Validation of medical service insurance claims as a surrogate for ascertaining vitiligo cases.

The epidemiology of vitiligo, especially its disease burden on the healthcare system, can be assessed indirectly by analyzing health insurance claims data. Validating this approach is integral to ensuring accurate case identification and cohort characterization. The primary aim of this study was to develop and validate an indirect measure of vitiligo ascertainment using health insurance claims data. These data were used secondarily to identify demographic characteristics, body site involvement, vitiligo subtypes, disease associations, and treatments. This study assessed the validity of identifying vitiligo from billing claims within a Canadian provincial universal health insurance program, versus vitiligo cases accrued from direct medical chart reviews. Claims-based algorithms combining ICD-9-CM diagnostic code 709 with treatment-specific data were derived and tested to identify vitiligo patients. This was compared against cases arising from the manual review of medical records of 606 patient with a diagnostic code for "dyschromia" (ICD-9-CM diagnostic code 709) from January 1 to December 31, 2016. Based on the chart reviews, 204 (33.7%) patients were confirmed to have vitiligo. 42 separate claims-based algorithms combining ICD-9-CM diagnostic code 709 with treatment data specific to vitiligo were modeled and individually tested to evaluate their accuracy for vitiligo ascertainment. One algorithm achieved a sensitivity, specificity, PPV and NPV of 86.8% (95% CI 82.1-91.4), 92.5% (95% CI 90.0-95.1), 85.5% (95% CI 80.7-90.3), and 93.2% (95% CI 90.8-95.7), respectively. There was a 2.2 female-to-male ratio. The most common medical treatments were tacrolimus (74.5%) and topical corticosteroids (54.3%). Hypertension (24.2%) and hypothyroidism (19.6%) were the predominant co-morbidities associated with vitiligo. Health insurance claims data can be used to indirectly ascertain vitiligo for epidemiologic purposes with relatively high diagnostic performance between 85.5 and 93.2%.

Pressure induced superconductivity in MnSe.

The rich phenomena in the FeSe and related compounds have attracted great interests as it provides fertile material to gain further insight into the mechanism of high temperature superconductivity. A natural follow-up work was to look into the possibility of superconductivity in MnSe. We demonstrated in this work that high pressure can effectively suppress the complex magnetic characters of MnSe, and induce superconductivity with Tc ~ 5 K at pressure ~12 GPa confirmed by both magnetic and resistive measurements. The highest Tc is ~ 9 K (magnetic result) at ~35 GPa. Our observations suggest the observed superconductivity may closely relate to the pressure-induced structural change. However, the interface between the metallic and insulating boundaries may also play an important role to the pressure induced superconductivity in MnSe.

Stigma interdependence among pregnant HIV-infected couples in a cluster randomized controlled trial from rural South Africa.

BACKGROUND: Stigma can exacerbate negative health outcomes in people living with HIV (PLWH). This longitudinal, cluster randomized controlled trial in rural Mpumalanga, South Africa, examined the interdependence of HIV-related stigma among pregnant couples living with HIV, and the potential impact of a lay health worker delivered intervention, Protect Your Family, on changes in stigma over time across couples, controlling for physical intimate partner violence (IPV), verbal IPV, gender, HIV knowledge, and months since HIV diagnosis. Using a form of the Actor-Partner Interdependence model, changes in stigma over time were also examined within each dyad of seroconcordant participants with HIV. METHOD: Antenatal clinics were randomized to experimental or control conditions, and participants completed baseline antenatal and 12-month postpartum assessments. Both women and male partners participated in intervention sessions in gender concordant groups and couple or individual sessions. RESULTS: Multilevel models (N = 1475) revealed stigma was related to condition and verbal intimate partner violence, but not time. Using an Actor-Partner Interdependence cross-lagged path model to examine within dyad changes in stigma for seroconcordant couples (n = 201), intervention condition participants' stigma levels were not interdependent over time. Women's 12-month stigma was related to their partners' stigma at baseline in the control condition, but not in the intervention condition. DISCUSSION: Compared to women in the control condition, postpartum stigma among women in the intervention condition was not related to their male partners' stigma, suggesting that women's perception of stigma became uncoupled from that of their partners. The intervention may have promoted female empowerment to shape their own beliefs and attitudes towards what it means to be infected with HIV, and express their own agency in responding to how others treat them and they treat themselves.

Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenic Escherichia coli as a prophylactic against diarrhea.

BACKGROUND: . Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A. METHODS: . This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 1010 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD). RESULTS: . A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups. CONCLUSIONS: . Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrum-derived antibodies.

