STRIKE-HBV: establishing an HBV screening programme in Kilifi, Kenya-challenges, successes and lessons learnt.

OBJECTIVES: Chronic hepatitis B infection affects 65 million people in the WHO African Region, but only 4.2% of these are diagnosed and 0.2% on treatment. Here, we present a short report describing establishment of a hepatitis B virus (HBV) programme in Kenya. We share experiences, successes and challenges to support development of future programmes. METHODS: From March 2023, we began the 'STRIKE-HBV' Study to identify people living with HBV (PLWHB) in Kilifi, Kenya. We employed local staff and provided education and training. Individuals were identified through three routes: (1) we offered free-of-charge HBV testing for all non-pregnant adults attending Kilifi Country Hospital (KCH) outpatient department; (2) we invited PLWHB to reattend for review; and (3) we invited close contacts of PLWHB for screening and vaccination if HBV was negative. All those seropositive for HBV were offered a comprehensive liver health assessment. RESULTS: We have established a framework for HBV screening, assessment and linkage to care in Kilifi. Between March 2023 and March 2024, we collected data for 80 PLWHB, comprising (1) screening of 1862 people of whom 30 were seropositive, (2) enrolment of 38 people known to be living with HBV and (3) testing of 97 close contacts of PLWHB, of whom 12 were positive. Among a limited subset with elastography data, we identified 9 of 59 as having significant fibrosis, and a further 6 people had laboratory aspartate transaminase (AST) to platelet ratio index (APRI) scores in keeping with fibrosis. We encountered challenges including procurement delays for hepatitis B surface antigen testing kits and HBV vaccinations, and issues accessing liver elastography. CONCLUSIONS: HBV screening was well received by the Kilifi population, has identified people at risk of liver disease progression and is improving linkage to care and vaccination at KCH. Future HBV programmes in WHO Africa can build on this experience as we work to develop accessible, affordable and acceptable care pathways.

Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations.

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Risk Factors of Microbial Keratitis in Uganda: A Case Control Study.

Purpose: Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda.Methods: Using a nested case control, we recruited healthy community controls for patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018. Controls were individually matched for age, gender and village of the cases on a 1:1 ratio. We collected information on demographics, occupation, HIV and Diabetes Mellitus status. In STATA version 14.1, multivariable conditional logistic regression was used to generate odds ratios for risk factors of MK and a likelihood ratio test used to assess statistical significance of associations.Results: Two hundred and fifteen case-control pairs were enrolled. The HIV positive patients among the cases was 9% versus 1% among the controls, p = .0003. Diabetes 7% among the cases versus 1.4% among the controls, p = .012. Eye trauma was 29% versus 0% among the cases and controls. In the multivariable model adjusted for age, sex and village, HIV (OR 83.5, 95%CI 2.01-3456, p = .020), Diabetes (OR 9.38, 95% CI 1.48-59.3, p = .017) and a farming occupation (OR 2.60, 95%CI 1.21-5.57, p = .014) were associated with MK. Compared to a low socio-economic status, a middle status was less likely to be associated with MK (OR 0.29, 95%CI 0.09-0.89, p < .0001).Conclusion: MK was associated with HIV, Diabetes, being poor and farming as the main occupation. More studies are needed to explore how these factors predispose to MK.

Epidemiology of Microbial Keratitis in Uganda: A Cohort Study.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda.Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60).Results: 313 individuals were enrolled. Median age was 47 years (range 18-96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8-32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04-2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12-4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03-1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70-26.6], p < .0001).Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions.

Predictors of loss to follow up among patients with type 2 diabetes mellitus attending a private not for profit urban diabetes clinic in Uganda - a descriptive retrospective study.

