Trends in different contraception methods among women attending the Melbourne Sexual Health Centre from 2011 to 2020.

OBJECTIVES: The efficacy and availability of contraception have changed in the last several decades; however, unintended pregnancies continue to be an issue in Australia. This study aimed to describe trends in contraception in women attending a sexual health service over 9 years. STUDY DESIGN: Repeated cross-sectional study. METHODS: Women aged 16-49 years attending Melbourne Sexual Health Centre between 2011 and 2020 were included. Women were asked what methods of contraception they currently use. Contraception were categorised into long-acting reversible contraception (LARC; e.g. intrauterine devices and implants classified as highly effective), moderately effective contraception (e.g. oral contraception pill), less effective contraception (e.g. condom and withdrawal) and no contraception, as defined by US Centers for Disease Control and Prevention guidelines. Multivariable logistic regression was used to examine the factors associated with the use of moderate-high-efficacy contraception. RESULTS: A total of 38,288 women were included with a median age of 25 (interquartile range: 22-29). Between 2011 and 2020, there was a decreasing trend in condom (63.3%-56.1%; Ptrend <0.001) and oral contraception (27.2%-20.5%; Ptrend <0.001) use, whilst there was an increasing trend in the use of LARCs: implant (4.6%-6.0%; Ptrend = 0.002) and intrauterine device (2.8%-11.8%; Ptrend <0.001). Increasing age was associated with decreased odds of using moderate-high-efficacy contraception (Ptrend <0.001). Compared with Oceanian-born women, Asian (adjusted odds ratios [aOR] = 0.63, 95% confidence interval [CI]: 0.56-0.72) and Middle Eastern-born women (aOR = 0.60, 95% CI: 0.48-0.74) had lower odds of using moderate-high-efficacy contraception, whilst European (aOR = 1.23, 95% CI:1.07-1.41) and North American-born women (aOR = 1.51, 95% CI: 1.22-1.87) had higher odds of using moderate-high-efficacy contraception. CONCLUSIONS: Between 2011 and 2020, LARC use has increased, whilst less effective contraceptives, such as condom and oral contraception, have decreased among women at Melbourne Sexual Health Centre. Further research is required to understand age and ethnic disparities in contraception methods for future family planning programmes.

Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders.

PURPOSE: Tumour genomic profiling is of increasing importance in early phase trials to match patients to targeted therapeutics. Mutations vary by demographic group; however, regional differences are not characterised. This was investigated by comparing mutation prevalence for common cancers presenting to Newcastle Experimental Cancer Medicine Centre (ECMC) to The Cancer Genome Atlas (TCGA) and utility of trial matching modalities. METHODS: Detailed clinicogenomic data were obtained for patients presenting September 2017-December 2020. Prevalence of mutations in lung, colorectal, breast and prostate cancer was compared to TCGA GDC Data Portal. Experimental Cancer (EC) Trial Finder utility in matching trials was compared to a Molecular Tumour Board (MTB) and commercial sequencing reports. RESULTS: Of 311 patients with advanced cancer, this consisted of lung (n = 131, 42.1%), colorectal (n = 44, 14.1%), breast (n = 36, 11.6%) and prostate (n = 18, 5.6%). More than one mutation was identified in the majority (n = 260, 84%). Significant prevalence differences compared to TCGA were identified, including a high prevalence of EGFR in lung (P = 0.001); RB1 in breast (P = 0.0002); and multiple mutations in prostate cancer. EC Trial Finder demonstrated significantly different utility than sequencing reports in identifying trials (P = 0.007). CONCLUSIONS: Regional differences in mutations may exist with advanced stage accounting for prevalence of specific mutations. A national Trial Finder shows utility in finding targeted trials whilst commercial sequencing reports may over-report 'actionable' mutations. Understanding local prevalence and trial availability could increase enrolment onto matched early phase trials.

Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Formation of dislocations via misfit strain across interfaces in epitaxial BaTiO3and SrIrO3heterostructures.

Dislocations often occur in thin films with large misfit strain as a result of strain energy accumulation and can drastically change the film properties. Here the structure and dislocations in oxide heterostructures with large misfit strain are investigated on atomic scale. When grown on SrTiO3(001), the dislocations in both the monolithic BaTiO3thin film and its superlattices with SrIrO3appear above a critical thickness around 6 nm. The edge component of the dislocations is seen in both cases with the Burgers vector ofa⟨100⟩. However, compared to monolithic BaTiO3, the dislocation density is slightly lower in BaTiO3/SrIrO3superlattices. In the superlattice, when considering the SrTiO3lattice constant as the reference, BaTiO3has a larger misfit strain comparing with SrIrO3. It is found that in both cases, the formation of dislocation is only affected by the critical thickness of the film with larger lattice misfit (BaTiO3), regardless of the existence of a strong octahedral tilt/rotation mismatch at BaTiO3/SrIrO3interface. Our findings suggest that it is possible to control the position of dislocations, an important step toward defect engineering.

