Publications by authors named "Daniel Reed"

98 Publications

Variation in disturbance to a foundation species structures the dynamics of a benthic reef community.

Ecology 2021 Feb 10:e03304. Epub 2021 Feb 10.

Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA, USA, 93106.

Disturbance and foundation species can both have strong impacts on ecosystem structure and function, but studies of their interacting effects are hindered by the long lifespans and slow growth of most foundation species. Here, we investigated the extent to which foundation species may mediate the impacts of disturbance on ecological communities, using the kelp forest ecosystem as a study system. Giant kelp (Macrocystis pyrifera) grows rapidly and experiences wave disturbance from winter storms. We developed and analyzed a model of the effects of variable storm regimes on giant kelp population dynamics and of the cascading effects on kelp-mediated competition between benthic community members in kelp forests. Simulations of severe storm regimes resulted in a greater abundance of understory macroalgae and a lower abundance of sessile invertebrates than did milder regimes. Both the cascading effects of periodic loss of giant kelp as well as the degree to which storms directly impacted the benthos (in the form of scouring) influenced the outcome of competition between benthic community members. The model's qualitative predictions were consistent with empirical data from a 20-year time series of community dynamics, suggesting that interannual variability in disturbance that affects giant kelp abundance can have strong consequences for benthic community structure. Our findings point to the value of long-term studies in elucidating the interacting effects of disturbance and foundation species.
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http://dx.doi.org/10.1002/ecy.3304DOI Listing
February 2021

Evidence that spillover from Marine Protected Areas benefits the spiny lobster (Panulirus interruptus) fishery in southern California.

Sci Rep 2021 Jan 29;11(1):2663. Epub 2021 Jan 29.

Marine Science Institute, University of California Santa Barbara, Santa Barbara, CA, 93116, USA.

Marine Protected Areas (MPAs) are designed to enhance biodiversity and ecosystem services. Some MPAs are also established to benefit fisheries through increased egg and larval production, or the spillover of mobile juveniles and adults. Whether spillover influences fishery landings depend on the population status and movement patterns of target species both inside and outside of MPAs, as well as the status of the fishery and behavior of the fleet. We tested whether an increase in the lobster population inside two newly established MPAs influenced local catch, fishing effort, and catch-per-unit-effort (CPUE) within the sustainable California spiny lobster fishery. We found greater build-up of lobsters within MPAs relative to unprotected areas, and greater increases in fishing effort and total lobster catch, but not CPUE, in fishing zones containing MPAs vs. those without MPAs. Our results show that a 35% reduction in fishing area resulting from MPA designation was compensated for by a 225% increase in total catch after 6-years, thus indicating at a local scale that the trade-off of fishing ground for no-fishing zones benefitted the fishery.
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http://dx.doi.org/10.1038/s41598-021-82371-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846765PMC
January 2021

Adapting isotonic dose-finding to a dynamic set of drug combinations with application to a phase I leukemia trial.

Clin Trials 2021 Jan 10:1740774520983484. Epub 2021 Jan 10.

Department of Public Health Sciences, Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, VA, USA.

Background/aims: This article describes the proposed design of a phase I study evaluating the safety of ceramide nanoliposome and vinblastine among an initial set of 19 possible dose combinations in patients with relapsed/refractory acute myeloid leukemia and patients with untreated acute myeloid leukemia who are not candidates for intensive induction chemotherapy.

Methods: Extensive collaboration between statisticians and clinical investigators revealed the need to incorporate several adaptive features into the design, including the flexibility of adding or eliminating certain dose combinations based on safety criteria applied to multiple dose pairs. During the design stage, additional dose levels of vinblastine were added, increasing the dimension of the drug combination space and thus the complexity of the problem. Increased complexity made application of existing drug combination dose-finding methods unsuitable in their current form.

Results: Our solution to these challenges was to adapt a method based on isotonic regression to meet the research objectives of the study. Application of this adapted method is described herein, and a simulation study of the design's operating characteristics is conducted.

Conclusion: The aim of this article is to bring to light examples of novel design applications as a means of augmenting the implementation of innovative designs in the future and to demonstrate the flexibility of adaptive designs in satisfying changing design conditions.
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http://dx.doi.org/10.1177/1740774520983484DOI Listing
January 2021

A narrative-informed evaluation of tree of life for parents of children with physical health conditions.

Clin Child Psychol Psychiatry 2021 Jan 24;26(1):51-63. Epub 2020 Nov 24.

Royal Manchester Children's Hospital, Manchester, UK.

Background: Parents of children with chronic health conditions can face many challenges. The Tree of Life narrative therapy group intervention aims to connect parents with their skills and resources before collectively exploring the 'storms' (challenges) they face. A narrative-informed evaluation aimed to story the parents' experiences of attending the group.

Methods: Seven parents attended a Tree of Life group intervention and then participated in a narrative-informed group interview to generate stories regarding their experience of the group. The interview was recorded with consent and later transcribed.

Results: A thematic analysis was undertaken and highlighted that the group offered parents a 'safe place to stand' to talk about difficulties; a different perspective on their situation; connection with the skills of other parents; new ideas to introduce more independence to their child; and togetherness within the 'storms' (challenges).

Conclusions: The narrative-informed evaluation offered opportunities to further thicken parents' preferred identity stories whilst also contributing to the evidence base of narrative-informed group interventions for parents.
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http://dx.doi.org/10.1177/1359104520972457DOI Listing
January 2021

3D ultrasound to quantify lateral hip displacement in children with cerebral palsy: a validation study.

Dev Med Child Neurol 2020 12 18;62(12):1389-1395. Epub 2020 Aug 18.

Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Aim: To assess the validity of a new index, lateral head coverage (LHC), for describing hip dysplasia in a population of children with cerebral palsy (CP).

