We use eddy covariance measurements of net ecosystem productivity (NEP) from 21 FLUXNET sites (153 site-years of data) to investigate relationships between phenology and productivity (in terms of ...both NEP and gross ecosystem photosynthesis, GEP) in temperate and boreal forests. Results are used to evaluate the plausibility of four different conceptual models. Phenological indicators were derived from the eddy covariance time series, and from remote sensing and models. We examine spatial patterns (across sites) and temporal patterns (across years); an important conclusion is that it is likely that neither of these accurately represents how productivity will respond to future phenological shifts resulting from ongoing climate change. In spring and autumn, increased GEP resulting from an ‘extra’ day tends to be offset by concurrent, but smaller, increases in ecosystem respiration, and thus the effect on NEP is still positive. Spring productivity anomalies appear to have carry-over effects that translate to productivity anomalies in the following autumn, but it is not clear that these result directly from phenological anomalies. Finally, the productivity of evergreen needleleaf forests is less sensitive to phenology than is productivity of deciduous broadleaf forests. This has implications for how climate change may drive shifts in competition within mixed-species stands.
Background:
Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF).
Objective:
The objective of this study ...was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive.
Methods:
A retrospective cohort study of pregabalin users with HF were propensity score–matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups.
Results:
The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58).
Conclusion and Relevance:
This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.
Abstract Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver ...particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n = 60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. From the Clinical Editor In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.
Approximately 12% of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex, and only a small percentage of the infected individuals develop cancer, often many years to ...decades after the initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability, and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan and Weinberg (2000 and 2011) is used to dissect the viral, host, and environmental cofactors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), human T cell lymphotropic virus-1 (HTLV-1), and Kaposi’s sarcoma herpesvirus (KSHV).
Mesri et al. use the Hallmarks of Cancer framework established by Hanahan and Weinberg to dissect the viral, host, and environmental cofactors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses, including EBV, HPV 16/18, HBV, HCV, HTLV-1, and KSHV.
The proliferation of digital cameras co-located with eddy covariance instrumentation provides new opportunities to better understand the relationship between canopy phenology and the seasonality of ...canopy photosynthesis. In this paper we analyze the abilities and limitations of canopy color metrics measured by digital repeat photography to track seasonal canopy development and photosynthesis, determine phenological transition dates, and estimate intra-annual and interannual variability in canopy photosynthesis. We used 59 site-years of camera imagery and net ecosystem exchange measurements from 17 towers spanning three plant functional types (deciduous broadleaf forest, evergreen needleleaf forest, and grassland/crops) to derive color indices and estimate gross primary productivity (GPP). GPP was strongly correlated with greenness derived from camera imagery in all three plant functional types. Specifically, the beginning of the photosynthetic period in deciduous broadleaf forest and grassland/crops and the end of the photosynthetic period in grassland/crops were both correlated with changes in greenness; changes in redness were correlated with the end of the photosynthetic period in deciduous broadleaf forest. However, it was not possible to accurately identify the beginning or ending of the photosynthetic period using camera greenness in evergreen needleleaf forest. At deciduous broadleaf sites, anomalies in integrated greenness and total GPP were significantly correlated up to 60 days after the mean onset date for the start of spring. More generally, results from this work demonstrate that digital repeat photography can be used to quantify both the duration of the photosynthetically active period as well as total GPP in deciduous broadleaf forest and grassland/crops, but that new and different approaches are required before comparable results can be achieved in evergreen needleleaf forest.
Aboveground litter production is an important biogeochemical pathway in forests whereby carbon and nutrients enter soil detrital pools. However, patterns and controls of aboveground litter production ...are often based on an understanding of how autumnal, foliar inputs are related to aboveground tree production. Here we use three separate data sources of aboveground litter production in temperate forests to ask how aboveground woody productivity affects foliar litter production in light of other factors, such as the climate sensitivity of litter production and the seasonality of not only foliar but also fine woody debris and reproductive litter inputs. We find that foliar litter production increases with aboveground woody production, and this relationship is modified both by plant functional group and climate. Basal area also provides a crucial control on litter production. Conifer forests produce approximately half as much foliar litter as broadleaf deciduous forests. Litter production is sensitive to both among-site and among-year variation in climate, such that more litter is produced in warmer, wetter locations and years. On average 72% of aboveground litter is foliar material, with the remaining split about evenly between fine woody debris and reproductive material, and although about 88% of broadleaf litter falls during autumn, only about 61% of needles, 37% of fine woody debris and 43% of reproductive material falls during the same period. Together these results illustrate key differences in the controls of litter production in coniferous and deciduous forests, and highlight the importance of often overlooked litter fluxes, including non-autumn and non-foliar litterfall.
Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure ...(IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in
,
,
,
,
,
,
,
, and
were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (
< 10
) (PDC80). While missense mutations in
,
,
, and
were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (
< 10
) (MPR80). The same coding SNP in
which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (
5.54 × 10
) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have
associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.
...using electronic health records, we demonstrated that an increased medication risk score was associated with increased hazard ratio for death in a population of 427,103 patients followed for seven ...years 12. ...the definition of inappropriate drugs limited to Beer's list of medications is significant. ...we strongly believe that inappropriate drugs harm patients, not the contrary.
Objective. To model the relationship of common pharmacy education assessment data including student demographics, pre-pharmacy performance, core didactic performance, and external testing measures to ...identify predictors of student readiness for advanced pharmacy practice experiences (APPEs).
Methods. The associations between 23 predictive covariates from 226 graduating students from 2015-2018 (5786 observations) and APPE readiness as measured by midpoint core APPE scores were modeled. Multiple linear and Poisson regression models with backward selection were used. A selection criterion of p >.10 was used for covariate elimination from the model. Three models were evaluated: average of all midpoint core APPE rotation scores; average of midpoint acute care pharmacy practice and ambulatory care APPE rotation scores; and number of midpoint core clerkship failing scores.
Results. The average age of the population at admission was 25.4±4.5 years, 47% were female, and 75.2% had prior degrees. Across the three prediction models, knowledge-retention covariates were the strongest predictors. Total score on the Pharmacy Curriculum Outcomes Assessment was a modest yet consistent predictor across the models. All other significant predictors were unique to the various models.
Conclusion. This four-year, population-based modeling study of the relationship of common pharmacy education assessment data to APPE midpoint scores shows a modest correlation with knowledge-based measures. There is a need for greater innovation in this area of research.
Objective. To quantitatively determine scholarly activity among tenure-track faculty at US departments of pharmacy practice over a 10-year period.
Methods. A search of PubMed was performed for ...articles by department of pharmacy practice tenure track (DPP-TT) faculty from January 1, 2010, through December 31, 2019. DPP-TT faculty working in departments of pharmacy practice were identified through faculty rosters published on the American Association Colleges of Pharmacy website or college or school internet sites. Tenure-track faculty listed as working in a department of pharmacy practice, clinical pharmacy, or pharmacotherapy were included. An objective third party confirmed the data obtained. Each publication was classified by scope (eg, clinical pharmacology, health economics/outcome research, biomedical informatics, basic science, review, editorial/letter, or case report). DPP-TT faculty productivity was calculated by dataset frequency distribution. Descriptive statistics and analysis of variance were used to compare data across demographic strata.
Results. One hundred thirty-seven institutions employed 2147 pharmacy practice faculty. These faculty published 20,059 (9.3±16.3/10 years/faculty member) papers. Six institutions had no tenure-track designation. There was a 2.5-fold increase in publication rates from 2010-2019 (P <.0001). Public vs private schools’ productivity was 207.8 vs 69.0 publications per institution, respectively (P <.001). The ratio of male to female DPP-TT faculty per institution was 62% to 38%, with male faculty publishing an average of 12.1±19.1 each, and female faculty publishing an average of 7.4±13.8 each (P <.0001). Faculty ranks were 37% assistant professor; 36% associate professor; and 26% professor, with an average of 4.0±7.3, 8.6±12.4, and 17.4±24.6 publications per faculty, respectively. Regionally, US pharmacy practice faculty located in the West produced the most publications, followed by those in the Northeast, South, and Midwest (P <.0001).
Conclusions. These national DPP-TT publication data demonstrate that scholarly productivity increased from 2010 through 2019, across a wide variety of publication scopes.
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