Spin disorder control of topological spin texture.

Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

Rational design of a bacterial import system for new-to-nature molecules.

Integration of novel compounds into biological processes holds significant potential for modifying or expanding existing cellular functions. However, the cellular uptake of these compounds is often hindered by selectively permeable membranes. We present a novel bacterial transport system that has been rationally designed to address this challenge. Our approach utilizes a highly promiscuous sulfonate membrane transporter, which allows the passage of cargo molecules attached as amides to a sulfobutanoate transport vector molecule into the cytoplasm of the cell. These cargoes can then be unloaded from the sulfobutanoyl amides using an engineered variant of the enzyme γ-glutamyl transferase, which hydrolyzes the amide bond and releases the cargo molecule within the cell. Here, we provide evidence for the broad substrate specificity of both components of the system by evaluating a panel of structurally diverse sulfobutanoyl amides. Furthermore, we successfully implement the synthetic uptake system in vivo and showcase its functionality by importing an impermeant non-canonical amino acid.

Bioprocess in-line monitoring and control using Raman spectroscopy and Indirect Hard Modeling (IHM).

Process in-line monitoring and control are crucial to optimize the productivity of bioprocesses. A frequently applied Process Analytical Technology (PAT) tool for bioprocess in-line monitoring is Raman spectroscopy. However, evaluating bioprocess Raman spectra is complex and calibrating state-of-the-art statistical evaluation models is effortful. To overcome this challenge, we developed an Indirect Hard Modeling (IHM) prediction model in a previous study. The combination of Raman spectroscopy and the IHM prediction model enables non-invasive in-line monitoring of glucose and ethanol mass fractions during yeast fermentations with significantly less calibration effort than comparable approaches based on statistical models. In this study, we advance this IHM-based approach and successfully demonstrate that the combination of Raman spectroscopy and IHM is capable of not only bioprocess monitoring but also bioprocess control. For this purpose, we used this combination's in-line information as input of a simple on-off glucose controller to control the glucose mass fraction in Saccharomyces cerevisiae fermentations. When we performed two of these fermentations with different predefined glucose set points, we achieved similar process control quality as approaches using statistical models, despite considerably smaller calibration effort. Therefore, this study reaffirms that the combination of Raman spectroscopy and IHM is a powerful PAT tool for bioprocesses.

Condensed Layer Deposition of Nanoscopic TiO2 Overlayers on High-Surface-Area Electrocatalysts.

Encapsulating an electrocatalytic material with a semipermeable, nanoscopic oxide overlayer offers a promising approach to enhancing its stability, activity, and/or selectivity compared to an unencapsulated electrocatalyst. However, applying nanoscopic oxide encapsulation layers to high-surface-area electrodes such as nanoparticle-supported porous electrodes is a challenging task. This study demonstrates that the recently developed condensed layer deposition (CLD) method can be used for depositing nanoscopic (sub-10 nm thick) titanium dioxide (TiO2) overlayers onto high-surface-area platinized carbon foam electrodes. Characterization of the overlayers by transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) showed that the films are amorphous, while X-ray photoelectron spectroscopy confirmed that they exhibit TiO2 stoichiometry. Electrodes were also characterized by hydrogen underpotential deposition (Hupd) and carbon monoxide (CO) stripping, demonstrating that the Pt electrocatalysts remain electrochemically active after encapsulation. Additionally, copper underpotential deposition (Cuupd) measurements revealed that TiO2 overlayers are effective at blocking Cu2+ from reaching the TiO2/Pt buried interface and were used to estimate that between 43 and 98% of Pt surface sites were encapsulated. Overall, this study shows that CLD is a promising approach for depositing nanoscopic protective overlayers on high-surface-area electrodes.

Strategies to prevent, diagnose and treat kidney disease related to systemic arterial hypertension: a narrative review from the Mexican Group of Experts on Arterial Hypertension.

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.

