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Synchrotron radiation provides the necessary spatial and temporal resolution for non-invasive operando studies of dynamic processes under complex environmental conditions. Here a new environmental cell for simultaneous in situ dynamic X-ray imaging and measuring acoustic properties of geological samples is presented. The primary purpose of this cell is to study gas-hydrate formation in porous geo-materials and its influence on their acoustic properties. The cell is designed for cylindrical samples of 9 mm in diameter, confining and pore pressures up to 12 MPa, and temperatures from -20°C to room temperature. The cell is portable and can be easily assembled and operated at different X-ray sources. This cell enables a wide range of experiments studying physical/chemical processes in the Earth subsurface that change the mechanical properties of rocks (geochemical reactions, phase transitions, etc.).

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From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.

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Serial in vitro and in vivo tests for chloroquine sensitivity of Plasmodium falciparum were carried out from 1979 to 1982 in an area of E. Africa where chemosuppression with chloroquine had been attempted since 1977. Within 1(1/2) years there were signs of a decreasing drug response. Chloroquine resistance was first detected in 1981 and this increased markedly in 1982. Other contributory causes for the rise of parasite rates in children were possibly a decline in the efficiency of the drug distribution system and also immunological factors. Evidence of resistance to pyrimethamine was also found. Observations were made of the heterogeneity of the parasites' responses with emerging resistance. Implications for the future are discussed.

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Thirty-four males and 45 females who participated in household surveys 15 or 25 years earlier in rural Denmark were interviewed in 1982 about present and past food habits. Comparison of the information from the survey and the two interviews indicates that recall of past diet is strongly influenced by present dietary habits. As the relative classification of individuals according to their food habits appears to have changed little over time, information on current diet, perhaps supplemented by information on particular changes, can provide useful classification of individuals for epidemiologic purposes.

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Out of 72 Kaposi's sarcoma patients diagnosed between 1951 and March 1976 at Kuluva Hospital, West Nile District, Uganda, 64 with known co-ordinates were plotted on a map. Sixty-two of these were noted to live at an altitude of 853 metres or more (greater than or equal to 2,800 feet). Twenty-four patients were thought to be still alive and visits were made to their homes. Space-time grouping of four cases was noted on two occasions, although analysis did not reveal statistically significant clustering. A case-control study employing an interview questionnaire with 32 variables was performed on 19 patients and their age- and sex-matched neighbourhood controls, and sera were collected from both groups and from their families for estimation of viral antibody titres. The results demonstrated that cases tended to be post-pubertal males, a high proportion of whom had been bitten by a blood-sucking insect identified as being similar to Haematopota. Both cases and controls had raised antibody levels to cytomegalovirus, but cases obtained their drinking water more commonly from rivers whereas controls tended to use water from springs, boreholes or pipes.

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In an epidemiological survey in the West Nile District of Uganda, 70 pathologically confirmed BL cases were detected over a 5-yr period; this corresponded to an annual incidence rate of 1.6 per 100,000 general population or about 5 per 100,000 children in the age group 5-14 yr. Of the confirmed cases which were examined by EBV/DNA molecular hybridization, 96% were found to contain an average of 38 EBV genome equivalents per tumour cell, whereas none of the examined unconfirmed cases did. Duplicate hybridization assays in two laboratories were in close agreement. Serological testing showed that 91% of the confirmed BL cases had elevated EBV/VCA titres (greater than or equal to 160) and 64% were EA(D)-positive (greater than or equal to 10). Most of the cases with high EBV/genome content had high VCA titres, but there was a poor correlation between the two parameters among all cases. This study confirms that in high BL incidence areas the association between EBV and this lymphoma is almost constant, whereas it is exceptional in low-incidence areas. This further supports the aetiological implication of EBV in the endemicity of this tumor in equatorial Africa.

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A prospective epidemiological study was carried out in the West Nile District of Uganda from 1972 to 1979 in order to investigate the aetiological role of the Epstein-Barr virus (EBV) in Burkitt's lymphoma (BL). By 1976, fourteen BL cases had been detected among the 42,000 children originally bled in the study area. Testing of sera from BL candidates and neighbourhood controls showed that children who develop BL later have EBV/VCA titres several dilutions higher than their age- and sex-matched neighbours. This appearance of a strong EBV activity long before BL development was taken as evidence of a causal role of EBV in BL. In order to add to the unique material of pre-bled BL cases, BL detection was continued up to March 1979 when field work became impossible in Uganda. Two additional pre-bled BL cases were found during this extension of the study. The serological and virological evaluation of these additional cases showed that the EBV/VCA titres, but not the EA and EBNA titres, were about two dilutions higher in the BL candidates than in the controls. Hybridization assays showed that both lymphomas contained EBV/DNA in the tumour cells. These additional results thus confirm the findings in the first 14 cases and strengthen the epidemiological evidence for a causal role of the EBV in endemic BL.

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White atrophy (atrophie blanche) in the medial ankle region due to chronic venous insufficiency (stasis syndrome) was studied in 12 patients by fluorescence video microscopy [1,8]. After intravenous bolus injection of 1 ml of 20% Na-fluorescein the dynamic phenomena of transcapillary and interstitial diffusion of the dye were analyzed by a videodensitometer which has moved on single frames of the TV-recordings across white atrophy at different times after dye appearance. White atrophy is characterized by 3 main areas: 1) the avascular field sensu strictu, 2) the border region with enlarged and tortuous capillary loops, and 3) the more remote capillaries showing less altered morphology. The dye reached the ankle skin after 39.2 +/- 13.3 S and leaved rapidly the intravascular compartment. In the region of the border capillaries, the maximal fluorescent light intensity was reached after 5 min, in the centre of the avascular field only after 40 min. Initially, the densitometer curves show a 'valley' which is slowly filled up by the dye. At 40 min and later on the highest light intensities were measured in the central parts of the avascular field ('mountain'), where the clearance was just beginning. The slow diffusion of the small tracer into the avascular field explains that white atrophy is a predilection site for venous ulcer formation.

