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Aims We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. Methods and results Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136). Conclusion Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.

- Label: BACKGROUND NlmCategory: BACKGROUND content: "Sub-Saharan Africa and south Asia contributed 81% of 5\xC2\xB79 million under-5 deaths and 77% of 2\xC2\xB76 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts." - Label: METHODS NlmCategory: METHODS content: "The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhi\xC3\xA7a, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths." - Label: FINDINGS NlmCategory: RESULTS content: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. - Label: INTERPRETATION NlmCategory: CONCLUSIONS content: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. - Label: FUNDING NlmCategory: BACKGROUND content: Bill & Melinda Gates Foundation.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths. Funding Information: This study was supported by the Bill & Melinda Gates Foundation (grant number INV-016202). There was also partial support from the Department of Science and Technology and National Research Foundation: South African Research Chair Initiative in Vaccine Preventable Diseases; and the South African Medical Research Council. Declaration of Interests: All other authors have nothing to disclose. Ethics Approval Statement: The study was approved by the Human Research Ethics Committee at the University of the Witwatersrand (HREC approval number: M200313). Informed consent was obtained from relatives of the deceased.

Background Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. Methods This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12–15 medical specialists. Results We enrolled 153 neonatal deaths, 106 aged 3–28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause. Conclusions MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths., Minimally invasive tissue sampling and clinical history were utilized to attribute cause of death in South African neonates. Leading underlying causes of death were prematurity, complications of intrapartum events, and congenital malformations. The leading immediate cause of death was infection.

Background Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. Methods This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization’s International Classification of Diseases, Tenth Revision application to perinatal deaths. Results A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). Conclusions In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause., Minimally invasive tissue sampling, placental examination, and clinical history were utilized to attribute cause of death in South African stillbirths. The leading underlying maternal causes included hypertensive disorders, hemorrhage, and chorioamnionitis, and immediate fetal causes were antepartum hypoxia and infection.

Background: There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies. Methods and Results: We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased NPPA expression levels (21.6-fold, P =0.004), decreased transcripts of genes important in cell survival, and enrichment of extracellular matrix genes. Decompensated CPMR was associated with downregulation of SERCA2 (0.77-fold, P =0.009) and mitochondrial gene expression levels and upregulation of genes related to inflammation, the extracellular matrix, and apoptosis, which were refractory to carvedilol therapy. Conclusions: Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.

The ability of carotid intima–media thickness (IMT) to predict risk beyond plaque is controversial. In 952 participants (critical limb ischemia [CLI] or stroke, n = 473; community, n = 479), we assessed whether relationships with events for IMT complement the impact of plaque in young patients depending on the extent of thrombotic versus atherosclerotic disease. The extent of atherosclerotic versus thrombotic occlusion was determined in 54 patients with CLI requiring amputations. Thrombotic occlusion in CLI was associated with younger age ( P < .0001) and less plaque ( P = .02). Independent relations between plaque and CLI were noted in older (>50 years; P < .005 to .38) participants, while independent relations between plaque and stroke ( P < .005 to

Background. Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004. Objectives. To describe the outcomes of the adult liver transplant programme at WDGMC. Methods. This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) ( N =275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality. Results. A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8 hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection. Conclusions. This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.

This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.

Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.

BACKGROUND Invasive cervical carcinoma (ICC) accounts for 23% of all cancer-related deaths in Zimbabwean women. Trials for a national program of genotype-specific human papillomavirus (HPV) vaccines are underway to prevent cervical carcinoma, but the distribution of HPV types among women with ICC according to HIV status is unknown. METHODS To determine prevalence and distribution of high-risk HPV genotypes by HIV status in women with ICC, we performed a cross-sectional study on women referred for ICC testing at 4 urban referral hospitals in Zimbabwe from June 2014 to December 2015. Cervical biopsies were obtained for histology and HPV genotyping. HIV serology testing was performed. HPV testing was performed using MY09/MY11 polymerase chain reaction followed by typing using dot-blot hybridization. RESULTS Of 107 participants with histologically proven ICC, HIV prevalence was 49.5% (53/107). HIV-positive women tended to be younger (median age 44 years) than HIV-negative women (median age 59 years). HPV prevalence was 94% (101/107), ranging from 1 to 5 genotypes per participant. HPV 16 (81.5%), 18 (24%), 33 (13%), 35 (11%), 56 (9%), and 45 (7.4%) were the most prevalent genotypes among HIV-negative participants; HPV 16 (67.9%), 18 (43.4%), 56 (18.9%), 45 (15.1%), 33 (11.3%), and 58 (9.4%) were the most prevalent among HIV-positive participants. Eighty-three percent of women were infected with either HPV-16 or HPV-18. CONCLUSIONS Effective vaccination programs against HPV 16 and HPV 18 could prevent up to 83% of cases of cervical cancer in Zimbabwe. HIV may influence distribution of some HPV genotypes given the significant increase in prevalence of HPV 18 among HIV-positive participants.

Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV.

Background: Invasive cervical carcinoma (ICC) accounts for 23% of all cancer-related deaths in Zimbabwean women. Trials for a national program of genotype-specific HPV vaccines are underway to prevent cervical carcinoma, but the distribution of HPV types among women with ICC according to HIV status is unknown.Methods: To determine prevalence and distribution of high-risk HPV genotypes by HIV status in women with ICC, we performed a cross-sectional study on women referred for ICC testing at four urban referral hospitals in Zimbabwe from June 2014-December 2015. Cervical biopsies were obtained for histology and HPV genotyping. HIV serology testing was performed. HPV testing was performed using MY09/MY11 PCR followed by typing using dot blot hybridization.Results: Of 107 participants with histologically-proven, HIV prevalence was 49.5% (53/107). HIV-positive women tended to be younger (median age 44 years) than HIV-negative women (median age 59 years). HPV prevalence was 94% (101/107), ranging from 1-5 genotypes per participant. HPV 16 (81.5%), 18 (24%), 33 (13%), 35 (11%), 56 (9%) and 45(7.4%) were the most prevalent genotypes amongst HIV-negative participants; HPV 16 (67.9%), 18 (43.4%), 56 (18.9%), 45 (15.1%), 33 (11.3%), and 58 (9.4%) were most prevalent amongst HIV-positive participants. 83% of women were infected with either HPV-16 or HPV-18.Conclusion: Effective vaccination programs against HPV 16 and 18 could prevent up to 83% of cases of cervical cancer in Zimbabwe. HIV may influence distribution of some HPV genotypes given the significant increase in prevalence of HPV 18 amongst HIV positive participants.

Background. Pleural effusions are a common reason for presentation to healthcare facilities. Blind closed pleural biopsy can be a useful tool to diagnose their cause, especially in resource-limited settings. Objectives. To determine the aetiology, frequency and change in profile of histopathological diagnoses made at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over the period 1 January 2001 - 31 December 2015. Methods. Pleural biopsies performed at CHBAH and analysed by histopathologists from the National Health Laboratory Service at the hospital over the study period were retrospectively reviewed by accessing reports from two databases (DISA and TrakCare). The subjects’ ages, genders, HIV status and histopathological diagnoses as well as adenosine deaminase and Ziehl-Neelsen results were recorded. Results. A total of 1 013 samples were included in the study, with 780 considered adequate for assessment. The most common diagnosis was granulomatous inflammation (48.1%, n =375), with the most common type being necrotising granulomatous inflammation (73.6%, n =276). Ten percent of biopsies ( n =78) showed malignancy, most commonly adenocarcinoma, with 46.2% ( n =36) metastatic and 23.1% ( n =18) primary lung adenocarcinoma. The odds of being diagnosed with malignancy showed increasing statistical significance above the age of 40 years: 40 - 49 years odds ratio (OR) 8.7, 95% confidence interval (CI) 1.1 - 66.9 ( p =0.038); 50 - 59 years OR 12.4, 95% CI 1.6 - 95.0 ( p =0.015); ≥60 years OR 23.0, 95% CI 3.1 - 171.3 ( p =0.002). HIV seropositivity was associated with lower odds of being diagnosed with malignancy compared with HIV-negative patients (OR 0.5, 95% CI 0.2 - 0.9; p =0.040), with greater odds of a ‘non-cancer’ diagnosis in HIV-positive patients (including granulomatous inflammation and pleuritis (OR 2.16, 95% CI 1.03 - 4.51; p =0.040)). Conclusions. Blind closed pleural biopsy has a role to play in the diagnosis of exudative pleural effusions in resource-limited settings, particularly for patients suspected to have tuberculosis (TB) or malignancy. TB remains a common cause of exudative pleural effusions. Patients aged >40 years presenting with an exudative pleural effusion should routinely have pleural biopsy performed. However, this study showed a high frequency of inadequate specimens from closed pleural biopsy. Training in the performance of this procedure to increase diagnostic rates is recommended.

