Defying the law, negotiating change The Futanke’s opposition to the national ban on FGM in Senegal

This thesis is concerned with the politics of the preservation and ‘abandonment’ of female circumcision in Fouta Toro, Senegal. The focal point of analysis is the overt opposition to the law criminalising female genital cutting in 1999, and development projects raising awareness about excision in human rights and reproductive health education programmes. As an ethnography of the politics around bodily practices in the light of governmental and non-governmental intervention, the thesis looks at how different interest groups justify their position towards excision. This is a timely enquiry, given the Senegalese government’s ‘acceleration programme of the complete abandonment of excision by 2015’ and some Futanke leaders’ non-compliance with, and opposition to this intervention. After providing details about ‘the ban’ on ‘female genital mutilation’ in Senegal and a critical reflection on the events that are seen to have led to the call for this ban, I carefully disentangle what ‘the opposition to the law’ is and who disagrees with ‘the abandonment’ of the practice in Fouta Toro. The central part of the thesis is guided by an analysis of how excision is embedded in constructions of personhood, sociality and ethnic identity, and how the body is imagined and located in this process. I show how conceptions of ethnic purity and pride are formulated in terms of fear about a ‘loss of culture’ and ‘foreign invasion’ which nourishes discourses of opposition to the law and non-governmental intervention. Others use ‘human rights’ associated with non-governmental organisations and the state as a vehicle to express their views against excision and those who oppose its criminalisation. I examine how idioms like ‘the state’, ‘human rights’ and ‘Futanke way of life’ feature in discourses around the ban of excision in Fouta Toro, and how respectability and honour are maintained through competing representations of the female body as a site of morality. Some claim the female body – a reproducer of cultural identities – with reference to duties through kin obligations, others with reference to ‘human rights’ and ‘the state’. Based on 15 months’ ethnographic fieldwork in Fouta Toro and nine years working in and researching the impact of development in Senegal, this dissertation contributes to scholarship on Fouta Toro and indicates how governmental and non-governmental intervention stirs up the caste-related power structures of a society led by the Tooroɓɓe since the Islamic revolution in the 18th century. It shows how the female body is located as a site of morality, key to the reproduction of cultural identities

Enzyme Immobilization Strategies and Electropolymerization Conditions to Control Sensitivity and Selectivity Parameters of a Polymer-Enzyme Composite Glucose Biosensor

In an ongoing programme to develop characterization strategies relevant to biosensors for in-vivo monitoring, glucose biosensors were fabricated by immobilizing the enzyme glucose oxidase (GOx) on 125 μm diameter Pt cylinder wire electrodes (PtC), using three different methods: before, after or during the amperometric electrosynthesis of poly(ortho-phenylenediamine), PoPD, which also served as a permselective membrane. These electrodes were calibrated with H2O2 (the biosensor enzyme signal molecule), glucose, and the archetypal interference compound ascorbic acid (AA) to determine the relevant polymer permeabilities and the apparent Michaelis-Menten parameters for glucose. A number of selectivity parameters were used to identify the most successful design in terms of the balance between substrate sensitivity and interference blocking. For biosensors electrosynthesized in neutral buffer under the present conditions, entrapment of the GOx within the PoPD layer produced the design (PtC/PoPD-GOx) with the highest linear sensitivity to glucose (5.0 ± 0.4 μA cm−2 mM−1), good linear range (KM = 16 ± 2 mM) and response time (< 2 s), and the greatest AA blocking (99.8% for 1 mM AA). Further optimization showed that fabrication of PtC/PoPD-GOx in the absence of added background electrolyte (i.e., electropolymerization in unbuffered enzyme-monomer solution) enhanced glucose selectivity 3-fold for this one-pot fabrication protocol which provided AA-rejection levels at least equal to recent multi-step polymer bilayer biosensor designs. Interestingly, the presence of enzyme protein in the polymer layer had opposite effects on permselectivity for low and high concentrations of AA, emphasizing the value of studying the concentration dependence of interference effects which is rarely reported in the literature

Rapid Evolutionary Rates and Unique Genomic Signatures Discovered in the First Reference Genome for the Southern Ocean Salp, Salpa thompsoni (Urochordata, Thaliacea)

