Specifying sickle cell disease interventions: A study protocol of the Sickle Cell Disease Implementation Consortium (SCDIC)

Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that results in a lifetime of anemia, severe pain, and end-organ damage that can lead to premature mortality. While the SCD field has made major medical advances, much needs to be done to improve the quality of care for people with SCD. This study capitalizes on the Sickle Cell Disease Implementation Consortium (SCDIC), a consortium of eight academic sites aiming to test implementation strategies that could lead to more accelerated application of the NHLBI guidelines for treating SCD. This report documents the process to support the consortium by specifying the interventions being developed. Methods This study consists of three steps. The Principal Investigator of each site and two site representatives who are knowledgeable of the intervention (e.g., study coordinator or the person delivering the intervention) will answer an online survey aiming to capture components of the interventions. This survey will be completed by the site representatives three times during the study: during the development of the interventions, after one year of the interventions being implemented, and at the end of this study (after 2 years). A site visit and semi-structured interview (Step 2) in the first year of the process will capture the context of the sites. Step 3 comprises of the development of a framework with the details of the multi-component SCDIC interventions at the sites. Discussion The outcome of this study, a framework of the SCDIC, will enable accurate replication and extension of published research, facilitating the translation of SCD studies to diverse populations and settings and allowing for theory testing of the effects of the intervention components across studies in different contexts and for different populations. Trial registration ClinicalTrial.Gov (#NCT03380351). Registered December 21, 2017

Spatial and Temporal Distribution of Clouds Observed by MODIS Onboard the Terra and Aqua Satellites

The Moderate Resolution Imaging Spectroradiometer (MODIS) was developed by NASA and launched aboard the Terra spacecraft on December 18, 1999 and Aqua spacecraft on May 4, 2002. A comprehensive set of remote sensing algorithms for the retrieval of cloud physical and optical properties have enabled over twelve years of continuous observations of cloud properties from Terra and over nine years from Aqua. The archived products from these algorithms include 1 km pixel-level (Level-2) and global gridded Level-3 products. In addition to an extensive cloud mask, products include cloud-top properties (temperature, pressure, effective emissivity), cloud thermodynamic phase, cloud optical and microphysical parameters (optical thickness, effective particle radius, water path), as well as derived statistics. Results include the latitudinal distribution of cloud optical and radiative properties for both liquid water and ice clouds, as well as latitudinal distributions of cloud top pressure and cloud top temperature. MODIS finds the cloud fraction, as derived by the cloud mask, is nearly identical during the day and night, with only modest diurnal variation. Globally, the cloud fraction derived by the MODIS cloud mask is approx.67%, with somewhat more clouds over land during the afternoon and less clouds over ocean in the afternoon, with very little difference in global cloud cover between Terra and Aqua. Overall, cloud fraction over land is approx.55%, with a distinctive seasonal cycle, whereas the ocean cloudiness is much higher, around 72%, with much reduced seasonal variation. Cloud top pressure and temperature have distinct spatial and temporal patterns, and clearly reflect our understanding of the global cloud distribution. High clouds are especially prevalent over the northern hemisphere continents between 30 and 50 . Aqua and Terra have comparable zonal cloud top pressures, with Aqua having somewhat higher clouds (cloud top pressures lower by 100 hPa) over land due to afternoon deep convection. The coldest cloud tops (colder than 230 K) generally occur over Antarctica and the high clouds in the tropics (ITCZ and the deep convective clouds over the western tropical Pacific and Indian sub-continent)

Boreal forest CO2 exchange and evapotranspiration predicted by nine ecosystem process models: Intermodel comparisons and relationships to field measurements

Nine ecosystem process models were used to predict CO2 and water vapor exchanges by a 150-year-old black spruce forest in central Canada during 1994–1996 to evaluate and improve the models. Three models had hourly time steps, five had daily time steps, and one had monthly time steps. Model input included site ecosystem characteristics and meteorology. Model predictions were compared to eddy covariance (EC) measurements of whole-ecosystem CO2exchange and evapotranspiration, to chamber measurements of nighttime moss-surface CO2release, and to ground-based estimates of annual gross primary production, net primary production, net ecosystem production (NEP), plant respiration, and decomposition. Model-model differences were apparent for all variables. Model-measurement agreement was good in some cases but poor in others. Modeled annual NEP ranged from −11 g C m−2 (weak CO2source) to 85 g C m−2 (moderate CO2 sink). The models generally predicted greater annual CO2sink activity than measured by EC, a discrepancy consistent with the fact that model parameterizations represented the more productive fraction of the EC tower “footprint.” At hourly to monthly timescales, predictions bracketed EC measurements so median predictions were similar to measurements, but there were quantitatively important model-measurement discrepancies found for all models at subannual timescales. For these models and input data, hourly time steps (and greater complexity) compared to daily time steps tended to improve model-measurement agreement for daily scale CO2 exchange and evapotranspiration (as judged by root-mean-squared error). Model time step and complexity played only small roles in monthly to annual predictions

Soil Microbial Networks Shift Across a High-Elevation Successional Gradient.