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

The effect of the evolving HIV epidemic on cancer has been sparsely documented in Africa. We report results on the risk of cancer associated with HIV-1 infection using data from an ongoing study. A case-control analysis was used to estimate the relative risk (odds ratio, OR) of cancer types known to be AIDS defining: Kaposi's sarcoma (n = 333), non-Hodgkin lymphoma (NHL, n = 223) and cancers of the cervix (n = 1,586), and 11 cancer types possibly associated with HIV infection: Hodgkin lymphoma (n = 154), cancers of other anogenital organs (n = 157), squamous cell cancer of the skin (SCC, n = 70), oral cavity and pharynx (n = 319), liver (n = 83), stomach (n = 142), leukemia (n = 323), melanoma (n = 53), sarcomas other than Kaposi's (n = 93), myeloma (n = 189) and lung cancer (n = 363). The comparison group comprised 3,717 subjects with all other cancer types and 682 subjects with vascular disease. ORs were adjusted for age, sex (except cervical cancer), year of diagnosis, education and number of sexual partners. Significantly increased risks associated with HIV-1 infection were found for HIV/AIDS associated Kaposi's sarcoma (OR = 47.1, 95% CI = 31.9-69.8), NHL (OR = 5.9, 95% CI = 4.3-8.1) and cancer of the cervix (OR = 1.6, 95% CI = 1.3-2.0); Hodgkin's disease (OR = 1.6, 95% CI = 1.0-2.7), cancers of anogenital organs other than the cervix (OR = 2.2; 95% CI = 1.4-3.3) and SCC (OR = 2.6, 95% CI = 1.4-4.9) were also significantly increased. No significant associations were found between HIV and any of the other cancers examined. Risks for HIV-related cancers are consistent with previous studies in Africa, and are lower when compared to those observed in developed countries.

Airborne hyperspectral imagery was used to study the distribution of white mica minerals in Archean (3.2 Ga) submarine hydrothermal systems associated with volcanogenic massive sulfide mineralization in a well-exposed volcanic sequence of the Soansville greenstone belt in the Pilbara, Western Australia. White mica mineral abundance and distribution maps were compared with published hydrothermal alteration maps and differences were interpreted using whole-rock geochemistry and temperature estimates from oxygen isotope geothermometric studies of hydrothermally altered rocks. Three different zones were identified from the hyperspectral imagery: 1) Al-rich white mica zones in the upper parts of the volcanic sequence which are related to recharge of unevolved seawater, 2) Al-poor white mica zones at middle and upper levels of the volcanic sequence predominantly related to K alteration by more-evolved hydrothermal fluids, and 3) high to intermediate Al-content white mica zones in lower levels of the sequence and in cross-cutting zones related to intense alteration by laterally flowing and upwelling evolved fluids. The integrated study of the spatial distribution of hyperspectrally detected white mica minerals together with published maps and rock analyses allowed characterization of the hydrothermal systems and reconstruction of paleo fluid pathways.

During the 1970s and 1980s, the Applied Geochemistry Research Group, Imperial College of Science and Technology, London, investigated gas geochemistry for mineral exploration in regions of exotic overburden. Mercury vapour anomalies were determined over structurally controlled mineralization in arid terrain but the necessity of adequate trace levels of mercury in the mineralization at depth to provide detectable signals in the vapour phase near surface was recognized as a limitation. Anomalous soil air disequilibria of oxygen and carbon dioxide were found above the suboutcrop of several types of oxidizing sulphide mineralization: oxygen in soil air is depleted due to oxygen consumption by sulphide oxidation reactions; these produce sulphur dioxide which, as sulphuric acid, reacts with any carbonates associated with the mineralization to generate, and increase the soil air content of, carbon dioxide. Carbonyl sulphide, one of the sparingly soluble metastable gases produced in trace quantities by sulphide oxidation, was found adsorbed on soil particles over concealed sulphide mineralization; conspicuously strong anomalies were found in glacial clay overlying fault-hosted mineralization, consistent with a numerical model of gas migration in complex media. Although, in the subsequent two decades, models and methods for geochemical exploration in regions of exotic overburden have increasingly focused on metal ion transport from depth to surface, a steady flow of reports of research into, and successful applications of, mercury, oxygen, carbon dioxide and metastable trace gases generated by sulphide oxidation continues.

In the southwestern part of the Ashanti Belt, the results of fractal and Fry analyses of the spatial pattern of 51 known mines/prospects of (mostly lode) gold deposits and the results of analysis of their spatial associations with faults and fault intersections suggest different predominant structural controls on lode gold mineralisation at local and district scales. Intersections of NNE- and NW-trending faults were likely predominantly involved in local-scale structural controls on lode gold mineralisation, whilst NNE-trending faults were likely predominantly involved in district-scale structural controls on lode gold mineralisation. The results of the spatial analyses facilitate the conceptualisation and selection of spatial evidence layers for lode gold prospectivity mapping in the study area. The applications of the derived map of lode gold prospectivity and a map of radial density of spatially coherent lode gold mines/prospects results in a one-level prediction of 37 undiscovered lode gold prospects. The applications of quantified radial density fractal dimensions of the spatial pattern of spatially coherent lode gold mines/prospects result in an estimate of 40 undiscovered lode gold prospects. The study concludes finally that analysis of the spatial pattern of discovered mineral deposits is the key to a strong link between mineral prospectivity mapping and assessment of undiscovered mineral deposits.

