POSITIVE FACTORIZATIONS VIA PLANAR MAPPING CLASSES AND BRAIDS

In this thesis we seek to better understand the planar mapping class group inorder to find factorizations of boundary multitwists, primarily to generate and studysymplectic Lefschetz pencils by lifting these factorizations. Traditionally this methodis applied to a disk or sphere with marked points, utilizing factorizations in the stan-dard and spherical braid groups, whereas in our work we allow for multiple boundary components. Dehn twists along these boundaries give rise to exceptional sections of Lefschetz fibrations over the 2–sphere, equivalently, to Lefschetz pencils with base points. These methods are able to derive an array of known examples of Lefshetz fibrations while giving their maximal exceptional sections. In particular, a family of examples we obtain, which recapture unpublished examples by Baykur, Hamada and Korkmaz, allows us to demonstrate that two well-known inequalities on the number of non-separating and separating vanishing cycles are in fact sharp for every genus g ≥ 2

Identifying prognostic indicators for cognitive stimulation therapy for dementia: protocol for a systematic review and individual participant data meta-analysis

Background Cognitive stimulation therapy (CST) is the only non-pharmacological, treatment for dementia recommended by the UK National Institute for Health and Care Excellence, following multiple international trials demonstrating beneficial cognitive outcomes in people with mild-to-moderate dementia. However, there is limited understanding of whether treatment prognosis is influenced by sociodemographic and clinical variables (such as dementia subtype and gender), information which could inform clinical decision-making. Aim We describe the protocol for a systematic review and individual patient data meta-analysis assessing the prognostic factors related to CST. In publishing this protocol, we hope to increase the transparency of our work, and keep healthcare professionals aware of the latest evidence for effective CST. Method A systematic review will be conducted with searches of the bibliographic databases Medline, EMBASE and PsycINFO, from inception to 7 February 2023. Studies will be included if they are clinical trials of CST, use the Alzheimer's Disease Assessment Scale – Cognitive Subscale (gold-standard measure of cognition in dementia in clinical trials) and include participants with mild-to-moderate dementia. Following harmonisation of the data-set, mixed-effect models will be constructed to explore the relationship between the prognostic indicators and change scores post-treatment. Conclusions This is the first individual patient data meta-analyses on CST, and has the potential to significantly optimise patient care. Previous analyses suggest people with advanced dementia could benefit more from CST treatment. Given that CST is currently used post-diagnosis in people with mild-to-moderate dementia, the implications of confirming this finding, among identifying other prognostic indicators, are profound

Reductions in hypothalamic Gfap expression, glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice

BACKGROUND: Neuronal and glial differentiation in the murine hypothalamus is not complete at birth, but continues over the first two weeks postnatally. Nutritional status and Leptin deficiency can influence the maturation of neuronal projections and glial patterns, and hypothalamic gliosis occurs in mouse models of obesity. Gnasxl constitutes an alternative transcript of the genomically imprinted Gnas locus and encodes a variant of the signalling protein Gαs, termed XLαs, which is expressed in defined areas of the hypothalamus. Gnasxl-deficient mice show postnatal growth retardation and undernutrition, while surviving adults remain lean and hypermetabolic with increased sympathetic nervous system (SNS) activity. Effects of this knock-out on the hypothalamic neural network have not yet been investigated. RESULTS: RNAseq analysis for gene expression changes in hypothalami of Gnasxl-deficient mice indicated Glial fibrillary acid protein (Gfap) expression to be significantly down-regulated in adult samples. Histological analysis confirmed a reduction in Gfap-positive glial cell numbers specifically in the hypothalamus. This reduction was observed in adult tissue samples, whereas no difference was found in hypothalami of postnatal stages, indicating an adaptation in adult Gnasxl-deficient mice to their earlier growth phenotype and hypermetabolism. Especially noticeable was a loss of many Gfap-positive α-tanycytes and their processes, which form part of the ependymal layer that lines the medial and dorsal regions of the 3(rd) ventricle, while β-tanycytes along the median eminence (ME) and infundibular recesses appeared unaffected. This was accompanied by local reductions in Vimentin and Nestin expression. Hypothalamic RNA levels of glial solute transporters were unchanged, indicating a potential compensatory up-regulation in the remaining astrocytes and tanycytes. CONCLUSION: Gnasxl deficiency does not directly affect glial development in the hypothalamus, since it is expressed in neurons, and Gfap-positive astrocytes and tanycytes appear normal during early postnatal stages. The loss of Gfap-expressing cells in adult hypothalami appears to be a consequence of the postnatal undernutrition, hypoglycaemia and continued hypermetabolism and leanness of Gnasxl-deficient mice, which contrasts with gliosis observed in obese mouse models. Since α-tanycytes also function as adult neural progenitor cells, these findings might indicate further developmental abnormalities in hypothalamic formations of Gnasxl-deficient mice, potentially including neuronal composition and projections