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Burkitt's lymphomas (BL) is frequent in the tropical lowland of Africa but rare--even in the tropics--at altitudes higher than 5,000 feet above sea level. Serological surveys were carried out in Uganda and Tanzania to see whether the variation in BL incidence from high to low areas is paralleled by a variation in the extent of infection with the putative Epstein-Barr virus. Sera were collected from samples of the general child population living at high and low altitudes in the West Nile District in Uganda and in North Mara, Tanzania. All sera from these surveys were tested for anti-EBV antibodies to Viral Capsid Antigens (VCA) and to Early Antigens (EA) at the International Agency for Research on Cancer in Lyon, France. The results showed that both the prevalence and the strength of positive EBV (VCA and EA) titres are nearly similar in the lowlands and on the high plateux in East Africa. This lack of association between BL incidence and extent of EBV infection fails to support the notion of a causal role between the virus and the tumor, but does not totally exclude this possibility since some other environmental factor which is essential for BL development, may have a geographical distribution that parallels that of BL.

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Forty cases of Burkitts' lymphoma (BL) in North Mara, Tanzania, with onset between 1971 and 1977, were analysed for evidence of space-time clustering. Previous analyses in East Africa had produced conflicting results. The Knox method used in those analyses dichotomizes the space and time scales and does not take into account the degree of closeness. The Mantel method, a generalization of Knox's, does permit closeness between pairs of cases to enter into computations. To see whether this method could clarify matters, previously reported data sets from West Nile, Uganda and North Mara were reanalysed. Unexplained differences were found between West Nile and North Mara with respect to age, sex and temporal distributions of BL, and between the eastern and western parts of North Mara with respect to incidence. In West Nile between 1961 and 1965, there was clustering. All of the Mantel analyses and a few of the Knox analyses were highly significant (p less than 0.0025). Since 1966, evidence of clustering is weak. In North Mara, there was no statistical evidence of space-time clustering between 1971 and 1977, as there was none between 1964 and 1970. The conflicting results in East Africa are compatible with a model involving several factors which "move about", or with a single factor which is sporadic in some areas but constant in others. Alternatively, artifactual biases or coincidence may have created or wiped out the appearance of clustering. Results of space-time clustering analyses permit little discrimination between infectious and non-infectious etiologic hypotheses. Either one type or both may be operating.

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Sera collected from Burkitt's lymphoma (BL) patients before and after tumor manifestation were tested for antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), measles virus (MV) and adenovirus type 5, using the immunofluorescent (IF) techniques in all instances except for MV where complement fixation (CF) was used. It was found that none of these viruses showed higher antibody levels in BL patients than in controls, either before or after the appearance of the tumor. The patients came from the West Nile District of Uganda.

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Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.

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Epidemiological data relating to all 202 patients diagnosed with Burkitt's Lymphoma (BL) in the West Nile District of Uganda in the period 1961 to 1975 have been reviewed and analysed. Statistically significant evidence of space-time clustering of cases, first reported for the period 1961-65, was also present during 1972-73, but not during other periods. The patients involved in such clusters were found to be older than other patients (P less than 0.001). The average annual incidence of BL in the District was 2.45 x 10(-5) and overall there was no change in the incidence during the study period. However, there were statistically significant changes in incidence in different counties, which could not be explained as case-ascertainment artifacts. One sib pair of patients with BL was found and the series also included 7 instances of BL in two cousins. It is suggested that study of variation in the intensity and type of malarial infestation in different areas at different times may help explain the epidemiological findings and suggest what, if any, aspects of this infection are critical for inducing BL.

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A case-control study was undertaken of Cantonese NPC patients hospitalized in the Queen Elizabeth Hospital, Hong Kong. One age- and sex-matched control was selected for each NPC case from hospitalized patients with cancers other than NPC. A total of 150 NPC patients and 150 controls were interviewed in order to compare the two groups with respect to socio-economic status, dietary habits and health status. In addition to the individual patients and controls, healthy members of their respective households were also interviewed, in order to obtain information not influenced by the experience of having cancer. Weaning habits were compared in the households of NPC patients and those of controls by asking women who had ever breast fed a child about food supplements they had given to the baby during, and immediately after, weaning. The following factors were found to be positively associated with NPC: (1) belonging to the four lowest occupational classes; (2) practicing Buddhism or ancestor worship and having religious altars in the house; and (3) having a history of previous illnesses of the ear or nose after the age of 15 years. The following factors were found to be negatively associated with NPC: (1) eating of bread; (2) eating of tinned food; and (3) use of spices. The study of weaning habits disclosed that salted fish was given to babies just after weaning more often in households with an NPC case than in control households. A multivariate analysis showed that traditional lifestyle and the consumption of salted fish during weaning are independent risk factors for NPC. This analysis also revealed that two or three of the many expressions of a traditional lifestyle included in the study could account for the total increase in NPC risk associated with this way of life, although it is quite possible that other, as yet unidentified, factors are just as important.

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The prospective study carried out by the International Agency for Research on Cancer on the relationships between E.B.V. infection and Burkitt's Lymphoma development as well as their partial malaria chemoprophylaxy proposals, are discussed as an example of studying the role of a virus and of co-factors in one human cancer.

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