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Assessment of operative risk in colorectal cancer surgery: the Cleveland Clinic Foundation colorectal cancer model.

INTRODUCTION: Predictive models play a pivotal role in the provision of risk-adjusted, operative mortality rates. The purpose of the study was to describe the development of a dedicated prognostic index for quantifying operative risk in colorectal cancer surgery. METHODS: Data were collected from 5,034 consecutive patients undergoing major surgery in a single center from October 1976 to July 2002. Primary end point was 30-day operative mortality. A multilevel Bayesian logistic regression model was developed to adjust for case-mix and accommodate the variability of outcomes between surgeons. The model was internally validated (split-sample) and tested using measures of discrimination, calibration, and subgroup analysis. RESULTS: The patients' median age was 66 (range, 18-98) years. Operative mortality was 2.3 percent with no significant variability between surgeons or through time. Multivariate analysis identified the following independent risk factors: age (odds ratio = 1.5 per 10-year increase), American Society of Anesthesiologists grade (odds ratio for ASA II, III, IV-V vs. I = 2.6, 4.3, 6.8), TNM staging (odds ratio for Stage IV vs. I-III = 2.6), mode of surgery (odds ratio for urgent vs. nonurgent = 2.1) no-cancer resection vs. cancer resection (odds ratio = 4.5), and hematocrit level. The model offered adequate discrimination (area under receiver operator characteristic curve = 0.801) and excellent agreement between observed and model-predicted outcomes over ten major colorectal procedures (P = 0.191). CONCLUSIONS: The colorectal cancer model provided an accurate means of estimating risk for individual patients in the preoperative setting. It has important implications in everyday practice, because it may be used as an adjunct in the process of informed consent and for monitoring surgical performance through time.

Adolescent↗

Prediction of postoperative mortality in elderly patients with colorectal cancer.

PURPOSE: This study was designed to develop a model for predicting postoperative mortality in elderly patients undergoing surgery for colorectal cancer. METHODS: This multicenter study was conducted by using routinely collected clinical data, assessing patients older than aged 80 years, with 30-day operative mortality as the primary end point. Data were collected from The Association of Coloproctology of Great Britain and Ireland database, encompassing 8,077 newly diagnosed colorectal cancer patients undergoing resectional surgery in 79 hospitals between April 2000 to March 2002, The Association of Coloproctology Malignant Bowel Obstruction Study, encompassing 1,046 patients with malignant bowel obstruction in 148 hospitals, between April 1998 to March 1999, and The Wales-Trent audit, encompassing 3,522 newly diagnosed colorectal cancer patients, between July 1992 to June 1993. A multilevel logistic regression model was developed to adjust for case-mix and to accommodate the variability of outcomes between the three study populations. The model was internally validated using a Bayesian resampling technique and tested using measures of discrimination, calibration, and subgroup analysis. RESULTS: A total of 2,533 patients satisfied the inclusion criteria, with a 30-day mortality of 15.6 percent. Multivariate analysis identified the following independent risk factors: age (odds ratio for 85-90, 90-95, >95 vs. 80-85 = 1.1, 1.8, 2.9), American Society of Anesthesiology grade (odds ratio for Grade III, IV vs. I-II = 2.7, 6.1), operative urgency (odds ratio for emergency vs. elective = 1.9), no cancer excision vs. resection (odds ratio = 1.2), and metastatic disease (odds ratio for metastases vs. no metastases = 1.9). The model offered adequate discrimination (area under receiver operator curve = 0.732) and excellent agreement between observed and predicted outcomes during eight colorectal procedures (P = 0.885). CONCLUSIONS: The elderly colorectal cancer model can accurately estimate 30-day mortality in patients older than aged 80 years undergoing surgery for colorectal cancer. Because the mortality can be considerable, this may have important implications when determining management for this group of patients.

Age Factors↗

A national study on lymph node retrieval in resectional surgery for colorectal cancer.

