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A beautifully illustrated book showcasing masterpieces of European porcelain from The Met's renowned collection The quest to discover the process of making porcelain was one of the defining aspects of post-Renaissance Europe, and it had significant artistic, technical, and commercial ramifications. This beautifully illustrated book showcases ninety works, spanning the late 16th to the mid-19th century, and reflecting the major currents of European porcelain production. Each work is shown in glorious new photography, accompanied by analysis and interpretation by one of the leading experts in European decorative arts. Featuring blue-and-white wares from Italy, rare examples of German Meissen, French Sevres, British Chelsea porcelain, and much more, this is a long-overdue survey of the greatest porcelain treasures from The Met's vast collection.

In this prospective study of more than 65,000 women, fine particulate air pollution was found to be associated with an increased risk of cardiovascular events and death from cardiovascular causes. These observations add to the growing evidence that air pollution, especially fine particulate matter, has important adverse health consequences. Fine particulate air pollution was found to be associated with an increased risk of cardiovascular events and death from cardiovascular causes. Exposure to air pollution has been associated with death and hospitalization from cardiovascular causes. 1 Uncertainty remains about the magnitude of these associations, the mechanisms, and the effects of long-term exposure to pollutants, as compared with short-term exposure. Although previous studies of daily increases in exposure to pollution have assessed both fatal and nonfatal events, 2 studies investigating long-term exposure — estimating average exposure during years of follow-up — have evaluated mortality only on the basis of death certificates. 3 – 8 The increase in mortality associated with long-term exposure to air pollution is larger than that seen in studies of short-term exposure, and . . .

Background Exposure to traffic-related air pollution (TRAP) is considered a trigger for acute cardiovascular events. Diesel Exhaust (DE) is a major contributor to TRAP in the world. We evaluated the effect of DE inhalation on circulating blood cell populations, hematological indices, and systemic inflammatory cytokines in humans using a specialized facility. Methods In a randomized double-blind crossover study balanced to order, 17 metabolic syndrome (MetS) and 15 healthy subjects inhaled filtered air (FA) or DE exposure in two-hour sessions on different days with a minimum 2-week washout period. We collected blood pre-exposure, 7, and 22 hours after exposure initiation and measured the complete blood count and differential. We performed multiplex cytokine assay to measure the changes in the systemic inflammatory cytokines, and endothelial adhesion molecules (n=15). A paired analysis compared the effect of DE and FA exposures for the change from pre-exposure to the subsequent time points. Results A significant increase in the hematocrit was noted 7 hrs after DE [1.4% (95% CI: 0.9 to 1.9%)] compared to FA exposure [0.5% (95% CI: -0.09 to 1.0%); p=0.008. The hemoglobin levels increased non-significantly at 7 hrs post DE [0.3 gm/dL (95% CI: 0.2 to 0.5 gm/dL)] versus FA exposure [0.2 gm/dL (95% CI: 0 to 0.3 gm/dL)]; p=0.06. Furthermore, the platelet count increased 22 hrs after DE exposure in healthy, but not in MetS subjects [DE: 16.6 (95% CI: 10.2 to 23) thousand platelets/mL versus [FA: 3.4 (95% CI: -9.5 to 16.3) thousand platelets/mL)]; p=0.04. No DE effect was observed for WBC, neutrophils, lymphocytes or erythrocytes. Using the multiplex assay, small borderline significant increases in matrix metalloproteinase-9, interleukins (IL)-1beta, 6 and 10 occurred 7 hrs post exposure initiation, whereas E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule -1, and myeloperoxidase 22 hrs post exposure. Conclusions Our results suggest that short-term DE exposure results in hemoconcentration and thrombocytosis, which are important determinants of acute cardiovascular events. Multiplex assay showed a non-significant increase in IL-1β and IL-6 immediately post exposure followed by myeloperoxidase and endothelial activation molecules. Further specific assays in a larger population will improve our understanding of the systemic inflammatory mechanisms following acute exposure to TRAP. Clinical trials registration number Study was conducted between 2004 to 2006, prior to expectation for registration.

