57 research outputs found
Emerging climate-driven disturbance processes: Widespread mortality associated with snow-to-rain transitions across 10° of latitude and half the range of a climate-threatened conifer
Climate change is causing rapid changes to forest disturbance regimes worldwide. While the consequences of climate change for existing disturbance processes, like fires, are relatively well studied, emerging drivers of disturbance such as snow loss and subsequent mortality are much less documented. As the climate warms, a transition from winter snow to rain in high latitudes will cause significant changes in environmental conditions such as soil temperatures, historically buffered by snow cover. The Pacific coast of North America is an excellent test case, as mean winter temperatures are currently at the snow–rain threshold and have been warming for approximately 100 years post-Little Ice Age. Increased mortality in a widespread tree species in the region has been linked to warmer winters and snow loss. Here, we present the first high-resolution range map of this climate-sensitive species, Callitropsis nootkatensis (yellow-cedar), and document the magnitude and location of observed mortality across Canada and the United States. Snow cover loss related mortality spans approximately 10° latitude (half the native range of the species) and 7% of the overall species range and appears linked to this snow–rain transition across its range. Mortality is commonly >70% of basal area in affected areas, and more common where mean winter temperatures is at or above the snow–rain threshold (>0 °C mean winter temperature). Approximately 50% of areas with a currently suitable climate for the species (< 2 °C) are expected to warm beyond that threshold by the late 21st century. Regardless of climate change scenario, little of the range which is expected to remain suitable in the future (e.g., a climatic refugia) is in currently protected landscapes (<1–9%). These results are the first documentation of this type of emerging climate disturbance and highlight the difficulties of anticipating novel disturbance processes when planning for conservation and management.Ye
Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1
The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right. In this model, autoinflammation was caused by mutation in the actin regulatory gene WDR1 We report a homozygous missense mutation in WDR1 in two siblings causing periodic fevers with immunodeficiency and thrombocytopenia. We found impaired actin dynamics in patient immune cells. Patients had high serum levels of IL-18, without a corresponding increase in IL-18-binding protein or IL-1β, and their cells also secreted more IL-18 but not IL-1β in culture. We found increased caspase-1 cleavage within patient monocytes indicative of increased inflammasome activity. We transfected HEK293T cells with pyrin and wild-type and mutated WDR1 Mutant protein formed aggregates that appeared to accumulate pyrin; this could potentially precipitate inflammasome assembly. We have extended the findings from the mouse model to highlight the importance of WDR1 and actin regulation in the activation of the inflammasome, and in human autoinflammation
Illnesses and Injuries at Nature Preschools
Thesis (Master's)--University of Washington, 2017-06This study investigated the incidence of illness and injury at nature preschools compared to conventional preschools. For 14 weeks, teachers at five nature and four conventional preschools logged the number of child absences due to illness and the number of injuries that occurred at preschool. This study found no difference in illness incidence by preschool type and no serious injuries during the course of the study. Girls at nature preschools had a higher incidence of minor injury compared to girls at conventional preschools. For boys, no significant differences in minor injuries by type of preschool were noted. Overall, the study found that nature preschools are a healthy and safe child care model
MOESM1 of H1N1 influenza vaccination in HIV-infected women on effective antiretroviral treatment did not induce measurable antigen-driven proliferation of the HIV-1 proviral reservoir
Additional file 1. Additional figures
Role of Lewis and Brønsted Acidity in Metal Chloride Catalysis in Organic Media: Reductive Etherification of Furanics
Metal
chlorides are demonstrated to behave as bifunctional acid
catalysts in organic media in the one-pot reductive etherification
of 5-hydroxymethylfurfural (HMF) in 2-propanol toward production of
biodiesel. Two competing reaction pathways, direct etherification
to 5-(isopropoxymethyl)Âfurfural and reductive etherification to 2,5-bisÂ(isopropoxymethyl)Âfuran,
are proposed with the selectivity depending on the metal ion. Furfural
and furfuryl alcohol are used as model compounds to investigate each
pathway individually. The roles of Lewis/Brønsted acidity of
metal chlorides solution are elucidated by kinetic studies in conjunction
with salt speciation using electrospray soft ionization mass spectrometer.
Brønsted acidic species, generated from alcoholysis of the metal
chlorides, are the predominant catalytically active species in etherification.
On the other hand, partially hydrolyzed metal cations produced by
alcoholysis/hydrolysis are responsible Lewis acid centers for furfural
reduction to furfuryl alcohol. Isotopic labeling experiments, in combination
with GCMS and <sup>1</sup>H NMR analysis, reveal an intermolecular
hydrogen transfer from the α-C of 2-propanol to the α-C
of furfural as the rate-limiting step of furfural hydrogenation
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Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners. Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied. Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160. Eight of 29 couples examined yielded viral sequences from both tissues. Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males. The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood. Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men. No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites. The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions. The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections. Identification of the viral characteristics associated with transmission would facilitate vaccine design. This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants. The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages. These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants
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Impact of Comorbidities at Diagnosis of Acute Myeloid Leukemia on One-Year Mortality
Abstract
The hematopoietic cell transplantation comorbidity index (HCT-CI) was specifically developed to assign weighted scores to comorbidities existing prior to allogeneic HCT; thus stratifying post-HCT mortality risks. The utility of comorbidities assessed prior to treatment for AML is unknown. Here, we a) investigated the impact of each comorbidity on 1-year overall mortality of patients (pts) with newly diagnosed AML, b) designed and validated a new comorbidity score (AML-CI) comparing its performance to that of the HCT-CI, and c) identified other relevant risk factors for AML outcomes.