Polygenic Risk in Families With Spontaneous Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome that predominantly affects women. Evidence to date suggests a complex genetic architecture, while a family history is reported for a minority of cases. Objective: To determine the contribution of rare and common genetic variants to SCAD risk in familial cases, the latter via the comparison of a polygenic risk score (PRS) with those with sporadic SCAD and healthy controls. Design, Setting, and Participants: This genetic association study analyzed families with SCAD, individuals with sporadic SCAD, and healthy controls. Genotyping was undertaken for all participants. Participants were recruited between 2017 and 2021. A PRS for SCAD was calculated for all participants. The presence of rare variants in genes associated with connective tissue disorders (CTD) was also assessed. Individuals with SCAD were recruited via social media or from a single medical center. A previously published control database of older healthy individuals was used. Data were analyzed from January 2022 to October 2023. Exposures: PRS for SCAD comprised of 7 single-nucleotide variants. Main Outcomes and Measures: Disease status (familial SCAD, sporadic SCAD, or healthy control) associated with PRS. Results: A total of 13 families with SCAD (27 affected and 12 unaffected individuals), 173 individuals with sporadic SCAD, and 1127 healthy controls were included. A total of 188 individuals with SCAD (94.0%) were female, including 25 of 27 with familial SCAD and 163 of 173 with sporadic SCAD; of 12 unaffected individuals from families with SCAD, 6 (50%) were female; and of 1127 healthy controls, 672 (59.6%) were female. Compared with healthy controls, the odds of being an affected family member or having sporadic SCAD was significantly associated with a SCAD PRS (where the odds ratio [OR] represents an increase in odds per 1-SD increase in PRS) (affected family member: OR, 2.14; 95% CI, 1.78-2.50; adjusted P = 1.96 × 10-4; sporadic SCAD: OR, 1.63; 95% CI, 1.37-1.89; adjusted P = 5.69 × 10-4). This association was not seen for unaffected family members (OR, 1.03; 95% CI, 0.46-1.61; adjusted P = .91) compared with controls. Further, those with familial SCAD were overrepresented in the top quintile of the control PRS distribution (OR, 3.70; 95% CI, 2.93-4.47; adjusted P = .001); those with sporadic SCAD showed a similar pattern (OR, 2.51; 95% CI, 1.98-3.04; adjusted P = .001). Affected individuals within a family did not share any rare deleterious variants in CTD-associated genes. Conclusions and Relevance: Extreme aggregation of common genetic risk appears to play a significant role in familial clustering of SCAD as well as in sporadic case predisposition, although further study is required.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein.

The COVID-19 pandemic has highlighted the need for vaccines capable of providing rapid and robust protection. One way to improve vaccine efficacy is delivery via microarray patches, such as the Vaxxas high-density microarray patch (HD-MAP). We have previously demonstrated that delivery of a SARS-CoV-2 protein vaccine candidate, HexaPro, via the HD-MAP induces potent humoral immune responses. Here, we investigate the cellular responses induced by HexaPro HD-MAP vaccination. We found that delivery via the HD-MAP induces a type one biassed cellular response of much greater magnitude as compared to standard intramuscular immunization.

Strain Assessment in Aortic Stenosis: Pathophysiology and Clinical Utility.

Contemporary echocardiographic criteria for grading aortic stenosis severity have remained relatively unchanged, despite significant advances in noninvasive imaging techniques over the last 2 decades. More recently, attention has shifted to the ventricular response to aortic stenosis and how this might be quantified. Global longitudinal strain, semiautomatically calculated from standard two-dimensional echocardiographic images, has been the focus of extensive research. Global longitudinal strain is a sensitive marker of subtle hypertrophy-related impairment in left ventricular function and has shown promise as a relatively robust prognostic marker, both independently and when added to severity classification systems. Herein we review the pathophysiological basis underpinning the potential utility of global longitudinal strain in the assessment of aortic stenosis, as well as its potential role in quantifying myocardial recovery and prognostic discrimination following aortic valve replacement.

Exchange Bias Between van der Waals Materials: Tilted Magnetic States and Field-Free Spin-Orbit-Torque Switching.

Magnetic van der Waals heterostructures provide a unique platform to study magnetism and spintronics device concepts in the 2D limit. Here, studies of exchange bias from the van der Waals antiferromagnet CrSBr acting on the van der Waals ferromagnet Fe3GeTe2 (FGT) are reported. The orientation of the exchange bias is along the in-plane easy axis of CrSBr, perpendicular to the out-of-plane anisotropy of the FGT, inducing a strongly tilted magnetic configuration in the FGT. Furthermore, the in-plane exchange bias provides sufficient symmetry breaking to allow deterministic spin-orbit torque switching of the FGT in CrSBr/FGT/Pt samples at zero applied magnetic field. A minimum thickness of the CrSBr of >10 nm is needed to provide a non-zero exchange bias at 30 K.

Room-Temperature, Current-Induced Magnetization Self-Switching in A Van Der Waals Ferromagnet.

