All-optical phase and amplitude regeneration properties of a 40 Gbit/s DPSK black-box phase sensitive amplifier

We experimentally study the pure amplitude and phase regeneration capabilities of a blackbox degenerate four wave mixing (FWM) based bit-rate-flexible phase sensitive amplifier (PSA) for a 40 Gbit/s differential phase-shift keyed (DPSK) signal

Patterns of Public Participation: Opportunity Structures and Mobilization from a Cross-National Perspective

PURPOSE: The paper summarizes data from twelve countries, chosen to exhibit wide variation, on the role and place of public participation in the setting of priorities. It seeks to exhibit cross-national patterns in respect of public participation, linking those differences to institutional features of the countries concerned. DESIGN/METHODOLOGY/APPROACH: The approach is an example of case-orientated qualitative assessment of participation practices. It derives its data from the presentation of country case studies by experts on each system. The country cases are located within the historical development of democracy in each country. FINDINGS: Patterns of participation are widely variable. Participation that is effective through routinized institutional processes appears to be inversely related to contestatory participation that uses political mobilization to challenge the legitimacy of the priority setting process. No system has resolved the conceptual ambiguities that are implicit in the idea of public participation. ORIGINALITY/VALUE: The paper draws on a unique collection of country case studies in participatory practice in prioritization, supplementing existing published sources. In showing that contestatory participation plays an important role in a sub-set of these countries it makes an important contribution to the field because it broadens the debate about public participation in priority setting beyond the use of minipublics and the observation of public representatives on decision-making bodies

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.Massachusetts Institute of Technology. Faculty Discretionary Research FundNational Institutes of Health (U.S.) (Award UL1 RR 025758)Harvard Catalyst (Grant

Patterns of public participation: opportunity structures and mobilization from a cross-national perspective

Purpose: The paper summarizes data from twelve countries, chosen to exhibit wide variation, on the role and place of public participation in the setting of priorities. It seeks to exhibit cross-national patterns in respect of public participation, linking those differences to institutional features of the countries concerned. Design/methodology/approach: The approach is an example of case-orientated qualitative assessment of participation practices. It derives its data from the presentation of country case studies by experts on each system. The country cases are located within the historical development of democracy in each country. Findings: Patterns of participation are widely variable. Participation that is effective through routinized institutional processes appears to be inversely related to contestatory participation that uses political mobilization to challenge the legitimacy of the priority setting process. No system has resolved the conceptual ambiguities that are implicit in the idea of public participation. Originality/value: The paper draws on a unique collection of country case studies in participatory practice in prioritization, supplementing existing published sources. In showing that contestatory participation plays an important role in a sub-set of these countries it makes an important contribution to the field because it broadens the debate about public participation in priority setting beyond the use of minipublics and the observation of public representatives on decision-making bodies

Separation of reducing sugars from lignocellulosic hydrolysate: Membrane experiments & system dynamic modelling

Separation of fermentable sugars after hydrolysis of lignocellulosic biomass plays a vital role in second-generation biofuel production. Byproducts and solid fractions generated during pretreatment and hydrolysis can have adverse effects on fermentation efficiency. Previous studies have shown that a maximum of 40% (w/w) of sugar yield can be obtained by sequential UF and NF permeate recovery. This study aimed to introduce a multi-step membrane filtration process to recover fermentable sugars while removing inhibitory bi-products. Fermentable sugar recovery was investigated using a recirculation flow between various stages of separation. The experimental results demonstrated that by introducing NF permeate recirculation to the UF unit a sequential UF/NF system can achieve 60% (w/w%) recovery of reducing sugars. Based on the experimental results, a ‘Simultaneous ultrafiltration and nanofiltration model’ was developed using system dynamics. The model was used to predict the final sugar concentration and sugar yield using sugar permeability in each membrane as the dynamic variability. The model predicts that high sugar permeability (or selective permeability) through the ultrafiltration mostly affects the efficiency of the system, which still is a challenge

Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands

Advancing Mathematical Models of Mycobacterium tuberculosis Transmission to Support Vaccine Introduction

