Dapsone hydroxylamine induces premature removal of human erythrocytes by membrane reorganization and antibody binding

N-hydroxylation of dapsone leads to the formation of the toxic hydroxylamines responsible for the clinical methaemoglobinaemia associated with dapsone therapy. Dapsone has been associated with decreased lifespan of erythrocytes, with consequences such as anaemia and morbidity in patients treated with dapsone for malaria. Here, we investigated how dapsone and/or its hydroxylamine derivative (DDS-NHOH) induced erythrocyte membrane alterations that could lead to premature cell removal.

Exits, entrances and entrepreneurship : an exploration of economic theories of entrepreneurship through new independent entry and infant exit

The thesis began as a study of new firm formation. Preliminary research suggested that infant death rate was considered to be a closely related problem and the search was for a theory of new firm formation which would explain both. The thesis finds theories of exit and entry inadequate in this respect and focusses instead on theories of entrepreneurship, particularly those which concentrate on entrepreneurship as an agent of change. The role of information is found to be fundamental to economic change and an understanding of information generation and dissemination and the nature and direction of information flows is postulated to lead coterminously to an understanding of entrepreneurhsip and economic change. The economics of information is applied to theories of entrepreneurhsip and some testable hypotheses are derived. The testing relies on etablishing and measuring the information bases of the founders of new firms and then testing for certain hypothesised differences between the information bases of survivors and non-survivors. No theory of entrepreneurship is likely to be straightforwardly testable and many postulates have to be established to bring the theory to a testable stage. A questionnaire is used to gather information from a sample of firms taken from a new micro-data set established as part of the work of the thesis. Discriminant Analysis establishes the variables which best distinguish between survivors and non-survivors. The variables which emerge as important discriminators are consistent with the theory which the analysis is testing. While there are alternative interpretations of the important variables, collective consistency with the theory under test is established. The thesis concludes with an examination of the implications of the theory for policy towards stimulating new firm formation.

Is breast best? Perceptions of infant feeding

This study explored the reasons why young women from low income areas are among those least likely to breastfeed. Focus groups were conducted with 15 health professionals and 11 young, first time mothers were interviewed. Health professionals participating believed that white communities endorsed bottle feeding while Pakistani and Bangladeshi communities, although they accepted breastfeeding more readily, were likely to give prelacteal feeds of non-breast milk and to delay weaning. The interviews with mothers revealed a belief that 'breast is best' but factors intervened in a detrimental way resulting in the decision not to breastfeed or in early cessation. Participating mothers expected breastfeeding to be painful and were preoccupied with feeding and weight gain. The desire to have 'fat bonnie babies' demonstrated the mothers' moral attempts to be perceived as 'good mothers' although their actions went against the knowledge that 'breast is best'. Recommendations include educating health professionals about subcultures in their communities and reversing the misconception that breast milk is insufficient for a baby's healthy development. Promoting breastfeeding must include the crucial message that breast milk contains all the nourishment a baby needs.

Objective and psychophysical studies of infant visual development

Distortion or deprivation of vision during an early `critical' period of visual development can result in permanent visual impairment which indicates the need to identify and treat visually at-risk individuals early. A significant difficulty in this respect is that conventional, subjective methods of visual acuity determination are ineffective before approximately three years of age. In laboratory studies, infant visual function has been quantified precisely, using objective methods based on visual evoked potentials (VEP), preferential looking (PL) and optokinetic nystagmus (OKN) but clinical assessment of infant vision has presented a particular difficulty. An initial aim of this study was to evaluate the relative clinical merits of the three techniques. Clinical derivatives were devised, the OKN method proved unsuitable but the PL and VEP methods were evaluated in a pilot study. Most infants participating in the study had known ocular and/or neurological abnormalities but a few normals were included for comparison. The study suggested that the PL method was more clinically appropriate for the objective assessment of infant acuity. A study of normal visual development from birth to one year was subsequently conducted. Observations included cycloplegic refraction, ophthalmoscopy and preferential looking visual acuity assessment using horizontally and vertically oriented square wave gratings. The aims of the work were to investigate the efficiency and sensitivity of the technique and to study possible correlates of visual development. The success rate of the PL method varied with age; 87% of newborns and 98% of infants attending follow-up successfully completed at least one acuity test. Below two months monocular acuities were difficult to secure; infants were most testable around six months. The results produced were similar to published data using the acuity card procedure and slightly lower than, but comparable with acuity data derived using extended PL methods. Acuity development was not impaired in infants found to have retinal haemorrhages as newborns. A significant relationship was found between newborn binocular acuity and anisometropia but not with other refractive findings. No strong or consistent correlations between grating acuity and refraction were found for three, six or twelve months olds. Improvements in acuity and decreases in levels of hyperopia over the first week of life were suggestive of recovery from minor birth trauma. The refractive data was analysed separately to investigate the natural history of refraction in normal infants. Most newborns (80%) were hyperopic, significant astigmatism was found in 86% and significant anisometropia in 22%. No significant alteration in spherical equivalent refraction was noted between birth and three months, a significant reduction in hyperopia was evident by six months and this trend continued until one year. Observations on the astigmatic component of the refractive error revealed a rather erratic series of changes which would be worthy of further investigation since a repeat refraction study suggested difficulties in obtaining stable measurements in newborns. Astigmatism tended to decrease between birth and three months, increased significantly from three to six months and decreased significantly from six to twelve months. A constant decrease in the degree of anisometropia was evident throughout the first year. These findings have implications for the correction of infantile refractive error.

