The possible drivers and implications of an observed latitudinal cline in disease resistance of a host tree were examined. Mycosphaerella leaf disease (MLD) damage, caused by Teratosphaeria species, was assessed in five Eucalyptus globulus (Tasmanian blue gum) common garden trials containing open-pollinated progeny from 13 native-forest populations. Significant population and family within population variation in MLD resistance was detected, which was relatively stable across different combinations of trial sites, ages, seasons and epidemics. A distinct genetic-based latitudinal cline in MLD damage among host populations was evident. Two lines of evidence argue that the observed genetic-based latitudinal trend was the result of direct pathogen-imposed selection for MLD resistance. First, MLD damage was positively associated with temperature and negatively associated with a prediction of disease risk in the native environment of these populations; and, second, the quantitative inbreeding coefficient (QST) significantly exceeded neutral marker FST at the trial that exhibited the greatest MLD damage, suggesting that diversifying selection contributed to differentiation in MLD resistance among populations. This study highlights the potential for spatial variation in pathogen risk to drive adaptive differentiation across the geographic range of a foundation host tree species.
Teratosphaeria; Eucalyptus globulus (Tasmanian blue gum); pathogen-imposed selection; disease risk; latitudinal cline; genetic variation
Falls and fractures contribute to morbidity and mortality in bradykinetic rigid syndromes.
The authors performed a retrospective case notes review at the Queen Square Brain Bank for Neurological Disorders and systematically explored the relation between clinical features and falls and fractures in 782 pathologically diagnosed cases (474 with Parkinson's disease (PD); 127 progressive supranuclear palsy (PSP); 91 multiple system atrophy (MSA); 46 dementia with Lewy bodies (DLB); 27 vascular parkinsonism; nine Alzheimer's disease; eight corticobasal degeneration).
Falls were recorded in 606 (77.5%) and fractures in 134 (17.1%). In PD, female gender, symmetrical onset, postural instability, and autonomic instability all independently predicted time to first fall. In PD, PSP, and MSA latency to first fall was shortest in those with older age of onset of disease. Median latency from disease onset to first fall was shortest in Richardson's syndrome (12 months), MSA (42), and PSP‐parkinsonism (47), and longest in PD (108). In all patients fractures of the hip were more than twice as common as wrist and forearm fractures. Fractures of the skull, ribs, and vertebrae occurred more frequently in PSP than in other diseases.
Measures to prevent the morbidity associated with falls and fractures in bradykinetic rigid syndromes may be best directed at patients with the risk factors identified in this study.
Parkinson's disease; bradykinetic rigid syndromes; falls; fractures
Adaptive optics imaging of cone photoreceptors has provided unique insight into the structure and function of the human visual system and has become an important tool for both basic scientists and clinicians. Recent advances in adaptive optics retinal imaging instrumentation and methodology have allowed us to expand beyond cone imaging. Multi-wavelength and fluorescence imaging methods with adaptive optics have allowed multiple retinal cell types to be imaged simultaneously. These new methods have recently revealed rod photoreceptors, retinal pigment epithelium (RPE) cells, and the smallest retinal blood vessels. Fluorescence imaging coupled with adaptive optics has been used to examine ganglion cells in living primates. Two-photon imaging combined with adaptive optics can evaluate photoreceptor function non-invasively in the living primate retina.
retina; adaptive optics; imaging, photoreceptors; retinal pigment epithelium; retinal ganglion cells
Few data exist on how the HIV/AIDS epidemic may influence population mental health. The associations were examined between knowing someone who died of HIV/AIDS and common mental disorders among South African adults.
Between 2002 and 2004, a nationally representative sample of 4351 adults were interviewed about personally knowing someone who died of HIV/AIDS, and the World Health Organization Composite International Diagnostic Interview was used to generate psychiatric diagnoses for depression, anxiety and substance abuse disorders during the preceding 12 months based on the Diagnostic and Statistical Manual, 4th edition (DSM-IV).
Overall, 42.2% of the sample knew someone who died of HIV/AIDS, and 16.5% met the criteria for at least one DSM-IV diagnosis. Individuals who knew someone who died of HIV/AIDS were significantly more likely to have any DSM-IV defined disorder, including any depressive, anxiety or substance-related disorder (p<0.001 for all associations). In multivariate models adjusted for participant demographic characteristics, life events and socioeconomic status, individual disorders significantly associated with knowing someone who died of HIV/AIDS included generalised anxiety disorder, social phobia and alcohol/drug dependence or abuse. Based on these results, it is estimated that up to 15% of 12-month DSM-IV disorders in the South African adult population may be related to knowing someone who died of HIV/AIDS.
