Residual stress distribution in steel butt welds measured using neutron and synchrotron diffraction.

70 keV synchrotron radiation and thermal neutrons have been employed to investigate the residual stress characteristics in a fully restrained, steel, butt weld. The focus is on the values of the subsurface and through-thickness strain/stress variation in the middle of the weld. The advantages and limitations of the techniques have been addressed, in relation to the gauge volume, the stress-free reference sample and positioning. The measurement of residual stress around the weld achieved in this work significantly improves the resolution at which residual stress in welded components has been determined.

New algorithm to model protein-protein recognition based on surface complementarity. Applications to antibody-antigen docking.

A novel algorithm is presented which models protein-protein interactions using surface complementarity. The method is applied to antibody-antigen docking. A steric scoring scheme, based upon a soft potential, is used to assess complementarity, and a simple electrostatic model is then used to remove infeasible interactions. The soft potential allows for structural changes that occur during docking. Biochemical knowledge is necessary to reduce the number of docking orientations produced by the method to a manageable size. The information used includes the known epitope residues and a single loose distance constraint. The method is applied to all three crystallographically determined antibody-lysozyme complexes, HyHEL-10, D1.3 and HyHEL-5. For the first time, a predicted antibody structure (that of D1.3) is used as a docking target. In the four systems modelled, the method identifies between 15 and 40 possible docking orientations. The root-mean-square (r.m.s.) deviation between these orientations and the relevant crystallographic complex is measured in the interface region. For all four complexes an orientation is found with r.m.s. deviation in the range 1.9 A and 4.8 A. The algorithm is implemented on a single instruction/multiple datastream (SI/MD) architecture computer. The use of a parallel architecture computer ensures detailed coverage of the search space, whilst still maintaining a search time of two days.

Prediction of the three-dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein.

We have predicted the three-dimensional structures of the serine protease subunits (gamma-NGF, alpha-NGF, and EGF-BP) of the high molecular weight complexes of nerve growth factor (7S NGF) and epidermal growth factor (HMW-EGF) from the mouse submandibular gland (from the X-ray crystal structures of two related glandular kallikreins). The conformations of three of the six loops surrounding the active site are relatively well defined in the models of gamma-NGF and EGF-BP, but three other loops are likely to have flexible conformations. Although the amino acid sequence of alpha-NGF is closely related to those of gamma-NGF and EGF-BP, it is catalytically inactive. Model-building studies on alpha-NGF suggested that mutations (in alpha-NGF) just prior to the active site serine (195) and an unusual N-terminal sequence are consistent with alpha-NGF having a zymogen-like conformation (similar to that in chymotrypsinogen). An hypothetical model of the quaternary structure of HMW-EGF has been constructed using this model of EGF-BP and the NMR structure of murine EGF. The C-terminal arm of EGF was modeled into the active site of EGF-BP based on data indicating that the C-terminal arginine of EGF occupies the S1 subsite of EGF-BP. Data suggesting one of the surface loops of EGF-BP is buried in the HMW-EGF complex and symmetry constraints were important in deriving a schematic model. A molecular docking program was used to fit EGF to EGF-BP.

Clinical effects of L-5-hydroxytryptophan administration in chronic schizophrenic patients.

L-5-Hydroxytryptophan (L-5HTP) and the peripheral decarboxylase inhibitor carbidopa were administered to chronic schizophrenic patients in three separate experiments using a double-blind placebo-controlled crossover design. The three experiments were: (i) L-5HTP administration to 15 patients who had been withdrawn from all neuroleptic medication; (ii) L-5HTP administration to seven patients maintained on haloperidol; (iii) L-5HTP administration to nine patients maintained on chlorpromazine. Although the groups were diagnostically homogeneous, individual responses were highly variable. Considering each group as a whole, the only significant changes in rated psychosis consisted of an increase in the first group consequent to coming off neuroleptic medication and an increase in psychosis scores associated with adding L-5HTP to chlorpromazine. Neuroleptics apparently sensitize the central nervous system to the effects of L-5HTP loading. Acute exacerbations of psychosis induced by L-5HTP can be reversed by neuroleptics. Our experience does not give encouragement to the hypothesis that schizophrenic illnesses arise consequent to a deficit of serotonergic function that can be treated by giving a serotonin precursor in pharmacological quantities.

