Enhancement of risk of tick-borne infection: environmental and parasitological aspects of the problem.
The appearance of phenotypic (and probably genetic) exoskeleton anomalies in Ixodes ticks, first discovered and described elsewhere, seems to be a global phenomenon clearly related to environment pollution by heavy metal ions. These external markers of cadmium accumulation in the tick indicate an enhanced risk of tick-borne infection related to an increased vectorial capacity. This manifests itself in the ability of infected ticks both to quest longer and to show increased locomotory activity (hunting) compared with normal ticks. Ticks with exoskeleton anomalies show a greater susceptibility to different microorganisms, including tick-borne pathogens, and more intense pathogen replication with a higher prevalence of multi-infection.


Immunolocalization of Kex2 protease identifies a putative late Golgi compartment in the yeast Saccharomyces cerevisiae.
The Kex2 protein of the yeast Saccharomyces cerevisiae is a membrane-bound, Ca2(+)-dependent serine protease that cleaves the precursors of the mating pheromone alpha-factor and the M1 killer toxin at pairs of basic residues during their transport through the secretory pathway. To begin to characterize the intracellular locus of Kex2-dependent proteolytic processing, we have examined the subcellular distribution of Kex2 protein in yeast by indirect immunofluorescence. Kex2 protein is located at multiple, discrete sites within wild-type yeast cells (average, 3.0 +/- 1.7/mother cell). Qualitatively similar fluorescence patterns are observed at elevated levels of expression, but no signal is found in cells lacking the KEX2 gene. Structures containing Kex2 protein are not concentrated at a perinuclear location, but are distributed throughout the cytoplasm at all phases of the cell cycle. Kex2-containing structures appear in the bud at an early, premitotic stage. Analysis of conditional secretory (sec) mutants demonstrates that Kex2 protein ordinarily progresses from the ER to the Golgi but is not incorporated into secretory vesicles, consistent with the proposed localization of Kex2 protein to the yeast Golgi complex.


Annual healthcare spending attributable to cigarette smoking: an update.
Fifty years after the first Surgeon General's report, tobacco use remains the nation's leading preventable cause of death and disease, despite declines in adult cigarette smoking prevalence. Smoking-attributable healthcare spending is an important part of overall smoking-attributable costs in the U.S. To update annual smoking-attributable healthcare spending in the U.S. and provide smoking-attributable healthcare spending estimates by payer (e.g., Medicare, Medicaid, private insurance) or type of medical services. Analyses used data from the 2006-2010 Medical Expenditure Panel Survey linked to the 2004-2009 National Health Interview Survey. Estimates from two-part models were combined to predict the share of annual healthcare spending that could be attributable to cigarette smoking. The analysis was conducted in 2013. By 2010, 8.7% (95% CI=6.8%, 11.2%) of annual healthcare spending in the U.S. could be attributed to cigarette smoking, amounting to as much as $170 billion per year. More than 60% of the attributable spending was paid by public programs, including Medicare, other federally sponsored programs, or Medicaid. These findings indicate that comprehensive tobacco control programs and policies are still needed to continue progress toward ending the tobacco epidemic in the U.S. 50 years after the release of the first Surgeon General's report on smoking and health.


Measuring deviant sexual interest in adolescents using the emotional Stroop task.
Adolescent sexual abusers are a heterogeneous group of offenders that often receive generic assessment and treatment services that are modeled on research findings from adult sex offender samples. The emotional Stroop task has been used to measure deviant sexual interest in adult samples. The purpose of the present study was to test whether the emotional Stroop task could also be used to assess deviant sexual interest in adolescent samples. Three groups of adolescents (a) sexual abusers (n = 24); (b) offending controls (n = 21); and (c) nonoffending controls (n = 21) completed two emotional Stroop tasks related to deviant sexual interest and tests of executive function. Adolescent sexual abusers were significantly slower to color-name some word stimuli than both adolescent offending controls and adolescent nonoffending controls. However, the task was unable to differentiate between the groups on most of the Stroop word categories. Very little research has been conducted with adolescent offender samples and the emotional Stroop task. Reaction time (RT) and Stroop bias outcome data for adolescent samples appear to be more unsystematic and weaker than has been observed in previous adult data. Based on potential difficulties with reading and development, the emotional Stroop task may not be a task suitable for measuring deviant sexual interest in adolescent samples.


Evaluation of Methods for the Concentration and Extraction of Viruses from Sewage in the Context of Metagenomic Sequencing.
Viral sewage metagenomics is a novel field of study used for surveillance, epidemiological studies, and evaluation of waste water treatment efficiency. In raw sewage human waste is mixed with household, industrial and drainage water, and virus particles are, therefore, only found in low concentrations. This necessitates a step of sample concentration to allow for sensitive virus detection. Additionally, viruses harbor a large diversity of both surface and genome structures, which makes universal viral genomic extraction difficult. Current studies have tackled these challenges in many different ways employing a wide range of viral concentration and extraction procedures. However, there is limited knowledge of the efficacy and inherent biases associated with these methods in respect to viral sewage metagenomics, hampering the development of this field. By the use of next generation sequencing this study aimed to evaluate the efficiency of four commonly applied viral concentrations techniques (precipitation with polyethylene glycol, organic flocculation with skim milk, monolithic adsorption filtration and glass wool filtration) and extraction methods (Nucleospin RNA XS, QIAamp Viral RNA Mini Kit, NucliSENS® miniMAG®, or PowerViral® Environmental RNA/DNA Isolation Kit) to determine the viriome in a sewage sample. We found a significant influence of concentration and extraction protocols on the detected viriome. The viral richness was largest in samples extracted with QIAamp Viral RNA Mini Kit or PowerViral® Environmental RNA/DNA Isolation Kit. Highest viral specificity were found in samples concentrated by precipitation with polyethylene glycol or extracted with Nucleospin RNA XS. Detection of viral pathogens depended on the method used. These results contribute to the understanding of method associated biases, within the field of viral sewage metagenomics, making evaluation of the current literature easier and helping with the design of future studies.


Investigator-initiated trials of targeted oncology agents: why independent research is at risk?
Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies. An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and industry researchers, patients, and government regulatory and postregulatory agencies-examined the growing schism between academia and industry and identified several causes of declining academic research. The authors propose solutions to sustain investigator-initiated research and provide a new model whereby expert organisations provide a forum for academia and industry to plan studies within a regulatory framework to support licensure/authorisation and reimbursement for new molecularly targeted agents and biomarkers. Investigator-initiated trials have led to the discovery and development of innovative, safe, and effective cancer treatments. To ensure that such research continues, action will be required on the parts of legislative and regulatory bodies, industry, universities, patient advocacy organisations, and preclinical and clinical academic scientists.


High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.
Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.


Sex hormones, personality characters and professional status among Saudi females.
The relationship between male and female sex hormones (testosterone, estradiol and progesterone), personality characters and professional status was studied. The study was conducted in Riyadh City, Kingdom of Saudi Arabia between September 2003 and May 2003. The participants completed a questionnaire consisting of personal information regarding age, profession, educational level and medical history. Then the participant went through an adjective checklist. Hormones were determined from blood samples provided by the participant. The result indicated that the higher the professional levels, the higher was the testosterone concentrations, but not estradiol or estrogen concentration. Furthermore, females with higher testosterone concentration (university lecturers, bank managers, bank employee, medical doctors and technical workers) identify themselves as independent, strong, assertive, impulsive, resourceful, spontaneous, uninhibited, rational, patient and arguing. Whereas, females with lower testosterone concentrations (housewives and clerical workers) view themselves as civilized, socialized, calm, quite, sentimental, shy, nice, sensitive, warmhearted, sympathetic, thoughtful, warm, practical and kind. The current study emphasizes the positive relationship between strong personality characters, high professional status and male sex hormone level (testosterone) in females.


