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This dissertation is about the moral importance of irony. In the first chapter, I introduce the topic. I argue that having values makes us vulnerable to facing choice situations that we properly regard as absurd, and I articulate a form of ironic playacting as an apt response to those choice situations. The subsequent chapters draw out the implications of this account. The second chapter treats akrasia. I defend the virtues of an overlooked kind of self-awareness in akrasia. In doing so, I articulate the importance of taking oneself seriously in a way that will make akrasia apt to seem absurd and to call for ironic playacting. In the third chapter, I argue that contentment and affirmation play a wide-ranging role in our practical thinking, in light of their ubiquitous connection to what we value, and this makes us apt to encounter absurd choice situations that call for irony. In the fourth chapter, I consider a common but puzzling phenomenon: the way in which the thought that some emotion is “not worth it” shows the emotion not to be fitting. My explanation of this phenomenon shows how we can end up in emotionally absurd situations that call for ironic playacting.

The kidney is a complex organ that governs many physiological parameters. It is roughly divided into three parts, the renal pelvis, medulla, and cortex. Covering the cortex is the renal capsule, a serosal tissue that provides protection and forms a barrier for the kidney. Serosal tissues of many organs have been recently shown to play a vital role in homeostasis and disease. Analyses of the cells that reside in these tissues have identified distinct cell types with unique phenotypes. Surprisingly, despite the importance of serosal tissues, little is known about cells of the renal capsule. Here, we characterized this niche and found that it is mainly comprised of fibroblasts and macrophages, but also includes many other diverse cell types. Characterizing renal capsule-associated macrophages, we found that they consist of a distinct subset (i.e., TLF+macrophages) that is nearly absent in the kidney parenchyma. Injury, disease, and other changes within the kidney, affected the cell composition and phenotype of the renal capsule, indicating its dynamic and vibrant response to changes within the organ parenchyma. Lastly, we studied age-related changes in the renal capsule and found that aging affected the cell composition and pro-inflammatory phenotype of macrophages, increased CD8 T cells and other lymphocyte counts, and promoted a senescence-associated phenotype in fibroblasts. Taken together, our data illustrate the complexity and heterogeneity of the renal capsule and its underlying changes during aging and disease, improving our understanding of the kidney serosa that may be valuable for novel renal therapies.

Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery.Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by 1H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by “targeted profiling” followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups.Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308).Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions.Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry. Cancer Epidemiol Biomarkers Prev; 20(1); 140–7. ©2010 AACR.

Supplementary Table 1 from Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics

We present evidence of how researchers from developing countries are represented in three areas of research: conference presentations, articles in journals, and citations. We find that the bulk of ...

The aging brain exhibits a decline in the regenerative populations of neural stem cells (NSCs), which may underlie age-associated defects in sensory and cognitive functions1–6. While mechanisms that restore old NSC function have started to be identified7–23, the role of lipids – especially complex lipids – in NSC aging remains largely unclear. Using lipidomic profiling by mass spectrometry, we identify age-related lipidomic signatures in young and old quiescent NSCs in vitro and in vivo. These analyses reveal drastic changes in several complex membrane lipid classes, including phospholipids and sphingolipids in old NSCs. Moreover, poly-unsaturated fatty acids (PUFAs) strikingly increase across complex lipid classes in quiescent NSCs during aging. Age-related changes in complex lipid levels and side chain composition are largely occurring in plasma membrane lipids, as revealed by lipidomic profiling of isolated plasma membrane vesicles. Experimentally, we find that aging is accompanied by modifications in plasma membrane biophysical properties, with a decrease in plasma membrane order in old quiescent NSCs in vitro and in vivo. To determine the functional role of plasma membrane lipids in aging NSCs, we performed genetic and supplementation studies. Knockout of Mboat2, which encodes a phospholipid acyltransferase, exacerbates age-related lipidomic changes in old quiescent NSCs and impedes their ability to activate. As Mboat2 expression declines with age, Mboat2 deficiency may drive NSC decline during aging. Interestingly, supplementation of plasma membrane lipids derived from young NSCs boosts the ability of old quiescent NSCs to activate. Our work could lead to lipid-based strategies for restoring the regenerative potential of NSCs in old individuals, which has important implications for countering brain decline during aging.

