Explore the vast range of titles available.

\"Informed decisions concerning undiscovered mineral resources cannot be made without an understanding of the technological, environmental, or economic difficulties that might be encountered. Quantitative Mineral Resource Assessments: An Integrated Approach offers a modern quantitative assessment that explicates the diverse factors that affect mineral-related decisions, so that potential consequences can be more easily assessed, uncertainty and risk reduced, and courses of action determined without bias. The integrated approach focuses on three assessment parts and the models that support them and is designed so that consequences of alternative courses of action can be examined with respect to land use, exploration, or mineral-resource development. Drawing upon newly developed deposit density models, frequency distributions, and previously unpublished experiments, the book provides an essential and practical approach for making critical decisions.\" \"Written for governmental and industrial policy makers, managers of exploration, planners of regional development, and similar decision makers, the book brings together for the first time the widely scattered literature on the subject. It also captures the necessary ingredients of the diverse disciplines of economic geology, statistics, mineral economics, and geology that are an integral part of quantitative mineral resource assessments. With this wealth of information, the book will serve not only as a guide for professionals but also as a comprehensive reference for those studying or researching mineral resources.\"--BOOK JACKET.

In the summer of 1999, West Nile virus was recognised in the western hemisphere for the first time when it caused an epidemic of encephalitis and meningitis in the metropolitan area of New York City, NY, USA. Intensive hospital-based surveillance identified 59 cases, including seven deaths in the region. We did a household-based seroepidemiological survey to assess more clearly the publichealth impact of the epidemic, its range of illness, and risk factors associated with infection. We used cluster sampling to select a representative sample of households in an area of about 7·3 km2 at the outbreak epicentre. All individuals aged 5 years or older were eligible for interviews and phlebotomy. Serum samples were tested for IgM and IgG antibodies specific for West Nile virus. 677 individuals from 459 households participated. 19 were seropositive (weighted seroprevalence 2·6% [95% CI 1·2–4·1). Six (32%) of the seropositive individuals reported a recent febrile illness compared with 70 of 648 (11%) seronegative participants (difference 21% [0–47]). A febrile syndrome with fatigue, headache, myalgia, and arthralgia was highly associated with seropositivity (prevalence ratio 7·4 [1·5–36·6]). By extrapolation from the 59 diagnosed meningoencephalitis cases, we conservatively estimated that the New York outbreak consisted of 8200 (range 3500–13 000) West Nile viral infections, including about 1700 febrile infections. During the 1999 West Nile virus outbreak, thousands of symptomless and symptomatic West Nile viral infections probably occurred, with fewer than 1% resulting in severe neurological disease.

The relation between Euler's planar elastic curves and vortex filaments evolving by the localized induction equation (LIE) of hydrodynamics was discovered by Hasimoto in 1971. Basic facts about (an integrable case of) Kirchhoff elastic rods are described here, which amplify the connection between the variational problem for rods and the soliton equation LIE. In particular, it is shown that the centerline of the Kirchhoff rod is an equilibrium for a linear combination of the first three conserved Hamiltonians in the LIE hierarchy.

Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.

Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer. We did this open-label, single-arm, multicentre, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. In cohort A of the trial, adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumours, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy were enrolled. All enrolled patients were assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent. The primary endpoint was clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter for up to 5 years. Efficacy was assessed in all patients who received at least one dose of the study drug and met BCG-unresponsive criteria. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing. Between Dec 9, 2015, and April 1, 2018, we screened 334 patients for inclusion. 186 patients did not meet inclusion criteria, and 47 patients were assigned to cohort B (patients with BCG-unresponsive high grade Ta or any grade T1 papillary disease without carcinoma in situ; results will be reported separately). 101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96). Median follow-up was 36·4 months (IQR 32·0–40·7). 39 (41%; 95% CI 30·7–51·1) of 96 patients with BCG-unresponsive carcinoma in situ of the bladder with or without papillary tumours had a complete response at 3 months. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients; the most common were arthralgia (in two [2%] patients) and hyponatraemia (in three [3%] patients). Serious treatment-related adverse events occurred in eight (8%) patients. There were no deaths that were considered treatment related. Pembrolizumab monotherapy was tolerable and showed promising antitumour activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer who declined or were ineligible for radical cystectomy and should be considered a a clinically active non-surgical treatment option in this difficult-to-treat population. Merck Sharp & Dohme.