Data-driven prospectivity mapping can be undermined by dissimilarity in multivariate spatial data signatures of deposit-type locations. Most cases of data-driven prospectivity mapping, however, make use of training sets of randomly selected deposit-type locations with the implicit assumption that they are coherent (i.e., with similar multivariate spatial data signatures). This study shows that the quality of data-driven prospectivity mapping can be improved by using a training set of coherent deposit-type locations. Analysis and selection of coherent deposit-type locations was performed via logistic regression, by using multiple sets of deposit occurrence favourability scores of univariate geoscience spatial data as independent variables and binary deposit occurrence scores as dependent variable. The set of coherent deposit-type locations and three sets of randomly selected deposit-type locations were each used in data-driven prospectivity mapping via application of evidential belief functions. The prospectivity map based on the training set of coherent deposit-type locations resulted in lower uncertainty, better goodness-of-fit to the training set, and better predictive capacity against a cross-validation set of economic deposits of the type sought. This study shows that explicit selection of training set of coherent deposit-type locations should be applied in data-driven prospectivity mapping.

This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone (OROS) hydromorphone, Janssen-Cilag, Beerse, Belgium) and twice-daily extended-release (ER) oxycodone in patients with chronic, moderate to severe osteoarthritis (OA) pain. OROS hydromorphone is currently available only in Europe.Adults who met American College of Rheumatology clinical criteria for OA of the knee or hip with moderate to severe mean daily pain intensity despite chronic use of stable doses of NSAIDs or other nonsteroidal, nonopioid therapies were eligible for participation in this randomized, open-label study. The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase. OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID, respectively. Patients maintained diaries in which they rated their pain (from 0 = none to 3 = severe) and pain relief (from 0 = no relief to 4 = complete relief). Other assessments completed every 14 days included patient and investigator global evaluations of treatment effectiveness (scale from 1 = poor to 5 = excellent), the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, and the Medical Outcomes Study (MOS) Sleep Scale. Adverse events (whether observed by study personnel, identified in response to questioning, or spontaneously reported) and vital signs were monitored throughout the study. The primary efficacy measures were the mean pain relief score at end point and the time from initiation of treatment to the third day of moderate to complete pain relief, as reported in the patient diary. Noninferiority analyses were conducted on all primary and secondary efficacy variables.One hundred thirty-eight patients (71 OROS hydromorphone, 67 ER oxycodone) received treatment (safety population), and 83 (60.1%) completed the study. Data from 124 patients were included in the efficacy analyses; the majority of these patients were white (85.5%) and female (69.4%), with a mean age of 63.6 years. The most commonly affected joint was the knee (79.8 %). At end point, the OROS hydromorphone group had a mean pain relief score of 2.3 (median, 2.0) and the ER oxycodone group had a mean pain relief score of 2.3 (median, 2.3) (95% CI, -0.30 to infinity). The mean time to the third day of moderate to complete pain relief was 6.2 days (median, 4.0) in the OROS hydromorphone group and 5.5 days (median, 5.0) in the ER oxycodone group (95% CI, -0.31 to infinity). Mean pain intensity decreased from baseline to end point by 0.6 point in the OROS hydromorphone group and by 0.4 point in the ER oxycodone group. Mean scores on the patient global evaluation improved by a respective 1.2 and 1.0 points (median, 1 in both groups). Approximately two thirds of patients in each group (67.2% and 66.7%) rated the overall effectiveness of treatment as good to excellent at end point. There were no statistically significant differences between groups in total WOMAC scores at end point, and similar improvements from baseline in the WOMAC physical function, stiffness, and pain scales were observed in both groups. Whereas MOS sleep outcomes scores improved from baseline in both groups, OROS hydromorphone was associated with a significantly greater improvement on the MOS Sleep Problems Index I compared with ER oxycodone (P0.045). Adverse events were comparable in both groups; the most frequently reported adverse events were nausea (35.2% and 29.9%), constipation (29.6% and 25.4%), somnolence (25.4% and 17.9%), vomiting (16.9% and 11.9%), and dizziness (14.1% and 22.4%). Adverse events led to study discontinuation in 35.2% (25/71) of patients in the OROS hydromorphone group and 32.8% (22/67) in the ER oxycodone group. Discontinuations due to adverse events during the titration phase were numerically greater in the OROS hydromorphone group (29.6% [21/71]) than in the ER oxycodone group (19.4% [13/67]). Only 1 serious adverse event (diarrhea in a patient receiving OROS hydromorphone) was considered possibly related to study drug.Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip. The tolerability profiles of the 2 agents were similar.

