Reflections on a masterclass: poverty, social welfare and data in Sri Lanka

As part of the first ever Colombo Development Dialogue held in April 2018, a masterclass with Dr Rajesh Venugopal was organised by South Asia Centre, LSE in collaboration with UNDP in Sri Lanka. Amayaa Wijesinghe, of the University of Colombo, reports her experience

Novel Trends in Sensor Developments for Strategic Technologies in the Modern Era

Advanced trends of sensor technology are the key components within machine applications

A simple model for DNA denaturation

Following Poland and Scheraga, we consider a simplified model for the denaturation transition of DNA. The two strands are modeled as interacting polymer chains. The attractive interactions, which mimic the pairing between the four bases, are reduced to a single short range binding term. Furthermore, base-pair misalignments are forbidden, implying that this binding term exists only for corresponding (same curvilinear abscissae) monomers of the two chains. We take into account the excluded volume repulsion between monomers of the two chains, but neglect intra-chain repulsion. We find that the excluded volume term generates an effective repulsive interaction between the chains, which decays as $1/r^{d-2}$. Due to this long-range repulsion between the chains, the denaturation transition is first order in any dimension, in agreement with previous studies.Comment: 10 page

The Intrinsic Plasticity Of Medial Vestibular Nucleus Neurons During Vestibular Compensation: A Systematic Review And Meta-Analysis