While it is well established that microbial composition and diversity shift along environmental gradients, how interactions among microbes change is poorly understood. Here, we tested how community structure and species interactions among diverse groups of soil microbes (bacteria, fungi, non-fungal eukaryotes) change across a fundamental ecological gradient, succession. Our study system is a high-elevation alpine ecosystem that exhibits variability in successional stage due to topography and harsh environmental conditions. We used hierarchical Bayesian joint distribution modeling to remove the influence of environmental covariates on species distributions and generated interaction networks using the residual species-to-species variance-covariance matrix. We hypothesized that as ecological succession proceeds, diversity will increase, species composition will change, and soil microbial networks will become more complex. As expected, we found that diversity of most taxonomic groups increased over succession, and species composition changed considerably. Interestingly, and contrary to our hypothesis, interaction networks became less complex over succession (fewer interactions per taxon). Interactions between photosynthetic microbes and any other organism became less frequent over the gradient, whereas interactions between plants or soil microfauna and any other organism were more abundant in late succession. Results demonstrate that patterns in diversity and composition do not necessarily relate to patterns in network complexity and suggest that network analyses provide new insight into the ecology of highly diverse, microscopic communities

Specific dose-dependent effects of ethane 1,2-dimethanesulfonate in rat and mouse Leydig cells and non-steroidogenic cells on programmed cell death

The mechanism by which ethane 1,2-dimethanesulfonate (EDS) selectively kills Leydig cells is poorly understood. To characterize further the cell-specific actions of EDS, we studied biochemical and morphological changes during apoptosis in different Leydig cell and non-steroidogenic cell models.Rat testicular and H540 tumor Leydig cells were killed by 1-2 mM EDS, whereas 20 mM EDS were required for MA-10 cells. This higher concentration of EDS was also necessary for activation of apoptosis in non-steroidogenic Chinese hamster ovary cells, whereas COS-1 monkey kidney cells were resistant. These variable effects of EDS on apoptosis were independent of new protein synthesis and, interestingly, could be delayed by co-incubation with dibutyrl cyclic AMP. Along with cell death, we also observed chromosomal fragmentation and other hallmarks indicative of apoptosis as evidenced by DNA laddering and fluorescent microscopy. Time-lapse photography with a confocal microscope showed that the time of onset, duration and even the sequence of apoptotic events between individual H540 cells was heterogeneous. When the dose of EDS was gradually increased from 2 to 10 mM, the proportion of cells showing normal apoptotic features gradually decreased. Intriguingly, treatment with 10 mM EDS did not result in death for most cells and was marked by an absence of DNA laddering and ultrastructural features of apoptosis and necrosis. However, incubation with 20 mM EDS resulted in necrosis.These results demonstrated that the effects of EDS on cell survival are not specific to Leydig cells, that different cell types have different sensitivities to EDS and that stimulation of the cAMP pathway may mitigate EDS action. The data obtained with H540 cells further revealed that EDS can induce two types of programmed cell death

A NuSTAR observation of the reflection spectrum of the low mass X-ray binary 4U 1728-34

We report on a simultaneous NuSTAR and Swift observation of the neutron star low-mass X-ray binary 4U 1728-34. We identified and removed four Type I X-ray bursts during the observation in order to study the persistent emission. The continuum spectrum is hard and well described by a black body with $kT=$ 1.5 keV and a cutoff power law with $\Gamma=$ 1.5 and a cutoff temperature of 25 keV. Residuals between 6 and 8 keV provide strong evidence of a broad Fe K$\alpha$ line. By modeling the spectrum with a relativistically blurred reflection model, we find an upper limit for the inner disk radius of $R_{\rm in}\leq2 R_{\rm ISCO}$. Consequently we find that $R_{\rm NS}\leq23$ km, assuming M=1.4{\mbox{\rm\,M_{\mathord\odot}}} and $a=0.15$. We also find an upper limit on the magnetic field of $B\leq2\times10^8$ G.Comment: 9 pages, 8 figure

To rush into the secret house of death: The fate of a Tournaisian plant

Tournaisian-age failure of marginal lacustrine sediments, and their bulk collapse into an inland rift-basin lake in the Moncton Subbasin, Canada, led to the entrainment of rare, almost complete, three-dimensionally preserved non-woody trees. Preservation of these unique fossils from the Albert Formation was a consequence of contemporaneous seismicity. Synsedimentary structures include an array of soft-sediment deformational features and a field of cross-cutting sand boils indicating multiple seismic shocks >4.6 Mw. This tectonically controlled event, entombing trees whose novel growth form is both evolutionarily and ecologically transitionary and unlike other Paleozoic plants, is a one-off in the paleobotanical record

YPFS Lessons Learned Oral History Project: An Interview with Stephen King

Suggested Citation Form: King, Stephen J. “Lessons Learned Interview. Interview by Steve Kasoff and Matthew Lieber. Yale Program on Financial Stability Lessons Learned Oral History Project. 11 February 2021. Transcript. https://ypfs.som.yale.edu/library/ypfs-lesson-learned-oral-history-project-interview-stephen-kin