Psychiatric training and practice in the People's Republic of China.

Improved political relations between the United States and the People's Republic of China have led to closer contact in many areas. The authors trace the development of psychiatric training and practice in China with emphasis on the years after 1949. Since then, China has expanded psychiatric services to meet the needs of a vast population and has developed a theoretical approach to psychiatry that emphasizes sociopolitical factors. Additional information given to the authors in 1973 by psychiatrists in Nanking and Shanghai is presented and correlated with reports by other recent visitors to the People's Republic of China.

A standardisation approach to the control of socioeconomic confounding in small area studies of environment and health.

OBJECTIVE: To assess how effectively a routine adjustment can be made for socio-economic confounding in small area studies of environment and health using indirect standardisation and small area deprivation indices, including analysis of the appropriate size of population unit on which to base the deprivation index and the importance of region and urban/rural status as axes of stratification. METHODS: Standardised morbidity ratios were calculated for cancers in Great Britain for 1981 and standardised mortality ratios for all cause mortality in Great Britain between 1982 and 1985. Deprivation indices were calculated for enumeration districts and wards from 1981 small area census statistics. Cancers and deaths were allocated to enumeration districts via their postcode. Standardised morbidity and mortality ratios were calculated by quintile of enumeration district according to the deprivation index. Standardised mortality ratios were further analysed by deprivation of ward, region, and urban/rural status. RESULTS: Strong relationships were found between all cause mortality and the incidence of selected cancers and deprivation quintile-there was up to a twofold difference in lung cancer incidence between the highest and lowest quintile. The deprivation index can be used to measure gradients of deprivation according to the distance from industrial sites. The deprivation index for enumeration districts showed similar discrimination of mortality as the index forwards. There is some interaction between deprivation and region in their effect on the standardised mortality ratios, leading to a small bias in the estimation of expected numbers if this is not taken into account. The relationship between deprivation, urban/rural status, and mortality is complex and confounded by region, but mortality tends to be higher in urban than in rural areas within quintiles of deprivation. DISCUSSION: Whether calculated for enumeration districts or wards, the main problems in the interpretation of the deprivation index may be its limited correlation with the risk factors of interest and its concentration on present rather than past socioeconomic status. Indirect standardisation based on stratification for deprivation and other variable involves a trade off between bias and precision in determining the fineness and the number of axes of stratification. Some bias may occur due to interaction between region and deprivation and the effects of urban/rural status. Complementary approaches including modeling and proportional mortality or morbidity analyses may be needed and the possibility of residual socioeconomic confounding must always be considered. CONCLUSION: There is potential for important socioeconomic confounding in small area studies of environmental pollution and health where the health outcome under examination has a strong relationship to socioeconomic status and where the putative excess risk due to pollution may be small. One method of controlling for confounding is to use an ecological measurement of deprivation in small areas, and to adjust for deprivation by indirect standardisation. However, residual socioeconomic confounding can be expected, which may seriously complicate the interpretation of small area studies.

The investigation and outcome of reported cases of elder abuse: the Forsyth County Aging Study.

This study summarizes the outcome of all investigations of elder abuse conducted in Forsyth County, North Carolina, during a 3-year period ending December 1991. Of the 123 cases investigated, 23 were confirmed as elder abuse. There were no statistically significant differences in age, sex, race, living arrangements, mental status, mobility, or source of report between confirmed and unconfirmed cases. Unconfirmed compared to confirmed cases were more likely to reside in a nursing home and/or to be ill. The most frequently substantiated charge was exploitation of resources (46%). Only 3% of charges of physical abuse were substantiated. Among confirmed cases, 70% were offered and accepted protective services.