2D layered materials with broken inversion symmetry are being extensively pursued as  spin source layers to realize high-efficiency magnetic switching. Such low-symmetry layered systems are, however, scarce. In addition, most layered magnets with perpendicular magnetic anisotropy show a low Curie temperature. Here, the experimental observation of spin-orbit torque magnetization self-switching at room temperature in a layered polar ferromagnetic metal, Fe2.5 Co2.5 GeTe2 is reported. The spin-orbit torque is generated from the broken inversion symmetry along the c-axis of the crystal. These results provide a direct pathway toward applicable 2D spintronic devices.

Ultra-Stable ITO-Free Organic Solar Cells and Modules Processed from Non-Halogenated Solvents under Indoor Illumination.

Organic Photovoltaics (OPV) is a very promising technology to harvest artificial illumination and power smart devices of the Internet of Things (IoT). Efficiencies as high as 30.2% have been reported for OPVs under warm white light-emitting diode (LED) light. This is due to the narrow spectrum of indoor light, which leads to an optimal bandgap of ≈1.9 eV. Under full sunlight, OPV devices often suffer from poor stability compared to the established inorganic PV technologies such as crystalline silicon. This study focuses on a potentially very cost-effective Indium Tin Oxide (ITO) free cell stack with absorber materials processed from non-halogenated solvents. These organic solar cells and modules with efficiencies up to 21% can already achieve remarkable stabilities under typical indoor illumination. Aging under 50,000 lux LED lighting leads to very little degradation after more than 11 000 h. This light dose corresponds to more than 110 years under 500 lux. For modules encapsulated with a flexible barrier, extrapolated lifetimes of more than 41 years are achieved. This shows that OPV is mature for the specific application under indoor illumination. Due to the large number of potential organic semiconducting materials, further efficiency increase can be expected.

Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study.

BACKGROUND: Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England. METHODS: We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019. FINDINGS: In 2019, the probability of dying from a cancer before age 80 years ranged from 0·10 (95% credible interval [CrI] 0·10-0·11) to 0·17 (0·16-0·18) for women and from 0·12 (0·12-0·13) to 0·22 (0·21-0·23) for men. Variation in the probability of dying was largest for lung cancer among women, being 3·7 times (95% CrI 3·2-4·4) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3·2 times (2·6-4·1) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1·2 times [1·1-1·4] higher in the district with the highest probability than the lowest probability for women and 1·2 times [1·0-1·4] for men), and leukaemia (1·1 times [1·0-1·4] for women and 1·2 times [1·0-1·5] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0·74 (95% CrI 0·72-0·76) for women and 0·79 (0·78-0·81) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6·6% (95% CrI 0·3-13·1) to 30·1% (25·6-34·5) for women and from 12·8% (7·1-18·8) to 36·7% (32·2-41·2) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0·80. INTERPRETATION: Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level. FUNDING: Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.

Secondary retensioning of a tether-based device for transapical transcatheter mitral valve implantation.

OBJECTIVES: Relevant paravalvular leakage (PVL) due to prosthesis dislodgement is a rare but potentially severe complication after transcatheter mitral valve implantation (TMVI). Due to the epicardial anchoring mechanism of the Tendyne® TMVI system, repositioning of the valve stent may be possible by retensioning of the tether. This multicentre study aimed to investigate the procedural and short-term safety as well as efficacy of retensioning manoeuvres. METHODS: From 2017 to 2021, N = 18 patients who underwent secondary tether retensioning were identified. Baseline, procedural and follow-up data were available from N = 11 patients and analysed according to the Mitral Valve Research Consortium definitions. Continuous variables are shown as median with interquartile range. RESULTS: All patients [age 75 years (73.5, 85.0), 64% male (N = 7), EuroSCORE II 6.2% (5.8, 11.6)] presented with post-procedural PVL [63.6% (N = 7) with PVL ≥3+]. Of these, 54% (N = 6) showed signs of haemolysis. The majority were severely symptomatic [New York Heart Association ≥III (91%, N = 10)]. Procedural outcomes revealed no acute complications and no mortality. At discharge, PVL was completely eliminated in 91% (N = 10) of patients with 1 case of remaining moderate PVL. At 30 days, Mitral Valve Research Consortium device success was achieved in 82% (N = 9) of patients. Two patients required open surgical mitral valve replacement due to persistent and recurrent PVL. In 89% (N = 8) of patients with successful retensioning procedure, New York Heart Association class was I/II. There was no 30-day mortality. CONCLUSIONS: This multicentre study demonstrates technical feasibility, procedural safety and acute efficacy of retensioning procedures in the majority of patients. The potential to retension the tether in transapical TMVI may provide additional management advantages in populations at high surgical risk.

