The influence of weather on community gastroenteritis in Australia.

Infectious gastroenteritis is a common illness in Australia as elsewhere. Data from a year-long national gastroenteritis survey in 2001-2002 showed that gastroenteritis was more common in the northern and hotter part of Australia. These data were used to quantify associations between local weather variables and gastroenteritis in people aged >5 years while controlling for socioeconomic status. A distributed lag model was used to examine the influence of weather over a period of days prior to an event and the maximal effect was found at a lag of 2-5 days. The total effect over the preceding week indicated a relative increase from baseline in the probability of gastroenteritis of 2·48% (95% CI 1·01-3·97) for each degree rise (°C) over that period. Given the very high burden of gastroenteritis, this represents a substantial effect at the population level and has relevance for health predictions due to climate change.

Atrial fibrillation and anticoagulation in a stroke unit population.

BACKGROUND: Atrial fibrillation (AF) is an important predisposing factor for ischaemic stroke. There is evidence to suggest that even in appropriate candidates warfarin therapy is underutilized. We assessed the prevalence of AF in an Australian stroke unit to determine the degree of undertreatment at presentation. METHODS: A retrospective analysis of all patients admitted to our Stroke Unit between October 2004 and September 2006 was carried out. All patients with a diagnosis of AF, either new or old, were then selected from this group to determine the overall prevalence and anticoagulation status. Data regarding prior stroke, stroke severity and discharge anticoagulation status were also determined. RESULTS: Data from a total of 500 patients were analysed. Our results showed that AF-related strokes accounted for a large proportion (28%) of all admissions and were associated with a larger neurological deficit. Most patients (68%) with a prior diagnosis of AF without having obvious contraindications were either not anticoagulated or under-anticoagulated when presenting with an ischaemic stroke or transient ischaemic attack. CONCLUSION: Our results stress the importance of initiating and maintaining anticoagulation in patients with AF and without obvious contraindications to minimize the risk of subsequent stroke.

Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES: To assess the effects of an oral, monobacterial whole-cell, killed, nontypeable H. influenzae vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January Week 4 2006), EMBASE (1990 to September 2005) and ISI Current Contents (2004 to May 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of the H. influenzae vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three authors extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable H. influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. The vaccine reduced the incidence of bronchitic episodes at three months after vaccination (rate ratio is 0.69; 95% CI 0.41 to 1.14) and at six months after vaccination (rate ratio 0.82; 95% CI 0.62 to 1.09). If these results been statistically significant, they would have represented a reduction in acute bronchitic attacks for vaccinated individuals of 31% at three months, and 18% at six. The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16 to 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16 to 0.75). AUTHORS' CONCLUSIONS: Vaccinating patients with recurrent acute exacerbations of chronic bronchitis in the autumn may reduce the number and severity of exacerbations over the following winter. A large clinical trial is needed.

Age group differences in psychological distress: the role of psychosocial risk factors that vary with age.

BACKGROUND: There is continuing controversy about how age affects depression and anxiety, with a lack of consistent results across studies. Two reasons for this inconsistency are age bias in measures and different patterns of exposure to risk factors across age groups in various studies. METHOD: Data on anxiety and depression symptoms were collected in a community survey of 7485 persons aged 20-24, 40-44 or 60-64 years. These measures were investigated for factorial invariance across age groups. Data were also collected on a wide range of potential risk factors, including social, physical health and personal factors, with the aim of determining whether these factors might partly or wholly account for age group differences. RESULTS: The invariance of correlated latent factors representing anxiety and depression was examined across age groups, and a generalized measure of psychological distress was computed. Depression, anxiety and psychological distress showed a decline across age groups for females and a decline from 40-44 to 60-64 years for males. Some of these age differences were accounted for by other risk factors, with the most important being recent crises at work and negative social relationships with family and friends. CONCLUSION: Psychological distress generally declined across the age range 20-64 years and this was not attributable to measurement bias. Differential exposure to risk factors explained some, but not all, of the age group difference. Therefore other mechanisms that explain the lower level of distress in older age groups remain to be identified.

General practice encounters for psychological problems in rural, remote and metropolitan areas in Australia.