A preliminary genome sequence has been assembled for the Southern Ocean salp, Salpa thompsoni (Urochordata, Thaliacea). Despite the ecological importance of this species in Antarctic pelagic food webs and its potential role as an indicator of changing Southern Ocean ecosystems in response to climate change, no genomic resources are available for S. thompsoni or any closely related urochordate species. Using a multiple-platform, multiple-individual approach, we have produced a 318,767,936-bp genome sequence, covering \u3e50% of the estimated 602 Mb (±173 Mb) genome size for S. thompsoni. Using a nonredundant set of predicted proteins, \u3e50% (16,823) of sequences showed significant homology to known proteins and ∼38% (12,151) of the total protein predictions were associated with Gene Ontology functional information. We have generated 109,958 SNP variant and 9,782 indel predictions for this species, serving as a resource for future phylogenomic and population genetic studies. Comparing the salp genome to available assemblies for four other urochordates, Botryllus schlosseri, Ciona intestinalis, Ciona savignyi and Oikopleura dioica, we found that S. thompsoni shares the previously estimated rapid rates of evolution for these species. High mutation rates are thus independent of genome size, suggesting that rates of evolution \u3e1.5 times that observed for vertebrates are a broad taxonomic characteristic of urochordates. Tests for positive selection implemented in PAML revealed a small number of genes with sites undergoing rapid evolution, including genes involved in ribosome biogenesis and metabolic and immune process that may be reflective of both adaptation to polar, planktonic environments as well as the complex life history of the salps. Finally, we performed an initial survey of small RNAs, revealing the presence of known, conserved miRNAs, as well as novel miRNA genes; unique piRNAs; and mature miRNA signatures for varying developmental stages. Collectively, these resources provide a genomic foundation supporting S. thompsoni as a model species for further examination of the exceptional rates and patterns of genomic evolution shown by urochordates. Additionally, genomic data will allow for the development of molecular indicators of key life history events and processes and afford new understandings and predictions of impacts of climate change on this key species of Antarctic pelagic ecosystems

Successful Downstaging of High Rectal and Recto-Sigmoid Cancer by Neo-Adjuvant Chemo-Radiotherapy

© 2008 Libertas Academica Ltd. All rights reserved.Purpose: The benefit of neoadjuvant therapy for tumours above the peritoneal reflection is not clear. The purpose of this study is to demonstrate the feasibility and downstaging of treating locally advanced tumours from high rectum to distal sigmoid with preoperative chemoradiotherapy (CRT).Methods and Materials: Seventeen patients with high rectal, rectosigmoid or distal sigmoid tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI findings indicating T4 disease or threatened circumferential resection margin. All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned conformal RT, 45 Gy in 25 fractions, with a boost of 5.4–9 Gy in 3–5 fractions. Thirteen patients were treated with concomitant oral or intravenous Fluoropyrimidine chemotherapy.Results: Median follow-up was 37 months. Overall survival was 82.35% (95% Confidence Interval (CI) 54.7–93.9) and disease free survival 81.25% (95% CI 52.5–93.5). Only 1 patient suffered loco-regional relapse. Chemotherapy regimens were well tolerated, though some patients required dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage, i.e. ‘downstaged’. Six patients (35.3%) achieved complete pathological response. Clear margins were attained in all but 1 patient. Three patients were converted from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3 grade IV late toxicities (LENT-SOMA).Conclusions: Locally advanced high rectal and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable toxicity, impressive down-staging, and clear surgical margins

Quantum-safe HIBE: does it cost a Latte?

The United Kingdom (UK) government is considering advanced primitives such as identity-based encryption (IBE) for adoption as they transition their public-safety communications network from TETRA to an LTE-based service. However, the current LTE standard relies on elliptic-curve-based IBE, which will be vulnerable to quantum computing attacks, expected within the next 20-30 years. Lattices can provide quantum-safe alternatives for IBE. These schemes have shown promising results in terms of practicality. To date, several IBE schemes over lattices have been proposed, but there has been little in the way of practical evaluation. This paper provides the first complete optimised practical implementation and benchmarking of Latte, a promising Hierarchical IBE (HIBE) scheme proposed by the UK National Cyber Security Centre (NCSC) in 2017 and endorsed by European Telecommunications Standards Institute (ETSI). We propose optimisations for the KeyGen, Delegate, Extract and Gaussian sampling components of Latte, to increase attack costs, reduce decryption key lengths by 2x-3x, ciphertext sizes by up to 33%, and improve speed. In addition, we conduct a precision analysis, bounding the Rényi divergence of the distribution of the real Gaussian sampling procedures from the ideal distribution in corroboration of our claimed security levels. Our resulting implementation of the Delegate function takes 0.4 seconds at 80-bit security level on a desktop machine at 4.2GHz, significantly faster than the order of minutes estimated in the ETSI technical report. Furthermore, our optimised Latte Encrypt/Decrypt implementation reaches speeds up to 9.7x faster than the ETSI implementation