Method: LHC is derived from 3D ultrasound assessment. Twenty-two children (15 males, seven females; age 4-15y) with CP undergoing routine hip surveillance were recruited prospectively for the study. Each participant had both a planar radiograph acquired as part of their routine care and a 3D ultrasound assessment within 2 months. Reimer's migration percentage (RMP) and LHC were measured by the same assessor, and the correlation between them calculated using Pearson's correlation coefficient. The repeatability of LHC was investigated with three assessors, analysing each of 10 images three times. Inter- and intra-assessor variation was quantified using intraclass correlation coefficients.

Results: LHC was strongly correlated with RMP (Spearman's rank correlation coefficient=-0.86, p<0.001). LHC had similar inter-assessor reliability to that reported for RMP (intraclass correlation coefficient=0.97 and intra-assessor intraclass correlation coefficient=0.98).

Interpretation: This is an initial validation of the use of 3D ultrasound in monitoring hip development in children with CP. LHC is comparable with RMP in estimating hip dysplasia with similar levels of reliability that are reported for RMP.
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http://dx.doi.org/10.1111/dmcn.14647DOI Listing
December 2020

Gilteritinib: An FMS-like tyrosine kinase 3/AXL tyrosine kinase inhibitor for the treatment of relapsed or refractory acute myeloid leukemia patients.

J Oncol Pharm Pract 2020 Jul 26;26(5):1200-1212. Epub 2020 Apr 26.

Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, USA.

Acute myeloid leukemia has recently undergone a significant transition into identifying and successfully inhibiting driver mutations leading to disease. One of the most common mutations in acute myeloid leukemia involves the protein FMS-like tyrosine kinase 3 (FLT3), which leads to ligand-independent activation of intracellular signaling cascades leading to the survival and proliferation of the acute leukemia blast cell. Preclinical studies have demonstrated the presence of two dominant types of mutations of this protein: internal tandem duplication and tyrosine kinase domain mutations. Successful inhibition of this protein has proven to be challenging. While FLT3 has been shown to be successfully inhibited and shown to improve overall survival in the frontline therapy of acute myeloid leukemia in combination with cytarabine and anthracycline, relapsed and refractory (R/R) patients have not been shown to be a successful population until recently. A phase III trial (ADMIRAL trial) demonstrated significant overall survival benefit in patients receiving gilteritinib compared to patients receiving salvage chemotherapy. This review will provide an overview of the preclinical, clinical, and practical use of gilteritinib in the treatment of patients with relapsed and refractory acute myeloid leukemia with mutation.
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http://dx.doi.org/10.1177/1078155220918006DOI Listing
July 2020

Dental management of scleroderma patients using pentoxifylline plus vitamin E with and without TheraBite to reduce trismus: Two case reports and brief review of literature.

Clin Case Rep 2020 Feb 17;8(2):247-253. Epub 2020 Jan 17.

GPR Ohio State University College of Dentistry Columbus OH USA.

To provide evidence supporting the off label use of pentoxifylline and vitamin E especially by dentists with TheraByte to reduce trismus in scleroderma patients.
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http://dx.doi.org/10.1002/ccr3.2572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044382PMC
February 2020

Prospective Initiative to Reduce Mucosal Barrier Injuries and Bloodstream Infections in Patients With Hematologic Malignancy Receiving Inpatient Chemotherapy.

JCO Oncol Pract 2020 03 8;16(3):e306-e312. Epub 2020 Jan 8.

University of Virginia Health System, Charlottesville, VA.

Purpose: Mucosal barrier injury (MBI) occurs during periods of prolonged neutropenia in patients receiving cytotoxic chemotherapy for hematologic malignancies. This can lead to laboratory-confirmed bloodstream infections (LCBIs) and subsequent complications, including sepsis, organ failure, and possible death. There are no published prevention strategies for MBI. The purpose of our proposal was to decrease our MBI-LCBI events per month by 25%.

Methods: A multidisciplinary team was assembled to achieve this proposal. Cause-and-effect diagrams in addition to Pareto charts were used to investigate potential interventions. Using Plan-Do-Study-Act (PDSA) cycles, multiple tests of change were designed over the course of 3 years.

Results: The number of baseline events per month for MBI-LCBIs was 1.1. With the completion of the first PDSA cycle, the MBI-LCBI events dropped to 1.0 event per month. A second PDSA cycle involving implementation of an oral care kit improved to 0.35 events per month. This unfortunately was not sustained, and a root cause analysis demonstrated that physician noncompliance with ordering the oral kit was the main reason. After the change of a physician-driven protocol to a nurse-driven protocol, the third PDSA cycle resulted in a decrease in MBI-LCBI events to 0.89 events per month.

Conclusion: To our knowledge, this is the first published report of an intervention to prevent MBI-LCBI events. Through a multidisciplinary approach and with quality improvement tools, we were able to demonstrate a significant reduction in MBI-LCBI events.
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http://dx.doi.org/10.1200/JOP.19.00344DOI Listing
March 2020

Foundation species promote community stability by increasing diversity in a giant kelp forest.

Ecology 2020 05 19;101(5):e02987. Epub 2020 Feb 19.

Marine Science Institute, University of California, Santa Barbara, California, 93106, USA.

Foundation species structure communities, promote biodiversity, and stabilize ecosystem processes by creating locally stable environmental conditions. Despite their critical importance, the role of foundation species in stabilizing natural communities has seldom been quantified. In theory, the stability of a foundation species should promote community stability by enhancing species richness, altering the population fluctuations of individual species, or both. Here we tested the hypothesis that the stability of a marine foundation species, the giant kelp Macrocystis pyrifera, increased the stability of the aggregate biomass of a phylogenetically diverse assemblage of understory algae and sessile invertebrates that compete for space beneath the giant kelp canopy. To achieve this goal, we analyzed an 18-yr time series of the biomass of giant kelp and its associated benthic community collected from 32 plots distributed among nine shallow reefs in the Santa Barbara Channel, USA. We showed that the stability of understory algae and sessile invertebrates was positively and indirectly related to the stability of giant kelp, which primarily resulted from giant kelp's direct positive association with species richness. The stability of all community types was positively related to species richness via increased species stability and species asynchrony. The stabilizing effects of richness were three to four times stronger when algae and invertebrates were considered separately rather than in combination. Our finding that diversity-stability relationships were stronger in communities consisting of species with similar resource requirements suggests that competition for shared resources rather than differential responses to environmental conditions played a more important role in stabilizing the community. Increasing threats to structure-forming foundation species worldwide necessitates a detailed understanding of how they influence their associated community. This study is among the first to show that dampened temporal fluctuations in the biomass of a foundation species is an important determinant of the stability of the complex communities it supports.
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http://dx.doi.org/10.1002/ecy.2987DOI Listing
May 2020

A bioassay system of autologous human endothelial, smooth muscle cells, and leukocytes for use in drug discovery, phenotyping, and tissue engineering.