Using the Past to Predict the Present: Confidence Intervals for Regression Equations in Phylogenetic Comparative Methods.
Two phylogenetic comparative methods, independent contrasts and generalized least squares models, can be used to determine the statistical relationship between two or more traits. We show that the two approaches are functionally identical and that either can be used to make statistical inferences about values at internal nodes of a phylogenetic tree (hypothetical ancestors), to estimate relationships between characters, and to predict values for unmeasured species. Regression equations derived from independent contrasts can be placed back onto the original data space, including computation of both confidence intervals and prediction intervals for new observations. Predictions for unmeasured species (including extinct forms) can be made increasingly accurate and precise as the specificity of their placement on a phylogenetic tree increases, which can greatly increase statistical power to detect, for example, deviation of a single species from an allometric prediction. We reexamine published data for basal metabolic rates (BMR) of birds and show that conventional and phylogenetic allometric equations differ significantly. In new results, we show that, as compared with nonpasserines, passerines exhibit a lower rate of evolution in both body mass and mass-corrected BMR; passerines also have significantly smaller body masses than their sister clade. These differences may justify separate, clade-specific allometric equations for prediction of avian basal metabolic rates.


Transcriptional termination by RNA polymerase I requires the small subunit Rpa12p.
We identify Rpa12p of RNA polymerase I (Pol I) as a termination factor. Combined analyses using transcription run-on, electron microscopy-visualized chromatin spreading and RT-PCR have been applied to the rRNA-encoding genes of Saccharomyces cerevisiae. These confirm that Pol I termination occurs close to the Reb1p-dependent terminator in wild-type strains. However, deletion mutants for the 3' end-processing enzyme Rnt1p or the Rpa12p subunit of Pol I both show Pol I transcription in the spacer. For Deltarpa12, these spacer polymerases are devoid of nascent transcripts, suggesting they are immediately degraded. The homology of Rpa12p to the small subunit Rpb9p of Pol II and Rpc11p of Pol III, both implicated in transcriptional termination, points to a common termination mechanism for all three classes of RNA polymerase.


Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D.
Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.


Retargeted oncolytic measles strains entering via the EGFRvIII receptor maintain significant antitumor activity against gliomas with increased tumor specificity.
Among the best-characterized genetic alterations in gliomas is the amplification of the epidermal growth factor receptor (EGFR) gene, present in approximately 40% of glioblastoma multiforme, and frequently associated with the EGFRvIII gene rearrangement. We have previously shown that attenuated vaccine strains of measles virus have potent antitumor activity against gliomas, and identified H protein mutations, which ablate recognition of the natural measles virus receptors CD46 and SLAM. Retargeted recombinant viruses were generated from the measles Edmonston-NSe vaccine strain displaying a single-chain antibody against EGFRvIII at the COOH terminus of H and containing the marker green fluorescent protein (GFP) gene in position 1. Two different H mutants were employed: H(SNS) (V451S, Y481N, and A527S)-CD46 blind, and H(AA) (Y481A and R533A)-CD46 and SLAM blind. MV-GFP virus was used as a positive control. Both EGFRvIII-retargeted viruses had significant antitumor activity against EGFRvIII-expressing glioblastoma multiforme but no cytopathic effect against normal cells. In an orthotopic model of EGFRvIII-expressing GBM39 xenografts, there was comparable therapeutic efficacy between retargeted strains and unmodified MV-GFP and statistically significant prolongation of survival in treated animals compared with the control group (P = 0.001). Formation of syncytia was observed in tumors treated with retargeted viruses, with a surrounding infiltrate consisting of macrophages and natural killer cells. In summary, EGFRvIII-retargeted oncolytic measles virus strains have comparable therapeutic efficacy with the unmodified MV-GFP strain against EGFRvIII-expressing glioma lines and xenografts with improved therapeutic index, a finding with potential translational implications in glioma virotherapy.


Aircraft-Assisted Pilot Suicides in the General Aviation Increased for One-Year Period after 11 September 2001 Attack in the United States.
Pilot aircraft-assisted suicides (AAS) are rare, and there is limited understanding of copycat phenomenon among aviators. The aim of this study was to evaluate the possible effect the 11 September 2001, terrorist attacks had on pilot AASs in the U.S. Fatal aviation accidents in the National Transportation Safety Board (NTSB) database were searched using the following search words: "suicide", "murder-suicide" and "homicide-suicide". The timeline between 11 September 1996, and 11 September 2004, was analyzed. Only those accidents in which NTSB judged that the cause of the accident was suicide were included in the final analysis. The relative risk (RR) of the pilot AASs in all fatal accidents in the U.S. was calculated in order to compare the one, two, and three-year periods after the September 11 terrorist attacks with five years preceding the event. The RR of a fatal general aviation aircraft accident being due to pilot suicide was 3.68-fold (95% confidence interval 1.04⁻12.98) during the first year after 11 September 2001, but there was not a statistically significant increase in the later years. This study showed an association, albeit not determinate causal effect, of a very specific series of simultaneous terrorist murder-suicides with subsequent pilot AASs.


Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study.
Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40-65 years, for whom 1-10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63-92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25-0·75]). The trial met the prespecified criteria for progression to a full trial. This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Research for Patient Benefit programme, National Institute for Health Research.


Does an expert-based evaluation allow us to go beyond the Impact Factor? Experiences from building a ranking of national journals in Poland.
This article discusses the Polish Journal Ranking, which is used in the research evaluation system in Poland. In 2015, the ranking, which represents all disciplines, allocated 17,437 journals into three lists: A, B, and C. The B list constitutes a ranking of Polish journals that are indexed neither in the Web of Science nor the European Reference Index for the Humanities. This ranking was built by evaluating journals in three dimensions: formal, bibliometric, and expert-based. We have analysed data on 2035 Polish journals from the B list. Our study aims to determine how an expert-based evaluation influenced the results of final evaluation. In our study, we used structural equation modelling, which is regression based, and we designed three pairs of theoretical models for three fields of science: (1) humanities, (2) social sciences, and (3) engineering, natural sciences, and medical sciences. Each pair consisted of the full model and the reduced model (i.e., the model without the expert-based evaluation). Our analysis revealed that the multidimensional evaluation of local journals should not rely only on the bibliometric indicators, which are based on the Web of Science or Scopus. Moreover, we have shown that the expert-based evaluation plays a major role in all fields of science. We conclude with recommendations that the formal evaluation should be reduced to verifiable parameters and that the expert-based evaluation should be based on common guidelines for the experts.


Retention of Native Protein Structures in the Absence of Solvent: A Coupled Ion Mobility and Spectroscopic Study.
Can the structures of small to medium-sized proteins be conserved after transfer from the solution phase to the gas phase? A large number of studies have been devoted to this topic, however the answer has not been unambiguously determined to date. A clarification of this problem is important since it would allow very sensitive native mass spectrometry techniques to be used to address problems relevant to structural biology. A combination of ion-mobility mass spectrometry with infrared spectroscopy was used to investigate the secondary and tertiary structure of proteins carefully transferred from solution to the gas phase. The two proteins investigated are myoglobin and β-lactoglobulin, which are prototypical examples of helical and β-sheet proteins, respectively. The results show that for low charge states under gentle conditions, aspects of the native secondary and tertiary structure can be conserved.


Interplay of Chemistry and Faceting at Grain Boundaries in a Model Al Alloy.
The boundary between two crystal grains can decompose into arrays of facets with distinct crystallographic character. Faceting occurs to minimize the system's free energy, i.e., when the total interfacial energy of all facets is below that of the topologically shortest interface plane. In a model Al-Zn-Mg-Cu alloy, we show that faceting occurs at investigated grain boundaries and that the local chemistry is strongly correlated with the facet character. The self-consistent coevolution of facet structure and chemistry leads to the formation of periodic segregation patterns of 5-10 nm, or to preferential precipitation. This study shows that segregation-faceting interplay is not limited to bicrystals but exists in bulk engineering Al alloys and hence affects their performance.


Effect of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records.
To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use. Population based cohort study in England. UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11. Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record. Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London. Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct. Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years). Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001). Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers. With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02). The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD. NCT01335672.


What did we learn from the HEMO Study? Implications of secondary analyses.
The HEMO Study was a randomized clinical trial designed to determine whether increasing hemodialysis dose above current standards, or using high-flux membranes, would improve patient outcome. The primary results of the trial showed no statistically significant effects of either dialysis dose or membrane flux on the primary outcome of mortality. This report examines the implications of secondary analyses involving subgroups and secondary outcome measures for the overall interpretation of the trial. The secondary analyses of the HEMO Study do not alter the conclusions of the primary analysis: In the context of conventional three times per week hemodialysis, neither the high-flux nor high-dose interventions substantially improved patient outcome compared to low-flux and standard-dose levels. However, certain secondary results from the trial are consistent with the hypothesis of subtle effects that may be magnified by more intensive therapies that extend beyond the limits of conventional three times per week dialysis. This hypothesis will be addressed by a pair of new randomized trials sponsored by the National Institute of Digestive and Kidney Disease (NIDDK), which will compare six times per week daily and nocturnal therapies with conventional three times per week dialysis.