INTRODUCTION: Tuberculosis causes substantial morbidity and mortality, with 10 million new cases and 1.5 million deaths per year worldwide. We may acquire a new tuberculosis prevention tool in the foreseeable future as the anti-tuberculosis vaccine candidate M72/AS01E is poised to enter phase III trials. If phase III trials demonstrate efficacy, we must ensure that models and model evidence are rapidly and reliably available to support decision making around whether to introduce the new vaccine. Prior mathematical models of tuberculosis vaccination have aimed to inform vaccine development, for example, by investigating the impact of varying vaccine durability and efficacy, or the host-infection status required for vaccine efficacy in low and high burden settings. These studies have identified vaccine characteristics most likely to achieve global tuberculosis control goals, providing core evidence for the World Health Organization (WHO) Preferred Product Characteristics for New Tuberculosis Vaccines. Collectively, this evidence has provided direction for vaccine research and development efforts, including the identification of indications and clinical trial endpoints. However, work to substantiate vaccine introduction, bridging the gap between development and broad-scale adoption, is limited. I address two aims in this thesis, corresponding to two research needs that we should meet to advance models to support vaccine introduction: 1. Estimate the epidemiologic impact, cost-effectiveness and affordability of new tuberculosis vaccines in India and China, incorporating drug-resistance transmission and acquisition. This aim reflects the need to adapt models to include locally important features of, and uncertainty in, tuberculosis epidemiology and health systems. 2. Describe how different assumptions of adapting social contact structures to long-term demographic trends in India—as a country undergoing the demographic transition—might affect vaccine impact estimates. This aim reflects the need to establish whether vaccine impact estimates are robust to structural decisions in model design. METHODS: I constructed an age-, drug-resistance, and treatment-history stratified difference equation-based dynamic transmission model of Mycobacterium tuberculosis, set in India and China, calibrated to epidemiologic data over 2000–2017. To this, I attached a country-specific cost model of programmatic tuberculosis control—including multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) diagnosis and treatment—and vaccine delivery. The calibrated model was used to estimate the epidemiologic impact and cost-effectiveness of a prevention-of-disease vaccine modelled on M72/AS01E, with 50% efficacy, conferring 10-years of protection over 2027–2050. To assess the affordability of vaccine deployment, I estimated the total cost of untargeted mass vaccination of all adults and adolescents (ages ≥ 10y) compared to 10-year wide age bands in India and China, while valuing the health benefits of vaccination at cost-effectiveness thresholds based on country-specific healthcare opportunity costs. Finally, I developed a second transmission model of tuberculosis to investigate whether adapting age-specific social contact patterns to evolving demography—using multiple update methods, each preserving different properties of social mixing matrices—affected model-based estimates of vaccine impact in an India-like scenario. Results Vaccination was found to substantially reduce future MDR/RR-TB in China and India, reducing incidence rate by 73% (uncertainty interval: 66–76) and 72% (UI: 65–77) in 2050, with a similar impact on drug-susceptible tuberculosis. In both countries, vaccination was found likely to be cost-effective at country-specific willingness to pay thresholds. Untargeted yet cost-effective large scale adult mass vaccination was estimated to require $21 billion (uncertainty interval: 16–27) and$15 billion (UI: 12–29) by 2050 in India and China, respectively. In India and China, targeting 50–59-year-olds and 60–69-year-olds, respectively, was found to avert the most disability-adjusted life-years per vaccine course delivered. Targeted yet cost-effective mass vaccination of these age groups was estimated to require $5 billion (UI: 4–6) and$6 billion (UI: 4–7) in India and China, respectively. Vaccine epidemiologic impact estimates remained robust to different methods of updating age-specific social contact structures to match secular trends in demography. Across a range of methods that spanned no updates to match demography, to methods that preserved both contact reciprocity (balanced total contacts between age groups) and assortativity (inherent preference for contact by age-group with another), the maximum difference in vaccine-mediated incidence rate reduction in 2050 was found to be 7%. CONCLUSIONS: In this thesis, I develop mathematical models that provide evidence to support decision making around tuberculosis vaccine introduction. This thesis makes three unique contributions to the tuberculosis vaccine modelling literature: estimating the impact of new tuberculosis vaccines on MDR/RR-TB, incorporating both direct and transmission effects of a vaccine, estimating the total maximum cost of large scale adult tuberculosis vaccination at country-specific healthcare opportunity cost-based thresholds, and investigating whether structural assumptions around how social contact patterns change with evolving demography affect estimates of vaccine impact. Vaccines are predicted to substantially and cost-effectively reduce the future burden of drug-resistant (and drug-susceptible) tuberculosis in India and China and could be an integral tool in MDR/RR-TB control efforts. The expected total cost of cost-effective untargeted mass adult vaccination for tuberculosis is likely to be substantial at current willingness-to-pay thresholds, but age-targeting may improve affordability. Funding for tuberculosis vaccines will require a careful situating within that for wider tuberculosis control efforts. Vaccine impact estimates may be reasonably robust to different methods of updating social contact patterns to evolving demography. This finding improves confidence in existing estimates of vaccine impact from long time-horizon models and increases the utility of model results in vaccine decision making. Overall, this thesis adds evidence in favour of tuberculosis vaccine introduction, contributing to the initial knowledge base that decision-makers may build on to address further context-specific questions regarding vaccine feasibility and implementation

Rational use of antibiotics by community health workers and caregivers for children with suspected pneumonia in Zambia: A cross-sectional mixed methods study

Background: Antibiotic resistance is an issue of growing global concern. One key strategy to minimise further development of resistance is the rational use of antibiotics, by providers and patients alike. Through integrated community case management (iCCM), children diagnosed with suspected pneumonia are treated with antibiotics; one component of an essential package to reduce child mortality and increase access to health care for remote populations. Through the use of clinical algorithms, supportive supervision and training, iCCM also offers the opportunity to improve the rational use of antibiotics and limit the spread of resistance in resource-poor contexts. This study provides evidence on antibiotic use by community health workers (CHWs) and caregivers to inform iCCM programmes, safeguarding current treatments whilst maximising access to care. Methods: 1497 CHW consultations were directly observed by non-clinical researchers, with measurement of respiratory rate by CHWs recorded by video. Videos were used to conduct a retrospective reference standard assessment of respiratory rate by experts. Fifty-five caregivers whose children were prescribed a 5-day course of antibiotics for suspected pneumonia were followed up on day six to assess adherence through structured interviews and pill counts. Six focus group discussions and nine in depth interviews were conducted with CHWs and caregivers to supplement quantitative findings. Results: The findings indicate that CHWs adhered to treatment guidelines for 92 % of children seen, prescribing treatment corresponding to their assessment. However, only 65 % of antibiotics prescribed were given for children with experts' confirmed fast breathing pneumonia. Qualitative data indicates that CHWs have a good understanding of pneumonia diagnosis, and although caregivers sometimes applied pressure to receive drugs, CHWs stated that treatment decisions were not influenced. 46 % of caregivers were fully adherent and gave their child the full 5-day course of dispersible amoxicillin. If caregivers who gave treatment for 3 to 5 days were considered, adherence increased to 76 %. Conclusions: CHWs are capable of prescribing treatment corresponding to their assessment of respiratory rate. However, rational use of antibiotics could be strengthened through improved respiratory rate assessment, and better diagnostic tools. Furthermore, a shorter course of dispersible amoxicillin could potentially improve caregiver adherence, reducing risk of resistance and cost