Experimental demonstration of quantum-inspired optical symmetric hypothesis testing.

We use a phase-sensitive measurement to perform a binary hypothesis testing, i.e., distinguish between one on-axis and two symmetrically displaced Gaussian point spread functions. In the sub-Rayleigh regime, we measure a total error rate lower than allowed by direct imaging. Our results experimentally demonstrate that linear-optical spatial mode transformations can provide useful advantages for object detection compared with conventional measurements, even in the presence of realistic experimental cross talk, paving the way for meaningful improvements in identifying, detecting, and monitoring real-world, diffraction-limited scenes.

The mitigated carbon emissions of transitioning to virtual medical school and residency interviews: A survey-based study.

PURPOSE: Prior to COVID, thousands of medical school and residency applicants traversed their countries for in-person interviews each year. However, data on the greenhouse gas emissions from in-person interviews is limited. This study estimated greenhouse gas emissions associated with in-person medical school and residency interviews and explored applicant interview structure preferences. METHODS: From March to June 2022, we developed and distributed a nine-question, website-based survey to collect information on applicant virtual interview schedule, demographics and preference for future interview format. We calculated theoretical emissions for all interviews requiring air travel and performed a content analysis of interview preference explanations. RESULTS: We received responses from 258 first-year and 253 fourth-year medical students at 26 allopathic US medical schools who interviewed virtually in 2020-2021 and 2021-2022, respectively. Residency applicants participating in the study were interviewed at a mean of 15.3 programs (SD 5.4) and had mean theoretical emissions of 4.31 tons CO2 eq. Medical school applicants participating in the study were interviewed at a mean of 6.9 programs and had mean theoretical emissions of 2.19 tons CO2 eq. Ninety percent of medical school applicants and 91% of residency applicants participating in the study expressed a preference for hybrid or virtual interviews going forward. CONCLUSION: In-person medical training interviews have significant greenhouse gas emissions. Virtual and hybrid alternatives have a high degree of acceptability among applicants.

Negative Nonlinear CD-ee Dependence in Polycrystalline BINOL Thin Films.

Generally, the relationship between the observed circular dichroism and the enantiomeric excess in chiral systems (CD-ee dependence) is linear. While positive nonlinear behavior has often been reported in the past, examples of negative nonlinear (NN) behavior in CD-ee dependence are rare and not well understood. Here, we present a strong NN CD-ee dependence within polycrystalline thin films of BINOL by using second-harmonic-generation circular dichroism (SHG-CD) and commercial CD spectroscopy studies. Theoretical calculations, microscopy, and FTIR studies are employed to further clarify the underlying cause of this observation. This behavior is attributed to the changing supramolecular chirality of the system. Systems exhibiting NN CD-ee dependence hold promise for highly accurate enantiomeric excess characterization, which is essential for the refinement of enantio-separating and -purifying processes in pharmaceuticals, asymmetric catalysis, and chiral sensing. Our findings suggest that a whole class of single-species systems, i.e., racemate crystals, might possess NN CD-ee dependence and thus provide us a vast playground to better understand and exploit this phenomenon.

Predicting ExWAS findings from GWAS data: a shorter path to causal genes.

GWAS has identified thousands of loci associated with disease, yet the causal genes within these loci remain largely unknown. Identifying these causal genes would enable deeper understanding of the disease and assist in genetics-based drug development. Exome-wide association studies (ExWAS) are more expensive but can pinpoint causal genes offering high-yield drug targets, yet suffer from a high false-negative rate. Several algorithms have been developed to prioritize genes at GWAS loci, such as the Effector Index (Ei), Locus-2-Gene (L2G), Polygenic Prioritization score (PoPs), and Activity-by-Contact score (ABC) and it is not known if these algorithms can predict ExWAS findings from GWAS data. However, if this were the case, thousands of associated GWAS loci could potentially be resolved to causal genes. Here, we quantified the performance of these algorithms by evaluating their ability to identify ExWAS significant genes for nine traits. We found that Ei, L2G, and PoPs can identify ExWAS significant genes with high areas under the precision recall curve (Ei: 0.52, L2G: 0.37, PoPs: 0.18, ABC: 0.14). Furthermore, we found that for every unit increase in the normalized scores, there was an associated 1.3-4.6-fold increase in the odds of a gene reaching exome-wide significance (Ei: 4.6, L2G: 2.5, PoPs: 2.1, ABC: 1.3). Overall, we found that Ei, L2G, and PoPs can anticipate ExWAS findings from widely available GWAS results. These techniques are therefore promising when well-powered ExWAS data are not readily available and can be used to anticipate ExWAS findings, allowing for prioritization of genes at GWAS loci.