The diversity of activity displayed by neurons of the central nervous system is unmatched by any other cell in the body. Each neuron displays a characteristic, stereotypic pattern of firing which often defines its functional role (Llinas, 1988). Some neurons are spontaneously active at rest, displaying pacemaker-like properties, while others are very quiescent until stimulated by synaptic inputs. Some neurons fire rapid, regular action potential trains which show little deterioration in frequency over time. Others fire only short bursts of action potentials and reduce their rate of firing quickly, producing very little response to even large inputs (Bean, 2007). These discharge characteristics are fundamentally determined by two main features: the intrinsic membrane properties of the neuron and the nature of the synaptic inputs the neuron receives. Intrinsic properties are those relating to the architecture of the neuronal membrane, intracellular ionic buffers that regular electrolyte concentrations and the types of ion channels expressed on the membrane and their pattern of distribution (Wijesinghe & Camp, 2011). Meanwhile, synaptic properties are determined by the types of transmitters arriving at the neuronal surface, the distribution of these synapses and their density over various functionally specialised regions of the neuron (Spruston, 2008). From the various permutations of these different properties emerges the vast array of different firing characteristics observed of individual neurons from different regions of the brain (Llinas, 2014). Despite the prevalent stereotypy observed across different subtypes of neurons, alterations in the local environment and external stimuli can induce changes in these basic properties. This phenomenon, known as neuronal plasticity, has been observed in normal physiological states and is believed to underlie experience-dependent changes in neural activity such as learning and memory (Mayford, Siegelbaum & Kandel, 2012; Sweatt, 2016). It has also been observed in various disease states and may act as a homeostatic mechanism to downregulate excitotoxicity or restore lost functional capacities (Beck & Yaari, 2008; Camp, 2012; Vitureira, Letellier & Goda, 2012; Yin & Yuan, 2014). These changes were first observed to occur in synapses, where high intensity stimuli induced changes that altered the likelihood of signal transmission at a particular synapse. Since then, the stimuli that induce synaptic plasticity and the cellular mechanisms that maintain these changes have been widely investigated (Bailey, Kandel & Harris, 2015; Kandel, 2001). However, it has now been recognised that intrinsic neuronal properties themselves are plastic and may contribute to some of the processes previously attributed to synaptic mechanisms alone (Desai, 2003; Hanse, 2008; Mozzachiodi & Byrne, 2010; Titley, Brunel & Hansel, 2017). A number of studies in the past 30 years have demonstrated important activity-dependent changes in firing dynamics that appear to be act along multiple timescales and influence network activity in a variety of ways. These changes, termed intrinsic plasticity, are manifest in the patterns and frequency of action potential discharge of individual neurons. This dynamism is primarily driven by alterations in ion channel expression, excitatory neurotransmitter receptor expression and intracellular buffering protein concentrations (Beraneck & Idoux, 2012; Camp & Wijesinghe, 2009). I am interested in the studying the basic intrinsic properties of individual neurons, how they determine discharge dynamics in networks, and the conditions that modulate these properties (for example see previous work in Camp & Wijesinghe, 2009; Wijesinghe & Camp, 2011; Wijesinghe, Solomon & Camp, 2013; Wijesinghe et al., 2015). In particular, I am interested in how pathological changes might influence the firing properties of downstream neurons. Typically, animal models with a simple neuronal circuit, an easily lesioned peripheral sensory organ and observable behaviours have been chosen for such studies. One such model system is the vestibular system, which maintains our sense of equilibrium. It is composed of an easily accessible neuronal circuit within the brainstem which is homologous between a number of species (Goldberg et al., 2012). It mediates basic reflexes that maintain gaze stability during head movement and stabilises dynamic posture (Bronstein, Patel & Arshad, 2015). This sensory modality also has a unique property of near immediate recovery following damage to the components that mediate it, a process known as vestibular compensation (Curthoys & Halmagyi, 1995). This process occurs in humans and can be reliably reproduced experimentally, making it a convenient model to bridge in vitro findings to clinical observations (Straka, Zwergal & Cullen, 2016). Recent studies have suggested that vestibular compensation may be behavioural correlate of a form of experience-dependent plasticity occurring within the vestibular nuclei of the brainstem (Dutia, 2010; Lacour & Tighilet, 2010; Macdougall & Curthoys, 2012). More interestingly, part of the recovery may be mediated by changes in the intrinsic properties of vestibular nucleus neurons in a way that is necessary for the process to occur. In the thesis that follows, I present the first comprehensive systematic review of the scientific literature searching for evidence to investigate the following hypothesis: intrinsic plasticity mediates changes observed during the acute phase of vestibular compensation. To determine the methodological quality of studies discovered through searches of electronic databases, I independently developed tools to assess the precision, validity and bias of each study. Based on a total of 17 studies which met pre-determined inclusion and exclusion criteria, I conclude that there is evidence in favour of the hypothesis. Then, pooling quantitative data from this evidence, I performed a meta-analysis which demonstrates a moderate, statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, their spontaneous discharge rate increases by 4 spikes/sec on average and their sensitivity (or gain) in response to current stimuli increases. Using this novel approach, I demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental studies with similar aims. I also identify a number of areas in which the reporting of experimentation in field of vestibular research can be improved to strengthen the quality and validity of future work. Despite the prevalent stereotypy observed different subtypes of neurons, alterations in the local environment and external stimuli can induce changes in these basic properties. This phenomenon, known as neuronal plasticity, has been observed in normal physiological states and is believed to underlie experience-dependent changes in neural activity such as learning and memory (Mayford, Siegelbaum et al. 2012, Sweatt 2016). It has also been observed in various disease states and may act as a homeostatic mechanism to downregulate excitotoxicity or restore lost functional capacities (Beck and Yaari 2008, Camp 2012, Vitureira, Letellier et al. 2012, Yin and Yuan 2014). These changes were first observed to occur in synapses, where high intensity stimuli induced changes that altered the likelihood of signal transmission at a particular synapse. Since then, the stimuli that induce synaptic plasticity and the cellular mechanisms that maintain these changes have been widely investigated (Kandel 2001, Bailey, Kandel et al. 2015). However, it has now been recognised that intrinsic neuronal properties themselves are plastic and may contribute to some of the processes previously solely attributed to synaptic mechanisms (Desai 2003, Hanse 2008, Mozzachiodi and Byrne 2010, Titley, Brunel et al. 2017). A number of studies in the past 20 years have demonstrated important activity dependent changes in firing dynamics that appear to be act along multiple timescales and influence network activity in a variety of ways. These changes, termed intrinsic plasticity, are manifest in the patterns and frequency of action potential discharge of individual neurons. This dynamism is primarily driven by alterations in ion channel expression, excitatory neurotransmitter receptor expression and intracellular buffering protein concentrations (Camp and Wijesinghe 2009, Beraneck and Idoux 2012). I am interested in the studying the basic intrinsic properties of individual neurons, how they determine discharge dynamics in networks, and the conditions that modulate these properties. In particular, I am interested in how pathological changes might influence the firing properties of downstream neurons. Typically, animal models with a simple neuronal circuit, an easily lesioned peripheral sensory organ and observable behaviours have been chosen for such studies. One such model system is the vestibular system, which maintains an animal’s sense of equilibrium. It is composed of an easily accessible neuronal circuit within the brainstem which is homologous between a number of species (Goldberg, Wilson et al. 2012). It mediates basic reflexes that maintain gaze stability during head movement (vestibuloocular reflex) and stabilises posture (vestibulospinal reflex) (Bronstein, Patel et al. 2015). This sensory modality also has a unique property of near immediate and complete recovery following damage to the components that mediate it, a process known as vestibular compensation (Curthoys and Halmagyi 1995). For example, following unilateral peripheral vestibular lesions, the acute symptom of vertigo and its behavioural effects abate spontaneously within days (Fetter 2016). This process occurs in humans and can be reliably reproduced experimentally, making it a convenient and ideal model to bridge in vitro findings to clinical observations (Straka, Zwergal et al. 2016). Recent studies have suggested that vestibular compensation may be a form of experience dependent plasticity which occurs within the brainstem vestibular reflex arc, most clearly in the vestibular nuclei (Dutia 2010, Lacour and Tighilet 2010, Macdougall and Curthoys 2012). More interestingly, part of the recovery may be mediated by changes in the intrinsic properties of vestibular nucleus neurons. Many of these changes are of the firing patterns and sensitivity to external stimuli, reflecting changes in the intrinsic properties of these. In the thesis that follows, I present a systematic review of the scientific literature looking for evidence to investigate the following hypothesis: intrinsic plasticity mediates changes observed during vestibular compensation. To determine the quality of studies revealed through searches of electronic databases, I independently developed tools to assess the precision, validity and bias of each study. Based on a total of 16 studies which met pre-determined inclusion and exclusion criteria, I conclude that there is moderate amount of moderate quality evidence, and a small amount of high quality evidence, in favour of the hypothesis. Further, using quantitative data from rodent models of compensation, I performed a meta-analysis which demonstrates strong, statistically significant evidence in favour of the hypothesis. In summary, published evidence to date supports the notion that unilateral vestibular lesions induce changes in the intrinsic membrane properties of medial vestibular nucleus neurons such that their spontaneous discharge rate increases and their sensitivity (or gain) in response to current stimuli increases

