Digital repeat photography is becoming widely used for near-surface remote sensing of vegetation. Canopy greenness, which has been used extensively for phenological applications, can be readily ...quantified from camera images. Important questions remain, however, as to whether the observed changes in canopy greenness are directly related to changes in leaf-level traits, changes in canopy structure, or some combination thereof.
We investigated relationships between canopy greenness and various metrics of canopy structure and function, using five years (2008-2012) of automated digital imagery, ground observations of phenological transitions, leaf area index (LAI) measurements, and eddy covariance estimates of gross ecosystem photosynthesis from the Harvard Forest, a temperate deciduous forest in the northeastern United States. Additionally, we sampled canopy sunlit leaves on a weekly basis throughout the growing season of 2011. We measured physiological and morphological traits including leaf size, mass (wet/dry), nitrogen content, chlorophyll fluorescence, and spectral reflectance and characterized individual leaf color with flatbed scanner imagery.
Our results show that observed spring and autumn phenological transition dates are well captured by information extracted from digital repeat photography. However, spring development of both LAI and the measured physiological and morphological traits are shown to lag behind spring increases in canopy greenness, which rises very quickly to its maximum value before leaves are even half their final size. Based on the hypothesis that changes in canopy greenness represent the aggregate effect of changes in both leaf-level properties (specifically, leaf color) and changes in canopy structure (specifically, LAI), we developed a two end-member mixing model. With just a single free parameter, the model was able to reproduce the observed seasonal trajectory of canopy greenness. This analysis shows that canopy greenness is relatively insensitive to changes in LAI at high LAI levels, which we further demonstrate by assessing the impact of an ice storm on both LAI and canopy greenness.
Our study provides new insights into the mechanisms driving seasonal changes in canopy greenness retrieved from digital camera imagery. The nonlinear relationship between canopy greenness and canopy LAI has important implications both for phenological research applications and for assessing responses of vegetation to disturbances.
We have constructed a new time-scale, TT(IPTA16), based on observations of radio pulsars presented in the first data release from the International Pulsar Timing Array (IPTA). We used two analysis ...techniques with independent estimates of the noise models for the pulsar observations and different algorithms for obtaining the pulsar time-scale. The two analyses agree within the estimated uncertainties and both agree with TT(BIPM17), a post-corrected time-scale produced by the Bureau International des Poids et Mesures (BIPM). We show that both methods could detect significant errors in TT(BIPM17) if they were present. We estimate the stability of the atomic clocks from which TT(BIPM17) is derived using observations of four rubidium fountain clocks at the US Naval Observatory. Comparing the power spectrum of TT(IPTA16) with that of these fountain clocks suggests that pulsar-based time-scales are unlikely to contribute to the stability of the best time-scales over the next decade, but they will remain a valuable independent check on atomic time-scales. We also find that the stability of the pulsar-based time-scale is likely to be limited by our knowledge of solar-system dynamics, and that errors in TT(BIPM17) will not be a limiting factor for the primary goal of the IPTA, which is to search for the signatures of nano-Hertz gravitational waves.
Summary Background Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous ...melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma. Methods In this ongoing single-centre, two-stage, phase 2, single-arm trial, patients (aged ≥16 years) with histologically confirmed metastatic ocular melanoma were enrolled. Key eligibility criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1, progressive metastatic disease, and adequate haematological, renal, and hepatic function. Metastasectomies were done to procure tumour tissue to generate autologous TIL cultures, which then underwent large scale ex-vivo expansion. Patients were treated with lymphodepleting conditioning chemotherapy (intravenous cyclophosphamide 60 mg/kg daily for 2 days followed by fludarabine 25 mg/m2 daily for 5 days, followed by a single intravenous infusion of autologous TILs and high-dose interleukin-2 720 000 IU/kg every 8 h). The primary endpoint was objective tumour response in evaluable patients per protocol using Response to Evaluation Criteria in Solid Tumors, version 1.0. An interim analysis of this trial is reported here. The trial is registered at ClinicalTrials.gov , number NCT01814046. Findings From the completed first stage and ongoing expansion stage of this trial, a total of 21 consecutive patients with metastatic uveal melanoma were enrolled between June 7, 2013, and Sept 9, 2016, and received TIL therapy. Seven (35%, 95% CI 16–59) of 20 evaluable patients had objective tumour regression. Among the responders, six patients achieved a partial response, two of which are ongoing and have not reached maximum response. One patient achieved complete response of numerous hepatic metastases, currently ongoing at 21 months post therapy. Three of the responders were refractory to previous immune checkpoint blockade. Common grade 3 or worse toxic effects were related to the lymphodepleting chemotherapy regimen and included lymphopenia, neutropenia, and thrombocytopenia (21 100% patients for each toxicity); anaemia (14 67% patients); and infection (six 29% patients). There was one treatment-related death secondary to sepsis-induced multiorgan failure. Interpretation To our knowledge, this is the first report describing adoptive transfer of autologous TILs to mediate objective tumour regression in patients with metastatic uveal melanoma. These initial results challenge the belief that metastatic uveal melanoma is immunotherapy resistant and support the further investigation of immune-based therapies for this cancer. Refinement of this T-cell therapy is crucial to improve the frequency of clinical responses and the general applicability of this treatment modality. Funding Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.
We examined racial/ethnic disparities in attention-deficit/hyperactivity disorder (ADHD) diagnosis and medication use and determined whether medication disparities were more likely due to ...underdiagnosis or undertreatment of African-American and Latino children, or overdiagnosis or overtreatment of white children.
We used a population-based, multisite sample of 4297 children and parents surveyed over 3 waves (fifth, seventh, and 10th grades). Multivariate logistic regression examined disparities in parent-reported ADHD diagnosis and medication use in the following analyses: (1) using the total sample; (2) limited to children with an ADHD diagnosis or symptoms; and (3) limited to children without a diagnosis or symptoms.
Across all waves, African-American and Latino children, compared with white children, had lower odds of having an ADHD diagnosis and of taking ADHD medication, controlling for sociodemographics, ADHD symptoms, and other potential comorbid mental health symptoms. Among children with an ADHD diagnosis or symptoms, African-American children had lower odds of medication use at fifth, seventh, and 10th grades, and Latino children had lower odds at fifth and 10th grades. Among children who had neither ADHD symptoms nor ADHD diagnosis by fifth grade (and thus would not likely meet ADHD diagnostic criteria at any age), medication use did not vary by race/ethnicity in adjusted analysis.
Racial/ethnic disparities in parent-reported medication use for ADHD are robust, persisting from fifth grade to 10th grade. These findings suggest that disparities may be more likely related to underdiagnosis and undertreatment of African-American and Latino children as opposed to overdiagnosis or overtreatment of white children.
Few studies have examined the impact of obesity on health-related quality of life (HRQOL) in non-clinical community samples of children, and methodological limitations have hindered drawing firm ...conclusions, especially whether the impact is similar across racial/ethnic groups. The present aims were to examine at what levels of non-normal weight, school-aged children experience lower HRQOL and whether this differs among racial/ethnic groups, when controlling for socioeconomic status (SES) differences.
Cross-sectional community cohort survey.
Data are from the Healthy Passages, reporting on 4824 Latino, black and white 5th graders in a population-based survey conducted in three United States metropolitan areas. Children's weight status was classified from measured weight and height into underweight (1%), normal weight (52%), overweight (19%), obese (13%) and extremely obese (14%). Children reported their own HRQOL using the Pediatric Quality of Life Inventory and additional scales addressing global self-worth, physical appearance and body satisfaction. Parents reported children's overall health status.
Each increment in higher non-healthy weight class-overweight to obese to extremely obese-was associated with significantly lower scores in more domains of psychosocial HRQOL compared with that in normal weight. However, only extremely obese children reported significantly lower physical HRQOL. Differences among weight classes remained when adjusting for SES and were independent of race/ethnicity. Underweight children generally reported HRQOL that was not significantly different from normal weight children.
Overweight, obese and extremely obese 5th graders on average experience worse HRQOL than normal weight children, especially in psychosocial domains including self-worth and peer relationships, regardless of race/ethnicity. If messages can be conveyed in a sensitive and supportive manner, the desire to improve HRQOL could provide additional motivation for children and their parents in addressing unhealthy weight.
Pulsar-timing analyses are sensitive to errors in the Solar-system ephemerides (SSEs) that timing models utilize to estimate the location of the Solar-system barycentre, the quasi-inertial reference ...frame to which all recorded pulse times-of-arrival are referred. Any error in the SSE will affect all pulsars, therefore pulsar timing arrays (PTAs) are a suitable tool to search for such errors and impose independent constraints on relevant physical parameters. We employ the first data release of the International Pulsar Timing Array to constrain the masses of the planet–moons systems and to search for possible unmodelled objects (UMOs) in the Solar system. We employ 10 SSEs from two independent research groups, derive and compare mass constraints of planetary systems, and derive the first PTA mass constraints on asteroid-belt objects. Constraints on planetary-system masses have been improved by factors of up to 20 from the previous relevant study using the same assumptions, with the mass of the Jovian system measured at 9.5479189(3) × 10^−4 M_⊙. The mass of the dwarf planet Ceres is measured at 4.7(4) × 10^−10 M_⊙. We also present the first sensitivity curves using real data that place generic limits on the masses of UMOs, which can also be used as upper limits on the mass of putative exotic objects. For example, upper limits on dark-matter clumps are comparable to published limits using independent methods. While the constraints on planetary masses derived with all employed SSEs are consistent, we note and discuss differences in the associated timing residuals and UMO sensitivity curves.