Geographical variation in anophthalmia and microphthalmia in England, 1988-94.

OBJECTIVE: To investigate the geographical variation and clustering of congenital anophthalmia and microphthalmia in England, in response to media reports of clusters. DESIGN: Comparison of pattern of residence at birth of cases of anophthalmia and microphthalmia in England in 1988-94, notified to a special register, with pattern of residence of all births. Three groups studied included all cases, all severe cases, and all severe cases of unknown aetiology. OUTCOME MEASURES: Prevalence rates of anophthalmia and microphthalmia by region and district, and by ward population density and socioeconomic deprivation index of enumeration district grouped into fifths. Clustering expressed as the tendency for the three nearest neighbours of a case to be more likely to be cases than expected by chance, or for there to be more cases within circles of fixed radius of a case than expected by chance. RESULTS: The overall prevalence of anophthalmia and microphthalmia was 1.0 per 10 000 births. Regional and district variation in prevalence did not reach statistical significance. Prevalence was higher in rural than urban areas: the relative risk in the group of wards of lowest population density compared with the most densely populated group was 1.79 (95% confidence interval 1.15 to 2.81) for all cases and 2.37 (1.38 to 4. 08) for severe cases. There was no evidence of a trend in risk with socioeconomic deprivation. There was very little evidence of localised clustering. CONCLUSIONS: There is very little evidence to support the presence of strongly localised environmental exposures causing clusters of children to be born with anophthalmia or microphthalmia. The excess risk in rural areas requires further investigation.

Challenging the myths surrounding qualitative research in nursing.

The challenge of nursing in the 21st century is to ground nursing practice in nursing science. This article focuses on the role qualitative research has in advancing nursing science and the myths surrounding qualitative research in nursing. The authors challenge these myths and suggest precepts to guide future research and theory development in nursing. These precepts focus on philosophical origins concerning the nature reality and the nature of knowing. Such understanding is vital to conducting and evaluating qualitative research.

Host-phage interaction on Agrobacterium tumefaciens. IV. Phage-directed protein synthesis.

Gel electrophoretic and autoradiographic techniques were used to detect the temporal sequence of protein synthesis after infection of the sensitive strain Agrobacterium tumefaciens with phage LV-1. Three classes of protein were detected: early proteins, class I, which include a protein capable of shutting off host protein synthesis; class II, proteins which are detected after 30 min; and late proteins, class III, which include the phage-directed endolysin and five additional proteins that appear 45 min after infection.

Host-bacteriophage interaction in Agrobacterium tumefaciens. 3. Phage-coded endolysins.

Endolysins were detected in a sensitive strain of Agrobacterium tumefaciens (B6) after infection with phage LV-1 and in the lysogen A. tumefaciens V-1 after induction with mitomycin C. A similar endolysin was found in mitomycin C-induced A. tumefaciens C-58, which apparently harbors a defective prophage.

Medical education in the People's Republic of China.

Medical education in the People's Republic of China is described as it was seen on a 10-week trip in 1973. The information was collected from five medical schools which were visited personally as well as from practitioners and citizens. An overview of the health care system indicates the relationships between education and practice. The three-year medical curricula from the five medical schools are reasonably similar; and in the state-controlled system of health care they are integrated with postgraduate training and continuing education. Goals of the educational programs, entrance procedures, and the medical school experience are discussed. The literature on medical education and practice in China is reviewed and compared with the data available during this recent visit. The lessons which might be learned are the methods of offering health care to massive populations and the organization of health professionals and paraprofessionals for such programs.

Cancer incidence near radio and television transmitters in Great Britain. II. All high power transmitters.