These novel data suggest that AIDS-related mortality may contribute substantially to the burden of mental disorders in settings of high HIV prevalence. While this finding requires further investigation, these data suggest the need to strengthen mental health services in communities where HIV/AIDS is prevalent.
OBJECTIVE--To describe trends in hospital admission rates for asthma in England and Wales (1976-85), the East Anglian region (from 1976 to 1991-2), and Wales (1980-90). DESIGN--Descriptive study. SETTING--Hospitals in England and Wales; hospitals in the East Anglian Regional Health Authority; hospitals in Wales. MAIN OUTCOME MEASURES--Hospital admissions for asthma as principal diagnosis in England and Wales (Hospital In-patient Enquiry, 1976-85), for the East Anglian region (Hospital In-patient Enquiry, 1976-7; Hospital Activity Analysis, 1978-86; Regional Information System, 1987-8 to 1991-2), and for Wales (Hospital Activity Analysis, 1980-90). RESULTS--Rates for England and Wales as a whole showed a steady upward trend throughout the period examined. Rates in East Anglia, though they were similar to the national trends in the early years, showed a peak in 1985 (for males and females) with some indication of a decline in rates thereafter. Rates for Wales showed an upward trend until 1988 (for both males and females) after which they showed a decline. CONCLUSIONS--Interpretation of the East Anglian trends is made more difficult by the change in England in 1987 of the system for the collection of hospital admission data. The fact that the rates for the East Anglian region seem to decline before this change and other considerations suggest that the observed trends, although partly reflecting the disruption of the coding during the changeover in systems, may not be entirely artefactual. The possible roles of diagnostic transfer and changes in the delivery of care, asthma treatment, admission and readmission policies, and the severity and prevalence of asthma in changing admission rates are considered. The changing trends in admission rates for East Anglia and Wales reflect recently published trends for mortality from asthma in England.
The prevalence of personality disorders (PD) in the South African population is largely unknown. Thus, we undertook to estimate prevalence, demographic correlates, co-morbidity and treatment rates of DSM-IV PD among South Africans.
Sampling and Methods
A three-stage probability sample design was used. Of the 4,433 interviews obtained, based on quality control criteria, 4,315 interviews were retained for analysis. All participants were screened for PD and axis I disorders with the World Health Organisation Composite International Diagnostic Interview. The multiple imputation method was then used to estimate prevalence.
The multiple imputation prevalence estimate in the total sample was 6.8%. All three PD clusters were significantly co-morbid with each other and with other axis I disorders. Male gender was the only significant predictor of PD. Of note was the finding that less than one fifth of participants with a possible PD diagnosis had received treatment for a mental health or substance abuse problem in the previous 12 months.
The high co-morbidity of PD with axis I disorders in South Africa is consistent with previous reports elsewhere. However, more research is indicated to determine the reasons for the higher prevalence of cluster A disorders than of cluster B and C disorders in this population.
Diagnostic and Statistical Manual of Mental Disorders, axis I disorders; Personality disorders, prevalence; South Africa
South Africa’s history and current social conditions suggest that mental disorders are likely to be a major contributor to disease burden, but there has been no national study using standardized assessment tools.
The South African Stress and Health Study was a nationally representative in-person psychiatric epidemiological survey of 4351 adults (aged ≥18 years) that was conducted as part of the WHO World Mental Health (WMH) Survey Initiative between January 2002 and June 2004. Twelve-month prevalence and severity of DSM-IV disorders, treatment, and sociodemographic correlates were assessed with Version 3.0 of the WHO Composite International Diagnostic Interview (CIDI 3.0).
The 12-month prevalence of any DSM-IV/CIDI disorder was 16.5%, with 26.2% of respondents with disorder classified as severe cases and an additional 31.1% as moderately severe cases. The most common disorders were agoraphobia (4.8 %), major depressive disorder (4.9%) and alcohol abuse or dependence (4.5 %). Twenty-eight percent of adults with a severe or moderately severe disorder received treatment compared to 24.4% of mild cases. Some 13.8% of persons with no disorder received treatment. Treatment was mostly provided by the general medical sector with few people receiving treatment from mental health providers.
Psychiatric disorders are much higher in South Africa than in Nigeria and there is a high level of unmet need among persons with severe and moderately severe disorders.
