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\"This book presents an alternate history of colonial India in the 18th and the 19th centuries. It traces the transitions and transformations during this period through art, literature, music, theatre, satire, textile, regime changes, personal histories, and migration. The essays in the volume examine historical events and movements which questioned the traditional parameters of identity, and forged a new direction for the people and the nation. Viewing the age though diverse disciplinary angles, the book also reflects on the various reimaginings of India at the time. This volume will be of interest to academics and researchers of modern Indian history, cultural studies, and literature. It will also appeal to scholars interested in the anthropological, sociological, and psychological contexts of imperialism\"-- Provided by publisher.

In a randomized trial, over 2700 patients with obstructive sleep apnea and cardiovascular disease were assigned to CPAP plus usual care or to usual care alone. At a mean of 3.7 years, the rate of adverse cardiovascular events did not differ significantly between the groups. Obstructive sleep apnea causes episodic hypoxemia and nocturnal sympathetic nervous system activation 1 and elevates blood pressure 2 and markers of oxidative stress, inflammation, and hypercoagulation. 3 , 4 Large negative intrathoracic pressure swings also impose mechanical stress on the heart and great vessels. 5 – 7 Population-based and sleep-clinic–based cohort studies have shown an association between obstructive sleep apnea and cardiovascular events, 8 – 16 particularly stroke. 17 Randomized, controlled trials have shown that treatment with continuous positive airway pressure (CPAP) lowers systolic blood pressure by 2 to 3 mm Hg in patients with normotensive obstructive sleep apnea 18 and by 6 to 7 mm Hg in patients with . . .

Despite substantial public interest, few recommendations on the promotion of good sleep health exist to educate health care providers and the general public on the importance of sleep for overall health. The aim of this American Thoracic Society (ATS) statement is to provide a review of the current scientific literature to assist health care providers, especially pulmonologists and sleep physicians, in making recommendations to patients and the general public about the importance of achieving good quality and adequate quantity of sleep. ATS members were invited, based on their expertise in sleep medicine, and their conclusions were based on both empirical evidence identified after comprehensive literature review and clinical experience. We focus on sleep health in both children and adults, including the impact of occupation on sleep, the public health implications of drowsy driving, and the common sleep disorders of obstructive sleep apnea and insomnia. This ATS statement also delineates gaps in research and knowledge that should be addressed and lead to new focused research priorities to advance knowledge in sleep and sleep health. Good quality and quantity of sleep are essential for good health and overall quality of life; therefore a strong recommendation was made for the implementation of public education programs on the importance of sleep health.

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 ( PRIM1 ) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV 1 /FVC), and an eQTL of matrix metallopeptidase 15 ( MMP15 ) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 ( HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases.

Objectives: Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling. Design: Online questionnaire circulated via three tertiary IBD centres and Crohn’s Colitis Australia. Methods: Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated. Results: There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn’s disease and ulcerative colitis demonstrated a good fit. In Crohn’s disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn’s disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis. Conclusion: In Crohn’s disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn’s disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority. Plain language summary Depression influences fatigue in inflammatory bowel disease Fatigue is common in people with inflammatory bowel disease. Studies investigating the causes of fatigue in people with inflammatory bowel disease have consistently identified depression, anxiety, sleep quality and IBD activity as factors associated with fatigue. People with inflammatory bowel disease were asked about their fatigue levels, sleep quality, depression, anxiety and inflammatory bowel disease activity. These responses were used to generate a model to explain the interaction between these factors and how they influence fatigue. The contribution of each of these factors to fatigue was then determined. Depression had the largest overall contribution. The influence of inflammatory bowel disease activity on fatigue occurred mostly through its impact on other factors such as depression and sleep quality. Consideration should be given to screening for and treating depression in people with inflammatory bowel disease and fatigue.

Background/objectivesNeck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference.MethodsWe conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) individuals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis.ResultsWe identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10−9) but not in women (P = 0.08). The association was replicated in men (N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis (N = 15090, P = 2.94 × 10−7; replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 (PDZRN3) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins.ConclusionsOur study suggests that neck circumference may have unique genetic basis independent of BMI.

Acquired cisplatin resistance in cervical cancer therapy is principally caused by reduction in intracellular drug accumulation, which is exerted by hyperactivation of the oncogenic PI3K/Akt signaling axis and overexpression of cisplatin-exporter MRP2 along with prosurvival effectors NF-κB and IAPs in cervical cancer cells. These activated prosurvival signaling cascades drive drug efflux and evasion of apoptosis for rendering drug-resistant phenotypes. Our study challenges the PI3K/Akt axis in a cisplatin-resistant cervical cancer scenario with phenethylisothiocyanate (PEITC) for chemosensitization of SiHa R , a cisplatin-resistant sub-line of SiHa and 3-methylcholanthrene–induced cervical cancer mice models. SiHa R exhibited higher MRP2, p-Akt Thr308 , NF-κB, XIAP, and survivin expressions which cumulatively compromised cisplatin retention capacity and accumulated PEITC better than SiHa. SiHa R appeared to favor PEITC uptake as its accumulation rates were found to be positively correlated with MRP2 expressions. PEITC treatment in SiHa R for 3 h prior to cisplatin exposure revived intracellular platinum levels, reduced free GSH levels, generated greater ROS, and altered mitochondrial membrane potential compared to SiHa. Western blot and immunofluorescence results indicated that PEITC successfully downregulated MRP2 in addition to suppressing p-Akt Thr308 , XIAP, survivin, and NF-κB expressions. In mice models, administration of 5 mg/kg body-weight PEITC priming dosage prior to treatment with 3 mg/kg body-weight of cisplatin remediated cervical histology and induced tumor regression in contrast to the group receiving the same dosage of cisplatin only. This suggested PEITC as a potential chemosensitizing agent in light of acquired cisplatin resistance in cervical cancer and established its candidature for Phase I clinical trial.

Introduction Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. Methods An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. Results In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32–52 years), and the majority had Crohn’s disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. Conclusion Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Background: Insomnia and obstructive sleep apnoea are the two most common sleep disorders and frequently co-exist. Patients with comorbid insomnia and sleep apnoea experience worse daytime function, mental health and physical health than patients with either disorder alone. General practitioners may face unique challenges in the assessment and management of this prevalent and debilitating condition. Objective: This article aims to provide an overview of the prevalence, consequences, assessment and management of patients with comorbid insomnia and sleep apnoea in Australian general practice. Discussion: Patients with either insomnia or sleep apnoea should be assessed for both conditions. Treatments for both disorders should be offered to patients with both conditions. The recommended treatment for insomnia is cognitive behavioural therapy, whereas the recommended first-line treatment for moderate and severe obstructive sleep apnoea is lifestyle/weight management advice (where relevant) and continuous positive airway pressure therapy.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea–hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10−8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki–Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.