Thermally generated spin current in the topological insulator Bi2Se3.

We present measurements of thermally generated transverse spin currents in the topological insulator Bi2Se3, thereby completing measurements of interconversions among the full triad of thermal gradients, charge currents, and spin currents. We accomplish this by comparing the spin Nernst magneto-thermopower to the spin Hall magnetoresistance for bilayers of Bi2Se3/CoFeB. We find that Bi2Se3 does generate substantial thermally driven spin currents. A lower bound for the ratio of spin current density to thermal gradient is [Formula: see text] = (4.9 ± 0.9) × 106 [Formula: see text], and a lower bound for the magnitude of the spin Nernst ratio is -0.61 ± 0.11. The spin Nernst ratio for Bi2Se3 is the largest among all materials measured to date, two to three times larger compared to previous measurements for the heavy metals Pt and W. Strong thermally generated spin currents in Bi2Se3 can be understood via Mott relations to be due to an overall large spin Hall conductivity and its dependence on electron energy.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

Exploring the intratumoral heterogeneity of DNA ploidy in prostate cancer.

BACKGROUND: Prostate cancer is morphologically and molecularly heterogeneous. Genomic heterogeneity might be mirrored by variability in DNA ploidy. Aneuploidy is a hallmark of genomic instability and associated with tumor aggressiveness. Little attention has been paid to the biological significance of the diploid tumor cell population that often coexists with aneuploid populations. Here, we investigated the role of DNA ploidy in tumor heterogeneity and clonal evolution. METHODS: Three radical prostatectomy specimens with intratumoral heterogeneity based on nuclear features on H&E were selected. DNA content of each subpopulation was determined by DNA image cytometry and silver in situ hybridization (SISH). Genomic evolution was inferred from array comparative genomic hybridization (aCGH). Additionally, immunohistochemistry was used to examine the stemness-associated marker ALDH1A1. RESULTS: Nuclear morphology reliably predicted DNA ploidy status in all three cases. In one case, aCGH analysis revealed several shared deletions and one amplification in both the diploid and the aneuploid population, suggesting that these populations could be related. In the other two cases, a statement about relatedness was not possible. Furthermore, ALDH1A1 was expressed in 2/3 cases and exclusively observed in their diploid populations. CONCLUSIONS: In this proof-of-concept study, we demonstrate the feasibility to predict the DNA ploidy status of distinct populations within one tumor by H&E morphology. Future studies are needed to further investigate the clonal relationship between the diploid and the aneuploid subpopulation and test the hypothesis that the aneuploid population is derived from the diploid one. Finally, our analyses pointed to an enrichment of the stemness-associated marker ALDH1A1 in diploid populations, which warrants further investigation in future studies.

Superior efficacy of a skin-applied microprojection device for delivering a novel Zika DNA vaccine.

Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine.

Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18-50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID50] measles, ~4300 CCID50 rubella); high-dose MR-HD-MAPs (~9300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2-8 °C for at least 24 months. When MR HD-MAPs stored at 2-8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Synthesis of graded CdS1-xSex nanoplatelet alloys and heterostructures from pairs of chalcogenoureas with tailored conversion reactivity.

A mixture of N,N,N'-trisubstituted thiourea and cyclic N,N,N',N'-tetrasubstituted selenourea precursors were used to synthesize three monolayer thick CdS1-xSex nanoplatelets in a single synthetic step. The microstructure of the nanoplatelets could be tuned from homogeneous alloys, to graded alloys to core/crown heterostructures depending on the relative conversion reactivity of the sulfur and selenium precursors. UV-visible absorption and photoluminescence spectroscopy and scanning transmission electron microscopy electron energy loss spectroscopy (STEM-EELS) images demonstrate that the elemental distribution is governed by the relative precursor conversion kinetics. Slow conversion kinetics produced nanoplatelets with larger lateral dimensions, behavior that is characteristic of precursor conversion limited growth kinetics. Across a 10-fold range of reactivity, CdS nanoplatelets have 4× smaller lateral dimensions than CdSe nanoplatelets grown under identical conversion kinetics. The difference in size is consistent with a rate of CdSe growth that is 4× greater than the rate of CdS. The influence of the relative sulfide and selenide growth rates, the duration of the nucleation phase, and the solute composition on the nanoplatelet microstructure are discussed.