Background. Before the 1930s, squamous cell carcinoma (SCC) of the oesophagus was almost unknown among black South Africans. From the 1930s the annual frequency rose. A dietary cause was sought, the staple diet of black people having changed from sorghum to maize (corn), with traditional beer being brewed from maize. Carcinogenic N-nitrosamines in traditional beer were suggested as a cause of SCC of the oesophagus, with Fusarium moniliforme , a corn saprophyte, thought to play a role. Objectives. To confirm the presence of N-nitrosamines in traditional beer and demonstrate a mechanism for the oncogenesis of oesophageal carcinoma. Methods. Analysis by high-performance liquid chromatography was conducted for the identification of nitrosamines in traditional beer samples, and molecular docking studies were employed to predict the affinity between N-nitrosamines and the S100A2 protein. Results. Carcinogenic N-nitrosamines were identified in all six samples of traditional beer examined ( N =18 analyses), and docking studies confirmed a high affinity of the nitrosamine N-nitrosopyrrolidone with the S100A2 protein. This may result in the altered expression of the S100A2 protein, leading to tumour progression and prognosis. Conclusion. It is suggested that carcinogenic N-nitrosamines in traditional beer are a major factor in the causation of SCC of the oesophagus in black South Africans. N-nitrosamines have been shown to produce cancer experimentally, but there has not been conclusive epidemiological evidence that N-nitrosamines are carcinogenic to humans. This study is the first to demonstrate the potential link between N-nitrosamines and a human tumour.

Buruli ulcer (BU), a skin ulceration caused by Mycobacterium ulcerans (MU), is the second most widespread mycobacterium infection in Ghana. Its infection pathway is possibly related to the potable and agricultural water supply. This study aims to identify environmental factors that influence infection in a part of Ghana. It examines the significance of contaminated surface drainage channels and groundwater using conditional autoregressive (CAR) statistical modelling. This type of modelling implies that the spatial pattern of BU incidence in one community depends on the influence of the environment in neighbouring communities. Covariates were included to assess the spatial relationship between environmental risk factors and BU incidence in the study area. The study reveals an association between (a) the mean As content of soil and spatial distribution of BU and (b) the distance to sites of gold mining and spatial distribution of BU. We conclude that both arsenic in the natural environment and gold mining influence BU infection.

This paper describes a hybrid fuzzy weights-of-evidence (WofE) model for mineral potential mapping that generates fuzzy predictor patterns based on (a) knowledge-based fuzzy membership values and (b) data-based conditional probabilities. The fuzzy membership values are calculated using a knowledge-driven logistic membership function, which provides a framework for treating systemic uncertainty and also facilitates the use of multiclass predictor maps in the modeling procedure. The fuzzy predictor patterns are combined using Bayes’ rule in a log-linear form (under an assumption of conditional independence) to update the prior probability of target deposit-type occurrence in every unique combination of predictor patterns. The hybrid fuzzy WofE model is applied to a regional-scale mapping of base-metal deposit potential in the south-central part of the Aravalli metallogenic province (western India). The output map of fuzzy posterior probabilities of base-metal deposit occurrence is classified subsequently to delineate zones with high-favorability, moderate favorability, and low-favorability for occurrence of base-metal deposits. An analysis of the favorability map indicates (a) significant improvement of probability of base-metal deposit occurrence in the high-favorability and moderate-favorability zones and (b) significant deterioration of probability of base-metal deposit occurrence in the low-favorability zones. The results demonstrate usefulness of the hybrid fuzzy WofE model in representation and in integration of evidential features to map relative potential for mineral deposit occurrence.

Analysis and synthesis of multi-disciplinary geoscience information from geological literature/maps and from digitally-processed aeromagnetic and gravity data pertinent to the Aravalli province were carried out to address some hitherto unresolved questions about the tectonostratigraphy of this Archaean–Proterozoic metallogenic province. Based on the magnetic anomalies, several tectonic domains were identified. These domains, bounded by regional-scale geophysical lineaments, have distinct crustal, lithological, metamorphic, and metallogenic characteristics and correlate broadly with lithostratigraphic belts identified by several earlier workers. New interpretations on the tectonostratigraphy and the base-metal mineralization controls in the Aravalli province are as follows. The Hindoli sequences, in the eastern parts of the province, constitute an independent Palaeo–Proterozoic tectonic domain and do not form part of the Archaean basement complex. The base-metal-bearing metasedimentary enclaves in the central parts of the province also constitute an independent Palaeo–Proterozoic tectonic domain, which is quite distinct from the surrounding (basement complex?) rocks. The base-metal-bearing metavolcano-sedimentary sequences in the western parts of the province constitute an independent Neo–Proterozoic tectonic domain. The base-metal deposits in the province are spatially associated with the regional-scale lineaments and with the mafic metavolcanic rocks deduced from the aeromagnetic data. The regional-scale lineaments, which possibly represent Proterozoic crustal-scale faults, are plausible structural controls on the base-metal mineralization in the province. The mafic metavolcanic rocks are plausible heat-source controls on the SEDEX- and/or VMS-type base-metal mineralizations and are possible metal-source controls on the VMS-type base-metal mineralization in the province.