BACKGROUND: Although the prevalence of type 2 diabetes mellitus is increasing in Uganda, data on loss to follow up (LTFU) of patients in care is scanty. We aimed to estimate proportions of patients LTFU and document associated factors among patients attending a private not for profit urban diabetes clinic in Uganda. METHODS: We conducted a descriptive retrospective study between March and May 2017. We reviewed 1818 out-patient medical records of adults diagnosed with type 2 diabetes mellitus registered between July 2003 and September 2016 at St. Francis Hospital - Nsambya Diabetes clinic in Uganda. Data was extracted on: patients' registration dates, demographics, socioeconomic status, smoking, glycaemic control, type of treatment, diabetes mellitus complications and last follow-up clinic visit. LTFU was defined as missing collecting medication for six months or more from the date of last clinic visit, excluding situations of death or referral to another clinic. We used Kaplan-Meier technique to estimate time to defaulting medical care after initial registration, log-rank test to test the significance of observed differences between groups. Cox proportional hazards regression model was used to determine predictors of patients' LTFU rates in hazard ratios (HRs). RESULTS: Between July 2003 and September 2016, one thousand eight hundred eighteen patients with type 2 diabetes mellitus were followed for 4847.1 person-years. Majority of patients were female 1066/1818 (59%) and 1317/1818 (72%) had poor glycaemic control. Over the 13 years, 1690/1818 (93%) patients were LTFU, giving a LTFU rate of 34.9 patients per 100 person-years (95%CI: 33.2-36.6). LTFU was significantly higher among males, younger patients (< 45 years), smokers, patients on dual therapy, lower socioeconomic status, and those with diabetes complications like neuropathy and nephropathy. CONCLUSION: We found high proportions of patients LTFU in this diabetes clinic which warrants intervention studies targeting the identified risk factors and strengthening follow up of patients.

Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study.

OBJECTIVES: We assessed the prevalence and risk factors associated with virological failure among female sex workers living with HIV on antiretroviral therapy (ART) in Kampala, Uganda. METHODS: We conducted a cross-sectional study between January 2015 and December 2016 using routinely collected data at a research clinic providing services to women at high risk of STIs including HIV. Plasma samples were tested for viral load from HIV-seropositive women aged ≥18 years who had been on ART for at least 6 months and had received adherence counselling. Samples from women with virological failure (≥1000 copies/mL) were tested for HIV drug resistance by population-based sequencing. We used logistic regression to identify factors associated with virological failure. RESULTS: Of 584 women, 432 (74%) with a mean age of 32 (SD 6.5) were assessed, and 38 (9%) were found to have virological failure. HIV resistance testing was available for 78% (28/38), of whom 82.1% (23/28) had at least one major drug resistance mutation (DRM), most frequently M184V (70%, 16/23) and K103N (65%, 15/23). In multivariable analysis, virological failure was associated with participant age 18-24 (adjusted OR (aOR)=5.3, 95% CI 1.6 to 17.9), self-reported ART non-adherence (aOR=2.6, 95% CI 1.2 to 5.8) and baseline CD4+ T-cell count ≤350 cells/mm3 (aOR=3.1, 95% CI 1.4 to 7.0). CONCLUSIONS: A relatively low prevalence of virological failure but high rate of DRM was found in this population at high risk of transmission. Younger age, self-reported ART non-adherence and low CD4+ T-cell count on ART initiation were associated with increased risk of virological failure.

Delay Along the Care Seeking Journey of Patients with Microbial Keratitis in Uganda.

Purpose: To describe the care seeking journey and causes of delay among patients with Microbial Keratitis in Uganda. Methods: A prospective cohort of patients presenting with microbial keratitis at the two main eye units in Southern Uganda (2016-2018). We collected information on demographics, home address, clinical history, and presentation pathway including, order of facilities where patients went to seek care, treatment advice, cost of care, and use of Traditional Eye Medicine. Presentation time was noted. We compared "direct" presenters versus "indirect" presenters and analysed predictors of delay. Results: About 313 patients were enrolled. All were self-referred. Only 19% of the patients presented directly to the eye hospital. Majority (52%) visited one facility before presenting, 19% visited two facilities, 9% visited three facilities, and 2% visited four facilities. The cost of care increased with increase in the number of facilities visited. People in a large household, further distance from the eye hospital and those who used Traditional Eye Medicine were less likely to come directly to the eye hospital. Visiting another facility prior to the eye hospital and use of Traditional Eye Medicine aOR 1.58 (95%CI 1.03-2.43), p = .038 were associated with delayed presentation to the eye hospital. Conclusion: This study provided information on patient journeys to seek care. Delay was largely attributable to having visited another health facility: a referral mechanism for microbial keratitis was non-existent. There is need to explore how these health system gaps can be strengthened.

Feasibility of conducting HIV combination prevention interventions in fishing communities in Uganda: A pilot cluster randomised trial.

