Negotiating the transition to adulthood :

PhD ThesisThis thesis explores the everyday lives and experiences of young Poles aged sixteen to twenty-four who are living and growing up in Northumberland, rural north east England, as they make their transitions to adulthood. Transitions to adulthood are always complicated and complex. Since the 1970s traditional pathways into adult life have become less standardised, heterogeneous, differentiated and elongated, and it has also been argued that there is an increase of individualisation across cohorts, with individual agency serving a greater role in shaping the lifecourse (Furlong and Cartmel, 2007; Jones, 2009). The young people who took part in this research migrated to Northumberland from Poland, with their families, after European Union enlargement in 2004. Existing research has developed a clear and nuanced picture about those Poles who migrated to the UK after 2004 (e.g. Burrell, 2009). However, very little attention has been paid to the perspectives of those young people who migrated with their families. Based on fifteen interviews with stakeholders (e.g. school teachers and community members), and forty interviews and eleven lifegrids with the young Poles, this research makes sense of how the experience of migration to the UK has influenced how this group of young people think about themselves, and in what ways this then shapes the choices and decisions that they were making on their transitions to adulthood. At first it could be assumed that there was something quite ordinary about the transitions to adulthood the young Poles were making; they could be mapped onto those discussed by the stakeholders in the first phase of the research and documented in the existing literature. However, the young Poles’ transitions were more complex than this. The young Poles frequently made reference to the sacrifices that their parents had made in order to provide them with opportunities. There was an expectation that they would do well at school and go on to university. However, some of the young Poles felt that the experience of migration constrained their transitions. The age that they migrated from Poland impacted on their experiences. Many of the young Poles played significant roles in their families, for example being expected to act as translators when parents spoke little or no English. They felt these experiences made them more mature in relation to their peers. Some of the young Poles talked about their Polishness being an asset or employable skill as they made their transitions. I explore how the young Poles constructed and negotiated their identities in their everyday lives, and through particular events, drawing on examples iv from Christmas, the Polish Saturday School or on return visits to Poland. Overall, the thesis demonstrates that Polishness and the experience of migration exerts a strong influence over their identities and lives as they make their transitions to adulthood

The UCB particle monitor: A tool for logging frequency of smoking and the intensity of second-hand smoke concentrations in the home

Second-hand tobacco smoke (SHS) exposure generates a large public health burden. Recent legislation has moved to prohibit smoking in public places and there are concerns that this may lead to an increase in exposures in private homes. Measurement of SHS aerosol has tended to use active pumped samples or longer-term diffusive badges. Pumped methods are noisy and poorly tolerated in home settings while diffusive badges do not provide real-time data. The UCB particle monitor (UCB-PM) is a modified smoke-alarm device capable of logging changes in airborne particulate matter over extended periods and has been used successfully to measure biomass fuel smoke concentrations in developing world settings This study has examined the use of the UCB-PM to measure SHS aerosol in both controlled laboratory conditions and a pilot field trial over a 7 day period in a smoker's home. Comparisons with a pumped sampler (TSI Sidepak Personal Aerosol Monitor) indicate good agreement over a range of exposure concentrations but there is evidence of a threshold effect at approximately 0.5 mg/m3 of fine particulate measured as PM2.5. While this threshold effect undermines the ability of the device to provide useful data on the time-weighted average SHS concentration, the field trial indicates that that the UCB-PM has a sensitivity of about 71% and a specificity of 98%. The device has many advantages including zero noise operation, low cost and long battery life and may be a useful tool in quitting and smoke-free home intervention studies