Mental disorders; mental health services; South Africa
To assess the prevalence of both diagnosed and undiagnosed diabetes mellitus in an area of predominantly Asian population the Coventry diabetes study is carrying out house to house screening for diabetes in people aged 20 and over in Foleshill, Coventry. In the first five of 12 areas to be studied 2130 of 2283 Asian (93.3%) and 1242 of 1710 white subjects (72.6%) aged 20-79 agreed to be screened. The prevalence of diabetes adjusted to 1987 demographic estimates was 11.2% in Asian men and 8.9% in Asian women whereas it was 2.8% in white men and 4.3% in white women. The excess of diabetes in Asian subjects was predominantly of non-insulin-dependent diabetes, and no significant differences in body mass were found to account for the higher prevalence. Diabetes had not been diagnosed previously in at least 26% of the white and 30% of the Asian diabetics screened, and it is estimated that in this community the condition remains undiagnosed in 42% of white and 40% of Asian diabetics.
Racial residential segregation is a fundamental cause of racial disparities in health. The physical separation of the races by enforced residence in certain areas is an institutional mechanism of racism that was designed to protect whites from social interaction with blacks. Despite the absence of supportive legal statutes, the degree of residential segregation remains extremely high for most African Americans in the United States. The authors review evidence that suggests that segregation is a primary cause of racial differences in socioeconomic status (SES) by determining access to education and employment opportunities. SES in turn remains a fundamental cause of racial differences in health. Segregation also creates conditions inimical to health in the social and physical environment. The authors conclude that effective efforts to eliminate racial disparities in health must seriously confront segregation and its pervasive consequences.
Objective To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler.
Design This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months.
Setting 646 general practices throughout the United Kingdom.
Subjects 6614 patients with obstructive airways disease (1667 patient years of exposure).
Main outcome measures Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects.
Results There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively).
Conclusion The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies.
Key messagesCredibility of postmarketing surveillance studies is expected to increase after the introduction of guidelines covering their conduct The study design successfully fulfilled the requirements of these guidelines in terms of the number, rate, and geographical spread of patients recruitedSafety of salbutamol inhalers using hydrofluoroalkane and chlorofluorocarbon as propellants is similarImportant differences in study design/conduct and outcome between a postmarketing surveillance study and a randomised clinical trial merit further consideration.
OBJECTIVE--To determine the efficacy and morbidity of fine loop diathermy excision of the cervical transformation zone as applied to the management of outpatients with abnormal cervical smears. DESIGN--Prospective programme trial with six month follow up. SETTING--Two hospital based colposcopy clinics. PATIENTS--616 Patients aged 16-60 with abnormal cervical smears. INTERVENTIONS--After colposcopic and cytological assessment excision of the cervical transformation zone by fine loop diathermy under local anaesthesia in the outpatient department. MAIN OUTCOME MEASURES--Time to complete the treatment, immediate morbidity in terms of discomfort and bleeding, and cytological and colposcopic findings at six months. RESULTS--Treatment was completed in a mean of 3.47 minutes (SD 1.99). Immediate morbidity was minimal, and histological specimens were adequate in over 90% of cases. Almost two thirds of patients were treated at their first visit to the clinic. 58 Patients (9.4%) failed to attend for follow up at six months and one had had a hysterectomy. Of the 557 patients who attended for colposcopic and cytological follow up at six months, 506 (91%) were normal cytologically and 19 (3.4%) had histologically confirmed persistence of cervical intraepithelial neoplasia. The overall confirmed failure rate of the technique was 4.4%. CONCLUSION--Loop diathermy excision is an effective treatment with low morbidity and is an appropriate modality for patients with abnormal cervical smears.
It is important that the introduction of breast screening is closely monitored. The anticipated effect on breast cancer mortality will take 10 years or more fully to emerge, and will only occur if a succession of more short-term end points are met. Data from the Swedish two-county randomised trial provide targets that should be achieved, following a logical progression of compliance with the initial invitation, prevalence and stage distribution at the prevalence screen, the rate of interval cancers after the initial screen, the pick-up rate and stage distribution at later screening tests, the rate of interval cancers after later tests, the absolute rate of advanced cancer and finally the breast cancer mortality rate. For evaluation purposes, historical data on stage at diagnosis is desirable; it is suggested that tumour size is probably the most relevant variable available in most cases.