FASEB J 2020 01 5;34(1):1745-1754. Epub 2019 Dec 5.

Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK.

Blood vessels are comprised of endothelial and smooth muscle cells. Obtaining both types of cells from vessels of living donors is not possible without invasive surgery. To address this, we have devised a strategy whereby human endothelial and smooth muscle cells derived from blood progenitors from the same donor could be cultured with autologous leukocytes to generate a same donor "vessel in a dish" bioassay. Autologous sets of blood outgrowth endothelial cells (BOECs), smooth muscle cells (BO-SMCs), and leukocytes were obtained from four donors. Cells were treated in monoculture and cumulative coculture conditions. The endothelial specific mediator endothelin-1 along with interleukin (IL)-6, IL-8, tumor necrosis factor α, and interferon gamma-induced protein 10 were measured under control culture conditions and after stimulation with cytokines. Cocultures remained viable throughout. The profile of individual mediators released from cells was consistent with what we know of endothelial and smooth muscle cells cultured from blood vessels. For the first time, we report a proof of concept study where autologous blood outgrowth "vascular" cells and leukocytes were studied alone and in coculture. This novel bioassay has usefulness in vascular biology research, patient phenotyping, drug testing, and tissue engineering.
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http://dx.doi.org/10.1096/fj.201901379RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972557PMC
January 2020

Enasidenib in acute myeloid leukemia: clinical development and perspectives on treatment.

Cancer Manag Res 2019 30;11:8073-8080. Epub 2019 Aug 30.

Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.

Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.
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http://dx.doi.org/10.2147/CMAR.S162784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724422PMC
August 2019

Seascape genetics of the stalked kelp Pterygophora californica and comparative population genetics in the Santa Barbara Channel.

J Phycol 2020 02 6;56(1):110-120. Epub 2019 Nov 6.

Department of Biological Sciences, University of Wisconsin - Milwaukee, Milwaukee, Wisconsin, 53201, USA.

We conducted a population genetic analysis of the stalked kelp, Pterygophora californica, in the Santa Barbara Channel, California, USA. The results were compared with previous work on the genetic differentiation of giant kelp, Macrocystis pyrifera, in the same region. These two sympatric kelps not only share many life history and dispersal characteristics but also differ in that dislodged P. californica does not produce floating rafts with buoyant fertile sporophytes, commonly observed for M. pyrifera. We used a comparative population genetic approach with these two species to test the hypothesis that the ability to produce floating rafts increases the genetic connectivity among kelp patches in the Santa Barbara Channel. We quantified the association of habitat continuity and oceanographic distance with the genetic differentiation observed in stalked kelp, like previously conducted for giant kelp. We compared both overall (across all patches) and pairwise (between patches) genetic differentiation. We found that oceanographic transit time, habitat continuity, and geographic distance were all associated with genetic connectivity in P. californica, supporting similar previous findings for M. pyrifera. Controlling for differences in heterozygosity between kelp species using Jost's D , we showed that global differentiation and pairwise differentiation were similar among patches between the two kelp species, indicating that they have similar dispersal capabilities despite their differences in rafting ability. These results suggest that rafting sporophytes do not play a significant role in effective dispersal of M. pyrifera at ecologically relevant spatial and temporal scales.
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http://dx.doi.org/10.1111/jpy.12918DOI Listing
February 2020

A prospective study on urine alkalization with an oral regimen consisting of sodium bicarbonate and acetazolamide in patients receiving high-dose methotrexate.

Cancer Manag Res 2019 30;11:8065-8072. Epub 2019 Aug 30.

Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.

Purpose: Intravenous (IV) sodium bicarbonate is typically used in alkalization regimens for the safe use of the chemotherapeutic agent high-dose methotrexate (HDMTX). Urine parameters including urine output and pH are important in order to minimize the risk of kidney injury, which increases adverse effects and hospital length of stay following HDMTX. IV sodium bicarbonate has been on shortage, and there are limited literature describing the safety of alternative regimens.

Patients And Methods: A single institution, prospective analysis of non-Hodgkin's lymphoma and acute lymphoblastic leukemia patients receiving HDMTX for central nervous system (CNS) prophylaxis or disease. Patients received an oral (PO) regimen of sodium bicarbonate and acetazolamide to achieve a urine pH >7. This cohort was compared to a subsequent IV sodium bicarbonate control cohort. Multiple co-primary safety outcomes assessed the incidences of acute kidney injury and delayed methotrexate clearance as well as change in liver function tests. Secondary outcomes included time to urine pH, time to urine output, and length of stay.

Results: A total of 126 encounters were studied for the primary safety outcome. There was no difference between AKI incidence in patients receiving the PO alkalization regimen compared to patients receiving IV sodium bicarbonate (14.5% vs 9.3%, respectively, =0.41). There was no difference in methotrexate clearance between the PO and IV groups (26.5% vs 37.2%, respectively, =0.21). The use of PO alkalization regimen is estimated to have saved 2002 vials of IV sodium bicarbonate and was approximately US$226 less expensive per encounter.

Conclusion: This analysis supports the use of PO regimens to achieve urine alkalization necessary for safe administration of HDMTX during periods of IV sodium bicarbonate shortage. Further studies may determine optimal dosing strategies that decrease length of stay and ensure noninferiority of efficacy outcomes with PO regimens for urine alkalization with HDMTX.
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http://dx.doi.org/10.2147/CMAR.S190084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720153PMC
August 2019

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan.

