Immune therapy in inflammatory bowel disease and models of colitis.
A proliferation of animal models has not only improved our understanding of inflammatory bowel disease, it has also formed the basis of new treatment strategies. A search was conducted using the National Library of Medicine for articles discussing immune therapies for inflammatory bowel disease. This was supplemented by findings from the authors' own laboratory. An overview of the different animal models is presented. These models are used to highlight the recent human trials of immune therapies. Potential future therapies are also discussed. Immune therapies have altered the management of patients with inflammatory bowel disease. In future they will influence not only the indications for surgery but also its timing and outcome.


Exposure to atheroma-relevant 7-oxysterols causes proteomic alterations in cell death, cellular longevity, and lipid metabolism in THP-1 macrophages.
The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome. Human THP-1 macrophages were exposed to an atheroma-relevant mixture of 7β-hydroxycholesterol and 7-ketocholesterol. Two-dimensional gel electrophoresis and mass spectrometry techniques were used to analyse the alterations in macrophage proteome, which resulted in the identification of 19 proteins with significant differential expression upon oxysterol loading; 8 increased and 11 decreased. The expression patterns of 11 out of 19 identified significant proteins were further confirmed by tandem-mass spectrometry, including further validation of increased histone deacetylase 2 and macrophage scavenger receptor types I and II expressions by western blot analysis. Identified proteins with differential expression in the cell model have been associated with i) signalling imbalance in cell death and cellular longevity; ii) lipid uptake and metabolism in foam cells; and iii) inflammatory proteins. The presented findings highlight a new proteomic platform for further studies into the functional roles of macrophages in atherosclerosis, and present a cell model for future studies to modulate the macrophage proteome by potential anti-atherosclerotic agents.


The immunoglobulin heavy chain gene 3' enhancers induce Bcl2 deregulation and lymphomagenesis in murine B cells.
Human follicular B-cell lymphoma is associated with the t(14;18) chromosomal translocation that juxtaposes the Bcl2 proto-oncogene with the immunoglobulin heavy chain (Igh) locus, resulting in the deregulated expression of Bcl2. Our previous studies have shown that the Igh 3' enhancers deregulate the Bcl2 expression in vitro. However, the effects of the Igh 3' enhancer elements on Bcl2 expression in vivo are not known. To investigate the role of the Igh 3' enhancers in Bcl2 deregulation, we used gene targeting to generate knock-in mice in which four DNase I-hypersensitive regions from the murine Igh 3' region were integrated 3' of the Bcl2 locus. Increased levels of Bcl2 mRNA and protein were observed in the B cells of Igh-3'E-bcl2 mice. B cells from Igh-3'E-bcl2 mice showed an extended survival in vitro compared with B cells from wild-type (Wt) mice. The Bcl2 promoter shift from P1 (the 5' promoter) to P2 (the 3' promoter) was observed in B cells from Igh-3'E-bcl2 mice, similar to human t(14;18) lymphomas. The IgH-3'E-bcl2 mice developed monoclonal B-cell follicular lymphomas, which were slowly progressive. These studies show that the Igh 3' enhancers have an important role in the deregulation of Bcl2 and B-cell lymphomagenesis in vivo.


Ex vivo characterization of human thymic dendritic cell subsets.
Interactions between thymic dendritic cells (DC) and thymocytes are critical for proper development of T-cells. We identified human thymic DC populations on the basis of CD123, CD11c and CD14 expression. High levels of CD123 (IL-3R) and CD45RA defined the plasmacytoid DC (pDC) subset. Human thymic CD11c(+) DC expressed CD45RO and myeloid-related markers (CD13, CD33 and CD11b). CD11c(+) DC could be separated into two main subsets based on differential expression of CD14: CD11c(+) CD14(-) and CD11c(+) CD14(+) cells. Spontaneous production of IL-10 and IFNgamma without exogenous stimulation, was observed in the three DC subsets. Important phenotype modifications were observed in pDC cultures supplemented with IL-3. A down-regulation of CD123 and appearance of myeloid markers such as CD11b and CD11c on CD45RA(+) cells was noticed within the first 48h; at a later time there was a shift from CD45RA to CD45RO expression, as well as appearance of CD14 expression. CD11c(+) cells emerging in pDC culture did not express high levels of HLA-DR, CD83 and co-stimulatory molecules. This suggests an in vitro evolution of human thymic pDC toward a myeloid phenotype found in the CD11c(+) subset of thymic DC.