Com o diabo no corpo: os terríveis papagaios do Brasil colônia

Desde a Antiguidade, papagaios, periquitos e afins (Psittacidae) fascinaram os europeus por seu vivo colorido e uma notável capacidade de interação com seres humanos. A descoberta do Novo Mundo nada faria além de acrescentar novos elementos ao tráfico de animais exóticos há muito estabelecido pelos europeus com a África e o Oriente. Sem possuir grandes mamíferos, a América tropical participaria desse comércio com o que tinha de mais atrativo, essencialmente felinos, primatas e aves - em particular os papagaios, os quais eram embarcados em bom número. Contudo, a julgar pelos documentos do Brasil colônia, esses voláteis podiam inspirar muito pouca simpatia, pois nenhum outro animal - exceto as formigas - foi tantas vezes mencionado como praga para a agricultura. Além disso, alguns psitácidas mostravam-se tão loquazes que inspiravam a séria desconfiança de serem animais demoníacos ou possessos, pois só três classes de entidades - anjos, homens e demônios - possuíam o dom da palavra. Nos dias de hoje, vários representantes dos Psittacidae ainda constituem uma ameaça para a agricultura, enquanto os indivíduos muito faladores continuam despertando a suspeita de estarem possuídos pelo demônio. Transcendendo a mera curiosidade, essa crença exemplifica o quão intrincadas podem ser as relações do homem com o chamado “mundo natural”, revelando um universo mais amplo e multifacetado do que se poderia supor a princípio. Nesse sentido, a existência de aves capazes de falar torna essa relação ainda mais complexa e evidencia que as dificuldades de estabelecer o limite entre o animal e o humano se estendem além dos primatas e envolvem as mais inusitadas espécies zoológicas.Since ancient times, parrots and their allies (Psittacidae) have fascinated Europeans by their striking colors and notable ability to interact with human beings. The discovery of the New World added new species to the international exotic animal trade, which for many centuries had brought beasts to Europe from Africa and the Orient. Lacking large mammals, tropical America participated in this trade with its most appealing species, essentially felines, primates and birds - especially parrots - which were shipped in large numbers. It should be noted, however, that at times these birds were not well liked. In fact, according to documents from colonial Brazil, only the ants rank higher than parrots as the animals most often mentioned as agricultural pests. On the other hand, some of these birds were so chatty that people suspected them to be demonic or possessed animals, since only three classes of beings - angels, men and demons - have the ability to speak. Nowadays, several Psittacidae still constitute a threat to agriculture, and the suspicion that extremely talkative birds were demon possessed has also survived. More than a joke or a mere curiosity, this belief exemplifies how intricate man’s relationships with the “natural world” may be. In this sense, the existence of birds that are able to speak adds a further twist to these relationships, demonstrating that the problem of establishing a boundary between the animal and the human does not only involve primates, but also includes some unusual zoological species

Direct cardiac massage without major thoracotomy: Feasibility and systemic blood flow

