Abiotic redox reactions in hydrothermal mixing zones: decreased energy availability for the subsurface biosphere

© The Author(s), 202. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in McDermott, J. M., Sylva, S. P., Ono, S., German, C. R., & Seewald, J. S. Abiotic redox reactions in hydrothermal mixing zones: decreased energy availability for the subsurface biosphere. Proceedings of the National Academy of Sciences of the United States of America, 117(34), (2020): 20453-20461, doi:10.1073/pnas.2003108117.Subseafloor mixing of high-temperature hot-spring fluids with cold seawater creates intermediate-temperature diffuse fluids that are replete with potential chemical energy. This energy can be harnessed by a chemosynthetic biosphere that permeates hydrothermal regions on Earth. Shifts in the abundance of redox-reactive species in diffuse fluids are often interpreted to reflect the direct influence of subseafloor microbial activity on fluid geochemical budgets. Here, we examine hydrothermal fluids venting at 44 to 149 °C at the Piccard hydrothermal field that span the canonical 122 °C limit to life, and thus provide a rare opportunity to study the transition between habitable and uninhabitable environments. In contrast with previous studies, we show that hydrocarbons are contributed by biomass pyrolysis, while abiotic sulfate (SO42−) reduction produces large depletions in H2. The latter process consumes energy that could otherwise support key metabolic strategies employed by the subseafloor biosphere. Available Gibbs free energy is reduced by 71 to 86% across the habitable temperature range for both hydrogenotrophic SO42− reduction to hydrogen sulfide (H2S) and carbon dioxide (CO2) reduction to methane (CH4). The abiotic H2 sink we identify has implications for the productivity of subseafloor microbial ecosystems and is an important process to consider within models of H2 production and consumption in young oceanic crust.Financial support was provided by the National Aeronautics and Space Administration (NASA) Astrobiology program (Awards NNX09AB75G and 80NSSC19K1427 to C.R.G. and J.S.S.) and the NSF (Award OCE-1061863 to C.R.G. and J.S.S.). Ship and vehicle time for cruise FK008 was provided by the Schmidt Ocean Institute. We thank the ROV Jason II and HROV Nereus groups, and the captain, officers, and crew of R/V Atlantis (AT18-16) and R/V Falkor (FK008) for their dedication to skillful operations at sea. We thank our scientific colleagues from both cruises, as well as Meg Tivey, Frieder Klein, and Scott Wankel for insightful discussions. We are grateful to the editor and two anonymous reviewers for providing helpful comments and suggestions

Acceptability and usability of computerized cognitive assessment among Australian Indigenous residents of the Torres Strait Islands

Objectives: This cross-sectional study aimed to investigate the acceptability and usability of the Cogstate Brief Battery (CBB) in a community-based sample of Australian Indigenous people from the Torres Strait region, based on a user experience framework of human-computer interaction. Methods: Two-hundred community participants completed the four subtests of the CBB on an iPad platform, during a free adult health check on two islands in the region, between October and December 2016. Acceptability was defined as completing the learning trial of a task and usability as continuing a task through to completion, determined by examiner acumen and internal Cogstate completion and integrity criteria. These were combined into a single dichotomous completion measure for logistic regression analyses. Performance-measured as reaction times and accuracy of responses-was analyzed using linear regression analyses. Results: CBB completion ranged from 82.0% to 91.5% across the four tasks and the odds of completing decreased with age. After adjusting for age, iPad/tablet familiarity increased the odds of completion for all tasks while level of education and employment increased the odds for some tasks only. These variables accounted for 18.0%-23.8% of the variance in reaction times on speeded tasks. Age and education had the most effect, although semipartial correlations were modest. Conclusions: When administered in a health-screening context, the acceptability and usability of the CBB were greatest in young- to middle-aged participants with some education and iPad/tablet experience. Older and more vulnerable participants may have benefited from additional time and practice on the CBB prior to administration

Dementia Risk Models in an Australian First Nations Population: Cross-Sectional Associations and Preparation for Follow-Up

Background: Reducing the burden of dementia in First Nations populations may be addressed through developing population specific methods to quantify future risk of dementia. Objective: To adapt existing dementia risk models to cross-sectional dementia prevalence data from a First Nations population in the Torres Strait region of Australia in preparation for follow-up of participants. To explore the diagnostic utility of these dementia risk models at detecting dementia. Methods: A literature review to identify existing externally validated dementia risk models. Adapting these models to cross-sectional data and assessing their diagnostic utility through area under the receiver operating characteristic curve (AUROC) analyses and calibration using Hosmer-Lemeshow Chi2. Results: Seven risk models could be adapted to the study data. The Aging, Cognition and Dementia (AgeCoDe) study, the Framingham Heart Study (FHS), and the Brief Dementia Screening Indicator (BDSI) had moderate diagnostic utility in identifying dementia (i.e., AUROC >0.70) before and after points for older age were removed. Conclusion: Seven existing dementia risk models could be adapted to this First Nations population, and three had some cross-sectional diagnostic utility. These models were designed to predict dementia incidence, so their applicability to identify prevalent cases would be limited. The risk scores derived in this study may have prognostic utility as participants are followed up over time. In the interim, this study highlights considerations when transporting and developing dementia risk models for First Nations populations

Subseafloor microbial communities in hydrogen-rich vent fluids from hydrothermal systems along the Mid-Cayman Rise