PURPOSE: This study was designed to develop a mathematical model for predicting the number of lymph nodes harvested in bowel cancer resection specimens based on the current clinical practice in the United Kingdom. METHODS: Prospective clinical data were collected from 8,409 newly diagnosed bowel cancer patients presenting to 79 hospitals in Great Britain and Ireland during a variable 12-month period from 2000 to 2002. A two-level hierarchical regression model was used to identify predictors for lymph node harvest. The model was internally validated by comparing observed and model predicted lymph node harvest for patient subgroups. RESULTS: Inclusion criteria were satisfied by 5,164 patients. The average lymph node harvest was 11.7 nodes with significant between-center variability in lymph node harvest (range, 5.5-21.3 nodes). Increasing age, American Society of Anesthesiology grade, and preoperative radiotherapy were associated with a reduction of lymph node harvest (P < 0.001). Abdominoperineal resection of the rectum and transverse colectomy were the lowest yield procedures for lymph node harvest. Independent predictors of lymph node harvest were age, American Society of Anesthesiology grade, Dukes stage, operative urgency, type of resection, and preoperative radiotherapy. When tested, the model was found to accurately predict lymph node harvest for group statistics (comparison of observed and model predicted lymph node harvest F(1,5154) = 0.63; P = 0.427). CONCLUSIONS: The results of the study suggest that the minimum number of lymph nodes harvested in colorectal cancer surgery cannot be set at a fixed value. The lymph node harvest model provides a simple tool to the frontline clinician for comparing standards between multidisciplinary bowel cancer teams.

Age Factors↗

Fitness for purpose evaluation in problem based learning should consider the requirements for establishing descriptive causation.

Debate continues about what existing evaluations of the impact of Problem Based Learning tell us and about how future evaluations should be designed. This paper argues that establishing descriptive causation should be an important goal of such evaluations. Minimizing threats to internal validity is of key importance to establishing descriptive causation. It is argued that whilst not a panacea randomized experiments offer particular advantages in this respect. This is illustrated through comparison of examples of evaluations of Problem Based Learning that have used different types of study design.

Health Personnel↗

Development of an instrument to assess and predict satisfaction and poor tolerance among patients undergoing endoscopic procedures.

We aimed to test the reliability of a developed questionnaire that measures and predict aversive endoscopic experience. Two questionnaires (pre- and postprocedure) were given to patients presenting for routine endoscopy. The first questionnaire elicited demographics, prior endoscopic experience, history of drug or alcohol use, patient expectations, and levels of anxiety and nervousness before procedure. After endoscopy, tolerance and willingness to repeat the examination were determined. The primary outcome of "adverse endoscopic experience" (AEE) was defined as a score of > or =5 on the postprocedure overall level of satisfaction or unwillingness to repeat endoscopy. Thirteen of 148 subjects reported an AEE. Items measuring the primary outcome were internally validated by reliability analysis which significantly correlated with measures of aversive experience like pain, nervousness, and suffering during the procedure. Preprocedure factors that were associated with AEE in the univariate analysis and multivariate analysis were nervousness (P = 0.02) and chronic use of psychotropic drugs or alcohol (P = 0.03). In conclusion, we have developed a questionnaire that reliably measures aversive endoscopic experience. Nervousness before procedure and chronic use of psychotropic drugs are reliable predictors of such experience.

Adult↗

Methods to account for attrition in longitudinal data: do they work? A simulation study.

Attrition threatens the internal validity of cohort studies. Epidemiologists use various imputation and weighting methods to limit bias due to attrition. However, the ability of these methods to correct for attrition bias has not been tested. We simulated a cohort of 300 subjects using 500 computer replications to determine whether regression imputation, individual weighting, or multiple imputation is useful to reduce attrition bias. We compared these results to a complete subject analysis. Our logistic regression model included a binary exposure and two confounders. We generated 10, 25, and 40% attrition through three missing data mechanisms: missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR), and used four covariance matrices to vary attrition. We compared true and estimated mean odds ratios (ORs), standard deviations (SDs), and coverage. With data MCAR and MAR for all attrition rates, the complete subject analysis produced results at least as valid as those from the imputation and weighting methods. With data MNAR, no method provided unbiased estimates of the OR at attrition rates of 25 or 40%. When observations are not MAR or MCAR, imputation and weighting methods may not effectively reduce attrition bias.