A small area study of cancer incidence, 1974-1986, near 20 high power television (TV) and frequency modulation (FM) radio transmitters in Great Britain was carried out to place in context the findings of an earlier study around the Sutton Coldfield transmitter. The national database of postcoded cancer registrations was used with population and socioeconomic data from the 1981 census. Cancers examined were adult leukemias, skin melanoma, and bladder cancer, following the findings in the earlier study of significant declines in risk of these cancers with distance from the Sutton Coldfield transmitter. Childhood leukemia and brain cancer were also examined. Statistical analysis was performed for all transmitters combined, four overlapping groups of transmitters defined by their transmission characteristics, and for all transmitters separately. There were 3,305 adult leukemia cases from 0-10 km (observed/expected (O/E) ratio = 1.03, 95% confidence interval (CI) 1.00-1.07). A decline in risk of adult leukemia was found for all transmitters combined (p = 0.05), two of the transmitter groups, and three of the single transmitters; for all transmitters combined, observed excess risk was no more than 15% at any distance up to 10 km, and there was no observed excess within 2 km of transmitters (O/E ratio = 0.97, 95% CI 0.78-1.21). For childhood leukemia and brain cancer, and adult skin melanoma and bladder cancer, results were not indicative of a decline in risk with distance from transmitters. The magnitude and pattern of risk found in the Sutton Coldfield study did not appear to be replicated. The authors conclude that the results at most give no more than very weak support to the Sutton Coldfield findings.

Cancer incidence near radio and television transmitters in Great Britain. I. Sutton Coldfield transmitter.

A small area study of cancer incidence in 1974-1986 was carried out to investigate an unconfirmed report of a "cluster" of leukemias and lymphomas near the Sutton Coldfield television (TV) and frequency modulation (FM) radio transmitter in the West Midlands, England. The study used a national database of postcoded cancer registrations, and population and socioeconomic data from the 1981 census. Selected cancers were hematopoietic and lymphatic, brain, skin, eye, male breast, female breast, lung, colorectal, stomach, prostate, and bladder. Expected numbers of cancers in small areas were calculated by indirect standardization, with stratification for a small area socioeconomic index. The study area was defined as a 10 km radius circle around the transmitter, within which 10 bands of increasing distance from the transmitter were defined as a basis for testing for a decline in risk with distance, and an inner area was arbitrarily defined for descriptive purposes as a 2 km radius circle. The risk of adult leukemia within 2 km was 1.83 (95% confidence interval 1.22-2.74), and there was a significant decline in risk with distance from the transmitter (p = 0.001). These findings appeared to be consistent over the periods 1974-1980, 1981-1986, and were probably largely independent of the initially reported cluster, which appeared to concern mainly a later period. In the context of variability of leukemia risk across census wards in the West Midlands as a whole, the Sutton Coldfield findings were unusual. A significant decline in risk with distance was also found for skin cancer, possibly related to residual socioeconomic confounding, and for bladder cancer. Study of other radio and TV transmitters in Great Britain is required to put the present results in wider context. No causal implications can be made from a single cluster investigation of this kind.

Assessment of the reproducibility of clinical coding in routinely collected hospital activity data: a study in two hospitals.

