Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice.
Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. Enzymatic analysis of cortex homogenates from Mo(vbr) mice showed an approximately twofold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities as compared with controls. Assessment of mitochondrial respiratory function was performed using digitonin-treated homogenates of the cortex, which exhibited the main characteristics of isolated brain mitochondria. Despite the substantial changes in respiratory chain enzyme activities, no significant differences were found in maximal pyruvate or succinate oxidation rates of brain cortex homogenates from Mo(vbr) and control mice. Inhibitor titrations were used to determine flux control coefficients of NADH:CoQ oxidoreductase and cytochrome c oxidase on the rate of mitochondrial respiration. Application of amobarbital to titrate the activity of NADH:CoQ oxidoreductase showed very similar flux control coefficients for control and mutant animals. Alternately, titration of respiration with azide revealed for Mo(vbr) mice significantly sharper inhibition curves than for controls, indicating a more than twofold elevated flux control coefficient of cytochrome c oxidase. Owing to the reserve capacity of respiratory chain enzymes, the reported changes in activities do not seem to affect whole-brain high-energy phosphates, as observed in a previous study using 31P NMR.


Effects of actinomycin d and puromycin on the acth-induced ultrastructural transformation of mitochondria of cortical cells of rat adrenals in tissue culture.
The ultrastructure of the mitochondria of the cultured cortical cells of rat adrenals was studied. In vivo it was found that the zona fasciculata mitochondria have vesicular internal structure. 600-A vesicles appear free in the matrix or as protrusions of the inner mitochondrial membrane. In tissue cultures of the fetal and newborn rat adrenal cortex it was seen that ACTH induces transformation of the tubulo-vesicular internal structure of the mitochondria to 600-A vesicles. Actinomycin D and puromycin inhibited this transformation if they were added with ACTH. When added alone, these inhibitors of protein synthesis induced no change in the ultrastructure of the mitochondria in cultured cortical cells of rat adrenals.


Generation of broadband radially polarized terahertz radiation directly on a cylindrical metal wire.
We demonstrate the ability to directly generate broadband THz surface plasmons via optical rectification on a cylindrical metal wire. This is accomplished by milling a single circumferential groove into the wire and overcoating it with a poled polymer that exhibits a bulk second order susceptibility. An attractive feature of this approach is the potential to generate THz pulses that are limited in duration only by the duration of the optical pump pulse. While a photoconductive detector is used in the present demonstration, we discuss further refinements to the system that should allow for significant enhancement of the nonlinear optical conversion efficiency and detection bandwidth.


Vaccination Is a Suitable Tool in the Control of Aujeszky's Disease Outbreaks in Pigs Using a Population Dynamics P Systems Model.
Aujeszky's disease is one of the main pig viral diseases and results in considerable economic losses in the pork production industry. The disease can be controlled using preventive measures such as improved stock management and vaccination throughout the pig-rearing period. We developed a stochastic model based on Population Dynamics P systems (PDP) models for a standard pig production system to differentiate between the effects of pig farm management regimes and vaccination strategies on the control of Aujeszky's disease under several different epidemiological scenarios. Our results suggest that after confirming the diagnosis, early vaccination of most of the population (>75%) is critical to decrease the spread of the virus and minimize its impact on pig productivity. The direct economic cost of an outbreak of Aujeszky's disease can be extremely high on a previously uninfected farm (from 352-792 Euros/sow/year) and highlights the positive benefits of investing in vaccination measures to control infections. We demonstrate the usefulness of computational models as tools in the evaluation of preventive medicine programs aimed at limiting the impact of disease on animal production.


Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.
The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.


Characterization and phylogenetic affiliation of Actinobacteria from tropical soils with potential uses for agro-industrial processes.
Secondary metabolites produced by Actinobacteria of tropical soils represent a largely understudied source of novel molecules with relevant application in medicine, pharmaceutical and food industries, agriculture, and environmental bioremediation. The present study aimed to characterize sixty-nine Actinobacteria isolated from compost and tropical soils using morphological, biochemical, and molecular methods. All the isolates showed high variation for morphological traits considering the color of pigments of the aerial and vegetative mycelium and spore chain morphology. The enzymatic activity of amylase, cellulase, and lipase was highly variable. The amylase activity was detected in 53 (76.81%) isolates. Eighteen isolates showed enzymatic index (EI) > 4.0, and the isolates ACJ 45 (Streptomyces curacoi) and ACSL 6 (S. hygroscopicus) showed the highest EI values (6.44 and 6.42, respectively). The cellulase activity varied significantly (P ≤ 0.05) among the isolates. Twenty-nine isolates (42.02%) showed high cellulase activity, and the isolates ACJ 48 (S. chiangmaiensis) and ACJ 53 (S. cyslabdanicus) showed the highest EI values (6.56 for both isolates). The lipase activity varied statistically (P ≤ 0.05) with fourteen isolates (20.29%) considered good lipase producers (EI > 2.0). The isolate ACSL 6 (S. hygroscopicus) showed the highest EI value of 2.60. Molecular analysis of partial 16S rRNA gene sequencing revealed the existence of 49 species, being 38 species with only one representative member and 11 species represented by one or more strains. All species belonged to three genera, namely Streptomyces (82.61%), Amycolatopsis (7.25%), and Kitasatospora (10.14%). The present results showed the high biotechnological potential of different Actinobacteria from tropical soils.


Pathways for Electron Transfer at MgO-Water Interfaces from Ab Initio Molecular Dynamics.
The nature of electron transfer across metal oxide-water interfaces depends significantly on the band gap of the oxide and its band edge energies relative to the potentials of relevant aqueous redox couples. Here we focus on the water interface with MgO, a prototypical wide band gap oxide whose conduction band edge is close in energy to that of water. We investigate the behavior of an excess electron at and out of equilibrium near the interface using ab initio molecular dynamics based on hybrid density functional theory. Our simulations show that under equilibrium conditions the excess electron (donated by an Al impurity in MgO) localizes to a midgap defect state comparable in energy and shape to a hydrated electron in bulk water. To characterize the electron transfer from the conduction band of MgO to interfacial product states, we dope near-equilibrium configurations of the pristine MgO-water system with Al and run short trajectories of these instantaneously out-of-equilibrium systems. We observe two distinct products associated with the excess electron: a surface-localized electron (esurf-) and an aqueous hydrogen radical (H•). The H• pathway exhibits a much higher activation barrier despite being more exoergic, making esurf- the kinetic product. Our characterization of the pathways on the basis of Marcus theory is consistent with the poor observed utility of MgO for water radiolysis. Moreover, we anticipate that the computational framework employed here will be broadly applicable to assessing electron transfer mechanisms at aqueous, photocatalytic interfaces.


Survival data and prognostic factors seen in Pakistani patients with esophageal cancer.
Esophageal cancer is common in Pakistan. An attempt has been made for the first time to look at the survival data and prognostic factors associated with esophageal cancer in this region. We did a retrospective review of 263 cases seen at the Aga Khan University Hospital in Karachi. Data analysis was done using the Kaplan-Meier method and the Cox proportional hazard model. Squamous cell carcinoma was noted in 81% of the cases, whereas adenocarcinoma was the second most common. At the time of diagnosis, early-stage disease was found in 25%, locally advanced in 41% and metastatic in 34% of all cases. Mean age at diagnosis was 56 years, with 59% males and 41% females. Survival data were available in 89 cases. Median survival was 7 months. On univariate analysis, the following factors were of prognostic significance: obstruction, histology, albumin level at diagnosis, age and platelet count. On multivariate analysis, three factors were found prognostic: presence or absence of obstruction, squamous cell carcinoma versus adenocarcinoma and platelet count. We found that patients with squamous cell carcinoma and absence of thrombocytopenia and obstruction had a better overall survival. However, this is a limited retrospective analysis; we therefore recommend that these prognostic factors be evaluated in larger studies.


Cost-effectiveness of HIV/AIDS interventions in Africa: a systematic review of the evidence.
Evidence for cost-effectiveness of interventions for HIV/AIDS in Africa is fragmentary. Cost-effectiveness is, however, highly relevant. African governments face difficult choices in striking the right balance between prevention, treatment, and care, all of which are necessary to deal comprehensively with the epidemic. Reductions in drug prices have raised the priority of treatment, though treatment access is restricted. We assessed the existing cost-effectiveness data and its implications for value-for-money strategies to combat HIV/AIDS in Africa. We undertook a systematic review using databases and consultations with experts. We identified over 60 reports that measured both the cost and effectiveness of HIV/AIDS interventions in Africa. 24 studies met our inclusion criteria and were used to calculate standardised estimates of the cost (US$ for year 2000) per HIV infection prevented and per disability-adjusted life-year (DALY) gained for 31 interventions. Cost-effectiveness varied greatly between interventions. A case of HIV/AIDS can be prevented for $11, and a DALY gained for $1, by selective blood safety measures, and by targeted condom distribution with treatment of sexually transmitted diseases. Single-dose nevirapine and short-course zidovudine for prevention of mother-to-child transmission, voluntary counselling and testing, and tuberculosis treatment, cost under $75 per DALY gained. Other interventions, such as formula feeding for infants, home care programmes, and antiretroviral therapy for adults, cost several thousand dollars per infection prevented, or several hundreds of dollars per DALY gained. A strong economic case exists for prioritisation of preventive interventions and tuberculosis treatment. Where potentially exclusive alternatives exist, cost-effectiveness analysis points to an intervention that offers the best value for money. Cost-effectiveness analysis is an essential component of informed debate about priority setting for HIV/AIDS.