Bias↗

Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition.

We have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in Tripanozoma cruzi, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F--Snedecor and Wilk's lambda for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave--Group--Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol--water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.

Animals↗

Social participation and employment status after kidney transplantation: a systematic review.

OBJECTIVE: To summarize and assess literature regarding social participation of recipients after successful kidney transplantation. METHODS: A systematic review including a literature search in Medline (1980-2003) and five other databases, and assessment of methodological quality of selected studies by two reviewers applying a checklist of twelve criteria. RESULTS: Seventeen studies out of 1443 identified references were selected. Quality scores for internal validity ranged from 0% to 50% (median 20%). Employment was the most used indicator of social participation and two studies briefly reported on vacation and recreation. Employment rate ranged from 18% to 82%, however differences in defining categories of employment or lack of description were present. Study populations were heterogeneous with regard to demographic and clinical characteristics. Three studies identified pre-transplant employment status as predictor of post-transplant employment. Other potential risk factors were not consistent across studies. CONCLUSION: Measurement of social participation focuses mainly on employment status. Quality assessment revealed shortcomings in reporting and validity of studies, whereby valid conclusions regarding the degree of social participation after kidney transplantation cannot be drawn. Future research should supplement the focus on employment status by examining other aspects of social participation as well as potential risk factors.

Employment↗

The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors.

A recent large-scale, open-label, randomized, controlled trial in 11, 324 myocardial infarction (MI) survivors has shown low-dose fish oil, but not vitamin E, to reduce significantly the cumulative rate of all-cause death, nonfatal MI, and nonfatal stroke. Neither intervention significantly reduced the other primary endpoint, the cumulate rate of cardiovascular death, nonfatal MI, and nonfatal stroke. Analysis of secondary endpoints indicated that the benefits of the 875 mg fish oil capsules containing 850 to 882 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ethyl esters was in reducing mortality and not in a reduction of nonfatal MI. It was a safe intervention. The internal validity and external validity of the data was examined and the findings placed in clinical perspective. Important questions remain about the benefits of increased plant sources of n-3 polyunsaturated fatty acids (PUFA) for those who cannot obtain or consume fish. Also the benefits of diet versus fish oil supplementation haven't been determined precisely. Although it seems reasonable to increase sources of n-3 PUFA in the diet for those at high risk of coronary heart disease, current data do not support a policy of promoting fish oil capsules for secondary prevention of coronary heart disease.

Dietary Supplements↗

Echinococcosis and allergy.

The larval stages of Echinococcus granulosus and E. multilocularis are involved in parasitic diseases in humans: cystic echinococcosis (CE) ("hydatid disease") and alveolar echinococcosis (AE), respectively. Both diseases and parasites have tight links with allergy because of the immunological characteristics that contribute to maintain the larvae in their human host as well as their potential in inducing clinical anaphylactic reactions in some patients. Clinical observations in patients and data obtained from mass screenings in various countries have identified both forms of echinococcosis as "polar diseases," i.e., diseases where immunological background of the patients was related to the clinical presentation and course. In particular, abortive cases (i.e., spontaneous cures) have been found in many subjects in endemic areas. On the other hand, immune suppression was associated with severe disease. AE especially might be considered as an opportunistic infection. Experimental and clinical studies have shown that Th1-related immune response was associated with protection and Th2-related response was associated with parasite growth. Genetic characteristics of the host are related to both occurrence and severity of AE and are associated with the extent of IL-10 secretion, which is a major feature of chronic progressing echinococcosis. Anaphylactic reactions, including urticaria, edema, respiratory symptoms, and anaphylactic shock due to spontaneous or provoked rupture of the parasitic cyst, are well known in CE. Anaphylactic reactions in AE are far less frequent, and have been observed in rare cases at time of metastatic dissemination of the parasitic lesions. Echinococcus-specific IgE is present in most of the patients and associated with severity. Specific histamine release by circulating basophils stimulated with E. granulosus antigens is present in all patients with CE and AE. Echinococcus allergens include (1) AgB 12-kDa subunit, a protease inhibitor and a potent Th2 inducer; (2) Ag5, a serine protease; (3) EA 21, a specific cyclophilin, with a homology with other types of cyclophilins; (4) Eg EF-1 beta/delta an elongation factor, with a homology with Strongyloides stercoralis EF that shares the same IgE epitope. A clinical cross-reaction with Thiomucase, a mucopolysaccharidase used in arthritis treatment, has recently been published. However, despite the potential risk of allergic reactions, the dogma "never puncture a hydatid cyst" is no longer valid. International experience of therapeutic technique of "puncture, aspiration, injection, re-aspiration" of hydatid cysts developed at the beginning of the 1980s has proved to be successful in a variety of selected indications that have been reviewed by WHO recommendations. A better understanding of the immunological background of echinococcosis in humans has led to new therapeutic developments, such as immunomodulation using interferon alpha. Th2-driven immunological response and IL-10-related tolerance state are common characteristics of atopic allergy and echinococcosis. The example of echinococcosis stresses the ambiguous links that exist between parasitic and allergic diseases, and show the usefulness of comparing these diseases to better understand how immune deviation may lead to pathological events and to find new therapeutic and.or preventive agents.

