A field-validated ensemble species distribution model of Eriogonum pelinophilum, an endangered subshrub in Colorado, USA.

Understanding the suitable habitat of endangered species is crucial for agencies such as the Bureau of Land Management to plan management and conservation. However, few species distribution models are directly validated, potentially limiting their application in management. In preparation for a Species Status Assessment of clay-loving wild buckwheat (Eriogonum pelinophilum), an endangered subshrub found in southwest Colorado, we ran a series of species distribution models to estimate the species' potential occupied habitat and validated these models in the field. A 1-meter resolution digital elevation model derived from LiDAR and a high-resolution geology mapping helped identify biologically relevant characteristics of the species' habitat. We employed a weighted ensemble model based on two Random Forest and one Boosted Regression Tree model, and discrimination performance of the ensemble model was high (AUC-PR = 0.793). We then conducted a systematic field survey of model habitat suitability predictions, during which we discovered 55 new subpopulations of the species and demonstrated that new species observations were strongly associated with model predictions (p < .0001, Cliff's delta = 0.575). We further refined our original models by incorporating the additional species occurrences collected in the field survey, a new explanatory variable, and a more diverse set of models. These iterative changes marginally improved performance of the ensemble model (AUC-PR = 0.825). Direct validation of species distribution models is extremely rare, and our field survey provides strong validation of our model results. This helps increase confidence to utilize predictions in planning. The final model predictions greatly improve the Bureau of Land Management's understanding of the species' habitat and increase our ability to consider potential habitat in planning land use activities such as road development and travel management.

Costs of Care and Location of Death in Community-Based Pediatric Palliative Care.

Background: Children with complex chronic conditions (CCCs) are dying at home with increased frequency, yet the number of studies on the financial feasibility of community-based pediatric palliative care is limited. Objective: The objectives of this study were to (1) describe characteristics of patients who died in a community-based palliative care program and (2) evaluate cost differences associated with participant characteristics and location of death. Design: A retrospective cohort analysis of administrative and electronic medical record data was employed. Setting/Subjects: Children enrolled in the community-based pediatric palliative care program, CompassionNet, who died between 2008 and 2015 were included (N = 224). Measurements: Demographic data, program expense, and paid claims were extracted from an insurance provider database and clinical data from the electronic medical record. Results: Sixty-six (29%) of the children were <1 year old at death; 80 (36%) were 1-9 years old, and 78 (35%) were 10-22 years old. Malignancy was the most common primary CCC diagnosis for the 158 children/adolescents (n = 89, 56%), whereas neuromuscular conditions (n = 20, 30%) were most frequent for infants. Death at home occurred 21% of the time for infants, 48% for children of ages 1-9 years, and 46% for children of ages 10-22 years. The mean total cost in the final year of life for pediatric patients was significantly related to location of death, a malignancy diagnosis, and participation in Medicaid. The largest estimated difference was between costs of care associated with death at home ($121,111) versus death in the hospital ($200,050). Conclusions: Multidisciplinary community-based pediatric palliative care teams provide the opportunity for a home death to be realized as desired. Significant cost differences associated with location of death may support program replication and sustainability.

Endocrine treatment of high grade serous ovarian carcinoma; quantification of efficacy and identification of response predictors.

OBJECTIVES: The role of endocrine therapy (ET) in high grade serous ovarian carcinoma (HGSOC) is poorly defined due to the lack of phase III data and significant heterogeneity of clinical trials performed. In this study, we sought to identify predictive factors of endocrine sensitivity in HGSOC. METHODS: HGSOC patients who received at least four weeks of ET for relapsed disease following one line of chemotherapy at the Edinburgh Cancer Centre were identified. Exclusion criteria were use of endocrine therapy as maintenance therapy or of unknown duration. Duration of therapy and best CA125 response as per modified GCIG criteria were recorded. Oestrogen receptor (ER) histoscore, treatment free interval, prior lines of chemotherapy, and type of ET were evaluated as predictive factors. RESULTS: Of 431 patients identified, 269 were eligible (77.0% letrozole, 18.6% tamoxifen, 2.2% megesterol acetate, 2.2% other). The median duration of therapy was 126 days (range 28-1427 days). 32.7% remained on ET for ≥180 days and 14.1% for ≥365 days. The CA125 response and clinical benefit rates (response or stable disease) were 8.1% and 40.1% respectively. ER histoscore >200 (P = 0.0016) and a treatment free interval of ≥180 days (P < 0.0001) were independent predictive factors upon multivariable analysis. CONCLUSIONS: ET should be considered as a viable strategy to defer subsequent chemotherapy for relapsed HGSOC. Patients with an ER histoscore >200 and a treatment free interval of ≥180 days are most likely to derive benefit.

Quantitation of oligonucleotides by phosphodiesterase digestion followed by isotope dilution mass spectrometry: proof of concept.

The importance of DNA as a regulatory analyte is well-known. Recent years have seen an increased interest in the quantitation of this analyte. Accurate quantitative measurements have been hampered by the lack of well-characterized standards and pure materials for this large-molecular-weight analyte. Outlined here is an approach for the accurate and reproducible quantitation of an oligonucleotide that is solely reliant on the availability of pure, well-characterized deoxynucleotides and not a sequence-specific pure DNA standard. The proposed procedure is intended to provide an accurate and definitive method for the quantitation of DNA for reference measurements as an improved alternative to the more conventional UV absorbance-based methods. For proof of concept, a gravimetrically prepared oligonucleotide solution was enzymatically digested to its constituent monomer-deoxynucleotide monophosphates (dNMPs), of which there are four different types. Qualitative mass spectrometry was used to confirm the 100% successful completion of the enzymatic digestion step. The dNMPs were then separated by liquid chromatography (LC) before being detected by electrospray ionization (ESI) mass spectrometry (MS). The method of quantitation was based on isotope dilution mass spectrometry (IDMS) analysis of the four different monomer units. The concentrations of the four dNMP residues were then summed to obtain the original concentration of the oligonucleotide. The concentrations determined by liquid chromatography/mass spectrometry (LC/MS) and also by liquid chromatography-tandem mass spectrometry (LC/MS/MS) differed by <2.5 and 1%, respectively, from the gravimetrically assigned value. These differences were well within the uncertainty of the gravimetrically assigned value. This highly accurate method, suitable for the definitive quantitation of oligonucleotides, should be ideal for characterizing primary calibration standards and certified reference materials that can then be used to underpin the more conventional quantitative techniques of UV and fluorescence spectroscopy.