Stabilization of carbon in composts and biochars in relation to carbon sequestration and soil fertility.
There have been increasing interests in the conversion of organic residues into biochars in order to reduce the rate of decomposition, thereby enhancing carbon (C) sequestration in soils. However energy is required to initiate the pyrolysis process during biochar production which can also lead to the release of greenhouse gasses. Alternative methods can be used to stabilize C in composts and other organic residues without impacting their quality. The objectives of this study include: (i) to compare the rate of decomposition among various organic amendments and (ii) to examine the effect of clay materials on the stabilization of C in organic amendments. The decomposition of a number of organic amendments (composts and biochars) was examined by monitoring the release of carbon-dioxide using respiration experiments. The results indicated that the rate of decomposition as measured by half life (t(1/2)) varied between the organic amendments and was higher in sandy soil than in clay soil. The half life value ranged from 139 days in the sandy soil and 187 days in the clay soil for poultry manure compost to 9989 days for green waste biochar. Addition of clay materials to compost decreased the rate of decomposition, thereby increasing the stabilization of C. The half life value for poultry manure compost increased from 139 days to 620, 806 and 474 days with the addition of goethite, gibbsite and allophane, respectively. The increase in the stabilization of C with the addition of clay materials may be attributed to the immobilization of C, thereby preventing it from microbial decomposition. Stabilization of C in compost using clay materials did not impact negatively the value of composts in improving soil quality as measured by potentially mineralizable nitrogen and microbial biomass carbon in soil.


A social cost-benefit criterion for evaluating Voluntary Counseling and Testing with an application to Tanzania.
There are many interventions for HIV/AIDS that require that people know their status and hence require a HIV test. Testing that is driven by a desire to prevent the spread of the disease often has an indirect effect on others. These external effects need to be identified, quantified and included as part of the benefits and costs of testing. Pioneering analyses of HIV testing by Philipson and Posner have introduced the economic calculus of individual expected benefits and costs of activities into an understanding of the HIV epidemic. What is required for social evaluations is an extension of the analysis to ensure that external effects are included. The objective of this paper is two-fold. First we seek to formulate cost-benefit criteria that incorporate fully the external effects in the evaluation of Voluntary Counseling and Testing (VCT). We achieve this by recasting the individual calculus of benefits and costs to a couple setting. We can then compare an individual's cost-benefit analysis of being tested with social criteria that look at outcomes from a couple's perspective for both separate and dual/joint testing. Second we aim to apply our social criteria to VCT programs as they currently operate in Tanzania and how these programs might operate in the future when they are scaled up to relate to the general population. We develop social criteria for evaluating separate and dual VCT using a couple's perspective with and without altruism. Therefore, the welfare function is based on two individual expected utility functions viewed as a couple, either married or regular partners. The benefits are the averted lives lost whenever discordant couples are revealed. The costs of VCT are the benefits of unprotected sex that the couple foregoes and the costs of the testing and counseling. The cost-benefit criteria are applied to VCT programs in Tanzania. The four main ingredients estimated are: the foregone benefit of unprotected sex (measured by the compensated wage differentials charged by commercial sex workers); the probability of infection; the cost of an infection (measured by both the value of a statistical life and the human capital approaches) and the cost of a single test (which includes behavior-modifying counseling). We find separate testing in existing VCT programs to be only marginally worthwhile. However, in scaled-up programs the benefit-cost ratio is over three. Dual testing is always more beneficial than separate testing. However, this advantage is reduced in scaled-up programs. VCT should be greatly expanded throughout Tanzania as future returns would be even higher for both separate and joint counseling and HIV testing.


Targeting Corticotroph HDAC and PI3-Kinase in Cushing Disease.
Cushing disease (CD) is a life-threatening disorder. Therapeutic goals include symptom relief, biochemical control, and tumor growth inhibition. Current medical therapies for CD by and large exert no action on tumor growth. To identify drugs that inhibit corticotroph tumor adrenocorticotropic hormone (ACTH) secretion and growth. High throughput screen employing a novel "gain of signal" ACTH AlphaLISA assay. Academic medical center. Corticotroph tumor tissues from patients with CD. None. Potent inhibitors of corticotroph tumor ACTH secretion and growth. From a kinase inhibitor library, we identified the dual PI3K/HDAC inhibitor CUDC-907 as a potent inhibitor of murine and human corticotroph tumor ACTH secretion (median effective concentration 1-5 nM), and cell proliferation (median inhibitory concentration 5 nM). In an in vivo murine corticotroph tumor xenograft model, orally administered CUDC-907 (300 mg/kg) reduced corticotroph tumor volume (TV [cm3], control 0.17 ± 0.05 vs CUDC-907 0.07 ± 0.02, P < .05) by 65% and suppressed plasma ACTH (ACTH [pg/mL] control 206 ± 27 vs CUDC-907 47 ± 7, P < .05) and corticosterone (corticosterone [ng/mL] control 180 ± 87 vs CUDC-907 27 ± 5, P < .05) levels by 77% and 85% respectively compared with controls. We also demonstrated that CUDC-907 acts through HDAC1/2 inhibition at the proopiomelanocortin transcriptional level combined with its PI3K-mediated inhibition of corticotroph cell viability to reduce ACTH secretion. Given its potent efficacy in in vitro and in vivo models of CD, combined with proven safety and tolerance in clinical trials, we propose CUDC-907 may be a promising therapy for CD.


Platelets Enhance Dendritic Cell Responses against Staphylococcus aureus through CD40-CD40L.
Staphylococcus aureus is a major human pathogen that can cause mild to severe life-threatening infections in many tissues and organs. Platelets are known to participate in protection against S. aureus by direct killing and by enhancing the activities of neutrophils and macrophages in clearing S. aureus infection. Platelets have also been shown to induce monocyte differentiation into dendritic cells and to enhance activation of dendritic cells. Therefore, in the present study, we explored the role of platelets in enhancing bone marrow-derived dendritic cell (BMDC) function against S. aureus We observed a significant increase in dendritic cell phagocytosis and intracellular killing of a methicillin-resistant Staphylococcus aureus (MRSA) strain (USA300) by thrombin-activated platelets or their releasates. Enhancement of bacterial uptake and killing by DCs is mediated by platelet-derived CD40L. Coculture of USA300 and BMDCs in the presence of thrombin-activated platelet releasates invokes upregulation of the maturation marker CD80 on DCs and enhanced production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and IL-6. Overall, these observations support our hypothesis that platelets play a critical role in the host defense against S. aureus infection. Platelets stimulate DCs, leading to direct killing of S. aureus and enhanced DC maturation, potentially leading to adaptive immune responses against S. aureus.


The Reliability of Cone Density Measurements in the Presence of Rods.
Recent advances in adaptive optics scanning light ophthalmoscopy (AOSLO) have enabled visualization of cone inner segments through nonconfocal split-detection, in addition to rod and cone outer segments revealed by confocal reflectance. Here, we examined the interobserver reliability of cone density measurements in both AOSLO imaging modalities. Five normal subjects (nine eyes) were imaged along the horizontal and vertical meridians using a custom AOSLO with confocal and nonconfocal split-detection modalities. The resulting images were montaged using a previously described semiautomatic algorithm. Regions of interest (ROIs) were selected from the confocal montage at 190 μm, and from split-detection and confocal montages at 900 and 1800 μm from the fovea. Four observers (three experts, one naïve) manually identified cone locations in each ROI, and these locations were used to calculate bound densities. Intraclass correlation coefficients and Dice's coefficients were calculated to assess interobserver agreement. Interobserver agreement was high in cone-only images (confocal 190 μm: 0.85; split-detection 900 μm: 0.91; split-detection 1800 μm: 0.89), moderate in confocal images at 900 μm (0.68), and poor in confocal images at 1800 μm (0.24). Excluding the naïve observer data substantially increased agreement within confocal images (190 μm: 0.99; 900 μm: 0.80; 1800 μm: 0.68). Interobserver measurements of cone density are more reliable in rod-free retinal images. Moreover, when using manual cell identification, it is essential that observers are trained, particularly for confocal AOSLO images. This study underscores the need for additional reliability studies in eyes containing pathology where identifying cones can be substantially more difficult.