Anaphylaxis↗

Comparison of risk factors for candidemia versus bacteremia in hospitalized patients.

BACKGROUND: Classic risk factors for candidemia include use of total parenteral nutrition (TPN), hospital location, use of central venous catheter, and others. Unfortunately, most of these variables are now also risk factors for antibiotic-resistant bacteria. Thus, use of these risk factors to identify patients at high risk for candidemia is difficult. The purpose of this study was to compare these classic risk factors for candidemia in patients with bloodstream infections to determine the relative strength of these predictors in differentiating patients with candidemia and bacteremia. METHODS: Clinical data were collected from the medical charts of patients who had been hospitalized between 2002 and 2004. Patients with their first episode of candidemia or bacteremia during their hospital stays were included. Risk factors were assessed using a multivariate logistic regression model and internally validated using a bootstrap analysis. A p-value < 0.05 was considered significant. RESULTS: A total of 164 patients (82 with candidemia) were evaluated. According to the logistic analysis, patients who had stayed in the intensive care unit (ICU) (OR = 6.24; 95% CI: 2.58-15.09) or had been using TPN (OR = 4.69; 95% CI: 1.76-12.48) were more likely to have candidemia than bacteremia. While patients with pulmonary (OR = 0.15; 95% CI: 0.055-0.39) or cardiac disease (OR = 0.21; 95% CI: 0.086-0.51) had a greater chance to have bacteremia than candidemia (p < 0.01 for all variables). These results were further validated using bootstrap analysis. CONCLUSION: Among classic risk factors for candidemia, the ICU location at the time of culture and TPN use were most predictive of candidemia while certain medical disorders predicted patients at the highest risk for bacteremia. These results can be used to help identify patients most likely to benefit from empiric antifungal therapy.

Adult↗

High sodium-low potassium environment and hypertension.