Nat Commun 2019 08 12;10(1):3637. Epub 2019 Aug 12.

The Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia.

Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer.
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http://dx.doi.org/10.1038/s41467-019-10968-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691013PMC
August 2019

Diversity loss is predicted to increase extinction risk of specialist animals by constraining their ability to expand niche.

J Theor Biol 2019 09 24;476:44-50. Epub 2019 May 24.

School of Biology, Newcastle University, Ridley Building 2, Newcastle upon Tyne NE1 7RU, UK.

Specialist animals are at a greater risk of extinction in the face of environmental change than generalist ones. The inability of some specialist taxa to expand host range through evolution may exacerbate or cause their high extinction risk. Here we use connectionism (a framework for modelling animal behaviour) to predict the environmental and physiological factors that predispose some specialist taxa to an 'evolutionary dead-end'. Neural networks are evolved to become resource-specialised in a resource-abundant and resource-diverse 'historical' environment while losing 'genes' that should restrict their ability to expand their host range. Networks are subsequently challenged to escape their dead-end by expanding host range in a 'contemporary' environment that may have depleted resource abundance and diversity (as many human impacted environments do). Loss of diversity in available resources universally constrains the ability of networks to expand host range and this effect is very robust to network conformation. Environmental resource abundance is more variable in its effect. Networks are generally robust to loss of genetic diversity during the evolution of specialisation except at very high rates of loss. By omitting historical specialisation, we show that the effect of resource diversity on host range expansion is not a universal network property but something that is often specific to specialist organisms. Historical specialisation also slightly reduces the robustness of networks in the contemporary environment to loss of genetic diversity during the specialisation process. Fundamentally, simulations predict that loss of local resource diversity will further increase the vulnerability of specialists to extinction by constraining their ability to expand host range in the face of environmental change.
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http://dx.doi.org/10.1016/j.jtbi.2019.05.016DOI Listing
September 2019

Climate and fishing drive regime shifts in consumer-mediated nutrient cycling in kelp forests.

Glob Chang Biol 2019 09 12;25(9):3179-3192. Epub 2019 Jun 12.

Marine Science Institute, University of California, Santa Barbara, California.

Globally, anthropogenic pressures are reducing the abundances of marine species and altering ecosystems through modification of trophic interactions. Yet, consumer declines also disrupt important bottom-up processes, like nutrient recycling, which are critical for ecosystem functioning. Consumer-mediated nutrient dynamics (CND) is now considered a major biogeochemical component of most ecosystems, but lacking long-term studies, it is difficult to predict how CND will respond to accelerating disturbances in the wake of global change. To aid such predictions, we coupled empirical ammonium excretion rates with an 18-year time series of the standing biomass of common benthic macroinvertebrates in southern California kelp forests. This time series of excretion rates encompassed an extended period of extreme ocean warming, disease outbreaks, and the abolishment of fishing at two of our study sites, allowing us to assess kelp forest CND across a wide range of environmental conditions. At their peak, reef invertebrates supplied an average of 18.3 ± 3.0 µmol NH  m  hr to kelp forests when sea stars were regionally abundant, but dropped to 3.5 ± 1.0 µmol NH  m  hr following their mass mortality due to disease during a prolonged period of extreme warming. However, a coincident increase in the abundance of the California spiny lobster, Palinurus interupptus (Randall, 1840), likely in response to both reduced fishing and a warmer ocean, compensated for much of the recycled ammonium lost to sea star mortality. Both lobsters and sea stars are widely recognized as key predators that can profoundly influence community structure in benthic marine systems. Our study is the first to demonstrate their importance in nutrient cycling, thus expanding their roles in the ecosystem. Climate change is increasing the frequency and severity of warming events, and rising human populations are intensifying fishing pressure in coastal ecosystems worldwide. Our study documents how these projected global changes can drive regime shifts in CND and fundamentally alter a critical ecosystem function.
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http://dx.doi.org/10.1111/gcb.14706DOI Listing
September 2019

Species insurance trumps spatial insurance in stabilizing biomass of a marine macroalgal metacommunity.

Ecology 2019 07 13;100(7):e02719. Epub 2019 May 13.

Marine Science Institute, University of California, Santa Barbara, California, 93106, USA.

Because natural ecosystems are complex, it is difficult to predict how their variability scales across space and levels of organization. The species-insurance hypothesis predicts that asynchronous dynamics among species should reduce variability when biomass is aggregated either from local species populations to local multispecies communities, or from metapopulations to metacommunities. Similarly, the spatial-insurance hypothesis predicts that asynchronous spatial dynamics among either local populations or local communities should stabilize metapopulation biomass and metacommunity biomass, respectively. In combination, both species and spatial insurance reduce variation in metacommunity biomass over time, yet these insurances are rarely considered together in natural systems. We partitioned the extent that species insurance and spatial insurance reduced the annual variation in macroalgal biomass in a southern California kelp forest. We quantified variability and synchrony at two levels of organization (population and community) and two spatial scales (local plots and region) and quantified the strength of species and spatial insurance by comparing observed variability and synchrony in aggregate biomass to null models of independent species or spatial dynamics based on cyclic-shift permutation. Spatial insurance was weak, presumably because large-scale oceanographic processes in the study region led to high spatial synchrony at both population- and community-level biomass. Species insurance was stronger due to asynchronous dynamics among the metapopulations of a few common species. In particular, a regional decline in the dominant understory kelp species Pterygophora californica was compensated for by the rise of three subdominant species. These compensatory dynamics were associated with positive values of the Pacific Decadal Oscillation, indicating that differential species tolerances to warmer temperature and nutrient-poor conditions may underlie species insurance in this system. Our results illustrate how species insurance can stabilize aggregate community properties in natural ecosystems where environmental conditions vary over broad spatial scales.
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http://dx.doi.org/10.1002/ecy.2719DOI Listing
July 2019

Treatment of Refractory ALK Rearranged Anaplastic Large Cell Lymphoma With Alectinib.

