Cavity-Enhanced 2D Material Quantum Emitters Deterministically Integrated with Silicon Nitride Microresonators.

Optically active defects in 2D materials, such as hexagonal boron nitride (hBN) and transition-metal dichalcogenides (TMDs), are an attractive class of single-photon emitters with high brightness, operation up to room temperature, site-specific engineering of emitter arrays with strain and irradiation techniques, and tunability with external electric fields. In this work, we demonstrate a novel approach to precisely align and embed hBN and TMDs within background-free silicon nitride microring resonators. Through the Purcell effect, high-purity hBN emitters exhibit a cavity-enhanced spectral coupling efficiency of up to 46% at room temperature, exceeding the theoretical limit (up to 40%) for cavity-free waveguide-emitter coupling and demonstrating nearly a 1 order of magnitude improvement over previous work. The devices are fabricated with a CMOS-compatible process and exhibit no degradation of the 2D material optical properties, robustness to thermal annealing, and 100 nm positioning accuracy of quantum emitters within single-mode waveguides, opening a path for scalable quantum photonic chips with on-demand single-photon sources.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

The neonicotinoid insecticide thiamethoxam enhances expression of stress-response genes in Zea mays in an environmentally specific pattern.

Recent studies indicate that thiamethoxam (TMX), a neonicotinoid insecticide, can affect plant responses to environmental stressors, such as neighboring weeds. The molecular mechanisms behind both stable and environmentally specific responses to TMX likely involve genes related to defense and stress responses. We investigated the effect of a TMX seed treatment on global gene expression in maize coleoptiles both under normal conditions and under low ratio red to far-red (R:FR) light stress induced by the presence of neighboring plants. The neighboring plant treatment upregulated genes involved in biotic and abiotic stress responses and affected specific photosynthesis and cell-growth related genes. Low R:FR light may enhance maize resistance to herbivores and pathogens. TMX appears to compromise resistance. The TMX treatment stably repressed many genes that encode proteins involved in biotic stress responses, as well as cell-growth genes. Notably, TMX effects on many genes' expression were conditional on the environment. In response to low R:FR, plants treated with TMX engage genes in the JA pathway, as well as other stress-related response pathways. Neighboring weeds may condition TMX-treated plants to become more stress tolerant.

Nanotechnology for catalysis and solar energy conversion.

This roadmap on Nanotechnology for Catalysis and Solar Energy Conversion focuses on the application of nanotechnology in addressing the current challenges of energy conversion: 'high efficiency, stability, safety, and the potential for low-cost/scalable manufacturing' to quote from the contributed article by Nathan Lewis. This roadmap focuses on solar-to-fuel conversion, solar water splitting, solar photovoltaics and bio-catalysis. It includes dye-sensitized solar cells (DSSCs), perovskite solar cells, and organic photovoltaics. Smart engineering of colloidal quantum materials and nanostructured electrodes will improve solar-to-fuel conversion efficiency, as described in the articles by Waiskopf and Banin and Meyer. Semiconductor nanoparticles will also improve solar energy conversion efficiency, as discussed by Boschloo et al in their article on DSSCs. Perovskite solar cells have advanced rapidly in recent years, including new ideas on 2D and 3D hybrid halide perovskites, as described by Spanopoulos et al 'Next generation' solar cells using multiple exciton generation (MEG) from hot carriers, described in the article by Nozik and Beard, could lead to remarkable improvement in photovoltaic efficiency by using quantization effects in semiconductor nanostructures (quantum dots, wires or wells). These challenges will not be met without simultaneous improvement in nanoscale characterization methods. Terahertz spectroscopy, discussed in the article by Milot et al is one example of a method that is overcoming the difficulties associated with nanoscale materials characterization by avoiding electrical contacts to nanoparticles, allowing characterization during device operation, and enabling characterization of a single nanoparticle. Besides experimental advances, computational science is also meeting the challenges of nanomaterials synthesis. The article by Kohlstedt and Schatz discusses the computational frameworks being used to predict structure-property relationships in materials and devices, including machine learning methods, with an emphasis on organic photovoltaics. The contribution by Megarity and Armstrong presents the 'electrochemical leaf' for improvements in electrochemistry and beyond. In addition, biohybrid approaches can take advantage of efficient and specific enzyme catalysts. These articles present the nanoscience and technology at the forefront of renewable energy development that will have significant benefits to society.