OBJECTIVE: Previous Australian research suggests there is very little difference in the prevalence of mental health disorders across rural, remote and metropolitan areas. However, mental health specialists are particularly scarce in rural and remote areas and some researchers have argued that non-metropolitan residents rely heavily on general practitioners (GPs) for mental health care. This article investigated rates of GP services for psychological problems across rural, remote and metropolitan areas. METHOD: The Bettering the Evaluation and Care of Health (BEACH) program, Medicare and Pharmaceutical Benefits Scheme data were used in this report. Data included all psychological, depression and anxiety problems reported as managed by GPs and prescriptions for mental health medications (written and filled). Problem and medication rates are given per 100 patient encounters and per 1000 population. RESULTS: Only a few regional differences were evident in the rate of psychological problems and prescriptions for mental health medications per 100 GP-patient encounters. However, rural and remote residents visited GPs less frequently than their metropolitan counterparts. Lower rates of GP encounters for psychological problems were evident for residents of most non-metropolitan areas (per 1000 population). Additionally, GPs prescribed mental health medications at half the rate for residents of remote areas than capital cities. CONCLUSIONS: General practitioners provide fewer mental health services per capita in non-metropolitan areas. This difference could represent completely untreated psychological problems or fewer follow-up consultations. While non-metropolitan residents have limited access to specialists, rates of GP encounters for psychological problems are also very low.

Cohort difference in sexual orientation: results from a large age-stratified population sample.

BACKGROUND: There is some community survey evidence for a cohort difference in female sexual orientation. OBJECTIVE: To determine whether there is a cohort difference in sexual orientation in Australia. METHODS: A community survey was carried out with a sample of 7,447 adults from the age groups 20-24, 40-44 and 60-64 years. As part of this survey respondents were asked a question on sexual orientation which was answered privately. RESULTS: A strong age cohort difference was found for women, with younger women more frequently reporting a homosexual or bisexual orientation. By contrast, no age cohort difference was found for men. CONCLUSION: These findings suggest that a heterosexual orientation may have become less common in younger cohorts of Australian women. This finding is consistent with data from other recent studies.

Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses or bacteria. It can be fatal. Antibiotic therapy has not been particularly useful in clearing bacteria such as nontypeable Haemophilus influenzae (NTHi) because they colonise the upper respiratory tract. An oral NTHi vaccine has been developed to protect against recurrent acute episodes in chronic bronchitis. OBJECTIVES: To assess the effects of an oral whole cell nontypeable Haemophilus influenzae (NTHi) vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003); MEDLINE (1966 to 2003); EMBASE (1990 - 2003); Extramed (1994 to 2003); ISI Current Contents (1993 to 2003); Carl Uncover (1988 to 2003) and contacted investigators of the studies. SELECTION CRITERIA: Randomised trials comparing the effects of an oral monobacterial NTHi vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three reviewers extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable Haemophilus influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. Oral vaccination using a monobacterial whole cell killed nontypeable Haemophilus influenzae significantly reduced the incidence of bronchitic episodes at three months after vaccination (Poisson rate ratio 0.666; 95% confidence interval [CI] 0.500, 0.887; p = 0.005) and perhaps at six months after vaccination (Poisson rate ratio 0.831; 95% CI 0.669, 1.031; p = 0.093). The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16, 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16, 0.75). REVIEWER'S CONCLUSIONS: Vaccination, in the autumn, of patients with recurrent acute exacerbations of chronic bronchitis reduced the number and severity of exacerbations over the winter months. A large clinical trial to assess longer term prognosis is needed.

Interaction between mother's and father's affection as a risk factor for anxiety and depression symptoms--evidence for increased risk in adults who rate their father as having been more affectionate than their mother.

BACKGROUND: Retrospective reports of low care from either parent are found to be associated with increased risk for anxiety and depression in adulthood. Furthermore, fathers are generally reported as having been less caring than mothers, which raises the issue of whether greater care from fathers across the whole population would benefit mental health. METHODS: A community survey was carried out in Canberra, Australia, with 2404 adults aged 20-24 and 2530 aged 40-44. Respondents retrospectively reported on affection shown by their parents and on other aspects of family functioning. These data were analysed in relation to risk for anxiety and depressive symptoms and neuroticism. RESULTS: Retrospective reporting of greater affection from both fathers and mothers was generally associated with fewer anxiety and depression symptoms and lower neuroticism. However, there was a significant interaction effect, such that mental health was worse in families where the father was reported to show a higher level of affection but the mother a lower level. Such families were found to have a range of problems, including higher rates of emotional problems in the parents, conflict in the home, parental separation or divorce, and parental mistreatment. These family problems accounted for much of the interaction effect observed. CONCLUSIONS: Greater affection from the father is not always associated with lower risk for anxiety and depression. Where the father is more affectionate than the mother there tends to be increased family problems and increased risk. It is possible that family problems lead fathers to show increased affection to their children or mothers to show reduced affection.

