Background:
Prior to national spread, the Department of Veterans Affairs implemented a pilot of the life-sustaining treatment decisions initiative (LSTDI) to promote proactive goals of care ...conversations (GoCC) with seriously ill patients, including policy and practice standards, an electronic documentation template and order set, and implementation support.
Aim:
To describe a 2-year pilot of the LSTDI at 4 demonstration sites.
Design:
Prospective observational study.
Setting/Participants:
A total of 6664 patients who had at least one GoCC.
Results:
Descriptive statistics characterized patient demographics, goals of care, LST decisions, and risk of hospitalization or mortality among patients with at least one GoCC. Participants were on average 71.4 years old, 93.2% male, 87.1% white, and 64.7% urban; 27.3% died by the end of the pilot period. Fifteen percent lacked decision-making capacity (DMC). Nonmutually exclusive goals included to be cured (7.6%), to prolong life (34%), to improve/maintain quality of life (61.5%), to be comfortable (53%), to obtain support for family/caregiver (8.4%), to achieve life goals (2.1%), and other (10.5%). Many GoCCs resulted in a do not resuscitate (DNR) order (58.8%). Patients without DMC were more likely to have comfort-oriented goals (77.3% vs 48.8%) and a DNR (84% vs 52.6%). Chart abstraction supported content validity of GoCC documentation.
Conclusion:
The pilot demonstrated that standardizing practices for eliciting and documenting GoCCs resulted in customized documentation of goals of care and LST decisions of a large number of seriously ill patients and established the feasibility of spreading standardized practices throughout a large integrated health care system.
Reconstructions of volcanic aerosol radiative forcing are required to understand past climate variability. Currently, reconstructions of pre‐20th century volcanic forcing are derived from sulfate ...concentrations measured in polar ice cores, mainly using a relationship between the average ice‐sheet sulfate deposition and stratospheric sulfate aerosol burden based on a single explosive eruption—the 1991 eruption of Mt. Pinatubo. Here we estimate volcanic radiative forcings and associated uncertainty ranges from ice‐core sulfate records of eight of the largest bipolar deposition signals in the last 2,500 years using statistical emulation of a perturbed parameter ensemble of aerosol‐climate model simulations of explosive eruptions. Extensive sampling of different combinations of eruption source parameters using the emulators reveals that a very wide range of eruptions in different seasons with different sulfur dioxide emissions, eruption latitudes, and emission altitudes produce ice‐sheet sulfate deposition consistent with ice‐core records. Consequently, we find a large range in the volcanic forcing that can be directly attributed to the unknown eruption source parameters. We estimate that the uncertainty in volcanic forcing caused by many plausible eruption realizations leads to uncertainties in the global mean surface cooling of around 1°C for the largest unidentified historical eruptions. Our emulators are available online (https://cemac.github.io/volcanic-forcing-deposition) where eruption realizations for given ice‐sheet sulfate depositions can be explored.
Plain Language Summary
Explosive volcanic eruptions inject sulfur into the atmosphere, forming sulfate particles that reflect sunlight and cause surface cooling. To understand past climate variability it is important to quantify the climate effects of historical eruptions. However, there are no direct observations of the sulfur emissions and cooling from eruptions that occurred hundreds of years ago, and volcanic climate effects must be inferred from indirect measurements. Volcanic sulfate is deposited onto Earth's surface and can be found in layers of polar ice. Ice‐core sulfate records are used to identify the occurrence of past eruptions, and the size of the sulfate signals is used to estimate the amount of sulfate that was present in the atmosphere and consequently the climatic effect of the eruption. We explored the uncertainty in this calculation by using climate model simulations and novel statistics to infer the properties of eruptions that could lead to sulfate deposition that matches that from ice‐core records. We found there are many eruption scenarios that could lead to the same polar sulfate deposition but have different resulting magnitudes of surface cooling. Consequently, there is a large uncertainty in the climatic effect of historical eruptions, which affects our understanding of past climate variability.
Key Points
We use an aerosol‐climate model and statistical emulation to find eruption source parameters from eight bipolar sulfate deposition signals
Plausible eruptions have a wide range in sulfur dioxide emissions and latitude, and consequently, a large range in radiative forcing
Resulting uncertainties in global mean surface cooling for the largest unidentified historical eruptions are on the order of 1°C
The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children ...later diagnosed with ASD or non‐typical development (Non‐TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one‐carbon metabolites, on gene pathways and neurodevelopment. Genome‐wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies‐Learning Early Signs. Sixteen different one‐carbon metabolites, including folic acid, betaine, 5′‐methyltretrahydrofolate (5‐MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non‐TD and ASD, and to one‐carbon metabolites. Using differential gene expression analysis, six transcripts (TGR‐AS1, SQSTM1, HLA‐C, and RFESD) were associated with child outcomes (ASD, Non‐TD, and TD) with genome‐wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co‐expressed gene modules significantly correlated with 5‐MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5‐MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co‐expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one‐carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes.
Lay Summary
Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non‐typical neurodevelopment and were associated with maternal nutrients.
To determine the role of rhinoscopic evaluation and repeated serologic testing in assessing the success rate of intranasally administered clotrimazole for treatment of dogs with nasal aspergillosis.
...Prospective case series.
23 dogs with nasal aspergillosis.
Dogs with nasal aspergillosis were treated with an intranasal infusion of 1% clotrimazole solution. Response to treatment was assessed with repeated rhinoscopic evaluation, with histologic examination and fungal culture when available. Results of repeated serologic testing for aspergillosis were monitored throughout the treatment course.
11 of the 23 (48%) dogs had no rhinoscopic evidence of disease after the first treatment. Three of 7 dogs were free of disease after the second treatment, and 1 of 3 dogs was free after the third treatment. Presence or absence of nasal discharge and results of repeated serologic testing were not consistent with disease status. Overall, the efficacy of intranasally administered clotrimazole for treatment of nasal aspergillosis could be confirmed in 15 of 17 dogs. Delayed recurrence or reinfection was confirmed in 3 of 15 dogs. When recurrences were taken into account, the success rate was 67% (12/15 dogs).
Clinical signs were not predictive of disease state, and follow-up rhinoscopy is recommended to assess response to treatment. The success rate of intranasally administered clotrimazole was similar to rates in previous reports; however, the number of dogs with recurrent disease was relatively high. Monitoring of the results of serologic testing is not recommended for use in determining response to treatment.
Although pediatric electronic prescribing systems are increasingly being used in pediatric care, many of these systems lack the clinical decision-support infrastructure needed to calculate a safe and ...effective rounded medication dose. This infrastructure is required to facilitate tailoring of established dosing guidance while maintaining the medication's therapeutic intent.
The goal of this project was to establish best practices for generating an appropriate medication dose and to create an interoperable rounding knowledge base combining best practices and dose-rounding information.
We interviewed 19 pediatric health care and pediatric pharmacy experts and conducted a literature review. After using these data to construct initial rounding tolerances, we used a Delphi process to achieve consensus about the rounding tolerance for each commonly prescribed medication.
Three categories for medication-rounding philosophy emerged from our literature review: (1) medications for which rounding is used judiciously to retain the intended effect; (2) medications that are rounded with attention to potential unintended effects; and (3) medications that are rarely rounded because of the potential for toxicity. We assigned a small subset of medications to a fourth category-inadequate data-for which there was insufficient information to provide rounding recommendations. For all 102 medications, we were able to arrive at a consensus recommendation for rounding a given calculated dose.
Results of this study provide the pediatric information technology community with a primary set of recommended rounding tolerances for commonly prescribed drugs. The interoperable knowledge base developed here can be integrated with existing and developing electronic prescribing systems, potentially improving prescribing safety and reducing cognitive workload.
Inherited variability in genes that influence androgen metabolism has been associated with risk of prostate cancer. The objective of this analysis was to evaluate interactions for prostate cancer ...risk by using classification and regression tree (CART) models (i.e., decision trees), and to evaluate whether these interactive effects add information about prostate cancer risk prediction beyond that of "traditional" risk factors.
We compared CART models with traditional logistic regression (LR) models for associations of factors with prostate cancer risk using 1,084 prostate cancer cases and 941 controls. All analyses were stratified by race. We used unconditional LR to complement and compare with the race-stratified CART results using the area under curve (AUC) for the receiver operating characteristic curves.
The CART modeling of prostate cancer risk showed different interaction profiles by race. For European Americans, interactions among CYP3A43 genotype, history of benign prostate hypertrophy, family history of prostate cancer, and age at consent revealed a distinct hierarchy of gene-environment and gene-gene interactions, whereas for African Americans, interactions among family history of prostate cancer, individual proportion of European ancestry, number of GGC androgen receptor repeats, and CYP3A4/CYP3A5 haplotype revealed distinct interaction effects from those found in European Americans. For European Americans, the CART model had the highest AUC whereas for African Americans, the LR model with the CART discovered factors had the largest AUC.
These results provide new insight into underlying prostate cancer biology for European Americans and African Americans.