Enhanced Mixing of Microvascular Self-Healing Reagents Using Segmented Gas-Liquid Flow.
Microvascular self-healing systems have previously been demonstrated to restore large-scale damage and achieve repeated healing of multiple damage events in polymers. However, the healing performance of these systems is often limited because the laminar nature of flow in microchannels results in poor mixing of two-part self-healing reagents. In this paper, we introduce segmented gas-liquid flow (SGLF) to enhance the mixing of reagents in microvascular self-healing systems. In SGLF, discrete liquid slugs containing self-healing reagents are separated by gas bubbles while flowing through a single microchannel. Recirculating streamlines within the liquid slugs can enhance the mixing of miscible liquids such as healing reagents. We investigate the effect of SGLF on mixing and healing for a two-stage chemistry used to restore large-scale damage in thermoset polymers. Additionally, we employ SGLF to deliver an epoxy-thiol chemistry, enabling the repeated recovery of fracture toughness in glass fiber-reinforced composites. In both systems, the mixing of healing agents delivered by SGLF is enhanced compared to alternative microvascular delivery strategies. For the two-stage chemistry, SGLF increases the maximum damage size that can be healed by 25% compared to laminar single-phase flow. Furthermore, there are concomitant increases in the extent of polymerization and the mechanical properties of the restored material, including a fivefold increase in the peak load sustained during a push-out test. For the epoxy-thiol chemistry, SGLF enables multiple healing cycles with healing efficiency above 100%. On the basis of these results, we envision that SGLF could improve performance for a variety of microvascular self-healing systems with different host materials, damage modes, and healing chemistries.


Economic evaluation of screening for open-angle glaucoma.
The aim of this study was to assess the cost-effectiveness of screening for open-angle glaucoma (OAG) in the United Kingdom, given that OAG is an important cause of blindness worldwide. A Markov model was developed to estimate lifetime costs and benefits of a cohort of patients facing, alternatively, screening or current opportunistic case finding strategies. Strategies, varying in how screening would be organized (e.g., invitation for assessment by a glaucoma-trained optometrist [GO] or for simple test assessment by a technician) were developed, and allowed for the progression of OAG and treatment effects. Data inputs were obtained from systematic reviews. Deterministic and probabilistic sensitivity analyses were performed. Screening was more likely to be cost-effective as prevalence increased, for 40 year olds compared with 60 or 75 year olds, when the re-screening interval was greater (10 years), and for the technician strategy compared with the GO strategy. For each age cohort and at prevalence levels of < or =1 percent, the likelihood that either screening strategy would be more cost-effective than current practice was small. For those 40 years of age, "technician screening" compared with current practice has an incremental cost-effectiveness ratio (ICER) that society might be willing to pay when prevalence is 6 percent to 10 percent and at over 10 percent for 60 year olds. In the United Kingdom, the age specific prevalence of OAG is much lower. Screening by GO, at any age or prevalence level, was not associated with an ICER < pound 30,000. Population screening for OAG is unlikely to be cost-effective but could be for specific subgroups at higher risk.


Rhythmic training, literacy, and graphomotor skills in kindergarteners.
The aim of this manuscript is twofold: first, to investigate the relationship between rhythmic, phonological and graphomotor skills in kindergarten children; and second, to evaluate the possible impact of rhythmic training on the two other skills. To that end, we selected a sample of 78 children in Québec. Forty-two children received rhythmic training (experimental group) and 34 arts training (active control group) during the same period (10 weeks). Before and after training, children in both groups were assessed for general skills (forward and backward memory span, vocabulary, non-verbal ability), rhythmic skills (synchronization and discrimination tasks), literacy skills (phonological skills - syllable counting, syllable deletion, rhyme discrimination - and invented spelling skills) and graphomotor skills (legibility of letter writing, quality of copying of geometric shapes). Results showed correlations between the child's rhythmic and literacy skills, as well as between rhythm synchronization and pen pressure. In addition, rhythmic training showed improvement in rhythmic abilities, but this did not transfer to literacy or graphomotor development (apart from a significant increase in the duration of pauses in both groups at post-test, with a larger improvement for the rhythm group). These results are discussed in terms of duration and intensity of learning, and they highlight the possible benefits of informal rhythm practices in the classroom.


Affective and Cognitive Conditions are Stronger Predictors of Success with Community Reintegration than Gait and Balance Performance in Veterans with Mild Traumatic Brain Injury.
Optimal community reintegration is an integral part of the clinical management of patients with mild traumatic brain injury. We sought the contribution and inter-relation of such variables as balance, executive function, and affective regulation to the community reintegration of veterans with mTBI. We examined the statistical relationship among the above variables by conducting a series of objective evaluations to assess the balance, gait, executive function, affective regulation, and scores representing the patients' issues with community reintegration. The data were statistically analyzed for correlation and regression. High correlation was found among scores for balance and gait, executive function and affective regulation. The first and second best predictors of success with patient's community reintegration were data representing affective regulation and cognitive impairments, respectively. However, the data for dynamic balance correlated weakly and insignificantly with scores for the three subsets of community reintegration. We revealed varying degrees of correlation among balance, executive function and affective regulation, and as they related to the community reintegration success of patients with mTBI. The strongest, intermediate and weakest predictors for these patients' success with community reintegration represented those for affective regulation, executive function, and dynamic balance and gait performance, respectively.