Multiplicative reasoning professional development programme : evaluation

The Multiplicative Reasoning Project (MRP) delivered by the National Centre for Excellence in the Teaching of Mathematics (NCETM) in 2013/14 focused on developing teachers' understanding and capacity to teach topics that involved multiplicative reasoning to Key Stage 3 (KS3) pupils. Multiplicative reasoning refers to the mathematical understanding and capability to solve problems arising from proportional situations often involving an understanding and application of fractions as well as decimals, percentages, ratios and proportions. The aspects of multiplicative reasoning addressed in the NCETM project were proportional and fractional relationships. The teaching approaches encouraged were the use of mathematical models, visual approaches and problem solving strategies. Approximately 60 teachers in 30 schools engaged in 3 regional professional development networks, led by professional development leaders, supported by university researchers. Specific project materials were created by a team of curriculum developers. The impact of MRP on pupil outcomes was evaluated using a 3-level Clustered Randomised Control Trial (CRT) research design. The trial ran between October 2013 and June 2014 and involved 8,777 year 7 (Y7), year 8 (Y8) and year 9 (Y9) pupils (level 1) clustered into 418 Y7, Y8 and Y9 mathematics classes (level 2) clustered into 60 secondary schools. Approximately half the schools, teachers and pupils participated in the intervention and half formed a control group. Progress was compared between the two groups of pupils using Key Stage 2 (KS2) data as a base line and GL Assessment Progress in Mathematics Test (PiM) tests as an outcome measure. This is a measure of general mathematical attainment that is correlated with national tests

Differential Mechanisms of Septic Human Pulmonary Microvascular Endothelial Cell Barrier Dysfunction Depending on the Presence of Neutrophils

Sepsis is characterized by injury of pulmonary microvascular endothelial cells (PMVEC) leading to barrier dysfunction. Multiple mechanisms promote septic PMVEC barrier dysfunction, including interaction with circulating leukocytes and PMVEC apoptotic death. Our previous work demonstrated a strong correlation between septic neutrophil (PMN)-dependent PMVEC apoptosis and pulmonary microvascular albumin leak in septic mice in vivo; however, this remains uncertain in human PMVEC. Thus, we hypothesize that human PMVEC apoptosis is required for loss of PMVEC barrier function under septic conditions in vitro. To assess this hypothesis, human PMVECs cultured alone or in coculture with PMN were stimulated with PBS or cytomix (equimolar interferon γ, tumor necrosis factor α, and interleukin 1β) in the absence or presence of a pan-caspase inhibitor, Q-VD, or specific caspase inhibitors. PMVEC barrier function was assessed by transendothelial electrical resistance (TEER), as well as fluoroisothiocyanate-labeled dextran and Evans blue-labeled albumin flux across PMVEC monolayers. PMVEC apoptosis was identified by (1) loss of cell membrane polarity (Annexin V), (2) caspase activation (FLICA), and (3) DNA fragmentation [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)]. Septic stimulation of human PMVECs cultured alone resulted in loss of barrier function (decreased TEER and increased macromolecular flux) associated with increased apoptosis (increased Annexin V, FLICA, and TUNEL staining). In addition, treatment of septic PMVEC cultured alone with Q-VD decreased PMVEC apoptosis and prevented septic PMVEC barrier dysfunction. In septic PMN–PMVEC cocultures, there was greater trans-PMVEC macromolecular flux (both dextran and albumin) vs. PMVEC cultured alone. PMN presence also augmented septic PMVEC caspase activation (FLICA staining) vs. PMVEC cultured alone but did not affect septic PMVEC apoptosis. Importantly, pan-caspase inhibition (Q-VD treatment) completely attenuated septic PMN-dependent PMVEC barrier dysfunction. Moreover, inhibition of caspase 3, 8, or 9 in PMN–PMVEC cocultures also reduced septic PMVEC barrier dysfunction whereas inhibition of caspase 1 had no effect. Our data demonstrate that human PMVEC barrier dysfunction under septic conditions in vitro (cytomix stimulation) is clearly caspase-dependent, but the mechanism differs depending on the presence of PMN. In isolated PMVEC, apoptosis contributes to septic barrier dysfunction, whereas PMN presence enhances caspase-dependent septic PMVEC barrier dysfunction independently of PMVEC apoptosis

Conservation planning in an uncertain climate: Identifying projects that remain valuable and feasible across future scenarios