This paper hypothesizes that arsenic in drinking water indirectly contributes to Buruli ulcer (BU), a skin disease caused by Mycobacterium ulcerans (MU) infection. Samples of groundwater and surface water used as drinking water by the population in Ghana's Amansie West district (part of which has a high prevalence of BU), were collected near rural settlements and analysed for arsenic. Arsenic concentration levels per settlement were compared with BU prevalence. A positive exposure-response relationship was obtained between arsenic in surface water and BU (r2 = 0.82). However, there is no significant exposure-response relation between groundwater and BU.

We present a new method to detect and reconstruct fluid pathways in fossil hydrothermal systems that is based on systematic study of white micas in hydrothermally altered rock, using near-infrared spectroscopy. This method, developed in an Early Archean volcanic sequence in the Panorama district in Western Australia, uses new near-infrared spectroscopic data and published geological and geochemical data of fossil submarine hydrothermal systems in the area. Analysis of new near-infrared spectroscopic data revealed that the abundance of white mica and its Al content in altered volcanic rock vary systematically along fossil fluid pathways, from zones of low-temperature recharge to zones of high-temperature discharge, as a function of hydrothermal fluid chemistry, temperature of alteration, coexisting minerals, and composition of volcanic host rock. The abundance of white mica relative to that of chlorite and the Al content of white micas can be used to discriminate among the hydrothermal alteration facies along these fluid pathways, which permits detection and reconstruction of fossil fluid pathways.

Arsenic occurs naturally in the earth's crust and is widely distributed in the environment. Natural mineralization and activities of microorganisms enhance arsenic mobilization in the environment but human intervention has exacerbated arsenic contamination. Although arsenic is useful for industrial, agricultural, medicinal and other purposes, it exerts a toxic effect in a variety of organisms, including humans. Arsenic exposure may not only affect and disable organs of the body, especially the skin, but may also interfere with the proper functioning of the immune system. This paper, therefore, generally highlights the toxic effects of arsenic as well as its mobilization in the natural environment and possible controls. It also briefly attempts to outline the impact of arsenic on the immune system, whose alteration could lead to viral/bacterial infections. Keywords: Arsenic, Immune system, Anthropogenic, Microorganisms, Season

A GIS-based hybrid neuro-fuzzy approach to mineral potential mapping implements a Takagi–Sugeno type fuzzy inference system in a four-layered feed-forward adaptive neural network. In this approach, each unique combination of predictor patterns is considered a feature vector whose components are derived by knowledge-based ordinal encoding of the constituent predictor patterns. A subset of feature vectors with a known output target vector (i.e., unique conditions known to be associated with either a mineralized or a barren location), extracted from a set of all feature vectors, is used for the training of an adaptive neuro-fuzzy inference system. Training involves iterative adjustment of parameters of the adaptive neuro-fuzzy inference system using a hybrid learning procedure for mapping each training vector to its output target vector with minimum sum of squared error. The trained adaptive neuro-fuzzy inference system is used to process all feature vectors. The output for each feature vector is a value that indicates the extent to which a feature vector belongs to the mineralized class or the barren class. These values are used to generate a favorability map. The procedure is applied to regional-scale base metal potential mapping in a study area located in the Aravalli metallogenic province (western India). The adaptive neuro-fuzzy inference system demarcates high favorability zones occupying 9.75% of the study area and identifies 96% of the known base metal deposits. This result is significant both in terms of reduction in search area and the percentage of deposits identified.