The effect of podophyllotoxin on microtubule dynamics.
We have investigated the effects of podophyllotoxin on the dynamic properties of microtubules assembled from pure tubulin dimer. Excess podophyllotoxin causes the complete disassembly of microtubules, through formation of a tubulin-GTP-podophyllotoxin ternary complex with a dissociation rate constant of 160 s-1 at 37 degrees C, similar to that found upon extensive isothermal dilution in this buffer system. Addition of substoichiometric concentrations of podophyllotoxin causes partial disassembly of microtubules through production of an equivalent amount of the ternary complex. Microtubule length measurements and incorporation of [3H]GTP-tubulin dimer show that podophyllotoxin can suppress the dynamic instability of tubulin dimer microtubules and that it acts substoichiometrically in so doing. We interpret the action of substoichiometric podophyllotoxin on microtubule ends in terms of effects on interconversion of growing and shrinking microtubules in a dynamic system in which tubulin-GTP-podophyllotoxin is kinetically analogous to tubulin-GTP in addition and to tubulin-GDP in dissociation. The ability to suppress dynamic instability may be one way in which drugs such as podophyllotoxin, acting at relatively low concentrations, are able to arrest cell growth and development in a selective way, without necessarily affecting the integrity of the major part of the cytoskeletal microtubule network.


Three spiroplasmas isolated from Haematopota sp. (Diptera:Tabanidae) in France.
On August 1991, three spiroplasmas (Tab 2A, Tab 2B and Tab 4C) were isolated from Haematopota sp. flies collected from Indre-et-Loire, France. Isolations were made at 28 degrees C in MD1 medium from ground individual flies, but not from external washings. All isolates adapted well to SP4 medium at 30 and 37 degrees C and were triple cloned before serological identification. Using the cross deformation test, the 3 isolates were compared with 42 known spiroplasmas isolated from diseased plants, flowers, various insects and ticks belonging to 25 serological groups. Each isolate cross-reacted with others and exhibited weak 1-way reactions with TABS-2 or PLHS-1, two spiroplasmas isolated in the United States from respectively Tabanus abactor Philip and Panorpa helena L, a scorpion-fly. These results suggest that Tab 2A, Tab 2B and Tab 4C together with TABS-2 and PLHS-1 may represent, members of a new serological supergroup.


Where babies come from: supply and demand in an infant marketplace.
Persistent demand from people who have been denied the blessings of parenthood has created an assisted-reproduction market that stretches around the globe and encompasses hundreds of thousands of people. In the United States alone, nearly 41,000 children were born via in vitro fertilization (IVF) in 2001. Roughly 6,000 came from donated eggs, and almost 600 were carried by surrogate mothers. U.S. legislators have been reluctant to regulate this market. As a result, there are no national policies for IVF, which requires creating--and often discarding--embryos, or for many other technologies. State laws vary widely, and many states have no legislation on these subjects whatsoever. Although fertility specialists generally seem delighted to practice in an unregulated gray area, a modicum of regulation and the establishment of agreed-upon norms could lead to substantially lower prices, wider access, and an expansion of the market to the millions who have not yet sought out assisted reproduction. Among those millions are fertile individuals seeking to ensure that they'll be able to produce offspring in the future. For example, the technology already permits young women to freeze their eggs, thus preserving their fertility (in case, for instance, they marry late in life). The fertility trade is in some ways analogous to the markets for personal computers and DVD players, which were initially considered luxury items but migrated to the mass market, earning manufacturers the revenues to finance further innovation. A widening of availability and the introduction of property rights, rules, and institutional policies would make the marketplace more sensitive to the social, medical, and ethical issues that are emerging from the science. For example: Should there be age limits on infertility treatment? Should new procedures be subject to rigorous testing? It is time for U.S. society to begin discussion of these complex questions.


Comparative study of behavioural tests in the SOD1G93A mouse model of amyotrophic lateral sclerosis.
In preclinical trials, a sensitive functional test is required to detect changes in the motor behaviour of the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). We evaluated changes in body weight and motor impairment in behavioural tests, such as the rotarod, the hanging-wire test and the treadmill, of transgenic and wild type mice. We found differences in detection of the onset of symptoms and progression of the disease between the different tests assessed. Moreover, the data showed significant gender differences in the motor behaviour of this mouse model. The rotarod and the hanging-wire test were more sensitive to detect early motor impairment. Moreover, the results suggested that the rotarod and hanging-wire became the most accurate tests rather than treadmill to characterise the ALS disease phenotype.


PCA-based spatially adaptive denoising of CFA images for single-sensor digital cameras.
Single-sensor digital color cameras use a process called color demosiacking to produce full color images from the data captured by a color filter array (CAF). The quality of demosiacked images is degraded due to the sensor noise introduced during the image acquisition process. The conventional solution to combating CFA sensor noise is demosiacking first, followed by a separate denoising processing. This strategy will generate many noise-caused color artifacts in the demosiacking process, which are hard to remove in the denoising process. Few denoising schemes that work directly on the CFA images have been presented because of the difficulties arisen from the red, green and blue interlaced mosaic pattern, yet a well-designed "denoising first and demosiacking later" scheme can have advantages such as less noise-caused color artifacts and cost-effective implementation. This paper presents a principle component analysis (PCA)-based spatially-adaptive denoising algorithm, which works directly on the CFA data using a supporting window to analyze the local image statistics. By exploiting the spatial and spectral correlations existing in the CFA image, the proposed method can effectively suppress noise while preserving color edges and details. Experiments using both simulated and real CFA images indicate that the proposed scheme outperforms many existing approaches, including those sophisticated demosiacking and denoising schemes, in terms of both objective measurement and visual evaluation.


Light trapping in periodically textured amorphous silicon thin film solar cells using realistic interface morphologies.
The influence of realistic interface morphologies on light trapping in amorphous silicon thin-film solar cells with periodic surface textures is studied. Realistic interface morphologies are obtained by a 3D surface coverage algorithm using the substrate morphology and layer thicknesses as input parameters. Finite difference time domain optical simulations are used to determine the absorption in the individual layers of the thin-film solar cell. The influence of realistic interface morphologies on light trapping is determined by using solar cells structures with the same front and back contact morphologies as a reference. Finally the optimal surface textures are derived.


Why you can't be in sync with schizophrenia patients.
Most individuals with schizophrenia will be confronted with some form of stigma. In recent years, clinicians and family members have increasingly contested the term "schizophrenia". Many of them discuss changing this name, as a means to fight stigma. Up until now, surprisingly, most research has been conducted using self-reports and behavioral research is lacking. The aim of our study was to assess through an experimental design if the term "schizophrenia" itself modifies social behaviours. Forty participants were asked to engage in a synchronization task with a dot displayed on a screen and moved by another person. Non-clinicians participants had to synchronize their movements as accurately as possible with either a "schizophrenia" patient, a patient with "neuro-emotional integration disorder" or a "healthy" subject, kept out of sight. Each condition was counterbalanced between participants. In fact, the movements of the dot were pre-recorded (five trajectories) and were therefore identical for all three conditions. Measuring the error between the displayed and performed trajectories, participants exhibited more errors when they thought they were interacting with a patient in comparison to the "healthy" subject. Post-hoc analysis revealed an even higher difference between "schizophrenia" and "healthy" conditions. Altogether, our results show a significant behavioral impact of the term "schizophrenia" with possibly negative consequences on social interactions. The effect of changing the name reduces this impact but remains unclear.


Effects of long-term nocturnal nasal ventilation on spontaneous breathing during sleep in neuromuscular and chest wall disorders.
Nocturnal nasal intermittent positive pressure ventilation (NIPPV) is an effective means of normalizing awake blood gases in patients with respiratory insufficiency due to neuromuscular or chest wall dysfunction. However, little attention has been paid to the effects of long-term ventilation on spontaneous breathing during sleep in such patients. The purpose of this study was to determine whether spontaneous breathing during sleep improved after long-term nasal ventilation. Fourteen patients with documented nocturnal respiratory failure, who had been treated with nocturnal NIPPV for at least 6 months, were reviewed with an all night polysomnograph on a night without ventilatory support. The severity of nocturnal desaturation both in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep without nocturnal ventilation was compared to desaturation measured during the initial diagnostic study. Spontaneous daytime blood gas values (mean +/- SD) were significantly improved at follow-up compared to values obtained prior to nasal ventilation: arterial oxygen tension (Pa,O2): 7.5 +/- 1.2 to 10.2 +/- 1.3 kPa (p < 0.005); arterial carbon dioxide tension (Pa,CO2) 8.2 +/- 1.6 to 6.4 +/- 0.7 kPa (p < 0.001). Significant improvements in inspiratory muscle strength were also observed with maximal inspiratory pressure (Pl, max) increasing from a baseline value of 41 +/- 18 to 65 +/- 26% predicted measured prior to the night of ventilation withdrawal (p < 0.003). Spontaneous breathing during sleep after long-term treatment was markedly improved although still abnormal. During NREM sleep without ventilatory support, oxygen desaturation was significantly less severe compared to the initial study (arterial oxygen saturation (Sa,O2) 88 +/- 4 vs 78 +/- 8%; p < 0.001). Minimum Sa,O2 during REM sleep similarly improved from a mean value of 49 +/- 14% during the diagnostic night to 73 +/- 10% at review follow-up (p < 0.001). In 12 patients, transcutaneous carbon dioxide was measured continuously during sleep on both occasions and demonstrated significantly less CO2 retention during follow-up compared to control studies both in NREM (p < 0.003) and REM sleep states (p < 0.004). Long-term nocturnal ventilation produces improved respiratory drive both asleep and awake and improved arousal responses to abnormal blood gases.


Mitochondrial DNA content increase in response to cigarette smoking.
An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy. Total DNA was extracted from exfoliated cells in saliva. DNA from a nuclear gene, beta-actin, and two mitochondrial genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real-time PCR. mtDNA content was correlated with age, exposure history, and other variables using multivariate regression analyses. A significant increase (P<0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I and Cox II, respectively) and former smokers (31% and 34%) when compared with never smokers. This association persisted after adjustment for other significant factors including age, alcohol drinking, and income (P<0.001). Increased mtDNA content was positively associated with pack-years of smoking (P=0.02). Despite an average smoking cessation interval of 21 years in former smokers, tobacco cessation interval was not statistically significantly associated with mtDNA content. Smoking is associated with increased mtDNA content in a dose-dependent fashion. Mitochondrial DNA alterations in response to smoking persist for several decades after smoking cessation, consistent with long-term, smoking-related damage.


Effect of pulsing in low-level light therapy.
Low level light (or laser) therapy (LLLT) is a rapidly growing modality used in physical therapy, chiropractic, sports medicine and increasingly in mainstream medicine. LLLT is used to increase wound healing and tissue regeneration, to relieve pain and inflammation, to prevent tissue death, to mitigate degeneration in many neurological indications. While some agreement has emerged on the best wavelengths of light and a range of acceptable dosages to be used (irradiance and fluence), there is no agreement on whether continuous wave or pulsed light is best and on what factors govern the pulse parameters to be chosen. The published peer-reviewed literature was reviewed between 1970 and 2010. The basic molecular and cellular mechanisms of LLLT are discussed. The type of pulsed light sources available and the parameters that govern their pulse structure are outlined. Studies that have compared continuous wave and pulsed light in both animals and patients are reviewed. Frequencies used in other pulsed modalities used in physical therapy and biomedicine are compared to those used in LLLT. There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to define these effects for different disease conditions and pulse structures.


Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.
Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).


Late complications after gastric reservoir reduction with external wrap.
Numerous surgical procedures have been introduced to facilitate weight loss in morbidly obese individuals. Gastric reservoir reduction, wrapping the stomach with an inert fabric, is one such procedure. Nissen fundoplication has been performed in conjunction with this approach to prevent postoperative gastroesophageal reflux. Gastric perforation and functional gastroesophageal obstruction occurring as late as 71 months after this operation represent late complications. Perforation has developed in 14.6% of stomachs wrapped with polypropylene mesh. Nissen fundoplication may contribute to this complication.


Studying Cavitation Enhanced Therapy.
Interest in the therapeutic applications of ultrasound is significant and growing, with potential clinical targets ranging from cancer to Alzheimer's disease. Cavitation - the formation and subsequent motion of bubbles within an ultrasound field - represents a key phenomenon underpinning many of these treatments. There remains, however, considerable uncertainty regarding the detailed mechanisms of action by which cavitation promotes therapeutic effects and there is a need to develop reliable monitoring techniques that can be implemented clinically. In particular, there is significant variation between studies in the exposure parameters reported as successfully delivering therapeutic effects and the corresponding acoustic emissions. The aim of this paper is to provide design guidelines and an experimental protocol using widely available components for performing studies of cavitation-mediated bioeffects, and include real-time acoustic monitoring. It is hoped that the protocol will enable more widespread incorporation of acoustic monitoring into therapeutic ultrasound experiments and facilitate easier comparison across studies of exposure conditions and their correlation to relevant bio-effects.


Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke.
Pneumonia is the most common medical complication after stroke. Although several risk factors have been reported, the role of common comorbidities in the development of pneumonia is not well established. Moreover, there is discrepancy in the literature regarding the impact of pneumonia on stroke outcomes. This is a multicenter retrospective cohort study including consecutive patients with ischemic stroke admitted to Regional Stroke Centers participating in the Registry of Canadian Stroke Network in July 2003-March 2007. Pneumonia was defined as a complication that occurred within the first 30 days of the stroke and was confirmed radiographically. The main outcome measure was adjusted 30-day mortality. Secondary outcomes were adjusted 7- and 365-day mortality, institutionalization, length of stay, and modified Rankin score on discharge. We also assessed the impact of organized stroke care on pneumonia development and mortality. Overall, 8,251 patients were included in the study. Stroke-associated pneumonia was observed in 587 patients (7.1%). Pneumonia increased 30-day (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.8-2.7]) and 1-year mortality (OR 3.0 [95% CI 2.5-3.7]), but not 7-day mortality. Pneumonia was associated with poor functional outcome. Higher access to organized inpatient care resulted in a reduction of 30-day mortality (OR 0.50 [95% CI 0.41-0.61]). Older age, male sex, stroke severity, dysphagia, chronic obstructive pulmonary disease, coronary artery disease, nonlacunar ischemic stroke, and preadmission dependency were independent predictors of pneumonia. Development of pneumonia after stroke was associated with mortality at 30 days and 1 year, longer length of stay, and dependency at discharge. Patients who received more inpatient stroke services had reduced mortality after pneumonia.


Local Structure of Sulfur Vacancies on the Basal Plane of Monolayer MoS2.
The nature of the S-vacancy is central to controlling the electronic properties of monolayer MoS2. Understanding the geometric and electronic structures of the S-vacancy on the basal plane of monolayer MoS2 remains elusive. Here, operando S K-edge X-ray absorption spectroscopy shows the formation of clustered S-vacancies on the basal plane of monolayer MoS2 under reaction conditions (H2 atmosphere, 100-600 °C). First-principles calculations predict spectral fingerprints consistent with the experimental results. The Mo K-edge extended X-ray absorption fine structure shows the local structure as coordinatively unsaturated Mo with 4.1 ± 0.4 S atoms as nearest neighbors (above 400 °C in an H2 atmosphere). Conversely, the 6-fold Mo-Mo coordination in the crystal remains unchanged. Electrochemistry confirms similar active sites for hydrogen evolution. The identity of the S-vacancy defect on the basal plane of monolayer MoS2 is herein elucidated for applications in optoelectronics and catalysis.