Conservation actors face the challenge of allocating limited resources despite uncertainty about future climate conditions. In many cases, the potential value and feasibility of proposed projects vary across climate scenarios. A key goal is to identify areas where conservation outcomes can balance both environmental and human needs. We developed a conservation prioritization framework that jointly considers the value and feasibility of candidate projects across future climate scenarios. We then applied this framework to the challenge of meeting environmental flow targets across the Red River basin of the south-central United States. To estimate the conservation feasibility of meeting environmental flow goals in a river reach in each climate scenario, we used a basin-wide hydrologic planning tool to quantify the reduction in societal water usage needed to meet environmental flow targets. To estimate the biodiversity value of each river reach in each climate scenario, we used climate-driven species distribution models and species’ conservation status. We found that river reaches in the east-central portion of the basin may be good candidates for conservation investments, because they had high biodiversity value and high sociopolitical feasibility in all future climate scenarios. In contrast, sites in the arid western reaches of the basin had high biodiversity value, but low feasibility of achieving environmental flow goals. Our framework should have broad applicability given that the value and feasibility of conservation projects vary across climate scenarios in ecosystems around the world. It may serve as a coarse filter to identify sites for more detailed analyses and could be integrated with complementarity-based approaches to conservation planning to balance species’ representation across projects. A free Plain Language Summary can be found within the Supporting Information of this article

A null mutation for tissue inhibitor of metalloproteinases-3 (Timp-3) impairs murine bronchiole branching morphogenesis.

Tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix (ECM) degradation by matrix metalloproteinases (MMPs). We have examined the role of TIMP-3 on ECM homeostasis and bronchiole branching morphogenesis during murine embryogenesis. Employing an in vitro organ culture system, we found decreased bronchiolar branching in null lungs when compared with wild type (WT) counterparts after 2 days in culture. When a synthetic inhibitor of MMPs at low dose was added to the culture system, branching was augmented regardless of genotype. Gelatin and in situ zymography revealed that null lungs exhibited enhanced activation of MMPs throughout lung development. We analysed the impact of increased MMP activity on a number of ECM molecules by Western blot analysis, but found that only fibronectin abundance was consistently reduced in the null lungs throughout development. To confirm that our observed defect in culture was not simply a developmental delay in the null lung, we examined null and WT lungs from newborn pups. Here, we found not only a reduced number of bronchioles in the null, but also that the bronchiole tubes were dilated compared with controls and that alveologenesis was attenuated. We propose that the deletion of TIMP-3 disrupts the exquisite TIMP/MMP balance required for proper focal ECM proteolysis, which leads to correct bronchiole branching morphogenesis in the developing mouse lung

Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice

Background: Despite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60 - 70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice. Methods: Male C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that of the elderly). Mice were prevented from becoming obese by food restriction (given 70-90% of ad libitum consumption amount). Between 20 and 22 months, a subgroup of mice ran voluntarily on wheels, alternating 1-3 days of running with 1-2 days of rest. At 22 months, mice were intraperitoneally injected with sterile saline (control) or 3.75 g/kg fecal slurry (septic). At 7 h post injection, we examined (1) neutrophil influx in the lung and liver by measuring myeloperoxidase and/or neutrophil elastase in the tissue homogenates by spectrophotometry, (2) interleukin 6 (IL6) and KC in the lung lavage by ELISA, (3) pulmonary surfactant function by measuring percentage of large aggregates, (4) capillary plugging (pro-coagulant response) in skeletal muscle by intravital microscopy, (5) endothelial nitric oxide synthase (eNOS) protein in skeletal muscle (eNOS-derived NO is putative inhibitor of capillary plugging) by immunoblotting, and (6) systemic blood platelet counts by hemocytometry. Results: Sepsis caused high levels of pulmonary myeloperoxidase, elastase, IL6, KC, liver myeloperoxidase, and capillary plugging. Sepsis also caused low levels of surfactant function and platelet counts. Running exercise increased eNOS protein and attenuated the septic responses. Conclusions: Voluntary running protects against exacerbated sepsis-induced inflammatory and pro-coagulant responses in aged mice. Protection against pro-coagulant responses may involve eNOS upregulation. The present discovery in aged mice calls for clinical investigation into potential beneficial effects of exercise on septic outcomes in the elderly