Utilization of coupled eigenmodes in Akiyama atomic force microscopy probes for bimodal multifrequency sensing.

Akiyama atomic force microscopy probes represent a unique means of combining several of the desirable properties of tuning fork and cantilever probe designs. As a hybridized mechanical resonator, the vibrational characteristics of Akiyama probes result from a complex coupling between the intrinsic vibrational eigenmodes of its constituent tuning fork and bridging cantilever components. Through a combination of finite element analysis modeling and experimental measurements of the thermal vibrations of Akiyama probes we identify a complex series of vibrational eigenmodes and measure their frequencies, quality factors, and spring constants. We then demonstrate the viability of Akiyama probes to perform bimodal multi-frequency force sensing by performing a multimodal measurement of a surface's nanoscale photothermal response using photo-induced force microscopy imaging techniques. Further performing a parametric search over alternative Akiyama probe geometries, we propose two modified probe designs to enhance the capability of Akiyama probes to perform sensitive bimodal multifrequency force sensing measurements.

Space-Time Quantum Metasurfaces.

Metasurfaces have recently entered the realm of quantum photonics, enabling manipulation of quantum light using a compact nanophotonic platform. Realizing the full potential of metasurfaces at the deepest quantum level requires the ability to tune coherent light-matter interactions continuously in space and time. Here, we introduce the concept of space-time quantum metasurfaces for arbitrary control of the spectral, spatial, and spin properties of nonclassical light using a compact photonic platform. We show that space-time quantum metasurfaces allow on-demand tailoring of entanglement among all degrees of freedom of a single photon. We also show that spatiotemporal modulation induces asymmetry at the fundamental level of quantum fluctuations, resulting in the generation of steered and vortex photon pairs out of vacuum. Space-time quantum metasurfaces have the potential to enable novel photonic functionalities, such as encoding quantum information into high-dimensional color qudits using designer modulation protocols, sculpting multispectral and multispatial modes in spontaneous emission, and generating reconfigurable hyperentanglement for high-capacity quantum communications.

Near-Field Radiative Heat Transfer Eigenmodes.

The near-field electromagnetic interaction between nanoscale objects produces enhanced radiative heat transfer that can greatly surpass the limits established by far-field blackbody radiation. Here, we present a theoretical framework to describe the temporal dynamics of the radiative heat transfer in ensembles of nanostructures, which is based on the use of an eigenmode expansion of the equations that govern this process. Using this formalism, we identify the fundamental principles that determine the thermalization of collections of nanostructures, revealing general but often unintuitive dynamics. Our results provide an elegant and precise approach to efficiently analyze the temporal dynamics of the near-field radiative heat transfer in systems containing a large number of nanoparticles.

Nonlinear dynamics of topological Dirac fermions in 2D spin-orbit coupled materials.

The graphene family materials are two-dimensional staggered monolayers with a gapped energy band structure due to intrinsic spin-orbit coupling. The mass gaps in these materials can be manipulated on-demand via biasing with a static electric field, an off-resonance circularly polarized laser, or an exchange interaction field, allowing the monolayer to be driven through a multitude of topological phase transitions. We investigate the dynamics of spin-orbit coupled graphene family materials to unveil topological phase transition fingerprints embedded in the nonlinear regime and show how these signatures manifest in the nonlinear Kerr effect and in third-harmonic generation processes. We show that the resonant nonlinear spectral response of topological fermions can be traced to specific Dirac cones in these materials, enabling characterization of topological invariants in any phase by detecting the cross-polarized component of the electromagnetic field. By shedding light on the unique processes involved in harmonic generation via topological phenomena our findings open an encouraging path towards the development of novel nonlinear systems based on two-dimensional semiconductors of the graphene family.

Surface-wave-assisted nonreciprocity in spatio-temporally modulated metasurfaces.