Abstract Objective The quality of primary care delivered to Medicaid-insured children with disabilities (CWD) is unknown. We used the newly validated CWD algorithm (CWDA) to examine CWD prevalence ...among Medicaid enrollees 1 to 18 years old, primary care quality for CWD, and differences in primary care quality for CWD and non-CWD. Methods Cross-sectional study using 2008 Medicaid Analytic eXtract claims data from 9 states, including children with at least 11 months of enrollment (N = 2,671,922 enrollees). We utilized CWDA to identify CWD and applied 12 validated or endorsed pediatric quality measures to assess preventive/screening, acute, and chronic disease care quality. We compared quality for CWD and non-CWD unmatched and matched on age, sex, and number of nondisabling chronic conditions and outpatient encounters. Results CWDA identified 5.3% (n = 141,384) of our study population as CWD. Care quality levels for CWD were below 50% on 8 of 12 quality measures (eg, adolescent well visits 44.9%, alcohol/drug treatment engagement 24.9%). CWD care quality was significantly better than the general population of non-CWD by +0.9% to +15.6% on 9 measures, but significantly worse for 2 measures, chlamydia screening (−3.4%) and no emergency department visits for asthma (−5.0%; all P < .01 to .001). Differences in care quality between CWD and non-CWD were generally smaller or changed direction when CWD were compared to a general population or matched group of non-CWD. Conclusions One in 20 Medicaid-insured children is CWD, and the quality of primary care delivered to CWD is suboptimal. Areas needing improvement include preventive/screening, acute care, and chronic disease management.
This trial sought to determine, for the first time, the validity in human vaccinations of using two different recombinant vaccines in diversified prime-and-boost regimens to enhance T-cell responses ...to a tumor antigen.
Eighteen patients with advanced tumors expressing carcinoembryonic antigen (CEA) were randomized to receive either recombinant vaccinia (rV)-CEA followed by three avipox-CEA vaccinations, or avipox-CEA (three times) followed by one rV-CEA vaccination. Subsequent vaccinations in both cohorts were with avipox-CEA. Immunologic monitoring was performed using a CEA peptide and the enzyme-linked immunospot assay for interferon gamma production.
rV-CEA followed by avipox-CEA was superior to the reverse order in the generation of CEA-specific T-cell responses. Further increases in CEA-specific T-cell precursors were seen when local granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin (IL)-2 were given with subsequent vaccinations. The treatment was extremely well tolerated. Limited clinical activity was seen using vaccines alone in this patient population. Antibody production against CEA was also observed in some of the treated patients.
rV-CEA was more effective in its role as a primer of the immune system; avipox-CEA could be given up to eight times with continued increases in CEA T-cell precursors. Future trials should use rV-CEA first followed by avipox-CEA. Vaccines specific to CEA are able to generate CEA-specific T-cell responses in patients without significant toxicity. T-cell responses using vaccines alone may be inadequate to generate significant anticancer objective responses in patients with advanced disease. Cytokines such as GM-CSF and IL-2 may play a key role in generating such responses.
Abstract The Pediatric Quality Measures Program is developing readmission measures for pediatric use. We sought to describe the importance of readmissions in children and the challenges of developing ...readmission quality measures. We consider findings and perspectives from research studies and commentaries in the pediatric and adult literature, characterizing arguments for and against using readmission rates as measures of pediatric quality and discussing available evidence and current knowledge gaps. The major topic of debate regarding readmission rates as pediatric quality measures is the relative influence of hospital quality versus other factors within and outside of health systems on readmission risk. The complex causation of readmissions leads to disagreement, particularly when rates are publicly reported or tied to payment, about whether readmissions can be prevented and how to achieve fair comparisons of readmission performance. Despite these controversies, the policy focus on readmissions has motivated widespread efforts by hospitals and outpatient providers to evaluate and reengineer care processes. Many adult studies demonstrate a link between successful initiatives to improve quality and reductions in readmissions. More research is needed on methods to enhance adjustment of readmission rates and on how to prevent pediatric readmissions.
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