The contribution of smoking and smokeless tobacco to oesophageal squamous cell carcinoma risk in the African oesophageal cancer corridor: Results from the ESCCAPE multicentre case-control studies.

Tobacco use is a well-established risk factor for oesophageal squamous cell carcinoma (ESCC) but the extent of its contribution to the disease burden in the African oesophageal cancer corridor has not been comprehensively elucidated, including by type of tobacco use. We investigated the contribution of tobacco use (smoking and smokeless) to ESCC in Tanzania, Malawi and Kenya. Hospital-based ESCC case-control studies were conducted in the three countries. Incident cases and controls were interviewed using a comprehensive questionnaire which included questions on tobacco smoking and smokeless tobacco use. Logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of ESCC associated with tobacco, adjusted for age, sex, alcohol use, religion, education and area of residence. One thousand two hundred seventy-nine cases and 1345 controls were recruited between August 5, 2013, and May 24, 2020. Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR 3.09, 95%CI 1.83-5.23), and in Malawi (OR 2.45, 95%CI 1.80-3.33) and lesser in Kenya (OR 1.37, 95%CI 0.94-2.00). Exclusive smokeless tobacco use was positively associated with ESCC risk, in Tanzania, Malawi and Kenya combined (OR 1.92, 95%CI 1.26-2.92). ESCC risk increased with tobacco smoking intensity and duration of smoking. Tobacco use is an important risk factor of ESCC in Tanzania, Malawi and Kenya. Our study provides evidence that smoking and smokeless tobacco cessation are imperative in reducing ESCC risk.

Shock-Tube Measurements of Atomic Nitrogen Collisional Excitation in 8000-12000 K Partially Ionized Nitrogen-Argon Mixtures.

We report on shock-tube experiments measuring the collisional excitation of atomic nitrogen using tunable diode laser absorption spectroscopy (TDLAS). Conditions behind the reflected shocks ranged from 8000 to 12000 K and 0.1 to 1.1 atm in mixtures of 1 or 2% molecular nitrogen (N2) in argon (Ar). Absorption from the transition between atomic nitrogen quantum states 4P to 4D at 868 nm was used to monitor the formation of electronically excited nitrogen. Population measurements of the 4P state were made at a rate of 50 kHz. In connection with these measurements, a multitemperature kinetic mechanism is proposed for nitrogen excitation. Measurements suggest a multistage process. In early test times, a period of induction due to N2 dissociation is followed by a rise via heavy particle excitation. The dominant channel causing this excitation is believed to be N + N ↔ N(4P) + N with a measured forward rate constant of 3.65 × 10-18 exp(-119892/T) [m3/s]. As test time evolves, the excitation of 4P, referred to as N*, is subsequently interrupted and then resumes, as the kinetic environment becomes increasingly electron-dominated. The most impactful reactions of the mechanism are optimized to reduce the residual between simulations and the measurements. The measured N* populations indicate strong, though indirect, sensitivity to adjacent processes, including the excitation of metastable nitrogen, and ionization channels.

A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies.

BACKGROUND: Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score. METHODS: From the ESCCAPE case-control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge. RESULTS: The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for 'very hot' vs 'hot'), waiting time before drinking/eating (1.76 (1.37, 2.26) for <2 vs 2-5 minutes), consumption speed (2.23 (1.78, 2.79) for 'normal' vs 'slow') and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3. CONCLUSIONS: Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic.

Minimally Invasive Postmortem Intestinal Tissue Sampling in Malnourished and Acutely Ill Children Is Feasible and Informative.

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.

Geophagia and risk of squamous cell esophageal cancer in the African esophageal cancer corridor: Findings from the ESCCAPE multicountry case-control studies.

Geophagia, the intentional practice of consuming soil, occurs across the African esophageal cancer corridor, particularly during pregnancy. We investigated whether this practice is linked to endemic esophageal squamous cell carcinoma (ESCC) in this region. We conducted ESCC case-control studies in Tanzania, Malawi and Kenya. Cases were patients with incident histologically/clinically confirmed ESCC and controls were hospital patients/visitors without digestive diseases. Participants were asked if they had ever eaten soil (never/regularly/pregnancy-only). Odds ratios (OR) are adjusted for sex, age, tobacco, alcohol, country, religion and marital status. Overall, 934 cases (Malawi 535, Tanzania 304 and Kenya females 95) and 995 controls provided geophagia information. Among controls, ever-geophagia was common in women (Malawi 49%, Kenya 43% and Tanzania 29%) but not in men (10% Malawi, <1% Tanzania). In women, ESCC ORs were 1.25 (95% CI: 0.70, 2.22) for regular versus never geophagia and 0.88 (95% CI: 0.64, 1.22) for pregnancy-only versus never. Findings were stronger based on comparisons of cases with hospital visitor controls and were null using hospital patients as controls. In conclusion, geophagia is too rare to contribute to the male ESCC burden in Africa. In women, the practice is common but we did not find consistent evidence of a link to ESCC. The study cannot rule out selection bias masking modest effects. Physical effects of geophagia do not appear to have a large impact on overall ESCC risk. Research with improved constituent-based geophagia exposure assessment is needed.