Background Health care costs and wait times for colorectal cancer treatment are increasing in Canada, but the association between the 2 remains unclear. Objective This study aimed to determine the association between wait times and health care costs and utilization. Design This is a population-based retrospective cohort study. Setting This study was conducted in Manitoba, Canada. Patients Patients diagnosed with colorectal cancer between 2004 and 2014 were sorted and ranked into quintiles based on the time from index contact for a colorectal cancer-related symptom to first treatment. Main outcome measures The primary outcome is risk-adjusted health care costs, and the secondary outcomes include health care utilization and overall mortality. Results We included a total of 6936 patients. Total wait times ranged between 0 and 762 days. In comparison with very short wait times, longer wait times were associated with significantly increased costs (short: mean cost ratio 1.21; 95% CI, 1.10-1.32; moderate: mean cost ratio 1.30; 95% CI, 1.19-1.43; long: mean cost ratio 1.48; 95% CI, 1.33-1.64; and very long: mean cost ratio 1.39; 95% CI, 1.26-1.54). Compared with very short wait times, longer wait times were associated with significantly lower risk of mortality (short: HR, 0.78; 95% CI, 0.71-0.86; moderate: HR, 0.72; 95% CI, 0.65-0.80; long: HR, 0.73; 95% CI, 0.66-0.82; very long: HR, 0.76; 95% CI, 0.68-0.85). The median number of pretreatment radiological and endoscopic investigations and surgeon clinic visits increased over the study period across all wait time categories. Limitations This is a nonrandomized, retrospective cohort study with potentially limited generalizability. Conclusion Patients with very short and short wait times are likely those diagnosed with life-threatening complications of colorectal cancer. Outside this window, patients with longer wait times experience increased health care costs and utilization with similar overall mortality. Improved care coordination and patient navigation may help contain the increasing wait times and associated increasing health care costs and utilization. See Video Abstract at http://links.lww.com/DCR/B81. ASOCIACION ENTRE LOS TIEMPOS DE ESPERA PARA EL TRATAMIENTO DE UN CANCER COLORRECTAL Y LOS COSTOS DE ATENCION MEDICA: UN ANALISIS DE POBLACION: los costos de atencion medica y los tiempos de espera para el tratamiento del cancer colorrectal estan aumentando en Canada, pero la asociacion entre los dos sigue sin estar clara.determinar la asociacion entre los tiempos de espera y los costos y la utilizacion de la atencion medicaun estudio de cohorte retrospectivo basado en la poblacion.Manitoba, Canadalos pacientes diagnosticados con cancer colorrectal entre 2004-2014 se clasificaron y sub-clasificaron en quintiles segun el tiempo desde el primer contacto indice de sintomas relacionados con cancer colorrectal hasta el primer tratamiento.El resultado primario son los costos de atencion medica ajustados al riesgo, y los resultados secundarios incluyen la utilizacion de la atencion medica y la mortalidad general.Incluimos un total de 6,936 pacientes. Los tiempos de espera totales oscilaron entre 0-762 dias. En comparacion con los tiempos de espera muy cortos, los tiempos de espera mas largos se asociaron con costos significativamente mayores (Corto: relacion de costo promedio 1.21, intervalo de confianza del 95% 1.10-1.32; Moderado: relacion de costo promedio 1.30, intervalo de confianza del 95% 1.19-1.43; Largo: media relacion de costo 1.48, intervalo de confianza del 95% 1.33-1.64; Muy largo: relacion de costo promedio 1.39, intervalo de confianza del 95% 1.26-1.54). En comparacion con tiempos de espera muy cortos, los tiempos de espera mas largos se asociaron con un riesgo de mortalidad significativamente menor (Corto: razon de riesgo 0.78, intervalo de confianza del 95% 0.71-0.86; Moderado: razon de riesgo 0.72, intervalo de confianza del 95% 0.65-0.80; Largo: peligro cociente 0.73, intervalo de confianza del 95% 0.66-0.82; Muy largo: cociente de riesgos 0.76, intervalo de confianza del 95% 0.68-0.85). La mediana del numero de investigaciones radiologicas y endoscopicas previas al tratamiento y las visitas al cirujano aumentaron durante el periodo de estudio en todas las categorias de tiempo de espera.estudio de cohortes retrospectivo, no aleatorio con generalizacion potencialmente limitadalos pacientes con tiempos de espera « muy cortos » y « cortos » son probablemente aquellos diagnosticados con complicaciones potencialmente mortales del cancer colorrectal. Fuera de esta ventana, los pacientes con tiempos de espera mas largos experimentan mayores costos de atencion medica y utilizacion con una mortalidad general similar. La coordinacion mejorada de la atencion y la navegacion del paciente pueden ayudar a contener el aumento de los tiempos de espera y el aumento de los costos y la utilizacion de la atencion medica. Consulte Video Resumen en http://links.lww.com/DCR/B81. (Traduccion-Dr. Edgar Xavier Delgadillo).

