Amazonian dark earths and Caboclo subsistence on the middle Madeira River, Brazil

This thesis examines the relationship between Amazonian Dark Earths (ADE) and Caboclo subsistence on the Middle Madeira River, Brazil. ADE are fertile anthropogenic (man-made) soils formed through practices of burning and waste disposal by pre-Columbian Amerindian populations. “Caboclo” is a social category that refers to the people of diverse origins that form the majority of the contemporary rural population of Brazilian Amazonia. Bitter manioc fields (roças) and homegardens (sítios) are the principal forms of Caboclo subsistence cultivation on ADE on the Middle Madeira River. Multi-sited ethnography shows that differences in historical ecology at both local and regional scales either enable or constrain Caboclo subsistence cultivation on ADE. At communities located on long-term landholdings with a history of egalitarian land-tenure and multi-generational kinship there is a rich body of local knowledge and practice relating to the cultivation of ADE. Interviews with 249 farmers in six localities demonstrate that bitter manioc cultivation in fertile soils (floodplain and ADE) tends to be characterised by intensive swidden systems with smaller fields, shorter fallows, and a predominance of what locals refer to as “weak” (low starch fast maturing) landraces. Bitter manioc cultivation in infertile soils (Oxisols and Ultisols) is characterised by more extensive shifting cultivation systems with larger fields, longer fallows and a predominance of what locals refer to as “strong” (high starch slow maturing) landraces. Interviews with 63 households at 16 communities show that homegardens on ADE combine the most common species of homegardens on Oxisols and in the Floodplain, with other species that occur most frequently on ADE. Homegardens on ADE exhibit significantly higher culturally salient species diversity when compared to homegardens on the other types of soil. Collectively, bitter manioc fields and homegardens constitute cultivated landscapes that show diverging agrobiodiversity on different soils, the outcome of an interplay between soil affordances, Caboclo agency and plant responses over time. These findings provide a springboard for some conclusions concerning the relationship between ADE and agriculture in the pre-Columbian period, drawing on what is known from the historical and archaeological record

Counter-conducts and the green grab:Forest peoples’ resistance to industrial resource extraction in the Saracá-Taquera National Forest, Brazilian Amazonia

This paper contributes to the theory of environmentality – the ‘conduct of conduct’ with regard to the environment - by incorporating Foucault’s notion of counter-conducts to elucidate the subjectivities emergent from the performance of dissent in relation to different forms of power - sovereign, disciplinary and biopower - through which a spatialized rational-technical governmentality of ‘green’ mining and logging is enacted in Saracá-Taquera National Forest (FLONA), Brazilian Amazonia. We analyse the counter-conductive subjectivities emergent from forest peoples’ political articulation through identity categories riberinhos and quilombolas (enshrined in the 1988 Constitution and subsequent laws), claiming of rights to delimit areas of traditional use and ancestral territories, along with direct action, critical discourse and reassertion of agroecological knowledge against industrial resource extraction. To capture the dynamic relation of the conduct of conduct to counter-conducts we draw on a late Foucauldian model of a self, wherein his earlier focus on how the Panopticon shapes self-discipline is complemented by a turn to care for and ethics of the self - practices of freedom through which subjects have the potential to transcend self-discipline. We use this lens to illuminate two case-studies, one focusing on mining, the other on timber, exploring how in this protected area - which permits the ‘sustainable’ industrial extraction of natural resources - the state, companies and an NGO try to shape forest peoples as ‘green’ subjects. Counter-conducts provide the theory of environmentality with a broader perspective on resistance foregrounding the production of political subjectivities in dissent whilst breaking with the resistance-domination binary

Convergent adaptations: bitter manioc cultivation systems in fertile anthropogenic dark earths and floodplain soils in central Amazonia

Shifting cultivation in the humid tropics is incredibly diverse, yet research tends to focus on one type: long-fallow shifting cultivation. While it is a typical adaptation to the highly-weathered nutrient-poor soils of the Amazonian terra firme, fertile environments in the region offer opportunities for agricultural intensification. We hypothesized that Amazonian people have developed divergent bitter manioc cultivation systems as adaptations to the properties of different soils. We compared bitter manioc cultivation in two nutrient-rich and two nutrient-poor soils, along the middle Madeira River in Central Amazonia. We interviewed 249 farmers in 6 localities, sampled their manioc fields, and carried out genetic analysis of bitter manioc landraces. While cultivation in the two richer soils at different localities was characterized by fast-maturing, low-starch manioc landraces, with shorter cropping periods and shorter fallows, the predominant manioc landraces in these soils were generally not genetically similar. Rather, predominant landraces in each of these two fertile soils have emerged from separate selective trajectories which produced landraces that converged for fast-maturing low-starch traits adapted to intensified swidden systems in fertile soils. This contrasts with the more extensive cultivation systems found in the two poorer soils at different localities, characterized by the prevalence of slow-maturing high-starch landraces, longer cropping periods and longer fallows, typical of previous studies. Farmers plant different assemblages of bitter manioc landraces in different soils and the most popular landraces were shown to exhibit significantly different yields when planted in different soils. Farmers have selected different sets of landraces with different perceived agronomic characteristics, along with different fallow lengths, as adaptations to the specific properties of each agroecological micro-environment. These findings open up new avenues for research and debate concerning the origins, evolution, history and contemporary cultivation of bitter manioc in Amazonia and beyond

Cultural valuation and biodiversity conservation in the Upper Guinea Forest, West Africa

The cultural valuation of biodiversity has taken on renewed importance over the last two decades as the ecosystem services framework has become widely adopted. Conservation initiatives increasingly use ecosystem service frameworks to render tropical forest landscapes and their peoples legible to market-oriented initiatives such as REDD+ and biodiversity offsetting schemes. Ecosystem service approaches have been widely criticized by scholars in the social sciences and humanities for their narrow focus on a small number of easily quantifiable and marketable services and a reductionist and sometimes simplistic approach to culture. We address the need to combine methods from each of the “three cultures” of natural science, quantitative social science, and qualitative social science/humanities in conceptualizing the relationship between cultural valuation and biodiversity conservation. We combine qualitative data with forest inventories and a quantitative index of cultural value to evaluate the relationship between cultural valuation and biodiversity conservation in Upper Guinea forest in Liberia, West Africa. Our study focuses on “sacred agroforests,” spaces that are associated with Mande macro-language speaking groups such as the Loma. We demonstrate that sacred agroforests are associated with different cultural values compared with secondary forests. Although biodiversity and biomass are similar, sacred agroforests exhibit a different species composition, especially of culturally salient species, increasing overall landscape agro-biodiversity. Sacred agroforests are also shaped and conserved by local cultural institutions revolving around ancestor worship, ritual, and the metaphysical conceptual category “salɛ.” We conclude that to understand the relationship between cultural valuation and biodiversity conservation, interpretivist approaches such as phenomenology should be employed alongside positivist ecosystem service frameworks

Getting shot of elves: healing, witchcraft and fairies in the Scottish witchcraft trials

This paper re-examines the evidence of the Scottish witchcraft trials for beliefs associated by scholars with "elf-shot." Some supposed evidence for elf-shot is dismissed, but other material illuminates the interplay between illness, healing and fairy-lore in early modern Scotland, and the relationship of these beliefs to witchcraft itself

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. Methods: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. Results: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. Discussion: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure