The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the “Practice ...parameter for the diagnosis and management of primary immunodeficiency.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host ...sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 × 10(-6)), and we observed a positive association with lymph node metastasis.
Humans strongly impact the dynamics of coastal systems, yet surprisingly few studies mechanistically link management of anthropogenic stressors and successful restoration of nearshore habitats over ...large spatial and temporal scales. Such examples are sorely needed to ensure the success of ecosystem restoration efforts worldwide. Here, we unite 30 consecutive years of watershed modeling, biogeochemical data, and comprehensive aerial surveys of Chesapeake Bay, United States to quantify the cascading effects of anthropogenic impacts on submersed aquatic vegetation (SAV), an ecologically and economically valuable habitat. We employ structural equation models to link land use change to higher nutrient loads, which in turn reduce SAV cover through multiple, independent pathways. We also show through our models that high biodiversity of SAV consistently promotes cover, an unexpected finding that corroborates emerging evidence from other terrestrial and marine systems. Due to sustained management actions that have reduced nitrogen concentrations in Chesapeake Bay by 23% since 1984, SAV has regained 17,000 ha to achieve its highest cover in almost half a century. Our study empirically demonstrates that nutrient reductions and biodiversity conservation are effective strategies to aid the successful recovery of degraded systems at regional scales, a finding which is highly relevant to the utility of environmental management programs worldwide.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The etiologic relationship between wasting and stunting is poorly understood, largely because of a lack of high-quality longitudinal data from children at risk of undernutrition.
The aim of this ...study was to describe the interrelationships between wasting and stunting in children aged <2 y.
This study involved a retrospective cohort analysis, based on growth-monitoring records spanning 4 decades from clinics in rural Gambia. Anthropometric data collected at scheduled infant welfare clinics were converted to z scores, comprising 64,342 observations on 5160 subjects (median: 12 observations per individual). Children were defined as “wasted” if they had a weight-for-length z score <–2 against the WHO reference and “stunted” if they had a length-for-age z score <–2.
Levels of wasting and stunting were high in this population, peaking at approximately (girls–boys) 12–18% at 10–12 months (wasted) and 37–39% at 24 mo of age (stunted). Infants born at the start of the annual wet season (July–October) showed early growth faltering in weight-for-length z score, putting them at increased risk of subsequent stunting. Using time-lagged observations, being wasted was predictive of stunting (OR: 3.2; 95% CI: 2.7, 3.9), even after accounting for current stunting. Boys were more likely to be wasted, stunted, and concurrently wasted and stunted than girls, as well as being more susceptible to seasonally driven growth deficits.
We provide evidence that stunting is in part a biological response to previous episodes of being wasted. This finding suggests that stunting may represent a deleterious form of adaptation to more overt undernutrition (wasting). This is important from a policy perspective as it suggests we are failing to recognize the importance of wasting simply because it tends to be more acute and treatable. These data suggest that stunted children are not just short children but are children who earlier were more seriously malnourished and who are survivors of a composite process.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).
We analyzed 1,550 adults with ...primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.
The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients.
The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification.
Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains ...poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare 'outlier' clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Molecular subtyping for pancreatic cancer has made substantial progress in recent years, facilitating the optimization of existing therapeutic approaches to improve clinical outcomes in pancreatic ...cancer. With advances in treatment combinations and choices, it is becoming increasingly important to determine ways to place patients on the best therapies upfront. Although various molecular subtyping systems for pancreatic cancer have been proposed, consensus regarding proposed subtypes, as well as their relative clinical utility, remains largely unknown and presents a natural barrier to wider clinical adoption.
We assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a single-sample classifier (SSC) using penalized logistic regression based on the most robust and replicable schema.
We demonstrate that a tumor-intrinsic two-subtype schema is most robust, replicable, and clinically relevant. We developed Purity Independent Subtyping of Tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX.
The flexibility and utility of PurIST on low-input samples such as tumor biopsies allows it to be used at the time of diagnosis to facilitate the choice of effective therapies for patients with pancreatic ductal adenocarcinoma and should be considered in the context of future clinical trials.
The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single ...individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Chief Editors Linda Cox, MD Department of Medicine Nova Southeastern University College of Osteopathic Medicine Davie, Florida Richard Lockey, MD Division of Allergy and Immunology Department of Internal Medicine University of South Florida College of Medicine and James A. Haley Veterans' Hospital Tampa, Florida Harold Nelson, MD Department of Medicine National Jewish Health Denver, Colorado Work Group Members Christopher Calabria, MD Glen Burnie, Maryland Thomas Chacko, MD Roswell, Georgia Ira Finegold, MD New York, New York Michael Nelson, MD, PhD Washington, DC Richard Weber, MD Denver, Colorado Joint Task Force Reviewers David Bernstein, MD Department of Medicine and Environmental Health University of Cincinnati College of Medicine Cincinnati, Ohio David A. Khan, MD Department of Internal Medicine University of Texas Southwestern Medical Center Dallas, Texas Joann Blessing-Moore, MD Departments of Medicine and Pediatrics Stanford University Medical Center Department of Immunology Palo Alto, California David M. Lang, MD Allergy/Immunology Section Division of Medicine Allergy and Immunology Fellowship Training Program Cleveland Clinic Foundation Cleveland, Ohio Richard A. Nicklas, MD Department of Medicine George Washington Medical Center Washington, DC John Oppenheimer, MD Department of Internal Medicine New Jersey Medical School Pulmonary and Allergy Associates Morristown, New Jersey Jay M. Portnoy, MD Section of Allergy, Asthma & Immunology The Children's Mercy Hospital Department of Pediatrics University of Missouri-Kansas City School of Medicine Kansas City, Missouri Christopher Randolph, MD Yale University New Haven, Connecticut Diane E. Schuller, MD Department of Pediatrics Pennsylvania State University Milton S. Hershey Medical College Hershey, Pennsylvania Sheldon L. Spector, MD Department of Medicine UCLA School of Medicine Los Angeles, California Stephen A. Tilles, MD Department of Medicine University of Washington School of Medicine Redmond, Washington Dana V. Wallace, MD Department of Medicine Nova Southeastern University Davie, Florida Invited Reviewers Don Aaronson, MD, JD, MPH Chicago, Illinois Desiree Larenas-Linnemann, MD Mexico city, Mexico Bryan Leatherman, MD Gulfport, Mississippi Sandra Y. Lin, MD Johns Hopkins Department of Otolaryngology-Head & Neck Surgery Baltimore, Maryland Oral and sublingual immunotherapy for food hypersensitivity Wesley Burkes, MD Duke University Raleigh, North Carolina Venom hypersensitivity David Golden, MD Baltimore, Maryland Theodore M. Freeman, MD Helotes, Texas Allergen extract section Derek Constable, PhD Spokane, Washington Robert Esch, PhD Lenoir, North Carolina Larry Garner, CPT, BA Spokane, Washington Richard Lankow, PhD Round Rock, Texas Greg Plunkett, PhD Round Rock, Texas Ronald Rabin, MD Rockville, Maryland Assigned Reviewers Paul Greenberger, MD Northwestern University Feinberg School of Medicine Chicago, Illinois Bryan Martin, DO Ohio State University Columbus, Ohio Preface This document was developed by the Joint Task Force on Practice Parameters, which represents the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & ...Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing “The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, or the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sensitivity to environmental context has been of interest for many years, but the nature of individual differences in environmental sensitivity has become of particular focus over the past 2 decades. ...What is particularly uncertain are the neural variables and processes that mediate the effects of environment on developmental outcomes. Accordingly, we provide a neurobehavioral foundation of reactivity to the environment in several steps. First, the different patterns of environmental sensitivity are defined to identify the significant factors involved in the manifestation of these patterns. Second, we focus on neurobiological reactivity as the construct underlying variation in sensitivity to the environment by (a) providing an organizing threshold model of elicitation of neurobiology by environmental context; and (b) integrating the literature on 2 sets of neuromodulators in terms of each modulator's (a) contribution to neural and behavioral reactivity to stimulation, and (b) relation to emotional-motivational systems (dopamine, opiates and oxytocin, corticotropin-releasing hormone) or the general modulation of those systems (serotonin, norepinephrine, and GABA). Discussion concludes with (a) a comprehensive neurobehavioral framework of environmental reactivity based on a combinatorial model of a supertrait, (b) methodological implications of the model, and (c) a developmental perspective on environmental reactivity.
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