Clin Lymphoma Myeloma Leuk 2019 06 11;19(6):e247-e250. Epub 2019 Mar 11.

Division of Hematology/Oncology, University of Virginia, Charlottesville, VA.

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http://dx.doi.org/10.1016/j.clml.2019.03.001DOI Listing
June 2019

The principles of tomorrow's university.

F1000Res 2018 11;7:1926. Epub 2018 Dec 11.

Northwestern University, Evanston, IL, USA.

In the 21st Century, research is increasingly data- and computation-driven. Researchers, funders, and the larger community today emphasize the traits of openness and reproducibility. In March 2017, 13 mostly early-career research leaders who are building their careers around these traits came together with ten university leaders (presidents, vice presidents, and vice provosts), representatives from four funding agencies, and eleven organizers and other stakeholders in an NIH- and NSF-funded one-day, invitation-only workshop titled "Imagining Tomorrow's University." Workshop attendees were charged with launching a new dialog around open research - the current status, opportunities for advancement, and challenges that limit sharing. The workshop examined how the internet-enabled research world has changed, and how universities need to change to adapt commensurately, aiming to understand how universities can and should make themselves competitive and attract the best students, staff, and faculty in this new world. During the workshop, the participants re-imagined scholarship, education, and institutions for an open, networked era, to uncover new opportunities for universities to create value and serve society. They expressed the results of these deliberations as a set of 22 principles of tomorrow's university across six areas: credit and attribution, communities, outreach and engagement, education, preservation and reproducibility, and technologies. Activities that follow on from workshop results take one of three forms. First, since the workshop, a number of workshop authors have further developed and published their white papers to make their reflections and recommendations more concrete. These authors are also conducting efforts to implement these ideas, and to make changes in the university system.  Second, we plan to organise a follow-up workshop that focuses on how these principles could be implemented. Third, we believe that the outcomes of this workshop support and are connected with recent theoretical work on the position and future of open knowledge institutions.
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http://dx.doi.org/10.12688/f1000research.17425.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338243PMC
September 2019

Loss of foundation species: disturbance frequency outweighs severity in structuring kelp forest communities.

Ecology 2018 11 30;99(11):2442-2454. Epub 2018 Oct 30.

Marine Science Institute, University of California, Santa Barbara, California, 93106, USA.

Disturbances often cause the disproportionate loss of foundation species but understanding how the frequency and severity of disturbance to such organisms influence biological communities remains unresolved. This gap in knowledge exists in part because of the rarity of ecologically meaningful studies capable of disentangling different elements of disturbance. Hence, we carried out a long-term (9 yr), large-scale (2,000 m plots), spatially replicated (4 sites) field experiment in which we manipulated disturbance to a globally distributed marine foundation species, the giant kelp Macrocystis pyrifera, and tracked community responses over time. To distinguish the effects of disturbance frequency and severity on the biodiversity and composition of temperate rocky reef communities, we simulated the repeated loss of giant kelp from destructive winter waves across a background of natural variation in disturbance. By following the response of over 200 taxa from the surrounding community, we discovered that the frequency of disturbance to giant kelp changed the biomass, diversity, and composition of community guilds in a manner commensurate with their dependence on the physical (i.e., benthic light and space), trophic (i.e., living and detrital biomass), and habitat (i.e., biogenic structure) resources mediated by this foundation species. Annual winter disturbance to giant kelp reduced living and detrital giant kelp biomass by 57% and 40%, respectively, enhanced bottom light by 22%, and halved the seafloor area covered by giant kelp holdfasts. Concomitantly, the biomass of understory algae and epilithic sessile invertebrates more than doubled, while the biomass of rock-boring clams, mobile invertebrates, and fishes decreased 30-61%. Frequent loss of giant kelp boosted understory algal richness by 82% and lowered sessile invertebrate richness by 13% but did not affect the biodiversity of mobile fauna. In contrast to changes driven by disturbance frequency, interannual variation in the severity of disturbance to giant kelp had weaker, less consistent effects, causing only modest changes in assemblages of sessile invertebrates, mobile invertebrate herbivores, and fishes. Our results broaden the foundation species concept by demonstrating that repeated disturbance to a dominant habitat-forming species can outweigh the influence of less frequent but severe disturbances for the surrounding community.
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http://dx.doi.org/10.1002/ecy.2485DOI Listing
November 2018

BioTIME: A database of biodiversity time series for the Anthropocene.

