significant (p-value <0.05) dominance effects on leaf fat, 10th rib backfat thickness, loin eye area, muscle pH and intramuscular fat content.

A genomic scan of porcine reproductive traits reveals possible quantitative trait loci (QTLs) for number of corpora lutea.

Reproductive traits have low heritabilities, are expressed in only one sex, and are not measurable until sexual maturity (Avalos and Smith, Anim Prod 44:153, 1987). Using traditional methods, selection for reproductive traits is relatively less effective than selecting for growth or carcass traits. Traits most affected by a small number of genes with major effects rather than many genes with small effects are most amenable to MAS. As part of our porcine genome scan to identify quantitative trait loci (QTLs) of economic importance in marker-assisted selective (MAS) breeding programs, we examined 8 reproductive and farrowing traits in the University of Illinois (UI) Meishan x Yorkshire Resource Family. Gilts were genotyped with 119 microsatellite markers (MS) with intervals averaging 24 cM over all 18 porcine autosomes. F-ratios supporting QTL location were calculated by the least squares regression method. Results suggestive of linkage at the 5% genome-wide level were observed for the number of stillborn piglets on Chromosome (Chr) 4 (SSC4) (p-value = 0.0001), corpora lutea on SSC8 (p-value = 0.00027), and gestation length on SSC9 (p-value = 0.00019). Results for additional loci relevant to litter size, number of corpora lutea on SSC15 and 7 (p-value = 0.0029 and 0.0028 at 107 and 150 cM, respectively), gestation length on SSC15 and 1 (p-value = 0.0017 and 0.0069 at 96 and 166 cM, respectively), uterine length on SSC7 and 5 (p-value = 0.0044 and 0.0075 at 148 and 1 cM, respectively) and piglets born per litter on SSC6 (p-value = 0.0075 at 102 cM), were not statistically significant at the 5% genome-wide level. Thus, the use of a linked marker to facilitate selection for reproductive traits has considerable potential. By using linked markers, selection can be applied to both sexes before sexual maturity, making genetic selection considerably more efficient and less costly.

Interval mapping of growth in divergent swine cross.

A genomic scan of 18 swine autosomal chromosomes was constructed with 119 polymorphic microsatellite (ms) markers to identify quantitative trait loci (QTL) for 11 growth traits in the University of Illinois Meishan x Yorkshire Swine Resource Family. A significant QTL effect was found for post-weaning average daily gain (ADG) between 5.5 and 56 kg of body weight that mapped between markers SW373 and SW1301 near the telomere of Chromosome (Chr) 1 q (SSC1). This QTL effect had a nominal (pointwise) p-value of 0.000007, a genome wide p-value of 0.012, and accounted for 26% of the F2 phenotypic variance. The same chromosome region also had significant effects on ADG between birth and 56 kg body weight (p-value =. 000227), and on ADG between 35 and 56 kg (p-value =.00077). These observations suggest that a significant QTL for post-weaning growth resides on SSC1.

A PCR-based genetic map for human chromosome 3.

Oligonucleotide primers for 125 simple sequence repeat microsatellite-based genetic markers have been assayed by polymerase chain reaction (PCR) in the CEPH reference family panel. These microsatellites include 101 dinucleotide repeats as well as 24 new tetranucleotide repeats. The average heterozygosity of this marker set was 72.4%. Genetic data were analyzed with the genetic mapping package LINKAGE. A subset of these microsatellite markers define a set of 56 uniquely ordered loci (> 1000:1 against local inversion) that span 271 cM. Sixty-seven additional loci were tightly linked to markers on the uniquely ordered map, but could not be ordered with such high precision. These markers were positioned by CMAP into confidence intervals. One hundred thirteen of the microsatellite markers were also tested on a chromosome 3 framework somatic cell hybrid panel that divides this chromosome into 23 cytogenetically defined regions, integrating the genetic and physical maps of this chromosome. The high density, high heterozygosity, and PCR format of this genetically and physically mapped set of markers will accelerate the mapping and positional cloning of new chromosome 3 genes.

Mapping of short tandem repeat polymorphisms on human chromosome 3.

Linkage analysis was used to determine map positions for 18 short tandem repeat polymorphisms that continuously span 186 cM of human chromosome 3. Mapping was based on the genotyping of 40 CEPH reference families. Loci order from pter-qter was D3S1252-D3S1235-D3S1234-D3S1233- D3S1254-D3S1251-D3S1215-RHO-ACPP- D3S1238-D3S1206-D3S196-D3S1237- (D3S1253,D3S1439)-D3S1243-D3S1232-SST. Odds against inversion of adjacent markers in all cases were 700:1 or better, except for the marker pair at D3S1253,D3S1439 that was not separated by any recombinants and therefore could not be ordered. Only one gap greater than 25 cM on the sex-equal map was observed.

Evidence for human meiotic recombination interference obtained through construction of a short tandem repeat-polymorphism linkage map of chromosome 19.

