The impact of artificial intelligence on the current and future practice of clinical cancer genomics.

Artificial intelligence (AI) is one of the most significant fields of development in the current digital age. Rapid advancements have raised speculation as to its potential benefits in a wide range of fields, with healthcare often at the forefront. However, amidst this optimism, apprehension and opposition continue to strongly persist. Oft-cited concerns include the threat of unemployment, harm to the doctor-patient relationship and questions of safety and accuracy. In this article, we review both the current and future medical applications of AI within the sub-speciality of cancer genomics

Consequences of the ‘Legs at odd angles’ mutation within the motor protein dynein and its possible implications in neurological disease

Cytoplasmic dynein is a retrograde motor protein complex that carries cargo such as organelles and growth factors along microtubules from the cell periphery towards the peri-nuclear region. The cytoplasmic dynein complex is centred around two homodimerised heavy chains, within which multiple mutations have been identified in human neurological diseases. The ‘Legs at odd angles’ (Loa) mouse has a missense ‘T’ to ‘A’ point mutation in the cytoplasmic dynein heavy chain gene (Dync1h1), resulting in a phenylalanine to tyrosine substitution at position 580. Mice homozygous for this mutation die within 24 hours of birth whilst heterozygote’s manifest an age-related and progressive neurodegeneration. Fixed and live-cell microscopy shows aberrant movement of endocytosed growth factors in Loa. Retrograde speed is reduced with a distinct lack of the fastest moving carriers. Moreover, the overall pattern of movement is altered with increased anterograde and side-steps occurring in Loa. Impaired endosomal trafficking of growth factors for degradation prolongs the activation of extracellular signal related kinases 1 and 2 (ERK 1/2) and increases the expression of the immediate early gene c-Fos in mouse embryonic fibroblasts. Motor neurons also show increased levels c-Fos however this can be induced by starvation, indicating their enhanced susceptibility to stress. The light chain (KLC) of dynein’s opposing motor - kinesin is one of many genes differentially expressed in Loa compared to wild-type. In addition, associations of KLC with the dynein complex is altered in Loa. Similarities between human neurological diseases and Loa both at the organism and cellular level make Loa a valuable tool towards understanding cellular mechanisms fundamental to the process of disease. Through understanding comes advancement towards therapeutic targets to improve the lives of thousands of people worldwide

Alien Registration- Garrett, Alice M. (Howland, Penobscot County)

https://digitalmaine.com/alien_docs/7969/thumbnail.jp

Adapting the Own Children Method to allow comparison of fertility between populations with different marriage regimes.

The Own Children Method (OCM) is an indirect procedure for deriving age-specific fertility rates and total fertility from children living with their mothers at a census or survey. The method was designed primarily for the calculation of overall fertility, although there are variants that allow the calculation of marital fertility. In this paper we argue that the standard variants for calculating marital fertility can produce misleading results and require strong assumptions, particularly when applied to social or spatial subgroups. We present two new variants of the method for calculating marital fertility: the first of these allows for the presence of non-marital fertility and the second also permits the more robust calculation of rates for social subgroups of the population. We illustrate and test these using full-count census data for England and Wales in 1911

Development of a point-of-care molecular diagnostic tool for malaria and schistosomiasis in low-resource settings

There is an imminent need for more sensitive and low-cost point-of-care diagnostics for low-resource settings. Molecular diagnostics are becoming increasingly relevant in global efforts for disease elimination, although, healthcare workers face practical and logistical problems in the implementation of such tests in low-resource laboratories and environments. This has propelled the development of tailored point-of-care (POC) molecular diagnostic tests, however, to date there is lack of investigations into POC molecular tests trialled in low-resource settings. The World Health Organization (WHO) have highlighted the importance of the elimination of malaria and schistosomiasis in the 2030 roadmap to achieve sustainable development goals. Work previously conducted within the Biomedical Research Division at The University of Glasgow resulted in the development of a low-cost POC molecular diagnostic platform for malaria. The technique is reliant on loop-mediated isothermal amplification (LAMP). This thesis describes the adaptation of the technique to aid the diagnosis of schistosomiasis. Furthermore, field-trials were undertaken in collaboration with the Vector Control Division in Uganda, to assess the logistics and feasibility of POC LAMP to detect plasmodium and schistosome DNA in rural low-resource-settings. Molecular detection of malaria and schistosomiasis has the potential to provide more sensitive diagnostic tests which will benefit current surveillance programs and epidemiological studies. Additionally, the assessment of field trials will assist those developing POC molecular tests for use in low-resource environments out-with clinical and laboratory settings. Due to the malleability of the technique, this could further benefit additional POC testing and disease surveillance studies in-the-field, thus, contributing to the development of future work in these areas