The high sodium-low potassium environment of civilized people, operating on a genetic substrate of susceptibility, is the cardinal factor in the genesis and perpetuation of "essential" hypertension. The noxious effects begin in childhood, when habits of excess salt consumption are acquired at the family table, and are perpetuated by continuing habit and by increasing use of convenience and snack foods with artificially high concentrations of sodium and low levels of potassium. Present methods of food preparation leach out the protective potassium. Extradietary sodium chloride is a condiment not a requirement. Some primitive populations clearly preferred potassium chloride to sodium chloride. Chronic expansion of extracellular fluid volume induced by excess salt consumption causes the central and peripheral circulatory regulatory mechanisms to work at cross purposes, resulting in increased arterial pressure. The protective effect of potassium is dramatic and easily demonstrable in animals and man but its mechanism is not known. It cannot be entirely a direct effect on blood pressure because rats protected with extra potassium against a moderately high salt intake live much longer than control rats but have the same elevated blood pressures. In hypertension with a demonstrable "cause," the high sodium-low potassium environment makes a bad matter worse. In nature, feral man and his forebears were not confronted with excessive sodium and deficient potassium; indeed, the reverse was the case. Evolution has provided powerful mechanisms for conserving sodium and eliminating potassium, but no efficient physiologic mechanisms for conserving potassium and eliminating excess sodium. Most laboratory animal "control" diets contain an amount of sodium that fully suppresses aldosterone secretion, and the same is true of the "average" diet of the American people. Inadequate attention to dietary sodium and potassium makes many studies in both animals and man of uncertain validity. Internally, essential hypertension is an exceedingly complex mosaic of physiologic interactions. Viewed from outside, it is a disorder for which genetic material sets the stage; excessive sodium precipitates it and perpetuates it. Extra salt makes all forms more rapidly progressive and accelerates the onset of terminal events; extra potassium is everywhere protective. When an entire population eats excessively of salt, hypertension will develop among those genetically susceptible, but epidemiologic studies of salt versus blood pressure will not show a relation of salt to hypertension. This is the saturation effect. Low sodium diets are therapeutically effective but generally regarded as an impossible or an unnecessary nuisance. Effective prevention programs must be instituted at as early an age as possible. The efficacy of a prophylactic/therapeutic low sodium-high potassium diet should be weighed against the uncertain hazards of a lifetime of pill taking.

Adolescent↗

A portable ergonomic observation method (PEO) for computerized on-line recording of postures and manual handling.

A new portable ergonomic observation method (PEO) is presented. It is applicable to most professions and work tasks and requires only moderate human resources for data collection and analysis. Observations are made in real time directly at the workplace using a portable personal or hand-held computer, and data are accessible for immediate analysis and presentation. Duration and number of events are calculated for postures at four body regions (arms, neck, trunk and knee) as well as for manual handling. An evaluation of the PEO method, assessing some important aspects of internal validity as well as intra- and inter-observer reliability, was carried out using video recordings. It showed acceptable validity for some types of physical exposure, and high intra- and inter-observer reliability. Practical experiences from using the PEO method in a field study and further improvements of the method are discussed.

Journal Article↗

The repeated pretest-posttest single-subject experiment: a new design for empirical clinical practice.

The logic of a new design for empirical clinical practice, the repeated pretest-posttest experiment, is described. This design is readily applicable by individual practitioners in the human services, possesses high internal validity, and presents minimal intrusiveness into the delivery of service. A single-case study is used to illustrate the application of the repeated pretest-posttest experiment in clinical research.

Adult↗

Assessment of change-agent expectations in reversal-to-baseline designs.

Questionnaires similar to those used in previous research to assess behavioral expectations produced by differing reversal-to-baseline rationales were presented to 160 male and female parents in rural South Dakota. Given two case histories, respondents were asked to predict, as simulated change agents, the frequency of problem behavior during reversal in an ABAB design intervention. The five rationales for reversal were: (a) withdrawal, (b) withdrawal and counter-expectancy, (c) problem switch and counter-expectancy, (d) fade and counter-expectancy and (e) inert treatment and counter-expectancy. While obtained means were close to those of a previous study, there were no significant sex or treatment effects. This fails to confirm the earlier results obtained from university undergraduates. Implications for internal validity of ABAB designs are discussed.

Adult↗

Use of a gamma-labeled bile acid (75SeHCAT) as a test of ileal function. Methods of improving accuracy.