Authors:
Maria Dornelas Laura H Antão Faye Moyes Amanda E Bates Anne E Magurran Dušan Adam Asem A Akhmetzhanova Ward Appeltans José Manuel Arcos Haley Arnold Narayanan Ayyappan Gal Badihi Andrew H Baird Miguel Barbosa Tiago Egydio Barreto Claus Bässler Alecia Bellgrove Jonathan Belmaker Lisandro Benedetti-Cecchi Brian J Bett Anne D Bjorkman Magdalena Błażewicz Shane A Blowes Christopher P Bloch Timothy C Bonebrake Susan Boyd Matt Bradford Andrew J Brooks James H Brown Helge Bruelheide Phaedra Budy Fernando Carvalho Edward Castañeda-Moya Chaolun Allen Chen John F Chamblee Tory J Chase Laura Siegwart Collier Sharon K Collinge Richard Condit Elisabeth J Cooper J Hans C Cornelissen Unai Cotano Shannan Kyle Crow Gabriella Damasceno Claire H Davies Robert A Davis Frank P Day Steven Degraer Tim S Doherty Timothy E Dunn Giselda Durigan J Emmett Duffy Dor Edelist Graham J Edgar Robin Elahi Sarah C Elmendorf Anders Enemar S K Morgan Ernest Rubén Escribano Marc Estiarte Brian S Evans Tung-Yung Fan Fabiano Turini Farah Luiz Loureiro Fernandes Fábio Z Farneda Alessandra Fidelis Robert Fitt Anna Maria Fosaa Geraldo Antonio Daher Correa Franco Grace E Frank William R Fraser Hernando García Roberto Cazzolla Gatti Or Givan Elizabeth Gorgone-Barbosa William A Gould Corinna Gries Gary D Grossman Julio R Gutierréz Stephen Hale Mark E Harmon John Harte Gary Haskins Donald L Henshaw Luise Hermanutz Pamela Hidalgo Pedro Higuchi Andrew Hoey Gert Van Hoey Annika Hofgaard Kristen Holeck Robert D Hollister Richard Holmes Mia Hoogenboom Chih-Hao Hsieh Stephen P Hubbell Falk Huettmann Christine L Huffard Allen H Hurlbert Natália Macedo Ivanauskas David Janík Ute Jandt Anna Jażdżewska Tore Johannessen Jill Johnstone Julia Jones Faith A M Jones Jungwon Kang Tasrif Kartawijaya Erin C Keeley Douglas A Kelt Rebecca Kinnear Kari Klanderud Halvor Knutsen Christopher C Koenig Alessandra R Kortz Kamil Král Linda A Kuhnz Chao-Yang Kuo David J Kushner Claire Laguionie-Marchais Lesley T Lancaster Cheol Min Lee Jonathan S Lefcheck Esther Lévesque David Lightfoot Francisco Lloret John D Lloyd Adrià López-Baucells Maite Louzao Joshua S Madin Borgþór Magnússon Shahar Malamud Iain Matthews Kent P McFarland Brian McGill Diane McKnight William O McLarney Jason Meador Peter L Meserve Daniel J Metcalfe Christoph F J Meyer Anders Michelsen Nataliya Milchakova Tom Moens Even Moland Jon Moore Carolina Mathias Moreira Jörg Müller Grace Murphy Isla H Myers-Smith Randall W Myster Andrew Naumov Francis Neat James A Nelson Michael Paul Nelson Stephen F Newton Natalia Norden Jeffrey C Oliver Esben M Olsen Vladimir G Onipchenko Krzysztof Pabis Robert J Pabst Alain Paquette Sinta Pardede David M Paterson Raphaël Pélissier Josep Peñuelas Alejandro Pérez-Matus Oscar Pizarro Francesco Pomati Eric Post Herbert H T Prins John C Priscu Pieter Provoost Kathleen L Prudic Erkki Pulliainen B R Ramesh Olivia Mendivil Ramos Andrew Rassweiler Jose Eduardo Rebelo Daniel C Reed Peter B Reich Suzanne M Remillard Anthony J Richardson J Paul Richardson Itai van Rijn Ricardo Rocha Victor H Rivera-Monroy Christian Rixen Kevin P Robinson Ricardo Ribeiro Rodrigues Denise de Cerqueira Rossa-Feres Lars Rudstam Henry Ruhl Catalina S Ruz Erica M Sampaio Nancy Rybicki Andrew Rypel Sofia Sal Beatriz Salgado Flavio A M Santos Ana Paula Savassi-Coutinho Sara Scanga Jochen Schmidt Robert Schooley Fakhrizal Setiawan Kwang-Tsao Shao Gaius R Shaver Sally Sherman Thomas W Sherry Jacek Siciński Caya Sievers Ana Carolina da Silva Fernando Rodrigues da Silva Fabio L Silveira Jasper Slingsby Tracey Smart Sara J Snell Nadejda A Soudzilovskaia Gabriel B G Souza Flaviana Maluf Souza Vinícius Castro Souza Christopher D Stallings Rowan Stanforth Emily H Stanley José Mauro Sterza Maarten Stevens Rick Stuart-Smith Yzel Rondon Suarez Sarah Supp Jorge Yoshio Tamashiro Sukmaraharja Tarigan Gary P Thiede Simon Thorn Anne Tolvanen Maria Teresa Zugliani Toniato Ørjan Totland Robert R Twilley Gediminas Vaitkus Nelson Valdivia Martha Isabel Vallejo Thomas J Valone Carl Van Colen Jan Vanaverbeke Fabio Venturoli Hans M Verheye Marcelo Vianna Rui P Vieira Tomáš Vrška Con Quang Vu Lien Van Vu Robert B Waide Conor Waldock Dave Watts Sara Webb Tomasz Wesołowski Ethan P White Claire E Widdicombe Dustin Wilgers Richard Williams Stefan B Williams Mark Williamson Michael R Willig Trevor J Willis Sonja Wipf Kerry D Woods Eric J Woehler Kyle Zawada Michael L Zettler Thomas Hickler

Glob Ecol Biogeogr 2018 Jul 24;27(7):760-786. Epub 2018 Jul 24.

Centre for Biological Diversity and Scottish Oceans Institute, School of Biology, University of St. Andrews St Andrews United Kingdom.

Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.

Main Types Of Variables Included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.

Spatial Location And Grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km (158 cm) to 100 km (1,000,000,000,000 cm).

Time Period And Grain: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.

Major Taxa And Level Of Measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.

Software Format: .csv and .SQL.
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http://dx.doi.org/10.1111/geb.12729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099392PMC
July 2018

Safety and effectiveness of apixaban compared to warfarin in dialysis patients.

Res Pract Thromb Haemost 2018 Apr 26;2(2):291-298. Epub 2018 Mar 26.

Division of Hematology & Oncology University of Virginia Charlottesville VA USA.