Mortality, Work and Migration. A Consideration of Age-specific Mortality from Tuberculosis in Scotland, 1861-1901

This paper provides an examination into some of the most enduring debates regarding tuberculosis mortality during the nineteenth century: those related to gender, geographic and temporal variations. We use populations reconstructed from individual census and civil register data for the period 1861 to 1901, comparing a growing urban area with a declining rural area, both with around 20,000 inhabitants in 1861. Our analysis shows that among young adults tuberculosis was linked to excess female mortality in the urban area and excess male mortality in the rural area. We demonstrate that in the town textile workers of both genders had particularly high mortality from tuberculosis, and that the only reason for higher overall female mortality was the predominance of young women in the textile labour force. We show that the age and gender-specific pattern of mortality in the rural area is consistent with higher male than female out-migration together with return migration of those who had contracted the disease elsewhere and needed care during their lengthy illness. We argue that the observed patterns are difficult to reconcile with the ‘bargaining-nutrition’ account of gendered patterns in tuberculosis mortality, and that they provide little support for nutrition as a key influence on the disease. However, our findings do reinforce Andrew Hinde’s recent argument that geographical patterns in sex-specific tuberculosis mortality rates were largely determined by migration patterns, and we discuss the implications of this for our understanding of the decline of the disease over the late nineteenth century

Reason and emotion in policy making: an ethnographic study

Recent policy analysis has had a growing interest in examining the everyday practices of policy work. Despite this, conceptions of what policy can and should encompass tend to be focused on its tangible outputs and products, in particular the texts and documents of policy and governance. Policy’s legitimacy is commonly considered to rest on its participants’ ability to make rational decisions motivated not by private reasons but by the public good. This has had serious implications for scholars’ ability to discuss the non-purposive, nonverbal and non-rational content in policy work. This thesis presents an ethnographic study of emotion in the context of policy work. Starting from informants’ own understandings of what emotion means in policy and politics, it focuses on a fifteen month period in the policy practices of a Scottish NGO and its stakeholders and participants. From the perspective of a participant observer policy worker, it uses observation, documents, and interviews to explore the way traditionally “rational” models of governance based on apparently objective knowledge and other non-rational, “caring” ways of knowing are brought to bear upon policy work through detailed examination of practice. Analysis of these practices begins by examining the way that informants described the anxieties caused by competing understandings of “good” governance. Emotion and rationality were considered mutually exclusive but equally essential components of policy making. This thesis proposes that the way these anxieties were managed by the Partnership’s policy participants was to split these incommensurable expectations of governance between two self-identifying groups: activists such as community organisers and professionals such as civil servants. Splitting knowledge in this way helped the wider policy making community to maintain their own sense of legitimacy and moral integrity while making use of “dangerous” knowledge

The impact of intrauterine exposures on neurodevelopmental outcomes in 8–10 year old children within a disadvantaged population

Introduction: Intrauterine exposures can have lasting impacts on offspring neurodevelopment. The aim of this thesis was to investigate the associations of antenatal depression and pregnancy complications on child cognitive and mental health at 8–10 years of age. Method: This is a follow-up study of the SCreening fOr Pregnancy Endpoints (SCOPE) cohort. During pregnancy, women completed a number of questionnaires, including the Edinburgh Postnatal Depression Scale (EPDS) at 15 weeks’ and 20 weeks’ gestation, and pregnancy complications recorded. Women were contacted 8–10 years after delivery for assessment of their child’s neurodevelopment. Cognitive testing utilised five tests from the Cambridge Neuropsychological Test Automated Battery, focusing on executive function, memory and reaction time. Mothers completed the Depression, Anxiety and Stress Scale (DASS-42) to assess their own mental health, and the Spence Children’s Anxiety Scale (SCAS) and the Child Anxiety Life Interference Scale (CALIS) to assess their child’s anxiety. Children completed the SCAS and CALIS questionnaires along with the Center for Epidemiological Studies Depression scale for Children (CES-DC). Results: Data were available for 273 mother-child pairs. Thirty-eight mothers scored ≥13 on the EPDS and were classed as having high antenatal depression, with the remainder classed as having low antenatal depression. For children of the high antenatal depression group, both the parent and to a lesser extent the child report, demonstrated increased likelihood of anxiety symptoms and anxiety interference. Children in this group were also at increased risk of errors on learning memory and spatial working memory task, and longer motor movement times. There were no differences in any other reaction time measures, delayed memory measures, or executive functioning or in risk of child self-reported depression symptoms between the groups. Next, groups were assigned based on the presence of one of the five major complications of pregnancy; preeclampsia (PE; n=38), small for gestational age (SGA; n=34), preterm birth (PTB; n=26), gestational diabetes mellitus (GDM; n=22) and gestational hypertension (GH; n=20) and developmental outcomes compared with controls (n=166). Children born following PE and/or SGA were most vulnerable to cognitive deficits, with poorer performance on executive functioning and memory tasks. Children born following GDM had better learning memory performance compared to controls. Children born SGA or after GH had longer movement and reaction times, respectively. Children born after PE reported higher anxiety and anxiety interference. Children born SGA were at increased risk of reporting anxiety interference. Interestingly, children born preterm had decreased likelihood of self-reported anxiety symptoms, while children born after GDM were at decreased risk of anxiety interference, including anxiety interference outside the home. Exposure to pregnancy complications had no effect on child depressive symptoms. Conclusion: Maternal antenatal depression and pregnancy complications are associated with neurodevelopmental outcomes in 8–10-year-old children. This has lifelong implications, reducing future job opportunities and socioeconomic success. Similarly, poor mental health in childhood and adolescence is associated with increased risk of long-term mental health problems. Recognition of factors that contribute to deficits in cognition and mental health provides opportunities for early interventions to improve long-term health and social outcomes.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201

Medical provision and urban-rural differences in maternal mortality in late nineteenth century Scotland.

This paper examines the effect of variable reporting and coding practices on the measurement of maternal mortality in urban and rural Scotland, 1861-1901, using recorded causes of death and women who died within six weeks of childbirth. This setting provides data (n = 604 maternal deaths) to compare maternal mortality identified by cause of death with maternal mortality identified by record linkage and to contrast urban and rural settings with different certification practices. We find that underreporting was most significant for indirect causes, and that indirect causes accounted for a high proportion of maternal mortality where the infectious disease load was high. However, distinguishing between indirect and direct maternal mortality can be problematic even where cause of death reporting appears accurate. Paradoxically, underreporting of maternal deaths was higher in urban areas where deaths were routinely certified by doctors, and we argue that where there are significant differences in medical provision and reported deaths, differences in maternal mortality may reflect certification practices as much as true differences. Better health services might therefore give the impression that maternal mortality was lower than it actually was. We end with reflections on the interpretation of maternal mortality statistics and implications for the concept of the obstetric transition

Above‐ and below‐ground assessment of carabid community responses to crop type and tillage

Carabid beetles are major predators in agro‐ecosystems. The composition of their communities within crop environments governs the pest control services they provide. An understudied aspect is the distribution of predacious carabid larvae in the soil. We used novel subterranean trapping with standard pitfall trapping, within a multi‐crop rotation experiment, to assess the responses of above‐ and below‐ground carabid communities to management practices. Crop and trap type significantly affected pooled carabid abundance with an interaction of the two, the highest numbers of carabids were caught in subterranean traps in barley under sown with grass. Trap type accounted for the most variance observed in carabid community composition, followed by crop. Tillage responses were only apparent at the species level for three of the eight species modelled. Responses to crop type varied by species. Most species had higher abundance in under‐sown barley, than grass, wheat and barley. Crop differences were greater in the subterranean trap data. For predaceous larvae, standard pitfalls showed lowest abundances in under‐sown barley, yet subterranean traps revealed abundances to be highest in this crop. Comprehensive estimation of ecosystem services should incorporate both above‐ and below‐ground community appraisal, to inform appropriate management