OBJECTIVE: We assessed feasibility of an HIV-combination-prevention trial among fishing communities in Uganda. DESIGN: Cluster randomised trial in four fishing communities on Lake Victoria, Uganda. Two intervention communities received a combination-prevention-package (behaviour change communication, condom promotion, HIV testing, voluntary male medical circumcision and referral for anti-retroviral therapy if HIV-positive). All four communities received routine government HIV care services. METHODS: Using household census data we randomly selected a cohort of consenting residents aged ≥18 years. A baseline sero-survey in July 2014 was followed by two repeat surveys in March and December 2015. We measured uptake of HIV prevention methods, loss-to-follow-up and HIV incidence, accounting for multistage survey design. RESULTS: A total of 862 participants were enrolled and followed for 15 months. Participation was 62% and 74% in the control and intervention arms respectively; Overall loss to follow up (LTFU) was 21.6% and was similar by arm. Self-reported abstinence/faithfulness increased between baseline and endline in both arms from 53% to 73% in the control arm, and 55% to 67% in the intervention arm. Reported condom use throughout the study period was 36% in the intervention arm vs 28% in the control arm; number of male participants reporting circumsicion in both arms from 58% to 79% in the intervention arm, and 39% to 46% in the control arm. Independent baseline predictors of loss-to-follow-up were: being HIV positive, residence in the community for <1 year, younger age, living in an urban area, and being away from the area for >1 month/year. CONCLUSIONS: Recruitment and retention of participants in longitudinal trials in highly mobile HIV fishing communities is challenging. Future research should investigate modes for locating and retaining participants, and delivery of HIV-combination prevention.

Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis.

Background: Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods: Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results: Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion: Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.

Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparum Infections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach.

Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P. falciparum antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL [high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81-15.64]. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02-1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1-22.2, P = 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against P. falciparum preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic P. falciparum antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to P. falciparum interact with EBV infection in the development of eBL.

Atherogenic Risk Assessment among Persons Living in Rural Uganda.

Background. Hypertension and dyslipidemia are independent risk factors for coronary heart disease and commonly coexist. Cardiovascular risk can be reliably predicted using lipid ratios such as the atherogenic index, a useful prognostic parameter for guiding timely interventions. Objective. We assessed the cardiovascular risk profile based on the atherogenic index of residents within a rural Ugandan cohort. Methods. In 2011, a population based survey was conducted among 7507 participants. Sociodemographic characteristics, physical measurements (blood pressure, weight, height, and waist and hip circumference), and blood sampling for nonfasting lipid profile were collected for each participant. Atherogenic risk profile, defined as logarithm base ten of (triglyceride divided by high density lipoprotein cholesterol), was categorised as low risk (<0.1), intermediate risk (0.1-0.24), and high risk (>0.24). Results. Fifty-five percent of participants were female and the mean age was 49.9 years (SD ± 20.2). Forty-two percent of participants had high and intermediate atherogenic risk. Persons with hypertension, untreated HIV infection, abnormal glycaemia, and obesity and living in less urbanised villages were more at risk. Conclusion. A significant proportion of persons in this rural population are at risk of atherosclerosis. Key identified populations at risk should be considered for future intervention against cardiovascular related morbidity and mortality. The study however used parameters from unfasted samples that may have a bearing on observed results.

The biogeography of red snow microbiomes and their role in melting arctic glaciers.

The Arctic is melting at an unprecedented rate and key drivers are changes in snow and ice albedo. Here we show that red snow, a common algal habitat blooming after the onset of melting, plays a crucial role in decreasing albedo. Our data reveal that red pigmented snow algae are cosmopolitan as well as independent of location-specific geochemical and mineralogical factors. The patterns for snow algal diversity, pigmentation and, consequently albedo, are ubiquitous across the Arctic and the reduction in albedo accelerates snow melt and increases the time and area of exposed bare ice. We estimated that the overall decrease in snow albedo by red pigmented snow algal blooms over the course of one melt season can be 13%. This will invariably result in higher melt rates. We argue that such a 'bio-albedo' effect has to be considered in climate models.

Adverse pregnancy outcomes in rural Uganda (1996-2013): trends and associated factors from serial cross sectional surveys.

OBJECTIVE: Community based evidence on pregnancy outcomes in rural Africa is lacking yet it is needed to guide maternal and child health interventions. We estimated and compared adverse pregnancy outcomes and associated factors in rural south-western Uganda using two survey methods. METHODS: Within a general population cohort, between 1996 and 2013, women aged 15-49 years were interviewed on their pregnancy outcome in the past 12 months (method 1). During 2012-13, women in the same cohort were interviewed on their lifetime experience of pregnancy outcomes (method 2). Adverse pregnancy outcome was defined as abortions or stillbirths. We used random effects logistic regression for method 1 and negative binomial regression with robust clustered standard errors for method 2 to explore factors associated with adverse outcome. RESULTS: One third of women reported an adverse pregnancy outcome; 10.8% (abortion = 8.4%, stillbirth = 2.4%) by method 1 and 8.5% (abortion = 7.2%, stillbirth = 1.3%) by method 2. Abortion rates were similar (10.8 vs 10.5) per 1000 women and stillbirth rates differed (26.2 vs 13.8) per 1000 births by methods 1 and 2 respectively. Abortion risk increased with age of mother, non-attendance of antenatal care and proximity to the road. Lifetime stillbirth risk increased with age. Abortion and stillbirth risk reduced with increasing parity. DISCUSSION: Both methods had a high level of agreement in estimating abortion rate but were markedly below national estimates. Stillbirth rate estimated by method 1 was double that estimated by method 2 but method 1 estimate was more consistent with the national estimates. CONCLUSION: Strategies to improve prospective community level data collection to reduce reporting biases are needed to guide maternal health interventions.