Temporal artery biopsy for giant cell arteritis.
To evaluate the influence of temporal artery biopsy (TAB) techniques on establishing a diagnosis of giant cell arteritis (GCA). A retrospective review of 141 TAB pathology records from 1996 to 2002 was conducted. Histopathology slides on 136 TAB were reviewed by a single, independent, blinded pathologist. The population included 101 (71.6%) women, mean age 75.8 years (range 45-92), and 40 men, mean age 73.9 years (range 47-90). The mean length of a TAB sample after formalin fixation was 1.76 cm (range 0.1-5.3). Surgeons performing the TAB represented 6 disciplines. Ophthalmologists had the largest volume, at 78 biopsies (55.3%), and the longest segments of artery, with a mean length of 2.37 cm (range 0.4-5.3) (p < 0.001). Comparison of biopsy interpretation provided a kappa coefficient of 0.8 (95% CI 0.69, 0.91). The 38 (27%) positive biopsies had a mean length of 2.07 cm (SD 1.1), and the 98 negative biopsies a mean length of 1.69 cm (SD 1.04) (p = 0.058). Biopsies < 1.0 cm length (n = 35, 25.7%) were less likely to be positive than those > or = 1.0 cm (p = 0.037). No significant differences in surgical discipline, hospital site, number of slides, or cross-sections/cm artery were found between the positive and negative biopsies. Biopsy specimens reported positive for GCA tended to be longer than those reported as negative. A "threshold" size of 1.0 cm is associated with increased diagnostic yield. Lack of standardization of biopsy harvesting and processing techniques may contribute to variable sensitivity of TAB.


Review: The effectiveness of Theraplay for children under 12 - a systematic literature review.
Theraplay is a relationship-focused model of treatment based on attachment theory involving both adult and child. The study aims to review the quality of Theraplay research and Theraplay's effectiveness for children aged 12 years and under with a range of presenting difficulties, to inform future practice and identify areas for further research. A systematic literature search was conducted using PsycINFO, CINAHL, MEDLINE and Web of Science. Quantitative studies using Theraplay only as a treatment for children aged 12 years and under with any presenting difficulty were identified. Additional manual searching was conducted, including eligible studies' reference lists. Critical appraisal tools were used to provide a narrative synthesis of Theraplay's effectiveness and research quality. Only six eligible articles were identified, meaning there was a lack of rigorous evidence eligible to offer conclusions into Theraplay's effectiveness. The review highlighted the small evidence base, mixed quality research methodology and high levels of heterogeneity in how Theraplay is practiced and evaluated. Of the eligible studies, Theraplay was found promising in its effectiveness when used with internalising and externalising difficulties, dual diagnoses and developmental disabilities. Theraplay is regularly practiced across the world; however, the evidence base of rigorous research to inform Theraplay's effectiveness and mechanisms of change is lacking. Firm conclusions could not be offered, although Theraplay was shown to be promising intervention for some presentations. Further research into Theraplay's effectiveness and key mechanisms of change are recommended to enhance the quality and depth of Theraplay literature.


Inequalities in use of health services among Jews and Arabs in Israel.
To compare the levels of utilization of health services in Jews and Arabs taking into account differences in levels of socioeconomic status (SES) in a country with a National Health Insurance Law (NHIL). A cross-sectional National Health Interview Survey was carried out in Israel based on a random sample of telephone numbers as part of the EUROHIS project (WHO European Health Interview Survey 2003-2004). A random telephone survey included 9,352 interviews. Questions included use of health care services, health status, and socioeconomic variables. After adjusting for sex, age, income, education, marital status, and self-reported chronic diseases, Arabs more often reported visiting a family physician (odds ratio [OR]=1.56, 95 percent confidence interval [CI]=1.35-1.81) and less often reported visiting a specialist (OR=0.73, 95 percent CI=0.60-0.89) compared with Jews. In addition, the odds ratio for hospitalization was similar among Arabs and Jews (OR=1.16, 95 percent CI=0.97-1.38). SES was associated with utilization of health care services only in the Jewish population. A different pattern of utilization of health care services was observed in Arabs and Jews. This was not explained by differences in socioeconomic levels. More research is needed regarding the distribution of services between Jews and Arabs.


Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease.
Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. An understanding of the pharmacokinetics and pharmacodynamics of mycophenolate in this population should assist the clinician with rational dosage decisions. This review aims to provide an overview of the published literature on the clinical pharmacokinetics of mycophenolate in autoimmune disease and a briefer summary of current pharmacodynamic knowledge, and to identify areas of potential future research in this field. A literature search was conducted using PubMed and EMBASE databases as well as bibliographies of relevant articles and 'on-line early' pages of key journals. Twenty-six pharmacokinetic/pharmacodynamic studies of mycophenolate in people with autoimmune disease were identified and appraised. Twenty-two of these studies used non-compartmental analysis techniques and four used population modelling methods to estimate mycophenolate pharmacokinetic parameters. Seven studies linked mycophenolate exposure to treatment outcomes. Only four studies measured free (unbound) as well as total mycophenolate exposure and only two studies characterised MPA disposition following enteric-coated mycophenolate sodium (EC-MPS) administration. Across all studies MPA displayed erratic and complex pharmacokinetics with substantial between-subject variability. Based on total drug measurement, the dose-normalised MPA area under the plasma concentration-time curve (AUC) from 0 to 12 h post-dose (AUC12) varied at least five- to ten-fold between subjects. Typical values for apparent oral clearance (CL/F) of MPA during nonlinear mixed-effects modelling ranged from 8.3 to 25.3 L/h. Patient renal function, serum albumin levels, sex, ethnicity, food intake, concurrent administration of interacting drugs such as antacids, metal-containing medications and proton pump inhibitors and polymorphisms in genes encoding uridine diphosphate glucuronosyltransferase were identified in some studies as having a significant influence on the pharmacokinetics of mycophenolate. Typical MPA CL/F values in autoimmune disease patients were generally slightly lower than values published previously in population pharmacokinetic studies involving renal allograft recipients, possibly because of usage of ciclosporin, poorer renal function or lower serum albumin levels in the renal transplant cohort. In a single crossover study involving ten subjects only, significantly higher MPA AUC12 and maximum MPA concentration (C max) and lower MPA CL/F were reported following EC-MPS administration compared to mycophenolate mofetil administration. MPA exposure correlated well with treatment efficacy in patients with autoimmune disease (response to treatment, active disease and disease markers); however the relationship between MPA exposure and adverse events (infectious episodes, haematological toxicity and gastrointestinal symptoms) was unclear. Further investigation is required in autoimmune diseases such as chronic plaque psoriasis and rheumatoid arthritis and following EC-MPS administration. The extent of within-subject variability in the pharmacokinetics of mycophenolate is largely unknown and potential covariate influences need to be confirmed in studies with large subject numbers. A relationship between MPA and MPA metabolite exposure and toxicity needs to be established. The contribution of pharmacogenetics to the pharmacokinetics and pharmacodynamics of mycophenolate warrants further investigation, as does the utility of therapeutic drug monitoring. Dosing to achieve a target MPA AUC12 >35 mg·h/L is likely to lead to better efficacy outcomes in patients with autoimmune disease (rather than just giving standard doses, which lead to a wide range of exposures). However, the relationship between mycophenolate exposure and toxicity requires further investigation to determine the upper end of a target AUC range.


Arthroscopic surgery for synovial chondromatosis of the hip: a systematic review of rates and predisposing factors for recurrence.
Synovial chondromatosis of the hip is a benign condition whereby pain and functional limitations occur due to numerous intra-articular osteochondral fragments produced by a metaplastic synovium. Recurrence not only worsens morbidity but may lead to malignant transformation. With reported recurrence rates as high as 22% by open surgical approaches and given the increasing use of hip arthroscopy for the treatment of synovial chondromatosis, we sought to quantify the recurrence rate after arthroscopy, as well as identify predisposing factors for recurrence. Using predetermined inclusion criteria, 3 electronic databases--Embase, Medline, and PubMed-were searched for relevant articles addressing arthroscopic surgery for synovial chondromatosis of the hip across all available dates up to and including February 16, 2014. A hand search of the reference sections of the included studies was also completed. Article screening was conducted in duplicate. Reviewer agreement statistics and descriptive statistics of the included studies are presented. From an initial retrieval of 2,542 studies, 14 studies satisfied the criteria for inclusion. A total of 197 patients (age range, 13 to 81 years) underwent hip arthroscopy for removal of intra-articular osteochondral fragments and synovectomy to alleviate both mechanical symptoms and pain. Follow-up periods ranged from 1 to 184 months, with approximately 7.6% of patients (15 of 197) lost to follow-up. The recurrence rate after hip arthroscopy was 7.1% (14 of 197), and the rate of minor complications, such as perineal and pedal neurapraxia, was 1%. For synovial chondromatosis of the hip, arthroscopic removal of osteochondral fragments with synovectomy is both safe and effective, with a mean recurrence rate of 7.1%. Level IV, systematic review of Level IV studies.


Robust DNA Methylation in the Clonal Raider Ant Brain.
Social insects are promising model systems for epigenetics due to their immense morphological and behavioral plasticity. Reports that DNA methylation differs between the queen and worker castes in social insects [1-4] have implied a role for DNA methylation in regulating division of labor. To better understand the function of DNA methylation in social insects, we performed whole-genome bisulfite sequencing on brains of the clonal raider ant Cerapachys biroi, whose colonies alternate between reproductive (queen-like) and brood care (worker-like) phases [5]. Many cytosines were methylated in all replicates (on average 29.5% of the methylated cytosines in a given replicate), indicating that a large proportion of the C. biroi brain methylome is robust. Robust DNA methylation occurred preferentially in exonic CpGs of highly and stably expressed genes involved in core functions. Our analyses did not detect any differences in DNA methylation between the queen-like and worker-like phases, suggesting that DNA methylation is not associated with changes in reproduction and behavior in C. biroi. Finally, many cytosines were methylated in one sample only, due to either biological or experimental variation. By applying the statistical methods used in previous studies [1-4, 6] to our data, we show that such sample-specific DNA methylation may underlie the previous findings of queen- and worker-specific methylation. We argue that there is currently no evidence that genome-wide variation in DNA methylation is associated with the queen and worker castes in social insects, and we call for a more careful interpretation of the available data.


Institutional Knots: A Comparative Analysis of Cord Blood Policy in Canada and the United States.
Umbilical cord blood is a rich source of blood stem cells, which are of critical clinical importance in the treatment of a variety of malignant and genetic conditions requiring stem cell transplantation. Many countries have established national public cord blood banks; such banks often coexist with a panoply of private options for cord blood banking. Until recently, Canada was the only G8 country without a national cord blood bank. This differs markedly from the United States, which years ago established a national cord blood bank policy and inventory. This article investigates potential reasons for this discrepancy through a comparative analysis of the evolution of programs and policies on national cord blood banking in Canada and the United States. My analysis suggests that cross-national discrepancies in policy on public cord blood banking were determined primarily by institutional factors, principal among them formal governmental structure and the legacy of past policies. Institutional entrepreneurialism in the health sector played a constitutive role in the earlier evolution of national cord blood policy in the United States as compared to Canada.


Cutting edge: is vasoactive intestinal peptide a type 2 cytokine?
A component of the chemical language shared by the immune and nervous system is the expression of neuropeptides by immune cells. Vasoactive intestinal peptide (VIP) was shown to be produced by T lymphocytes. Here we investigate whether T cell subsets differentially express VIP. Our studies indicate that, upon specific Ag stimulation, Th2 and T2 cells, but not Th1 and T1 cells derived from TCR transgenic (Tg) mice, express VIP mRNA and protein, and secrete VIP. Following immunization with the specific Ag, significant levels of VIP are present in the serum of syngeneic, non-Tg hosts that receive Th2, but not Th1 Tg cells. Th2 Tg cells recovered from the non-Tg hosts immunized with the specific Ag, but not with an irrelevant Ag, express intracellular VIP. Because VIP is produced by Ag-stimulated type 2 T cells, and differentially affects Th1 and Th2 cells, could VIP be viewed as a type 2 cytokine?


Characterization of the choroid-scleral junction and suprachoroidal layer in healthy individuals on enhanced-depth imaging optical coherence tomography.
Accurate measurements of choroidal thickness (CT) using enhanced-depth imaging optical coherence tomography (EDI-OCT) require a well-defined choroid-scleral junction (CSJ), which may appear in some eyes as a hyporeflective band corresponding to the suprachoroidal layer (SCL). To identify factors associated with the presence and thickness of the SCL in healthy participants and determine how different CSJ boundary definitions impact CT measurements. Secondary analysis of EDI-OCT images obtained prospectively from 74 eyes of 74 controls (mean age, 68.6 years) from the Age-Related Eye Disease Study 2 Ancillary SDOCT Study. The CSJ appearances were categorized as either having no visible SCL or a hyporeflective band corresponding to the SCL. Ocular parameters associated with the presence and thickness of the SCL were identified. Subfoveal CT was measured using 3 different posterior boundaries: (1) the posterior vessel border (vascular CT [VCT]), (2) inner border of the SCL (stromal CT [StCT]), and (3) inner border of the sclera (total CT [TCT]). Manual segmentation using custom software was used to compare VCT, StCT, and TCT across the macula. RESULTS The SCL was visible in 33 eyes (44.6%). Factors associated with SCL presence and thickness included hyperopic refractive error (R2 = 0.123; P = .045) and increased TCT (R2 = 0.215; P = .004), but not age, visual acuity, intraocular pressure, retinal foveal thickness, VCT, or StCT. In eyes where the SCL was not visible, mean [SD] subfoveal VCT was 222.3 [101.5] μm and StCT and TCT were 240.0 [99.0] μm, with a difference of 17.7 [16.0] μm (P < .001). In eyes where the SCL was visible, mean [SD] subfoveal VCT, StCT, and TCT were 221.9 [83.1] μm, 257.7 [97.3] μm, and 294.1 [104.8] μm, respectively, with the greatest difference of 72.2 [30.4] μm between VCT and TCT (P < .001). All 3 CT measurements were significantly different along all points up to 3.0 mm nasal and temporal to the fovea. A hyporeflective SCL is visible at the CSJ on EDI-OCT in nearly half of healthy individuals, and its presence correlates with hyperopia. Different posterior boundary definitions may result in significant differences in CT measurements and should be explicitly identified in future choroidal studies and segmentation algorithms.


The effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression.
Advanced gastric cancer is one of the most aggressive gastrointestinal malignancies, and ADAM (A disintegrin and metalloproteinase)-9 is a cell-surface membrane glycoprotein with oncogenic properties that is overexpressed in several cancers. Herein, we investigated the biologic mechanism of ADAM9 in the progression, proliferation, and invasion of gastric cancer. First, we detected ADAM's expression, processing, and protease activity in gastric cancer cells. Protease activity was moderately correlated with ADAM9 protein expression, but was better related to a processed smaller molecular weight (84 kDa) form of ADAM9. Knockdown of ADAM9 or specifically targeted monoclonal antibody (RAV-18) suppressed cancer cell proliferation and invasion in high ADAM9-expressing cells, not in low ADAM9-expressing cells. RAV-18 showed in vivo antitumor activity in a gastric cancer xenograft model. Hypoxia (1% oxygen) induced ADAM9 expression and functional activity in low ADAM9-expressing gastric cancer cells that was inhibited by siRNA knockdown or RAV-18 antibody to levels in normoxic cells. Overall, our studies show that ADAM9 plays an important role in gastric cancer proliferation and invasion, and that while expressed in some gastric cancer cells at high levels that are responsive to functional inhibition and antitumor activity of a catalytic site-directed antibody, other gastric cancer cells have low levels of expression and only when exposed to hypoxia do ADAM9 levels increase and the cells become responsive to ADAM9 antibody inhibition. Therefore, our findings suggest that ADAM9 could be an effective therapeutic target for advanced gastric cancer.


Low-frequency mechanical vibration induces apoptosis of A431 epidermoid carcinoma cells.
Cancer research is increasingly focused on discovering strategies to induce cancer cell apoptosis without affecting surrounding normal cells. One potential biocompatible method is mechanical vibration, which has been developed as part of the emerging field of mechanomedicine. Previous studies of mechanical vibration have employed high-frequency vibration, which damages healthy cells. In this study, we examined the effects of brief (1 h) low-frequency (20 Hz) mechanical vibration on glucose consumption and survival (apoptosis, necrosis, HMGB1 release) of the human epidermoid carcinoma cell line A431. We found that apoptosis, but not necrosis, was significantly increased at 48 h after mechanical vibration compared with cells maintained in static culture. In keeping with this, extracellular release of HMGB1, a necrosis marker, was lower in cultures of A431 cells subjected to mechanical vibration compared with control cells. Glucose consumption was increased in the first 24 h after mechanical vibration but returned to control levels before the onset of apoptosis. Although the precise intracellular mechanisms by which low-frequency mechanical vibration triggers apoptosis of A431 cells is unknown, these results suggest a possible role for metabolic pathways. Mechanical vibration may thus represent a novel application of mechanomedicine to cancer therapy.


Multifunctional and compact spectrometers based on cylindrical beam volume holograms.
We propose a new class of slitless spectrometers using cylindrical beam volume holograms. These holograms disperse an input beam in one direction in an output plane while they do not affect the beam in the perpendicular direction. We show that the spectral mapping of the input beam can be obtained in one direction and the beam can be independently modified in the perpendicular direction. Using this unique property, we demonstrate a spectral wrapping technique to considerably increase the operation spectral range of the slitless spectrometers, without sacrificing their resolution.