Isolation and Structure Elucidation of Additional Alkaloids from the Tropical Rainforest Tree Galbulimima baccata.

The structures of five new natural products (GB 27-GB 31, 1-5), isolated as minor components from the bark of Galbulimima baccata, have been determined by 2D NMR spectroscopy in combination with DFT calculations. Among the alkaloids, GB 31 (5) belongs to Class I, GB 27 (1) and 28 (2) belong to Class II, and GB 30 (4) belongs to Class III GB alkaloids. GB 31 is the first non-nitrogen-containing GB "alkaloid", being a biosynthetic oxidation product of himbacine, himandravine, or himbeline. GB 29 (3) has an entirely new natural product scaffold but belongs to Class IV (miscellaneous alkaloids). The isolation of a new Galbulimima scaffold has revealed a new pathway in the biosynthesis of the GB alkaloids. The new molecules isolated have shed further light on the biogenetic relationship among these structurally unique and complex groups of alkaloids. We present, for the first time, a unified biogenesis for the GB alkaloids that were first isolated in the 1950s and now number over 40 examples. This work also brings full circle the story of Galbulimima alkaloids. A life-long project of Wal Taylor involving one of his first students (Lew Mander) and one of his last students (Peter Karuso), a story stretching over six decades, has come to a final conclusion.

The Common Sunstar Crossaster papposus-A Neurotoxic Starfish.

Saxitoxins (STXs) are a family of potent neurotoxins produced naturally by certain species of phytoplankton and cyanobacteria which are extremely toxic to mammalian nervous systems. The accumulation of STXs in bivalve molluscs can significantly impact animal and human health. Recent work conducted in the North Sea highlighted the widespread presence of various saxitoxins in a range of benthic organisms, with the common sunstar (Crossaster papposus) demonstrating high concentrations of saxitoxins. In this study, an extensive sampling program was undertaken across multiple seas surrounding the UK, with 146 starfish and 5 brittlestars of multiple species analysed for STXs. All the common sunstars analysed (n > 70) contained quantifiable levels of STXs, with the total concentrations ranging from 99 to 11,245 µg STX eq/kg. The common sunstars were statistically different in terms of toxin loading to all the other starfish species tested. Two distinct toxic profiles were observed in sunstars, a decarbomylsaxitoxin (dcSTX)-dominant profile which encompassed samples from most of the UK coast and an STX and gonyautoxin2 (GTX2) profile from the North Yorkshire coast of England. Compartmentalisation studies demonstrated that the female gonads exhibited the highest toxin concentrations of all the individual organs tested, with concentrations >40,000 µg STX eq/kg in one sample. All the sunstars, male or female, exhibited the presence of STXs in the skin, digestive glands and gonads. This study highlights that the common sunstar ubiquitously contains STXs, independent of the geographical location around the UK and often at concentrations many times higher than the current regulatory limits for STXs in molluscs; therefore, the common sunstar should be considered toxic hereafter.

Multiple New Paralytic Shellfish Toxin Vectors in Offshore North Sea Benthos, a Deep Secret Exposed.