To determine whether increased exposure to particulate matter air pollution (PM), measured with personal, residential, or central site monitoring, was associated with pulmonary function decrements in either adults with COPD or children with asthma. We studied 57 adults with or without COPD and 17 children aged 6 to 13 years with physician-diagnosed asthma in Seattle during a 3-year panel study. Indoor and outdoor PM measurements were made at subjects’ homes. The subjects wore personal exposure monitors for 10 consecutive 24-h periods, and PM was also measured at a central outdoor location. We assessed the within-subject effect of particulate exposure on FEV1 and peak expiratory flow (PEF) in adults, and maximal midexpiratory flow (MMEF), PEF, FEV1, and symptoms in children. FEV1 decrements were associated with 1-day lagged central site PM ≤ 2.5 μm in diameter (PM2.5) in adult subjects with COPD. In children not receiving antiinflammatory medication, same day indoor, outdoor, and central site exposures to PM2.5 were associated with decrements in MMEF, PEF, and FEV1. Associations with PM2.5 and lung function decrements were also observed for 1-day lagged indoor (MMEF, PEF, FEV1) and personal (PEF only) exposures. Antiinflammatory medication use in children significantly attenuated the PM effect on airflow rates and volumes. This study found consistent decrements in MMEF in children with asthma who were not receiving medications. It is notable that effects were observed even though PM exposures were low for an urban area. These findings suggest the need for future larger studies of PM effects in this susceptible population that repeatedly measure spirometry to include MMEF and potentially more sensitive markers of airway inflammation such as exhaled breath condensate and exhaled nitric oxide.

Background: Traffic-related air pollution is consistently associated with cardiovascular morbidity and mortality. Recent human and animal studies suggest that exposure to air pollutants affects vascular function. Diesel exhaust (DE) is a major source of traffic-related air pollution. Objectives: Our goal was to study the effects of short-term exposure to DE on vascular reactivity and on mediators of vascular tone. Methods: In a double-blind, crossover, controlled exposure study, 27 adult volunteers (10 healthy and 17 with metabolic syndrome) were exposed in randomized order to filtered air (FA) and each of two levels of diluted DE (100 or 200$\\mu {\\rm g}/{\\rm m}^{3}$of fine particulate matter) in 2-hr sessions. Before and after each exposure, we assessed the brachial artery diameter (BAd) by B-mode ultrasound and collected blood samples for endothelin-1 (ET-1) and catecholamines. Postexposure we also assessed endothelium-dependent flow-mediated dilation (FMD). Results: Compared with FA, DE at$200\\ \\mu {\\rm g}/{\\rm m}^{3}$elicited a decrease in BAd (0.11 mm; 95% confidence interval, 0.02-0.18), and the effect appeared linearly dose related with a smaller effect at$100\\ \\mu {\\rm g}/{\\rm m}^{3}$. Plasma levels of ET-1 increased after$200\\ \\mu {\\rm g}/{\\rm m}^{3}$DE but not after FA (p = 0.01). There was no consistent impact of DE on plasma catecholamines or FMD. Conclusions: These results demonstrate that short-term exposure to DE is associated with acute endothelial response and vasoconstriction of a conductance artery. Elucidation of the signaling pathways controlling vascular tone that underlie this observation requires further study.

Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (E) to PM2.5(PM with aerodynamic diameter ≤ 2.5 μm) into its indoor-generated (Eig) and ambient-generated (Eag) components for 19 children with asthma. We then compared Eigand Eagto changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, Eagwas marginally associated with increases in eNO [5.6 ppb per 10-μ g/ m3increase in PM2.5; 95% confidence interval (CI), -0.6 to 11.9; p = 0.08]. Eigwas not associated with eNO (-0.19 ppb change per 10 μ g/ m3). Our predictive model allowed us to estimate Eagand Eigfor all 19 children. For those combined estimates, only Eagwas significantly associated with an increase in eNO (Eag: 5.0 ppb per 10-μ g/ m3increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; Eig: 3.3 ppb per 10-μ g/ m3increase in PM2.5; 95% CI, -1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5exposure is consistently associated with increases in eNO and the indoor-generated component is less strongly associated with eNO.