A feature fusion system for basal cell carcinoma detection through data-driven feature learning and patient profile.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer, which is highly damaging in its advanced stages. Computer-aided techniques provide a feasible option for early detection of BCC. However, automated BCC detection techniques immensely rely on handcrafting high-level precise features. Such features are not only computationally complex to design but can also represent a very limited aspect of the lesion characteristics. This paper proposes an automated BCC detection technique that directly learns the features from image data, eliminating the need for handcrafted feature design. METHODS: The proposed method is composed of 2 parts. First, an unsupervised feature learning framework is proposed which attempts to learn hidden characteristics of the data including vascular patterns directly from the images. This is done through the design of a sparse autoencoder (SAE). After the unsupervised learning, we treat each of the learned kernel weights of the SAE as a filter. Convolving each filter with the lesion image yields a feature map. Feature maps are condensed to reduce the dimensionality and are further integrated with patient profile information. The overall features are then fed into a softmax classifier for BCC classification. RESULTS: On a set of 1199 BCC images, the proposed framework achieved an area under the curve of 91.1%, while the visualization of learned features confirmed meaningful clinical interpretation of the features. CONCLUSION: The proposed framework provides a non-invasive fast BCC detection tool that incorporates both dermoscopic lesional features and clinical patient information, without the need for complex handcrafted feature extraction.

The distribution of calbindinD-28k and parvalbumin immunoreactive neurons in the somatosensory area of the pigeon pallium.

GABAergic interneurons regulate the degree of glutamatergic excitation and output of projection neurons. In this study, we investigated the distribution of calbindinD-28k (CB) and parvalbumin (PV) in the somatosensory area of the pigeon pallium using immunohistochemical method. Our results show that anatomical structures of the somatosensory area of the pigeon pallium consisted of several subdivisions including the hyperpallium, intercalated hyperpallium, mesopallium, nidopallium and basorostralis. Neuronal density was significantly higher in the intercalated hyperpallium and basorostralis than that in the other subdivisions. The density of the CB immunoreactive neurons was generally similar in all the subdivisions; however, the density of PV immunoreactive neurons was particularly prominent in the basorostralis compared with that in the other subdivisions. In addition, the mean proportion of PV immunoreactive neurons to total neurons was higher than that in the CB immunoreactive neurons in all the subdivisions. In brief, our present study shows that PV immunoreactive neurons in the somatosensory area of the pigeon pallium were significantly abundant compared with CB immunoreactive neurons. This finding needs more studies regarding CB- and PV-related functions in the somatosensory area of the avian pallium.

The location of projection neurons to the biceps brachii muscle in the telencephalon of the pigeon.

Few studies regarding the anatomical distribution of motor neurons innervating muscles of the arm have been demonstrated in avian brains. The purpose of this study was to finely determine the localization of cerebral neurons innervating the biceps brachii muscle in the pigeon. The cholera toxin B subunit (CTB) was employed as a retrograde tracer to determine the location of neurons controlling the biceps brachii muscle in the telencephalon following intramuscular injection in male pigeons (n = 7), which were killed 14 days after intramuscular injection with CTB. We found that CTB-labelled neurons were located contralaterally in the hyperpallium apicale of the rostral telencephalon and that most of the CTB-labelled neurons were pyramidal in shape. This study shows that CTB is easily taken up by nerve terminals which innervate the biceps brachii muscle of the pigeon and that cerebral motor neurons controlling the biceps brachii muscle are located in the hyperpallium apicale.

Can the diagnostic reliability of the thrombin generation test as a global haemostasis assay be improved? The impact of calcium chloride concentration.

BACKGROUND: Thrombin generation test (TGT) is a global haemostasis assay with a potential to predict bleeding tendencies and treatment effects in patients with haemophilia. Despite 15 years of clinical research, the diagnostic value of TGT remains controversial, possibly due to suboptimal sensitivity to coagulation deficiencies, robustness and reproducibility. OBJECTIVE: The goal of this study was to explore the effect of calcium chloride (CaCl2 ) concentration on the TGT's response to intrinsic coagulation factors (F) VIII, IX and XIa. METHODS: Normal and factor-deficient plasmas supplemented with lacking coagulation factor and different CaCl2 levels were tested by calibrated thrombinography assay. RESULTS: Thrombin peak height (TPH) was strongly CaCl2 dependent, increasing sharply from no TG at 5 mm to a peak at 13.8 mm of CaCl2 (95% confidence interval [CI]: 13.0, 14.5) in normal and normalized deficient plasmas and at 11.9 mm (CI: 9.7, 14.2) in deficient plasmas, and then decreasing slowly to a complete inhibition at 30-40 mm. In contrast, TG lag time, time to peak and endogenous thrombin potential were nearly insensitive to CaCl2 concentrations between 10 and 20 mm. The maximal difference between the TPH in deficient and supplemented plasmas was observed at 15.5 mm (CI: 12.8, 18.1). CONCLUSION: Variations in CaCl2 concentration in the assay mixture and sodium citrate concentrations in patient plasma samples may affect TGT responses, sensitivity and result in increased inter- and intra-laboratory variance. Implementation of TGT by clinical and quality control laboratories may require optimization of CaCl2 concentration.