To provide guides for exploration of porphyry copper mineralization at a district scale, we examine the spatial association between known porphyry copper deposits and geologic features in Benguet, Philippines. The spatial associations between the porphyry copper deposits and strike-slip fault discontinuities, batholithic pluton margins and porphyry plutons are quantified using weights of evidence modeling. In the training and testing district, the porphyry copper occurrences are associated spatially with strike-slip fault discontinuities, batholithic pluton margins and contacts of porphyry plutons within distances of 3 km, 2.25 km, and 1 km, respectively. In addition, the porphyry plutons are associated spatially with strike-slip fault discontinuities and contacts of batholithic plutons within a distance of 2.25 km and 3 km, respectively. Based on these significant spatial associations, predictive maps are generated to delineate zones favorable for porphyry copper mineralization and zones favorable for emplacement of porphyry plutons in Benguet province, Philippines. Validations of the predictive models demonstrate their efficacy in pointing to zones for subsequent follow-up exploration work.

The authors used data collected from 1995 to 1999, from an on-going cancer case–control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5–4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6–204.6) for lung cancer in women, and 23.9 (95% CI 9.5–60.3) for lung cancer and 23.6 (95% CI 4.6–121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7–46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1–7.5) in men working in ‘potentially noxious’ industries. ‘Frequent’ alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0–2.9, for women and odds ratio=1.8, 95% CI 1.2–2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8–7.9 in males and odds ratio=4.8, 95% CI 3.2–6.1 in females). The above results are broadly in line with international findings. British Journal of Cancer (2002) 86, 1751–1756. doi:10.1038/sj.bjc.6600338 www.bjcancer.com © 2002 Cancer Research UK

The 1785 km2 Takab area of northwest Iran is a region of high mineral potential but difficult access for which an innovative exploration approach is required. Interpretation of aeromagnetic, Landsat TM, geological and mineral occurrence data are used to recognize a combination of mapped geological features, spectral characteristics, and magnetic signatures that could be associated with epithermal gold, arsenic, antimony, and base metal deposits near Takab. Geological data such as permeable, reactive host rocks, surface igneous rocks, and structures are integrated with interpretations of remotely sensed data of hydrothermal alteration and subsurface igneous heat sources. Four binary maps representing diagnostic deposit recognition criteria were combined in a weights-of-evidence model, which uses the spatial distribution of 19 known mineral occurrences to calculate a final map of further gold and base metal potential in the Takab area.

An application of the theory of fuzzy sets to the mapping of gold mineralization potential in the Baguio gold mining district of the Philippines is described. Proximity to geological features is translated into fuzzy membership functions based upon qualitative and quantitative knowledge of spatial associations between known gold occurrences and geological features in the area. Fuzzy sets of favorable distances to geological features and favorable lithologic formations are combined using fuzzy logic as the inference engine. The data capture, map operations, and spatial data analyses are carried out using a geographic information system. The fuzzy predictive maps delineate at least 68% of the known gold occurrences that are used to generate the model. The fuzzy predictive maps delineate at least 76% of the “unknown” gold occurrences that are not used to generate the model. The results are highly comparable with the results of previous stream-sediment geochemical survey in the area. The results demonstrate the usefulness of a geologically constrained fuzzy set approach to map mineral potential and to redirect surficial exploration work in the search for yet undiscovered gold mineralization in the mining district. The method described is applicable to other mining districts elsewhere.

Gold mineralisation at Zarshuran, northwestern Iran, is hosted by Precambrian carbonate and black shale formations which have been intruded by a weakly mineralised granitoid. Granitoid intrusion fractured the sedimentary rocks, thereby improving conditions for hydrothermal alteration and mineralisation. Silicification is the principal hydrothermal alteration along with decalcification and argillisation. Three hydrothermal sulphide mineral assemblages have been identified: an early assemblage of pyrrhotite, pyrite and chalcopyrite; then widespread base metal sulphides, lead-sulphosalts and zoned euhedral arsenical pyrite; and finally late network arsenical pyrite, massive and colloform arsenical pyrite, colloform sphalerite, coloradoite, and arsenic–antimony–mercury–thallium-bearing sulphides including orpiment, realgar, stibnite, getchellite, cinnabar, lorandite and a Tl-mineral, probably christite. Most of the gold at Zarshuran is detectable only by quantitative electron microprobe and bulk chemical analyses. Gold occurs mainly in arsenical pyrite and colloform sphalerite as solid solution or as nanometre-sized native gold. Metallic gold is found rarely in hydrothermal quartz and orpiment. Pure microcrystalline orpiment, carbon-rich shale, silicified shale with visible pyrite grains and arsenic minerals contain the highest concentrations of gold. In many ways Zarshuran appears to be similar to the classic Carlin-type sediment-hosted disseminated gold deposits. However, relatively high concentrations of tellurium at Zarshuran, evidenced by the occurrence of coloradoite (HgTe), imply a greater magmatic contribution in the mineralising hydrothermal solutions than is typical of Carlin-type gold deposits.