There is conflicting evidence regarding the association between different size fractions of particulate matter (PM) and cardiac and respiratory morbidity and mortality. We investigated the short-term associations of four size fractions of particulate matter (PM(1), PM(2.5), PM(10), and PM(10-2.5)) and carbon monoxide with hospital admissions and emergency room (ER) visits for respiratory and cardiac conditions and mortality in Spokane, Washington. We used a log-linear generalized linear model to compare daily averages of PM and carbon monoxide with daily counts of the morbidity and mortality outcomes from January 1995 to June 2001. We examined pollution lags ranging from 0 to 3 days and compared our results to a similar log-linear generalized additive model. Effect estimates tended to be smaller and have larger standard errors for the generalized linear model. Overall, we saw no association with respiratory ER visits and any size fraction of PM. However, there was a suggestion of greater respiratory effect from fine PM when compared to coarse fraction. Carbon monoxide was associated with both all respiratory ER visits and visits for asthma at the 3-day lag. We feel that carbon monoxide may be serving as a marker for combustion-derived pollutants, which is one large component of the diverse air pollutant mixture. We also found no association with any size fraction of PM or CO with cardiac hospital admissions or mortality at the 0- to 3-day lag. We found no consistent associations between any size fraction of PM and cardiac or respiratory ER visits or hospital admissions.

Globalization has increased competitive pressures on firms. Together with rapid technological change, it has altered the environment in which firms operate. While globalization offers unprecedented opportunities for firms to act successfully, it simultaneously heightens the risks for firms lagging behind. In an open and liberalized world, increasing firm competitiveness has become a major challenge. This book provides a thorough analysis of the competitiveness of firms in the Middle East and North Africa Region (MENA). It is organized into four parts which detail the different issues related to firm competitiveness from global rules for business, regional business environment, corporate governance, and the key economic sectors of small/medium size enterprises, and tourism. In addition, the book also addresses key issues for the future of the region including the real challenges facing firms ' operations and efficiency, the ability of MENA firms to compete in global markets, the impact of small, and medium size enterprises on the stimulation of growth, and the economic potential of the tourism sector.

Checkpoint inhibitors are standard adjuvant treatment for stage IIB–IV resected melanoma, but many patients recur. Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence-free survival and distant metastasis-free survival versus pembrolizumab monotherapy in resected high-risk melanoma. We did an open-label, randomised, phase 2b, adjuvant study of mRNA-4157 plus pembrolizumab versus pembrolizumab monotherapy in patients, enrolled from sites in the USA and Australia, with completely resected high-risk cutaneous melanoma. Patients with completely resected melanoma (stage IIIB–IV) were assigned 2:1 to receive open-label mRNA-4157 plus pembrolizumab or pembrolizumab monotherapy. mRNA-4157 was administered intramuscularly (maximum nine doses) and pembrolizumab intravenously (maximum 18 doses) in 3-week cycles. The primary endpoint was recurrence-free survival in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov, NCT03897881. From July 18, 2019, to Sept 30, 2021, 157 patients were assigned to mRNA-4157 plus pembrolizumab combination therapy (n=107) or pembrolizumab monotherapy (n=50); median follow-up was 23 months and 24 months, respectively. Recurrence-free survival was longer with combination versus monotherapy (hazard ratio [HR] for recurrence or death, 0·561 [95% CI 0·309–1·017]; two-sided p=0·053), with lower recurrence or death event rate (24 [22%] of 107 vs 20 [40%] of 50); 18-month recurrence-free survival was 79% (95% CI 69·0–85·6) versus 62% (46·9–74·3). Most treatment-related adverse events were grade 1–2. Grade ≥3 treatment-related adverse events occurred in 25% of patients in the combination group and 18% of patients in the monotherapy group, with no mRNA-4157-related grade 4–5 events. Immune-mediated adverse event frequency was similar for the combination (37 [36%]) and monotherapy (18 [36%]) groups. Adjuvant mRNA-4157 plus pembrolizumab prolonged recurrence-free survival versus pembrolizumab monotherapy in patients with resected high-risk melanoma and showed a manageable safety profile. These results provide evidence that an mRNA-based individualised neoantigen therapy might be beneficial in the adjuvant setting. Moderna in collaboration with Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.