Expression and characterization of a codon-optimized blood coagulation factor VIII.

Essentials Recombinant factor VIII (FVIII) is known to be expressed at a low level in cell culture. To increase expression, we used codon-optimization of a B-domain deleted FVIII (BDD-FVIII). This resulted in 7-fold increase of the expression level in cell culture. The biochemical properties of codon-optimized BDD-FVIII were similar to the wild-type protein. SUMMARY: Background Production of recombinant factor VIII (FVIII) is challenging because of its low expression. It was previously shown that codon-optimization of a B-domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well recognized that synonymous mutations may affect the protein structure and function. Objectives To compare biochemical properties of a BDD-FVIII variants expressed from codon-optimized and wild-type cDNAs (CO and WT, respectively). Methods Each variant of the BDD-FVIII was expressed in several independent Chinese hamster ovary (CHO) cell lines, generated using a lentiviral platform. The proteins were purified by two-step affinity chromatography and analyzed in parallel by PAGE-western blot, mass spectrometry, circular dichroism, surface plasmon resonance, and chromogenic, clotting and thrombin generation assays. Results and conclusion The average yield of the CO was 7-fold higher than WT, whereas both proteins were identical in the amino acid sequences (99% coverage) and very similar in patterns of the molecular fragments (before and after thrombin cleavage), glycosylation and tyrosine sulfation, secondary structures and binding to von Willebrand factor and to a fragment of the low-density lipoprotein receptor-related protein 1. The CO preparations had on average 1.5-fold higher FVIII specific activity (activity normalized to protein mass) than WT preparations, which was attributed to better preservation of the CO structure as a result of considerably higher protein concentrations during the production. We concluded that the codon-optimization of the BDD-FVIII resulted in significant increase of its expression and did not affect the structure-function properties.

Gravity Spy: integrating advanced LIGO detector characterization, machine learning, and citizen science.

With the first direct detection of gravitational waves, the advanced laser interferometer gravitational-wave observatory (LIGO) has initiated a new field of astronomy by providing an alternative means of sensing the universe. The extreme sensitivity required to make such detections is achieved through exquisite isolation of all sensitive components of LIGO from non-gravitational-wave disturbances. Nonetheless, LIGO is still susceptible to a variety of instrumental and environmental sources of noise that contaminate the data. Of particular concern are noise features known as glitches, which are transient and non-Gaussian in their nature, and occur at a high enough rate so that accidental coincidence between the two LIGO detectors is non-negligible. Glitches come in a wide range of time-frequency-amplitude morphologies, with new morphologies appearing as the detector evolves. Since they can obscure or mimic true gravitational-wave signals, a robust characterization of glitches is paramount in the effort to achieve the gravitational-wave detection rates that are predicted by the design sensitivity of LIGO. This proves a daunting task for members of the LIGO Scientific Collaboration alone due to the sheer amount of data. In this paper we describe an innovative project that combines crowdsourcing with machine learning to aid in the challenging task of categorizing all of the glitches recorded by the LIGO detectors. Through the Zooniverse platform, we engage and recruit volunteers from the public to categorize images of time-frequency representations of glitches into pre-identified morphological classes and to discover new classes that appear as the detectors evolve. In addition, machine learning algorithms are used to categorize images after being trained on human-classified examples of the morphological classes. Leveraging the strengths of both classification methods, we create a combined method with the aim of improving the efficiency and accuracy of each individual classifier. The resulting classification and characterization should help LIGO scientists to identify causes of glitches and subsequently eliminate them from the data or the detector entirely, thereby improving the rate and accuracy of gravitational-wave observations. We demonstrate these methods using a small subset of data from LIGO's first observing run.

Stress, cortisol, and obesity: a role for cortisol responsiveness in identifying individuals prone to obesity.

There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity.

Natural history of deep vein thrombosis in children.