SUMMARYProtein aggregation, which can sometimes spread in a prion-like manner, is a hallmark of neurodegenerative diseases. However, whether prion-like aggregates form during normal brain aging remains unknown. Here we use quantitative proteomics in the African turquoise killifish to identify protein aggregates that accumulate in old vertebrate brains. These aggregates are enriched for prion-like RNA binding proteins, notably the ATP-dependent RNA helicase DDX5. We validate that DDX5 forms mislocalized cytoplasmic aggregates in the brains of old killifish and mice. Interestingly, DDX5’s prion-like domain allows these aggregates to propagate across many generations in yeast. In vitro, DDX5 phase separates into condensates. Mutations that abolish DDX5 prion propagation also impair the protein’s ability to phase separate. DDX5 condensates exhibit enhanced enzymatic activity, but they can mature into inactive, solid aggregates. Our findings suggest that protein aggregates with prion-like properties form during normal brain aging, which could have implications for the age-dependency of cognitive decline.

Background Prophylactic cholecystectomy following endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP-S) remains the gold standard management of choledocholithiasis. Some clinicians propose ERCP-S alone as the definitive management in the elderly, given perioperative complication risks. This retrospective cohort study aimed to assess the long-term efficacy and safety of non-operative management of choledocholithiasis in adults aged ≥70. Methodology A total of 252 patients aged ≥70 underwent ERCP from 2004 to 2014 at a single institution. The rates of cholecystectomy, ERCP, complications, and mortality were gathered. Data were linked to a provincial health database to capture follow-up visits to alternate hospitals. Predictors of operation, recurrence, and mortality were analyzed using multivariable regression. Results Following ERCP, of the 252 patients, 33 (13.1%) underwent prophylactic cholecystectomy within three months, while 219 (86.9%) were initially managed conservatively. Of the 219 patients, 147 (67.1%) experienced no further choledocholithiasis after conservative management, while 23 (10.5%) patients underwent cholecystectomy. The mean follow-up was 2.9 years. Delayed operative patients were younger (mean age: 77.56 vs. 82.90; p < 0.001) and had lower Charlson Comorbidity Index (CCI) (1.04 vs. 1.84; p = 0.030). When adjusted for age, CCI score, and sex, cholecystectomy was associated with increased survival, with an odds ratio of 0.48 (95% confidence interval = 0.26-0.90; p = 0.021). Perioperative complications occurred in 7/56 (12.5%) patients. Conclusions Recurrent choledocholithiasis is common in elderly patients. Despite recurrent symptoms, these patients are unlikely to undergo cholecystectomy. Surgeons operate on patients with greater life expectancy and fewer comorbidities with high success despite advanced patient age. Future prospective studies should examine objective criteria for prophylactic cholecystectomy in this population, given purported safety and benefits.