Improved tendon healing by a combination of Tanshinone IIA and miR-29b inhibitor treatment through preventing tendon adhesion and enhancing tendon strength.
Background: Despite significant advances in the materials and methods development used in surgical repair and postoperative rehabilitation, the adhesion formation remains the most common clinical problem in tendon injuries. Therefore, the development of novel therapies is necessary for targeting at preventing tendon adhesion formation and improving tendon strength. Methods: We used rat fibroblasts for in vitro experiments to determine the optimal concentration of TSA in rats, and then set up negative control group, TSA intervention group, mir-29b interference adenovirus intervention group and TSA and mir-29b interference adenovirus co-intervention group. By comparing cell proliferation and protein expression in different group, we verified the effect and mechanism of drugs on fibroblast function. At the same time, the Sprague-Dawley rat Achilles tendon model in vivo was established in this study, which was divided into sham operation group and operation group. Afterwards in the operation group, mir-29b inhibitor and placebo were injected every 3 days respectively. Then the injection inhibitor group was divided into 5 groups which mean TSA was injected into the marked area at 0, 6, 24 and 72 hours after operation for 1 week, finally all of the rats were died at 3 weeks after operation. Through the observation of general properties, histological observation of Achilles tendon injury, biomechanical test and cell and protein expression in rats' tendon cell, the effect of drugs on tendon adhesion formation was analyzed. Results: We demonstrated that the combination of miR-29b inhibitor and tanshinone IIA(TSA) could prevent tendon adhesion and also enhance tendon strength. Mechanically, the miR-29b inhibitor could activate the TGF-β/Smad3 pathway to trigger endogenous pathways and induce a high proliferation of fibroblast. Subsequently, we also found adding TSA after 6 hours of miR-29b treatment gave less cell cytotoxicity in our rat model with better outcome of less tendon adhesion and enhanced strength. Conclusion: We conclude that the use of miR-29b inhibitor at the end of the tendon break could initiate endogenous repair mechanism and subsequently use of TSA should be able to inhibit the exogenous repair mechanism. Therefore, the combination of both treatments could prevent tendon adhesion and ensure tendon strength. Our findings suggested that this approach would be a feasible approach for tendon repair.


Dynamics of gene transfer to retinal pigment epithelium.
To examine the nature and dynamics of gene transfer to human retinal pigment epithelium (RPE) using an adenoviral vector and adjuvants that may enhance the uptake of recombinant adenoviruses. Human RPE cultures (HRPE7) were transfected in vitro with varying concentrations (4, 20, 40, 120, and 200 pfu/microliter) and for varying periods (1, 2, 4, 16, 24, 48, and 72 hours) with a replication-deficient adenovirus (Ad.RSV. beta gal) containing the bacterial beta-galactosidase transgene (beta gal). The expression of beta gal was monitored by counting after X gal staining. The transgene expression profiles were compared to those of human F2000 fibroblasts under the same conditions. The adjuvant effect of sodium hyaluronate (HA) on the expression of beta gal was tested in F2000 and early and late passage human RPE cells for differing concentrations of HA, viral titers, and incubation times. Immunofluorescent cytochemistry was carried on HRPE7 and F2000 cells for the HA receptors, homing receptor CD44 (CD44), intercellular adhesion molecule 1 (ICAM-1), and the receptor for hyaluronan mediated motility (RHAMM). The number of HRPE7 and F2000 cells expressing the adenoviral transgene increased consistently with increasing incubation time and viral titer. There was a higher uptake of Ad.RSV. beta gal in HRPE7 cells compared to the F2000 fibroblasts under the same conditions. There was an increase of 28.1% and 41.4% in the number of RPE7 cells expressing adenoviral transgene and 16.2% and 15.8% F2000 fibroblast cells expressing the adenoviral transgene in the presence of 0.001% and 0.005% HA, respectively. Significant adjuvant effects on transgene expression also were shown in HRPE51 cells. It appears that the effects of increasing viral titer, length of incubation, and the presence of HA on transgene expression are at least additive. The appearance of CD44 and ICAM receptors on RPE7 and F2000 cells and RHAMM receptors on F2000 cells was similar. The RHAMM receptors in HRPE7 cells, however, were shown preferentially over the nucleus. On the basis of these results, the authors propose that adenovirus transgene expression increases with increasing incubation time and viral titer in cell culture. The rate of increase of expression differs between human RPE cells and the F2000 fibroblast cells, which may offer a targeting opportunity. The authors propose that the use of HA can offer both an adjuvant effect and a targeting advantage in terms of transferring adenoviral transgenes to human RPE in culture.