OBJECTIVE: To determine the natural history of deep vein thrombosis in children presented with a first episode in the lower extremity veins. METHODS: Children with objective diagnosis of acute deep vein thrombosis were followed up with ultrasound and clinical examination. Risk factors and clinical presentation were prospectively collected. The prevalence of recurrent deep vein thrombosis and the development of signs and symptoms of chronic venous disease were recorded. RESULTS: There were 27 children, 15 males and 12 females, with acute deep vein thrombosis, with a mean age of 4 years, range 0.1-16 years. The median follow-up was 23 months, range 8-62 months. The location of thrombosis involved the iliac and common femoral vein in 18 patients and the femoral and popliteal veins in 9. Only one vein was affected in 7 children, two veins in 14 and more than two veins in 6. Recurrent deep vein thrombosis occurred in two patients, while no patient had a clinically significant pulmonary embolism. Signs and symptoms of chronic venous disease were present at last follow-up in 11 patients. There were nine patients with vein collaterals, but no patient developed varicose veins. Reflux was found in 18 veins of 11 patients. Failure of recanalization was seen in 7 patients and partial recanalization in 11. Iliofemoral thrombosis (p = 0.012) and failure to recanalize (p = 0.036) increased significantly the risk for developing signs and symptoms. CONCLUSIONS: Children with acute proximal deep vein thrombosis develop mild chronic venous disease signs and symptoms at mid-term follow-up and are closely related with iliofemoral thrombosis and failure to recanalization.

Disappearance of nodal gap across the insulator-superconductor transition in a copper-oxide superconductor.

The parent compound of the copper-oxide high-temperature superconductors is a Mott insulator. Superconductivity is realized by doping an appropriate amount of charge carriers. How a Mott insulator transforms into a superconductor is crucial in understanding the unusual physical properties of high-temperature superconductors and the superconductivity mechanism. Here we report high-resolution angle-resolved photoemission measurement on heavily underdoped Bi2Sr2-xLaxCuO(6+δ) system. The electronic structure of the lightly doped samples exhibit a number of characteristics: existence of an energy gap along the nodal direction, d-wave-like anisotropic energy gap along the underlying Fermi surface, and coexistence of a coherence peak and a broad hump in the photoemission spectra. Our results reveal a clear insulator-superconductor transition at a critical doping level of ~0.10 where the nodal energy gap approaches zero, the three-dimensional antiferromagnetic order disappears, and superconductivity starts to emerge. These observations clearly signal a close connection between the nodal gap, antiferromagnetism and superconductivity.

Determining the impact of instrument variation and automated software algorithms on the TGT in hemophilia and normalized plasma.

BACKGROUND: Despite increasing recognition as a more precise test of in vivo hemostatic conditions, standardization of the thrombin generation test (TGT) continues to hinder its development as routine clinical practice. Prior efforts largely focused on comparing the effects of experimental conditions and different reagents. Commercialized kits, instruments and software have been introduced to calculate the TG curve and its parameters. However, modified versions of the TGT continue to be used worldwide on a variety of microplate reader instruments and processed using individualized algorithms. No prior study has compared the effect of instrument choice and its inherent noise profile on the processing of the TG curve and its common endpoint parameters. MATERIALS AND METHODS: Hemophilia A plasma supplemented with buffer or Factor VIII, mimicking hemophilic or normalized samples respectively, was monitored for thrombin generation after activation with TF on six different fluorescent microplate readers. Each instrument was optimized for TGT signal recording prior to testing. An automated software package containing various mathematical algorithms was utilized to compute the TG curves and parameters, and compare different TG processing approaches. RESULTS: Instruments produced unique noise profiles and end-point parameters that were incomparable in absolute signal terms. Similar relative hemophilic responses were obtained across various instruments when the normalized plasma sample was used as an internal standard. Smoothing algorithms corrected destructive instrument noise. CONCLUSIONS: Instrument-induced errors from numerical differentiation during TG curve processing cannot be eliminated by external calibrators, and require careful qualification of the instrument and implementation of noise-reducing software algorithms.

Complete microscale profiling of tumor microangiogenesis: a microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization.

Complete profiling would substantially facilitate the fundamental understanding of tumor angiogenesis and of possible anti-angiogenesis cancer treatments. We developed an integrated synchrotron-based methodology with excellent performances: detection of very small vessels by high spatial resolution (~1 µm) and nanoparticle contrast enhancement, in vivo dynamics investigations with high temporal resolution (~1 ms), and three-dimensional quantitative morphology parametrization by computer tracing. The smallest (3-10 µm) microvessels were found to constitute >80% of the tumor vasculature and exhibit many structural anomalies. Practical applications are presented, including vessel microanalysis in xenografted tumors, monitoring the effects of anti-angiogenetic agents and in vivo detection of tumor vascular rheological properties.