Pseudomonas aeruginosa is capable of natural transformation in biofilms

Natural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation. P. aeruginosa has a remarkable level of genome plasticity and diversity that suggests a high degree of horizontal gene transfer and recombination but is thought to be incapable of natural transformation. Here we show that P. aeruginosa possesses homologues of all proteins known to be involved in natural transformation in other bacterial species. We found that P. aeruginosa in biofilms is competent for natural transformation of both genomic and plasmid DNA. Furthermore, we demonstrate that type-IV pili (T4P) facilitate but are not absolutely essential for natural transformation in P. aeruginosa

Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids

This work presents the fabrication, characterisation and the performance of a wearable, robust, flexible and disposable chemical barcode device based on a micro-fluidic platform that incorporates ionic liquid polymer gels (ionogels). The device has been applied to the monitoring of the pH of sweat in real time during an exercise period. The device is an ideal wearable sensor for measuring the pH of sweat since it does not contents any electronic part for fluidic handle or pH detection and because it can be directly incorporated into clothing, head- or wristbands, which are in continuous contact with the skin. In addition, due to the micro-fluidic structure, fresh sweat is continuously passing through the sensing area providing the capability to perform continuous real time analysis. The approach presented here ensures immediate feedback regarding sweat composition. Sweat analysis is attractive for monitoring purposes as it can provide physiological information directly relevant to the health and performance of the wearer without the need for an invasive sampling approac

Establishment of Centromeric Chromatin by the CENP-A Assembly Factor CAL1 Requires FACT-Mediated Transcription

SummaryCentromeres are essential chromosomal structures that mediate accurate chromosome segregation during cell division. Centromeres are specified epigenetically by the heritable incorporation of the centromeric histone H3 variant CENP-A. While many of the primary factors that mediate centromeric deposition of CENP-A are known, the chromatin and DNA requirements of this process have remained elusive. Here, we uncover a role for transcription in Drosophila CENP-A deposition. Using an inducible ectopic centromere system that uncouples CENP-A deposition from endogenous centromere function and cell-cycle progression, we demonstrate that CENP-A assembly by its loading factor, CAL1, requires RNAPII-mediated transcription of the underlying DNA. This transcription depends on the CAL1 binding partner FACT, but not on CENP-A incorporation. Our work establishes RNAPII passage as a key step in chaperone-mediated CENP-A chromatin establishment and propagation

1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model

Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84-1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT(1)) expression associates with poor outcomes. CysLT(1) antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT(1) expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08-4.78), solidifying the disease relevance of CysLT(1) in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-alpha. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT(1) and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM

A study protocol for a randomised controlled feasibility trial of an intervention to increase activity and reduce sedentary behaviour in people with severe mental illness: Walking fOR Health (WORtH) Study

Abstract Background People with severe mental illness (SMI) are less physically active and more sedentary than healthy controls, contributing to poorer physical health outcomes in this population. There is a need to understand the feasibility and acceptability, and explore the effective components, of health behaviour change interventions targeting physical activity and sedentary behaviour in this population in rural and semi-rural settings. Methods This 13-week randomised controlled feasibility trial compares the Walking fOR Health (WORtH) multi-component behaviour change intervention, which includes education, goal-setting and self-monitoring, with a one-off education session. It aims to recruit 60 inactive adults with SMI via three community mental health teams in Ireland and Northern Ireland. Primary outcomes are related to feasibility and acceptability, including recruitment, retention and adherence rates, adverse events and qualitative feedback from participants and clinicians. Secondary outcome measures include self-reported and accelerometer-measured physical activity and sedentary behaviour, anthropometry measures, physical function and mental wellbeing. A mixed-methods process evaluation will be undertaken. This study protocol outlines changes to the study in response to the COVID-19 pandemic. Discussion This study will address the challenges and implications of remote delivery of the WORtH intervention due to the COVID-19 pandemic and inform the design of a future definitive randomised controlled trial if it is shown to be feasible. Trial registration The trial was registered on clinicaltrials.gov ( NCT04134871 ) on 22 October 2019