Induced topological phases at the boundary of 3D topological superconductors.

We present tight-binding models of 3D topological superconductors in class DIII that support a variety of winding numbers. We show that gapless Majorana surface states emerge at their boundary in agreement with the bulk-boundary correspondence. At the presence of a Zeeman field, the surface states become gapped and the boundary behaves as a 2D superconductor in class D. Importantly, the 2D and 3D winding numbers are in agreement, signifying that the topological phase of the boundary is induced by the phase of the 3D bulk. Hence, the boundary of a 3D topological superconductor in class DIII can be used for the robust realization of localized Majorana zero modes.

Alcohol consumption and oesophageal squamous cell cancer risk in east Africa: findings from the large multicentre ESCCAPE case-control study in Kenya, Tanzania, and Malawi.

BACKGROUND: The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. METHODS: We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV; <30% ABV) drinkers or drinkers of some high-ABV drinks, as well as the number of drinks consumed, average weekly ethanol intake, and the contribution of each drink type to overall ethanol consumption. Cases were patients aged 18 years and older with incident primary ESCC, confirmed histologically for the majority of cases, and a clinical diagnosis for the remainder. Controls were frequency-matched on age and sex in a 1:1 ratio with cases. The controls were recruited from the same hospitals as cases and included outpatients, inpatients, and hospital visitors who did not have cancer or any other digestive disease. Consenting participants took part in face-to-face interviews in which they were asked whether they had ever consumed alcohol (the primary exposure variable); those who had were asked follow-up questions about their consumption habits for different alcoholic drinks. FINDINGS: 1279 cases and 1346 controls were recruited between Aug 5, 2013, and May 24, 2020, including 430 cases and 440 controls from Kenya, 310 cases and 313 controls from Tanzania, and 539 cases and 593 controls from Malawi. 65 (4·8%) of 1344 cases were excluded. Consistent positive associations with ESCC risk were found for ever having consumed alcohol in Kenyan men and Tanzanian men, and for daily number of drinks and estimated ethanol intake in Kenya, Tanzania (both sexes) and Malawian women. Corresponding population-attributable fractions of ESCC for those reporting ever drinking alcohol (vs never drinking) were 65% (95% CI 52-78) in Kenyan men and 23% (<1-45) in Kenyan women, and 56% (95% CI 36-76) in Tanzanian men and 5% (0-42) in Tanzanian women. Increased risk and population-attributable fractions were almost entirely due to risks in high-ABV drinkers. INTERPRETATION: Alcohol appears to be a substantial contributor to ESCC risk in east Africa, particularly among men, and a large fraction of ESCC could be prevented by cessation or reduction of alcohol consumption. Future studies should consider independent ascertainment of alcohol intake to assess the potential of under-reporting in Malawi. FUNDING: US National Cancer Institute, Wereld Kanker Onderzoek Fonds, and the IARC Environment and Lifestyle Epidemiology Branch. TRANSLATIONS: For the Swahili and Chichewa translations of the abstract see Supplementary Materials section.

Systematic review: the etiology of esophageal squamous cell carcinoma in low-income settings.

INTRODUCTION: Esophageal carcinoma causes over 380 000 deaths per year, ranking sixth worldwide in mortality amongst all malignancies. Globally, the squamous cell subtype is most common and accounts for 80% of esophageal cancers. Nonetheless, esophageal squamous cell carcinoma is much more poorly understood than esophageal adenocarcinoma, including what is driving such high prevalences, why it often presents in young patients, and shows such marked geographical delineations Areas covered: The current literature was searched for articles focusing on aetiopathogenesis of squamous cell esophageal carcinoma via a systematic review, particularly in low-resource settings. This was supplemented by papers of interest known to the authors. Expert commentary: Current putative mechanisms include polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde, cyclo-oxygenase-2 pathways, androgen and their receptor levels, as well as smoking & alcohol, micronutrient deficiencies and diet, mycotoxins, thermal damage, oral hygiene and microbiotal factors, inhaled smoke, viral infections such as HPV, and chronic irritative states. Etiology is likely multifactorial and varies geographically. Though smoking and alcohol play a predominant role in high-income settings, there is strong evidence that mycotoxins, diet and temperature effects may play an under-recognized role in low and middle-income settings.