Sex is associated with the persistence of non-optimal vaginal microbiota following treatment for bacterial vaginosis: a prospective cohort study.

OBJECTIVE: Determine the associations between factors and sexual practices and the composition of the vaginal microbiome (VM) of women treated for bacterial vaginosis (BV). DESIGN: Prospective cohort study. SETTING: The Melbourne Sexual Health Centre, Melbourne, Australia. POPULATION: Seventy-five reproductive-age women diagnosed with clinical BV, treated with first-line antibiotics and followed for up to 6 months. METHODS: Women self-collected vaginal swabs and completed questionnaires at enrolment, the day following antibiotics and monthly for up to 6months until BV recurrence or no BV recurrence (n = 430 specimens). Bacterial composition was determined using 16S rRNA gene amplicon sequencing. The effects of ongoing factors on VM composition (utilising 291 monthly specimens) were assessed using generalised estimating equations population-averaged models, which accounted for repeated measures within individuals. MAIN OUTCOME MEASURES: The relative abundance of vaginal bacterial taxa. RESULTS: Women who reported ongoing sex with a regular sexual partner (RSP) had a VM comprised of increased relative abundance of non-optimal BV-associated bacteria (Adjusted co-efficient [Adjusted co-eff] = 11.91, 95% CI 3.39to20.43, P = 0.006) and a decreased relative abundance of optimal, Lactobacillus species (Adjusted co-eff = -12.76, 95% CI -23.03 to -2.49, P = 0.015). A history of BV was also associated with a decreased relative abundance of Lactobacillus spp. (Adjusted co-eff = -12.35, 95% CI -22.68, P = 0.019). The relative abundance of Gardnerella, Atopobium and Sneathia spp. increased following sex with an RSP. CONCLUSIONS: Sex with an untreated RSP after BV treatment was associated with a VM comprised of non-optimal BV-associated bacteria. BV treatment approaches may need to include partner treatment if they are to achieve a sustained optimal VM associated with improved health outcomes. TWEETABLE ABSTRACT: Sex drives a return to a 'non-optimal' vaginal microbiota after antibiotics for bacterial vaginosis.

A custom amplicon sequencing approach to detect resistance associated mutations and sequence types in Mycoplasma genitalium.

BACKGROUND: Mycoplasma genitalium resistance to antibiotic treatments is increasing, with very limited treatment alternatives on the horizon. Surveillance via sequencing of multiple M. genitalium loci would allow: monitoring of known antibiotic resistance mutations, associations between resistance/treatment failure and specific mutations, and strain typing for epidemiological purposes. In this study we assessed the performance of a custom amplicon sequencing approach, which negates the cost of library preparation for next generation sequencing. METHODS: Fifty-two M. genitalium positive samples (cervical, vaginal, anal and rectal swabs, and urine) were used. Three regions associated with M. genitalium antibiotic resistance (23S rRNA, parC and gyrA genes) were targeted, in conjunction with a locus used for differentiation of sequence types in the mgpB gene, and findings compared to Sanger sequencing. RESULTS: Amplicon sequencing provided adequate sequence read coverage (>30×) for the majority of samples for 23S rRNA gene (96%) and mgpB (97%), parC (78%) and gyrA (75%). Single nucleotide polymorphisms (SNPs) were characterised in samples for 23S rRNA gene (94%), parC (56%) and gyrA (4%). Unlike Sanger sequencing, mixed mutations could be identified by the amplicon sequencing method, and ratios of mutation types determined. All results, with one exception, were concordant to Sanger sequence results. Sequence diversity in the mgpB region was represented by 15 sequence types, 4 being observed in multiple samples. CONCLUSIONS: We have demonstrated the utility of this custom amplicon sequencing approach for generating highly informative datasets with the capacity to identify and determine ratios of mixed sequences. The use of this customisable amplicon sequencing method enables cost effective, scalable amplicon sequencing of multiple target regions of interest in M. genitalium.

Emergent Spin Glass Behavior Created by Self-Assembled Antiferromagnetic NiO Columns in Ferrimagnetic NiFe2O4.

