Compressively sampling the optical transmission matrix of a multimode fibre.

The measurement of the optical transmission matrix (TM) of an opaque material is an advanced form of space-variant aberration correction. Beyond imaging, TM-based methods are emerging in a range of fields, including optical communications, micro-manipulation, and computing. In many cases, the TM is very sensitive to perturbations in the configuration of the scattering medium it represents. Therefore, applications often require an up-to-the-minute characterisation of the fragile TM, typically entailing hundreds to thousands of probe measurements. Here, we explore how these measurement requirements can be relaxed using the framework of compressive sensing, in which the incorporation of prior information enables accurate estimation from fewer measurements than the dimensionality of the TM we aim to reconstruct. Examples of such priors include knowledge of a memory effect linking the input and output fields, an approximate model of the optical system, or a recent but degraded TM measurement. We demonstrate this concept by reconstructing the full-size TM of a multimode fibre supporting 754 modes at compression ratios down to ∼5% with good fidelity. We show that in this case, imaging is still possible using TMs reconstructed at compression ratios down to ∼1% (eight probe measurements). This compressive TM sampling strategy is quite general and may be applied to a variety of other scattering samples, including diffusers, thin layers of tissue, fibre optics of any refractive profile, and reflections from opaque walls. These approaches offer a route towards the measurement of high-dimensional TMs either quickly or with access to limited numbers of measurements.

Seeing around corners with edge-resolved transient imaging.

Non-line-of-sight (NLOS) imaging is a rapidly growing field seeking to form images of objects outside the field of view, with potential applications in autonomous navigation, reconnaissance, and even medical imaging. The critical challenge of NLOS imaging is that diffuse reflections scatter light in all directions, resulting in weak signals and a loss of directional information. To address this problem, we propose a method for seeing around corners that derives angular resolution from vertical edges and longitudinal resolution from the temporal response to a pulsed light source. We introduce an acquisition strategy, scene response model, and reconstruction algorithm that enable the formation of 2.5-dimensional representations-a plan view plus heights-and a 180∘ field of view for large-scale scenes. Our experiments demonstrate accurate reconstructions of hidden rooms up to 3 meters in each dimension despite a small scan aperture (1.5-centimeter radius) and only 45 measurement locations.

Considering tumour volume for motion corrected DWI of colorectal liver metastases increases sensitivity of ADC to detect treatment-induced changes.

ADC is a potential post treatment imaging biomarker in colorectal liver metastasis however measurements are affected by respiratory motion. This is compounded by increased statistical uncertainty in ADC measurement with decreasing tumour volume. In this prospective study we applied a retrospective motion correction method to improve the image quality of 15 tumour data sets from 11 patients. We compared repeatability of ADC measurements corrected for motion artefact against non-motion corrected acquisition of the same data set. We then applied an error model that estimated the uncertainty in ADC repeatability measurements therefore taking into consideration tumour volume. Test-retest differences in ADC for each tumour, was scaled to their estimated measurement uncertainty, and 95% confidence limits were calculated, with a null hypothesis that there is no difference between the model distribution and the data. An early post treatment scan (within 7 days of starting treatment) was acquired for 12 tumours from 8 patients. When accounting for both motion artefact and statistical uncertainty due to tumour volumes, the threshold for detecting significant post treatment changes for an individual tumour in this data set, reduced from 30.3% to 1.7% (95% limits of agreement). Applying these constraints, a significant change in ADC (5th and 20th percentiles of the ADC histogram) was observed in 5 patients post treatment. For smaller studies, motion correcting data for small tumour volumes increased statistical efficiency to detect post treatment changes in ADC. Lower percentiles may be more sensitive than mean ADC for colorectal metastases.

Computational periscopy with an ordinary digital camera.

Computing the amounts of light arriving from different directions enables a diffusely reflecting surface to play the part of a mirror in a periscope-that is, perform non-line-of-sight imaging around an obstruction. Because computational periscopy has so far depended on light-travel distances being proportional to the times of flight, it has mostly been performed with expensive, specialized ultrafast optical systems1-12. Here we introduce a two-dimensional computational periscopy technique that requires only a single photograph captured with an ordinary digital camera. Our technique recovers the position of an opaque object and the scene behind (but not completely obscured by) the object, when both the object and scene are outside the line of sight of the camera, without requiring controlled or time-varying illumination. Such recovery is based on the visible penumbra of the opaque object having a linear dependence on the hidden scene that can be modelled through ray optics. Non-line-of-sight imaging using inexpensive, ubiquitous equipment may have considerable value in monitoring hazardous environments, navigation and detecting hidden adversaries.

Combinatorial Treatment Effects in a Cell Culture Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, and as its prevalence increases, so does its detrimental impact on society. The currently available therapies have limited efficacy, leaving AD patients on an irrevocably fatal path of this disease. OBJECTIVE: The purpose of this study was to test efficacy of a novel combinatorial treatment approach to alleviate AD-like pathology. METHODS: We selected four naturally occurring compounds and used them in different combinations to test their effect on AD-like pathology. Employing a well-established cell culture AD model system, we evaluated levels of several diverse biomarkers associated with a number of cellular pathways associated with AD. The readouts included: amyloid-ß peptides, anti-inflammatory and anti-apoptotic proteins, oxidative enzymes, and reactive oxygen species. RESULTS: Using this approach, we demonstrated that the compounds delivered in combination had higher efficacy than individual treatments. Specifically, we observed significant reduction in levels of the amyloid-ß peptides, as well as pro-inflammatory proteins and reactive oxygen species. Similarly, delivery of compounds in combination resulted in an increased expression of anti-apoptotic proteins and anti-oxidative enzymes. Collectively, these modifications in AD pathology biomarkers reflect a promising therapeutic and preventive strategy to combat this disease. CONCLUSION: The above findings support a novel therapeutic approach to address a currently unmet medical need, which would benefit not only AD patients and their caregivers, but also society as a whole.

Transcranial Doppler-Based Surrogates for Cerebral Blood Flow: A Statistical Study.

It is commonly assumed that perfusion in a given cerebral territory can be inferred from Blood Flow Velocity (BFV) measurements in the corresponding stem artery. In order to test this hypothesis, we construct a cerebral blood flow (CBF) estimator based on transcranial Doppler (TCD) blood flow velocity and ten other easily available patient characteristics and clinical parameters. A total of 261 measurements were collected from 88 older patients. The estimator is based on local regression (Random Forest). Its performance is analyzed against baseline CBF from 3-D pseudocontinuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI). Patient specific CBF predictions are of poor quality (r = 0.41 and p-value = 4.5 × 10-12); the hypothesis is thus not clearly supported by evidence.

Integrated molecular, physiological and in silico characterization of two Halomonas isolates from industrial brine.

Two haloalkaliphilic bacteria isolated from industrial brine solutions were characterized via molecular, physiological, and in silico metabolic pathway analyses. Genomes from the organisms, designated Halomonas BC1 and BC2, were sequenced; 16S ribosomal subunit-based phylogenetic analysis revealed a high level of similarity to each other and to Halomonas meridiana. Both strains were moderate halophiles with near optimal specific growth rates (≥60 % µ max) observed over <0.1-5 % (w/v) NaCl and pH ranging from 7.4 to 10.2. Isolate BC1 was further characterized by measuring uptake or synthesis of compatible solutes under different growth conditions; in complex medium, uptake and accumulation of external glycine betaine was observed while ectoine was synthesized de novo in salts medium. Transcriptome analysis of isolate BC1 grown on glucose or citrate medium measured differences in glycolysis- and gluconeogenesis-based metabolisms, respectively. The annotated BC1 genome was used to build an in silico, genome-scale stoichiometric metabolic model to study catabolic energy strategies and compatible solute synthesis under gradients of oxygen and nutrient availability. The theoretical analysis identified energy metabolism challenges associated with acclimation to high salinity and high pH. The study documents central metabolism data for the industrially and scientifically important haloalkaliphile genus Halomonas.

Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin.

Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.

Fungi on the skin: dermatophytes and Malassezia.