Filling the Radon domain in computed tomography by local convex combination.
Radon data interpolation is a necessary procedure in computed tomography (CT), especially for reconstruction from divergent beam scanning. In a polar-grid representation, the Radon data of a fanbeam projection are populated on an arc, rather on a radial line. Collectively, the Radon data generated from a fanbeam CT system are unevenly populated: The population becomes sparser as the polar distance increases. In CT reconstruction, the Fourier central slice theorem requires a radial scanline full of Radon data. Therefore the vacant entries of a scanline must be filled by interpolation. In addition, interpolation is also required in polar-to-Cartesian conversion. In this paper we propose a practical interpolation technique for filling the vacant entries by local convex combination. It is a linear interpolant that generates a value for a grid point from the available data lying in its neighborhood, by a weighted average, with the weights corresponding to the inverse distances. In fact, the linear convex combination serves as a general flat-smoothing operation in filling a vacancy. Specifically, this technique realizes a variety of linear interpolations, including nearest-neighbor replication, two-point collinear, three-point triangulation, and four-point quadrilateral, and local extrapolation, in a unified framework. Algorithms and a simulation demonstration are provided.


Alcohol and drug use among adolescents: an educational overview.
Alcohol and drug use continues to be a significant global problem with many health and economic consequences. Multiple studies have shown that the majority of adults who end up with an alcohol/drug use disorder have their first contact with these substances as adolescents. This article aims to briefly summarize current prevalence and impact on society, as well as its etiology, comorbid psychiatric disorders, and treatment and prevention of adolescent drug and alcohol use. Alcohol and substance use impacts both the user and society at large, from health risks to the user to increased early pregnancies, car accidents, financial cost, and productivity cost. Substance use and abuse results from intricate interactions between genetic and environmental influences. Also, substance abuse along with a comorbid psychiatric disorder is more common than a solitary substance use disorder in adolescents. Current options for the treatment of substance abuse disorders range from various therapy-based strategies, including behavioral and family-based therapies, to the use of medications. More attention must be placed on the importance of prevention of use, as well as progression of use to dependence. Successful prevention requires a comprehensive plan that needs to include, but should not be limited to, increasing education of all gatekeepers and limiting access of substances and alcohol through policy and reinforcement of those policies. Education of parents, pediatricians, school nurses, teachers, and mental health workers is essential to ensure that children at risk are identified in time to provide appropriate interventions.


Idiopathic toe walking: a comparison of treatment methods.
Eighty children with idiopathic toe walking (ITW) were examined 2-8 years (average, 34 months) after initial presentation to compare outcomes [passive ankle dorsiflexion (DF) and parental satisfaction] after three treatment modalities: observation, cast/brace treatment, or surgical triceps surae lengthening. Overall, 32% had a family history of ITW, 28% were born prematurely, and 16% had psychomotor delay. Forty-eight untreated patients showed little change in passive ankle DF at final follow-up, and only 25% of parents were satisfied with the child's gait. Compared with untreated children, casting/bracing appeared to offer no significant improvement in ankle DF or parental satisfaction. Surgical treatment was performed in 15 children with more severe equinus contractures. Triceps surae lengthening resulted in significantly improved ankle DF and 67% parental satisfaction (p < 0.05). Toe walking may persist after all standard treatment methods, even in the absence of significant Achilles contracture.


DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9.
In response to genotoxic stress, a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint (DDC) signalling pathway positively contributes to genome maintenance. Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest, cells must tightly regulate the activity of the kinases involved in this pathway. Despite their importance, the mechanisms for monitoring and modulating DDC signalling are not fully understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae. On replication stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal. An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation. A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions. Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors.


Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vκ Gene Rearrangement in Pre-B Cells and Pro-B Cells.
To date there has not been a study directly comparing relative Igκ rearrangement frequencies obtained from genomic DNA (gDNA) and cDNA and since each approach has potential biases, this is an important issue to clarify. Here we used deep sequencing to compare the unbiased gDNA and RNA Igκ repertoire from the same pre-B cell pool. We find that ~20% of Vκ genes have rearrangement frequencies ≥2-fold up or down in RNA vs. DNA libraries, including many members of the Vκ3, Vκ4, and Vκ6 families. Regression analysis indicates Ikaros and E2A binding are associated with strong promoters. Within the pre-B cell repertoire, we observed that individual Vκ genes rearranged at very different frequencies, and also displayed very different Jκ usage. Regression analysis revealed that the greatly unequal Vκ gene rearrangement frequencies are best predicted by epigenetic marks of enhancers. In particular, the levels of newly arising H3K4me1 peaks associated with many Vκ genes in pre-B cells are most predictive of rearrangement levels. Since H3K4me1 is associated with long range chromatin interactions which are created during locus contraction, our data provides mechanistic insight into unequal rearrangement levels. Comparison of Igκ rearrangements occurring in pro-B cells and pre-B cells from the same mice reveal a pro-B cell bias toward usage of Jκ-distal Vκ genes, particularly Vκ10-96 and Vκ1-135. Regression analysis indicates that PU.1 binding is the highest predictor of Vκ gene rearrangement frequency in pro-B cells. Lastly, the repertoires of iEκ-/- pre-B cells reveal that iEκ actively influences Vκ gene usage, particularly Vκ3 family genes, overlapping with a zone of iEκ-regulated germline transcription. These represent new roles for iEκ in addition to its critical function in promoting overall Igκ rearrangement. Together, this study provides insight into many aspects of Igκ repertoire formation.