Five-year single-centre experience of carcinoma of the oesophagus from Blantyre, Malawi.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is increasing worldwide and has an exceptionally high prevalence in certain distinct geographical locations such as the African oesophageal SCC corridor. Despite this, there is a paucity of evidence to characterise the disease particularly in the Malawian context. METHOD: We retrospectively audited our endoscopy database over 5 years, including for patient demographics, endoscopy findings, therapeutic intervention and recommendations for treatment. RESULTS: 1586 patients with oesophageal cancer were identified from a total of 5882 endoscopy records from 2013 to 2017. Our cohort showed a larger proportion of oesophageal cancers found higher in the oesophagus compared with other African studies and a female preponderance in this upper-oesophagus disease subset though a male preponderance overall. 39% of patients with oesophageal cancer underwent bougie dilatation and 11% underwent palliative stent placement, which likely reflects local availability of resources. CONCLUSION: This study validates the observation that OSCC predominates in sub-Saharan Africa in Malawi over other forms of oesophageal carcinoma, though our cohort appears to have subtly distinct demographics and disease-specific data. This highlights the need to prioritise preventative and therapeutic strategies for OSCC in this and similar settings.

Intra-abdominal fat: Comparison of computed tomography fat segmentation and bioimpedance spectroscopy.

BACKGROUND: Intra-abdominal fat is an important factor in determining the metabolic syndrome/insulin resistance, and thus the risk of diabetes and ischaemic heart disease. Computed Tomography (CT) fat segmentation represents a defined method of quantifying intra-abdominal fat, with attendant radiation risks. Bioimpedance spectroscopy may offer a method of assessment without any risks to the patients. A comparison is made of these two methods. METHODS: This was a preliminary study of the utility of multifrequency bioimpedance spectroscopy of the mid abdomen as a measure of intra-abdominal fat, by comparison with fat segmentation of an abdominal CT scan in the -30 to -190 HU range. RESULTS: There was a significant (P < 0.01) correlation between intra-abdominal fat and mid-upper arm circumference, as well as the bioimpedance parameter, the R/S ratio. Multivariate analysis showed that these were the only independant variables and allowed the derivation of a formula to estimate intra-abdominal fat: IAF = 0.02 × MAC - 0.757 × R/S + 0.036. CONCLUSIONS: Circumabdominal bioimpedance spectroscopy may prove a useful method of assessing intra-abdominal fat, and may be suitable for use in studies to enhance other measures of body composition, such as mid-upper arm circumference.

Psychosis in the British Army: a 2-year follow-up study.

BACKGROUND: Recent research into mental illness in military populations has tended to focus on minor mental illness and the consequences of trauma. The literature contains very little on serious mental illness, including its occupational implications. AIMS: To identify the incidence and factors associated with nonaffective psychosis in British Army personnel, to evaluate service quality in terms of duration of untreated psychosis, and to identify predictors of occupational outcome after 2 years, to inform future management of similar cases. METHODS: A retrospective study of the case notes of all Army personnel admitted to the U.K. military psychiatric inpatient facility in Catterick Garrison with a nonaffective psychosis over a 4-year period between 1999 and 2002 was performed. RESULTS: There were 48 cases of nonaffective psychosis and 14 cases of schizophrenia, corresponding to mean annual incidences of 0.11 cases per 1,000 and 0.03 cases per 1,000, respectively. The mean duration of untreated psychosis was 11 months, and 29 cases (60%) were diagnosed and treated in < 4 months. Officer status and longer duration of service predicted retention. Only eight patients (16.7%) were still in service at 2 years. CONCLUSIONS: These findings indicate (1) there is a low incidence of nonaffective psychosis, (2) the military performs well in early detection and intervention in psychosis, and (3) a well-established military career and the premorbid psychological stability this implies predict a good occupational outcome.

Acute military psychiatric casualties from the war in Iraq.

BACKGROUND: The view that most military personnel evacuated from war zones are suffering from combat stress reactions, or are otherwise traumatised by the horrors of war, has an impact on all aspects of military psychiatry. AIMS: To delineate the reasons for psychiatric aeromedical evacuation from Iraq from the start of build-up of UK forces in January 2003 until the end of October that year, 6 months after the end of formal hostilities. METHOD: A retrospective study was conducted of field and in-patient psychiatric assessments of 116 military personnel evacuated to the UK military psychiatric in-patient facility in Catterick Garrison. RESULTS: Evacuees were mainly non-combatants (69%). A significant proportion were in reserve service (21%) and had a history of contact with mental health services (37%). Only 3% had a combat stress reaction. In over 85% of cases evacuation was for low mood attributed to separation from friends or family, or difficulties adjusting to the environment. CONCLUSIONS: These findings have implications especially for screening for suitability for deployment, and for understanding any longer-term mental health problems arising in veterans from Iraq.