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"Reynolds, Mark"
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Calcium phosphate cements for bone engineering and their biological properties
Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.
Journal Article
The Safety of Inpatient Health Care
Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted.
We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events.
In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%).
Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).
Journal Article
Flows of X-ray gas reveal the disruption of a star by a massive black hole
High-resolution X-ray spectra reveal highly ionized X-ray gas flows in a nearby tidal disruption event, ASASSN-14li, near to the black hole of the galaxy PGC 043234.
A star at the event horizon
ASASSN-14li is a tidal disruption event close to the black hole of the nearby galaxy PGC 043234, first discovered in images obtained on 22 November 2014 by the All-Sky Automated Survey for Supernovae. Such events occur when a star gets too near to a massive black hole and is torn apart by extreme tidal forces. Jon Miller
et al
. report high-resolution X-ray spectra of ASASSN-14li that indicate flows of highly ionized X-ray gas consistent with a rotating wind from the inner, super-Eddington-flow region of a nascent accretion disk, or with a filament of disrupted stellar gas near to the apocentre of an elliptical orbit. These findings are consistent with both fundamental and very recent theoretical predictions for the structure and evolution of tidal disruption events.
Tidal forces close to massive black holes can violently disrupt stars that make a close approach. These extreme events are discovered via bright X-ray
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flares in galactic centres. Prior studies based on modelling decaying flux trends have been able to estimate broad properties, such as the mass accretion rate
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. Here we report the detection of flows of hot, ionized gas in high-resolution X-ray spectra of a nearby tidal disruption event, ASASSN-14li in the galaxy PGC 043234. Variability within the absorption-dominated spectra indicates that the gas is relatively close to the black hole. Narrow linewidths indicate that the gas does not stretch over a large range of radii, giving a low volume filling factor. Modest outflow speeds of a few hundred kilometres per second are observed; these are below the escape speed from the radius set by variability. The gas flow is consistent with a rotating wind from the inner, super-Eddington region of a nascent accretion disk, or with a filament of disrupted stellar gas near to the apocentre of an elliptical orbit. Flows of this sort are predicted by fundamental analytical theory
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Journal Article
Using ricelands to provide temporary shorebird habitat during migration
To help mitigate large wetland losses in California, The Nature Conservancy launched a dynamic conservation incentive program to create temporary wetland habitats in harvested and fallow rice fields for shorebirds migrating along the Pacific Flyway. Farmers were invited to participate in a reverse auction bidding process and winning bids were selected based on their cost and potential to provide high quality shorebird habitat. This was done in 2014 and 2015, for separate enrollment periods that overlapped with spring and fall migration, both before and after the traditional post-harvest flooding period. To assess the success of the program, we monitored shorebird use of fields that were enrolled (treatments), and others that were subject to typical rice farm management (controls). To put these observations in context, we used satellites to simultaneously monitor the extent of shallow-water habitat across the ~215,000 ha of ricelands in the area. Results showed that providing habitat during migration, when it is typically unavailable in rice fields, yielded the largest average shorebird densities ever reported for agriculture in the region. Treatment fields had significantly greater shorebird density, richness and diversity than control fields in both spring and fall (especially September–early October, and late March–early April), but in fall the difference was greater. Shorebird responses to habitat provisioning, and regional habitat conditions, were variable from year to year, and highly dynamic within a given season. Overall, shorebirds densities were found to be negatively related to the total amount of flooded habitat in the rice landscape. Factors that affected habitat availability included allocation schedules of water deliveries from reservoirs, and rainfall patterns, both of which were influenced by drought. Collectively, these results suggest that appropriately managed agricultural lands have great potential to provide high value habitat for shorebirds during times of habitat deficit, including migration, and that fall may be a particularly impactful time to create additional habitat. Migratory species face great challenges due to the climate change, conversion of historical stopover sites, and other factors, but dynamic conservation programs offer promise that, at least in certain instances, their needs can still be met.
Journal Article
Integrating citizen science data with expert surveys increases accuracy and spatial extent of species distribution models
Aim Information on species’ habitat associations and distributions, across a wide range of spatial and temporal scales, is a fundamental source of ecological knowledge. However, collecting information at relevant scales is often cost prohibitive, although it is essential for framing the broader context of more focused research and conservation efforts. Citizen science has been signalled as an increasingly important source to fill in data gaps where information is needed to make comprehensive and robust inferences on species distributions. However, there are perceived trade‐offs of combining highly structured, scientific survey data with largely un‐structured, citizen science data. Methods We explore these trade‐offs by applying a simplified approach of filtering citizen science data to resemble structured survey data and analyse both sources of data under a common framework. To accomplish this, we integrated high‐resolution survey data on shorebirds in the northern Central Valley of California with observations in eBird for the entire region that were filtered to improve their quality. Results The integration of survey data with the filtered citizen science data resulted in improved inference and increased the extent and accuracy of distribution models on shorebirds for the Central Valley. The structured surveys improved the overall accuracy of ecological inference over models using citizen science data only by increasing the representation of data collected from high‐quality habitats for shorebirds. Main conclusions The practical approach we have shown for data integration can also be used to improve the efficiency of designing biological surveys in the context of larger, citizen science monitoring efforts, ultimately reducing the financial and time expenditures typically required of monitoring programs and focused research. The simple method we present can be used to integrate other types of data with more localized efforts, ultimately improving our ecological knowledge on the distribution and habitat associations of species of conservation concern worldwide.
Journal Article
Advanced smart biomaterials and constructs for hard tissue engineering and regeneration
Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.
Journal Article
Abundance models improve spatial and temporal prioritization of conservation resources
Conservation prioritization requires knowledge about organism distribution and density. This information is often inferred from models that estimate the probability of species occurrence rather than from models that estimate species abundance, because abundance data are harder to obtain and model. However, occurrence and abundance may not display similar patterns and therefore development of robust, scalable, abundance models is critical to ensuring that scarce conservation resources are applied where they can have the greatest benefits. Motivated by a dynamic land conservation program, we develop and assess a general method for modeling relative abundance using citizen science monitoring data. Weekly estimates of relative abundance and occurrence were compared for prioritizing times and locations of conservation actions for migratory waterbird species in California, USA. We found that abundance estimates consistently provided better rankings of observed counts than occurrence estimates. Additionally, the relationship between abundance and occurrence was nonlinear and varied by species and season. Across species, locations prioritized by occurrence models had only 10–58% overlap with locations prioritized by abundance models, highlighting that occurrence models will not typically identify the locations of highest abundance that are vital for conservation of populations.
Journal Article
Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma
Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG). TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we report the first case of a TRK fusion-driven HGG treated with larotrectinib—the first selective pan-TRK inhibitor in clinical development. This 3-year-old girl had failed multiple therapies including chemotherapy and radiotherapy. Tumour profiling confirmed an ETV6–NTRK3 fusion. Treatment with larotrectinib led to rapid clinical improvement with near total resolution of primary and metastatic lesions on MRI imaging. This is the first report of a TRK fusion glioma successfully treated with a TRK inhibitor.
Journal Article