Elasticity as an indicator of cell responses to topography and chemically modified surfaces: an atomic force microscopy approach

This thesis will describes how microfabrication techniques can be combined with Atomic Force Microscopy (AFM) to investigate the potential for cellular elasticity to be used as an indicator of cell behaviour and responses to chemical and topographical surface modifications. To this end, a robust and reliable AFM protocol has been developed to take in to account the many changeable parameters encountered when performing live cell indentation measurements. Complimented with traditional molecular biological methods, such as immunofluorescence staining and confocal microscopy, the biomechanical properties and functions of cells have been investigated to see how they respond to simple chemical and topographical cues. Simple surface topographies have frequently been exploited to learn more about cell behaviour and subsequent function however the mechanisms by which the cells senses the surrounding cues and interprets them accordingly has remained somewhat unknown. It is the hypothesis of the work presented here that the arrangement of the internal cytoskeleton as influenced by external factors in responsible for the transmission of tensile strength to the cytoplasm and on to the nuclear membrane. This in turn has the potential to alter transcription within the nucleus ultimately affecting over all cell function

Multimodal characterization of the late effects of traumatic brain injury: a methodological overview of the Late Effects of Traumatic Brain Injury Project

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer’s and Parkinson’s disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional MRI, and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study

Long-term endurance and power training may facilitate motor unit size expansion to compensate for declining motor unit numbers in older age

The evidence concerning the effects of exercise in older age on motor unit (MU) numbers, muscle fiber denervation and reinnervation cycles is inconclusive and it remains unknown whether any effects are dependent on the type of exercise undertaken or are localized to highly used muscles. MU characteristics of the vastus lateralis (VL) were assessed using surface and intramuscular electromyography in eighty-five participants, divided into sub groups based on age (young, old) and athletic discipline (control, endurance, power). In a separate study of the biceps brachii (BB), the same characteristics were compared in the favored and non-favored arms in eleven masters tennis players. Muscle size was assessed using MRI and ultrasound. In the VL, the CSA was greater in young compared to old, and power athletes had the largest CSA within their age groups. Motor unit potential (MUP) size was larger in all old compared to young (p < 0.001), with interaction contrasts showing this age-related difference was greater for endurance and power athletes than controls, and MUP size was greater in old athletes compared to old controls. In the BB, thickness did not differ between favored and non-favored arms (p = 0.575), but MUP size was larger in the favored arm (p < 0.001). Long-term athletic training does not prevent age-related loss of muscle size in the VL or BB, regardless of athletic discipline, but may facilitate more successful axonal sprouting and reinnervation of denervated fibers. These effects may be localized to muscles most involved in the exercise

Estimation of Pap-test coverage in an area with an organised screening program: challenges for survey methods

BACKGROUND: The cytological screening programme of Viterbo has completed the second round of invitations to the entire target population (age 25–64). From a public health perspective, it is important to know the Pap-test coverage rate and the use of opportunistic screening. The most commonly used study design is the survey, but the validity of self-reports and the assumptions made about non respondents are often questioned. METHODS: From the target population, 940 women were sampled, and responded to a telephone interview about Pap-test utilisation. The answers were compared with the screening program registry; comparing the dates of Pap-tests reported by both sources. Sensitivity analyses were performed for coverage over a 36-month period, according to various assumptions regarding non respondents. RESULTS: The response rate was 68%. The coverage over 36 months was 86.4% if we assume that non respondents had the same coverage as respondents, 66% if we assume they were not covered at all, and 74.6% if we adjust for screening compliance in the non respondents. The sensitivity and specificity of the question, "have you ever had a Pap test with the screening programme" were 84.5% and 82.2% respectively. The test dates reported in the interview tended to be more recent than those reported in the registry, but 68% were within 12 months of each other. CONCLUSION: Surveys are useful tools to understand the effectiveness of a screening programme and women's self-report was sufficiently reliable in our setting, but the coverage estimates were strongly influenced by the assumptions we made regarding non respondents