The herd incidence of confirmed Mycobacterium bovis infection in cattle in the south-west of England has been approximately ten times that of the remainder of England and Wales; this greater incidence has been attributed to infection from badgers. The incidence of herds with only non-visible lesioned tuberculin test reactors, from which M. bovis was not isolated, has also remained higher in the south-west region. The incidences of these latter unconfirmed incidents were compared in parishes in the south-west region in which M. bovis in cattle had been confirmed, and those where M. bovis had not been confirmed, for the period 1979-83. This analysis was carried out both for those parishes in which herds had been subjected to annual tuberculin testing and for those subjected to biennial tuberculin testing. The incidence of unconfirmed incidents was significantly higher in parishes in which confirmed incidents had occurred, and this difference was found in both the annual and biennially tested parishes. The relative risks for the incidence of unconfirmed incidents in annually and biennially tested parishes were 1.89 and 2.56, respectively. The incidence of unconfirmed incidents in biennially tested parishes was lower than in annually tested parishes. The incidence of non-specific tuberculin test reactor herds was estimated from tuberculin test results in the eastern region of England during a period when tuberculosis was not confirmed in cattle. A comparison of this incidence and that of unconfirmed incidents in the south-west region suggests that approximately 70% of the unconfirmed incidents in the south-west were related to exposure to M. bovis. The results of the analyses indicate that unconfirmed incidents cannot be completely ignored in epidemiological analyses and studies of bovine tuberculosis in the problem areas of the south-west region of England.
Modified brilliant green agar (BGA), Muller-Kauffmann tetrathionate, Rappaport's and selenite F broths were compared for their efficiency in isolating salmonellas from pigs and their excreta. It was concluded that BGA and Rappaport's broth were the media of choice. Where searches were made for Salmonella cholerae-suis alone, the use of a trehalose McConkey agar provided a rapid method of differentiating S. cholerae-suis, which does not ferment trehalose, from the majority of other salmonellas, which do ferment trehalose. Casualties were collected from two farms where infection with S. cholerae-suis was endemic. The isolation rates of S. cholerae-suis from different carcase sites were compared in order to determine the relative importance of the salivary, upper respiratory and faecal routes of excretion. S. cholerae-suis was isolated from numerous carcase sites in carriers including the salivary glands, tonsils, trachea and lungs. However, isolations from the nasal passages, mouth, pharynx and gastro-intestinal tract of carriers were either infrequent or absent. When, in a further study, S. cholerae-suis was isolated from only 3/414 faeces, 1/170 nasal swabs and not at all from 170 oral swabs taken from live pigs, it was concluded that there must be more significant modes of transmission than from the salivary glands, upper respiratory or gastro-intestinal tracts. Cannibalism was considered to be a possibility. In contrast to S. cholerae-suis, other salmonellas were frequently isolated from randomly collected faeces and from the gastro-intestinal tract as well as other sites in casualties.
Phenotype distributions of some genetic polymorphisms are reported in a sample of 721 diabetics and 515 non-diabetic, non-blood donor controls. Reference is also made, in the case of the ABO and Rhesus systems, to previously published results for blood donors resident in the Durham area. Non-insulin-taking diabetics show an increased frequency of blood group A1 (and A1 + A2) when compared with controls. This difference is particularly marked in male diabetics. When diabetics are compared with age matched controls, the difference is confined to the older cases. It is proposed that this effect is predominantly the result of a deficiency of group A1 in controls rather than the result of increased susceptibility to the disease among A1 people. No association with any of the Rhesus phenotypes is shown. In non-diabetics, the results suggest an enhanced survival value for the rr genotype. No significant associations are seen when the MNSs, Kell, Lewis, Duffy, haptoglobin, red cell acid phosphatase, phosphoglucomutase, adenylate kinase, and adenosine deaminase distributions in these groups of subjects are compared.-
Death rates from ischaemic heart disease (IHD) in English and Welsh counties are correlated, in both men and women, with the infant mortality rates of those counties when the individuals whose deaths are considered were young, thus confirming previous findings in Norway. In England and Wales, however, there is an equally good correlation between deaths from IHD and infant mortality patterns up to and including that for the same time period as the IHD deaths. The British data provide no grounds for concluding from these relationships that living conditions during early life per se bear a causal relationship to deaths from IHD.