According to most classifications, Sub‐Saharan Africa is the region of the world with the highest presence of fragile states. In this paper we examine the relationship between fragility and poverty, suggesting that countries may become trapped in a vicious circle of fragility and low levels of wellbeing. We consider fragility as a continuum and begin by reviewing available measures. These show the high presence of fragility in Sub‐Saharan Africa and allow the more fragile countries to be identified. There is seen to be a strong association between fragility, poor growth performance, and lower wellbeing in Sub‐Saharan Africa. Building on the strong evidence for the two‐way relationship between economic growth and poverty, we present an analysis of how the vicious circle linking poorer welfare outcomes and fragility may be able to be broken. We argue that building successful institutions is key here, and this can be enabled by specific policy interventions that are both poverty reducing and productive.

The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is the control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof-of-concept for the feeding flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males (but not in females) and impacts the transcriptomes of killifish livers in a sex-specific manner. Moreover, combining our automated feeding system with a video camera, we establish a quantitative associative learning assay to provide an integrative measure of cognitive performance for the killifish. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a scalable manner previously impossible with traditional vertebrate model organisms.

The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is the control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof of concept for the feeding flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males (but not in females) and impacts the transcriptomes of killifish livers in a sex-specific manner. Moreover, combining our automated feeding system with a video camera, we establish a quantitative associative learning assay to provide an integrative measure of cognitive performance for the killifish. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a scalable manner previously impossible with traditional vertebrate model organisms.

Background Clinical and patient-reported outcomes are positively affected when efforts to increase patient understanding of underlying diseases and foster patient participation are part of care pathways. The prevalence of liver diseases is increasing globally, and successful communication of results from liver diagnostic tests will be important for physicians to ensure patient engagement and encourage adherence to lifestyle changes and therapy. Here, we aimed to explore the impact of non-invasive liver tests on patient experience and patient comprehension of liver disease in chronic liver disease diagnostic pathways typically managed with liver biopsies. Results 101 participants diagnosed with a range of liver disease aetiologies (90 patients, 11 caregivers) underwent a multiparametric magnetic resonance imaging (MRI) test. A subset of 33 participants was subjected to transient elastography (TE) with FibroScan® in addition to multiparametric MRI. MRI results were analysed using LiverMultiScan™. Participants received results on their liver-health status followed by a semi-structured interview to assess the scan procedure experience, comprehension of the results, and experiences of liver disease. A subset of participants (N = 5) was also engaged in the design, execution, and thematic analysis of the interview transcripts of the study. Analysis of semi-structured interviews revealed: (1) Presentation and discussion of the LiverMultiScan visual report by a physician was an effective contributor to better patient experience and increased comprehension of liver disease. (2) Patients demonstrated preference for non-invasive tests over biopsy for management of liver disease. (3) Patients reported positive experiences with the MRI test during the path for liver disease management. Conclusions Patients presented with visual reports of liver test results developed increased understanding of liver disease care which may have contributed to an overall more positive experience. Patients reported that clinical information obtained through non-invasive methods and transmitted through visual reports contributed to clarity, understanding and overall increased satisfaction. We conclude that a shift toward non-invasive testing and visual reporting of clinical information (e.g. picture of liver with visual scale) when possible are likely to contribute to improved physician engagement with patients and lead to better outcomes in the management of chronic liver diseases. Plain English summary Evidence suggests that patient experience and understanding can affect several aspects of clinical care and patient well-being. In this study, 101 patients and patient caregivers affected by liver diseases were recruited to determine how patient experiences of liver disease were affected with the introduction of non-invasive evaluation of the liver with an MRI or ultrasound-based elastography. All 101 participants received an MRI followed by a LiverMultiScan report. 33 participants received an additional FibroScan and report. Following the reports, participants were interviewed and asked to reflect on factors which affected their experience of the procedure and the understanding of their results. We focused on factors related to the layout of the standardised report and the delivery of its results. The interviews were transcribed and analysed for common themes and patterns. Patients and patient advocacy groups were involved in the design and conduct of the study, and analysis of the interview transcripts. Here, we report the perception of patients and patient caregivers on the quality of care and diagnostic experience. Trial registration ClinicalTrials.gov identifier—NCT02877602.

