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Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3‐kinase (PI3K) and its product phosphatidylinositol (3,4,5)‐trisphosphate (PIP 3 ). We demonstrate that adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However, in the CNS, axonal PIP 3 decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect; however, expression of p110δ restored axonal PIP 3 and increased regenerative axon transport. p110δ expression enhanced CNS regeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonal PIP 3 as a key reason for intrinsic regeneration failure and demonstrate that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion. Synopsis CNS axons lose the ability to regenerate with maturity, whilst PNS axons do not. This study shows that PIP 3 levels decline in CNS neurons at the time when regenerative ability is lost. CNS overexpression of one isoform of PI3K, p110δ, enhances axonal PIP 3, axon transport, and regenerative ability. p110α and p110δ were found to be required for axon regeneration in adult PNS neurons, however PI3K and PIP 3 declined in CNS neurons as they developed to maturity. p110α or p110δ were overexpressed in mature CNS neurons, but only p110δ restored PIP 3 and regeneration, whilst the activating H1047R mutation was required in p110α to promote regeneration similarly. p110δ mediated regeneration through multiple downstream pathways, including mTOR, pS6, CRMP2, ARF6, and increased axonal transport of integrins and Rab11‐positive endosomes. Transgenic expression of p110δ or hyperactive p110α H1047R stimulated axon regeneration after optic nerve injury and increased RGC survival, whilst viral delivery of p110δ led to further enhanced axon regeneration. Graphical Abstract CNS axons lose the ability to regenerate with maturity, whilst PNS axons do not. This study shows that PIP 3 levels decline in CNS neurons at the time when regenerative ability is lost. CNS overexpression of one isoform of PI3K, p110δ, enhances axonal PIP 3, axon transport, and regenerative ability.

A toddler presented with melaena on a background of a possible enteric duplication cyst, diagnosed in the neonatal period which ‘vanished’. What was later confirmed to be a small bowel duplication cyst was not seen on follow-up ultrasounds and thus the patient was managed expectantly until presentation as an emergency. Our case highlights the challenges faced in managing cystic abdominal structures in infancy and the potential consequences of expectant management. We discuss whether cross-sectional imaging or diagnostic laparoscopy should be advocated when duplications cysts are considered amongst the differentials of a lesion on ultrasound.

A review of the current status of robotic surgery use in paediatrics

Non-typhoidal Salmonella spp.are Gram-negative bacilli, which typically cause a clinical picture of gastroenteritis and, less commonly, patients may become a chronic carrier of the pathogen within their gallbladder. We describe a rare clinical presentation of a non-typhoidal Salmonella spp. infection as acute calculus cholecystitis in an adult patient. Salmonella enterica subsp. Salamae (ST P4271) was grown from cholecystostomy fluid, and the patient subsequently underwent a laparoscopic cholecystectomy that demonstrated a necrotic gallbladder fundus. We advise that microbiological sampling of bile is essential, especially in the context of foreign travel, to detect unusual pathogens as in this case or common pathogens that may have unusual antimicrobial resistance. Given the necrotic gallbladder as in this case, we also advise that early cholecystectomy should be strongly considered in these patients.

Financial development as a concept is multifaceted with no clear measurement or definition. Inference via individual proxies may result in an incomplete understanding of the relationship between financial development and economic growth, since sole proxies are unlikely to capture the true capacity of financial development. To address this issue, this paper utilizes a multiple indicators multiple causes (MIMIC) model to create a more complete measure of financial development. In doing this, we treat banking sector and stock market developments as two latent indicators of financial development and use the MIMIC model to predict them which are used as their proxies. Using data from 101 countries over the period 1990–2014, we use the predicted values of the two latent variables as regressors, among other controls, in the growth regression. We find a robust negative relationship between banking sector development and economic growth, whereas the effect of stock market development on economic growth is positive up to a threshold after which the effect becomes negative.

Managers must repeatedly make important decisions regarding the composition of their firm’s capital structure, the amount of profit they should return to investors, and the form in which such payment, if any, should be delivered. The dynamic and reoccurring nature of such salient decisions mean that the financial policies of firms do not simply manifest themselves in arbitrary or random fashions but evolve to follow distinct dynamic patterns. Through the combination of one theoretical and two empirical chapters, this thesis evaluates the underlying mechanisms behind such dynamic trends by exploiting the uniqueness of India’s emerging market context. The first study of the thesis establishes the economic impact of estimator choice on the implied speed of financial policy adjustment. The chapter utilises Monte Carlo experiments to present an extensive appraisal of the dynamic panel estimators commonly employed in the corporate finance literature. The chapter finds the least squares dummy variable corrected estimator of Kiviet (1995) and the quasi-maximum likelihood fixed-effect estimator of Hsiao et al. (2002) to be the most robust estimators across a range of experiments. In contrast, the chapter unearths that the popular generalized method of moments estimators are highly sensitive to changes in dynamic persistence, cross-sectional heterogeneity and panel unbalancedness and are therefore prone to yielding spurious estimates of financial policy adjustment. The second study investigates, empirically, how Indian listed firms facing alternative adjustment costs transition towards their capital structure target over the course of the business cycle. Accordingly, by bringing together both cross-sectional and time-series elements of autoregressive heterogeneity, the chapter finds the adjustment speeds of Indian firms to be largely pro-cyclical. Furthermore, the chapter uncovers that firms with the highest earnings and the greatest investment opportunities adjust significantly quicker in both periods of macroeconomic growth and macroeconomic decline relative to their financially constrained counterparts. The final study of this thesis investigates if the dividend decisions of Indian listed firms are influenced by the actions and characteristics of their industry peers. The chapter adopts a Spatial-Durbin style modelling approach to show that the dividend decisions made by local industry peers bear the greatest economic influence on the dividend decisions made by Indian listed firms. The chapter finds that the informational content embedded within peer dividend decisions is economically more important for dividend increases and dividend decreases than any other firm or industry related characteristics. Moreover, the chapter illustrates that the tangible decisions of peers are most economically meaningful in periods of heighten macroeconomic uncertainty, when the opaqueness of firms own information is likely to be most severe. Accordingly, the evidence of proximity related peer effects put forward in our final study presents a clear criticism of the extant literature that has predominately focused on the role of firm-specific factors on corporate payout decisions.