Background: Open-chest cardiac massage (OC-CM) provides higher blood pressure and flow than closed-chest compression and may improve the probability of successful resuscitation from cardiac arrest. Its clinical use has been limited by its requirement for a major thoracotomy. The present pilot study tested the technical feasibility of performing effective direct cardiac massage without a major thoracic incision, by using a simple, manually-powered plunger-like device, inserted through a small thoracic incision, to cyclically compress the cardiac ventricles. The method was termed minimally-invasive direct cardiac massage (MID-CM). Systemic blood flow using MID-CM was compared to that with OC-CM, by both direct systemic hemodynamic measurements, cumulative metabolic indicators of the ratio of whole body oxygen delivery and oxygen consumption, and a metabolic index of pulmonary blood flow. Methods: In 12 large swine, baseline systemic and pulmonary hemodynamic measurements were performed. Arterial and mixed venous blood gases and metabolic indicators of systemic blood flow were measured. Ventricular fibrillation was induced and after 4 min, animals underwent either bimanual OC-CM (N = 6) or MID-CM (N = 6). At 10, 20 and 30 min, hemodynamic and metabolic measurements were repeated. Results: Systemic Blood Pressure: Aortic systolic and diastolic blood pressures were reduced from baseline levels with both OC-CM and MID-CM. No difference in pressure was noted between OC-CM and MID-CM groups. Pulmonary Artery Pressure: Pulmonary artery systolic pressure was elevated from baseline during OC-CM and MID-CM. Pulmonary artery diastolic pressures remained constant throughout the resuscitation period in both groups. No differences in pulmonary systolic or diastolic pressure were noted between OC-CM and MID-CM groups. A trend towards higher pulmonary systolic pressures appeared with MID-CM. Thermodilution Blood Flow: Cardiac index fell from baseline levels with OC-CM and MID-CM. No difference in cardiac index was noted between OC-CM and MID-CM groups. Metabolic Indices: Mixed venous O 2 saturation decreased from baseline levels during resuscitation in both experimental groups, with a further decrease at 30 min compared to 10- and 20-min levels. No difference was noted between OC-CM and MID-CM groups at any point. Arterial pH was reduced from baseline levels at 30 min in both groups compared to baseline but no difference was noted between groups. Arterio-venous P co 2 difference increased above baseline levels with both OC-CM and MID-CM. No difference was noted between groups. Lactate levels displayed a progressive increase up to 30 min in both groups compared to baseline. No differences were noted between OC-CM and MID-CM groups for any time-period. Conclusions: Direct cardiac massage without major thoracotomy is technically feasible. The level of systemic blood flow that can be achieved with MID-CM is hemodynamically and metabolically equivalent to that obtained using conventional bimanual OC-CM

Open-chest cardiac massage without major thoracotomy: metabolic indicators of coronary and cerebral perfusion

Objective: to compare the coronary and cerebral perfusion achieved using a novel method of minimally-invasive, direct cardiac massage to that obtained using bimanual, open-chest cardiac massage. Design: prospective, controlled animal study with repeated measures. Setting: university research laboratory. Subjects: large domestic swine. Interventions: aortic, coronary sinus, jugular venous and pulmonary artery catheters were placed. Following an equilibration period, ventricular fibrillation was induced. After 4 min of untreated ventricular fibrillation, animals underwent bimanual, open-chest cardiac massage ( N=6) or minimally-invasive, direct cardiac massage using a novel device for direct cardiac compression ( N=6). Adrenaline was administered at a dose of 1 mg intravenously every 5 min. Measurements: systemic metabolic parameters, (arterial P O 2 , P CO 2 and lactate concentration) and coronary sinus and jugular venous metabolic parameters (pH, PV O 2 , SV O 2 , PV CO 2 and lactate concentration) were measured and calculated (coronary sinus/jugular-arterial SV O 2 , coronary sinus/jugular-arterial P CO 2 and lactate differences) at baseline and at 10, 20 and 30 min following induction of ventricular fibrillation. Animals were euthanised after 30 min with no attempt at defibrillation. Main Results: oxygen tension and oxygen saturation of coronary sinus blood declined significantly during the experimental period, but no differences were noted between treatment groups. The coronary sinus-arterial oxygen saturation difference increased during the study with no significant differences between groups. Coronary sinus P CO 2 and the coronary sinus-arterial P CO 2 difference increased significantly in both experimental groups during cardiac massage. No inter-group differences were noted. A similar relationship was noted in coronary sinus lactate values. The coronary sinus-arterial lactate difference displayed a positive balance at all intervals with no differences noted between group values. The oxygen tension and oxygen saturation of jugular venous blood, were reduced from baseline levels with both treatments. The jugular-arterial oxygen saturation difference increased in both groups compared to baseline values. Between group values were significantly different only at the 20 min interval. Both the jugular venous P CO 2 and the jugular-arterial P CO 2 gradient were elevated at all intervals, but no inter-group differences were noted. Jugular venous lactate concentration rose steadily with time in both groups. No significant increase in the jugular-arterial lactate gradient was noted at any time point. Conclusions: minimally-invasive, direct cardiac massage provides coronary and cerebral perfusion similar to that achieved using standard open-chest cardiac massage. This method may provide a more effective substitute for standard, closed-chest cardiac massage in cases of refractory cardiac arrest