Spin glass (SG) is a magnetic state with spin structure incommensurate with lattice and charge. Fundamental understanding of its behavior has a profound impact on many technological problems. Here, we present a novel case of interface-induced spin glass behavior via self-assembly of single-crystalline NiO microcolumns in a single-crystalline NiFe2O4 matrix. Scanning transmission electron microscopy indicates that the hexagonal-shaped NiO columns are along their [211] direction and oriented along the [111] direction of the NiFe2O4 matrix. Magnetic force microscopy reveals magnetic anisotropy between NiO columns (antiferromagnetic transition temperature TN ∼ 523 K) and NiFe2O4 matrix (ferrimagnetic transition temperature TFI ∼ 860 K). This leads to spin disorder/frustration at atomically sharp NiFe2O4/NiO interfaces responsible for spin glass behavior below TSG ∼ 28 K. Our results demonstrate that self-assembly of magnetically distinct microstructures into another crystalline and magnetically ordered matrix is an effective way to create novel spin states at interfaces.

Interface-induced magnetic polar metal phase in complex oxides.

Polar metals are commonly defined as metals with polar structural distortions. Strict symmetry restrictions make them an extremely rare breed as the structural constraints favor insulating over metallic phase. Moreover, no polar metals are known to be magnetic. Here we report on the realization of a magnetic polar metal phase in a BaTiO3/SrRuO3/BaTiO3 heterostructure. Electron microscopy reveals polar lattice distortions in three-unit-cells thick SrRuO3 between BaTiO3 layers. Electrical transport and magnetization measurements reveal that this heterostructure possesses a metallic phase with high conductivity and ferromagnetic ordering with high saturation moment. The high conductivity in the SrRuO3 layer can be attributed to the effect of electrostatic carrier accumulation induced by the BaTiO3 layers. Density-functional-theory calculations provide insights into the origin of the observed properties of the thin SrRuO3 film. The present results pave a way to design materials with desired functionalities at oxide interfaces.

Raman interrogation of the ferroelectric phase transition in polar metal LiOsO3.

Ferroelectric (FE) distortions in a metallic material were believed to be experimentally inaccessible because itinerant electrons would screen the long-range Coulomb interactions that favor a polar structure. It has been suggested by Anderson and Blount [P. W. Anderson, E. I. Blount, Phys. Rev. Lett. 14, 217-219 (1965)] that a transition from paraelectric phase to FE phase is possible for a metal if, in the paraelectric phase, the electrons at the Fermi level are decoupled from the soft transverse optical phonons, which lead to ferroelectricity. Here, using Raman spectroscopy combined with magnetotransport measurements on a recently discovered FE metal LiOsO3, we demonstrate active interplay of itinerant electrons and the FE order: Itinerant electrons cause strong renormalization of the FE order parameter, leading to a more gradual transition in LiOsO3 than typical insulating FEs. In return, the FE order enhances the anisotropy of charge transport between parallel and perpendicular to the polarization direction. The temperature-dependent evolution of Raman active in-plane 3Eg phonon, which strongly couples to the polar-active out-of-the-plane A2u phonon mode in the high-temperature paraelectric state, exhibits a deviation in Raman shift from the expectation of the pseudospin-phonon model that is widely used to model many insulating FEs. The Curie-Weiss temperature (θ ≈ 97 K) obtained from the optical susceptibility is substantially lower than T s, suggesting a strong suppression of FE fluctuations. Both line width and Fano line shape of 3Eg Raman mode exhibit a strong electron-phonon coupling in the high-temperature paraelectric phase, which disappears in the FE phase, challenging Anderson/Blount's proposal for the formation of FE metals.

Atomic-scale determination of spontaneous magnetic reversal in oxide heterostructures.

Interfaces between transition metal oxides are known to exhibit emerging electronic and magnetic properties. Here we report intriguing magnetic phenomena for La2/3Sr1/3MnO3 films on an SrTiO3 (001) substrate (LSMO/STO), where the interface governs the macroscopic properties of the entire monolithic thin film. The interface is characterized on the atomic level utilizing scanning transmission electron microscopy and electron energy loss spectroscopy (STEM-EELS), and density functional theory (DFT) is employed to elucidate the physics. STEM-EELS reveals mixed interfacial stoichiometry, subtle lattice distortions, and oxidation-state changes. Magnetic measurements combined with DFT calculations demonstrate that a unique form of antiferromagnetic exchange coupling appears at the interface, generating a novel exchange spring-type interaction that results in a remarkable spontaneous magnetic reversal of the entire ferromagnetic film, and an inverted magnetic hysteresis, persisting above room temperature. Formal oxidation states derived from electron spectroscopy data expose the fact that interfacial oxidation states are not consistent with nominal charge counting. The present work demonstrates the necessity of atomically resolved electron microscopy and spectroscopy for interface studies. Theory demonstrates that interfacial nonstoichiometry is an essential ingredient, responsible for the observed physical properties. The DFT-calculated electrostatic potential is flat in both the LSMO and STO sides (no internal electric field) for both Sr-rich and stoichiometric interfaces, while the DFT-calculated charge density reveals no charge transfer/accumulation at the interface, indicating that oxidation-state changes do not necessarily reflect charge transfer and that the concept of polar mismatch is not applicable in metal-insulator polar-nonpolar interfaces.