Emerging photonic functionalities are mostly governed by the fundamental principle of Lorentz reciprocity. Lifting the constraints imposed by this principle could circumvent deleterious effects that limit the performance of photonic systems. Most efforts to date have been limited to waveguide platforms. Here, we propose and experimentally demonstrate a spatio-temporally modulated metasurface capable of complete violation of Lorentz reciprocity by reflecting an incident beam into far-field radiation in forward scattering, but into near-field surface waves in reverse scattering. These observations are shown both in nonreciprocal beam steering and nonreciprocal focusing. We also demonstrate nonreciprocal behavior of propagative-only waves in the frequency- and momentum-domains, and simultaneously in both. We develop a generalized Bloch-Floquet theory which offers physical insights into Lorentz nonreciprocity for arbitrary spatial phase gradients, and its predictions are in excellent agreement with experiments. Our work opens exciting opportunities in applications where free-space nonreciprocal wave propagation is desired.

Highly Plasmonic Titanium Nitride by Room-Temperature Sputtering.

Titanium nitride (TiN) has recently emerged as an attractive alternative material for plasmonics. However, the typical high-temperature deposition of plasmonic TiN using either sputtering or atomic layer deposition has greatly limited its potential applications and prevented its integration into existing CMOS device architectures. Here, we demonstrate highly plasmonic TiN thin films and nanostructures by a room-temperature, low-power, and bias-free reactive sputtering process. We investigate the optical properties of the TiN films and their dependence on the sputtering conditions and substrate materials. We find that our TiN possesses one of the largest negative values of the real part of the dielectric function as compared to all other plasmonic TiN films reported to date. Two-dimensional periodic arrays of TiN nanodisks are then fabricated, from which we validate that strong plasmonic resonances are supported. Our room-temperature deposition process can allow for fabricating complex plasmonic TiN nanostructures and be integrated into the fabrication of existing CMOS-based photonic devices to enhance their performance and functionalities.

Diet and lupus: what do the patients think?

OBJECTIVES: Cardiovascular disease is the leading cause of mortality in patients with systemic lupus erythematosus. Therefore, using diet to control blood lipid levels and modify cardiovascular disease risk could be a promising therapeutic strategy to control disease symptoms. The primary objective of this study was to learn about systemic lupus erythematosus patient experiences with diet, including their opinion on considering diet as a therapeutic option. The secondary objective was to obtain this information in a cost- and time-effective manner. METHODS: A lay summary and a 15-question diet-based online survey were publicly available for 3 weeks. Social media was used to promote the survey through relevant charities, hospitals and research groups. RESULTS: A total of 300 responses were received, 284 from patients with systemic lupus erythematosus. Patients reported that there was a lack of clinical counselling regarding diet, with only 24% stating their doctor had spoken to them about diet. Despite this, 100% of patients stated they would change their diet if they knew it would help their symptoms and 83% would take part in a future diet-based clinical trial. Text analysis of patient research suggestions identified a particular interest in using diet to treat fatigue and manage disease flares. CONCLUSIONS: This project successfully gathered patient information regarding diet and systemic lupus erythematosus over a short timeframe using an anonymous social media platform. The survey provided evidence that patients support further research and potential diet intervention studies investigating the effect of diet on the symptoms of systemic lupus erythematosus.

Late diagnosis, delayed presentation and late presentation among persons enrolled in a clinical HIV cohort in Ontario, Canada (1999-2013).