UNLABELLED We report an unusual presentation of polyarteritis nodosa in a 2-y-old child. The child presented with a mass of the left leg adjacent to the calf, and the biopsy showed polyarteritis nodosa. Further investigations confirmed systemic features, and X-rays showed a periosteal reaction. CONCLUSION Childhood polyarteritis nodosa may present with a lower limb inflammatory mass.

A systematic approach for identifying mineral exploration target areas from reconnaissance stream sediment data without sufficient a-priori control information has been demonstrated in a portion of western Albay Province in the southern Bicol Peninsula of the Philippines. The approach involved devising a rapid method of catchment basin mapping using a geographic information system (GIS) so that the areal influence of the catchment basins may be incorporated in the geochemical data analysis. Areal proportions of mapped rock units occurring in the sample catchment basins and observed Mn and Fe contents in stream sediments are used as independent variables in multiple regression analysis to predict element contents in stream sediments related to lithologic and chemical controls. The predicted element contents are filtered-out from the original data to leave residuals in which the effects of other factors (e.g., mineralization) may be seen. A simple correction for the effects of downstream dilution is applied; this allows for the different sizes of the sample catchment basins so that positive geochemical residuals are enhanced. The inter-relationship of the different positive residuals in ‘highly enriched’ samples are investigated through principal components analysis to determine and quantify an ‘anomalous geochemical signature’. Lastly, the ‘anomalous geochemical signature’ is integrated with ‘proximity’ to faults/fractures to determine favourable target areas. For the test region, the lithologic controls explain between 80% and 100% of the variability in most of the elements studied. Chemical controls account for generally less than 5% of the variability in the data. Most of the dilution-corrected residuals reveal high relative enrichment in certain areas underlain by andesite and/or diorite. An anomalous Cu-Mg-Fe-Zn geochemical signature is disclosed by the principal components analysis of the dilution-corrected residuals in ‘highly enriched’ samples. Most sample catchment basins defined by this ‘anomalous geochemical signature’ pertain to areas underlain by andesitic rocks. Integration of the ‘anomalous geochemical signature’ and ‘proximity’ to faults/fractures reveals that some of these anomalous sample catchment basins are favourable target areas. These areas are interpreted to contain andesite-hosted stockwork or stringer zones that once formed part of a complete stratigraphic sequence of a volcanogenic massive sulphide occurrence. The results demonstrate the usefulness and ability of the procedures followed to extract significant anomalies from the reconnaissance geochemical data without the benefit of sufficient a-priori control data to aid in anomaly recognition. Similar procedures could also be applied elsewhere.

The scale and shape of areas and volumes of contamination at and below the Earth's surface are summarized. It is argued that in terms of their anomalous chemical composition, spatial distribution and relation with the host matrix, analogies can be drawn between bodies of contamination and deposits of metalliferous minerals. It is recommended that bodies of contamination are explored in much the same ways as mineral deposits. Additional attention must be given to their greater chemical complexity and degree of mobility. Characterization of clays and other sorbents is particularly important in contaminated soils and sediments. The scavenging property of clays means that they act as natural immobilizers of contaminants and can be employed as contaminant containment barriers. Clays are, however, vulnerable to alteration and degradation of their sorption capacity, which can lead to the release of absorbed contaminants.

Ophthalmomyiasis externa is the infestation of the superficial external ocular structures by fly larvae. This is a particularly rare condition, which has nevertheless been reported in several countries worldwide. Presented herein are the clinicopathologic features of ophthalmomyiasis externa which occurred in an adult patient. The patient responded well to treatment following thorough ophthalmological examination and prompt diagnosis.

Primary Au mineralization at Posse is hosted within felsic meta-volcanic rocks of the Proterozoic Mara Rosa volcano-sedimentary sequence. The weathered zone above ore is characterized by a degraded laterite profile dominated by a saprolitic zone above which is a stone line rich in quartz and pisoliths. More than 80% of the Au in the primary ore is present as native Au intermixed with telluride minerals and the distribution of Ag within the Au grains is heterogeneous. During weathering telluride minerals are readily oxidized leaving a Fe-oxide material intermixed with unaltered native Au. Both mechanical and chemical processes have contributed to the redistribution of Au. The role of organic and hydroxy complexes are thought to be important in the chemical remobilization of Au near the surface. Reprecipitation of Au takes place in the saprolite resulting in Au grains with well-developed crystalline morphology. The fineness of these grains is similar to that of primary Au but the distribution of Ag is typically homogeneous. Gold has also been reprecipitated, especially in the stone line, by adsorption onto iron-oxides, causing Au enrichment in the coarse fractions. The stone line and topsoil are dominated by relatively large primary and reprecipitated Au grains, due to the preferential mechanical removal of the fine-grained Au by surficial erosion.