Major obstetric haemorrhage in Metro East, Cape Town, South Africa: a population-based cohort study using the maternal near-miss approach.
Major obstetric haemorrhage is a leading cause of maternal mortality and accounts for one-third of maternal deaths in of Africa. This study aimed to assess the population-based incidence, causes, management and outcomes of major obstetric haemorrhage and risk factors associated with poor maternal outcome. Women with major obstetric haemorrhage who met the WHO maternal near-miss criteria or died in the Metro East region, Cape Town, South Africa, were evaluated from November 2014-November 2015. Major obstetric haemorrhage was defined as haemorrhage in pregnancies of at least 20 weeks' gestation or occurring up to 42 days after birth, and leading to hysterectomy, hypovolaemic shock or blood transfusion of ≥5 units of Packed Red Blood Cells. A logistic regression model was used to analyse associations with poor outcome, defined as major obstetric haemorrhage leading to massive transfusion of ≥8 units of packed red blood cells, hysterectomy or death. The incidence of major obstetric haemorrhage was 3/1000 births, and the incidence of massive transfusion was 4/10.000 births in the Metro East region (32.862 births occurred during the studied time period). Leading causes of haemorrhage were placental abruption 45/119 (37.8%), complications of caesarean section 29/119 (24.4%) and uterine atony 13/119 (10.9%). Therapeutic oxytocin was administered in 98/119 (82.4%) women and hysterectomy performed in 33/119 (27.7%). The median numbers of packed red blood cells and units of Fresh Frozen Plasma transfused were 6 (interquartile range 4-7) and 3 (interquartile range 2-4), ratio 1.7:1. Caesarean section was independently associated with poor maternal outcome: adjusted OR 4.01 [95% CI 1.58, 10.14]. Assessment of major obstetric haemorrhage using the Maternal Near Miss approach revealed that placental abruption and complications of caesarean section were the major causes of major obstetric haemorrhage. Caesarean section was associated with poor outcome.


Surface seals reduce 1,3-dichloropropene and chloropicrin emissions in field tests.
Reducing emissions is essential for minimizing the impact of soil fumigation on the environment. Water application to the soil surface (or water seal) has been demonstrated to reduce 1,3-dichloropropene (1,3-D) emissions in soil column tests. This study determined the effectiveness of water application to reduce emissions of 1,3-D and chloropicrin (CP) in comparison to other surface seals under field conditions. In a small-plot field trial on a Hanford sandy loam soil (coarse-loamy, mixed, superactive, nonacid, thermic Typic Xerorthents) in the San Joaquin Valley, CA. Telone C35 (61% 1,3-D and 35% CP) was shank-applied at a depth of 46 cm at a rate of 610 kg ha-1. Soil surface seal treatments included control (no tarp and no water application), standard high density polyethylene (HDPE) tarp over dry and pre-irrigated soil, virtually impermeable film (VIF) tarp, initial water application by sprinklers immediately following fumigation, and intermittent water applications after fumigation. The atmospheric emissions and gas-phase distribution of fumigants in soil profile were monitored for 9 d. Among the surface seals, VIF and HDPE tarp over dry soil resulted in the lowest and the highest total emission losses, respectively. Intermittent water applications reduced 1,3-D and CP emissions significantly more than HDPE tarp alone. The initial water application also reduced emission peak and delayed emission time. Pre-irrigated soil plus HDPE tarp reduced fumigant emissions similarly as the intermittent water applications and also yielded the highest surface soil temperature, which may improve overall soil pest control.


Modal analysis and device considerations of thin high index dielectric overlay slab waveguides.
The effect of adding a thin high index dielectric overlay layer onto a 3-layer slab waveguide demonstrates several interesting features that can be exploited in integrated optical device configurations. A simple modal analysis is employed to examine the behavior of guided light launched from a 3-layer waveguide structure then coupled and propagated in the 4-layer overlay region. Modal properties typically overlooked in conventional slab waveguides are made use of in the design and theoretical analysis of an MMI device and optical index of refraction sensor. The optical structure presented here can form the backdrop waveguide design for more complex and active devices.


The interleukin 6 -174 C/C genotype predicts greater rhinovirus illness.
In adults and children with respiratory syncytial virus (RSV) infection, a polymorphism in the interleukin 6 (IL-6) promoter at position -174 predicts illness magnitude. In addition, polymorphisms in the interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) genes are associated with immune responsiveness and the frequency of complications. Here, the effect of these polymorphisms on illness and seroconversion during infection with rhinovirus type 39 (RV39) was evaluated. Seventy-two adults were genotyped for the selected polymorphisms, experimentally exposed to RV39, and followed to track infection, seroconversion, and symptoms and signs of illness. Regression analysis was used to determine whether these polymorphisms predicted seroconversion and illness magnitude in 57 infected subjects. The low-production IL-6 -174 phenotype (C/C genotype) was associated with greater symptom magnitudes, and the IFN-gamma phenotype +874 predicted the frequency of seroconversion. No relationship between the IL-10 or TNF-alpha polymorphisms and any measured outcome was documented. The concentration of IL-6 protein, as measured in nasal wash fluids from subjects, was positively correlated with symptom magnitude, but it was independent of the IL-6 -174 genotypes representing the high- and low-production phenotypes. These results document statistically significant associations between the IL-6 -174 and IFN-gamma +874 polymorphisms and specific responses to experimental RV39 infection. For the IL-6 -174 polymorphism, the results replicate those for experimental RSV infection.


Region-specific insertion of transposons in combination with selection for high plasmid transferability and stability accounts for the structural similarity of IncP-1 plasmids.
The overall architecture of IncP-1 plasmids is very conserved in that the accessory genes are typically located in one or two specific regions: between oriV and trfA and between the tra and trb operons. Various hypotheses have been formulated to explain this, but none have been tested experimentally. We investigated whether this structural similarity is due to region-specific transposition alone or also is reliant on selection for plasmids with insertions limited to these two regions. We first examined the transposition of Tn21Km into IncP-1beta plasmid pBP136 and found that most Tn21Km insertions (67%) were located around oriV. A similar experiment using the oriV region of IncP-1beta plasmid pUO1 confirmed these results. We then tested the transferability, stability, and fitness cost of different pBP136 derivatives to determine if impairment of these key plasmid characters explained the conserved plasmid architecture. Most of the pBP136 derivatives with insertions in transfer genes were no longer transferable. The plasmids with insertions in the oriV-trfA and tra-trb regions were more stable than other plasmid variants, and one of these also showed a significantly lower fitness cost. In addition, our detailed sequence analysis of IncP-1 plasmids showed that Tn402/5053-like transposons are situated predominantly between the tra and trb operons and close to the putative resolution site for the ParA resolvase, a potential hot spot for those transposons. Our study presents the first empirical evidence that region-specific insertion of transposons in combination with selection for transferable and stable plasmids explains the structural similarity of IncP-1 plasmids.


Cytological analysis of cytoplasmic incompatibility induced by Cardinium suggests convergent evolution with its distant cousin Wolbachia.
Cytoplasmic incompatibility (CI) is a conditional sterility in numerous arthropods that is caused by inherited, intracellular bacteria such as Wolbachia Matings between males carrying CI-inducing Wolbachia and uninfected females, or between males and females infected with different Wolbachia strains, result in progeny that die during very early embryogenesis. Multiple studies in diploid (Drosophila) and haplodiploid (Nasonia) insects have shown that CI-Wolbachia cause a failure of the paternally derived chromatin from resolving into distinct chromosomes. This leads to the formation of chromatin bridges and other mitotic defects as early as the first mitotic division, and to early mitotic arrest. It is currently unknown if CI-inducing symbionts other than Wolbachia affect similar cellular processes. Here, we investigated CI caused by an unrelated bacterium, Cardinium, which naturally infects a parasitic wasp, Encarsia suzannae CI crosses in this host-symbiont system resulted in early mitotic defects including asynchrony of paternal and maternal chromosome sets as they enter mitosis, chromatin bridges and improper chromosome segregation that spanned across multiple mitotic divisions, triggering embryonic death through accumulated aneuploidy. We highlight small differences with CI-Wolbachia, which could be due to the underlying CI mechanism or host-specific effects. Our results suggest a convergence of CI-related cellular phenotypes between these two unrelated symbionts.


Establishing quality in colorectal surgery.
The review aimed to offer a contemporary perspective of the quality of current colorectal surgery. A literature search was undertaken to identify relevant indicators. Citations were included if they related to quality in colorectal surgery. The search terms used included the Medical Subject Heading terms and Boolean characters: 'colon' OR 'colorectal', OR 'rectal' OR 'rectum' AND 'Quality Indicators', OR 'Quality Assurance', OR 'Quality of healthcare', OR 'Reference Standards', OR 'Quality' plus a variable floating term. A two-person independent review was undertaken from resulting citations and their consequent reference lists. The search was limited to citations from 2000 to 2010 in humans and to the English language. Metrics identified as potential quality indicators in colorectal surgery are discussed according to the structure, process and outcome framework. A clear appreciation of the scope of individual metrics for quality appraisal purposes is necessary if they are to be used meaningfully for performance benchmarking.