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Microbiology 18 (2016): 1970–1987, doi:10.1111/1462-2920.13173.Warm fluids emanating from hydrothermal vents can be used as windows into the rocky subseafloor habitat and its resident microbial community. Two new vent systems on the Mid-Cayman Rise each exhibits novel geologic settings and distinctively hydrogen-rich vent fluid compositions. We have determined and compared the chemistry, potential energy yielding reactions, abundance, community composition, diversity, and function of microbes in venting fluids from both sites: Piccard, the world's deepest vent site, hosted in mafic rocks; and Von Damm, an adjacent, ultramafic-influenced system. Von Damm hosted a wider diversity of lineages and metabolisms in comparison to Piccard, consistent with thermodynamic models that predict more numerous energy sources at ultramafic systems. There was little overlap in the phylotypes found at each site, although similar and dominant hydrogen-utilizing genera were present at both. Despite the differences in community structure, depth, geology, and fluid chemistry, energetic modelling and metagenomic analysis indicate near functional equivalence between Von Damm and Piccard, likely driven by the high hydrogen concentrations and elevated temperatures at both sites. Results are compared with hydrothermal sites worldwide to provide a global perspective on the distinctiveness of these newly discovered sites and the interplay among rocks, fluid composition and life in the subseafloor.National Aeronautics and Space Administration Grant Number: NNX09AB756; Alfred P. Sloan Foundation; NSF Grant Number: OCE10618

Potentially preventable dementia in a First Nations population in the Torres Strait and Northern Peninsula Area of North Queensland, Australia: A cross sectional analysis using population attributable fractions

Dementia is highly prevalent among Australia's First Nations peoples, including Torres Strait Islander and Aboriginal peoples in Far North Queensland (FNQ). It is likely that historically recent exposure to modifiable risk factors underlies these rates, and a large proportion of dementia may be potentially preventable. Data from two adult community health checks (2015-2018) were analyzed to determine the prevalence of 11 modifiable dementia risk factors among the First Nations residents of the Torres Strait and Northern Peninsula Area of FNQ. Population attributable fractions (PAF%) for dementia were calculated using age-standardized prevalence estimates derived from these health checks and relative risks obtained from previous meta-analyses in other populations. PAF% estimates were weighted for communality to account for overlap of risk factors. Half (52·1%) of the dementia burden in this population may be attributed to 11 potentially modifiable risk factors. Hypertension (9·4%), diabetes mellitus (9·0%), obesity (8·0%), and smoking (5·3%) were the highest contributing risk factors. The contribution of depression (2·0%) and alcohol (0·3%) was lower than other global and national estimates. While the adjusted PAF% for social isolation was low based on the adult community health check data (1·6%), it was higher (4·2%) when official census data were analyzed. These results suggest that a substantial proportion of dementia in FNQ First Nations peoples could potentially be prevented. Government investment in preventative health now is essential to reduce the future burden of dementia

Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data

Background: Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). Methods: We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018-19), National Aboriginal and Torres Strait Islander Social Survey (2014-15), National Health Survey (2017-18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. Findings: A large proportion (38·2%, 95% CI 37·2-39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1-46·7) for First Nations Australians, 36·4% (34·8-38·1) for European ancestry, and 33·6% (30·1-37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6-41·6) for all Australians. Physical inactivity (8·3%, 7·5-9·2), hearing loss (7·0%, 6·4-7·6), and obesity (6·6%, 6·0-7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. Interpretation: Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate

Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data

Background: Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). // Methods: We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018–19), National Aboriginal and Torres Strait Islander Social Survey (2014–15), National Health Survey (2017–18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. // Findings: A large proportion (38·2%, 95% CI 37·2–39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1–46·7) for First Nations Australians, 36·4% (34·8–38·1) for European ancestry, and 33·6% (30·1–37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6–41·6) for all Australians. Physical inactivity (8·3%, 7·5–9·2), hearing loss (7·0%, 6·4–7·6), and obesity (6·6%, 6·0–7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. // Interpretation: Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate. // Funding: Australian National Health and Medical Research Council and University College London Hospitals’ National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

Primary care biomarkers and dementia in people of the Torres Strait, Australia: extended data analysis

Objective: Dementia disproportionately affects First Nations populations. Biomarkers collected in primary care may assist with determining dementia risk. Our previous underpowered study showed some suggestive associations between baseline biomarkers with follow-up dementia or cognitive impairment. The current study extended this work with a larger linked dataset. Study design and setting: Probabilistic data linkage was used to combine four baseline datasets with one follow-up assessment of dementia status 0–20 years later in a First Nations population in Australia. Mixed Effects Generalized Linear Regression models were used to test associations between baseline measures and follow-up status, accounting for repeated measures within individuals. Results: Linked data were available for 88 individuals, with 101–279 baseline observations, depending on the type of measure. Higher urinary albumin to creatine ratio was associated with greater risk of cognitive impairment/dementia, whereas body weight and key lipid markers were negatively associated. There was no clear trend when these associations were examined by timing of measurement (i.e., ≤10 years or >10 years before a dementia assessment). Conclusions: The results of this study support findings from our previous work and indicate that microalbuminuria can be an early indicator of dementia risk in this population. The weight and lipid profile findings reflect the mixed results in the published literature and require further investigation and interpretation