Strategic marketing plan for an online service provider in the property management industry

Outlines the development of a strategic marketing plan for a company offering online rent payment, apartment search and property management services to property owners, managers and tenants. Data was gatherd from both primary (customers survey) and secondary sources to develop a strategic marketing plan for 2006

Oxygen therapy in respiratory disorders

PhDOxygen therapy remains a cornerstone of medical practice and is generally regarded as being safe. However, there is a lack of clinical evidence to support the routine use of oxygen therapy, and in certain conditions, injudicious oxygen may cause harm. In this thesis, I will present two audits and three randomised controlled trials of oxygen therapy. Methods A prospective audit of the prescription and use of oxygen therapy before and after the introduction of an oxygen prescription section on a drug chart A retrospective audit of ambulance oxygen administration, in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) Two randomised controlled trials of high flow versus titrated oxygen in 150 patients with community acquired pneumonia and 106 patients with acute severe asthma A randomised controlled trial of 24 subjects with obesity hypoventilation syndrome (OHS) comparing 100% oxygen with air Results Oxygen prescription is suboptimal in hospital inpatients. Whilst an oxygen prescription section improved prescription, this intervention did not improve clinical practice Over 70% of patients presenting with AECOPD received high flow oxygen prior to presentation to the emergency department. The risk of adverse outcomes increased progressively with increased PaO2 High concentration oxygen leads to a rise in PaCO2 compared to titrated oxygen, when administered to patients presenting with asthma or pneumonia Breathing 100% oxygen leads to a rise in PaCO2 in patients with OHS Conclusion This series of studies has shown that further measures are warranted to ensure the safe practice of oxygen therapy in the pre-hospital and hospital setting. In addition, the findings suggest that the potential for high concentration oxygen therapy to increase PaCO2 is not limited to COPD but may occur in other respiratory conditions in which abnormal gas exchange or respiratory drive are present

ROLE OF BUDDHIST SPIRITUAL PRACTICE IN THE LIVES AND HEALTH OF BUDDHIST NUNS LIVING WITH A CHRONIC ILLNESS IN SRI LANKA

This study focused on the role of Buddhist spiritual practice in the lives and health of Sri Lankan Buddhist nuns with a chronic illness. The concept of spirituality has emerged recurrently in research as a means to cope with chronic illness. The question as to whether Buddhism, as observed in traditionally Buddhist countries, influences coping in chronic illness, has received little attention. Buddhism covers several sects and even within the same sect practices vary depending on each socio-cultural environment. Any attempt to study Buddhism\u27s role in chronic illness requires isolating not only a sect, but also a country in which it is practiced. A focus on Sri Lankan Buddhism is important because it is generally believed that the oldest form of Theravada Buddhism remains preserved in Sri Lanka. The choice of the Buddhist nun serves the pragmatic purpose of allowing a female researcher access to conduct interviews in privacy. In order to ground the findings in the data, this descriptive ethnography followed the iterative, and recursive linguistic approach of Spradley (1979, 1980). The 45 primary participants, Sri Lankan Buddhist nuns with a chronic illness were selected through a snow-ball sampling strategy. Twenty secondary informants were identified to shed light on the topic from health-care, lay-Buddhist, and Buddhist-scholar perspective. Participant observation and semistructured interviews were used to explore cultural domains, to clarify each domain with taxonomies, and finally to uncover cultural themes. The repeating cultural theme was identified as responsibility, which took four forms: responsibility to the Buddha, to others (social circle), to self-liberate oneself through meditation, and to find security in old age. Nuns shaped their Buddhist spiritual practices to suit their sense of these responsibilities. The role of spiritual practice in their health was mediated by the strength of their resolve to fulfill their responsibility and resources, against a backdrop of the Buddhist phenomenon of impermanence. Their coping styles ranged from health-seeking to resigned acceptance. Incorporating the viewpoints of primary and secondary informants indicated these behaviors resembled constructs of the theory of Salutogenesis (Antonovsky 1979). Implications for nursing research, education, practice, and policy are discussed