The use of apixaban for stroke prophylaxis or for the treatment of venous thromboembolism in end stage renal disease (ESRD) patients maintained on dialysis is based on one single-dose pharmacokinetic study. There is a deficiency of clinical evidence supporting safety in this population. The purpose of this study was to determine the safety and efficacy of apixaban compared with warfarin in dialysis patients. This is a retrospective cohort study conducted at the University of Virginia Medical Center. A total of 124 ESRD patients maintained on dialysis who either received apixaban (n = 74) or warfarin (n = 50) between January 1, 2014 and October 31, 2016 were included in the study. We used multivariable logistic regression to compare the likelihood of patients experiencing a bleeding event based on anticoagulant therapy. The apixaban group experienced fewer overall bleeding events than the warfarin group (18.9% vs 42.0%; =.01); this significant difference persisted in adjusted analysis (OR = 0.15; 95% CI = 0.05-0.46; =.001). Major bleeding events were less frequent in the apixaban group compared with patients on warfarin (5.4% vs 22.0%; =.01). There were no recurrent ischemic strokes in either groups. A lower, non-significant, incidence of recurrent VTE was found in patients on apixaban compared with warfarin (4.4% vs 28.6%; =.99). Compared to warfarin, our findings suggest that apixaban is a safe and effective alternative in patients with ESRD maintained on dialysis, with apixaban patients experiencing fewer bleeding events than warfarin patients.
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http://dx.doi.org/10.1002/rth2.12083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055495PMC
April 2018

Improved estimates of net primary production, growth, and standing crop of Macrocystis pyrifera in Southern California.

Ecology 2018 09 3;99(9):2132. Epub 2018 Aug 3.

Marine Science Institute, University of California, Santa Barbara, California, 93106, USA.

The giant kelp Macrocystis pyrifera forms subtidal forests on shallow reefs in temperate regions of the world. It is one of the fastest-growing multicellular autotrophs on Earth and its high productivity supports diverse marine food webs. In 2008, we published a method for estimating biomass and net primary production (NPP) of giant kelp along with five years of data, to provide a more integrated measure of NPP than those yielded by previous methods. Our method combines monthly field measurements of standing crop and loss rates with a model of kelp biomass dynamics to estimate instantaneous mass-specific growth rates and NPP for each season of each year. We have since improved our approach to account for several previously unresolved sources of biomass loss. These improvements have led to a near doubling of our prior estimates of growth and NPP. At our site with the most persistent stand of giant kelp, NPP averages ~5.2 kg dry mass·m ·yr and results from the rapid growth (~3.5% per d) of a relatively small standing biomass (~0.4 kg dry mass/m on average) that turns over ~12 times annually. Here we provide revised estimates of seasonal biomass, growth, and NPP for the five years covered by our previous publication (2002-2006), along with more than a decade of additional data (2007-2017). We also present updated relationships for predicting giant kelp biomass and NPP from much more easily obtained measurements of frond density. These data can be used to understand the mechanisms that drive variation in giant kelp NPP at a wide range of temporal scales. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper.
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http://dx.doi.org/10.1002/ecy.2440DOI Listing
September 2018

Giant kelp, , increases faunal diversity through physical engineering.

Proc Biol Sci 2018 03;285(1874)

Marine Science Institute, University of California, Santa Barbara, CA 93106, USA.

Foundation species define the ecosystems they live in, but ecologists have often characterized dominant plants as foundational without supporting evidence. Giant kelp has long been considered a marine foundation species due to its complex structure and high productivity; however, there is little quantitative evidence to evaluate this. Here, we apply structural equation modelling to a 15-year time series of reef community data to evaluate how giant kelp affects the reef community. Although species richness was positively associated with giant kelp biomass, most direct paths did not involve giant kelp. Instead, the foundational qualities of giant kelp were driven mostly by indirect effects attributed to its dominant physical structure and associated engineering influence on the ecosystem, rather than by its use as food by invertebrates and fishes. Giant kelp structure has indirect effects because it shades out understorey algae that compete with sessile invertebrates. When released from competition, sessile species in turn increase the diversity of mobile predators. Sea urchin grazing effects could have been misinterpreted as kelp effects, because sea urchins can overgraze giant kelp, understorey algae and sessile invertebrates alike. Our results confirm the high diversity and biomass associated with kelp forests, but highlight how species interactions and habitat attributes can be misconstrued as direct consequences of a foundation species like giant kelp.
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http://dx.doi.org/10.1098/rspb.2017.2571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879622PMC
March 2018

Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase A Proves Renal Origins of Urinary PGI-M and TX-M.

Circ Res 2018 02 3;122(4):555-559. Epub 2018 Jan 3.

From the National Heart and Lung Institute, Imperial College London, United Kingdom (J.A.M., N.S.K., D.M.R.); Blizard Institute, Queen Mary University of London, United Kingdom (R.B.K., W.E.W., M.V.C., M.M.Y., T.D.W.); National Institute for Environmental Health Sciences, Research Triangle, NC (M.L.E., D.C.Z.); Department of Nephrology (W.E.W., M.M.Y.) and Immunology Department (H.L.), Barts Health NHS Trust, London, United Kingdom; and Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, TN (G.L.M.).

Rationale: The balance between vascular prostacyclin, which is antithrombotic, and platelet thromboxane A, which is prothrombotic, is fundamental to cardiovascular health. Prostacyclin and thromboxane A are formed after the concerted actions of cPLAα (cytosolic phospholipase A) and COX (cyclooxygenase). Urinary 2,3-dinor-6-keto-PGF (PGI-M) and 11-dehydro-TXB (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A formation within the circulation and used to explain COX biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney.

Objective: We report data from a remarkable patient carrying an extremely rare genetic mutation in cPLAα, causing almost complete loss of prostacyclin and thromboxane A, who was transplanted with a normal kidney resulting in an experimental scenario of whole-body cPLAα knockout, kidney-specific knockin. By studying this patient, we can determine definitively the contribution of the kidney to the productions of PGI-M and TX-M and test their validity as markers of prostacyclin and thromboxane A in the circulation.

Methods And Results: Metabolites were measured using liquid chromatography-tandem mass spectrometry. Endothelial cells were grown from blood progenitors. Before kidney transplantation, the patient's endothelial cells and platelets released negligible levels of prostacyclin (measured as 6-keto-prostaglandin F) and thromboxane A (measured as TXB), respectively. Likewise, the urinary levels of PGI-M and TX-M were very low. After transplantation and the establishment of normal renal function, the levels of PGI-M and TX-M in the patient's urine rose to within normal ranges, whereas endothelial production of prostacyclin and platelet production of thromboxane A remained negligible.