The relationship between food intake and cancer of the large bowel was assessed by calculating the average intakes of foods, nutrients and dietary fibre in the different regions of Great Britain and relating these to the regional pattern of death from colon and rectal cancers between 1969 and 1973. No significant associations were found with the consumption of fat, animal protein or beer, nor with current estimates of total dietary fibre intake. Average intakes of the pentose fraction of total dietary fibres, and of vegetables other than potatoes, were negatively correlated with the truncated age- and sex-standardized death rates from colon cancer (r = -0.960 and -0.940). Specific components of dietary fibre may therefore inhibit colon carcinogenesis.
Optimal cell yield of Pseudomonas aeruginosa grown under denitrifying conditions was obtained with 100 mM nitrate as the terminal electron acceptor, irrespective of the medium used. Nitrite as the terminal electron acceptor supported poor denitrifying growth when concentrations of less than 15 mM, but not higher, were used, apparently owing to toxicity exerted by nitrite. Nitrite accumulated in the medium during early exponential phase when nitrate was the terminal electron acceptor and then decreased to extinction before midexponential phase. The maximal rate of glucose and gluconate transport was supported by 1 mM nitrate or nitrite as the terminal electron acceptor under anaerobic conditions. The transport rate was greater with nitrate than with nitrite as the terminal electron acceptor, but the greatest transport rate was observed under aerobic conditions with oxygen as the terminal electron acceptor. When P. aeruginosa was inoculated into a denitrifying environment, nitrate reductase was detected after 3 h of incubation, nitrite reductase was detected after another 4 h of incubation, and maximal nitrate and nitrite reductase activities peaked together during midexponential phase. The latter coincided with maximal glucose transport activity.
The joint control of rate of key pecking in pigeons by stimulus-reinforcer and response-reinforcer relationships was studied in the context of a two-component multiple schedule of reinforcement. Food presentation was always associated with one component and extinction with the other. The stimulus-reinforcer relationship was manipulated by varying the relative durations of the two components. In the food-presentation component, a fixed rate of reinforcement, independent of rate of responding, was generated by a schedule referred to as “T*”. One aspect of the response-reinforcer relationship, contiguity, was manipulated by varying the percentage of delayed reinforcers. With the multiple T* extinction schedule, stimulus-reinforcer and response-reinforcer relationships could be varied independently of one another. Rate of key pecking was sensitive to manipulations of both relationships. However, significant differential effects due to either the stimulus-reinforcer or response-reinforcer relationship were obtained only when the other relationship was weak: stimulus-reinforcer and response-reinforcer relationships interacted in the joint control of responding.
stimulus-reinforcer relationship; response-reinforcer relationship; relative component duration; percentage delayed reinforcement; multiple schedule; T* schedule; key peck; pigeon
Fifteen pigeons were exposed to either response-independent or response-dependent schedules of water reinforcement, whereby water was injected directly into the unrestrained pigeons' mandibles. Key-contact responses were released by a lighted key correlated with water, but not by a lighted key uncorrelated with water. A negative response-reinforcer contingency suppressed autoshaped key-contact responses, resulting in responding directed away from the lighted key. In all pigeons, water injected directly into the mandibles elicited a consummatory fixed-action pattern of “mumbling” and swallowing. The lighted key correlated with water released a broader set of both appetitive and consummatory responses: approach to the lighted key, “bowing”, “rooting”, “mumbling”, and swallowing. Key-contact responses were “rooting” and “mumbling” motions of the beak on the surface of the key. Views of autoshaping based on stimulus substitution or stimulus surrogation do not fully explain the origin of autoshaped responses not previously elicited by the reinforcer. The present findings are consonant with views of conditioning that emphasize the large degree of biological pre-organization in conditioned response patterns, and the importance of associative factors in the control of such patterns.
autoshaping; respondent conditioning; stimulus substitution; stimulus surrogation; “learned release”; water reinforcer; species-specific behavior; key peck; pigeon
The mean isolation rates of salmonellas from the mesenteric lymph nodes and faeces of healthy mink were 16·7% of 618 animals from three farms and 3·9% of 772 animals from four farms respectively. Salmonella senftenberg was the most commonly isolated serotype. S. typhimurium, S. dublin, S. livingstone, S. menston, S. enteritidis, S. bredeney and S. infantis were also seen.
The prevalence of salmonellosis in 316 dead mink from 12 farms was 0·6%.
The epidemiological aspects are discussed.
Serratia marcescens was isolated on a new medium—commercial deoxyribonuclease agar with the addition of cephalothin (1,000 μg/ml) and Toluidine Blue (1,000 μg/ml). It was detected in water samples even though it comprised only 0.1 to 0.0001% of the total bacterial population.