The object of the present study was to improve the accuracy of measurements of ileal function obtained by abdominal scanning and fecal counting after oral administration of the gamma-labeled bile acid 75seleno-homocholic acid-taurine (75SeHCAT), as current techniques do not distinguish between retention of the bile acid within the enterohepatic circulation from retention within the colon, and are also affected by incomplete stool collection when using the fecal method. We have therefore introduced the following modifications: (a) simultaneous ingestion of 51CrCl3 as a nonabsorbable correction marker for both the abdominal scanning and fecal counting methods; and (b) the use of 75SeHCAT counts over the gallbladder area on abdominal scanning, because these counts should be independent of colonic retention. We have studied 42 subjects, including 6 healthy controls, 6 ileal resection subjects, 15 ulcerative colitis patients, and 15 patients with unresected ileal Crohn's disease. Colonic retention (0%-68% per day) caused a variable overestimate of 75SeHCAT absorption. Corrected measurements of the fecal absorption index determined by a gamma-counter and of the abdominal absorption coefficient determined by a gamma-camera correlated well with each other (r = 0.92, p less than 0.0001), providing an internal validation of the 51CrCl3 modification. The fecal absorption index could also be determined from the carmine-rich stool collection of a single day, and this also correlated well with the abdominal absorption coefficient (r = 0.81, p less than 0.0001). Gallbladder scanning alone was simpler, involving only one isotope, but it correlated less well with the fecal absorption index than did the abdominal absorption coefficient (r = -0.64, p less than 0.001).

Adult↗

Generalized oddity performance in preschool children: a bimodal training procedure.

Oddity performance requires relational discriminative responding, which typically is difficult to establish in children with MAs below five. In Experiment 1, a combination intrasubject reversal and multiple baseline across subjects design was used to establish the internal validity of a bimodal intervention in establishing generalized oddity performance. Six of seven children demonstrated oddity responding when presented with stimuli that instantiated the oddity relation in the visual and auditory modalities simultaneously. Oddity performance was evaluated with both reversal assessments and assessments with new sets of stimuli. The newly acquired oddity performance was durable; the six children continued to respond discriminatively when returned to a visual-only task on which they previously had been unsuccessful. Utilizing a reversal assessment more stringent than that of Experiment 1, Experiment 2 replicated this effect. The present studies are the first to demonstrate the utility of bimodal training in establishing oddity performance. The bimodal procedure is discussed with respect to the theoretical positions of Gibson, Dinsmoor, and Dixon.

Attention↗

Bluetongue: laboratory diagnosis.

Definitive diagnosis of bluetongue virus (BTV) infection, often subclinical in domestic and wild ruminant relies heavily on laboratory techniques for BTV isolation and demonstration of BTV antigens, viral nucleic acids and antibodies. The virus can be isolated from blood components, mainly the erythrocyte fraction, collected from affected animals during the period of febrile response. Semen collected from male animals at the peak of viremia and tissues from affected animals and fetuses may also be used for BTV isolation. The primary procedure for BTV isolation is inoculation of embryonated chicken eggs with a subpassage onto cell cultures (e.g. BKH-21, Vero cell lines). In addition to the conventional techniques such as fluorescent antibody staining and virus neutralization procedures for sero-grouping and serotyping of BTV isolates, immunohistochemical, immunoenzymatic and immunoelectron microscopic techniques, using monoclonal antibodies (MAb), offer more rapid, specific and sensitive approaches for BTV identification and antigen detection. The progress of molecular biology, especially the development of genetic probes for hybridization analysis and polymerase chain reaction techniques for detection of BTV nucleic acids hold the promise of most efficient diagnostic assays. Among the various serogroup-specific assays for antibody detection, the agar gel immunodiffusion (AGID) and competitive (C) ELISA are the most widely used tests. Because of its limitations (i.e. anticomplementary serum and complexity of the procedure) the complement fixation (CF) test is virtually abandoned and is used in only a few laboratories. Although the AGID test is simple to perform and rapid, it is not highly sensitive or quantitative and has limitations in its specificity. Sera containing antibodies to other group of Orbiviruses (e.g. epizootic hemorrhagic disease) may result in non-specific reaction in the AGID test. Among several ELISAs that have recently been developed, the C.ELISA in which a group-specific MAb to BTV is used, has proved to be the most sensitive and specific assay for detection of antibodies to BTV. Following extensive national and international validation, the C.ELISA is gradually replacing the AGID as a universal test to certify ruminants for trade purposes and to diagnose BT infection in domestic and wild animals. The cell culture-based microtiter serum neutralization (MTSN) is the most commonly used assay for the detection of serotype-specific antibodies to the recognized BTVs in animal sera. The MTSN may be used to type virus isolates and also to monitor animal population for specific serotypes of BTV in epidemiological investigations.

Animals↗