The attenuation of low-frequency broadband noise in a light, small form-factor is an intractable challenge. In this paper, a new technology is presented which employs the highly efficient visco-thermal loss mechanism of a micro-perforated plate (MPP) and successfully lowers its frequency response by combining it with decorated membrane resonators (DMR). Absorption comes from the membranes but primarily from the MPP, as the motion of the two membranes causes a pressure differential across the MPP creating airflow through the perforations. This combination of DMR and MPP has led to the Segmented Membrane Sound Absorber (SeMSA) design, which is extremely effective at low-frequency broadband sound absorption and which can achieve this at deep sub-wavelength thicknesses. The technology is compared to other absorbers to be found in the literature and the SeMSA outperforms them all in either the 20–1000 Hz or 20–1200 Hz range for depths of up to 120 mm. This was verified through analytical, finite element and experimental analyses.

Routinely collected data about health in medical records, registries and hospital activity statistics is now routinely collected in an electronic form. The extent to which such sources of data are now being routinely accessed to deliver efficient clinical trials, is unclear. The aim of this study was to ascertain current practice amongst a United Kingdom (UK) cohort of recently funded and ongoing randomised controlled trials (RCTs) in relation to sources and use of routinely collected outcome data. Recently funded and ongoing RCTs were identified for inclusion by searching the National Institute for Health Research journals library. Trials that have a protocol available were assessed for inclusion and those that use or plan to use routinely collected health data (RCHD) for at least one outcome were included. RCHD sources and outcome information were extracted. Of 216 RCTs, 102 (47%) planned to use RCHD. A RCHD source was the sole source of outcome data for at least one outcome in 46 (45%) of those 102 trials. The most frequent sources are Hospital Episode Statistics (HES) and Office for National Statistics (ONS), with the most common outcome data to be extracted being on mortality, hospital admission, and health service resource use. Our study has found that around half of publicly funded trials in a UK cohort (NIHR HTA funded trials that had a protocol available) plan to collect outcome data from routinely collected data sources. This is much higher than the figure of 8% found in a cohort of 189 RCTs published since 2000, the majority of which were carried out in North America (McCord et al., 2019).

Background: Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors.Methods: This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23).Findings: 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0·11). Safety results were consistent with the known safety profile of tocilizumab.Interpretation: The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options.Funding: Versus Arthritis and the National Institute for Health Research Clinical Research Network: Children.

"Established to manage the art collections of one of Auckland city’s former businessmen, the Mackelvie Trust Board has operated for over 125 years. The Trust was set up to administer James Tannock Mackelvie’s(1824−85) collection of European paintings, books, decorative arts and objets de vertu including bronzes, clocks, coins and natural treasures now held at the Auckland Art Gallery, the Auckland War Memorial Museum and the Auckland Public Library. This article will explain how part of the collection came to be at the Auckland War Memorial Museum, how the Trustees administered the will, and how the Trust Board itself evolved to include professional expertise. The impact of this evolution on Mackelvie’s gifts and bequest and the collection’s development is one of the most important findings. After an evaluation of the collection’s management over time, it is concluded that while the Mackelvie Trust Board has always endeavoured to implement Mackelvie’s wishes, financial and physical restrictions led to certain compromises regarding control and display of the collection. Nevertheless, the Trustees have always acted in good faith and protected Mackelvie’s legacy for the enjoyment of future generations of Aucklanders and visitors to the city."