Hepatitis C virus acquisition among Egyptians: analysis of a 10-year surveillance of acute hepatitis C.
To identify current risk factors for hepatitis C virus (HCV) acquisition among Egyptians. Patients with acute HCV were identified through a surveillance system of acute hepatitis in four fever hospitals in Egypt between 2002 and 2012. Case-control analysis was conducted, cases being incident acute symptomatic HCV and controls being acute hepatitis A identified at the same hospitals. The questionnaire covered iatrogenic, community and household exposures to HCV in the 1-6 months prior to onset of symptoms. Multivariate models were built to identify risk factors associated with HCV acquisition among non-drug users and drug users separately. Among non-drug users, hospital admission was independently associated with acute HCV infection (OR = 4.2, 95% CI = 1.7-10.5). Several iatrogenic procedures, for example admission in a surgery unit, sutures, IV injections and IV infusions, highly correlated with hospital admission, were also associated with acute HCV infection and could have been used in the final model instead of hospital admission. Among drug users, identified risk factors were multiple sexual relations (OR = 4.0, 95% CI = 1.1-14.7), intravenous drug use (OR = 3.9, 95% CI = 1.2-13.0) and shaving at the barbershops (OR = 8.7, 95% CI = 2.4-31.4). Illiteracy and marriage were significant risk factors in both groups. Invasive medical procedures are still a major risk for acquiring new HCV infections in Egypt, as is illicit drug use in spreading HCV infection.


Identification of strains of Alcaligenes and Agrobacterium by a polyphasic approach.
The number of stable discriminant biochemical characters is limited in the genera Alcaligenes and Agrobacterium, whose species are consequently difficult to distinguish from one another by conventional tests. Moreover, genomic studies have recently drastically modified the nomenclature of these genera; for example, Alcaligenes xylosoxidans was transferred to the genus Achromobacter in 1998. Twenty-five strains of Achromobacter xylosoxidans, three strains of an Agrobacterium sp., five strains of an Alcaligenes sp., and four unnamed strains belonging to the Centers for Disease Control and Prevention group IVc-2 were examined. These strains were characterized by conventional tests, including biochemical tests. The assimilation of 99 carbohydrates, organic acids, and amino acids was studied by using Biotype-100 strips, and rRNA gene restriction patterns were obtained with the automated Riboprinter microbial characterization system after cleavage of total DNA with EcoRI or PstI restriction endonuclease. This polyphasic approach allowed the two subspecies of A. xylosoxidans to be clearly separated. Relationships between five strains and the Ralstonia paucula type strain were demonstrated. Likewise, three strains were found to be related to the Ochrobactrum anthropi type strain. We showed that substrate assimilation tests and automated ribotyping provide a simple, rapid, and reliable means of identifying A. xylosoxidans subspecies and that these two methods can be used as alternative methods to characterize unidentified strains rapidly when discriminant biochemical characters are missing.


Scaling-up access to antiretroviral therapy for children: a cohort study evaluating care and treatment at mobile and hospital-affiliated HIV clinics in rural Zambia.
Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia. Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility. Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4(+) T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4(+) T-cell percentages. HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas.


Interphase chromosome positioning in in vitro porcine cells and ex vivo porcine tissues.
In interphase nuclei of a wide range of species chromosomes are organised into their own specific locations termed territories. These chromosome territories are non-randomly positioned in nuclei which is believed to be related to a spatial aspect of regulatory control over gene expression. In this study we have adopted the pig as a model in which to study interphase chromosome positioning and follows on from other studies from our group of using pig cells and tissues to study interphase genome re-positioning during differentiation. The pig is an important model organism both economically and as a closely related species to study human disease models. This is why great efforts have been made to accomplish the full genome sequence in the last decade. This study has positioned most of the porcine chromosomes in in vitro cultured adult and embryonic fibroblasts, early passage stromal derived mesenchymal stem cells and lymphocytes. The study is further expanded to position four chromosomes in ex vivo tissue derived from pig kidney, lung and brain. It was concluded that porcine chromosomes are also non-randomly positioned within interphase nuclei with few major differences in chromosome position in interphase nuclei between different cell and tissue types. There were also no differences between preferred nuclear location of chromosomes in in vitro cultured cells as compared to cells in tissue sections. Using a number of analyses to ascertain by what criteria porcine chromosomes were positioned in interphase nuclei; we found a correlation with DNA content.


Identifying Axial Spondyloarthritis in Patients With Inflammatory Bowel Disease Using Computed Tomography.
The diagnosis of axial spondyloarthritis (axSpA) is hampered by diagnostic delay. Computed tomography (CT) undertaken for nonmusculoskeletal (non-MSK) indications in patients with inflammatory bowel disease (IBD) offers an opportunity to identify sacroiliitis for prompt rheumatology referral. This study aims to identify what proportion of patients with IBD who underwent abdominopelvic CT for non-MSK indications have axSpA and to explore the role of a standardized screening tool to prospectively identify axSpA on imaging. Abdominopelvic CT scans of patients with verified IBD, aged 18 to 55 years, performed for non-MSK indications were reviewed by radiologists for the presence of CT-defined sacroiliitis (CTSI), using criteria from a validated CT screening tool. All patients identified were sent a screening questionnaire, and those with self-reported chronic back pain (CBP), CBP duration of greater than 3 months, and age of onset of less than 45 years were invited for rheumatology review. CTSI was identified in 60 out of 301 (19.9%) patients. Out of these 60 patients, 32 (53%) responded to an invitation to participate, and 27 out of 32 (84.3%) were enrolled. Of these, 8 had a preexisting axSpA diagnosis and 5 did not report CBP. In total, 14 patients underwent rheumatology assessment, and 3 out of 14 (21.4%, 95% CI 4.7-50.8) had undiagnosed axSpA. In total, 11 out of 27 (40.7%, 95% CI 22.4-61.2) patients had a rheumatologist-verified diagnosis of axSpA. In this study, 5% (3/60) of patients with IBD undergoing abdominopelvic CT for non-MSK indications with CTSI were found to have undiagnosed axSpA and, overall, 18.3% (11/60) were found to have axSpA. This reveals a significant hidden population of axSpA and highlights the need for a streamlined pathway from sacroiliitis detection to rheumatology referral.


Juvenile delinquency and psychopathic traits: an empirical study with Portuguese adolescents.
The objective of the present study was to analyze the role of psychopathic traits in juvenile delinquency. Using a sample of 543 young males from the Juvenile Detention Centers of the Portuguese Ministry of Justice and from schools in the Lisbon region, a group of high psychopathic traits (n = 281) and a group of low psychopathic traits (n = 262) were formed based on the Portuguese version of Antisocial Process Screening Device (APSD). Results showed that youths with high psychopathic traits start engaging in criminal activities earlier in life, come into contact with the justice system earlier in life, and have higher levels of conduct disorder, behavior problems, and delinquent behaviors as well as lower levels of self-esteem.


cHRV Uncovering Daily Stress Dynamics Using Bio-Signal from Consumer Wearables.
Knowing the dynamics of one's daily stress is essential to effective stress management in the context of smart and connected health. However, there lacks a practical and unobtrusive means to obtain real-time and longitudinal stress information. In this paper, we attempt to derive a convenient HRV-based (heart rate variability) biomarker named cHRV, which can be used to reliably reflect stress dynamics. cHRV's key advantage lies in its low maintenance and high practicality. It can be efficiently calculated only using data from photoplethysmography (PPG) sensors, the mainstream heart rate sensor embedded in most of the consumer wearables like Apple Watch. Benefiting from the proliferation of wearables, cHRV is ideal for day-to-day stress monitoring. To evaluate its feasibility and performance, we have conducted 14 in-lab controlled experiments. The result shows that the proposed cHRV has strong correlation with the stress dynamics (r > 0.95), therefore exhibits great potential for continuous stress assessment.


The Evaluation of Fetal Cardiac Remote Screening in the Second Trimester of Pregnancy Using the Spatio-Temporal Image Correlation Method.
We prospectively performed remote fetal cardiac screening using the spatio-temporal image correlation (STIC), and examined the usefulness and problems of remote screening. We performed heart screening for all pregnant women at four obstetrics clinics over the three years from 2009 to 2014. The STIC data from 15,404 examinations in normal pregnancies (16-27 weeks, median 25 weeks) were analyzed. Obstetricians and sonographer collected STIC data from four-chamber view images. Eight pediatric cardiologists analyzed the images offline. A normal heart was diagnosed in 14,002 cases (90.9%), an abnormal heart was diagnosed in 457 cases (3.0%), and poor images were obtained in 945 cases (6.1%). 138 cases had congenital heart disease (CHD) after birth, and severe CHD necessitating hospitalization occurred in 36 cases. We were not able to detect CHD by screening in 12 cases. The sensitivity and specificity of STIC in CHD screening was 50% and 99.5%, respectively. The sensitivity and specificity of STIC in screening for severe CHD was 82% and 99.9%, respectively. The STIC method was useful in fetal remote screening for CHD. However, the fact that > 10% of images that could not be analyzed by this method was a problem.


[The potential use of ayahuasca in psychiatry].
Ayahuasca is a decoctum made of admixture plants containing dimethyltryptamine and harmine. For millennia it has been used as a central element of spiritual, religious, initiation, and other - foremost healing - rituals, originally by the indigenous groups of the Amazon basin and later by the mestizo populations of the region. During the last two decades the brew has raised increased scientific and lay interest about its healing potentials within the framework of Western therapeutic settings. The typical ayahuasca effects consist of strong somatic reactions, vivid visions, relived personal memories, cathartic emotions, and insightful, introspective experiences when the emerging mental contents take different context and get deeper perspectives. The ayahuasca-experience can be exhausting necessitating the presence of an experienced leader for helping participants to pass difficult phases and for maximizing therapeutic benefits. No health damaging adverse effect has been confirmed thus far as result of its well-structured, institutionalized use. The scientific investigation of ayahuasca is hindered by legal issues, methodical problems, and sociocultural preconceptions. The present review outlines the therapeutic potentials of ayahuasca use in psychiatry with its psychobiological and spiritual background.


Psychology. The nature of personality: genes, culture, and national character.
Personality traits have a strong genetic foundation, are highly stable over time, and predict important societal outcomes, including health and occupational success. In his Perspective, Robins discusses Terracciano et al.'s finding that cultures differ somewhat in aggregate personality levels but those differences are not accurately reflected in stereotypes about national character. Robins discusses reasons why national stereotypes are inaccurate, as well as broader issues concerning individual and cultural sources of variation in personality.


An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.
The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.


The Challenge of Treating Children With Hepatitis C Virus Infection.
The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. Recently, in April 2017, the association of sofosbuvir with ribavirin and the fixed-dose combination sofosbuvir/ledipasvir have been approved by the Food and Drug Administration for treatment of children with chronic HCV infection 12 years of age and older. The only drugs currently approved for children younger than 12 years are pegylated interferon and ribavirin. There are 6 registered ongoing pediatric trials assessing safety and efficacy of DAAs, but their current completion timelines are years away. Herein, we summarize the state of the art of DAAs' development for adult and children and highlight the crucial importance of overcoming barriers to treating children with HCV.


Copy number variability of expression plasmids determined by cell sorting and Droplet Digital PCR.
Plasmids are widely used for molecular cloning or production of proteins in laboratory and industrial settings. Constant modification has brought forth countless plasmid vectors whose characteristics in terms of average plasmid copy number (PCN) and stability are rarely known. The crucial factor determining the PCN is the replication system; most replication systems in use today belong to a small number of different classes and are available through repositories like the Standard European Vector Architecture (SEVA). In this study, the PCN was determined in a set of seven SEVA-based expression plasmids only differing in the replication system. The average PCN for all constructs was determined by Droplet Digital PCR and ranged between 2 and 40 per chromosome in the host organism Escherichia coli. Furthermore, a plasmid-encoded EGFP reporter protein served as a means to assess variability in reporter gene expression on the single cell level. Only cells with one type of plasmid (RSF1010 replication system) showed a high degree of heterogeneity with a clear bimodal distribution of EGFP intensity while the others showed a normal distribution. The heterogeneous RSF1010-carrying cell population and one normally distributed population (ColE1 replication system) were further analyzed by sorting cells of sub-populations selected according to EGFP intensity. For both plasmids, low and highly fluorescent sub-populations showed a remarkable difference in PCN, ranging from 9.2 to 123.4 for ColE1 and from 0.5 to 11.8 for RSF1010, respectively. The average PCN determined here for a set of standardized plasmids was generally at the lower end of previously reported ranges and not related to the degree of heterogeneity. Further characterization of a heterogeneous and a homogeneous population demonstrated considerable differences in the PCN of sub-populations. We therefore present direct molecular evidence that the average PCN does not represent the true number of plasmid molecules in individual cells.


TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate.
Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.


Hospital performance, the local economy, and the local workforce: findings from a US National Longitudinal Study.
Pay-for-performance is an increasingly popular approach to improving health care quality, and the US government will soon implement pay-for-performance in hospitals nationwide. Yet hospital capacity to perform (and improve performance) likely depends on local resources. In this study, we quantify the association between hospital performance and local economic and human resources, and describe possible implications of pay-for-performance for socioeconomic equity. We applied county-level measures of local economic and workforce resources to a national sample of US hospitals (n = 2,705), during the period 2004-2007. We analyzed performance for two common cardiac conditions (acute myocardial infarction [AMI] and heart failure [HF]), using process-of-care measures from the Hospital Quality Alliance [HQA], and isolated temporal trends and the contributions of individual resource dimensions on performance, using multivariable mixed models. Performance scores were translated into net scores for hospitals using the Performance Assessment Model, which has been suggested as a basis for reimbursement under Medicare's "Value-Based Purchasing" program. Our analyses showed that hospital performance is substantially associated with local economic and workforce resources. For example, for HF in 2004, hospitals located in counties with longstanding poverty had mean HQA composite scores of 73.0, compared with a mean of 84.1 for hospitals in counties without longstanding poverty (p<0.001). Hospitals located in counties in the lowest quartile with respect to college graduates in the workforce had mean HQA composite scores of 76.7, compared with a mean of 86.2 for hospitals in the highest quartile (p<0.001). Performance on AMI measures showed similar patterns. Performance improved generally over the study period. Nevertheless, by 2007--4 years after public reporting began--hospitals in locationally disadvantaged areas still lagged behind their locationally advantaged counterparts. This lag translated into substantially lower net scores under the Performance Assessment Model for hospital reimbursement. Hospital performance on clinical process measures is associated with the quantity and quality of local economic and human resources. Medicare's hospital pay-for-performance program may exacerbate inequalities across regions, if implemented as currently proposed. Policymakers in the US and beyond may need to take into consideration the balance between greater efficiency through pay-for-performance and socioeconomic equity.


Dynamical organization of the cytoskeletal cortex probed by micropipette aspiration.
Bleb-based cell motility proceeds by the successive inflation and retraction of large spherical membrane protrusions ("blebs") coupled with substrate adhesion. In addition to their role in motility, cellular blebs constitute a remarkable illustration of the dynamical interactions between the cytoskeletal cortex and the plasma membrane. Here we study the bleb-based motions of Entamoeba histolytica in the constrained geometry of a micropipette. We construct a generic theoretical model that combines the polymerization of an actin cortex underneath the plasma membrane with the myosin-generated contractile stress in the cortex and the stress-induced failure of membrane-cortex adhesion. One major parameter dictating the cell response to micropipette suction is the stationary cortex thickness, controlled by actin polymerization and depolymerization. The other relevant physical parameters can be combined into two characteristic cortex thicknesses for which the myosin stress (i) balances the suction pressure and (ii) provokes membrane-cortex unbinding. We propose a general phase diagram for cell motions inside a micropipette by comparing these three thicknesses. In particular, we theoretically predict and experimentally verify the existence of saltatory and oscillatory motions for a well-defined range of micropipette suction pressures.


First Report of Pepper chat fruit viroid in Traded Tomato Seed, an Interception by Australian Biosecurity.
Pepper chat fruit viroid (PCFVd), a species of Pospiviroid, was first discovered in a capsicum crop in the Netherlands in 2006 (4) and was then reported only in Thailand (2) and Canada. The mechanism of international spread was not known, but movement with traded seed was suspected. PCFVd is transmissible through capsicum seed (4) and very probably through tomato seed, like other pospiviroids. The viroid causes disease in capsicum and tomato and experiments by others indicate a capacity to cause disease in potato. It poses a biosecurity threat to crops internationally. PCFVd was intercepted by the Australian Government Department of Agriculture, Fisheries, and Forestry (DAFF) in five shipments of tomato seed (Solanum lycopersicum) exported from Israel and Thailand in September and October 2012. Batches of up to 20,000 seeds were sampled from each seed lot in a shipment and total nucleic acids were extracted from sub-samples, each of about 400 seeds, following a method similar to Hoshino et al. (1). PCFVd was initially detected when reverse transcription PCR using the generic pospiviroid primers Pospi1-FW and Pospi1-RE (3) produced amplicons of 189 bp, which were then sequenced. The PCFVd specific primers AP FW1 and AP RE2 (4) were used to amplify the remainder of the viroid genome, which was directly sequenced. Overlapping sequences were aligned to produce complete sequences of 349 bases, one from seed from Thailand and two from seed from Israel (GenBank: KC762952, KC762953, KC762954). Searches of the GenBank nucleotide non-redundant database indicated close matches with sequences from PCFVd isolates from tomato in Thailand (2); alignments generated by BLAST showed the sequences differed from those from Thailand at only 2 to 18 nucleotide positions, equating to 95 to 99% identity. PCFVd sequences from seed from Thailand were almost identical (>99%) to the sequences from seed from Israel. Many sub-samples were negative, indicating that the number of contaminated seeds was very small in some shipments. The positive sub-samples as a proportion of the total number of sub-samples tested from the five shipments was 1/1, 1/5, 1/1, 12/50, and 7/50. Tomato and capsicum seed are produced in many countries and often traded through second countries. The infected tomato seed shipments intercepted by DAFF were destroyed or re-exported following Australian regulations. Other countries were informed through the International Plant Protection Convention. This pest viroid has not been intercepted by Australian authorities before and has not been detected in recent Australian survey work (data not shown). References: (1) S. Hoshino et al. Res. Bull. Plant Prot. Japan 42:75, 2006. (2) K. Reanwarakorn et al. New Dis. Rep. 24:6, 2011 (3) J. Th. J. Verhoeven et al. EJPP 110:823, 2004. (4) J. Th. J. Verhoeven et al. Virus Res. 144:209, 2009.


22q11.2 Deletion: Surgical and Speech Outcomes of Patients With Velopharyngeal Insufficiency Treated With a Superiorly Based Pharyngeal Flap as the Primary Surgery.
The most frequent palate diagnoses in patients with chromosome 22q11.2 deletion syndrome are a classic submucous cleft, occult, and velopharyngeal insufficiency without cleft, which generates alterations in speech that require surgery. Surgical protocols are controversial owing to syndrome characteristics that make their handling more complex. Pharyngeal flap pharyngoplasty is effective for this type of patient. The objective of this study is to examine the surgical management of velopharyngeal insufficiency in patients with chromosome 22 deletion, using a pharyngeal flap as the primary surgery. The clinical records of patients with chromosome 22 deletion and velopharyngeal insufficiency between 2015 and 2017 were analyzed retrospectively. Eight patients underwent pharyngeal flap pharyngoplasty as a primary surgery, including 1 with velopharyngeal insufficiency without a cleft, 1 with a classic submucous cleft, and 6 with occult submucous cleft. The pre- and postoperative protocol performed by speech therapists and surgeons included clinical evaluation of the oral cavity; perceptual, video recording, and nasometry speech evaluation; and videonasopharyngoscopy. All perceptual parameters and nasometry results significantly changed. Of the cases, 88% achieved a flap with the expected width and height and complete closure of the velopharyngeal sphincter. One patient required flap revision. Four of the 8 patients achieved normal resonance, and 2 of 8 showed mild hypernasality. Using the pharyngeal flap pharyngoplasty as a primary technique to correct velopharyngeal insufficiency in patients with chromosome 22 deletion provides satisfactory outcomes and decreases the number of surgeries. Preoperative planning must be conducted carefully and needs to be individualized to be successful.


Benefits of treatment with implantable cardioverter-defibrillators in patients with stable ventricular tachycardia without cardiac arrest.
The availability of implantable cardioverter-defibrillators (ICD) that are capable of antitachycardia pacing may lead to an increased use of ICDs in patients with haemodynamically tolerated ventricular tachycardia without a history of cardiac arrest. The frequency of potentially life-threatening fast ventricular tachycardias (cycle length < 250 ms) was investigated in patients who had a third generation ICD with endocardial leads implanted because they had haemodynamically tolerated ventricular tachycardia without a history of cardiac arrest. Between January 1990 and October 1993, 50 patients (age (mean (SD)) 60 (11); ejection fraction 39 (16)%; 82% with coronary artery disease and 8% with dilated cardiomyopathy) with haemodynamically tolerated ventricular tachycardia (cycle length (mean (SD)) 348 (60) ms; range 250-500 ms) and without a history of cardiac arrest were treated with third generation ICDs that were capable of antitachycardia pacing. Fast ventricular tachycardia had been induced in 14 (28%) during baseline electrophysiological study. The benefit of ICD treatment was estimated as the difference between total mortality and the occurrence of fast ventricular tachycardia that would have been fatal if it had not been terminated. During follow up of 17 (12) months, 33 patients (66%) had a total of 3861 episodes of ventricular tachycardia. 91% of these episodes were terminated by antitachycardia pacing. 11 patients (22%) had episodes of potentially life-threatening fast ventricular tachycardia and 3 of these also had inducible fast ventricular tachycardia. One patient died suddenly 27 months after implantation. The difference between survival without fast ventricular tachycardia and total mortality was 9%, 12%, 27%, and 27% at 6, 12, 18, and 24 months, respectively. About a fifth of patients who had been given an ICD to treat haemodynamically tolerated ventricular tachycardia and who had no history of cardiac arrest experienced fast ventricular tachycardia during follow up requiring immediate cardioversion. Prospective studies are needed to investigate whether the prognosis of patients with a history of haemodynamically tolerated ventricular tachycardia without cardiac arrest is improved by ICD therapy.


Effect of beta-alanyl-L-histidinato zinc on differentiation of osteoblastic MC3T3-E1 cells: increases in alkaline phosphatase activity and protein concentration.
The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone cell function was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus AHZ (10(-7)-10(-5) M) or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) produced a remarkable increase of alkaline phosphatase activity and protein concentration in osteoblastic cells. Thus increase were seen with the prolonged cultivation (12-21 days). With the culture of 1, 3 and 12 days, the effect of AHZ (10(-6) M) to increase alkaline phosphatase activity and protein concentration was more intensive than the effect of zinc sulfate (10(-6) M). The AHZ effects were completely abolished by the presence of cycloheximide (10(-6) M), indicating that AHZ stimulates protein synthesis in the cells. The present study suggests that AHZ has a stimulatory effect on cell differentiation, and that this effect is partly involved on protein synthesis in osteoblastic cells.


Grip strength across the life course: normative data from twelve British studies.
Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol. We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing). Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males' peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position. This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.


Temporally constrained ICA: an application to artifact rejection in electromagnetic brain signal analysis.
Independent component analysis (ICA) is a technique which extracts statistically independent components from a set of measured signals. The technique enjoys numerous applications in biomedical signal analysis in the literature, especially in the analysis of electromagnetic (EM) brain signals. Standard implementations of ICA are restrictive mainly due to the square mixing assumption-for signal recordings which have large numbers of channels, the large number of resulting extracted sources makes the subsequent analysis laborious and highly subjective. There are many instances in neurophysiological analysis where there is strong a priori information about the signals being sought; temporally constrained ICA (cICA) can extract signals that are statistically independent, yet which are constrained to be similar to some reference signal which can incorporate such a priori information. We demonstrate this method on a synthetic dataset and on a number of artifactual waveforms identified in multichannel recordings of EEG and MEG. cICA repeatedly converges to the desired component within a few iterations and subjective analysis shows the waveforms to be of the expected morphologies and with realistic spatial distributions. This paper shows that cICA can be applied with great success to EM brain signal analysis, with an initial application in automating artifact extraction in EEG and MEG.


