Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

A Comparison between the Use of Patient-worn Virtual Reality in Wound Care and Hand Surgery: How Does Virtual Reality Work?

As virtual reality (VR) technology becomes smaller and more affordable, it is gaining in popularity as a tool to address the patient experience of pain and anxiety during invasive procedures. In this study, we explore the effect of VR on the patient experience in two clinical environments of different anxiety levels to propose a possible mechanism of VR on pain and anxiety reduction. Method: Twenty-five wound care patients were randomly assigned to either a VR group or non-virtual reality (NVR) group, singly blinded. Pre-debridement, peri-debridement, and immediately postdebridement anxiety, fun, and pain scores were collected using a Likert scale (0 = least; 10 = most) from each group of patients. These measurements were compared among the VR versus NVR group in the setting of routine wound debridement procedures. The results are compared with our previously published data on patients who underwent wide awake local anesthesia no tourniquet (WALANT) hand surgery. Results: The WALANT surgery patients using VR experienced significant reduction in anxiety and increase in fun compared with the NVR group. In the wound debridement group with VR, there was improved fun, but no statistically significant reduction in pain or anxiety when compared with the NVR group. The mean score for anxiety was higher for awake hand surgery than for wound debridement cases (3.3 versus 1.7, P = 0.004). Conclusions: VR seems to be more effective in higher anxiety settings, could VR work via a neurological mechanism akin to the Melzack and Wall gate control theory of pain? VR may act primarily on the anxiety axis, providing negative feedback via cortical pathways to the amygdala.

The phylogeny and global biogeography of Primulaceae based on high-throughput DNA sequence data.

The angiosperm family Primulaceae is morphologically diverse and distributed nearly worldwide. However, phylogenetic uncertainty has obstructed the identification of major morphological and biogeographic transitions within the clade. We used target capture sequencing with the Angiosperms353 probes, taxon-sampling encompassing nearly all genera of the family, tree-based sequence curation, and multiple phylogenetic approaches to investigate the major clades of Primulaceae and their relationship to other Ericales. We generated dated phylogenetic trees and conducted broad-scale biogeographic analyses as well as stochastic character mapping of growth habit. We show that Ardisia, a pantropical genus and the largest in the family, is not monophyletic, with at least 19 smaller genera nested within it. Neotropical members of Ardisia and several smaller genera form a clade, an ancestor of which arrived in the Neotropics and began diversifying about 20 Ma. This Neotropical clade is most closely related to Elingamita and Tapeinosperma, which are most diverse on islands of the Pacific. Both Androsace and Primula are non-monophyletic by the inclusion of smaller genera. Ancestral state reconstructions revealed that there have either been parallel transitions to an herbaceous habit in Primuloideae, Samolus, and at least three lineages of Myrsinoideae, or a common ancestor of nearly all Primulaceae was herbaceous. Our results provide a robust estimate of phylogenetic relationships across Primulaceae and show that a revised classification of Myrsinoideae and several other clades within the family is necessary to render all genera monophyletic.

Guidelines for Wide-Awake Local Anesthesia Surgery with No Tourniquet in the Office Setting Using Field Preparation Sterility.

SUMMARY: Wide-awake local anesthesia surgery with no tourniquet, or WALANT, has become popular in surgery, especially among hand surgeons. With the increasing number of surgeons performing office-based procedures, this article provides guidelines that may be used in the office setting to help transition more traditional hospital operating room-based procedures to the office setting. This article outlines the benefits of performing office-based wide-awake local anesthesia surgery with no tourniquet and provides a step-by-step guide to performing procedures that can be easily incorporated into any hand surgeon's practice successfully and safely.

Virtual Reality Improves Patient Experience and Anxiety During In-office Carpal Tunnel Release.