Testing for the presence of cured patients: a simulation study.

An important but difficult problem in clinical trials is to determine the presence of cured patients when long-term survivors are observed. The likelihood ratio test has been studied for this purpose in the gamma mixture model. However, its asymptotic null distribution is not readily available due to a violation of boundary conditions in the standard asymptotic theory. In this paper, a simulation study is employed to examine a proposed asymptotic null distribution of the likelihood ratio test. We find that the distribution can also be used to approximate the asymptotic null distribution of the likelihood ratio test in the Weibull and log-normal mixture models when the censoring rate is not too light. However, the simulation study also shows that null distribution of the likelihood ratio test deviates significantly from the suggested distribution under moderate sample sizes when the censoring rate is small or the hazard rate is large. Consequently caution is needed in this case to determine the presence of cured patients. Finally, the results are used to confirm the presence of cured patients in a leukaemia study.

A nonparametric mixture model for cure rate estimation.

Nonparametric methods have attracted less attention than their parametric counterparts for cure rate analysis. In this paper, we study a general nonparametric mixture model. The proportional hazards assumption is employed in modeling the effect of covariates on the failure time of patients who are not cured. The EM algorithm, the marginal likelihood approach, and multiple imputations are employed to estimate parameters of interest in the model. This model extends models and improves estimation methods proposed by other researchers. It also extends Cox's proportional hazards regression model by allowing a proportion of event-free patients and investigating covariate effects on that proportion. The model and its estimation method are investigated by simulations. An application to breast cancer data, including comparisons with previous analyses using a parametric model and an existing nonparametric model by other researchers, confirms the conclusions from the parametric model but not those from the existing nonparametric model.

Analysis of variation in success rates in conjunctival autografting for primary and recurrent pterygium.

AIMS: To evaluate the success rates of conjunctival autografting for primary and recurrent pterygium performed in a tertiary ophthalmic centre. METHODS: The outcome of 139 cases with primary pterygia and 64 cases with recurrent pterygia who underwent excision with conjunctival autografting was retrospectively reviewed. Outcome was evaluated in terms of recurrence of pterygia onto the cornea. The recurrence rates were determined using Weibull survival functions, in a mixture model that included a component allowing for cure. The suitability of this model was verified using Turnbull's non-parametric method for interval censored data (1974). Estimated recurrence free probabilities were based on the fitted Weibull survival curves. RESULTS: Mean follow up was 8.4 months in the primary group, and 9.5 months for the recurrent group. 29 out of 139 cases of primary pterygia recurred (20.8%) while 20 out of 64 cases in the recurrent group (31.2%) recurred. Recurrence rates varied widely among surgeons, ranging from 5% to 82%. Recurrence rates were inversely related to previous experience in performing conjunctival grafting. The recurrence free probability was 84% at 3 months, 73% at 1 year for primary pterygia, and 80% at 3 months, 67% at 1 year for recurrent pterygia. There was no statistical difference in recurrence rates between primary and recurrent groups (p= 0.80). CONCLUSION: The success of conjunctival autografting for pterygium in this series varies widely, and may be related to a significant learning curve or differing surgical techniques for this procedure. This may account for the wide variation in reported success of this procedure in the ophthalmic literature.

The familial incidence of symptoms of scotopic sensitivity/Irlen syndrome: comparison of referred and mass-screened groups.

The familial incidence of Scotopic Sensitivity/Irlen Syndrome was investigated in two samples. One sample involved parents and siblings of 126 children identified with symptoms who had been referred for screening. The other sample involved parents and siblings of 33 children who had been identified with symptoms through mass screening of all children in Grades 3 to 6 at two local schools. Two different samples were taken to investigate the possibility of parental referral bias. Familial incidence may be inflated in a referred sample because some parents may be aware of their own symptoms and actively seek assistance. For the sample of children referred for screening, there was an 81% chance of either one or both parents showing similar symptoms and a 76% chance of siblings being similarly affected. For the sample of children identified through school screening, there was an 85%, chance of either one or both parents showing similar symptoms and a 54% chance of siblings being similarly affected. The data confirm previous estimates of incidence and suggest that Scotopic Sensitivity/Irlen Syndrome may be a genetically-based deficit in visual processing.