Enhanced Superconducting State in FeSe/SrTiO_{3} by a Dynamic Interfacial Polaron Mechanism.

The observation of substantially enhanced superconductivity of single-layer FeSe films on SrTiO_{3} has stimulated intensive research interest. At present, conclusive experimental data on the corresponding electron-boson interaction is still missing. Here we use inelastic electron scattering spectroscopy and angle resolved photoemission spectroscopy to show that the electrons in these systems are dressed by the strongly polarized lattice distortions of the SrTiO_{3}, and the indispensable nonadiabatic nature of such a coupling leads to the formation of dynamic interfacial polarons. Furthermore, the collective motion of the polarons results in a polaronic plasmon mode, which is unambiguously correlated with the surface phonons of SrTiO_{3} in the presence of the FeSe films. A microscopic model is developed showing that the interfacial polaron-polaron interaction leads to the superconductivity enhancement.

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.

Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial.

BACKGROUND: Advanced melanoma treatments often rely on immunotherapy or targeting mutations, with few treatment options for wild-type BRAF (BRAF-wt) melanoma. However, the mitogen-activated protein kinase pathway is activated in most melanoma, including BRAF-wt. We assessed whether inhibiting this pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy improved outcomes in patients with advanced BRAF-wt melanoma in a phase II, randomised and open-label trial. PATIENTS AND METHODS: Patients were randomised (1 : 1 : 1) to paclitaxel alone or with trametinib or pazopanib. Paclitaxel was given for a maximum of six cycles, while 2 mg trametinib and 800 mg pazopanib were administered orally once daily until disease progression or unacceptable toxicity. Participants and investigators were unblinded. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR). RESULTS: Participants were randomised to paclitaxel alone (n = 38), paclitaxel and trametinib (n = 36), or paclitaxel and pazopanib (n = 37). Adding trametinib significantly improved 6-month PFS [time ratio (TR), 1.47; 90% confidence interval (CI) 1.08-2.01, P = 0.04] and ORR (42% versus 13%; P = 0.01) but had no effect on OS (P = 0.25). Adding pazopanib did not benefit 6-month PFS; (TR 1.36; 90% CI 0.96-1.93; P = 0.14), ORR, or OS. Toxicity increased in both combination arms. CONCLUSION: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS.This study was registered with the EU Clinical Trials Register, EudraCT number 2011-002545-35, and with the ISRCTN registry, number 43327231.

Designing antiphase boundaries by atomic control of heterointerfaces.

Extended defects are known to have critical influences in achieving desired material performance. However, the nature of extended defect generation is highly elusive due to the presence of multiple nucleation mechanisms with close energetics. A strategy to design extended defects in a simple and clean way is thus highly desirable to advance the understanding of their role, improve material quality, and serve as a unique playground to discover new phenomena. In this work, we report an approach to create planar extended defects-antiphase boundaries (APB) -with well-defined origins via the combination of advanced growth, atomic-resolved electron microscopy, first-principals calculations, and defect theory. In La2/3Sr1/3MnO3 thin film grown on Sr2RuO4 substrate, APBs in the film naturally nucleate at the step on the substrate/film interface. For a single step, the generated APBs tend to be nearly perpendicular to the interface and propragate toward the film surface. Interestingly, when two steps are close to each other, two corresponding APBs communicate and merge together, forming a unique triangle-shaped defect domain boundary. Such behavior has been ascribed, in general, to the minimization of the surface energy of the APB. Atomic-resolved electron microscopy shows that these APBs have an intriguing antipolar structure phase, thus having the potential as a general recipe to achieve ferroelectric-like domain walls for high-density nonvolatile memory.

Doping effect on the physical properties of Ca10Pt3As8(Fe2As2)5 single crystals.