Most forests in North America remain nitrogen limited, although recent studies have identified forested areas that exhibit symptoms of N excess, analogous to overfertilization of arable land. ...Nitrogen excess in watersheds is detrimental because of disruptions in plant/soil nutrient relations, increased soil acidification and aluminum mobility, increased emissions of nitrogenous greenhouse gases from soil, reduced methane consumption in soil, decreased water quality, toxic effects on fresh-water biota, and eutrophication of coastal marine waters. Elevated nitrate (NO-
3) loss to groundwater or surface waters is the primary symptom of N excess. Additional symptoms include increasing N concentrations and higher N:nutrient ratios in foliage (i.e., N:Mg, N:P), foliar accumulation of amino acids or NO-
3, and low soil C:N ratios. Recent nitrogen-fertilization studies in New England and Europe provide preliminary evidence that some forests receiving chronic N inputs may decline in productivity and experience greater mortality. Long-term fertilization at Mount Ascutney, Vermont, suggests that declining and slow N-cycling coniferous stands may be replaced by fast-growing and fast N-cycling deciduous forests. Symptoms of N saturation are particularly severe in high-elevation, nonaggrading spruce-fir ecosystems in the Appalachian Mountains and in eastern hardwood watersheds at the Fernow Experimental Forest near Parsons, West Virginia. In the Los Angeles Air Basin, mixed conifer forests and chaparral watersheds with high smog exposure are N saturated and exhibit the highest streamwater NO-
3concentrations for wildlands in North America. High-elevation alpine watersheds in the Colorado Front Range and a deciduous forest in Ontario, Canada, are N saturated, although N deposition is moderate (∼8 kg·ha-1·yr-1). In contrast, the Harvard Forest hardwood stand in Massachusetts has absorbed >900 kg N/ha during 8 yr of N amendment studies without significant NO-
3leaching, illustrating that ecosystems vary widely in the capacity to retain N inputs. Overly mature forests with high N deposition, high soil N stores, and low soil C:N ratios are prone to N saturation and NO-
3leaching. Additional characteristics favoring low N retention capacity include a short growing season (reduced plant N demand) and reduced contact time between drainage water and soil (i.e., porous coarse-textured soils, exposed bedrock or talus). Temporal patterns of hydrologic fluxes interact with biotic uptake and internal cycling patterns in determining ecosystem N retention. Soils are the largest storage pool for N inputs, although vegetation uptake is also important. Recent studies indicate that nitrification may be widespread in undisturbed ecosystems, and that microbial assimilation of NO-
3may be a significant N retention mechanism, contrary to previous assumptions. Further studies are needed to elucidate the sites, forms, and mechanisms of N retention and incorporation into soil organic matter, and to test potential management options for mitigating N losses from forests. Implementation of intensive management practices in N-saturated ecosystems may only be feasible in high-priority areas and on a limited scale. Reduction of N emissions would be a preferable solution, although major reductions in the near future are unlikely in many areas due to economic, energy-use, policy, and demographic considerations.
To compare the sensitivity and specificity of serologic evaluation and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs.
Prospective study.
58 dogs with nasal discharge and 26 ...healthy dogs.
Dogs with nasal discharge were anesthetized and underwent computed tomography and rhinoscopy; nasal tissues were collected for histologic examination and fungal culture. Sera were assessed for antibodies against Aspergillus spp (healthy dog sera were used as negative control specimens). Nasal aspergillosis was diagnosed in dogs that had at least 2 of the following findings: computed tomographic characteristics consistent with aspergillosis, fungal plaques detected during rhinoscopy, and histologically detectable fungal hyphae in nasal tissue. Histologic characteristics of malignancy were diagnostic for neoplasia. Without evidence of neoplasia or fungal disease, nonfungal rhinitis was diagnosed.
Among the 58 dogs, 21 had nasal aspergillosis, 25 had nonfungal rhinitis, and 12 had nasal neoplasia. Fourteen aspergillosis-affected dogs and 1 dog with nonfungal rhinitis had serum antibodies against Aspergillus spp. Fungal culture results were positive for Aspergillus spp only for 17 dogs with aspergillosis. With regard to aspergillosis diagnosis, sensitivity, specificity, and positive and negative predictive values were 67%, 98%, 93%, and 84%, respectively, for serum anti-Aspergillus antibody determination and 81%, 100%, 100%, and 90%, respectively, for fungal culture.
Results suggest that seropositivity for Aspergillus spp and identification of Aspergillus spp in cultures of nasal tissue are highly suggestive of nasal aspergillosis in dogs; however, negative test results do not rule out nasal aspergillosis.
The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a ...better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 - 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year's meeting, which will be held at the Mayo Clinic at Rochester, MN, USA.
We investigated the effects of increased nitrate (NO
3
), alone and in combination with phosphorus (P), on phytoplankton, epilithon, and epipelon in shallow lakes of the Snowy Range, Wyoming, using ...two enclosure experiments during early and late summer. Phytoplankton responded strongly to N and N + P, but not to P, with increased cell density, chlorophyll a, and photosynthesis and shifts in composition from chrysophytes to cyanophytes, chlorophytes, and diatoms. Zooplankton density and biomass were unaltered despite the additional phytoplankton stock, probably as the result of poor food quality. In the late summer, algae on tiles responded to N and N + P additions with greater chlorophyll a and increases in cyanophyte and chlorophyte density. Algae on sediment dominated whole-enclosure algal biomass but were spatially variable and responded insignificantly to nutrients. Consequently, N controlled productivity and community composition of phytoplankton and algae on hard substrates but had less impact on ecosystem algal biomass because of the large pool of nutrient-sufficient sediment algae. Phytoplankton were more photosynthetically efficient than the benthos, however, such that primary productivity did shift more toward the water column.
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