In the past fifteen years, financial regulators from the developed world have attempted to create international regulatory standards in a variety of financial issue areas. Their negotiations are notable for the stark variation in the preferences of regulators toward international regulatory harmonization. Certain regulators actively resist any attempts at regulatory harmonization, while others are vocal in their advocacy for an international agreement. When will regulators seek to harmonize their rules with their foreign counterparts? I propose a principal-agent framework for analyzing regulator behavior that views international harmonization as a means of satisfying domestic political pressures. The framework predicts that regulators are more likely to seek international regulatory harmonization when confidence in the stability of financial institutions is declining, and when competitive pressures are increasing from foreign firms facing less stringent regulations. I explore the consistency of the framework with two important cases in the history of international financial regulation: the negotiations among bank regulators leading up to the 1988 Basel Accord on bank capital adequacy, and the negotiations among securities regulators over capital adequacy for securities firms between 1988 and 1992.I thank Gabe Aguilera, David Bach, Ethan Bueno de Mesquita, Dan Carpenter, Bill Clark, Mark Copelovitch, Jeff Frieden, Dan Gingerich, Dan Ho, Devesh Kapur, Joseph N. R. Sanberg, Ross Schaap, Allan Stam, Matt Stephenson, two anonymous reviewers, and the editors of IO for helpful comments, discussions, and feedback. I am also indebted to the thirty current and former regulators and financial industry executives who participated in interviews to advance this project. Finally, I thank the Weatherhead Center for International Affairs and the Center for European Studies for research funding.

Towards the end of their article, [Alexandra Mangili] and [Mark Gendreau] state that a US National Institute for Occupational Safety and Health (NIOSH) N95 mask should be placed on a passenger suspected of having severe acute respiratory infection (SARS), and that the passenger should be isolated. Not all N95 masks are appropriate. The N95 certification by NIOSH only guarantees that 95% of airborne particles (about 0.3 µm) will be filtered from ambient air. Such masks are intended for the protection of the wearer, not others. Indeed, some N95 masks feature one-way exhalation valves which enable unfiltered air to flow freely into the environment.4 Consequently, they should not be worn by someone suspected of having SARS or any other respiratory infection. Current NIOSH recommendations for air transportation of SARS patients recommend N95 masks for those with the patient, and a \"surgical mask\" for the patient.5 As Mangili and Gendreau note, the value of this intervention is unproven.

Previously, analgesics were avoided in suspected appendicitis to avoid masking the diagnosis. We determined use of analgesia in patients with appendicitis to determine recent trends over time and explore predictors of use of analgesia. A retrospective review of the National Hospital Ambulatory Medical Care Survey 2006–2010 was conducted including emergency department (ED) patients with acute appendicitis (ICD-9-CM 540.xx). The association between demographic and clinical information with ED visit prescription of analgesics/opioids was determined using univariate (χ2) and multivariate (logistic regression) analyses. There were an estimated 763000 ED patient visits for acute appendicitis from 2006 to 2010. Mean age was 32, 74% were under age 19, 69% were male. Sixty-four percent of patients received any analgesia in the ED and 58% received an opioid; use of analgesics did not change over time. Of all patients, 68% had computed tomographic (CT) imaging. There was a positive trend in analgesic use with increasing pain (27% for no pain to 71% for severe pain, P = .08); a similar trend was seen for opioids but was not significant (P = .12). Analgesic use was lower for elderly (age >65) patients (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.56) and private insurance (OR 0.14, 95% CI 0.05-0.43), and higher for patients with CT scans (OR 3.73, 95% CI 1.61-8.66). Pain severity was not associated with administration of analgesics after controlling for other factors. Use of analgesia and opioids analgesia has remained stable over time. Factors associated with prescription of any analgesia and opioids were older age and payment source. Use of CT was associated with prescription of analgesics.

Rocks used as construction aggregate in temperate climates deteriorate to differing degrees because of repeated freezing and thawing. The magnitude of the deterioration depends on the rock's properties. Aggregate, including crushed carbonate rock, is required to have minimum geotechnical qualities before it can be used in asphalt and concrete. In order to reduce chances of premature and expensive repairs, extensive freeze-thaw tests are conducted on potential construction rocks. These tests typically involve 300 freeze-thaw cycles and can take four to five months to complete. Less time consuming tests that (1) predict durability as well as the extended freeze-thaw test or that (2) reduce the number of rocks subject to the extended test, could save considerable amounts of money. Here we use a probabilistic neural network to try and predict durability as determined by the freeze-thaw test using four rock properties measured on 843 limestone samples from the Kansas Department of Transportation. Modified freeze-thaw tests and less time consuming specific gravity (dry), specific gravity (saturated), and modified absorption tests were conducted on each sample. Durability factors of 95 or more as determined from the extensive freeze-thaw tests are viewed as acceptable—rocks with values below 95 are rejected. If only the modified freeze-thaw test is used to predict which rocks are acceptable, about 45% are misclassified. When 421 randomly selected samples and all four standardized and scaled variables were used to train aprobabilistic neural network, the rate of misclassification of 422 independent validation samples dropped to 28%. The network was trained so that each class (group) and each variable had its own coefficient (sigma). In an attempt to reduce errors further, an additional class was added to the training data to predict durability values greater than 84 and less than 98, resulting in only 11% of the samples misclassified. About 43% of the test data was classed by the neural net into the middle group—these rocks should be subject to full freeze-thaw tests. Thus, use of the probabilistic neural network would meanthat the extended test would only need be applied to 43% of the samples, and 11% of the rocks classed as acceptable would fail early.