Conclusions: These data show that PGI-M and TX-M can be derived exclusively from the kidney without contribution from prostacyclin made by endothelial cells or thromboxane A by platelets in the general circulation. Previous work relying on urinary metabolites of prostacyclin and thromboxane A as markers of whole-body endothelial and platelet function now requires reevaluation.
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http://dx.doi.org/10.1161/CIRCRESAHA.117.312144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816977PMC
February 2018

Outcomes by molecular subtype after accelerated partial breast irradiation using single-entry catheters.

Brachytherapy 2018 Mar - Apr;17(2):415-424. Epub 2017 Nov 13.

Comprehensive Breast Center of Arizona, Phoenix, AZ.

Purpose: Tumor biology is being recognized as an important indicator of prognosis and risk of locoregional recurrence. Here, we determine actuarial recurrence rates by approximated molecular subtype for women treated with single-entry catheter accelerated partial breast irradiation (sAPBI).

Methods And Materials: One thousand four hundred eighty-six women with invasive cancer having known ER, PR, and Her2 status and at least 1-year of followup were treated using MammoSite, Contura, or SAVI sAPBI from 2002 to 2014 at our institution. Actuarial recurrence rates were determined for the following four approximated molecular subtypes using the Kaplan-Meier method: luminal A (n = 1081), luminal B (n = 164), Her2 (n = 123), and triple-negative breast cancer (TNBC; n = 118).

Results: With a median followup time of 3.3 years (range 1-13.6 years), the 5-year in-breast tumor recurrence rate was 2.6% overall, 2.1% for luminal A, 1.5% for luminal B, 4.9% for Her2, and 5.4% for TNBC. Luminal A and B subtypes, as compared with the more aggressive Her2 and TNBC subtypes combined, demonstrated lower 5-year in-breast tumor recurrence (2.1% vs. 5.1%, p = 0.021). The 5-year regional nodal recurrence rate was 1.4% overall, 1.4% for luminal A, 0% for luminal B, 1% for Her2, and 4.2% for TNBC. The 5-year locoregional control is 97.3% for luminal breast cancers and 93.8% for the more aggressive Her2 and TNBC subtypes collectively.

Conclusions: Luminal cancers demonstrated excellent 5-year locoregional control with sAPBI. Although caution should be used when treating patients with the more aggressive Her2 and TNBC subtypes, these subtypes have demonstrated higher LRR with mastectomy and whole-breast irradiation. Further randomized comparisons are needed to determine the optimal treatment for these higher risk patients.
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http://dx.doi.org/10.1016/j.brachy.2017.10.009DOI Listing
January 2019

Scale-specific drivers of kelp forest communities.

Oecologia 2018 01 3;186(1):217-233. Epub 2017 Nov 3.

Marine Science Institute, University of California, Santa Barbara, CA, 93106, USA.

Identifying spatial scales of variation in natural communities and the processes driving them is critical for obtaining a predictive understanding of biodiversity. In this study, we focused on diverse communities inhabiting productive kelp forests on shallow subtidal rocky reefs in southern California, USA. We combined long-term community surveys from 86 sites with detailed environmental data to determine what structures assemblages of fishes, invertebrates and algae at multiple spatial scales. We identified the spatial scales of variation in species composition using a hierarchical analysis based on eigenfunctions, and assessed how sea surface temperature (SST), water column chlorophyll, giant kelp biomass, wave exposure and potential propagule delivery strength contributed to community variation at each scale. Spatial effects occurring at multiple scales explained 60% of the variation in fish assemblages and 52% of the variation in the assemblages of invertebrates and algae. Most variation occurred over broad spatial scales (> 200 km) consistent with spatial heterogeneity in SST and potential propagule delivery strength, while the latter also explained community variation at medium scales (65-200 km). Small scale (1-65 km) community variation was substantial but not linked to any of the measured drivers. Conclusions were consistent for both reef fishes and benthic invertebrates and algae, despite sharp differences in their adult mobility. Our results demonstrate the scale dependence of environmental drivers on kelp forest communities, showing that most species were strongly sorted along oceanographic conditions over various spatial scales. Such spatial effects must be integrated into models assessing the response of marine ecosystems to climate change.
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http://dx.doi.org/10.1007/s00442-017-3994-1DOI Listing
January 2018

Using SDS-PAGE gel fingerprinting to identify soft-bodied wood-boring insect larvae to species.

Pest Manag Sci 2018 Mar 29;74(3):705-714. Epub 2017 Nov 29.

Tumbling Dice Ltd, Newcastle upon Tyne, UK.

Background: This paper describes the progress that we have made in assessing the feasibility of 'fingerprinting' using imaged SDS-PAGE gels of haemolymph proteins, to identify soft-bodied wood-boring insect larvae such as the Asian longhorn beetle, Anoplophora glabripennis (Motscholsky, 1853) (Coleoptera: Cerambycidae). Because of stringent import restrictions and difficulty in obtaining licences to work with these organisms, we opted to work with four species of scarab beetle, Mecynorhina polyphemus (Fabricius, 1781), Pachnoda sinuata (Fabricius, 1775), Eucidella shiratica (Csiki, 1909) and Eucidella shultzeorum (Kolbe, 1906) which have near identical larval morphologies.

Results: We show that this technology when combined with an advanced pattern matching system (Digital Automated Identification SYstem - DAISY) can classify soft-bodied insect larvae that are almost identical morphologically to species at a level of accuracy is in excess of 98%. The study also indicates that the technology copes well with noisy data and small training sets.

Conclusion: The experience gained in undertaking this study gives us confidence that we will be able to develop a field deployable system in the medium term. We believe that as a high-throughput identification tool, this technology is superior to competitor technologies (e.g. fingerprinting of imaged DNA gels) in terms of speed, cost and ease of use; and therefore, is suitable for low-cost deployment in the field. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.4766DOI Listing
March 2018

Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy.

Pulm Circ 2017 Jul-Sep;7(3):643-653. Epub 2017 Jun 27.

1 Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London, UK.

Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.
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http://dx.doi.org/10.1177/2045893217710224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841901PMC
June 2017