Ca10Pt3As8(Fe2As2)5 is a unique parent compound for superconductivity, which consists of both semiconducting Pt3As8 and metallic FeAs layers. We report the observation of superconductivity induced via chemical doping in either Ca site using rare-earth (RE) elements (RE = La, Gd) or Fe site using Pt. The interlayer distance and the normal-state physical properties of the doped system change correspondingly. The coupled changes include (1) superconducting transition temperature T c increases with increasing both doping concentration and interlayer distance, (2) our T c value is higher than previously reported maximum value for Pt doping in the Fe site, (3) both the normal-state in-plane resistivity and out-of-plane resistivity change from non-metallic to metallic behavior with increasing doping concentration and T c, and (4) the transverse in-plane magnetoresistance (MRab) changes from linear-field dependence to quadratic behavior upon increasing T c. For La-doped compound with the highest T c (~35 K), upper critical fields ([Formula: see text], [Formula: see text]), coherence lengths (ξ ab, ξ c), and in-plane penetration depth (λ ab) are estimated. We discuss the relationship between chemical doping, interlayer distance, and physical properties in this system.

Predicting hidden bulk phases from surface phases in bilayered Sr3Ru2O7.

The ability to predict hidden phases under extreme conditions is not only crucial to understanding and manipulating materials but it could also lead to insight into new phenomena and novel routes to synthesize new phases. This is especially true for Ruddlesden-Popper perovskite phases that possess interesting properties ranging from superconductivity and colossal magnetoresistance to photovoltaic and catalytic activities. In particular, the physical properties of the bilayer perovskite Sr3Ru2O7 at the surface are intimately tied to the rotation and tilt of the RuO6 octahedra. To take advantage of the extra degree of freedom associated with tilting we have performed first principles hybrid density functional simulations of uniaxial pressure applied along the c-axis of bulk Sr3Ru2O7 where we find that the octahedra become tilted, leading to two phase transitions. One is a structural transition at [Formula: see text]1.5 GPa, and the other is from a ferromagnetic (FM) metal to an antiferromagnetic (AFM) insulator at [Formula: see text]21 GPa whose AFM spin configuration is different from the AFM state near the FM ground state.

Interface-induced multiferroism by design in complex oxide superlattices.

Interfaces between materials present unique opportunities for the discovery of intriguing quantum phenomena. Here, we explore the possibility that, in the case of superlattices, if one of the layers is made ultrathin, unexpected properties can be induced between the two bracketing interfaces. We pursue this objective by combining advanced growth and characterization techniques with theoretical calculations. Using prototype La2/3Sr1/3MnO3 (LSMO)/BaTiO3 (BTO) superlattices, we observe a structural evolution in the LSMO layers as a function of thickness. Atomic-resolution EM and spectroscopy reveal an unusual polar structure phase in ultrathin LSMO at a critical thickness caused by interfacing with the adjacent BTO layers, which is confirmed by first principles calculations. Most important is the fact that this polar phase is accompanied by reemergent ferromagnetism, making this system a potential candidate for ultrathin ferroelectrics with ferromagnetic ordering. Monte Carlo simulations illustrate the important role of spin-lattice coupling in LSMO. These results open up a conceptually intriguing recipe for developing functional ultrathin materials via interface-induced spin-lattice coupling.

Nontrivial Berry phase in magnetic BaMnSb2 semimetal.

The subject of topological materials has attracted immense attention in condensed-matter physics because they host new quantum states of matter containing Dirac, Majorana, or Weyl fermions. Although Majorana fermions can only exist on the surface of topological superconductors, Dirac and Weyl fermions can be realized in both 2D and 3D materials. The latter are semimetals with Dirac/Weyl cones either not tilted (type I) or tilted (type II). Although both Dirac and Weyl fermions have massless nature with the nontrivial Berry phase, the formation of Weyl fermions in 3D semimetals require either time-reversal or inversion symmetry breaking to lift degeneracy at Dirac points. Here we demonstrate experimentally that canted antiferromagnetic BaMnSb2 is a 3D Weyl semimetal with a 2D electronic structure. The Shubnikov-de Hass oscillations of the magnetoresistance give nearly zero effective mass with high mobility and the nontrivial Berry phase. The ordered magnetic arrangement (ferromagnetic ordering in the ab plane and antiferromagnetic ordering along the c axis below 286 K) breaks the time-reversal symmetry, thus offering us an ideal platform to study magnetic Weyl fermions in a centrosymmetric material.

Molecular diagnosis of bacterial vaginosis: Does adjustment for total bacterial load or human cellular content improve diagnostic performance?

We investigated the utility of quantitative PCR assays for diagnosis of bacterial vaginosis and found that while the best model utilized bacterial copy number adjusted for total bacterial load (sensitivity=98%, specificity=93%, AUC=0.95[95%CI=0.93,0.97]), adjusting for total bacterial or human cell load did not consistently increase the diagnostic performance of the assays.