OBJECTIVES: Timely HIV diagnosis and presentation to medical care are important for treatment and prevention. Our objective was to measure late diagnosis, delayed presentation and late presentation among individuals in the Ontario HIV Treatment Network Cohort Study (OCS) who were newly diagnosed in Ontario. METHODS: The OCS is a multi-site clinical cohort study of people living with HIV in Ontario, Canada. We measured prevalence of late diagnosis [CD4 count < 350 cells/µL or an AIDS-defining condition (ADC) within 3 months of HIV diagnosis], delayed presentation (≥ 3 months from HIV diagnosis to presentation to care), and late presentation (CD4 count < 350 cells/µL or ADC within 3 months of presentation). We identified characteristics associated with these outcomes and explored their overlap. RESULTS: A total of 1819 OCS participants were newly diagnosed in Ontario from 1999 to 2013. Late diagnosis (53.0%) and presentation (54.0%) were common, and a quarter (23.1%) of participants were delayed presenters. In multivariable models, the participants of delayed presentation decreased over calendar time, but that of late diagnosis/presentation did not. Late diagnosis contributed to the majority (> 87%) of late presentation, and the prevalence of delayed presentation was similar among those diagnosed late versus early (13.4 versus 13.4%, respectively; P = 0.99). Characteristics associated with higher odds of late diagnosis/presentation in multivariable analyses included older age at diagnosis/presentation; African, Caribbean and Black race/ethnicity; Indigenous race/ethnicity; female sex; and being a male who did not report sex with men. There were lower odds of late diagnosis/presentation among participants who had ever injected drugs. In contrast, delayed presentation risk factors included younger age at diagnosis and having ever injected drugs. CONCLUSIONS: Late presentation is common in Ontario, as it is in other high-income countries. Our findings suggest that efforts to reduce late presentation should focus on facilitating earlier diagnosis for the populations identified in this analysis.

High-Temperature Refractory Metasurfaces for Solar Thermophotovoltaic Energy Harvesting.

Solar energy promises a viable solution to meet the ever-increasing power demand by providing a clean, renewable energy alternative to fossil fuels. For solar thermophotovoltaics (STPV), high-temperature absorbers and emitters with strong spectral selectivity are imperative to efficiently couple solar radiation into photovoltaic cells. Here, we demonstrate refractory metasurfaces for STPV with tailored absorptance and emittance characterized by in situ high-temperature measurements, featuring thermal stability up to at least 1200 °C. Our tungsten-based metasurface absorbers have close-to-unity absorption from visible to near-infrared and strongly suppressed emission at longer wavelengths, while our metasurface emitters provide wavelength-selective emission spectrally matched to the band-edge of InGaAsSb photovoltaic cells. The projected overall STPV efficiency is as high as 18% when a fully integrated absorber/emitter metasurface structure is employed, which is comparable to the efficiencies of the best currently available commercial single-junction PV cells and can be further improved to potentially exceed those in mainstream photovoltaic technologies. Our work opens a path forward for high-performance STPV systems based on refractory metasurface structures.

Acetylcholinesterase inhibition and antimicrobial activity of hydroxyl amides synthesized from natural products derivatives.

Thirteen natural products derivatives of hydroxyl amide class, three described for the first time, were synthesized by reaction of three indole acids and 3,4,5-trimethoxybenzoic acid with six different amino alcohols in the presence of triphenylphosphine and N-bromosuccinimide. The derivatives were tested against the Gram (+) bacteria Staphylococcus aureus and Bacillus cereus, Gram (-) Pseudomonas aeruginosa and Escherichia coli, besides the yeast Candida albicans. One of the compounds (7) was selectively active against C. albicans (91.3 ± 0.49% inhibition) showing a great potential as a new drug lead, since it was more active than the positive control, miconazole (88.7 ± 2.41% inhibition). Regarding bacterial inhibition, compounds demonstrated mild activity, but inhibition of compounds 9, 10 and 13 towards E. coli is of interest since it is difficult to find drugs selectively active against Gram (-) bacteria. Most of the compounds were very active in the acetylcholinesterase inhibition assay. Compound 7 was again the most active (93.2 ± 4.47%), being more potent than the control galantamine (90.3 ± 0.45%). The most active gallic acid derivatives, compounds 3, 7 and 8 have in common, besides gallic acid skeleton, a (CH2)2OH group, which may be one of the structural requirements for AChE inhibition.

Guided self-help to manage binge eating in a dietetic-led community weight management service.

An estimated 30% of patients accessing community weight management services experience symptoms of binge eating disorder (BED). Guided self-help (GSH) is the recommended first line of treatment for BED. This study is a preliminary investigation into the effectiveness of GSH delivered by dietitians for patients with binge eating within a weight management service and a consideration of the association between wellbeing, therapeutic relationship and outcomes. The study was conducted as a single group, pre- and post-intervention study with 24 patients reporting symptoms of binge eating who completed the self-help manual with guidance from a trained community dietitian. Primary outcomes were eating disorder psychopathology and behaviours (Eating Disorder Evaluation Questionnaire), depression and anxiety. Principle results showed a significant reduction on all subscales of eating disorder psychopathology, anxiety and depression. There was a reduction in loss of control over eating but the 40% reduction in binge episodes was not statistically significant. Mid-treatment sessional ratings were positively associated with outcome. In conclusion, the GSH intervention was appropriate for dietitian delivery to patients with obesity and binge eating behaviour. This research indicates potential for other dietetic-led weight management services to deliver such interventions and support patients with binge eating accessing their service.

Casimir force phase transitions in the graphene family.

The Casimir force is a universal interaction induced by electromagnetic quantum fluctuations between any types of objects. The expansion of the graphene family by adding silicene, germanene and stanene (2D allotropes of Si, Ge, and Sn), lends itself as a platform to probe Dirac-like physics in honeycomb staggered systems in such a ubiquitous interaction. We discover Casimir force phase transitions between these staggered 2D materials induced by the complex interplay between Dirac physics, spin-orbit coupling and externally applied fields. In particular, we find that the interaction energy experiences different power law distance decays, magnitudes and dependences on characteristic physical constants. Furthermore, due to the topological properties of these materials, repulsive and quantized Casimir interactions become possible.

Can intra-operative fluorescence play a significant role in hepatobiliary surgery?

Liver resection remains the cornerstone of curative treatment for hepatocellular carcinoma and colorectal cancer liver metastases. Its success is dependent upon the extent of resection achieved. To this end, intra-operative imaging techniques have been experimented with to aid the surgeon. Fluorescence guided surgery (FGS) utilises the properties of near infrared light emitting molecules to identify malignant tissue, enabling the surgeon to maximise resection of diseased tissue and minimise collateral damage. Data from early trials showed increased superficial lesion detection when using fluorescence to guide liver resection. However, with far greater tissue penetration, intra-operative ultrasound (IOUS) remains the gold-standard intra-operative imaging modality. Subsequent trials have shown that the concomitant use of both FGS and IOUS may increase tumour detection rates intra-operatively. This review provides a comprehensive analysis of the most compelling evidence regarding fluorescence in hepatobiliary surgery and addresses the challenges faced introducing it into common practice.

Metasurface Broadband Solar Absorber.

We demonstrate a broadband, polarization independent, wide-angle absorber based on a metallic metasurface architecture, which accomplishes greater than 90% absorptance in the visible and near-infrared range of the solar spectrum, and exhibits low absorptivity (emissivity) at mid- and far-infrared wavelengths. The complex unit cell of the metasurface solar absorber consists of eight pairs of gold nano-resonators that are separated from a gold ground plane by a thin silicon dioxide spacer. Our experimental measurements reveal high-performance absorption over a wide range of incidence angles for both s- and p-polarizations. We also investigate numerically the frequency-dependent field and current distributions to elucidate how the absorption occurs within the metasurface structure.

The Anatomical Society core regional anatomy syllabus for undergraduate medicine.

The Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving 'experts' (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: 'What do I need to know ?'

ARMC5 mutations are common in familial bilateral macronodular adrenal hyperplasia.

CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing's syndrome. Familial cases have been reported, but at the time we conducted this study, the genetic basis of BMAH was unknown. Recently, germline variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH and somatic, second-hit mutations in tumor nodules, were identified. OBJECTIVE: Our objective was to identify the genetic basis of familial BMAH. DESIGN: We performed whole exome capture and sequencing of 2 affected individuals from each of 4 BMAH families (BMAH-01, BMAH-02, BMAH-03, and BMAH-05). Based on clinical evaluation, there were 7, 3, 3, and 4 affected individuals in these families, respectively. Sanger sequencing of ARMC5 was performed in 1 other BMAH kindred, BMAH-06. RESULTS: Exome sequencing identified novel variants Chr16:g.31477540, c.2139delT, p.(Thr715Leufs*1) (BMAH-02) and Chr16:g.31473811, c.943C→T, p.(Arg315Trp) (BMAH-03) in ARMC5 (GRch37/hg19), validated by Sanger sequencing. BMAH-01 had a recently reported mutation Chr16:g.31476121, c.1777C→T, p.(Arg593Trp). Sanger sequencing of ARMC5 in BMAH-06 identified a previously reported mutation, Chr16:g. 31473688; c.799C→T, p.(Arg267*). The genetic basis of BMAH in BMAH-05 was not identified. CONCLUSIONS: Our studies have detected ARMC5 mutations in 4 of 5 BMAH families tested, confirming that these mutations are a frequent cause of BMAH. Two of the 4 families had novel mutations, indicating allelic heterogeneity. Preclinical evaluation did not predict mutation status. The ARMC5-negative family had unusual prominent hyperaldosteronism. Further studies are needed to determine the penetrance of BMAH in ARMC5 mutation-positive relatives of affected patients, the practical utility of genetic screening and genotype-phenotype correlations.

Marine natural seaweed products as potential antiviral drugs against Bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) is an etiologic agent that causes important economic losses in the world. It is endemic in cattle herds in most parts of the world. The purpose of this study was to evaluate the in vitro cytotoxic effect and antiviral properties of several marine natural products obtained from seaweeds: the indole alkaloid caulerpin (CAV, 1) and three diterpenes: 6-hydroxydichotoma-3,14-diene-1,17-dial (DA, 2), 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene (DB1, 3) and 8,10,18-trihydroxy-2,6-dolabelladiene (DB3, 4). The screening to evaluate the cytotoxicity of compounds did not show toxic effects to MDBK cells. The antiviral activity of the compounds was measured by the inhibition of the cytopathic effect on infected cells by plaque assay (PA) and EC50 values were calculated for CAV (EC=2,0± 5.8), DA (EC 2,8± 7.7), DB1 (EC 2,0±9.7), and DB3 (EC 2,3±7.4). Acyclovir (EC50 322± 5.9) was used in all experiments as the control standard. Although the results of the antiviral activity suggest that all compounds are promising as antiviral agents against BVDV, the Selectivity Index suggests that DB1 is the safest of the compounds tested.

Evaluation of the acute toxicity of dolabelladienotriol, a potential antiviral from the brown alga Dictyota pfaffii, in BALB/c mice

Dolabelladienotriol is a product extracted from the brown marine alga Dictyota pfaffii from Brazil that has been shown to have antiviral activity and low cytotoxicity. Our studies have evaluated the acute toxicity of dolabelladienotriol in BALB/c mice for ten days after administration of a single dose. Among the parameters considered were behavior, weight, biochemical and histological analyses of blood samples taken at three different times (Bs.0, Bs.1 and Bs.2) and optical microscopic examination of organs like liver, kidney, stomach and small intestine. Mice deaths were not observed at any dose during the ten day period. There were some changes in the biochemical analysis results for urea nitrogen (BUN) and alanine aminotransferase (ALT), but the changes were not significantly different from the reference levels of the animals before administration of the substance. Histological analyses of tissues were very similar for all animals. The alterations in liver and kidney tissues did not affect the animals´ behavior at any concentration, not even at 50 mg/kg, where the most significant changes in tissues were seen. This study indicates that dolabelladienotriol has low toxicity in administered dose range.