Publications by authors named "W Edward Hammond"

415 Publications

Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient Derived Xenografts and Direct from Patient Screening.

Cancer Discov 2021 Jun 14. Epub 2021 Jun 14.

Surgery, Memorial Sloan Kettering Cancer Center.

To repurpose therapeutics for fibrolamellar carcinoma (FLC) we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically, and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC, and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the anti-apoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-20-0872DOI Listing
June 2021

Clinician Burnout Associated With Sex, Clinician Type, Work Culture, and Use of Electronic Health Records.

JAMA Netw Open 2021 Apr 1;4(4):e215686. Epub 2021 Apr 1.

Duke University Health System, Durham, North Carolina.

Importance: Electronic health records (EHRs) are considered a potentially significant contributor to clinician burnout.

Objective: To describe the association of EHR usage, sex, and work culture with burnout for 3 types of clinicians at an academic medical institution.

Design, Setting, And Participants: This cross-sectional study of 1310 clinicians at a large tertiary care academic medical center analyzed EHR usage metrics for the month of April 2019 with results from a well-being survey from May 2019. Participants included attending physicians, advanced practice providers (APPs), and house staff from various specialties. Data were analyzed between March 2020 and February 2021.

Exposures: Clinician demographic characteristics, EHR metadata, and an institution-wide survey.

Main Outcomes And Measures: Study metrics included clinician demographic data, burnout score, well-being measures, and EHR usage metadata.

Results: Of the 1310 clinicians analyzed, 542 (41.4%) were men (mean [SD] age, 47.3 [11.6] years; 448 [82.7%] White clinicians, 52 [9.6%] Asian clinicians, and 21 [3.9%] Black clinicians) and 768 (58.6%) were women (mean [SD] age, 42.6 [10.3] years; 573 [74.6%] White clinicians, 105 [13.7%] Asian clinicians, and 50 [6.5%] Black clinicians). Women reported more burnout (survey score ≥50: women, 423 [52.0%] vs men, 258 [47.6%]; P = .008) overall. No significant differences in EHR usage were found by sex for multiple metrics of time in the EHR, metrics of volume of clinical encounters, or differences in products of clinical care. Multivariate analysis of burnout revealed that work culture domains were significantly associated with self-reported results for commitment (odds ratio [OR], 0.542; 95% CI, 0.427-0.688; P < .001) and work-life balance (OR, 0.643; 95% CI, 0.559-0.739; P < .001). Clinician sex significantly contributed to burnout, with women having a greater likelihood of burnout compared with men (OR, 1.33; 95% CI, 1.01-1.75; P = .04). An increased number of days spent using the EHR system was associated with less likelihood of burnout (OR, 0.966; 95% CI, 0.937-0.996; P = .03). Overall, EHR metrics accounted for 1.3% of model variance (P = .001) compared with work culture accounting for 17.6% of variance (P < .001).

Conclusions And Relevance: In this cross-sectional study, sex-based differences in EHR usage and burnout were found in clinicians. These results also suggest that local work culture factors may contribute more to burnout than metrics of EHR usage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.5686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058638PMC
April 2021

A thin line between life and death: Radial sap flux failure signals trajectory to tree mortality.

Plant Cell Environ 2021 May 3;44(5):1311-1314. Epub 2021 Mar 3.

USDA Forest Service, PNW Research Station, Corvallis, Oregon, USA.

This article comments on: Seeking the "point of no return" in the sequence of events leading to mortality of mature trees.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pce.14033DOI Listing
May 2021

Picture worth a thousand words: Updating repeat photography for 21st century ecologists.

Ecol Evol 2020 Dec 9;10(24):14113-14121. Epub 2020 Nov 9.

Department of Biology University of Central Oklahoma Edmond OK 73034 USA.

Anthropogenic climate change is altering every ecosystem on Earth. Understanding these changes requires quality baseline measurements of ecosystem states. While satellite imagery provides a coarse baseline for regional-scale changes in vegetation, landscape-scale observations are lacking. Ground-based repeat photographic points (RPP) can provide this finer baseline. As precise visual records of ecosystems at a particular time, RPP provide rich data for diverse uses. Current methodology for establishing RPP, developed in the era of film cameras, requires placement of permanent markers in a landscape to provide accurate repeats over time. Another form of RPP involves relocating sites of historic photographs, to assess change between historic and present-day photographs. Through a three-year field survey, we synthesized these techniques to modernize repeat photography for the 21st century ecologist.We established 100 RPP in the Peloncillo Mountains of New Mexico, recapturing 86 RPP in the three years (2015-2017) of the study. During our study, a large (>16,000 ha) complex of wildfires burned more than half of the RPP sites we established in the prior month, providing a unique opportunity to assess method accuracy after dramatic landscape disturbance by comparing burned, unburned, pre-, and post-fire RPP image recapture precision.Our method produced 92% mean similarity for 86 RPP between original and repeated photographs, with no difference between burned and unburned sites. Interval between photographs did not cause a decline in similarity.Our updated methods can be practically applied to nearly all terrestrial study systems. Landscape changes driven by human (e.g., effects of anthropogenic climate change, land use) and natural activities (e.g., wildfires, phenology, and hydrologic events) are especially well suited to our updated methods. Modern smartphones include the technology necessary (e.g., camera, GPS, and compass) to employ our method and provide a means for low-cost deployment of the technique in diverse landscapes. We encourage broad adoption of this technique to establish baseline RPP of ecosystems across the globe, and the formation of a centralized database for repeat photography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.7001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771177PMC
December 2020

Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: a propensity-matched analysis.

Lancet Oncol 2020 12;21(12):1611-1619

Division of Surgery, Baptist MD Anderson Cancer Center, Jacksonville, FL, USA. Electronic address:

Background: There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer.

Methods: For this propensity-matched analysis, we used data from the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. We included data from women aged 70 years or older with surgically treated, American Joint Committee on Cancer (AJCC) Stage I-III invasive triple-negative breast cancer diagnosed from 2004 to 2014. Patients with T1aN0M0 disease and those with incomplete data on oestrogen receptor status, progesterone receptor status, or HER2 status were excluded. To reduce bias, patients were subdivided into three groups: those who were recommended chemotherapy but did not receive it; those who received chemotherapy; and those for whom chemotherapy was not recommended and not given. The primary outcome was overall survival. Multivariate Cox regression analysis and propensity score matching were done to minimise bias.

Findings: Between Jan 1, 2004, and Dec, 31, 2014, 16 062 women with triple-negative breast cancer in the database met the inclusion criteria for this analysis. Median follow-up was 38·3 months (IQR 20·7-46·1, range 0-138·0; 95% CI 37·8-38·7). Collectively, the 5-year overall survival estimate of the 16 062 patients in the study cohort was 62·3% (95% CI 59·7-64·4). 5-year estimated overall survival was 68·5% (95% CI 66·4-70·6) for patients receiving chemotherapy, 61·1% (59·0-63·2) for patients recommended but not given chemotherapy, and 53·7% (51·8-55·8) for patients not recommended chemotherapy and not given chemotherapy (pooled log rank p<0·0001). Multivariate Cox regression analysis of a propensity score-matched sample comparing those who received chemotherapy with those who were recommended but not given chemotherapy (n=1884 matched pairs) identified improved overall survival with chemotherapy (hazard ratio [HR] 0·69 [95% CI 0·60-0·80]; p<0·0001). After stratifying the propensity score matching sample, this benefit persisted for node-negative women (HR 0·80 [95% CI 0·66-0·97]; p=0·007), node-positive women (0·76 [0·64-0·91]; p=0·006), and those with a comorbidity score greater than 0 (HR 0·74 [95% CI 0·59-0·94]; p=0·013).

Interpretation: These data support consideration of chemotherapy in the treatment of women aged 70 years or older with triple-negative breast cancer.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30538-6DOI Listing
December 2020