State of the Antarctic and Southern Ocean Climate System

This paper reviews developments in our understanding of the state of the Antarctic and Southern Ocean climate and its relation to the global climate system over the last few millennia. Climate over this and earlier periods has not been stable, as evidenced by the occurrence of abrupt changes in atmospheric circulation and temperature recorded in Antarctic ice core proxies for past climate. Two of the most prominent abrupt climate change events are characterized by intensification of the circumpolar westerlies (also known as the Southern Annular Mode) between ∼6000 and 5000 years ago and since 1200–1000 years ago. Following the last of these is a period of major trans-Antarctic reorganization of atmospheric circulation and temperature between A.D. 1700 and 1850. The two earlier Antarctic abrupt climate change events appear linked to but predate by several centuries even more abrupt climate change in the North Atlantic, and the end of the more recent event is coincident with reorganization of atmospheric circulation in the North Pacific. Improved understanding of such events and of the associations between abrupt climate change events recorded in both hemispheres is critical to predicting the impact and timing of future abrupt climate change events potentially forced by anthropogenic changes in greenhouse gases and aerosols. Special attention is given to the climate of the past 200 years, which was recorded by a network of recently available shallow firn cores, and to that of the past 50 years, which was monitored by the continuous instrumental record. Significant regional climate changes have taken place in the Antarctic during the past 50 years. Atmospheric temperatures have increased markedly over the Antarctic Peninsula, linked to nearby ocean warming and intensification of the circumpolar westerlies. Glaciers are retreating on the peninsula, in Patagonia, on the sub-Antarctic islands, and in West Antarctica adjacent to the peninsula. The penetration of marine air masses has become more pronounced over parts of West Antarctica. Above the surface, the Antarctic troposphere has warmed during winter while the stratosphere has cooled year-round. The upper kilometer of the circumpolar Southern Ocean has warmed, Antarctic Bottom Water across a wide sector off East Antarctica has freshened, and the densest bottom water in the Weddell Sea has warmed. In contrast to these regional climate changes, over most of Antarctica, near-surface temperature and snowfall have not increased significantly during at least the past 50 years, and proxy data suggest that the atmospheric circulation over the interior has remained in a similar state for at least the past 200 years. Furthermore, the total sea ice cover around Antarctica has exhibited no significant overall change since reliable satellite monitoring began in the late 1970s, despite large but compensating regional changes. The inhomogeneity of Antarctic climate in space and time implies that recent Antarctic climate changes are due on the one hand to a combination of strong multidecadal variability and anthropogenic effects and, as demonstrated by the paleoclimate record, on the other hand to multidecadal to millennial scale and longer natural variability forced through changes in orbital insolation, greenhouse gases, solar variability, ice dynamics, and aerosols. Model projections suggest that over the 21st century the Antarctic interior will warm by 3.4° ± 1°C, and sea ice extent will decrease by ∼30%. Ice sheet models are not yet adequate enough to answer pressing questions about the effect of projected warming on mass balance and sea level. Considering the potentially major impacts of a warming climate on Antarctica, vigorous efforts are needed to better understand all aspects of the highly coupled Antarctic climate system as well as its influence on the Earth\u27s climate and oceans

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Sustainable food security decision-making : an agent-based modelling approach.

Ensuring a consistent and regular availability of food is crucial for food security. Food markets, supplied through both domestic production and international trade, are governed by several risks emerging from unpredictable supply chain disruptions, volatility of commodity prices, along with other unforeseen circumstances such as natural disasters. To mitigate the challenges threatening the stability of food systems, decision-making within the food sector should be enhanced and robust to accommodate any changes that might cause food shortages. Dynamic models, that can predict the behavior of food systems in order to avoid potential future knock-on effects and deficits, are incumbent to ensure the sustainable performance of food systems. This study proposes a dynamic decision-making scheme that simulates strategies of the perishable food market under different circumstances. An agent-based model (ABM) is developed and implemented using python MESA library for a case study in Qatar, illustrating the potential performance of tomato under three different scenarios to be considered, namely: (a) baseline scenario - aiming to reflect current production and market conditions; (b) water resource efficiency scenario - basing decisions on crop water requirement (CWR) depending on weather conditions; and (c) economic risk scenario - applying the concept of forward contracts to hedge against future uncertainties in crop prices. The findings of this study demonstrate that under the baseline conditions, a tomato crop can be supplied through a combination of domestic production and imports depending on the available inventories and prices imposed by exporters. The results obtained for the CWR scenario suggest the need for total reliance on imports in order to meet domestic demand, as there is potentially high-water loss, which amounts to an average of 4.9 Billion m3 per year, if tomato is grown locally. In contrast, the results from the forward contract scenario recommend a 57% dependency on local production in order to mitigate the effects of volatility in global food prices, which contributes to a 63% reduction in environmental emissions. Findings of this research provide insight into the factors that influence strategic decision making by the food sector to enhance its economic and environmental performances under diverse circumstances