Cross‐border travel for business, personal and tourism purposes is an important component of trade in services. In 2013, travel accounted for 25% of services export in the world. Trade in services accounted for 12% of GDP in the world. Hence, the role of travel in many economies is substantial. The current paper studies the determinants of cross‐border flows of people with a particular emphasis on the role of visa policies. We adopt the UN General Assembly Affinity Index, a measure of the quality of bilateral relations between nations, to instrument for bilateral visa policy. We find that, ceteris paribus, imposing visa restrictions on a country reduces travel from that country by about 73% in 2010 implying restrictive visa policies discourage cross‐border travel significantly. This implies an adverse impact of restrictive visa policies on trade‐in‐services.

Purpose Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. Methods MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. Results The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. Conclusion The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

Equivalent circuit analysis is a powerful tool for analysing acoustic systems where a lumped element model is valid. These equivalent circuits allow an overall impedance of the structure to be estimated which facilitates predictions of the reflectivity, transmissibility and/or absorptivity of the system. Complex acoustic systems are represented by non-planar equivalent circuits which are challenging to simplify to a single overall impedance value using traditional Kirchoff’s Law simplifications. A two-point impedance method using graph theory allows the impedance of a circuit to be estimated without simplification. The graph theory method is applied to a type of acoustic absorber structure named SeMSA (Segmented Membrane Sound Absorber) which had previously been investigated for a two-segment cell design. This method allows the SeMSA analysis to be expanded to multi-sector designs with a wider parameter space. A local optimisation routine is applied to the graph theory impedance estimation to maximise acoustic absorption of SeMSA under consideration of absorber depth, causal optimality and the targeted noise spectra. Analytical predictions are validated using numerical simulations. The optimised multi-sector absorber demonstrates 70.5% white noise absorption in the 20–4500 Hz frequency range with an absorber depth of 16 mm and is just 0.5 mm from the theoretical minimum depth to achieve this absorption response.

Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department.Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia.Results. We analyzed 273 patients – 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values.Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Background: Hepatocellular carcinoma (HCC) has a very poor survival rate, especially for those who do not receive a potentially curative therapy. Methods: Treatment details were collected for 320 HCC patients diagnosed in Manitoba between January 2011 and December 2015. Patients had a mean age of 67.3 years, and 71.6% were men. Of these patients, 67 (20.9%) received curative treatment, 36 (11.3%) received non-curative treatment, and 217 (67.8%) received supportive care only; 71.3% of patients had liver cirrhosis. Alcoholic cirrhosis was the most common etiology of chronic liver disease (22.2%). Results: Those who received curative treatment had a significantly lower incidence of portal vein thrombosis and multinodular disease than those in other groups. Patients who received supportive care only had a higher incidence of ascites. We found no difference in the distribution of cirrhosis or portal hypertension among the treatment groups. The 2- and 5-year overall survival rates for the whole cohort were 27% and 14%, respectively. No significant change was found in 2-year survival for patients diagnosed in each year from 2011 to 2015 ( p = 0.250). Also, we found no significant change in proportion of treatment given to patients over the same period ( p = 0.432). Conclusion: The poor survival rate of HCC patients in Manitoba could potentially be improved by maximizing the use of local therapy and by implementing multidisciplinary–based case discussion. Efforts should also be directed toward early management of infective, alcoholic, and non-alcoholic steatohepatitis, which will, we hope, lead to a reduction in the incidence of HCC.

This chapter reconsiders the extent to which recent impressive growth performance in India has been associated with poverty reduction, using data collected by the Indian Human Development Surveys, a panel survey conducted in 2004/5 and 2010/11. The panel nature of the survey allows us to link income growth to poverty dynamics, and in particular to movements into and out of poverty as well as chronic poverty. While the overall story in India over this period is one of impressive poverty reduction, the data also reveal some cases of immiserizing growth. This chapter seeks to understand the nature and factors underlying immiserizing growth for the state of Chhattisgarh.