A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex) versus EPA, Cox-2 inhibitor (Celebrex), resistance training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients--ACCeRT study.
Cancer cachexia is a syndrome of progressive weight loss. Non-small cell lung cancer patients experience a high incidence of cachexia of 61%. Research into methods to combat cancer cachexia in various tumour sites has recently progressed to the combination of agents.The combination of the anti-cachectic agent Eicosapentaenoic acid (EPA) and the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib has been tested in a small study with some benefit. The use of progressive resistance training (PRT) followed by the oral ingestion of essential amino acids (EAA), have shown to be anabolic on skeletal muscle and acceptable in older adults and other cancer groups.The aim of this feasibility study is to evaluate whether a multi-targeted approach encompassing a resistance training and nutritional supplementation element is acceptable for lung cancer patients experiencing cancer cachexia. Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) is an open label, prospective, randomised controlled feasibility study with two parallel arms. All patients will be treated with EPA and the COX-2 inhibitor celecoxib on an outpatient basis at the study site. In the experimental group patients will participate in PRT twice a week, followed by the ingestion of essential amino acids high in leucine. A total of 21 patients are planned to be enrolled. Patients will be randomised using 1:2 ratio with 7 patients enrolled into the control arm, and 14 patients into the treatment arm. The primary endpoint is the acceptability of the above multi-targeted approach, determined by an acceptability questionnaire. To our knowledge ACCeRT offers for the first time the opportunity to investigate the effect of stimulating the anabolic skeletal muscle pathway with the use of PRT along with EAA alongside the combination of EPA and celecoxib in this population. Netherlands Trial Register (NTR): ACTRN12611000870954.


A preconscious neural mechanism of hypnotically altered colors: a double case study.
Hypnotic suggestions may change the perceived color of objects. Given that chromatic stimulus information is processed rapidly and automatically by the visual system, how can hypnotic suggestions affect perceived colors in a seemingly immediate fashion? We studied the mechanisms of such color alterations by measuring electroencephalography in two highly suggestible participants as they perceived briefly presented visual shapes under posthypnotic color alternation suggestions such as "all the squares are blue". One participant consistently reported seeing the suggested colors. Her reports correlated with enhanced evoked upper beta-band activity (22 Hz) 70-120 ms after stimulus in response to the shapes mentioned in the suggestion. This effect was not observed in a control condition where the participants merely tried to simulate the effects of the suggestion on behavior. The second participant neither reported color alterations nor showed the evoked beta activity, although her subjective experience and event-related potentials were changed by the suggestions. The results indicate a preconscious mechanism that first compares early visual input with a memory representation of the suggestion and consequently triggers the color alteration process in response to the objects specified by the suggestion. Conscious color experience is not purely the result of bottom-up processing but it can be modulated, at least in some individuals, by top-down factors such as hypnotic suggestions.


Transcatheter tissue engineered heart valves.
Valvular heart disease represents a leading cause of mortality worldwide. Transcatheter heart valve replacement techniques have been recently introduced into the clinical routine expanding the treatment options for affected patients. However, despite this technical progress toward minimally invasive, transcatheter strategies, the available heart valve prostheses for these techniques are bioprosthetic and associated with progressive degeneration. To overcome such limitations, the concept of heart valve tissue engineering has been repeatedly suggested for future therapy concepts. Ideally, a clinically relevant heart valve tissue engineering concept would combine minimally invasive strategies for both, living autologous valve generation as well as valve implantation. Therefore, merging transcatheter techniques with living tissue engineered heart valves into a trascatheter tissue engineered heart valve concept could significantly improve current treatment options for patients suffering from valvular heart disease. This report provides an overview on transcatheter tissue engineered heart valves and summarizes available pre-clinical data.


Evolution of Antimicrobial Resistance Levels of ESKAPE Microorganisms in a Peruvian IV-Level Hospital.
The members of the so-called ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are a frequent cause of severe infection, ranking among the most relevant causes of hospital infections. In Peru, few studies, often focused in a single ESKAPE microorganism, have been performed, but none providing an overall and comprehensive long-time analysis of the antibiotic resistance of ESKAPE microorganisms. In the present study, the evolution of antimicrobial resistance levels of ESKAPE microorganisms isolated during 2009 - 2010 (Period 1) and 2012 - 2014 (Period 2) in a IV-level hospital in Lima was analyzed. ESKAPE microorganisms were isolated from inpatients clinical samples. Bacterial identification, as well as antimicrobial susceptibility levels for up to 29 antimicrobial agents and presence of Extended-Spectrum β-Lactamases (only established in K. pneumoniae) were determined using automatic methods. Of 9,918 clinical isolates, 1,917/3,777 (50.8%) [JAN/2009-JUN/2010 (Period 1)] and 4764/6141 (46.4%) [JAN/2012-DEC/2014 (Period 2)] belonged to the ESKAPE group (P <0.0001). ESKAPE were more frequent in the intensive care unit (ICU) (P <0.0001). E. faecium decreased from 5.1% to 4.1% (P <0.5), S. aureus from 10.5% to 7.0% (P <0.05), and P. aeruginosa from 12.9% to 11.6% (P <0.05), while, A. baumannii increased from 5.0% to 6.7% (P <0.05), mainly related to an increase in ICU isolates (8.4% vs. 17.1%; P <0.05). Overall, high levels of antimicrobial resistance were detected, but with few exceptions (e.g. vancomycin in E. faecium), antibiotic resistance levels remained stable or lower in Period 2. Contrarily, A. baumannii showed significantly increased resistance to different cephalosporins, carbapenems and amoxicillin plus sulbactam. The introduction of a successful extensively drug-resistant A. baumannii clone in the ICU is suspected. The isolation of ESKAPE and levels of antibiotic resistance levels have reduced over time.


Observation of Fermi-Arc Spin Texture in TaAs.
We have investigated the spin texture of surface Fermi arcs in the recently discovered Weyl semimetal TaAs using spin- and angle-resolved photoemission spectroscopy. The experimental results demonstrate that the Fermi arcs are spin polarized. The measured spin texture fulfills the requirement of mirror and time-reversal symmetries and is well reproduced by our first-principles calculations, which gives strong evidence for the topologically nontrivial Weyl semimetal state in TaAs. The consistency between the experimental and calculated results further confirms the distribution of chirality of the Weyl nodes determined by first-principles calculations.


[Anesthetic management for a pediatric patient of Klippel-Trenaunay syndrome with giant head by hydrocephalus].
Klippel-Trenaunay syndrome (KTS) is a rare disorder associated with the triad of 1) capillary vascular malformation, 2) varicose veins and/or venous malformation, 3) and soft tissue and/or bony hypertrophy. A six-month old, 6.0-kg-weight male pediatric patient was scheduled for ventriculo-peritoneal shunt operation for hydrocephalus caused by obstructive aqueductus cerebri. At the age of three months, he was diagnosed as KTS by extensive capillary vascular malformation and soft tissue hypertrophy of the right leg. Physical examination showed prominent vascular malformation over his anterior thoracic and abdominal wall, and soft tissue hypertrophy was only on his right leg. Simultaneously, he was complicated with congenital hydrocephalus because of obstructive aqueductus cerebri. His head and skull were enlarged and his head measurement reached 55 cm (chest measurement 32 cm). Anesthetic management of KTS patients should be prepared with blood transfusion against massive hemorrhage and hypovolemic shock. Furthermore, KTS patients should be always considered to have airway difficulty due to the soft tissue hypertrophy, upper and airway hemangiomas. Therefore, we planned safer tracheal intubation following practice guidelines for management of the difficult airway.


Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: results of an open-label phase I and a randomized, standard-of-care-controlled phase I/II study.
Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product-fibrin pad-to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3-4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Phase I/II trial, NCT00598130.


Rates of DNA duplication and mitochondrial DNA insertion in the human genome.
The hundreds of mitochondrial pseudogenes in the human nuclear genome sequence (numts) constitute an excellent system for studying and dating DNA duplications and insertions. These pseudogenes are associated with many complete mitochondrial genome sequences and through those with a good fossil record. By comparing individual numts with primate and other mammalian mitochondrial genome sequences, we estimate that these numts arose continuously over the last 58 million years. Our pairwise comparisons between numts suggest that most human numts arose from different mitochondrial insertion events and not by DNA duplication within the nuclear genome. The nuclear genome appears to accumulate mtDNA insertions at a rate high enough to predict within-population polymorphism for the presence/absence of many recent mtDNA insertions. Pairwise analysis of numts and their flanking DNA produces an estimate for the DNA duplication rate in humans of 2.2 x 10(-9) per numt per year. Thus, a nucleotide site is about as likely to be involved in a duplication event as it is to change by point substitution. This estimate of the rate of DNA duplication of noncoding DNA is based on sequences that are not in duplication hotspots, and is close to the rate reported for functional genes in other species.


Color vision in sight recovery individuals.
Color vision has been consistently shown to be unaffected in animals that are raised in dark or in color-deprived environments. However, there are only a few studies that directly addressed the effect of congenital visual deprivation in color perception in humans. The goal of the current study was to assess the effect of congenital visual deprivation on color vision using a panel based color arrangement test. We investigated the recovery of color vision using the Farnsworth D15 test in a group of individuals who had experienced visual deprivation since birth due to bilateral dense congenital cataracts before undergoing cataract-reversal surgery (Congenital cataract, CC, n = 12). In addition, we tested two groups of control participants: (1) individuals who had had non-dense congenital cataract or developed cataract later in their childhood (Developmental cataract, DC, n = 10), and (2) sighted controls with normal or corrected to normal vision (n = 14). Based on the methods proposed by Vingrys and King-Smith (1988), we derived the following metrics of color vision performance: (1) total error score, (2) confusion index, (3) confusion angle, and (4) selectivity index. All of the measured indices of color vision performance were unaltered by a period of congenital visual deprivation. Our results support the view that, development of visual functions such as color discrimination and color arrangement does not depend on typical visual experience during a sensitive phase in early childhood.