Trophic flexibility and the persistence of understory birds in intensively logged rainforest.

Effects of logging on species composition in tropical rainforests are well known but may fail to reveal key changes in species interactions. We used nitrogen stable-isotope analysis of 73 species of understory birds to quantify trophic responses to repeated intensive logging of rainforest in northern Borneo and to test 4 hypotheses: logging has significant effects on trophic positions and trophic-niche widths of species, and the persistence of species in degraded forest is related to their trophic positions and trophic-niche widths in primary forest. Species fed from higher up the food chain and had narrower trophic-niche widths in degraded forest. Species with narrow trophic-niche widths in primary forest were less likely to persist after logging, a result that indicates a higher vulnerability of dietary specialists to local extinction following habitat disturbance. Persistence of species in degraded forest was not related to a species' trophic position. These results indicate changes in trophic organization that were not apparent from changes in species composition and highlight the importance of focusing on trophic flexibility over the prevailing emphasis on membership of static feeding guilds. Our results thus support the notion that alterations to trophic organization and interactions within tropical forests may be a pervasive and functionally important hidden effect of forest degradation.

Impacts of intensive logging on the trophic organisation of ant communities in a biodiversity hotspot.

Trophic organisation defines the flow of energy through ecosystems and is a key component of community structure. Widespread and intensifying anthropogenic disturbance threatens to disrupt trophic organisation by altering species composition and relative abundances and by driving shifts in the trophic ecology of species that persist in disturbed ecosystems. We examined how intensive disturbance caused by selective logging affects trophic organisation in the biodiversity hotspot of Sabah, Borneo. Using stable nitrogen isotopes, we quantified the positions in the food web of 159 leaf-litter ant species in unlogged and logged rainforest and tested four predictions: (i) there is a negative relationship between the trophic position of a species in unlogged forest and its change in abundance following logging, (ii) the trophic positions of species are altered by logging, (iii) disturbance alters the frequency distribution of trophic positions within the ant assemblage, and (iv) disturbance reduces food chain length. We found that ant abundance was 30% lower in logged forest than in unlogged forest but changes in abundance of individual species were not related to trophic position, providing no support for prediction (i). However, trophic positions of individual species were significantly higher in logged forest, supporting prediction (ii). Consequently, the frequency distribution of trophic positions differed significantly between unlogged and logged forest, supporting prediction (iii), and food chains were 0.2 trophic levels longer in logged forest, the opposite of prediction (iv). Our results demonstrate that disturbance can alter trophic organisation even without trophically-biased changes in community composition. Nonetheless, the absence of any reduction in food chain length in logged forest suggests that species-rich arthropod food webs do not experience trophic downgrading or a related collapse in trophic organisation despite the disturbance caused by logging. These food webs appear able to bend without breaking in the face of some forms of anthropogenic disturbance.

Assessing trophic position from nitrogen isotope ratios: effective calibration against spatially varying baselines.

Nitrogen isotope signatures (δ(15)N) provide powerful measures of the trophic positions of individuals, populations and communities. Obtaining reliable consumer δ(15)N values depends upon controlling for spatial variation in plant δ(15)N values, which form the trophic 'baseline'. However, recent studies make differing assumptions about the scale over which plant δ(15)N values vary, and approaches to baseline control differ markedly. We examined spatial variation in the δ(15)N values of plants and ants sampled from eight 150-m transects in both unlogged and logged rainforests. We then investigated whether ant δ(15)N values were related to variation in plant δ(15)N values following baseline correction of ant values at two spatial scales: (1) using 'local' means of plants collected from the same transect and (2) using 'global' means of plants collected from all transects within each forest type. Plant δ(15)N baselines varied by the equivalent of one trophic level within each forest type. Correcting ant δ(15)N values using global plant means resulted in consumer values that were strongly positively related to the transect baseline, whereas local corrections yielded reliable estimates of consumer trophic positions that were largely independent of transect baselines. These results were consistent at the community level and when three trophically distinct ant subfamilies and eight abundant ant species were considered separately. Our results suggest that assuming baselines do not vary can produce misleading estimates of consumer trophic positions. We therefore emphasise the importance of clearly defining and applying baseline corrections at a scale that accounts for spatial variation in plant δ(15)N values.