Premature cardiovascular events and mortality in south Asians with type 2 diabetes in the United Kingdom Asian Diabetes Study - effect of ethnicity on risk

Background/Aim - People of south Asian origin have an excessive risk of morbidity and mortality from cardiovascular disease. We examined the effect of ethnicity on known risk factors and analysed the risk of cardiovascular events and mortality in UK south Asian and white Europeans patients with type 2 diabetes over a 2 year period. Methods - A total of 1486 south Asian (SA) and 492 white European (WE) subjects with type 2 diabetes were recruited from 25 general practices in Coventry and Birmingham, UK. Baseline data included clinical history, anthropometry and measurements of traditional risk factors – blood pressure, total cholesterol, HbA1c. Multiple linear regression models were used to examine ethnicity differences in individual risk factors. Ten-year cardiovascular risk was estimated using the Framingham and UKPDS equations. All subjects were followed up for 2 years. Cardiovascular events (CVD) and mortality between the two groups were compared. Findings - Significant differences were noted in risk profiles between both groups. After adjustment for clustering and confounding a significant ethnicity effect remained only for higher HbA1c (0.50 [0.22 to 0.77]; P?=?0.0004) and lower HDL (-0.09 [-0.17 to -0.01]; P?=?0.0266). Baseline CVD history was predictive of CVD events during follow-up for SA (P?

Ethanol intake of paediatric intensive care patients

Background - Limiting the amount of alcohol in children's medicines is advisable but as alcohol is the second most common solvent used in liquid preparations, paediatric patients with increased medication intake may be exposed to a considerable alcohol intake. Few medicines are specifically designed for children in Paediatric Intensive Care (PICU), and therefore adult formulations are frequently administered, with high medication use further exposing a PICU patient to undesired alcohol intake. Aims - This small pilot study aimed to examiine the intake of a sample of PICU patients, highlight common medicines used on PICU containing alcohol, provide alternatives where possible and where alternatives are not possible, provide the prescriber with a list of the higher alcohol containing medicines. Method - A retrospective medication chart review was undertaken as a two point snap shot. Data collected included age, weight, medications prescribed and the formulations used at time of the study. The patients' sedation score was recorded. The electronic medicine compendium (EMC) was consulted for any ethanol content for the commercially available products. The manufacturer was contacted for ethanol content of all ‘specials’ and any commercial products found to contain ethanol from the EMC. The PICU patient's daily intake of ethanol was calculated. The calculation was converted to an adult equivalent alcohol unit intake and although this method of conversion is crude and does not take physiological differences of adult and children into account, it was done in order to provide the clinician with commonly used terminology in deciding the risk to the patient. Results - Twenty-eight patients were prescribed a range of 69 different medications. Of the 69 medicines, 12 products were found to contain ethanol. Patient ages ranged from a 26 week premature infant to 15 years old, weights ranges from 0.7 kg to 45 kg. Only 2 out of the 28 patients did not receive ethanol containing medications, and most patients were prescribed at least two medicines containing ethanol. Daily ethanol intake uncorrected for weight ranged from 0.006 ml to 2.18 ml (median 0.26 ml). Converting this to adult units per week, alcohol intake ranged from 0.07 to 15.2 units (median 1.4 units). The two patients receiving above 15 units/week adult equivalent were prescribed an oral morphine weaning regimen, therefore the high alcohol exposure was short term. The most common drugs prescribed containing alcohol were found to be nystatin, ranitidine, furosemide and morphine. No commercially available alcohol-free oral liquid preparations were found for ranitidine, furosemide or morphine at the time of the study. Correlation of the sedation score against ethanol intake was difficult to analyse as most patients were actively sedated. Conclusions - Polypharmacy in PICU patients increases the exposure to alcohol. Some commercially available medicines provide excessive ethanol intake, providing the clinician with ethical, potentially economical dilemmas of prescribing an unlicensed medicine to minimise ethanol exposure. Further research is required to evaluate the scope of the problem, effects of exposure and provision of alcohol free formulations.