We retrospectively collected comorbidities and laboratorydata from 1079 pts with newly diagnosed AML who received therapy at 5 institutions from 2008- 2012. Pts were aged ≤49 (29%), 50-59 (25%), 60-69 (26%), and ≥70 (20%) years old. Cytogenetic-risks were favorable (21%), intermediate (36%), or unfavorable (43%). Regimen intensity was low in 18%, intermediate in 63%, and high in 19%. HCT-CI comorbidities were evaluated per HCT-CI standard comorbidity definitions with the exception that renal comorbidity was defined per serum creatinine and/or creatinine clearance. Newly evaluated comorbiditiesincluded including hyperlipidemia, hypertension, deep venous thrombosis, gastroesophageal reflux disease, hypothyroidism, hypoalbuminemia, thrombocytopenia, neutropenia, anemia, elevated lactate dehydrogenase (LDH), smoking, and alcohol intake. Pts were randomly divided into a training (n=710) and a testing set (n=369). In the training set, the unadjusted hazard ratios (HRs) for 1-year overall mortality were calculated for each comorbidity as well as all adjustment factors: gender, age, race, cytogenetic-risks, regimen intensity, WBC, blast count, and marrow blast percentages. Only factors that were associated with overall mortality at a significance level of P <.10 proceeded to the multivariate model. Each comorbidity that entered the multivariate model was then adjusted for the effect of other comorbidities as well as gender, age, cytogenetic-risks, and regimen intensity (Table 1). The adjusted HRs were employedas weights for individual comorbidities. In the validation set, the new AML-CI incorporating comorbidities had comparable power of prediction for 1-year overall mortality as the HCT-CI (c-statistic estimates of 0.6 for each). Augmenting the HCT-CI with the three new covariates: platelets, albumin, and LDH yielded c-statistic estimate of 0.61. Other than comorbidities, age (c-statistic of 0.65) and cytogenetic-risks (c-statistic of 0.62) independently predicted overall mortality (Table 2).
Comorbidities at diagnosis of AML heavily influenced the survival of pts over the year following diagnosis. The new AML-CI has similar predictive power as the HCT-CI suggesting appropriateness of using the HCT-CI at diagnosis of AML given its familiarity to physicians. The augmented HCT-CI, age, and cytogenetic-risks independently stratified for risks of 1-year mortality. In the future, studying physical, cognitive, and social health might further clarify the prognostic role of increasing age. Targeting health limitations with interventions alongside specific AML-therapy might improve survival of patients.
Table 1. Components of a new AML-CI based on multivariate evaluation of impact of comorbidities on 1-year mortality after diagnosis of AML Comorbidities HR Assigned score for AML-CI Arrhythmia* 1.0 ─ Coronary Artery* 1.1 ─ Valvular* 1.3 1 Cerebrovascular * 1.3 1 Hepatic* Mild 1.2 ─ Moderate/severe 1.2 ─ Renal* Mild 1.1 ─ Moderate/severe .8 ─ Pulmonary* Mild .9 ─ Moderate/severe 1.1 ─ Diabetes* 1.3 1 Tumor* 1.7 1 Peptic Ulcer* 1.3 1 Psychiatric* 1.3 1 Hyperlipidemia 1.0 ─ HTN 1.2 ─ Albumin 200 - 500 1.5 1 >500 - 1000 1.4 1 >1000 2.2 2 Smoking Former 1.2 ─ Current 1.1 ─ *included comorbidities within HCT-CI
Table 2. Probabilities of 1-year survival per 6 different models in the validation set AML-CI HCT-CI Augmented HCT-CI* Score % OS Score % OS Score % OS 0-1 18 69 0 20 72 0-2 24 70 2 28 68 1-2 35 61 3-4 28 63 3 30 56 3-4 28 57 5-7 33 58 ≥4 23 45 ≥5 18 42 ≥8 15 34 Age Cytogenetic-risks Augmented HCTCI* + age + cyto Group % OS Group % OS Score % OS 0-49 27 81 Favorable 19 87 2-4 17 86 50-69 51 60 Intermediate 36 63 5-7 37 67 70+ 22 31 Unfavorable 45 45 8-10 27 54 ≥11 19 28 *included HCT-CI + albumin, platelet counts and LDH
Disclosures
Fathi: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy; Exelexis: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding. Sekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Lee:Kadmon: Consultancy; Bristol-Myers Squibb: Consultancy
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