Background and Objectives Liver failure following hepatic resection is a multifactorial complication. In experimental studies, infusion of N-acetylcysteine (NAC) can minimize hepatic parenchymal injury. Methods Patients undergoing liver resection were randomized to postoperative care with or without NAC. No blinding was performed. Overall complication rate was the primary outcome; liver failure, length of stay, and mortality were secondary outcomes. Due to safety concerns, a premature multivariate analysis was performed and included within the model randomization to NAC, preoperative ASA, extent of resection, and intraoperative vascular occlusion as factors. Results Two hundred and six patients were randomized (110 to conventional therapy; 96 to NAC). No significant differences were noted in overall complications (32.7% and 45.7%, P = 0.06) or hepatic failure (3.6% and 5.4%, P = 0.537) between treatment groups. There was significantly more delirium within the NAC group (2.7% and 9.8%, P

This study analyzes the relationship between forest households' livelihood strategies, and forest clearing, and the relationship of both to welfare. The analysis relies on a rich panel dataset collected on the Tsimane' communities in Bolivia to highlight how forest households combine sales and wage activities. Forest clearing is associated with all livelihood strategies, but the association with welfare differs depending on the strategy pursued. Households that clear more and that generate their earnings by combining agricultural sales and wage activities are better-off (judged in terms of assets) than those undertaking other strategies. By contrast, households in a subsistence strategy are not able to accumulate assets in the long run. Overall, households clear only small areas of forest, which has a positive effect on welfare and enables accumulation of assets.

Giant cell arteritis (GCA) can be diagnosed histopathologically by biopsy of the temporal artery, and clinically using the 5-point score of the 1990 American College of Rheumatology (ACR) classification. We aimed to find out whether some patients are referred for biopsy unnecessarily. We audited all referrals (n=100) made to the Department of Oral and Maxillofacial Surgery over 34 months, and used the ACR classification to find out whether patients had had a clinical diagnosis of GCA at referral (ACR score: 3 or more). We then compared them with the result of the biopsy. Of the 100 referred, 98 had a biopsy, and of them, 15 were diagnosed with GCA (2 results were not included). Thirteen of the 15 had already been diagnosed clinically (based on the ACR classification) at referral. Our results gave an ACR specificity of 96% (95% CI: 85% to 99%) but only 20% sensitivity (95% CI: 11% to 32%). There was a linear correlation of high ACR scores with histopathological confirmation. Biopsy is most beneficial when there is a degree of diagnostic uncertainty (ACR: 1 or 2), an atypical presentation, or when steroids may be relatively contraindicated. On the basis of our study, we designed a new referral form for biopsy based on the ACR criteria.

Most pancreatic cystic neoplasms (PCN) are thought to harbor a low malignant potential. This historical cohort study attempts to describe the natural history of these lesions in a provincial cohort, to assess the safety of non-surgical management. Pathological diagnosis of malignancy was the primary outcome measure of interest.All adult patients (age 18+) with PCN seen between 2000 and 2012 by the two main institutions in Manitoba were included in this study. PCN were graded as high and low risk, which dictated initial treatment plan (surgery or observation). Predictors of initial surgical treatment, delayed surgery in the observation group and the clinical/radiological predictors of malignancy were determined.497 patients were included in this study. 43 (8.7%) high-risk lesions underwent initial surgery, with 13 (30.2%) cases of malignancy discovered. 450 (90.5%) low-risk cysts were observed for a median of 17.3 months (range: 0.00-142.3). 29 (6.4%) cases of delayed surgery occurred, with malignancy discovered in five (17.2%).This study supports current selection criteria for management of PCNs. Due to the low incidence of malignancy in low-risk PCN, it appears that long-term observation is safe and should be the treatment modality of choice in the absence of high-risk features.