BACKGROUND: The aim of the study was to assess the reproducibility of clinical coding in two National Health Service hospitals within North West Thames region. METHODS: A retrospective audit was carried out, of clinical coding in hospital episode statistics, involving comparison of the codes assigned by local staff with those assigned by members of an external team unaware of the locally assigned codes. Where local and external coders disagreed, the records were reviewed for a third time by a further independent coder. The subjects were a random sample of 1607 non-maternity, non-psychiatric admissions occurring between 1991 and 1993, stratified for year and type of disease (asthma, diabetes, appendicitis, fractured femur and 'general'--a random selection of any diagnoses). The main outcome measures were the levels of exact agreement between local and external teams over codes for main diagnosis and procedure, and the level of approximate agreement (over the first three characters of the ICD-9 code for diagnosis and the letter and first two digits of the OPCS-4 code for procedure). For disagreements, the outcome measure was the level of agreement between the 'third' coder and the local and external coders. RESULTS: For the main diagnosis in the 'general' group at hospital A, internal and external coders agreed exactly in 43 per cent of the admissions examined and agreed 'approximately' in 55 per cent (kappa = 0.54). For hospital B the corresponding figures were 60 per cent and 72 per cent (kappa = 0.72). Approximate agreement was higher for the specific diseases considered, particularly for asthma (A: 86 per cent; B: 91 per cent) and fractured femur (A: 84 per cent; B: 89 per cent). For the main procedure at hospital A, there was exact agreement for 58 per cent and approximate agreement for 70 per cent (kappa = 0.66). For hospital B, the corresponding figures were 76 per cent and 83 per cent (kappa = 0.80). In cases of disagreement over the first three digits of the ICD-9 code for main diagnosis, the third coder disagreed with both local and external coders in 53 per cent at hospital A and 38 per cent at hospital B. Agreement was slightly better for discharges in 1992-1993 than in 1991-1992. CONCLUSIONS: The full clinical codes in NHS hospital episode statistics (HES) data should be treated with caution. The first three characters of ICD-9 codes for diagnoses and the OPCS-4 codes for procedures were more reliable. For some specific conditions such as asthma and fractured femur, reliability of the first three characters is much higher (for example, 86 per cent and 91 per cent for asthma in the two hospitals), but for the full codes can be worse. Secondary diagnoses or comorbidities may be significantly undercoded. A higher level of agreement in 1992-1993 than in 1991-1992 suggests that coding may be improving.

Cancer incidence near municipal solid waste incinerators in Great Britain.

By use of the postcoded database held by the Small Area Health Statistic Unit, cancer incidence of over 14 million people living near 72 municipal solid waste incinerators in Great Britain was examined from 1974-86 (England), 1974-84 (Wales) and 1975-87 (Scotland). Numbers of observed cases were compared with expected numbers calculated from national rates (regionally adjusted) after stratification by a deprivation index based on 1981 census small area statistics. Observed-expected ratios were tested for decline in risk with distance up to 7.5 km. The study was conducted in two stages: the first involved a stratified random sample of 20 incinerators; the second the remaining 52 incinerators. Over the two stages of the study was a statistically significant (P<0.05) decline in risk with distance from incinerators for all cancers combined, stomach, colorectal, liver and lung cancer. Among these cancers in the second stage, the excess from 0 to 1 km ranged from 37% for liver cancer (0.95) excess cases 10(-5) per year to 5% for colorectal cancer. There was evidence of residual confounding near the incinerators, which seems to be a likely explanation of the finding for all cancers, stomach and lung, and also to explain at least part of the excess of liver cancer. For this reason and because of a substantial level of misdiagnosis (mainly secondary tumours) found among registrations and death certificates for liver cancer, further investigation, including histological review of the cases, is to be done to help determine whether or not there is an increase in primary liver cancer in the vicinity of incinerators.

Case-control study of hospital admission with asthma in children aged 5-14 years: relation with road traffic in north west London.

BACKGROUND: Evidence for an association between road traffic pollution and asthma is inconclusive. We report a case-control study of hospital admissions for asthma and respiratory illness among children aged 5-14 in relation to proxy markers of traffic related pollution. METHODS: The study was based on routine hospital admissions data in 1992/3 and 1993/4 for North Thames (West) health region within the M25 motorway. Cases were defined as emergency admissions for asthma (n = 1380) or all respiratory illness including asthma (n = 2131), and controls (n = 5703) were other emergency admissions excluding accidents. Cases and controls were compared with respect to distance of residence from nearest main road or roads with peak hour traffic >1000 vehicles and traffic volume within 150 m of residence, obtained by Geographical Information System techniques. Statistical analysis included adjustment for age, sex, admitting hospital, and a deprivation score for the census enumeration district of residence. RESULTS: Adjusted odds ratios of hospital admission for asthma and respiratory illness for children living within 150 m of a main road compared with those living further away were, respectively, 0.93 (95% CI 0.82 to 1.06) and 1.02 (95% CI 0.92 to 1.14). CONCLUSIONS: This study showed no association between risk of hospital admission for asthma or respiratory illness among children aged 5-14 and proxy markers of road traffic pollution.