High-frequency nanofluidics: a universal formulation of the fluid dynamics of MEMS and NEMS.
A solid body undergoing oscillatory motion in a fluid generates an oscillating flow. Oscillating flows in Newtonian fluids were first treated by G.G. Stokes in 1851. Since then, this problem has attracted much attention, mostly due to its technological significance. Recent advances in micro- and nanotechnology require that this problem be revisited: miniaturized mechanical resonators with linear dimensions in microns and sub-microns-microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS), respectively-give rise to oscillating flows when operated in fluids. Yet flow parameters for these devices, such as the characteristic flow time and length scales, may deviate greatly from those in Stokes' solution. As a result, new and interesting physics emerges with important consequences to device applications. In this review, we shall provide an introduction to this area of fluid dynamics, called high-frequency nanofluidics, with emphasis on both theory and experiments.


Subdivision of Light Signaling Networks Contributes to Partitioning of C4 Photosynthesis.
Plants coordinate the expression of photosynthesis-related genes in response to growth and environmental changes. In species that conduct two-cell C4 photosynthesis, expression of photosynthesis genes is partitioned such that leaf mesophyll and bundle sheath cells accumulate different components of the photosynthetic pathway. The identities of the regulatory networks that facilitate this partitioning are unknown. Here, we show that differences in light perception between mesophyll and bundle sheath cells facilitate differential regulation and accumulation of photosynthesis gene transcripts in the C4 crop maize (Zea mays). Key components of the photosynthesis gene regulatory network differentially accumulated between mesophyll and bundle sheath cells, indicative of differential network activity across cell types. We further show that blue (but not red) light is necessary and sufficient to activate photosystem II assembly in mesophyll cells in etiolated maize. Finally, we demonstrate that 61% of all light-induced mesophyll and bundle sheath genes were induced only by blue light or only by red light, but not both. These findings provide evidence that subdivision of light signaling networks is a component of cellular partitioning of C4 photosynthesis in maize.


Social determinants of health among people working on informal gold mines in French Guiana: a multicentre cross-sectional survey.
Social determinants of health, such as living and working conditions, economical and environmental context and access to care, combine to impact the health of individuals and communities. In French Guiana (FG), the persons working in informal artisanal and small-scale gold mining in the rainforest are a particularly vulnerable population which lives in precarious conditions and far from the health system. Previous studies have demonstrated their high morbidity due to infectious diseases. This study aims to describe the social determinants of health in this specific population. This international multicentre cross-sectional survey included people working on the informal FG gold mines at the crossing points located at both borders with Suriname and Brazil. After collecting written informed consent, a structured questionnaire was administered. From September to December 2022, 539 gold miners were included. These poorly educated migrants, mainly from Brazil (99.1%) did not have access to drinkable water (95.4%), lived in close contact with wild fauna by hunting, eating bushmeat or being bitten and were exposed to mercury by inhalation (58.8%) or ingestion (80.5%). They report frequent accidents (13.5%) and chronic treatment interruptions (26.6% of the 11.9% reporting chronic treatment). Half of them considered themselves in good health (56.4%). This study shows a singular combination of adverse exposures of gold miners working in FG such as zoonoses, heavy metal poisoning, aggression of wild fauna. For ethical as well as public health reasons, actions towards health equity must be considered at different levels: individual, community, environmental, systemic and global level. As end users of minerals, we must assume our responsibilities for the well-being of the extractors by including health in political decisions to engage together in global health. NCT05540470.


Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children.
Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.


Catch Me if You Can: Streptococcus pyogenes Complement Evasion Strategies.
The human host has evolved elaborate protection mechanisms to prevent infection from the billions of microorganisms to which it host is exposed and is home. One of these systems, complement, is an evolutionary ancient arm of innate immunity essential for combatting bacterial infection. Complement permits the efficient labelling of bacteria with opsonins, supports phagocytosis, and facilitates phagocyte recruitment to the site of infection through the production of chemoattractants. However, it is by no means perfect, and certain organisms engage in an evolutionary arms race with the host where complement has become a major target to promote immune evasion. Streptococcus pyogenes is a major human pathogen that causes significant morbidity and mortality globally. S. pyogenes is also a member of an elite group of bacterial pathogens possessing a sophisticated arsenal of virulence determinants capable of interfering with complement. In this review, we focus on these complement evasins, their mechanism of action, and their importance in disease progression. Finally, we highlight new therapeutic options for fighting S. pyogenes, by interfering with one of its main mechanisms of complement evasion.


Methadone Therapy in Underserved Urban Community: QTc Prolongation and Life-Threatening Ventricular Arrhythmias.
Methadone has been associated with QTc prolongation and ventricular arrhythmias but the prevalence of QTc prolongation and association with ventricular arrhythmias remains unclear. We investigated this in our inner city urban community (Bronx, New York) that has a large number of patients on methadone. Telemetry records, nursing documentation and electronic charts of 291 patients spanning856 encounters were evaluated. QT was manually measured from ECG utilizing standardized QT measurement guidelines and was corrected for heart rate using Hodges formula. QTc >470 ms in males and >480 ms in females was considered to be prolonged. Patients had prolonged QTc, QTc >500 ms and ventricular arrhythmias during 25.6%, 14.1% and 3.4% of encounters, respectively. There was a very weak dose dependent relationship between methadone dose and QTc (Spearman's rho = 0.09).In addition to methadone, patients were on at least one QT prolonging drugs during 39% of the encounters. Patients who were receiving two interacting drugs in addition to methadone had the highest prevalence (29%) of QTc prolongation. Although the prevalence of QTc prolongation among patients on methadone therapy is high, the prevalence of ventricular arrhythmia is relatively low. Hospitalized patients on sustained methadone therapy are frequently on multiple additional QTc prolonging drugs. There is no significant dose dependent relationship between methadone dose and QTc. However, the concurrent use of methadone and interacting drugs lead to an increased prevalence of QTc prolongation.


Clonal identity and differences in primary cutaneous B-cell lymphoma occurring at different sites or time points in the same patient.
Primary cutaneous B-cell lymphomas (PCBCL) are rare. Marginal zone lymphomas and follicle center lymphomas (FCL) represent a majority of these cases, and a significant number of cases present with multiple lesions. It is unclear whether multiple lesions in PCBCL represent dissemination of a single clone or multiple new primary lymphomas. In the current study, we analyzed paired samples from 20 PCBCL patients at more than 1 site (16) or at the same site at different time points (4) and 12 patients with benign lymphoid infiltrates to investigate for the presence or absence of a clone, and if present, whether the clones were identical. Both IGH@ and IGK@ rearrangements were tested using the BIOMED-2 protocol. We identified a clone (IGH@ and/or IGK@) in 19 of 20 (95%) PCBCL patients and 2 of 12 (17%) benign lymphoid infiltrate patients. The B-cell clones were proven to be identical in 11 of 20 (55%) PCBCL patients, including 7 of 16(44%) biopsies from patients with 2 different sites and 4 of 4 biopsies (100%) from patients at the same site but different time points. In 4 cases (3 FCL and 1 marginal zone lymphoma), different clones were detected at different sites, suggesting the possibility of a second simultaneous primary lymphoma. Our results indicate that the presence of identical clones is highly suggestive of lymphoma. To our knowledge, this is the first report to investigate the detection of identical clones in 2 distinct biopsies in PCBCL patients. Although the study is small and the results need to be confirmed in a larger study, these findings suggest that a subset of PCBCL at different sites may represent different primary tumors rather than occurrence of a single disease.


Insurance Accounts: The Cultural Logics of Health Care Financing.
The financial exuberance that eventually culminated in the recent world economic crisis also ushered in dramatic shifts in how health care is financed, administered, and imagined. Drawing on research conducted in the mid-2000s at a health insurance company in Puerto Rico, this article shows how health care has been financialized in many ways that include: (1) privatizing public services; (2) engineering new insurance products like high deductible plans and health savings accounts; (3) applying financial techniques to premium payments to yield maximum profitability; (4) a managerial focus on shareholder value; and (5) prioritizing mergers and financial speculation. The article argues that financial techniques obfuscate how much health care costs, foster widespread gaming of reimbursement systems that drives up prices, and "unpool" risk by devolving financial and moral responsibility for health care onto individual consumers.