Background: This study examined how wide- awake local anesthesia no tourniquet (WALANT) surgery in the office versus the standard operating room (OR) impacts patient experience, and the effect wide awake virtual reality (WAVR) has in conjunction with WALANT on patient experience. Methods: This is a patient-reported outcome study of patients undergoing carpal tunnel release by a single surgeon between August 2017 and March 2021. Patients were classified by location; traditional OR versus WALANT in-office. In-office patients were further classified by whether they chose to use WAVR or not. Patients rated overall experience, enjoyability, and anxiety using a Likert scale (1-7). Results: The online survey had a 44.8% response rate. OR patients were twice as likely to report a neutral or negative experience (23% versus 11%, P = 0.03), significantly lower enjoyment scores (44% versus 20%, P = 0.0007)' and higher anxiety (42% versus 26%, P = 0.04) compared with office-based WALANT patients. With the addition of WAVR, office patients reported higher enjoyment than those who did not use WAVR (85% versus 73%, P = 0.05). Patients reporting an anxiety disorder were more likely to choose WAVR when compared with patients without anxiety disorder (73.8% versus 56.4%). When they chose WAVR, they had greater anxiolysis (79% versus 47%, P = 0.01)' and increased enjoyment (90% versus 59%, P = 0.005). Conclusions: This study demonstrates improved patient experience in the office setting, further amplified by WAVR. Preexisting anxiety disorder is a positive predictive variable toward the patients' choice to use WAVR.

Infection Rate Comparison during Transition from Hospital to Office WALANT Enabled by Virtual Reality.

We transitioned our hand practice from the operating room (OR) to our office-based procedure room (OPR) to offer wide-awake, local anesthesia, no tourniquet (WALANT). We have established that using wide-awake virtual reality improves patient comfort and anxiety during wide-awake procedures and helps facilitate our patients' choice of venue. We aimed to assess the effect of this transition on infection rates for procedures performed by a single surgeon in the OR versus the OPR. Methods: A retrospective chart review was performed on a single surgeon's adult patients who underwent elective and closed traumatic upper limb surgeries. A surgical site infection was defined as superficial or deep, based on clinical examination conducted by the surgeon, and was treated with antibiotics within a 4-week postoperative window. Results: From August 2017 to August 2019, 538 (216 OR and 322 OPR) consecutive cases met inclusion criteria. There were six (2.78%) superficial infections and zero deep space infections in the OR cohort compared with four (1.24%) superficial and zero deep space infections in the OPR cohort with no statistical significance. Two-thirds of cases were converted to WALANT and delivered in the office. Conclusions: This narrative study concurs with the current literature that WALANT in the office setting is as safe as the hospital OR-based procedures for selected elective cases. By transitioning suitable cases from the OR to the OPR, a surgeon's overall infection rate should not change.

Superior gluteal artery perforator flap salvaged via hyperbaric oxygen therapy.

The superior gluteal artery perforator (SGAP) flap can be challenging and in common with all flaps can develop venous and arterial insufficiency. Several prior studies have demonstrated the successful utility of hyperbaric oxygen therapy (HBOT) in the salvage of compromised flaps, mainly with deep inferior epigastric perforator, latissimus dorsi or transverse rectus abdominis myocutaneous flaps. SGAP flaps are autologous alternatives to abdominal-based flaps and provides adequate adipose tissue for breast reconstruction. We report a case of a woman in her 50s who underwent a delayed bilateral breast reconstruction using SGAP free flaps. Postoperatively, venous congestion of her right breast flap was noted for which she was referred for HBOT. An acceptable aesthetic result was achieved following 17 HBOT treatments. This is the first case we can find in the published literature of ischaemic SGAP free flap being salvaged by HBOT.

A Comprehensive Phylogenomic Platform for Exploring the Angiosperm Tree of Life.

The tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. The primary goals of this article are to (i) document our methods, (ii) describe our first data release, and (iii) present a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic data set for angiosperms to date, comprising 3099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96$\%$) and 2333 genera (17$\%$). A "first pass" angiosperm tree of life was inferred from the data, which totaled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns, for interactive presentation in the Kew Tree of Life Explorer. This species tree was generated using methods that were rigorous, yet tractable at our scale of operation. Despite limitations pertaining to taxon and gene sampling, gene recovery, models of sequence evolution and paralogy, the tree strongly supports existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated data set, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer and will be updated as further data become available. This major milestone toward a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardized nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the world's natural history collections. [Angiosperms; Angiosperms353; genomics; herbariomics; museomics; nuclear phylogenomics; open access; target sequence capture; tree of life.].

Microsatellites and petal morphology reveal new patterns of admixture in Orchis hybrid zones.

PREMISE: The genetic structure of hybrid zones provides insight into the potential for gene flow to occur between plant taxa. Four closely related European orchid species (Orchis anthropophora, O. militaris, O. purpurea, and O. simia) hybridize when they co-occur. We aimed to characterize patterns of hybridization in O. militaris-O. purpurea, O. purpurea-O. simia, and O. anthropophora-O. simia hybrid zones using molecular and morphological data. METHODS: We used 11 newly isolated nuclear microsatellites to genotype 695 individuals collected from seven hybrid zones and six allopatric parental populations in France. Geometric morphometric analysis was conducted using 15 labellum landmarks to capture the main aspects of petal shape. RESULTS: Backcrossing was asymmetric toward O. militaris in multiple O. militaris-O. purpurea hybrid zones. Hybrids in O. purpurea-O. simia and O. anthropophora-O. simia hybrid zones were largely limited to F1 and F2 generations, but further admixture had occurred. These patterns were reflected in labellum geometric morphometric data, which correlated strongly with nuclear microsatellite data in all three species combinations. CONCLUSIONS: The coexistence of parental and admixed individuals in these Orchis hybrid zones implies they are likely to be tension zones being maintained by a balance between gene flow into the hybrid zone and selection acting against admixed individuals. The pattern of admixture in the three species combinations suggests intrinsic selection acting on the hybrids is weaker in more closely related taxa.

Settling a family feud: a high-level phylogenomic framework for the Gentianales based on 353 nuclear genes and partial plastomes.

PREMISE: Comprising five families that vastly differ in species richness-ranging from Gelsemiaceae with 13 species to the Rubiaceae with 13,775 species-members of the Gentianales are often among the most species-rich and abundant plants in tropical forests. Despite considerable phylogenetic work within particular families and genera, several alternative topologies for family-level relationships within Gentianales have been presented in previous studies. METHODS: Here we present a phylogenomic analysis based on nuclear genes targeted by the Angiosperms353 probe set for approximately 150 species, representing all families and approximately 85% of the formally recognized tribes. We were able to retrieve partial plastomes from off-target reads for most taxa and infer phylogenetic trees for comparison with the nuclear-derived trees. RESULTS: We recovered high support for over 80% of all nodes. The plastid and nuclear data are largely in agreement, except for some weakly to moderately supported relationships. We discuss the implications of our results for the order's classification, highlighting points of increased support for previously uncertain relationships. Rubiaceae is sister to a clade comprising (Gentianaceae + Gelsemiaceae) + (Apocynaceae + Loganiaceae). CONCLUSIONS: The higher-level phylogenetic relationships within Gentianales are confidently resolved. In contrast to recent studies, our results support the division of Rubiaceae into two subfamilies: Cinchonoideae and Rubioideae. We do not formally recognize Coptosapelteae and Luculieae within any particular subfamily but treat them as incertae sedis. Our framework paves the way for further work on the phylogenetics, biogeography, morphological evolution, and macroecology of this important group of flowering plants.

A higher-level nuclear phylogenomic study of the carrot family (Apiaceae).

PREMISE: The carrot family (Apiaceae) comprises 466 genera, which include many well-known crops (e.g., aniseed, caraway, carrots, celery, coriander, cumin, dill, fennel, parsley, and parsnips). Higher-level phylogenetic relationships among subfamilies, tribes, and other major clades of Apiaceae are not fully resolved. This study aims to address this important knowledge gap. METHODS: Target sequence capture with the universal Angiosperms353 probe set was used to examine phylogenetic relationships in 234 genera of Apiaceae, representing all four currently recognized subfamilies (Apioideae, Azorelloideae, Mackinlayoideae, and Saniculoideae). Recovered nuclear genes were analyzed using both multispecies coalescent and concatenation approaches. RESULTS: We recovered hundreds of nuclear genes even from old and poor-quality herbarium specimens. Of particular note, we placed with strong support three incertae sedis genera (Platysace, Klotzchia, and Hermas); all three occupy isolated positions, with Platysace resolved as sister to all remaining Apiaceae. We placed nine genera (Apodicarpum, Bonannia, Grafia, Haplosciadium, Microsciadium, Physotrichia, Ptychotis, Tricholaser, Xatardia) that have never previously been included in any molecular phylogenetic study. CONCLUSIONS: We provide support for the maintenance of the four existing subfamilies of Apiaceae, while recognizing that Hermas, Klotzschia, and the Platysace clade may each need to be accommodated in additional subfamilies (pending improved sampling). The placement of the currently apioid genus Phlyctidocarpa can be accommodated by the expansion of subfamily Saniculoideae, although adequate morphological synapomorphies for this grouping are yet to be defined. This is the first phylogenetic study of the Apiaceae using high-throughput sequencing methods and represents an unprecedented evolutionary framework for the group.

Habitat specialisation controls ectomycorrhizal fungi above the treeline in the European Alps.

Alpine habitats are one of the most vulnerable ecosystems to environmental change, however, little information is known about the drivers of plant-fungal interactions in these ecosystems and their resilience to climate change. We investigated the influence of the main drivers of ectomycorrhizal (EM) fungal communities along elevation and environmental gradients in the alpine zone of the European Alps and measured their degree of specialisation using network analysis. We sampled ectomycorrhizas of Dryas octopetala, Bistorta vivipara and Salix herbacea, and soil fungal communities at 28 locations across five countries, from the treeline to the nival zone. We found that: (1) EM fungal community composition, but not richness, changes along elevation, (2) there is no strong evidence of host specialisation, however, EM fungal networks in the alpine zone and within these, EM fungi associated with snowbed communities, are more specialised than in other alpine habitats, (3) plant host population structure does not influence EM fungal communities, and (4) most variability in EM fungal communities is explained by fine-scale changes in edaphic properties, like soil pH and total nitrogen. The higher specialisation and narrower ecological niches of these plant-fungal interactions in snowbed habitats make these habitats particularly vulnerable to environmental change in alpine ecosystems.

Electric-field control of spin dynamics during magnetic phase transitions.

Controlling magnetization dynamics is imperative for developing ultrafast spintronics and tunable microwave devices. However, the previous research has demonstrated limited electric-field modulation of the effective magnetic damping, a parameter that governs the magnetization dynamics. Here, we propose an approach to manipulate the damping by using the large damping enhancement induced by the two-magnon scattering and a nonlocal spin relaxation process in which spin currents are resonantly transported from antiferromagnetic domains to ferromagnetic matrix in a mixed-phased metallic alloy FeRh. This damping enhancement in FeRh is sensitive to its fraction of antiferromagnetic and ferromagnetic phases, which can be dynamically tuned by electric fields through a strain-mediated magnetoelectric coupling. In a heterostructure of FeRh and piezoelectric PMN-PT, we demonstrated a more than 120% modulation of the effective damping by electric fields during the antiferromagnetic-to-ferromagnetic phase transition. Our results demonstrate an efficient approach to controlling the magnetization dynamics, thus enabling low-power tunable electronics.

Factors Affecting Targeted Sequencing of 353 Nuclear Genes From Herbarium Specimens Spanning the Diversity of Angiosperms.

The world's herbaria collectively house millions of diverse plant specimens, including endangered or extinct species and type specimens. Unlocking genetic data from the typically highly degraded DNA obtained from herbarium specimens was difficult until the arrival of high-throughput sequencing approaches, which can be applied to low quantities of severely fragmented DNA. Target enrichment involves using short molecular probes that hybridise and capture genomic regions of interest for high-throughput sequencing. In this study on herbariomics, we used this targeted sequencing approach and the Angiosperms353 universal probe set to recover up to 351 nuclear genes from 435 herbarium specimens that are up to 204 years old and span the breadth of angiosperm diversity. We show that on average 207 genes were successfully retrieved from herbarium specimens, although the mean number of genes retrieved and target enrichment efficiency is significantly higher for silica gel-dried specimens. Forty-seven target nuclear genes were recovered from a herbarium specimen of the critically endangered St Helena boxwood, Mellissia begoniifolia, collected in 1815. Herbarium specimens yield significantly less high-molecular-weight DNA than silica gel-dried specimens, and genomic DNA quality declines with sample age, which is negatively correlated with target enrichment efficiency. Climate, taxon-specific traits, and collection strategies additionally impact target sequence recovery. We also detected taxonomic bias in targeted sequencing outcomes for the 10 most numerous angiosperm families that were investigated in depth. We recommend that (1) for species distributed in wet tropical climates, silica gel-dried specimens should be used preferentially; (2) for species distributed in seasonally dry tropical climates, herbarium and silica gel-dried specimens yield similar results, and either collection can be used; (3) taxon-specific traits should be explored and established for effective optimisation of taxon-specific studies using herbarium specimens; (4) all herbarium sheets should, in future, be annotated with details of the preservation method used; (5) long-term storage of herbarium specimens should be in stable, low-humidity, and low-temperature environments; and (6) targeted sequencing with universal probes, such as Angiosperms353, should be investigated closely as a new approach for DNA barcoding that will ensure better exploitation of herbarium specimens than traditional Sanger sequencing approaches.

Virtual Reality Improves the Patient Experience during Wide-Awake Local Anesthesia No Tourniquet Hand Surgery: A Single-Blind, Randomized, Prospective Study.

Wide-awake local anesthesia no tourniquet surgery has been shown to decrease cost and hospital length of stay. The authors studied the use of virtual reality during wide-awake local anesthesia no tourniquet outpatient upper extremity surgery to assess its effect on patient pain, anxiety and fun. Patients undergoing wide-awake local anesthesia no tourniquet surgery were randomized to use (virtual reality) or not use (non-virtual reality) virtual reality during their procedures. Pain, fun, and anxiety were measured with a Likert scale at several time points, as were blood pressure and heart rate. A postoperative questionnaire was used to assess overall satisfaction. Virtual reality patients exhibited lower anxiety scores during injection, during the procedure, and at the end of the procedure. There were no differences in blood pressure, heart rate, or pain scores. Compared with non-virtual reality patients, virtual reality patients' fun scores were higher. Virtual reality patients felt the experience helped them to relax, and they would recommend virtual reality-assisted wide-awake local anesthesia no tourniquet surgery. Among patients with self-reported preexisting anxiety, virtual reality patients had lower pain and anxiety scores during injection of local anesthesia compared with non-virtual reality patients. This study demonstrates that readily available virtual reality hardware and software can provide a virtual reality experience that reduces patient anxiety both during the injection of local anesthesia and during the surgical procedure. (Plast. Reconstr. Surg. 144: 408, 2019.) CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, II.

The use and misuse of herbarium specimens in evaluating plant extinction risks.

Herbarium specimens provide verifiable and citable evidence of the occurrence of particular plants at particular points in space and time, and are vital resources for assessing extinction risk in the tropics, where plant diversity and threats to plants are greatest. We reviewed approaches to assessing extinction risk in response to the Convention on Biological Diversity's Global Strategy for Plant Conservation Target 2: an assessment of the conservation status of all known plant species by 2020. We tested five alternative approaches, using herbarium-derived data for trees, shrubs and herbs in five different plant groups from temperate and tropical regions. All species were previously fully assessed for the IUCN Red List. We found significant variation in the accuracy with which different approaches classified species as threatened or not threatened. Accuracy was highest for the machine learning model (90%) but the least data-intensive approach also performed well (82%). Despite concerns about spatial, temporal and taxonomic biases and uncertainties in herbarium data, when specimens represent the best available evidence for particular species, their use as a basis for extinction risk assessment is appropriate, necessary and urgent. Resourcing herbaria to maintain, increase and disseminate their specimen data is essential to guide and focus conservation action.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.