Lymphohaematopoietic malignancy around all industrial complexes that include major oil refineries in Great Britain.

OBJECTIVES: To examine the incidence of lymphohaematopoietic malignancy around industrial complexes that include major oil refineries in Great Britain after recent public and scientific concern of possible carcinogenic hazards of emissions from the petrochemical industry. METHODS: Small area study of the incidence of lymphohaematopoietic malignancies, 1974-91, within 7.5 km of all 11 oil refineries (grouped into seven sites) in Great Britain that were operational by the early 1970s and processed more than two million tonnes of crude oil in 1993. RESULTS: Combined analysis of data from all seven sites showed no significant (p < 0.05) increase in risk of these malignancies within 2 km or 7.5 km. Hodgkin's lymphoma, but no other malignancy, showed evidence (p = 0.02) of a decline in risk with distance from refineries, but there was an apparent deficit of cases of multiple myeloma near the refineries (p = 0.04). CONCLUSION: There was no evidence of association between residence near oil refineries and leukaemias, or non-Hodgkin's lymphoma. A weak positive association was found between risk of Hodgkin's disease and proximity to major petrochemical industry, and a negative association with multiple myeloma, which may be chance findings within the context of multiple statistical testing.

Cancer incidence and mortality near the Baglan Bay petrochemical works, South Wales.

OBJECTIVES: To study incidence and mortality of leukaemias, cancer of the larynx, and other cancers near the petrochemical plant at Baglan Bay, in response to local concerns of an alleged cluster of cancers in the vicinity. METHODS: This is a small area study of cancer incidence, 1974-84 and of mortality, 1981-91 based on the national postcoded data held by the Small Area Health Statistics Unit and with population and socioeconomic data from the 1981 census. The study is centred on BP Chemicals Ltd, Baglan Bay, Port Talbot, West Glamorgan, South Wales and includes a general population sample of 115,721 people (1981 census) living within 7.5 km of the plant. Cancer incidence and mortality for all cancers, leukaemias, and cancer of the larynx were examined within 7.5 km and 3 km of the plant, and tests for decline in risk of these cancers with distance from the plant were carried out. Mortality from several other cancers possibly associated with the petrochemical industry was also studied. RESULTS: There were 5417 incident cancer cases and 2458 cancer deaths within 7.5 km of the plant during the periods of study. There was an 8% excess incidence of all cancers within 7.5 km, and a 24% excess of cancer of the larynx, consistent with a general excess of these cancers in West Glamorgan, but no apparent decline in incidence with distance from the plant, nor excess mortality. There was also no evidence of decline in leukaemia incidence or mortality with distance, at all ages or in children. Among the other causes included in the mortality study, there was an excess of multiple myeloma within 7.5 km, especially among women, and a significant decline in mortality from non-Hodgkin's lymphomas although there was no excess overall within 7.5 km. CONCLUSIONS: The apparent excess incidence of all cancers and cancer of the larynx within 7.5 km of the BP Chemical Ltd works was consistent with an excess more generally in West Glamorgan, possibly related, at least to some extent, to cancer registration in Wales. There was no excess mortality from these cancers. The results for multiple myeloma and especially non-Hodgkin's lymphomas may have been chance findings in view of the multiple tests of significance carried out in the study. A study of lymphatic and haematopoietic cancers near oil refineries in Great Britain is to be undertaken that will help put the findings of the present study in wider context.