Emergent Magnetism with Continuous Control in the Ultrahigh-Conductivity Layered Oxide PdCoO2.

The current challenge to realizing continuously tunable magnetism lies in our inability to systematically change properties, such as valence, spin, and orbital degrees of freedom, as well as crystallographic geometry. Here, we demonstrate that ferromagnetism can be externally turned on with the application of low-energy helium implantation and can be subsequently erased and returned to the pristine state via annealing. This high level of continuous control is made possible by targeting magnetic metastability in the ultrahigh-conductivity, nonmagnetic layered oxide PdCoO2 where local lattice distortions generated by helium implantation induce the emergence of a net moment on the surrounding transition metal octahedral sites. These highly localized moments communicate through the itinerant metal states, which trigger the onset of percolated long-range ferromagnetism. The ability to continuously tune competing interactions enables tailoring precise magnetic and magnetotransport responses in an ultrahigh-conductivity film and will be critical to applications across spintronics.

The impact of genomic context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review.

INTRODUCTION: A critical need in the field of genotype-matched targeted therapy in cancer is to identify patients unlikely to respond to precision medicines. This will manage expectations of individualised therapies and avoid clinical progression to a point where institution of alternative treatments might not be possible. We examined the evidence base of the impact of genomic context on which targeted alterations are inscribed to identify baseline biomarkers distinguishing those obtaining the expected response from those with less benefit from targeted therapies. METHODS: A comprehensive narrative review was conducted: scoping searches were undertaken in PubMed, Cochrane Database of Systematic Reviews, and PROSPERO. Outcomes included in meta-analysis were progression-free and overall survival. Data were extracted from Kaplan-Meier and used to calculate hazard ratios. Studies presenting data on two molecular subcohorts (e.g. co-mutation versus no co-mutation) were included in fixed meta-analysis. Other studies were used for descriptive purposes. RESULTS: The presence of concomitant driver mutations, higher tumour mutational burden (TMB), greater copy number burden, and APOBEC signatures significantly reduces benefits of targeted therapy in lung cancers in never smokers (LCINS - less than 100 cigarettes per lifetime) and breast cancer, cancers with low TMB. LCINS have significantly poorer outcomes if their cancers harbour p53 co-mutations, an effect also seen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients (trastuzumab) and head and neck cancer patients [phosphoinositide 3-kinase (PI3K) inhibition]. PI3K co-alterations have less impact when targeting epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions, but significantly reduce the impact of targeting HER2 and MET amplifications. SMARCA4 co-mutations predict for poor outcome in patients treated with osimertinib and sotorasib. In BRAF-mutant melanoma, whilst there are no genomic features distinguishing exceptional responders from primary progressors, there are clear transcriptomic features dichotomising these outcomes. CONCLUSION: To our knowledge, this is the most comprehensive review to date of the impact of genomic context on outcomes with targeted therapy. It represents a valuable resource informing progress towards contextualised precision medicine.

Observing a previously hidden structural-phase transition onset through heteroepitaxial cap response.

Characterization of the onset of a phase transition is often challenging due to the fluctuations of the correlation length scales of the order parameters. This is especially true for second-order structural-phase transition due to minute changes involved in the relevant lattice constants. A classic example is the cubic-to-tetragonal second-order phase transition in SrTiO3 (STO), which is so subtle that it is still unresolved. Here, we demonstrate an approach to resolve this issue by epitaxially grown rhombohedral La0.7Sr0.3MnO3 (LSMO) thin films on the cubic STO (100) substrate. The shear strain induced nanotwinning waves in the LSMO film are extremely sensitive to the cubic-to-tetragonal structural-phase transitions of the STO substrate. Upon cooling from room temperature, the development of the nanotwinning waves is spatially inhomogeneous. Untwinned, atomically flat domains, ranging in size from 100 to 300 nm, start to appear randomly in the twinned phase between 265 and 175 K. At ∼139 K, the untwinned, atomically flat domains start to grow rapidly into micrometer scale and finally become dominant at ∼108 K. These results indicate that the low-temperature tetragonal precursor phase of STO has already nucleated at 265 K, significantly higher than the critical temperature of STO (∼105 K). Our work paves a pathway to visualize the onset stages of structural-phase transitions that are too subtle to be observed using direct-imaging methods.

Preserving US microbe collections sparks future discoveries.

Collections of micro-organisms are a crucial element of life science research infrastructure but are vulnerable to loss and damage caused by natural or man-made disasters, the untimely death or retirement of personnel, or the loss of research funding. Preservation of biological collections has risen in priority due to a new appreciation for discoveries linked to preserved specimens, emerging hurdles to international collecting and decreased funding for new collecting. While many historic collections have been lost, several have been preserved, some with dramatic rescue stories. Rescued microbes have been used for discoveries in areas of health, biotechnology and basic life science. Suggestions for long-term planning for microbial stocks are listed, as well as inducements for long-term preservation.

Exploiting Symmetry Mismatch to Control Magnetism in a Ferroelastic Heterostructure.

In the bulk, LaCoO_{3} (LCO) is a paramagnet, yet the low-temperature ferromagnetism (FM) is observed in tensile strained thin films, and its origin remains unresolved. Here, we quantitatively measured the distribution of atomic density and magnetization in LCO films by polarized neutron reflectometry (PNR) and found that the LCO layers near the heterointerfaces exhibit a reduced magnetization but an enhanced atomic density, whereas the film's interior (i.e., its film bulk) shows the opposite trend. We attribute the nonuniformity to the symmetry mismatch at the interface, which induces a structural distortion related to the ferroelasticity of LCO. This assertion is tested by systematic application of hydrostatic pressure during the PNR experiments. The magnetization can be controlled at a rate of -20.4% per GPa. These results provide unique insights into mechanisms driving FM in strained LCO films while offering a tantalizing observation that tunable deformation of the CoO_{6} octahedra in combination with the ferroelastic order parameter.

Photodissociation of Manganese Oxide Cluster Cations.

Manganese oxide cluster cations are produced by laser vaporization in a pulsed nozzle source and detected with time-of-flight mass spectrometry. The mass spectrum contains intense peaks for stoichiometries corresponding to (MnO) n+. Multiphoton photodissociation of these clusters yields smaller ions with the same stoichiometric ratio, either by sequential elimination of MnO units or by various fission processes with roughly equal efficiencies. Fragmentation of clusters containing excess oxygen also yields (MnO) n+ fragments. These apparently stable fragments are investigated further using density functional theory to determine their likely structures. The lowest energy structure for Mn2O2+ is found to be a planar ring, and those for Mn4O4+ and Mn6O6+ are cuboids. Mn3O3+ is predicted to have a six-membered ring structure and Mn5O5+ has a fused cube/ring configuration similar to the structure of the oxygen evolving center of Photosystem II. Open-shell, high-spin configurations on individual manganese atoms couple antiferromagnetically and ferromagnetically to produce low-spin and high-spin configurations on different sized clusters.

Cost analysis of robot-assisted choledochotomy and common bile duct exploration as an option for complex choledocholithiasis.

AIM: The aim of this study is to evaluate the clinical outcomes and cost-effectiveness of elective, robot-assisted choledochotomy and common bile duct exploration (RCD/CBDE) compared to open surgery for ERCP refractory choledocholithiasis. METHOD: A prospective database of all RCD/CBDE has been maintained since our first procedure in April 2007 though April 2016. With ethics approval, this database was compared with all contemporaneous elective open procedures (OCD/CBDE) performed since March 2005. Emergency procedures were excluded from analysis. Cost analysis was calculated using a micro-costing approach. Outcomes were analyzed on the basis of intent-to-treat. A p value of 0.05 denoted statistical significance. RESULTS: A total of 80 cases were performed since 2005 compromising 50 consecutive, unselected RCD/CBDE and 30 OCD/CBDE. Comparing RCD/CBDE to OCD/CBDE there were no significant differences between groups with respect to age (65 ± 20 vs. 67 ± 18 years, p = 0.09), gender (14/30 vs. 16/25 male/female, p = 0.52), ASA class or co-morbidities. The mean duration of surgery for RCD/CBDE trended longer compared to OCD/CBDE (205 ± 70 min vs. 174 ± 73 min, p = 0.08). However, there was significant reduction in postoperative complications with RCD/CBDE versus OCD/CBDE (22% vs. 56%, p = 0.002). Median hospital stay was also significantly reduced (6 vs 12 days, p = 0.01). The net overall hospital cost for RCD/CBDE was lower ($8449.88 CAD vs. $11671.2 CAD). CONCLUSION: In this single-centre, cohort study, robotic-assisted CD/CBDE for ERCP refractory common bile duct stones provides the dominating strategy of improved patient outcomes with a reduction of overall cost.

A Statewide Hospital-Based Safe Infant Sleep Initiative: Measurement of Parental Knowledge and Behavior.

Sleep-related infant deaths are a leading cause of infant mortality in Georgia, and these deaths are largely associated with unsafe sleep practices among caregivers. In early 2016, the Georgia Department of Public Health launched the Georgia Safe to Sleep Hospital Initiative, providing hospitals with safe infant sleep information and educational materials to be distributed to families and newborns. This study examined the knowledge and behaviors of a sample of Georgia parents after the implementation of the Hospital Initiative and identified the family characteristics and intervention components most closely associated with the knowledge and practice of safe infant sleep. The primary caretakers of all infants born in Georgia from August to October 2016 were invited to complete a web-based survey 1 month after hospital discharge. The final sample size included 420 parents of newborns, and the primary outcomes assessed included two measures of knowledge and four measures of infant sleep behaviors regarding infant sleep position and location. Most respondents demonstrated knowledge of the correct recommended sleep position (90%) and location (85%). Logistic regression revealed that receipt of information in the hospital was significantly correlated with safe sleep behaviors, and infant sleep habits tended to influence safe sleep practices. Additionally, Medicaid parents receiving bassinets from the hospital were 74% less likely to bed share (OR 0.26; 95% CI 0.007). Implementation of a statewide hospital initiative was associated with high levels of parental knowledge and behavior and may have been successful in reducing the practice of bed sharing among Medicaid parents.

Reversible Control of Interfacial Magnetism through Ionic-Liquid-Assisted Polarization Switching.

The ability to control magnetism of materials via electric field enables a myriad of technological innovations in information storage, sensing, and computing. We use ionic-liquid-assisted ferroelectric switching to demonstrate reversible modulation of interfacial magnetism in a multiferroic heterostructure composed of ferromagnetic (FM) La0.8Sr0.2MnO3 and ferroelectric (FE) PbZr0.2Ti0.8O3. It is shown that ionic liquids can be used to persistently and reversibly switch a large area of a FE film. This is a prerequisite for polarized neutron reflectometry (PNR) studies that are conducted to directly probe magnetoelectric coupling of the FE polarization to the interfacial magnetization.

Individual isotopic specializations predict subsequent inter-individual variation in movement in a freshwater fish.

Despite many similarities and intuitive links between individual dietary specialization and behavioral inter-individual variation, these phenomena have been studied in isolation, and empirical data confirming relationships between these intraspecific variance sources are lacking. Here we use stable isotope analysis and acoustic telemetry to test the hypothesis that individual specialization in trophic (δ15 N) and littoral/pelagic prey reliance (δ13 C) covary with inter-individual variation in movement in a group of 34 free-swimming burbot (Lota lota). By performing stable isotope analysis on tissues with differing isotopic turnover rates (anal fin and dorsal muscle), in 24 lethally sampled burbot, we demonstrate that individual specialization in trophic niche (δ15 N) and littoral/pelagic prey reliance (δ13 C) occurred within the population. By performing stable isotope analysis on anal fins of a group of telemetry tagged burbot, we were able to show that interactions between trophic niche and littoral/pelagic prey reliance, explained a significant proportion of the subsequent between-individual variance in mean movement rates. These findings demonstrate an empirical connection between behavioral inter-individual variation and dietary specialization, thus providing a substantial expansion of our understanding of the wider ecological consequences of these interesting phenomena.