An improved linkage map for human chromosome 19 containing 35 short tandem repeat polymorphisms (STRPs) and one VNTR (D19S20) was constructed. The map included 12 new (GATA)n tetranucleotide STRPs. Although total lengths of the male (114 cM) and female (128 cM) maps were similar, at both ends of the chromosome male recombination exceeded female recombination, while in the interior portion of the map female recombination was in excess. Cosmid clones containing the STRP sequences were identified and were positioned along the chromosome by fluorescent in situ hybridization. Four rounds of careful checking and removal of genotyping errors allowed biologically relevant conclusions to be made concerning the numbers and distributions of recombination events on chromosome 19. The average numbers of recombinations per chromosome matched closely the lengths of the genetic maps computed by using the program CRIMAP. Significant numbers of chromosomes with zero, one, two, or three recombinations were detected as products of both female and male meioses. On the basis of the total number of observed pairs of recombination events in which only a single informative marker was situated between the two recombinations, a maximal estimate for the rate of meiotic STRP "gene" conversion without recombination was calculated as 3 x 10(-4)/meiosis. For distances up to 30 cM between recombinations, many fewer chromosomes which had undergone exactly two recombinations were observed than were expected on the basis of the assumption of independent recombination locations. This strong new evidence for human meiotic interference will help to improve the accuracy of interpretation of clinical DNA test results involving polymorphisms flanking a genetic abnormality.

A microsatellite-based index map of human chromosome 11.

We have constructed a continuous index map of 25 microsatellite markers on human chromosome 11. The markers have been typed in 40 CEPH families, have heterozygosities of 69% or higher and can be typed by PCR. The odds against inversion of adjacent marker loci order are at least 10(5):1. The sex average map covers a total of 162 cM with no gap exceeding 15 cM. Total lengths for female and male maps are 205 and 123 cM, respectively. By use of a hybrid cell panel or by in situ hybridization, 16 of the markers have also been mapped cytogenetically, providing a good correlation of the index map with the cytogenetic map. The map will facilitate high resolution mapping of additional polymorphic loci and of disease genes on chromosome 11.

Genetic and physical map of 11 short tandem repeat polymorphisms on human chromosome 6.

A linkage map of 11 short tandem repeat polymorphisms was constructed for human chromosome 6. The order from p to qter was F13A1-D6S105-D6S254-D6S251-D6S252-D6S24 9-(ARG1-D6S87)-D6S250-D6S255-D6S253. For the region spanned by the 6q markers, the male map distance was less than half the female map distance (58 and 126.3 cM, respectively). Two-point linkage analysis was also used to position the markers relative to markers in the CEPH public database. Physical mapping of these markers was completed using a somatic cell hybrid panel that contained varying segments of chromosome 6. Two of the markers mapped to the short arm of chromosome 6; the remainder were spaced over 86.5 cM of the long arm from 6q13 to 6qter. The linkage and physical maps were completely consistent.

Linkage map of human chromosome 9 microsatellite polymorphisms.

Ten microsatellite markers composed of polymorphic (CA)n or (AAAT)n repeats were mapped to chromosome 9. PIC values for these markers ranged from 0.46 to 0.82. The marker at the D9S54 locus was localized to 9pter-p22 by means of a somatic cell hybrid; another marker at D9S103 was similarly localized to 9q34-qter. Two-point lod scores and individual meiotic recombination events were used to position the 10 markers relative to each other. The best order resulting from these analyses was D9S54-D9S104-[D9S52-D9S43-D9S50]-D9S53+ ++- [D9S106-D9S105]-D9S51-D9S103, with order of the loci within brackets uncertain. Two-point linkage analysis was also used to approximate the positions of the microsatellite markers relative to those of 33 markers contained in the public CEPH database (v.3) and to one other available microsatellite marker at the D9S15 locus.

Prescribing at the hospital-general practice interface. I: Hospital outpatient dispensing policies in England.

OBJECTIVE: To describe the outpatient dispensing policies of major acute hospitals in England. DESIGN: Postal questionnaire survey in November 1990. SETTING: All (278) major acute hospitals in England with more than 250 beds, excluding maternity, paediatric, or psychiatric hospitals; nine hospitals declined. PARTICIPANTS: Hospital chief pharmacists. MAIN OUTCOME MEASURES: Current dispensing policy and exceptions to it; when the policy was formed; and who was involved in its formation. RESULTS: Completed questionnaires were received from 200 (72%) of the hospitals approached. The quantities of drugs dispensed to outpatients ranged from zero in 12 hospitals to unlimited amounts in nine; nearly half (92) dispensed a 14 days' supply of drugs. The greater the restriction on outpatient dispensing, the more recently the policy had been introduced (chi 2 for trend = 7.15; df = 1; p less than 0.01). Permissible exceptions to the policy included the consultant's specific request (134 hospitals), difficulty in obtaining drugs in the community (102), urgent need for start of treatment (49), and certain types of patients (41) or drugs or their regimens (104). Groups who were neither represented on the hospital committee concerned with policy formation nor consulted before policy changes included regional health authorities in 122 hospitals, district health authorities in 101 hospitals, and general practitioners in 32 hospitals. CONCLUSIONS: Outpatient dispensing policies varied considerably among the hospitals surveyed, but they seemed to be moving towards greater restrictions on the supply of drugs given to outpatients.