A generalized F mixture model for cure rate estimation.

Cure rate estimation is an important issue in clinical trials for diseases such as lymphoma and breast cancer and mixture models are the main statistical methods. In the last decade, mixture models under different distributions, such as exponential, Weibull, log-normal and Gompertz, have been discussed and used. However, these models involve stronger distributional assumptions than is desirable and inferences may not be robust to departures from these assumptions. In this paper, a mixture model is proposed using the generalized F distribution family. Although this family is seldom used because of computational difficulties, it has the advantage of being very flexible and including many commonly used distributions as special cases. The generalised F mixture model can relax the usual stronger distributional assumptions and allow the analyst to uncover structure in the data that might otherwise have been missed. This is illustrated by fitting the model to data from large-scale clinical trials with long follow-up of lymphoma patients. Computational problems with the model and model selection methods are discussed. Comparison of maximum likelihood estimates with those obtained from mixture models under other distributions are included.

Tests for homogeneity of the risk difference when data are sparse.

Test statistics for the homogeneity of the risk difference for a series of 2 x 2 tables when the data are sparse is proposed. A weighted least squares statistic is commonly used to test for equality of the risk difference over the tables; however, when the data are sparse, this statistic can have anticonservative Type I error rates. Simulation is used to compare the proposed test statistics to the weighted least squares statistic. The weighted least squares statistic has the most anticonservative Type I error rates of all the statistics compared. We suggest the use of one of our proposed test statistics instead of the weighted least squares statistic.

Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision.

OBJECTIVES: To compare success rates of conjunctival autografting and bare sclera excision for primary and recurrent pterygium in the tropics and to evaluate risk factors for pterygium recurrence. METHODS: A prospective, controlled clinical trial was performed in which 123 primary and 34 recurrent pterygia, matched for age and pterygium morphology, were randomized in 2 separate studies to receive either bare sclera excision or conjunctival autograft. The surgical procedures were performed by one surgeon and reviewed at 1, 3, 6, and 12 months after surgery by an independent observer. Pterygium morphology was clinically graded as atrophic, intermediate, or fleshy according to an assessment of pterygium translucency. Risk factors were assessed using likelihood ratio tests. Weibull curves were used to estimate recurrence rates allowing for the interval censoring. RESULTS: In the group with primary pterygium (mean follow-up, 15.1 months), 38 (61%) of the 62 cases of bare sclera excision (heretofore referred to as the bare sclera group) had pterygium recur in contrast with 1 (2%) of the 61 cases of conjunctival autograft (heretofore referred to as the conjunctival autograph group) (P<.001, likelihood ratio X2 test). Nontranslucency, or fleshiness of the pterygium, and not age was a significant risk factor for recurrence in the bare sclera group (P<.001, likelihood ratio X2 test). In the group with recurrent pterygium (mean follow-up, 13.2 months), 14 (82%) of the 17 bare sclera group had pterygium recur, while no recurrences occurred among 17 cases in the conjunctival autograft group. Nontranslucency was again a highly significant factor for recurrence (P<.001, likelihood ratio X2 test). CONCLUSIONS: Pterygium recurrence is related to pterygium morphology and fleshiness of the pterygium is a significant risk factor for recurrence if bare sclera excision is performed. Conjunctival autografting for primary and recurrent pterygium is effective in reducing pterygium recurrence compared with bare sclera excision.

Estimating correlations from epidemiological data in the presence of measurement error.

Analysis of a major multi-site epidemiologic study of heart disease has required estimation of the pairwise correlation of several measurements across subpopulations. Because the measurements from each subpopulation were subject to sampling variability, the Pearson product moment estimator of these correlations produces biased estimates. This paper proposes a model that takes into account within and between sub-population variation, provides algorithms for obtaining maximum likelihood estimates of these correlations and discusses several approaches for obtaining interval estimates.

A phase III double-blind randomised study of rectal sucralfate suspension in the prevention of acute radiation proctitis.