The conservation value of South East Asia's highly degraded forests: evidence from leaf-litter ants.

South East Asia is widely regarded as a centre of threatened biodiversity owing to extensive logging and forest conversion to agriculture. In particular, forests degraded by repeated rounds of intensive logging are viewed as having little conservation value and are afforded meagre protection from conversion to oil palm. Here, we determine the biological value of such heavily degraded forests by comparing leaf-litter ant communities in unlogged (natural) and twice-logged forests in Sabah, Borneo. We accounted for impacts of logging on habitat heterogeneity by comparing species richness and composition at four nested spatial scales, and examining how species richness was partitioned across the landscape in each habitat. We found that twice-logged forest had fewer species occurrences, lower species richness at small spatial scales and altered species composition compared with natural forests. However, over 80 per cent of species found in unlogged forest were detected within twice-logged forest. Moreover, greater species turnover among sites in twice-logged forest resulted in identical species richness between habitats at the largest spatial scale. While two intensive logging cycles have negative impacts on ant communities, these degraded forests clearly provide important habitat for numerous species and preventing their conversion to oil palm and other crops should be a conservation priority.

Non-Hodgkin lymphoma and gluten-sensitive enteropathy: estimate of risk using meta-analyses.

OBJECTIVES: Gluten-sensitive enteropathy, including coeliac disease and dermatitis herpetiformis, is associated with non-Hodgkin lymphoma (NHL), and particularly enteropathy-associated T-cell lymphoma (EATCL). We conducted a meta-analysis to quantify the association. METHODS: Fifty-four risk estimates (range 0.28-300) were pooled using random-effects meta-analysis. Potential sources of variation were examined using sensitivity analyses and meta-regression. RESULTS: Thirty-one estimates with gluten-sensitive enteropathy diagnosed by serology then biopsy, serology alone, or recorded in medical notes accounted for half the variation in risks, giving a pooled estimate of 4.42 (95% confidence interval (CI) 3.72-5.26, I2 = 0%). Men and women had similar pooled risks. Risks were largest when these conditions were diagnosed using biopsy and lowest when self-reported. Study design, comparison population, geography or gluten-sensitive enteropathy type explained less of the variation. EATCL estimates ranged from 6 to 200; an association with diffuse large B-cell lymphoma (DLBCL) was also observed (pooled risk estimate = 1.97, 95% CI 1.23-3.15). CONCLUSIONS: Where gluten-sensitive enteropathy was diagnosed using modern techniques, NHL risk was increased fourfold. At this level, one in 2,000 persons with gluten-sensitive enteropathy develops NHL each year. In addition to EATCL, DLBCL and possibly other subtypes may be linked to these conditions, and these weaker associations could be investigated in large population-based cohorts with biological samples.

Illness patterns prior to diagnosis of lymphoma: analysis of UK medical records.

BACKGROUND: Increased understanding of the relationship between lymphomas and co-morbidities is likely to provide valuable insights into the natural history of these disorders. METHODS: 761 cases with lymphoma (310 diffuse large B-cell [DLBCL]; 226 follicular [FL]; and 225 Hodgkin [HL]) and 761 unaffected age and sex matched controls were recruited and their histories of infection and non-infection diagnoses in primary care records were compared using negative binomial regression. RESULTS: No differences were observed between the infectious illness patterns of DLBCL and FL cases and their matched controls over the 15 years preceding lymphoma diagnosis. A marked excess of infectious illness episodes was recorded for HL cases compared to their controls; evident at least a decade prior to HL diagnosis. For non-infectious consultations an excess of case over control visits emerged 4-6 years before DLBCL and FL diagnosis; no specific co-morbidity associations were found. No case-control differences for non-infectious conditions were apparent for HL. CONCLUSION: There are substantial variations in patterns of illness prior to diagnosis of the three lymphoma subtypes examined. The excess of infectious diagnoses prior to HL may point to underlying immune abnormality, but there was no suggestion of this for DLBCL and FL where a generalized excess of non-infectious conditions was evident.