Several human skin diseases and disorders are associated with two groups of fungi, the dermatophytes and Malassezia. Although these skin-related problems are not generally life threatening, they are among the most common diseases and disorders of mankind. These fungi are phylogenetically divergent, with the dermatophytes within the Ascomycota and Malassezia within Basidiomycota. Genome analysis indicates that the adaptations to the skin environment are different in these two groups of fungi. Malassezia are dependent on host lipids and secrete lipases and phospholipases that likely release host fatty acids. The dermatophytes encode multiple enzymes with potential roles in modulating host interactions: polyketide synthases, nonribosomal peptide synthetases, LysM, proteases, kinases, and pseudokinases. These two fungal groups have maximized their interactions with the host using two very different mechanisms.

Underrepresented minorities in academic medicine: is Florida better off?

OBJECTIVES: The state of Florida has experienced challenges recruiting and retaining underrepresented minority faculty in academic medicine, as well as maintaining a population-like balance of minority physicians practicing in the state. We sought to quantify the percentage of practicing minority physicians as compared to the general population of Florida and focus specifically on black, Hispanic, and Asian/Pacific Islander physicians in academic medicine. We hypothesized that because of the diversity of the state, the number of underrepresented minority academic physicians in Florida would be higher than the national average. METHODS: Data were derived and analyzed from a biennial survey initiated in 2007 that all physicians renewing licenses in Florida are required to complete. Fifty percent of the licensing cohort completes the survey annually. We focused on physician practice demographics and academic employment. RESULTS: Blacks make up 15.4% of the state population, 6.4% of practicing physicians, but only 3.9% of academic physicians. Hispanics are 22.8% of the state population, 19.2% of practicing physicians, but only 12.5% of academic physicians. Asians are 2.5% of the state population, 14.4% of practicing physicians, and 12.6% of academic physicians. Whites are 58% of the state population, 52% of practicing physicians, and 65% of academic physicians. CONCLUSIONS: There is disparity in clinical practice and academic medicine for blacks and Hispanics. Despite the diversity of the state, the disparity of blacks in academic medicine in Florida only marginally exceeds the national average. Asians and Hispanics make up the same percentage of academic physicians, but there are 10 times more Hispanics in the state. More research and programming are needed to further define and arrive at solutions to this problem.

Students' perceptions of the impact a creative arts journal has on their medical education.

BACKGROUND AND OBJECTIVES: Student-produced creative arts journals now exist in several medical schools. The Florida State University College of Medicine (FSUCOM) has created HEAL: Humanism Evolving through Arts and Literature. This study sought to determine what influence, if any, HEAL publications may have on medical students. METHODS: A survey utilizing Likert scale questions was sent to Florida State University medical students. Student responses were tabulated and analyzed using SAS 9.2 and MS Excel. A total of 241 (49.5%) students responded to the survey. RESULTS: About 81% of the respondents enjoyed reading HEAL. Many respondents agreed that HEAL promoted patient-centered care (55.9%) and could prevent burnout (61.8%). Sixty-four percent thought that HEAL helped them to understand their colleagues and classmates. CONCLUSIONS: This survey found that the medical students perceive HEAL as having positive value.

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

UNLABELLED: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci. IMPORTANCE: Malassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.

Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.

The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response.

Adolescent cigarette smokers' and non-cigarette smokers' use of alternative tobacco products.

INTRODUCTION: This study uses the most recent data from the nationally representative National Youth Tobacco Survey (NYTS) to examine the use of alternative tobacco products among U.S. cigarette smokers and non-cigarette smokers aged 14-17. Alternative tobacco product use is defined as use of one or more of the following products: smokeless tobacco, cigars, pipes, bidis, or kreteks. METHODS: Using the results from the 2004, 2006, and 2009 NYTS, multivariate logistic regressions were used to investigate separately the extent of alternative tobacco product use in current cigarette smokers and in those who reported not smoking cigarettes controlling for demographic and other independent influences. RESULTS: The results indicate that for adolescent smokers and nonsmokers, the use of one type of alternative tobacco product made it much more likely the individual would use one or more of the other alternative tobacco products. Non-cigarette smokers using these tobacco products appeared to exhibit symptoms of nicotine dependence comparable to those of cigarette smokers. CONCLUSIONS: More information on adolescent use of alternative tobacco products is needed. Current cigarette use declined 3.4% annually over 2004-2009 for the NYTS 14- to 17-year-old population, but this cohort's use of alternative tobacco products was unchanged. The number of adolescents aged 14-17 who did not smoke cigarettes but used alternative tobacco products increased 5.9% per year over the same period. Current surveillance measures need to be expanded in order to gain a more comprehensive understanding of adolescent alternative tobacco use.

Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins.

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.

Access to cigarettes by daily smokers in Florida's public middle schools and high schools.

INTRODUCTION: Youth who smoke daily have diverse methods for obtaining cigarettes, which range from commercial sources to essentially black market transactions. This study examines access to cigarettes, attitudes toward tobacco, and the demographic characteristics of youth who are daily cigarette smokers. METHODS: Biennial data from the Florida Youth Tobacco Survey, a representative sample of Florida public middle- and high-school students, were used. Daily smoking was categorized into ordinal categories of increasing intensity. Analysis was done with a logistic partial proportional odds model, which allowed the effects of the independent predictors to vary according to smoking intensity. RESULTS: The multivariate analysis revealed that males and females have different methods of obtaining cigarettes. Moreover, certain modes of access to cigarettes were related to daily smoking intensity. Males who obtained cigarettes from their parents or stole them from a store were much more likely to have a higher intensity of daily smoking. Females who gave someone money to buy their cigarettes or bought them from a person were more likely to smoke more cigarettes per day. Males, but not females, also perceived that increasing the number of cigarettes smoked per day provides social benefits in the form of more friends. CONCLUSIONS: Understanding how daily youth smokers obtain cigarettes is necessary if effective antitobacco policies are to be developed for these individuals. Daily youth smokers are at increased risk of becoming addicted to nicotine, making them more likely to transition to daily adult smoking.

Bypassing the local rural hospital for outpatient procedures.

PURPOSE: To assess the amount of local rural hospital outpatient department (HOPD) bypass for outpatient procedures. METHODS: We analyzed data on colonoscopies and upper gastrointestinal endoscopies performed in the state of Florida over the period 1997-2004. FINDINGS: Approximately, 53% of colonoscopy and 45% of upper gastrointestinal endoscopy patients bypassed their local rural hospital for treatment at either a free-standing ambulatory surgical center (ASC) or a nonlocal hospital outpatient department. Independent predictors of bypass included risk-adjusted severity of the patient's medical condition, insurance status, and race. Patients treated in ASCs were predominately healthier, white and commercially insured. Nonlocal HOPDs tend to treat a sicker cohort of patients who were publicly insured or under managed care. CONCLUSIONS: The results indicate that patients who bypass their local HOPD to an ASC differ from those bypassing to a nonlocal HOPD, and that patient factors influencing bypass for outpatient procedures differ from those influencing inpatient bypass. From a policy perspective, as procedures continue to migrate from the inpatient to the outpatient setting, bypassing the local rural hospital for treatment elsewhere could create conditions that negatively impact rural hospital operations.

How well does diagnosis-based risk-adjustment work for comparing ambulatory clinical outcomes?

This paper examines the empirical consistency of the Diagnosis Cost Groups/Hierarchical Condition Categories (DCG/HCC) risk-adjustment method for comparing 7-day mortality between hospital-based outpatient departments (HOPDs) and freestanding ambulatory surgery centers (ASCs). We used patient level data for the three most common outpatient procedures provided during the 1997-2004 period in Florida. We estimated base-line logistic regression models without any diagnosis-based risk adjustment and compared them to logistic regression models with the DCG/HCC risk-adjustment, and to conditional logit models with a matched cohort risk-adjustment approach. We also evaluated models that adjusted for primary diagnoses only, and then for all available diagnoses, to assess how the frequently absent secondary diagnoses fields in ambulatory surgical data affect risk-adjustment. We found that risk-adjustment using both diagnosis-based methods resulted in similar 7-day mortality estimates for HOPD patients in comparison with ASC patients in two out of three procedures. We conclude that the DCG/HCC risk-adjustment method is relatively consistent and stable, and recommend this risk-adjustment method for health policy research and practice with ambulatory surgery data. We also recommend using risk-adjustment with all available diagnoses.