In early 2018, a large easterly storm hit the East Anglian coast of the UK, colloquially known as the 'Beast from the East', which also resulted in mass strandings of benthic organisms. There were subsequent instances of dogs consuming such organisms, leading to illness and, in some cases, fatalities. Epidemiological investigations identified paralytic shellfish toxins (PSTs) as the cause, with toxins present in a range of species and concentrations exceeding 14,000 µg STX eq./kg in the sunstar Crossaster papposus. This study sought to better elucidate the geographic spread of any toxicity and identify any key organisms of concern. During the summers of 2018 and 2019, various species of benthic invertebrates were collected from demersal trawl surveys conducted across a variety of locations in the North Sea. An analysis of the benthic epifauna using two independent PST testing methods identified a 'hot spot' of toxic organisms in the Southern Bight, with a mean toxicity of 449 µg STX eq./kg. PSTs were quantified in sea chervil (Alcyonidium diaphanum), the first known detection in the phylum bryozoan, as well as eleven other new vectors (>50 µg STX eq./kg), namely the opisthobranch Scaphander lignarius, the starfish Anseropoda placenta, Asterias rubens, Luidia ciliaris, Astropecten irregularis and Stichastrella rosea, the brittlestar Ophiura ophiura, the crustaceans Atelecyclus rotundatus and Munida rugosa, the sea mouse Aphrodita aculeata, and the sea urchin Psammechinus miliaris. The two species that showed consistently high PST concentrations were C. papposus and A. diaphanum. Two toxic profiles were identified, with one dominated by dcSTX (decarbamoylsaxitoxin) associated with the majority of samples across the whole sampling region. The second profile occurred only in North-Eastern England and consisted of mostly STX (Saxitoxin) and GTX2 (gonyautoxin 2). Consequently, this study highlights widespread and variable levels of PSTs in the marine benthos, together with the first evidence for toxicity in a large number of new species. These findings highlight impacts to 'One Health', with the unexpected sources of toxins potentially creating risks to animal, human and environmental health, with further work required to assess the severity and geographical/temporal extent of these impacts.

An Analysis of the Optometric Applicant Pool Relative to Matriculants.

SIGNIFICANCE: The interplay of applicants to optometry school and matriculants has not been explored systematically. It is vital that the profession examines these trends to ensure a viable pipeline of future doctors of optometry. PURPOSE: The purpose of this study was to describe the demographics and academic qualifications of entering optometry classes from autumn 2010 through autumn 2018 of U.S.-based optometric institutions' application pool and matriculants (enrollees). METHODS: Data were gathered from reports generated from accredited schools and colleges of optometry in the United States and compiled by the Association of Schools and Colleges of Optometry (publicly available) and the Optometry Centralized Application Service. Metrics included the annual number of verified applicants, the annual number of matriculants, the home region of U.S.-based applicants, and the Optometry Admission Test (OAT) performance and grade point average of verified applicants. RESULTS: The number of verified applicants for autumn 2018 was 0.95% higher than that for autumn 2010, yet the number of matriculants in 2018 compared with 2010 increased by 11.2% with an applicant-to-matriculant ratio in 2010 of 1.53 compared with 1.39 in 2018. Grade point average and academic average OAT scores were stable from 2010 to 2018. The ratios of verified applicants with an academic average OAT score of at least 300 to matriculants were 0.87 for autumn 2018 and 0.92 for autumn 2010. The ratios of verified applicants with a grade point average of at least 3.00 to matriculants were 1.13 for autumn 2018 and 1.23 for autumn 2015. CONCLUSIONS: Evidence supports the conclusion that the applicant pool has remained essentially flat for the last decade, whereas the number of matriculants has increased substantially; thus, the number of qualified applicants to matriculants has logically decreased. In the last 2 years, optometric programs have responded by decreasing their institution's number of matriculants to accommodate the national trends.

First record of recurring reproduction of captive tawny nurse sharks Nebrius ferrugineus.

Between 2008 and 2015, a group of tawny nurse sharks Nebrius ferrugineus reproduced successfully in a captive environment on the central Red Sea coast of Saudi Arabia. Births occurred on an annual basis, except for 2013. Of 12 confirmed birthing events, the most recent (2015) was observed and recorded in detail, which further contributes to the limited reproductive knowledge of this monotypic species.

Syntheses of Gibberellins A15 and A24, the Key Metabolites in Gibberellin Biosynthesis.