Off-axis aberrations improve the resolution limits of incoherent imaging.

The presence of off-axis tilt and Petzval curvature, two of the lowest-order off-axis Seidel aberrations, are shown to improve the Fisher information of two-point separation estimation in an incoherent imaging system compared to an aberration-free system. Our results show that the practical localization advantages of modal imaging techniques within the field of quantum-inspired superresolution can be achieved with direct imaging measurement schemes alone.

Quantum Fisher information for estimating N partially coherent point sources.

A partially coherent object's localization parameters are shown to be theoretically estimable with higher precision than those of an incoherent object, and the maximum number of independent parameters that have non-vanishing precision in the sub-Rayleigh regime is 3 (compared to 2 for an incoherent object). Normalization schemes, which are crucial in the proper interpretation of quantum Fisher information results in the presence of partial coherence, are introduced and detailed.

MarkerDB: an online database of molecular biomarkers.

MarkerDB is a freely available electronic database that attempts to consolidate information on all known clinical and a selected set of pre-clinical molecular biomarkers into a single resource. The database includes four major types of molecular biomarkers (chemical, protein, DNA [genetic] and karyotypic) and four biomarker categories (diagnostic, predictive, prognostic and exposure). MarkerDB provides information such as: biomarker names and synonyms, associated conditions or pathologies, detailed disease descriptions, detailed biomarker descriptions, biomarker specificity, sensitivity and ROC curves, standard reference values (for protein and chemical markers), variants (for SNP or genetic markers), sequence information (for genetic and protein markers), molecular structures (for protein and chemical markers), tissue or biofluid sources (for protein and chemical markers), chromosomal location and structure (for genetic and karyotype markers), clinical approval status and relevant literature references. Users can browse the data by conditions, condition categories, biomarker types, biomarker categories or search by sequence similarity through the advanced search function. Currently, the database contains 142 protein biomarkers, 1089 chemical biomarkers, 154 karyotype biomarkers and 26 374 genetic markers. These are categorized into 25 560 diagnostic biomarkers, 102 prognostic biomarkers, 265 exposure biomarkers and 6746 predictive biomarkers or biomarker panels. Collectively, these markers can be used to detect, monitor or predict 670 specific human conditions which are grouped into 27 broad condition categories. MarkerDB is available at https://markerdb.ca.

Vibrio tarriae sp. nov., a novel member of the Cholerae clade.

A number of bacteria with close resemblance to Vibrio cholerae have been isolated over the years by the Centres for Disease Control and Prevention (CDC), which could not be assigned a proper taxonomic designation on the basis of the results from preliminary identification methods. Nine such isolates have been found to share 16S rRNA gene identity exceeding 99 % with V. cholerae, yet DNA-DNA hybridization (60.4-62.1 %) and average nucleotide identity values (94.4-95.1 %) were below the species cut-off, indicating a potentially novel species. Phylogenetic analysis of core genomes places this group of isolates in a monophyletic clade, within the 'Cholerae clade', but distinct from any other species. Extensive phenotypic characterization reveals unique biochemical properties that distinguish this novel species from V. cholerae. Comparative genomic analysis reveals a unique set of siderophore genes, indicating that iron acquisition strategies could be vital for the divergence of the novel species from a common ancestor with V. cholerae. On the basis of the genetic, phylogenetic and phenotypic differences observed, we propose that these isolates represent a novel species of the genus Vibrio, for which the name Vibrio tarriae sp. nov. is proposed. Strain 2521-89 T (= DSM 112461=CCUG 75318), isolated from lake water, is the type strain.

Dynamic Subspecies Population Structure of Vibrio cholerae in Dhaka, Bangladesh.

Cholera has been endemic to the Ganges Delta for centuries. Although the causative agent, Vibrio cholerae, is autochthonous to coastal and brackish water, cholera occurs continually in Dhaka, the inland capital city of Bangladesh which is surrounded by fresh water. Despite the persistence of this problem, little is known about the environmental abundance and distribution of lineages of V. cholerae, the most important being the pandemic generating (PG) lineage consisting mostly of serogroup O1 strains. To understand spatial and temporal dynamics of PG lineage and other lineages belonging to the V. cholerae species in surface water in and around Dhaka City, we used qPCR and high-throughput amplicon sequencing. Seven different freshwater sites across Dhaka were investigated for six consecutive months, and physiochemical parameters were measured in situ. Total abundance of V. cholerae was found to be relatively stable throughout the 6-month sampling period, with 2 × 105 to 4 × 105 genome copies/L at six sites and around 5 × 105 genome copies/L at the site located in the most densely populated part of Dhaka City. PG O1 V. cholerae was present in high abundance during the entire sampling period and composed between 24 and 92% of the total V. cholerae population, only showing occasional but sudden reductions in abundance. In instances where PG O1 lost its dominance, other lineages underwent a rapid expansion while the size of the total V. cholerae population remained almost unchanged. Intraspecies richness of V. cholerae was positively correlated with salinity, conductivity, and total dissolved solids (TDS), while it was negatively correlated with dissolved oxygen (DO) concentration in water. Interestingly, negative correlation was observed specifically between PG O1 and salinity, even though the changes in this variable were minor (0-0.8 ppt). Observations in this study suggest that at the subspecies level, population composition of naturally occurring V. cholerae can be influenced by fluctuations in environmental factors, which can lead to altered competition dynamics among the lineages.

Coherent mode decomposition of multiple quantum well light emission.

Developing a richer understanding of the various properties of light is central to the field of photonics. One often neglected degree of freedom (DOF) is the second-order correlation of the light field, known as coherence. To make proper use of this DOF, one needs to first obtain information about the field's coherence, which may be characterized through the cross spectral density (CSD) function. We present a measurement of the CSD of a ubiquitous, partially coherent source: a multiple quantum well device in its near-field region, where a photonic structure would commonly encounter the emitted field. We show a departure from the coherence area that is expected from an incoherent source and demonstrate the application of coherent mode decomposition as a way to further analyze the measured results.

Population Analysis of Vibrio cholerae in Aquatic Reservoirs Reveals a Novel Sister Species (Vibrio paracholerae sp. nov.) with a History of Association with Humans.

Most efforts to understand the biology of Vibrio cholerae have focused on a single group, the pandemic-generating lineage harboring the strains responsible for all known cholera pandemics. Consequently, little is known about the diversity of this species in its native aquatic environment. To understand the differences in the V. cholerae populations inhabiting regions with a history of cholera cases and those lacking such a history, a comparative analysis of population composition was performed. Little overlap was found in lineage compositions between those in Dhaka, Bangladesh (where cholera is endemic), located in the Ganges Delta, and those in Falmouth, MA (no known history of cholera), a small coastal town on the United States east coast. The most striking difference was the presence of a group of related lineages at high abundance in Dhaka, which was completely absent from Falmouth. Phylogenomic analysis revealed that these lineages form a cluster at the base of the phylogeny for the V. cholerae species and were sufficiently differentiated genetically and phenotypically to form a novel species. A retrospective search revealed that strains from this species have been anecdotally found from around the world and were isolated as early as 1916 from a British soldier in Egypt suffering from choleraic diarrhea. In 1935, Gardner and Venkatraman unofficially referred to a member of this group as Vibrio paracholerae. In recognition of this earlier designation, we propose the name Vibrio paracholerae sp. nov. for this bacterium. Genomic analysis suggests a link with human populations for this novel species and substantial interaction with its better-known sister species. IMPORTANCE Cholera continues to remain a major public health threat around the globe. Understanding the ecology, evolution, and environmental adaptation of the causative agent (Vibrio cholerae) and tracking the emergence of novel lineages with pathogenic potential are essential to combat the problem. In this study, we investigated the population dynamics of Vibrio cholerae in an inland locality, which is known as endemic for cholera, and compared them with those of a cholera-free coastal location. We found the consistent presence of the pandemic-generating lineage of V. cholerae in Dhaka, where cholera is endemic, and an exclusive presence of a lineage phylogenetically distinct from other V. cholerae lineages. Our study suggests that this lineage represents a novel species that has pathogenic potential and a human link to its environmental abundance. The possible association with human populations and coexistence and interaction with toxigenic V. cholerae in the natural environment make this potential human pathogen an important subject for future studies.

Experimental demonstration of superresolution of partially coherent light sources using parity sorting.

Analyses based on quantum metrology have shown that the ability to localize the positions of two incoherent point sources can be significantly enhanced over direct imaging through the use of mode sorting. Here we theoretically and experimentally investigate the effect of partial coherence on the sub-diffraction limit localization of two sources based on parity sorting. With the prior information of a negative and real-valued degree of coherence, higher Fisher information is obtained than that for the incoherent case. Our results pave the way to clarifying the role of coherence in quantum-limited metrology.

Experimental demonstration of superresolution of partially coherent light sources using parity sorting: erratum.

The authors include references that appeared on arXiv during the preparation of their paper [Opt. Express29, 22034 (2021)10.1364/OE.427734].

A carbon footprint study of the Canadian medical residency interview tour.

BACKGROUND: Each spring, thousands of Canadian medical students travel across the country to interview for residency positions, a process known as the CaRMS tour. Despite the large scale of travel, the CaRMS tour has received little environmental scrutiny. PURPOSE: To estimate the national carbon footprint of flights associated with the CaRMS tour, as well as reductions in emissions achievable by transitioning to alternative models. METHODS: We developed a three-question online commuter survey to collect the unique travel itineraries of applicants in the 2020 CaRMS tour. We calculated the emissions associated with all flights and modelled expected emissions for two alternative in-person interview models, and two virtual interview models. RESULTS: We collected 960 responses out of 2943 applicants across all 17 Canadian medical schools. We calculated the carbon footprint of flights for the 2020 CaRMS as 4239 tCO2e (tonnes of carbon dioxide equivalents), averaging 1.44 tCO2e per applicant. The average applicant's tour emissions represent 35.1% of the average Canadian's annual household carbon footprint, and the emissions of 26.7% of respondents exceeded their entire annual '2050 carbon budget.' Centralized in-person interviews could reduce emissions by 13.7% to 74.7%, and virtual interviews by at least 98.4% to 99.9%. CONCLUSIONS: Mandatory in-person residency interviews in Canada contribute significant emissions and reflect a culture of emissions-intensive practices. Considerable decarbonization of the CaRMS tour is possible, and transitioning to virtual interviews could eliminate the footprint almost entirely.

A Vibrio cholerae Core Genome Multilocus Sequence Typing Scheme To Facilitate the Epidemiological Study of Cholera.