Does maternal control during feeding moderate early infant weight gain?

OBJECTIVE. Our objective with this study was to examine whether observed maternal control during feeding at 6 months of age moderates the development of early infant weight gain during the first year of life. METHODS. Sixty-nine women were observed feeding their 6-month-old infants during a standard meal. Mealtimes were coded for maternal use of controlling feeding behavior. All infants were weighed at birth and at 6 and 12 months of age, and weight gain was calculated from birth to 6 months and from 6 to 12 months. Weight scores and weight gain scores were standardized for prematurity, age, and gender. RESULTS. Infant weight gain between 6 and 12 months of age was predicted by an interaction between early infant weight gain (birth to 6 months) and observed maternal control during feeding at 6 months. When maternal control was moderate or low, there was a significant interaction with weight gain from birth to 6 months in the prediction of later infant weight gain from 6 to 12 months, such that infants who showed slow early weight gain accelerated in their subsequent weight gain, and those with greater early weight gain decelerated. Conversely, when maternal control was high, infant weight gain followed the opposite pattern. CONCLUSION. Maternal control of solid feeding can moderate infant weight gain.

Maternal cognitions, psychopathologic symptoms, and infant temperament as predictors of early infant feeding problems:a longitudinal study

Objective: The current study examined the contribution of prenatal and postnatal maternal core beliefs, self-esteem, psychopathologic symptoms, and postnatal infant temperament to the prediction of infant feeding difficulties. Method: Ninety-nine women completed questionnaires assessing their core beliefs, psychopathology, and self-esteem during pregnancy and at 6 months postpartum. At 6 months, mothers also rated their infant's temperament and feeding, and were observed feeding their infants. Results: Maternal reports of child feeding difficulties were predicted by higher levels of emotional deprivation and entitlement core beliefs and lower levels of self-sacrifice and enmeshment core beliefs during pregnancy. Postnatal social isolation core beliefs, lower maternal self-esteem, and more difficult infant temperament added significantly to the variance explained by prenatal factors. Maternal core beliefs, self-esteem, psychopathology, and infant temperament failed to significantly predict independent observations of child food refusal. Conclusion: Maternal cognitions are implicated in the development of maternal reports of feeding difficulty.

The ‘first three years’ movement and the infant brain:a review of critiques

This article reviews a particular aspect of the critique of the increasing focus on the brain and neuroscience; what has been termed by some, 'neuromania'. It engages with the growing literature produced in response to the 'first three years' movement: an alliance of child welfare advocates and politicians that draws on the authority of neuroscience to argue that social problems such as inequality, poverty, educational underachievement, violence and mental illness are best addressed through 'early intervention' programmes to protect or enhance emotional and cognitive aspects of children's brain development. The movement began in the United States in the early 1990s and has become increasingly vocal and influential since then, achieving international legitimacy in the United States, Canada, New Zealand, Australia, the UK and elsewhere. The movement, and the brain-based culture of expert-led parent training that has grown with it, has been criticised for claiming scientific authority whilst taking a cavalier approach to scientific method and evidence; for being overly deterministic about the early years of life; for focusing attention on individual parental failings rather than societal or structural problems, for adding to the expanding anxieties of parents and strengthening the intensification of parenting and, ultimately, for redefining the parent-child relationship in biologised, instrumental and dehumanised terms. © 2014 John Wiley & Sons Ltd.

Infant voices: embryonic and neonatal personhood in two recent French Catholic novels

There are almost no literary or artistic representations that take the unborn or neonatal infants as their subject. Two exceptions to this as Claire Daudin’s Le Sourire and Antoine Beauquier’s Pavillon 7: la révolte des embryons. What these novels share is the ambition to frame such subjects as full and complete persons. Thus in their distinct ways both novels engage with the familial, social and biological problems that arise when personhood is attributed to embryos or neo-natal infants. Their creation of an embryonic or infant ‘voice’ associates the dignity of such subjects with divine origins.