Gibberellins (GAs) are essential phytohormones involved in numerous aspects of plant growth and development. Notably, the biochemistry and genetics of GA biosynthesis, which is associated with their endogenous regulation, have been largely resolved; however, a crucial unsolved question remains: the precise mechanism of the stepwise oxidation and subsequent removal of C-20 from C20 precursors, leading to bioactive C19 gibberellins, is still unresolved. To satisfy numerous requests from biologists, practical preparations of certain GAs that were isolated in miniscule quantities are highly demanded. Herein, we report the first practical syntheses of GA15 and GA24, the key C20 metabolites in gibberellin biosynthesis, from commercially available GA3. The protocols are robust and offer the capacity to produce GA24 and GA15 under gram scales in high overall yields and thus aid in further biological and related studies.

Acute hypoxaemia and vascular function in healthy humans.

NEW FINDINGS: What is the central question of this study? Endothelium-dependent flow-mediated dilatation (FMD) is impaired during acute (60 min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)-induced dilatation] is impaired during acute hypoxic exposure. What is the main finding and its importance? A graded impairment in FMD and GTN-induced dilatation was evident during acute (≤60 min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN-induced dilatation. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050 m), and FMD is impaired after acute exposure (<60 min) to normobaric hypoxia equivalent to ∼5050 m (inspired oxygen fraction âˆ¼0.11). Whether GTN-induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30 min of mild (end-tidal PO2 74 ± 2 mmHg) and moderate (end-tidal PO2 50 ± 3 mmHg) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, -1.2 ± 1.1 versus -3.1 ± 1.7%; P = 0.01) and GTN-induced dilatation (-2.1 ± 1.0 versus -4.2 ± 2.0%; P = 0.01); the declines in FMD and GTN-induced dilatation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6 ± 0.9 versus 0.8 ± 0.7%; P ≤ 0.01). After 30 min of normoxic time control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN-induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30 min of supine rest/inactivity.

Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial.

BACKGROUND: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). PATIENTS AND METHODS: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure-response analysis was undertaken. RESULTS: Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69-1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure-response analysis indicated that patients with higher ramucirumab exposure had longer OS. CONCLUSION: The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population. CLINICALTRIALSGOV IDENTIFIER: NCT01246960.

Microengineering Laser Plasma Interactions at Relativistic Intensities.

We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.

Abstracts reporting of HIV/AIDS randomized controlled trials in general medicine and infectious diseases journals: completeness to date and improvement in the quality since CONSORT extension for abstracts.

BACKGROUND: Sufficiently detailed abstracts of randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. We aimed at comparing reporting quality of RCTs in HIV/AIDS medicine before and after the publication of the 2008 CONSORT extension for abstracts and to investigate factors associated with better reporting quality. METHODS: We searched PubMed/Medline for HIV/AIDS RCTs published between 2006-07 (Pre-CONSORT) and 2014-15 (Post-CONSORT) in 40 leading general medicine and infectious diseases journals. Two investigators extracted data and scored abstracts. The primary outcome was the adjusted mean number of items reported among the 17 required. Proportions of abstracts reporting each of 17 items were considered as secondary outcome. The adjustment was done for journal field, CONSORT endorsement, abstract format, type of intervention, journal impact factor and authorship. This study received no funding. RESULTS: The adjusted mean number of reported items was 7.2 (95 % CI 6.6-7.7) in pre-CONSORT (n = 159) and 7.8 (95 % confidence interval [CI] 7.3-8.4) in post-CONSORT (n = 153) (mean difference 0.7; 95 % CI 0.1-1.2). Journal high impact factor (adjusted incidence rate ratio 2.16; 95 % CI 1.83-2.54), abstract with 13 authors or more (1.39; 95 % CI 1.07-1.79) and non-pharmacological intervention (1.19; 95 % CI 1.03-1.37) were independent factors for better reporting quality. There were significant improvements in reporting on participants, randomization, outcome results, registration and funding; regression for author contact; and no change for other items: title, design, interventions, objective, primary outcome, blinding, number randomized, recruitment, number analyzed, harms and conclusions. CONCLUSIONS: After the publication of the CONSORT extension for abstracts, the reporting quality of HIV/AIDS RCT abstracts in general medicine and infectious diseases journals has suboptimally improved. Thus, stricter adherence to the CONSORT for abstract are needed to improve the reporting quality of HIV/AIDS RCT abstracts.