Core genome multilocus sequence typing (cgMLST) has gained popularity in recent years in epidemiological research and subspecies-level classification. cgMLST retains the intuitive nature of traditional MLST but offers much greater resolution by utilizing significantly larger portions of the genome. Here, we introduce a cgMLST scheme for Vibrio cholerae, a bacterium abundant in marine and freshwater environments and the etiologic agent of cholera. A set of 2,443 core genes ubiquitous in V. cholerae were used to analyze a comprehensive data set of 1,262 clinical and environmental strains collected from 52 countries, including 65 newly sequenced genomes in this study. We established a sublineage threshold based on 133 allelic differences that creates clusters nearly identical to traditional MLST types, providing backwards compatibility to new cgMLST classifications. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying strains from the same outbreak and closely related isolates that could give clues on outbreak origin. Using cgMLST, we confirmed the South Asian origin of modern epidemics and identified clustering affinity among sublineages of environmental isolates from the same geographic origin. Advantages of this method are highlighted by direct comparison with existing classification methods, such as MLST and single-nucleotide polymorphism-based methods. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease of use. We anticipate this scheme will serve as a basis for a universally applicable and standardized classification system for V. cholerae research and epidemiological surveillance in the future. This cgMLST scheme is publicly available on PubMLST (https://pubmlst.org/vcholerae/).IMPORTANCE Toxigenic Vibrio cholerae isolates of the O1 and O139 serogroups are the causative agents of cholera, an acute diarrheal disease that plagued the world for centuries, if not millennia. Here, we introduce a core genome multilocus sequence typing scheme for V. cholerae Using this scheme, we have standardized the definition for subspecies-level classification, facilitating global collaboration in the surveillance of V. cholerae In addition, this typing scheme allows for quick identification of outbreak-related isolates that can guide subsequent analyses, serving as an important first step in epidemiological research. This scheme is also easily scalable to analyze thousands of isolates at various levels of resolution, making it an invaluable tool for large-scale ecological and evolutionary analyses.

Validity of the perturbation model for the propagation of MSF structures in 3D.

Mid-spatial frequency (MSF) structures on optical surfaces degrade system performance and a perturbation model is typically used to simplify the assessment of their effects. In this simple model, MSF phase structures are dragged along the nominal rays of a system to yield estimates of wavefronts in the exit pupil that may be used for further analysis. However, the validity of the perturbation model remains an open area of study. We extend our previous assessment of the validity of this model [K. Liang, Opt. Express 27, 3390-3408 (2019)] that was focused on the analysis of single-frequency MSF structures in two dimensions to now include error estimates for broad-spectra MSF structures in three dimensions.

Access to Focal Spasticity Care: A Cross Canada Survey of Physiatrists.

Successful management of focal spasticity requires access to botulinum toxin type A (BoNT-A) injections, physiotherapy, occupational therapy, and orthoses/bracing. To assess the quality of focal spasticity care across Canada, we sent a survey consisting of 22 questions to physiatrists involved in the management of outpatient spasticity. Thirty-four physiatrists from all 10 provinces responded to the survey. Wait time for BoNT-A treatment averaged 12.7 weeks from time of referral across Canada. More than 75% of patients faced barriers to obtaining physical therapy and orthoses. Access to best quality care for spasticity patients across Canada varies widely.

Theoretical analysis of quantum random walks with stress-engineered optics.

Quantum random walks (QRWs) are random processes in which the resulting probability density of the "walker" state, whose movement is governed by a "coin" state, is described in a nonclassical manner. Previously, Q-plates have been used to demonstrate QRWs with polarization and orbital angular momentum playing the roles of coin and walker states, respectively. In this theoretical analysis, we show how stress-engineered optics can be used to develop new platforms for complex QRWs through relatively simple optical elements. Our work opens up new paths to speed up classical-to-quantum transitions in robust photonic networks.

HMDB 4.0: the human metabolome database for 2018.

The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB's chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC-MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

Effects on the OTF of MSF structures with random variations.

In diamond-machined freeform manufacturing processes, a tool-tip often leaves behind characteristic mid-spatial frequency (MSF) structures on the optical surface. Unwanted movement between the tool-tip and the part results in MSF structures with random variations. Here, we analyze the effects of these MSF structures on the system's optical performance and derive simple analytic estimates for the optical transfer function in terms of the parameters of these structures. These expressions are expected to aid in MSF tolerancing.