Background: Some previous studies have reported that survivors of childhood cancer are at an increased risk of developing long-term mental health morbidity, whilst others have reported that this is not the case. Therefore, we analysed 5-year survivors of childhood cancer using the British Childhood Cancer Survivor Study (BCCSS) to determine the risks of aspects of long-term mental health dysfunction. Procedure: Within the BCCSS, 10 488 survivors completed a questionnaire that ascertained mental health-related information via 10 questions from the Short Form-36 survey. Internal analyses were conducted using multivariable logistic regression to determine risk factors for mental health dysfunction. External analyses were undertaken using direct standardisation to compare mental health dysfunction in survivors with UK norms. Results: This study has shown that overall, childhood cancer survivors had a significantly higher prevalence of mental health dysfunction for 6/10 questions analysed compared to UK norms. Central nervous system (CNS) and bone sarcoma survivors reported the greatest dysfunction, compared to expected, with significant excess dysfunction in 10 and 6 questions, respectively; the excess ranged from 4.4–22.3% in CNS survivors and 6.9–15.9% in bone sarcoma survivors. Compared to expected, excess mental health dysfunction increased with attained age; this increase was greatest for reporting ‘limitations in social activities due to health’, where the excess rose from 4.5% to 12.8% in those aged 16–24 and 45+, respectively. Within the internal analyses, higher levels of educational attainment and socio-economic classification were protective against mental health dysfunction. Conclusions: Based upon the findings of this large population-based study, childhood cancer survivors report significantly higher levels of mental health dysfunction than those in the general population, where deficits were observed particularly among CNS and bone sarcoma survivors. Limitations were also observed to increase with age, and thus it is important to emphasise the need for mental health evaluation and services across the entire lifespan. There is evidence that low educational attainment and being unemployed or having never worked adversely impacts long-term mental health. These findings provide an evidence base for risk stratification and planning interventions.

Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol (3,4,5)-trisphosphate (PIP ). We demonstrate that adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However, in the CNS, axonal PIP decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect; however, expression of p110δ restored axonal PIP and increased regenerative axon transport. p110δ expression enhanced CNS regeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonal PIP as a key reason for intrinsic regeneration failure and demonstrate that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion.

Purpose To compare the clinical outcomes and financial implications of the percutaneous endoscopic primary button gastrostomy (PEG-B) insertion using T-fastener technique with the percutaneous endoscopic gastrostomy tube insertion (PEG-T) using a push–pull technique. Methods Data were prospectively gathered on 122 patients undergoing gastrostomy insertion over a 3-year period (2016–2019). Our primary outcome measure was the number of second general anaesthetics (GA) required in relation to the gastrostomy tube. Secondary outcome measures included complications and cost. Results Following exclusion criteria of lap assisted, concomitant procedure or insufficient data, 105 patients were analysed. Sixty-two (61%) PEG-B were inserted using a T-fastener technique. Forty-three (39%) PEG-T were inserted using a push–pull technique. Two (3.2%) patients with a PEG-B required a GA change or reinsertion of device compared with 31 (72%) of the PEG-T group who underwent a tube change under GA to either a button or a new tube in the study period ( p  < 0.01). The requirement for GA changes in the PEG-T group results in a considerably higher cost for this approach than the PEG-B approach. There was no difference between the number of peri-operative and post-operative complications between the two groups; however, the PEG-T group appeared to have higher rate of major operative complications ( n  = 3 bowel injuries). Whereas in the PEG-B group: complications were minor technical issues and displacement requiring replacement under fluoroscopy. In the follow-up period, rates of granulation tissue requiring intervention and stoma site infections were equivalent between groups. Conclusion The PEG-B technique of placing a gastrostomy avoids the need for a replacement of gastrostomy tube under GA and its associated risk of repeat GA and financial cost. Furthermore, the technique is potentially associated with fewer major complications. We conclude, therefore, that the PEG-B approach reduces the interventional and financial burden on the patient, their family, and the healthcare provider, and could be considered as a safe alternative for paediatric gastrostomy insertion.

Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3). We found that neuronal PIP3 decreases with maturity in line with regenerative competence, firstly in the cell body and subsequently in the axon. We show that adult PNS neurons utilise two catalytic subunits of PI3K for efficient regeneration: p110α and p110δ. Overexpressing p110α in CNS neurons had no effect, however expression of p110δ restored axonal PIP3 and enhanced CNS regeneration in rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings demonstrate a deficit of axonal PIP3 as a reason for intrinsic regeneration failure and show that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion.