Giant Negative Thermal Expansion Induced by the Synergistic Effects of Ferroelectrostriction and Spin-Crossover in PbTiO3-Based Perovskites

The discovery of unusual negative thermal expansion (NTE) provides the opportunity to control the common but much desired property of thermal expansion, which is valuable not only in scientific interests but also in practical applications. However, most of the available NTE materials are limited to a narrow temperature range, and the NTE effect is generally weakened by means of various modifications. Here, we report an enhanced NTE effect that occurs over a wide temperature range (\alpha V = -5.24 * 10-5 {\deg}C^-1, 25-575 {\deg} C), and this NTE effect is accompanied by an abnormal enhanced tetragonality, a large spontaneous polarization, and a G-type antiferromagnetic ordering in the present perovskite-type ferroelectric of (1-x)PbTiO3-xBiCoO3. Specifically, for the composition of 0.5PbTiO3-0.5BiCoO3, an extensive volumetric contraction of ~4.8 % has been observed near the Curie temperature of 700 {\deg}C, which represents the highest level in PbTiO3-based ferroelectrics. According to our experimental and theoretical results, the giant NTE originates from a synergistic effect of the ferroelectrostriction and spin-crossover of cobalt on the crystal lattice. The actual NTE mechanism is contrasted with previous functional NTE materials, in which the NTE is simply coupled with one ordering such as electronic, magnetic, or ferroelectric ordering. The present study sheds light on the understanding of NTE mechanisms and it attests that NTE could be simultaneouslycoupled with different orderings, which will pave a new way toward the design of large NTE materials.Comment: 30 page

A sensitivity analysis of the New Zealand standard model of foot and mouth disease

Summary Disease simulation models can be a valuable tool for planning a response to exotic disease incursions, as they provide a fast, low-cost mechanism for identifying the likely outcomes of a range of outbreak scenarios and disease control strategies. To use these tools effectively and with confidence, decisionmakers must understand the simplifications and framing assumptions that underlie a model's structure. Sensitivity analysis, the analytical process of identifying which input variables are the key drivers of the model's output, is a crucial process in developing this understanding. This paper describes the application of a sampling-based sensitivity analysis to the New Zealand standard model (NZSM). This model is a parameter set developed for the InterSpread Plus model platform to allow the exploration of different outbreak scenarios for an epidemic of foot and mouth disease in New Zealand. Based on 200 iterations of the NZSM, run for a simulation period of 60 days, settings related to farm-to-saleyard movements and the detection of disease during the active surveillance phase of the epidemic had the greatest influence on the predicted number of infected premises. A small number of counter-intuitive findings indicated areas of model design, implementation and/or parameterisation that should be investigated further. A potentially useful result from this work would be information to aid the grouping or elimination of non-influential model settings. This would go some way towards reducing the overall complexity of the NZSM, while still allowing it to remain fit for purpose

Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study

Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

BACKGROUND Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. METHODS AND DESIGN A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. DISCUSSION TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12613000939796

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

BACKGROUND: Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES: To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. METHODS AND DESIGN: A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. DISCUSSION: TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN1261300093979

Thrombolysis ImPlementation in Stroke (TIPS): Evaluating the effectiveness of a strategy to increase the adoption of best evidence practice - protocol for a cluster randomised controlled trial in acute stroke care

Background: Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke.Objectives: To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months.Methods and design: A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mR