Re-calculating! Navigating through the osteosarcoma treatment roadblock.

The survival rates for patients with osteosarcoma have remained almost static for the past three decades. Current standard of care therapy includes chemotherapies such as doxorubicin, cisplatin, and methotrexate along with complete surgical resection and surgery with or without ifosfamide and etoposide for relapse, though outcomes are hoped to be improved through clinical trials. Additionally, increased understanding of the genetics, signaling pathways and microenvironmental factors driving the disease have led to the identification of promising agents and potential paths towards translation of an exciting array of novel targeted therapies. Here, we review the mechanism of action of these emerging therapies and how, with clinical translation, they can potentially improve the survival rates for osteosarcoma patients in the near future.

Ortho-para interconversion in cation-water complexes: The case of V+(H2O) and Nb+(H2O) clusters.

Vanadium and niobium cation-water complexes, V+(H2O) and Nb+(H2O), are produced by laser vaporization in a pulsed supersonic expansion, mass selected in a time-of-flight spectrometer, and studied with infrared photodissociation spectroscopy using rare gas atom (Ar, Ne) complex predissociation. The vibrational bands measured in the O-H stretching region contain K-type rotational sub-band structure, which provides insight into the structures of these complexes. However, rotational sub-bands do not exhibit the simple patterns seen previously for other metal ion-water complexes. The A rotational constants are smaller than expected and the normal 3:1 intensity ratios for K = odd:even levels for independent ortho:para nuclear spin states are missing for some complexes. We relied on highly correlated internally contracted multi-reference configuration interaction and Coupled Cluster [CCSD(T)] electronic structure calculations of those complexes with and without the rare gas atoms to investigate these anomalies. Rare gas atoms were found to bind via asymmetric motifs to the hydrated complexes undergoing large amplitude motions that vibrationally average to the quasi-C2v symmetry with a significant probability off the C2 axis, thus explaining the reduced A values. Both vanadium and niobium cations exhibit unusually strong nuclear spin coupling to the hydrogen atoms of water, the values of which vary with their electronic state. This catalyzes ortho-para interconversion in some complexes and explains the rotational patterns. The rate of ortho-para relaxation in the equilibrated complexes must therefore be greater than the collisional cooling rate in the supersonic expansion (about 106 s-1).

Schwann cells generated from neonatal skin-derived precursors or neonatal peripheral nerve improve functional recovery after acute transplantation into the partially injured cervical spinal cord of the rat.

The transplantation of Schwann cells (SCs) holds considerable promise as a therapy for spinal cord injury, but the optimal source of these cells and the best timing for intervention remains debatable. Previously, we demonstrated that delayed transplantation of SCs generated from neonatal mouse skin-derived precursors (SKP-SCs) promoted repair and functional recovery in rats with thoracic contusions. Here, we conducted two experiments using neonatal rat cells and an incomplete cervical injury model to examine the efficacy of acute SKP-SC transplantation versus media control (Experiment 1) and versus nerve-derived SC or dermal fibroblast (Fibro) transplantation (Experiment 2). Despite limited graft survival, by 10 weeks after injury, rats that received SCs from either source showed improved functional recovery compared with media- or fibroblast-treated animals. Compared with media treatment, SKP-SC-transplanted rats showed enhanced rubrospinal tract (RST) sparing/plasticity in the gray matter (GM) rostral to injury, particularly in the absence of immunosuppression. The functional benefits of SC transplantations over fibroblast treatment correlated with the enhanced preservation of host tissue, reduced RST atrophy, and/or increased RST sparing/plasticity in the GM. In summary, our results indicate that: (1) early transplantation of neonatal SCs generated from skin or nerve promotes repair and functional recovery after incomplete cervical crush injury; (2) either of these cell types is preferable to Fibros for these purposes; and (3) age-matched SCs from these two sources do not differ in terms of their reparative effects or functional efficacy after transplantation into the injured cervical spinal cord.

Full Electroresistance Modulation in a Mixed-Phase Metallic Alloy.

We report a giant, ∼22%, electroresistance modulation for a metallic alloy above room temperature. It is achieved by a small electric field of 2 kV/cm via piezoelectric strain-mediated magnetoelectric coupling and the resulting magnetic phase transition in epitaxial FeRh/BaTiO_{3} heterostructures. This work presents detailed experimental evidence for an isothermal magnetic phase transition driven by tetragonality modulation in FeRh thin films, which is in contrast to the large volume expansion in the conventional temperature-driven magnetic phase transition in FeRh. Moreover, all the experimental results in this work illustrate FeRh as a mixed-phase model system well similar to phase-separated colossal magnetoresistance systems with phase instability therein.

Tackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences.

OBJECTIVES: The hepatitis C virus (HCV) remains a significant public health issue. This study aimed to quantify the clinical and economic burden of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, with concurrent assessment of the impact of implementing a treatment prioritization approach. STUDY DESIGN AND METHODS: A previously published back projection, natural history and cost-effectiveness HCV model was adapted to a UK setting to estimate the disease burden of chronic hepatitis C and end-stage liver disease (ESLD) between 1980 and 2035. A published meta-regression analysis informed disease progression, and UK-specific data informed other model inputs. RESULTS: At 2015, prevalence of chronic hepatitis C is estimated to be 241,487 with 22.20%, 33.72%, 17.22%, 16.67% and 10.19% of patients in METAVIR stages F0, F1, F2, F3 and F4, respectively, but is estimated to fall to 193,999 by 2035. ESLD incidence is predicted to peak in 2031. Assuming all patients are diagnosed and treatment is prioritized in F3 and F4 using highly efficacious direct-acting antiviral (DAA) regimens, a 69.85% reduction in ESLD incidence is predicted between 2015 and 2035, and the cumulative discounted medical expenditure associated with the lifetime management of incident ESLD events is estimated to be £1,202,827,444. CONCLUSIONS: The prevalence of chronic hepatitis C is expected to fall in coming decades; however, the ongoing financial burden is expected to be high due to an increase in ESLD incidence. This study highlights the significant costs of managing ESLD that are likely to be incurred without the employment of effective treatment approaches.

Ferromagnetism and nonmetallic transport of thin-film α-FeSi(2): a stabilized metastable material.

A metastable phase α-FeSi_{2} was epitaxially stabilized on a silicon substrate using pulsed laser deposition. Nonmetallic and ferromagnetic behaviors are tailored on α-FeSi_{2} (111) thin films, while the bulk material of α-FeSi_{2} is metallic and nonmagnetic. The transport property of the films renders two different conducting states with a strong crossover at 50 K, which is accompanied by the onset of a ferromagnetic transition as well as a substantial magnetoresistance. These experimental results are discussed in terms of the unusual electronic structure of α-FeSi_{2} obtained within density functional calculations and Boltzmann transport calculations with and without strain. Our finding sheds light on achieving ferromagnetic semiconductors through both their structure and doping tailoring, and provides an example of a tailored material with rich functionalities for both basic research and practical applications.

Characterization of Fusarium Strains Recovered From Wheat With Symptoms of Head Blight in Kentucky.

Fusarium graminearum species complex (FGSC) members cause Fusarium head blight (FHB) of wheat (Triticum aestivum L.) and small grains in the United States. The U.S. population is diverse and includes several genetically distinct local emergent subpopulations, some more aggressive and toxigenic than the majority population. Kentucky is a transition zone between the Mid-Atlantic and Midwestern wheat production areas. Sixty-eight Fusarium strains were isolated from symptomatic wheat heads from central and western Kentucky and southern Indiana in 2007. A multilocus genotyping assay and a variety of additional molecular markers, including some novel markers developed using the F. graminearum genome sequence, were used to characterize the pathogen population. Five of the isolates were identified as members of two non-FGSC species, F. acuminatum and F. cf. reticulatum, but they did not cause symptoms in greenhouse tests. All the FGSC isolates belonged to the 15-ADON chemotype of F. graminearum. Comparative genetic analysis using variable nuclear tandem repeat (VNTR) markers indicated that the population in Kentucky and Indiana belonged to the dominant North American population, with some diversification likely due to local evolution. Telomere and RFLP fingerprinting markers based on repetitive sequences revealed a high degree of genetic diversity within the population, with unique genotypes found at each location, and multiple genotypes isolated from the same head.

Similar scaling of contralateral and ipsilateral cortical responses during graded unimanual force generation.

Hemibody movements are strongly considered as being under the control of the contralateral hemisphere of the cerebral cortex. However, some neuroimaging studies have found a bilateral activation of either the primary sensori-motor (SM1) areas or the rostral prefrontal cortex (PFC), during unimanual tasks. More than just bilateral, the activation of these areas was found to be symmetrical in some studies. However, the symmetrical response remains strongly controversial notably for handgrip force generations. We therefore aimed to examine the bilateral SM1 and rostral PFC area activations in response to graded submaximal force generation during a unilateral handgrip task. Fifteen healthy subjects performed 6 levels of force (ranging from 5 to 50% of MVC) during a handgrip task. We concomitantly measured the activation of bilateral SM1 and rostral PFC areas through near-infrared spectroscopy (NIRS) and the electromyographic (EMG) activity of the bilateral flexor digitorum superficialis (FDS) muscles. Symmetrical activation was found over the SM1 areas for all the investigated levels of force. At the highest level of force (i.e., 50% of MVC), the EMG of the passive FDS increased significantly and the ipsilateral rostral PFC activation was found more intense than the corresponding contralateral rostral PFC activation. We suggest that the visuo-guided control of force levels during a handgrip task requires the cross-talk from ipsi- to contralateral SM1 to cope for the relative complexity of the task, similar to that which occurs during complex sequential finger movement. We also propose alternative explanations for the observed symmetrical SM1 activation including (i) the ipsilateral corticospinal tract and (ii) interhemispheric inhibition (IHI) mechanism. The increase in EMG activity over the passive FDS could be associated with a release of IHI at 50% of MVC. Finally, our results suggest that the greater ipsilateral (right) rostral PFC activation may reflect the greater demand of attention required to control the motor output at high levels of force.

Temporal dynamics and population genetic structure of Fusarium graminearum in the upper Midwestern United States.

Fusarium graminearum sensu stricto causes Fusarium head blight (FHB) in wheat and barley, and contaminates grains with several trichothecene mycotoxins, causing destructive yield losses and economic impact in the United States. Recently, a F. graminearum strain collected from Minnesota (MN) was determined to produce a novel trichothecene toxin, called NX-2. In order to determine the spatial and temporal dynamics of NX-2 producing strains in MN, North Dakota (ND) and South Dakota (SD), a total of 463 F. graminearum strains were collected from three sampling periods, 1999-2000, 2006-2007 and 2011-2013. A PCR-RFLP based diagnostic test was developed and validated for NX-2 producing strains based on polymorphisms in the Tri1 gene. Trichothecene biosynthesis gene (Tri gene)-based polymerase chain reaction (PCR) assays and ten PCR-restriction fragment length polymorphism (RFLP) markers were used to genotype all strains. NX-2 strains were detected in each sampling period but with a very low overall frequency (2.8%) and were mainly collected near the borders of MN, ND and SD. Strains with the 3ADON chemotype were relatively infrequent in 1999-2000 (4.5%) but increased to 29.4% in 2006-2007 and 17.2% in 2011-2013. The distribution of 3ADON producing strains also expanded from a few border counties between ND and MN in 1999-2000, southward toward the border between SD and MN in 2006-2007 and westward in 2011-2013. Genetic differentiation between 2006-2007 and 2011-2013 populations (3%) was much lower than that between 1999-2000 and 2006-2007 (22%) or 1999-2000 and 2011-2013 (20%) suggesting that most change to population genetic structure of F. graminearum occurred between 1999-2000 and 2006-2007. This change was associated with the emergence of a new population consisting largely of individuals with a 3ADON chemotype. A Bayesian clustering analysis suggested that NX-2 chemotype strains are part of a previously described Upper Midwestern population. However, these analyses also suggest that the NX-2 isolates could represent a distinct population, but that interpretations of population assignment are influenced by the small number of NX-2 strains available for analysis.