BACKGROUND AND PURPOSE: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. MATERIALS AND METHODS: Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. RESULTS: There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 +/- 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 +/- 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. CONCLUSION: This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late toxicity.

The familial incidence of symptoms of Scotopic Sensitivity/Irlen syndrome.

The familial incidence of Scotopic Sensitivity/Irlen Syndrome was investigated using parents of 751 children identified with symptoms. Children were identified by methods independent of their parents' symptoms or lack of symptoms. For these children, there was an 84% chance of either one or both parents showing similar symptoms, with similar numbers of mothers identified with symptoms as fathers. The data suggest that Scotopic Sensitivity/Irlen Syndrome may be a genetically based deficit in visual processing, but the simplest genetic models do not appear to fit.

The follicular non-Hodgkin's lymphomas--I. The possibility of cure.

The follicular lymphomas pursue an indolent course in many patients. Long-term follow-up in large series is therefore necessary to establish whether cure is taking place, and if so, at what stage in the dissemination of the disease process it becomes unlikely. The time to, and site of relapse, together with its impact on survival has been studied in 398 patients entered into the British National Lymphoma Investigation limited and disseminated disease trials between 1974 and 1980. Relapse data were compared with various models to obtain maximum likelihood estimates of the proportions permanently remaining relapse-free following treatment. Long-term relapse-free survival was observed in 54.8 +/- 14.9% (95% CI) of patients at 15 years with Ann Arbor stage I disease, 29.2 +/- 13.6% in patients with stage II disease, 18.1 +/- 6.6% with stage III and 13.0 +/- 5.9% with IV disease. Relapse time-course data for all trial arms conform closely to lognormal distributions allowing maximum likelihood estimates of proportions remaining permanently relapse-free to be derived. Using this methodology, over a quarter of patients treated with involved radiotherapy alone or radiotherapy plus 6 months of chlorambucil in the limited disease (Ann Arbor stage I and II) trial are unlikely to relapse at any time in the future. Over 10% of patients treated in the disseminated disease trials with disease classified as Ann Arbor stage III are also statistically unlikely to relapse. The finding that a proportion of patients is statistically unlikely to experience a clinically obvious relapse is consistent with clinical cure. It is especially interesting that a small proportion of patients with disseminated disease and treated by chemotherapy have fallen into this category, but additional data are required to know at what point statistical cure becomes unlikely. Whether "clinical cure" is the same as "pathological cure" in this disease remains uncertain.

The follicular non-Hodgkin's lymphomas--II. Prognostic factors: what do they mean?

The Ann Arbor staging classification has long been recognised to have shortcomings when used to stage the follicular lymphomas. To date, the identification of important prognostic variables has not succeeded in producing a superior staging classification that reflects the stages of dissemination of these processes in a way that can be used in the testing of new therapeutic strategies. A fresh look is taken at these factors. Data from 398 patients entered into the British National Lymphoma Investigation trials between 1974 and 1980, were analysed to evaluate the performance of the Ann Arbor staging classification. Multiple regression and proportional hazards techniques were used to determine what factors independently influence response to initial treatment, the durability of that response and ultimate survival, and to isolate factors that relate to disease progression from those that have other mechanisms of action. The Ann Arbor staging classification fared poorly, minimally separating relapse-free and cause-specific survival probabilities in patients with the largest staging groupings, III and IV. Significant prognostic heterogeneity was seen in both of these stage groupings, with 22% of patients with stage IV disease on the basis of marrow involvement having slightly better outcomes than patients with stage III disease. Significant differences in outcome were also observed between patients of different age and sex in each Ann Arbor stage grouping. Increasing number of lymph node regions involved, constitutional symptoms, the presence of splenomegaly and increasing age were observed to have powerfully independent adverse influence on probability of complete response to treatment and cause-specific survival. The evolution of the follicular lymphomas is reflected at the clinical level by an increase in the number of lymph node regions involved and splenomegaly. Simple classifications based on simple counts of lymph node regions involved and splenomegaly are more successful than the Ann Arbor staging classification in subdividing the series into patient subgroups that, regardless of gender or age, experience significantly different probabilities of responding completely to therapy and, as a consequence, relapse-free and cause-specific survival expectations. The definition of poor prognosis in subgroups may be of value in selecting patients for newer and more intensive therapeutic approaches.