Morbidity and mortality in the surgical treatment of 10,329 adults with degenerative lumbar stenosis.
The purpose of this study was to evaluate the prospectively collected Scoliosis Research Society (SRS) database to assess the incidences of morbidity and mortality (M&M) in the operative treatment of degenerative lumbar stenosis, one of the most common procedures performed by spine surgeons. All patients who underwent surgical treatment for degenerative lumbar stenosis between 2004 and 2007 were identified from the SRS M&M database. Inclusion criteria for analysis included an age >or= 21 years and no history of lumbar surgery. Patients were treated with either decompression alone or decompression with concomitant fusion. Statistical comparisons were performed using a 2-sided Fisher exact test. Of the 10,329 patients who met the inclusion criteria, 6609 (64%) were treated with decompression alone, and 3720 (36%) were treated with decompression and fusion. Among those who underwent fusion, instrumentation was placed in 3377 (91%). The overall mean patient age was 63 +/- 13 years (range 21-96 years). Seven hundred nineteen complications (7.0%), including 13 deaths (0.1%), were identified. New neurological deficits were reported in 0.6% of patients. Deaths were related to cardiac (4 cases), respiratory (5 cases), pulmonary embolus (2 cases), and sepsis (1 case) etiologies, and a perforated gastric ulcer (1 case). Complication rates did not differ based on patient age or whether fusion was performed. Minimally invasive procedures were associated with fewer complications and fewer new neurological deficits (p = 0.01 and 0.03, respectively). The results from this analysis of the SRS M&M database provide surgeons with useful information for preoperative counseling of patients contemplating surgical intervention for symptomatic degenerative lumbar stenosis.


Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing.
Long QT syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for 3 cardiac ion channel α-subunits (LQT1 to LQT3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements. We set out to determine the prevalence and spectrum of large deletions/duplications in the major LQTS-susceptibility genes in unrelated patients who were mutation negative after point mutation analysis of LQT1- to LQT12-susceptibility genes. Forty-two unrelated, clinically strong LQTS patients were analyzed using multiplex ligation-dependent probe amplification, a quantitative fluorescent technique for detecting multiple exon deletions and duplications. The SALSA multiplex ligation-dependent probe amplification LQTS kit from MRC-Holland was used to analyze the 3 major LQTS-associated genes, KCNQ1, KCNH2, and SCN5A, and the 2 minor genes, KCNE1 and KCNE2. Overall, 2 gene rearrangements were found in 2 of 42 unrelated patients (4.8%, confidence interval 1.7 to 11). A deletion of KCNQ1 exon 3 was identified in a 10-year-old Caucasian boy with a corrected QT duration of 660 ms, a personal history of exercise-induced syncope, and a family history of syncope. A deletion of KCNQ1 exon 7 was identified in a 17-year-old Caucasian girl with a corrected QT duration of 480 ms, a personal history of exercise-induced syncope, and a family history of sudden cardiac death. In conclusion, because nearly 5% of patients with genetically elusive LQTS had large genomic rearrangements involving the canonical LQTS-susceptibility genes, reflex genetic testing to investigate genomic rearrangements may be of clinical value.


What is the cost of maintaining a kidney in upper-tract transitional-cell carcinoma? An objective analysis of cost and survival.
For many years, the gold standard in upper urinary tract transitional-cell carcinoma (UT-TCC) management has been nephroureterectomy with excision of the bladder cuff. Advances in endourologic instrumentation have allowed urologists to manage this malignancy. The feasibility and success of conservative measures for UT-TCC have been widely published, but there has not been an objective cost analysis performed to date. Our goal was to examine the direct costs of renal-sparing conservative measures v nephroureterectomy and subsequent chronic kidney disease (CKD) or end-stage renal disease (ESRD). Secondary analysis includes a discussion of survival and quality-of-life issues for both treatment cohorts. Retrospective review of a cohort of patients treated at our institution with renal-sparing ureteroscopic management of UT-TCC who were followed for a minimum of 2 years. The costs per case were based on equipment, anesthesia, surgeon fees, pathologic evaluation fees, and hospital stay. ESRD and CKD costs were estimated based on published reports. From 1996 to 2006, 254 patients were evaluated and treated for UT-TCC at our institution. A cohort of 57 patients was examined who had a minimum follow-up period of 2 years. Renal preservation in our series approached 81%, with cancer-specific survival of 94.7%. Assuming a worst-case scenario of a solitary kidney with recurrences at each follow-up for 5 years v nephroureterectomy and dialysis for the same period, an estimated $252,272 U.S. dollars would be saved. This savings would cover the expenses of five cadaveric renal transplantations. Conservative endoscopic management of UT-TCC in our experience should be the gold standard management for low-grade and superficial-stage disease. From a cost perspective, renal-sparing UT-TCC management is effective in reducing ESRD health care expenses.


An investigation of Turkish honeys: their physico-chemical properties, antioxidant capacities and phenolic profiles.
This study investigated some physico-chemical and biochemical characteristics of different honey types belonging to Turkish flora. Sixty-two honey samples were examined on the basis of pollen analyses, including 11 unifloral honeys (chestnut, heather, chaste tree, rhododendron, common eryngo, lavender, Jerusalem tea, astragalus, clover and acacia), two different honeydew honeys (lime and oak), and 7 different multifloral honeys. Electrical conductivity, moisture, Hunter color values, HMF, proline, diastase number, and sugar analyses of the honey samples were assessed for chemical characterization. Some phenolic components were analyzed by reverse phase high performance liquid chromatography (RP-HPLC) to determine honeys' phenolic profiles. Total phenolic compounds, total flavonoids, ferric reducing antioxidant capacity (FRAP) and 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging activity were measured as antioxidant determinants. The study results confirm that physico-chemical and biological characteristics of honeys are closely related to their floral sources, and that dark-colored honeys such as oak, chestnut and heather, have a high therapeutic potential.


Beyond proliferation--cell cycle control of neuronal survival and differentiation in the developing mammalian brain.
Cell cycle proteins are critical regulators of proliferation in dividing cells. Paradoxically, accumulating evidence supports the view that core components of the cell cycle also play key roles in the development of terminally differentiated postmitotic neurons. Distinct cell cycle proteins including cell cycle-dependent kinases may contribute to naturally occurring programmed neuronal cell death in the developing mammalian brain. In addition, recent studies have uncovered a novel role for the cell cycle-associated ubiquitination machinery in the control of axonal growth and patterning in the developing brain. The underlying molecular mechanisms regulating these distinct cell cycle-based developmental events in neurons are just beginning to be understood.


Comparison of the properties of glass, glass-ceramic and ceramic materials produced from coal fly ash.
Glass, glass-ceramic and ceramic materials were produced from thermal power plant fly ash without any additives. X-ray diffraction (XRD) analysis revealed the amorphous phase of the glass sample. Augite phase was detected in the glass-ceramic sample, while the enstatite and mullite phases occurred in the ceramic samples. Scanning electron microscopy (SEM) investigations showed that tiny crystallites homogeneously dispersed in the microstructure of the glass-ceramic sample and elongated crystals formed in the ceramic samples. Density values of the obtained samples are comparable to those of the commercially produced glass, glass-ceramic and ceramic samples. Toxicity characteristic leaching procedure (TCLP) results indicated that the produced samples could be taken as non-hazardous materials. Produced samples showed high resistance to alkali solutions in contrast to acidic solutions. Microstructural, physical, chemical and mechanical properties of the produced glass-ceramic samples are better than those of the produced glass and ceramic samples.


Nonadiabatic dynamics of floppy hydrogen bonded complexes: the case of the ionized ammonia dimer.
In the case of the ammonia dimer, we address the following questions: how ultrafast ionization dynamics is controlled by hydrogen bonding and whether we can control the products via selective ionization of a specific electron. We use quantum chemical calculations and ab initio non-adiabatic molecular dynamics simulations to model the femtosecond dynamics of the ammonia dimer upon ionization. The role of nuclear quantum effects and thermal fluctuations in predicting the structure of the dimer is emphasized; it is shown that the minimum energy and vibrationally averaged structures are rather different. The ground state structure subsequently controls the ionization dynamics. We describe reaction pathways, electronic population transfers and reaction yields with respect to ionization from different molecular orbitals. The simulations showed that the ionized ammonia dimer is highly unstable and its decay rate is primarily driven by the position of the electron hole. In the case of ground state ionization (i.e. the HOMO electron is ionized), the decay is likely to be preceded by a proton transfer (PT) channel yielding NH4(+) and NH2˙ fragments. The PT is less intense and slower compared with the ionized water dimer. After ionizing deeper lying electrons, mainly NH3(+)˙ and NH3 fragments are formed. Overall, our results show that the ionization dynamics of the ammonia and water dimers differ due to the nature of the hydrogen bond in these systems.