The discounted reproductive number for epidemiology.
The basic reproductive number, R(0), and the effective reproductive number, R, are commonly used in mathematical epidemiology as summary statistics for the size and controllability of epidemics. However, these commonly used reproductive numbers can be misleading when applied to predict pathogen evolution because they do not incorporate the impact of the timing of events in the life-history cycle of the pathogen. To study evolution problems where the host population size is changing, measures like the ultimate proliferation rate must be used. A third measure of reproductive success, which combines properties of both the basic reproductive number and the ultimate proliferation rate, is the discounted reproductive number R(d). The discounted reproductive number is a measure of reproductive success that is an individual's expected lifetime offspring production discounted by the background population growth rate. Here, we draw attention to the discounted reproductive number by providing an explicit definition and a systematic application framework. We describe how the discounted reproductive number overcomes the limitations of both the standard reproductive numbers and proliferation rates, and show that R(d) is closely connected to Fisher's reproductive values for different life-history stages.


Somatostatin analogue inhibits the mobility of prostate carcinoma cells: a new therapeutic method for advanced prostate carcinoma.
The somatostatin analogue (SA) Octreotide has been used as a therapeutic reagent for somatostatin receptor type 2a (SSTR2a)-positive cancers. The purpose of this study is to detect SSTR2a in human prostate carcinomas and to elucidate the effects of SA on SSTR2a-positive prostate carcinoma cells to determine the potential of this drug as a new therapeutic method for advanced prostate carcinoma. Immunohistochemical study of SSTR2a was performed on 95 prostate carcinoma cases, and the results showed expression of SSTR2a in 14 of the 95 cases (14.74%); the histological grade (Gleason) and capsular invasion of the prostate carcinoma were directly related to SSTR2a expression. Among the ten cases of lymph node metastasis, SSTR2a expression was markedly higher. In vitro studies were performed using SSTR2a-positive prostate cancer cells, DU145 and PC3. Migration and invasion abilities of DU145 and PC3 cells were inhibited by SA in a dose-dependent manner. This inhibition was reversed by Rho-kinase inhibitor Y-27632. Morphological changes of the prostate cancer cells treated with SA and Y27632 corroborate the migration and invasion assays, although SA had no effect on proliferation of DU145 and PC3 cells. In conclusion, the somatostatin analogue may be beneficial for patients with advanced prostate carcinoma or to protect from distal metastasis if they are positive for SSTR2a.


Effect of dietary omega-3 fatty acids on red blood cell lipid composition and plasma metabolites in the cockatiel, Nymphicus hollandicus.
Although dietary n-3 fatty acids have been extensively studied in poultry, they have not yet been prospectively investigated in psittacines, despite potential benefits for preventing and treating atherosclerosis, osteoarthritis, and other chronic disease processes. The objectives of this study were to investigate the incorporation of dietary n-3 fatty acids into red blood cells (RBC) and to determine the effects of supplementation of psittacine diets with fish or flax oil on plasma lipids and lipoproteins in the cockatiel. Adult cockatiels were fed a custom-formulated diet containing either 4% (wt/wt, as-fed) beef tallow (CON), 3% fish oil + 1% tallow (FSH), or 3.5% flax oil + 0.5% tallow (FLX; n = 20 per diet group). Baseline measurements were obtained for RBC fatty acid composition, triacylglycerides (TAG), and cholesterol. After 8 to 13 wk on the study diets, plasma chemistry profiles, lipoprotein density profiles, and RBC fatty acid composition were determined. At 8 wk, total plasma cholesterol was least in FSH birds (P < 0.05) and TAG concentrations were less in FSH birds than FLX birds (P < 0.05). Total n-3 fatty acids, docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid were markedly greater in the RBC of FSH birds than FLX or CON birds (P < 0.05). Alpha linolenic acid was greatest in FLX (P < 0.05). Initial and final BW, and nonlipid plasma chemistry values did not differ among diet groups. No adverse effects of dietary supplementation of cockatiels with 3.5% flax oil or 3% fish oil were observed during the 13-wk feeding period. Although fish and flax oils provided similar total n-3 PUFA to the diets, fish oil caused greater reductions in cholesterol and TAG, and greater total RBC n-3 incorporation. Thus, dietary modification of psittacine diets with long chain n-3 PUFA from fish oil appears safe and may be beneficial to these long-lived companion birds.


Hidden variables in bipartite networks.
We introduce and study random bipartite networks with hidden variables. Nodes in these networks are characterized by hidden variables that control the appearance of links between node pairs. We derive analytic expressions for the degree distribution, degree correlations, the distribution of the number of common neighbors, and the bipartite clustering coefficient in these networks. We also establish the relationship between degrees of nodes in original bipartite networks and in their unipartite projections. We further demonstrate how hidden variable formalism can be applied to analyze topological properties of networks in certain bipartite network models, and verify our analytical results in numerical simulations.


Relative growth of the anulus fibrosus and nucleus pulposus in human and kitten fetuses.
Growth in volume of the anulus fibrosus (AF) and nucleus pulposus (NP) was quantified using serial histological sections of human and kitten fetuses. Fetal intervertebral discs were studied that had clearly outlined AF and NP. Regression equations were calculated and graphs plotted by microcomputer. An increase in surface areas of these intervertebral structures was also recorded; however, volume was a better indicator of relative growth than was surface area. The AF volume of the fetal human increased more in proportion to the intervertebral disc than it did for the fetal kittens. There was significantly slower growth of the human NP compared to the kitten NP when related to the total intervertebral disc. The analysis for each species was done separately. Comparisons of the growth relationships of humans and kittens for the AF and NP were related to crown-rump length as the independent variable, and were different at the p less than or equal to 0.01 level of significance. The thoracic intervertebral discs were emphasized due to species-specific differential growth of the AF. The intercapital ligament (IC) was separated from mesenchyme over the dorsal surface of the kitten AF, and this affected the relationships of AF and NP volumes when compared to humans. Use of human histological sections is essential in the study of differential growth of the human vertebral column because fetal kittens have an IC that affects relative growth of both AF and NP.


Enhanced FTIR bench-top imaging of single biological cells.
A new optical system has recently been developed that enables infrared images to be obtained with a pixel resolution of 1 micron on a bench-top instrument using a thermal source. We present here imaging data from two contrasting cellular systems that represent different challenges. Renal carcinoma cells cytospun onto CaF2 have a largely rounded morphology and thus suffer from strong resonant Mie scattering. Skin fibroblast cells, cultured onto CaF2 on the other hand are very spread out so scatter less strongly but are so thin they deliver extremely weak signals. Using suitable pre-processing methods, including PCA noise reduction and RMieS correction, we demonstrate that useful high resolution images can be obtained from either sample.


Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases.
Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the X-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here, we present the X-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with antimalarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centers in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the development of a unique class of two-target and/or combination antimalarial therapy.


Effects of trazodone on behavioral and physiological signs of stress in dogs during veterinary visits: a randomized double-blind placebo-controlled crossover clinical trial.
To determine whether a single dose of trazodone administered to dogs before a veterinary visit reduced their behavioral and physiologic signs of stress and owners' stress during veterinary visits. 20 dogs and their owners. In this randomized double-blinded placebo-controlled crossover clinical trial, dogs with a history of anxiety during veterinary visits were scheduled for 2 veterinary visits 1 week apart and randomly assigned to receive a single oral dose of either trazodone (9 to 12 mg/kg) or a placebo 90 minutes before transport to the veterinary clinic for alternate visits between September 21 and November 3, 2019. For each visit, we collected and assessed owner-completed surveys of dog stress score (DSS) and owner stress score; various investigator-reported scores, including from video-recorded behavior analyses; and patient-related physiologic data. Dogs treated with trazodone versus placebo had lower mean DSSs, assessed by owners for physical examination and assessed by video analysis for time spent in the examination room; lower mean SD of normal-to-normal intervals, root mean square of successive heartbeat interval difference, and respiratory rate; and higher mean heart rate. No meaningful differences were observed in other behavioral or physiologic outcomes, including serum cortisol concentrations. A single dose of trazodone before transport reduced signs of stress during veterinary visits for dogs in the present study and may be useful as an anti-anxiety medication for similarly affected dogs, potentially resulting in higher-quality clinical examinations and improved patient welfare.