Evidence for selection on gene expression in cultivated rice (Oryza sativa).

Artificial selection has been used throughout plant domestication and breeding to develop crops that are adapted to diverse environments. Here, we investigate whether gene regulatory changes have been widespread targets of lineage-specific selection in cultivated lines Minghui 63 and Zhenshan 97 of rice, Oryza sativa. A line experiencing positive selection for either an increase or a decrease in genes' transcript abundances is expected to have an overabundance of expression quantitative trait locus (eQTL) alleles that increase or decrease those genes' expression, respectively. Results indicate that several genes that share Gene Ontology terms or are members of the same coexpression module have eQTL alleles from one parent that consistently increase gene expression relative to the second parent. A second line of evidence for lineage-specific selection is an overabundance of cis-trans pairs of eQTL alleles that affect gene expression in the same direction (are reinforcing). Across all cis-trans pairs of eQTL, including pairs that both weakly and strongly affect gene expression, there is no evidence for selection. However, the frequency of genes with reinforcing eQTL increases with eQTL strength. Therefore, there is evidence that eQTL with strong effects were positively selected during rice cultivation. Among 41 cis-trans pairs with strong trans eQTL, 31 have reinforcing eQTL. Several of the candidate genes under positive selection accurately predict phenotypic differences between Minghui 63 and Zhenshan 97. Overall, our results suggest that positive selection for regulatory alleles may be a key factor in plant improvement.

Colonisation of dentures by Staphylococcus aureus and MRSA in out-patient and in-patient populations.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen, and colonisation with this organism can result in localised or systemic infections which may be fatal. One hundred in-patients admitted to a London teaching hospital and 100 out-patients attending prosthetic dentistry clinics were recruited into this study. Of the 100 out-patients, 27 % harboured S. aureus on their dentures, compared to 33 % of in-patients. Only one out-patient had MRSA colonising their dentures whereas 12 % of the in-patients harboured MRSA. The median total bacterial count of the denture plaque samples was 6.2 × 10(7) cfu/sample and 6.9 × 10(7) cfu/sample for the out-patient and in-patient populations, respectively. In most instances, where present, S. aureus comprised less than 1 % of the total viable denture microbiota. Phage typing demonstrated that EMRSA-15 and non-typeable strains were harboured on dentures. The results of this study have revealed that dentures are a potential reservoir of MRSA and so account should be taken of these findings when planning decontamination procedures for elimination of this pathogen.

Influence of nocturnal and daytime sleep on initial orthostatic hypotension.

PURPOSE: The incidence of vasovagal syncope is more common in the morning. Previous researchers have reported negligible diurnal variation in the physiological responses associated with initial orthostatic hypotension (IOH). Nevertheless, physical activity and sleep prior to morning and afternoon test times have not been controlled and may influence the findings. We designed a semi-constant routine protocol to examine diurnal variation in cardiorespiratory and cerebrovascular responses to active standing. METHODS: At 06:00 and 16:00 hours, nine males (27 ± 9 years) completed an upright-stand protocol. Altimetry-measured sleep durations were 3.3 ± 0.4 and 3.2 ± 0.6 h immediately prior to the morning and afternoon test times. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv), mean arterial blood pressure (MAP), heart rate (HR), and end-tidal carbon dioxide were obtained. Intestinal body temperature and salivary melatonin concentrations were also measured. RESULTS: Compared with the afternoon, resting HR and body temperature were 4 ± 2 beats min(-1) and 0.45 ± 0.2 °C lower, respectively, whereas melatonin concentration was 28.7 ± 3.2 pg ml(-1) higher in the morning (P ≤ 0.02). Although all individuals experienced IOH at both times of the day, the initial decline in MAP during standing was 13 ± 4 mmHg greater in the afternoon (P = 0.01). Nevertheless, the decline in MCAv was comparable at both times of day (mean difference: 2 ± 3 cm s(-1); P = 0.5). CONCLUSION: These findings indicate that a bout of sleep in the afternoon in healthy young individuals results in greater IOH that is compensated for by effective cerebral blood flow regulation.