Complex strain evolution of polar and magnetic order in multiferroic BiFeO3 thin films.

Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO3 and EuTiO3. Despite this critical need, there are few studies on the strain evolution of magnetic order in BiFeO3 films. Here, in (110)-oriented BiFeO3 films, we reveal that while the polarization structure remains relatively unaffected, strain can continuously tune the orientation of the antiferromagnetic-spin axis across a wide angular space, resulting in an unexpected deviation of the classical perpendicular relationship between the antiferromagnetic axis and the polarization. Calculations suggest that this evolution arises from a competition between the Dzyaloshinskii-Moriya interaction and single-ion anisotropy wherein the former dominates at small strains and the two are comparable at large strains. Finally, strong coupling between the BiFeO3 and the ferromagnet Co0.9Fe0.1 exists such that the magnetic anisotropy of the ferromagnet can be effectively controlled by engineering the orientation of the antiferromagnetic-spin axis.

Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of the NRG Oncology RTOG 0517 trial.

BACKGROUND: Skeletal-related events (SREs), common sequelae of metastatic cancer, are reduced by bisphosphonates. In this study, it was postulated that radiopharmaceuticals, added to bisphosphonates, could further decrease the incidence of SREs. METHODS: NRG Oncology RTOG 0517 randomized patients with breast, lung, and prostate cancer and blastic bone metastases to either zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153). The primary endpoint was time to development of SREs. Secondary objectives included quality of life (QOL), pain control, overall survival (OS), and toxicity. RESULTS: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued between July 2006 and February 2011. The study closed early due to a lower than expected rate of SREs. 52 (42%) patients in the ZA arm and 49 (40%) in the radiopharmaceutical arm experienced an SRE. Median time free of SREs was 29.9 and 27.4 months, respectively (p = 0.84). Median OS in the ZA arm and radiopharmaceutical arms was 32.1 and 26.9 months, respectively (p = 0.37). Cox proportional hazards regression model showed that primary disease site (lung) and number of bone metastases (> 2) had a negative impact on OS (p < 0.0001, p = 0.01, respectively). The addition of radiopharmaceuticals to ZA led to a significant reduction in pain at 1 month based on BPI worst score (p = 0.02). No other group differences were noted for QOL or toxicity. CONCLUSION: The addition of radiopharmaceuticals to bisphosphonates did not alter time to SREs or OS for patients with breast, lung, prostate cancers and blastic bone metastases, although it was associated with significant pain reduction at 1 month. CLINICAL TRIAL REGISTRY: This protocol (RTOG 0517) is registered with ClinicalTrials.gov (NCT00365105), and may be viewed online at http://www.clinicaltrials.gov/ct2/show/NCT00365105?term=RTOG+0517&rank=1 .

A Strain-Driven Antiferroelectric-to-Ferroelectric Phase Transition in La-Doped BiFeO3 Thin Films on Si.

A strain-driven orthorhombic (O) to rhombohedral (R) phase transition is reported in La-doped BiFeO3 thin films on silicon substrates. Biaxial compressive epitaxial strain is found to stabilize the rhombohedral phase at La concentrations beyond the morphotropic phase boundary (MPB). By tailoring the residual strain with film thickness, we demonstrate a mixed O/R phase structure consisting of O phase domains measuring tens of nanometers wide within a predominant R phase matrix. A combination of piezoresponse force microscopy (PFM), transmission electron microscopy (TEM), polarization-electric field hysteresis loop (P-E loop), and polarization maps reveal that the O-R structural change is an antiferroelectric to ferroelectric (AFE-FE) phase transition. Using scanning transmission electron microscopy (STEM), an atomically sharp O/R MPB is observed. Moreover, X-ray absorption spectra (XAS) and X-ray linear dichroism (XLD) measurements reveal a change in the antiferromagnetic axis orientation from out of plane (R-phase) to in plane (O-phase). These findings provide direct evidence of spin-charge-lattice coupling in La-doped BiFeO3 thin films. Furthermore, this study opens a new pathway to drive the AFE-FE O-R phase transition and provides a route to study the O/R MPB in these films.