Rapid whole monoclonal antibody analysis by mass spectrometry: An ultra scale-down study of the effect of harvesting by centrifugation on the post-translational modification profile.
With the trend towards the generation and production of increasing numbers of complex biopharmaceutical (protein based) products, there is an increased need and requirement to characterize both the product and production process in terms of robustness and reproducibility. This is of particular importance for products from mammalian cell culture which have large molecular structures and more often than not complex post-translational modifications (PTMs) that can impact the efficacy, stability and ultimately the safety of the final product. It is therefore vital to understand how the operating conditions of a bioprocess affect the distribution and make up of these PTMs to ensure a consistent quality and activity in the final product. Here we have characterized a typical bioprocess and determined (a) how the time of harvest from a mammalian cell culture and, (b) through the use of an ultra scale-down mimic how the nature of the primary recovery stages, affect the distribution and make up of the PTMs observed on a recombinant IgG(4) monoclonal antibody. In particular we describe the use of rapid whole antibody analysis by mass spectrometry to analyze simultaneously the changes that occur to the cleavage of heavy chain C-terminal lysine residues and the glycosylation pattern, as well as the presence of HL dimers. The time of harvest was found to have a large impact upon the range of glycosylation patterns observed, but not upon C-terminal lysine cleavage. The culture age had a profound impact on the ratio of different glycan moieties found on antibody molecules. The proportion of short glycans increased (e.g., (G0F)(2) 20-35%), with an associated decrease in the proportion of long glycans with culture age (e.g., (G2F)(2) 7-4%, and G1F/G2F from 15.2% to 7.8%). Ultra scale-down mimics showed that subsequent processing of these cultures did not change the post-translational modifications investigated, but did increase the proportion of half antibodies present in the process stream. The combination of ultra scale-down methodology and whole antibody analysis by mass spectrometry has demonstrated that the effects of processing on the detailed molecular structure of a monoclonal antibody can be rapidly determined early in the development process. In this study we have demonstrated this analysis to be applicable to critical process design decisions (e.g., time of harvest) in terms of achieving a desired molecular structure, but this approach could also be applied as a selection criterion as to the suitability of a platform process for the preparation of a new drug candidate. Also the methodology provides means for bioprocess engineers to predict at the discovery phase how a bioprocess will impact upon the quality of the final product.


Comparative squamation of the lateral line canal pores in sharks.
The current study collected the first quantitative data on lateral line pore squamation patterns in sharks and assessed whether divergent squamation patterns are similar to experimental models that cause reduction in boundary layer turbulence. In addition, the hypothesis that divergent orientation angles are exclusively found in fast-swimming shark species was tested. The posterior lateral line and supraorbital lateral line pore squamation of the fast-swimming pelagic shortfin mako shark Isurus oxyrinchus and the slow-swimming epi-benthic spiny dogfish shark Squalus acanthias was examined. Pore scale morphology and pore coverage were qualitatively analysed and compared. In addition, pore squamation orientation patterns were quantified for four regions along the posterior lateral line and compared for both species. Isurus oxyrinchus possessed consistent pore scale coverage among sampled regions and had a divergent squamation pattern with multiple scale rows directed dorsally and ventrally away from the anterior margin of the pore with an average divergent angle of 13° for the first row of scales. Squalus acanthias possessed variable amounts of scale coverage among the sampled regions and had a divergent squamation pattern with multiple scale rows directed ventrally away from the anterior margin of the pore with an average angle of 19° for the first row of scales. Overall, the squamation pattern measured in I. oxyrinchus fell within the parameters used in the fluid flow analysis, which suggests that this pattern may reduce boundary layer turbulence and affect lateral line sensitivity. The exclusively ventral oriented scale pattern seen in S. acanthias possessed a high degree of divergence but the pattern did not match that of the fluid flow models. Given current knowledge, it is unclear how this would affect boundary layer flow. By studying the relationship between squamation patterns and the lateral line, new insights are provided into sensory biology that warrant future investigation due to the implications for the ecology, morphology and sensory evolution of sharks.


Maximizing accuracy and precision using individual and grouped exposure assessments.
Random errors in exposure data were explored to determine their effect on exposure-response relationships using individual, grouped, or combined (grouped and individual) exposure assessment methods. Monte Carlo simulations were conducted by generating small "studies" of one hundred subjects divided into four exposure groups. Observed exposure data were generated for each individual using assumed inter- and intraindividual variances and a lognormal distribution. The data were used to calculate the following three estimates of exposure: an individual mean, a group mean, and a hybrid estimate using the James-Stein shrinkage estimator. The exposure estimates were regressed on generated (continuous) "health outcomes," and the regression results were stored and analyzed. Random errors in exposure data resulted in attenuation of the exposure-response relationship when the individual estimates were used, especially when the within-subject variability was high. The attenuation was substantially controlled by the group mean estimate, however, at a cost of decreased precision. The hybrid estimator simultaneously controlled both bias and imprecision in the observed exposure-response function. While estimates of exposure based on individual means may result in attenuation of the exposure-response relationship, grouped estimates may control bias while decreasing precision. Combining individual and group estimates can simultaneously control both types of error. However, further research is required to determine how robust these findings are to different error structures, grouping strategies, exposure-response models, and exposure assessment methods.


Anesthetic use in newborn infants: the urgent need for rigorous evaluation.
Approximately 1.5 million neonates receive general anesthesia each year for a surgical procedure. Despite this being an essential practice, a number of recent studies now indicate that anesthetic exposure could cause toxicity and neuronal apoptosis in the developing brain. This could potentially influence long-term neurodevelopmental outcome, especially premature infants in need of multiple surgical procedures. Most anesthetic drugs routinely administered to neonates have not been adequately tested for safety or efficacy. Given the number of confounders, dosing is often extrapolated from adults. This is concerning since many different drugs can be administered concurrently, with few of these agents actually approved for use by the Food and Drug Administration. Since 1997, legislation has been passed in the United States and abroad encouraging more drug investigation in infants and children. This has resulted in over 500 labeling changes to products regarding safety and efficacy in various pediatric age groups. However, only three drugs routinely used as anesthetic agents in newborn infants have had any updated labeling (none in very premature infants). This "off-label" use without adequate testing must be addressed. Therefore, more clinical trials of common anesthetic agents used alone and in combination in neonates are urgently needed.


Epigenetic reprogramming by adenovirus e1a.
Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and transcriptional activation. e1a also associates transiently with promoters of antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased nucleosome density; and transcriptional repression. At later times, e1a and p107 bind mainly to promoters of development and differentiation genes, repressing transcription. The temporal order of e1a binding requires its interactions with p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming leading to cellular transformation.


Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology.
Within the past decade, clinical microbiology laboratories experienced revolutionary changes in the way in which microorganisms are identified, moving away from slow, traditional microbial identification algorithms toward rapid molecular methods and mass spectrometry (MS). Historically, MS was clinically utilized as a high-complexity method adapted for protein-centered analysis of samples in chemistry and hematology laboratories. Today, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS is adapted for use in microbiology laboratories, where it serves as a paradigm-shifting, rapid, and robust method for accurate microbial identification. Multiple instrument platforms, marketed by well-established manufacturers, are beginning to displace automated phenotypic identification instruments and in some cases genetic sequence-based identification practices. This review summarizes the current position of MALDI-TOF MS in clinical research and in diagnostic clinical microbiology laboratories and serves as a primer to examine the "nuts and bolts" of MALDI-TOF MS, highlighting research associated with sample preparation, spectral analysis, and accuracy. Currently available MALDI-TOF MS hardware and software platforms that support the use of MALDI-TOF with direct and precultured specimens and integration of the technology into the laboratory workflow are also discussed. Finally, this review closes with a prospective view of the future of MALDI-TOF MS in the clinical microbiology laboratory to accelerate diagnosis and microbial identification to improve patient care.


HIV testing practices and the potential role of HIV self-testing among men who have sex with men in Mexico.
The objective of this study was to characterize HIV testing practices among men who have sex with men in Mexico and intention to use HIV self-testing. In 2012, members of one of the largest social/sexual networking websites for men who have sex with men in Latin America completed an anonymous online survey. This analysis was restricted to HIV-uninfected men who have sex with men residing in Mexico. Multivariable logistic regression models were fit to assess factors associated with HIV testing and intention to use a HIV self-test. Of 4537 respondents, 70.9% reported ever having a HIV test, of whom 75.5% reported testing at least yearly. The majority (94.3%) indicated that they would use a HIV home self-test if it were available. Participants identifying as bisexual less often reported ever HIV testing compared to those identifying as gay/homosexual (adjusted odds ratio = 0.52, 95% confidence interval: 0.44-0.62). Having a physical exam in the past year was associated with increased ever HIV testing (adjusted odds ratio = 4.35, 95% confidence interval: 3.73-5.07), but associated with decreased interest in HIV self-testing (adjusted odds ratio = 0.66, 95% confidence interval: 0.48-0.89). The high intention to use HIV home self-testing supports the use of this method as an acceptable alternative to clinic- or hospital-based HIV testing.


Stabilization of the GluCl ligand-gated ion channel in the presence and absence of ivermectin.
Improving our understanding of the mechanisms and effects of anesthetics is a critically important part of neuroscience. The currently dominant theory is that anesthetics and similar molecules act by binding to Cys-loop receptors in the postsynaptic terminal of nerve cells and potentiate or inhibit their function. Although structures for some of the most important mammalian channels have still not been determined, a number of important results have been derived from work on homologous cationic channels in bacteria. However, partly due to the lack of a nervous system in bacteria, there are a number of questions about how these results relate to higher organisms. The recent determination of a structure of the eukaryotic chloride channel, GluCl, is an important step toward accurate modeling of mammalian channels, because it is more similar in function to human Cys-loop receptors such as GABAAR or GlyR. One potential issue with using GluCl to model other receptors is the presence of the large ligand ivermectin (IVM) positioned between all five subunits. Here, we have performed a series of microsecond molecular simulations to study how the dynamics and structure of GluCl change in the presence versus absence of IVM. When the ligand is removed, subunits move at least 2 Å closer to each other compared to simulations with IVM bound. In addition, the pore radius shrinks to 1.2 Å, all of which appears to support a model where IVM binding between subunits stabilizes an open state, and that the relaxed nonIVM conformations might be suitable for modeling other channels. Interestingly, the presence of IVM also has an effect on the structure of the important loop C located at the neurotransmitter-binding pocket, which might help shed light on its partial agonist behavior.


Affinity maturation in a human humoral response to influenza hemagglutinin.
Affinity maturation of the B cell antigen receptor (BCR) is a conserved and crucial component of the adaptive immune response. BCR lineages, inferred from paired heavy- and light-chain sequences of rearranged Ig genes from multiple descendants of the same naive B cell precursor (the lineages' unmutated common ancestor, "UCA"), make it possible to reconstruct the underlying somatic evolutionary history. We present here an extensive structural and biophysical analysis of a lineage of BCRs directed against the receptor binding site (RBS) of subtype H1 influenza virus hemagglutinin (HA). The lineage includes 8 antibodies detected directly by sequencing, 3 in 1 principal branch and 5 in the other. When bound to HA, the heavy-chain third complementarity determining region (HCDR3) fits with an invariant pose into the RBS, but in each of the 2 branches, the rest of the Fab reorients specifically, from its position in the HA-bound UCA, about a hinge at the base of HCDR3. New contacts generated by the reorientation compensate for contacts lost as the H1 HA mutated during the time between the donor's initial exposure and the vaccination that preceded sampling. Our data indicate that a "pluripotent" naive response differentiated, in each branch, into 1 of its possible alternatives. This property of naive BCRs and persistence of multiple branches of their progeny lineages can offer broader protection from evolving pathogens than can a single, linear pathway of somatic mutation.


Measurement error in the explanatory variable of a binary regression: regression calibration and integrated conditional likelihood in studies of residential radon and lung cancer.
In epidemiology, one approach to investigating the dependence of disease risk on an explanatory variable in the presence of several confounding variables is by fitting a binary regression using a conditional likelihood, thus eliminating the nuisance parameters. When the explanatory variable is measured with error, the estimated regression coefficient is biased usually towards zero. Motivated by the need to correct for this bias in analyses that combine data from a number of case-control studies of lung cancer risk associated with exposure to residential radon, two approaches are investigated. Both employ the conditional distribution of the true explanatory variable given the measured one. The method of regression calibration uses the expected value of the true given measured variable as the covariate. The second approach integrates the conditional likelihood numerically by sampling from the distribution of the true given measured explanatory variable. The two approaches give very similar point estimates and confidence intervals not only for the motivating example but also for an artificial data set with known properties. These results and some further simulations that demonstrate correct coverage for the confidence intervals suggest that for studies of residential radon and lung cancer the regression calibration approach will perform very well, so that nothing more sophisticated is needed to correct for measurement error.


A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis.
Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C(-/-) mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis.


The global financial crisis and health equity: early experiences from Canada.
It is widely acknowledged that austerity measures in the wake of the global financial crisis are starting to undermine population health results. Yet, few research studies have focused on the ways in which the financial crisis and the ensuing 'Great Recession' have affected health equity, especially through their impact on social determinants of health; neither has much attention been given to the health consequences of the fiscal austerity regime that quickly followed a brief period of counter-cyclical government spending for bank bailouts and economic stimulus. Canada has not remained insulated from these developments, despite its relative success in maneuvering the global financial crisis. The study draws on three sources of evidence: A series of semi-structured interviews in Ottawa and Toronto, with key informants selected on the basis of their expertise (n = 12); an analysis of recent (2012) Canadian and Ontario budgetary impacts on social determinants of health; and documentation of trend data on key social health determinants pre- and post the financial crisis. The findings suggest that health equity is primarily impacted through two main pathways related to the global financial crisis: austerity budgets and associated program cutbacks in areas crucial to addressing the inequitable distribution of social determinants of health, including social assistance, housing, and education; and the qualitative transformation of labor markets, with precarious forms of employment expanding rapidly in the aftermath of the global financial crisis. Preliminary evidence suggests that these tendencies will lead to a further deepening of existing health inequities, unless counter-acted through a change in policy direction. This article documents some of the effects of financial crisis and severe economic decline on health equity in Canada. However, more research is necessary to study policy choices that could mitigate this effect. Since the policy response to a similar set of economic shocks has globally varied and led to differential health and health equity outcomes, comparative studies are now possible to assess the successes and failures of specific policy responses. This raises the question of what types of public policy can mitigate against the negative health equity effects of severe economic recessions.


From the nonlinear Fokker-Planck equation to the Vlasov description and back: Confined interacting particles with drag.
Nonlinear Fokker-Planck equations endowed with power-law diffusion terms have proven to be valuable tools for the study of diverse complex systems in physics, biology, and other fields. The nonlinearity appearing in these evolution equations can be interpreted as providing an effective description of a system of particles interacting via short-range forces while performing overdamped motion under the effect of an external confining potential. This point of view has been recently applied to the study of thermodynamical features of interacting vortices in type II superconductors. In the present work we explore an embedding of the nonlinear Fokker-Planck equation within a Vlasov equation, thus incorporating inertial effects to the concomitant particle dynamics. Exact time-dependent solutions of the q-Gaussian form (with compact support) are obtained for the Vlasov equation in the case of quadratic confining potentials.


A hydrogen curing effect on surface plasmon resonance fiber optic hydrogen sensors using an annealed Au/Ta₂O₅/Pd multi-layers film.
In this paper, a response time of the surface plasmon resonance fiber optic hydrogen sensor has successfully improved with keeping sensor sensitivity high by means of hydrogen curing (immersing) process of annealed Au/Ta2O5/ Pd multi-layers film. The hydrogen curing effect on the response time and sensitivity has been experimentally revealed by changing the annealing temperatures of 400, 600, 800°C and through observing the optical loss change in the H2 curing process. When the 25-nm Au/60-nm Ta2O5/10-nm Pd multi-layers film annealed at 600°C is cured with 4% H2/N2 mixture, it is found that a lot of nano-sized cracks were produced on the Pd surface. After H2 curing process, the response time is improved to be 8 s, which is two times faster than previous reported one in the case of the 25-nm Au/60-nm Ta2O5/3-nm Pd multi-layers film with keeping the sensor sensitivity of 0.27 dB for 4% hydrogen adding. Discussions most likely responsible for this effect are given by introducing the α-β transition Pd structure in the H2 curing process.


Risk, governance and the experience of care.
Drawing on perspectives from the governmentality literature and the sociology of risk, this article explores the strategies, tools and mechanisms for managing risk in acute hospital trusts in the United Kingdom. The article uses qualitative material from an ethnographic study of four acute hospital trusts undertaken between 2008 and 2010 focusing on the provision of dignified care for older people. Extracts from ethnographic material show how the organisational mechanisms that seek to manage risk shape the ways in which staff interact with and care for patients. The article bridges the gap between the sociological analysis of policy priorities, management strategy and the organisational cultures of the NHS, and the everyday interactions of care provision. In bringing together this ethnographic material with sociological debates on the regulation of healthcare, the article highlights the specific ways in which forms of governance shape how staff care for their patients challenging the possibility of providing dignified care for older people.


Patients and informal caregivers' experiences of burden of treatment in lung cancer and chronic obstructive pulmonary disease (COPD): a systematic review and synthesis of qualitative research.
To identify, characterise and explain common and specific features of the experience of treatment burden in relation to patients living with lung cancer or chronic obstructive pulmonary disease (COPD) and their informal caregivers. Systematic review and interpretative synthesis of primary qualitative studies. Papers were analysed using constant comparison and directed qualitative content analysis. CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science searched from January 2006 to December 2015. Primary qualitative studies in English where participants were patients with lung cancer or COPD and/or their informal caregivers, aged >18 years that contain descriptions of experiences of interacting with health or social care in Europe, North America and Australia. We identified 127 articles with 1769 patients and 491 informal caregivers. Patients, informal caregivers and healthcare professionals (HCPs) acknowledged lung cancer's existential threat. Managing treatment workload was a priority in this condition, characterised by a short illness trajectory. Treatment workload was generally well supported by an immediacy of access to healthcare systems and a clear treatment pathway. Conversely, patients, informal caregivers and HCPs typically did not recognise or understand COPD. Treatment workload was balanced with the demands of everyday life throughout a characteristically long illness trajectory. Consequently, treatment workload was complicated by difficulties of access to, and navigation of, healthcare systems, and a fragmented treatment pathway. In both conditions, patients' capacity to manage workload was enhanced by the support of family and friends, peers and HCPs and diminished by illness/smoking-related stigma and social isolation. This interpretative synthesis has affirmed significant differences in treatment workload between lung cancer and COPD. It has demonstrated the importance of the capacity patients have to manage their workload in both conditions. This suggests a workload which exceeds capacity may be a primary driver of treatment burden. CRD42016048191.