Improving sensitivity in shotgun proteomics using a peptide-centric database with reduced complexity: protease cleavage and SCX elution rules from data mining of MS/MS spectra.
Correct identification of a peptide sequence from MS/MS data is still a challenging research problem, particularly in proteomic analyses of higher eukaryotes where protein databases are large. The scoring methods of search programs often generate cases where incorrect peptide sequences score higher than correct peptide sequences (referred to as distraction). Because smaller databases yield less distraction and better discrimination between correct and incorrect assignments, we developed a method for editing a peptide-centric database (PC-DB) to remove unlikely sequences and strategies for enabling search programs to utilize this peptide database. Rules for unlikely missed cleavage and nontryptic proteolysis products were identified by data mining 11 849 high-confidence peptide assignments. We also evaluated ion exchange chromatographic behavior as an editing criterion to generate subset databases. When used to search a well-annotated test data set of MS/MS spectra, we found no loss of critical information using PC-DBs, validating the methods for generating and searching against the databases. On the other hand, improved confidence in peptide assignments was achieved for tryptic peptides, measured by changes in DeltaCN and RSP. Decreased distraction was also achieved, consistent with the 3-9-fold decrease in database size. Data mining identified a major class of common nonspecific proteolytic products corresponding to leucine aminopeptidase (LAP) cleavages. Large improvements in identifying LAP products were achieved using the PC-DB approach when compared with conventional searches against protein databases. These results demonstrate that peptide properties can be used to reduce database size, yielding improved accuracy and information capture due to reduced distraction, but with little loss of information compared to conventional protein database searches.


Decreased bone ultrasound velocity in premature infants conceived with assisted reproduction.
Quantitative ultrasound (QUS) measurement of tibial speed of sound (SOS) can be used to determine bone strength. Children conceived with assisted reproduction treatments (ART) are taller than naturally conceived (NC) children, so we hypothesized that these infants would have higher SOS levels than NC infants. Thirty-seven ART (ART group) and 51 NC neonates (NC group) were included in the study. Tibial initial SOS (iSOS) was measured within 96 hours of birth using QUS. Measurements were performed weekly until the infant was discharged from the hospital. The iSOS levels of the ART group (2823.41±110.8 m/sec) were lower than those of the NC group (2917.14±145.6 m/sec) (p=0.001). A decrease in SOS levels was observed in 39 of 53 infants who had serial scans. The difference in SOS levels between the first and last scan was significant (p<0.02). In vitro manipulation during the periconceptual period can result in metabolic alterations in bone mineral content. Contrary to our null hypothesis, bone SOS of infants in the ART group was found to be lower than in the NC group. Moreover, bone SOS decreases in early postnatal life. This result emphasizes the fact that even with advances in nutritional care, the ex utero environment remains a poor substitute for in utero development.


Onset, progression and resolution of experimental peri-implant mucositis at different abutment surfaces: A randomized controlled two-centre study.
To assess the onset, progression and resolution of experimentally induced peri-implant mucositis lesions at abutments with different microstructures in humans. In a randomized, controlled, interventional two-centre study, a total of 28 patients had received 28 target implants and were randomly allocated to either partially microgrooved (test) or machined (control) healing abutments. The study was accomplished in three phases, including a wound healing period (WH) following implant placement (12 weeks), a plaque exposure phase (EP-21 days) and a resolution phase (RP-16 weeks). Clinical (e.g. bleeding on probing-BOP), immunological (MMP-8) and microbiological (DNA counts for 11 species) parameters were evaluated. The incidence of peri-implant mucositis at EPd21 was comparable in both test and control groups (60.0% versus 61.5%), but markedly lower at control abutments after a nonsurgical treatment and reconstitution of oral hygiene measures at RPw16 (46.7% versus 15.4%). At any follow-up visit (i.e. EP and RP), clinical parameters, MMP-8 levels and DNA counts of major bacterial species were not significantly different between both groups. The onset, progression and resolution of experimental peri-implant mucositis lesions were comparable in both groups.


Preconception care for women with type 2 diabetes mellitus: A mixed-methods study of provider knowledge and practice.
Preconception care may decrease adverse pregnancy outcomes associated with pre-existing diabetes mellitus. Aboriginal Australians are at high risk of type 2 diabetes mellitus (T2DM), with earlier onset. We explored practitioner views on preconception care delivery for women with T2DM in the Northern Territory, where 31% of births are to Aboriginal women. Mixed-methods study including cross-sectional survey of 156 health practitioners and 11 semi-structured interviews. Practitioners reported low attendance for preconception care however, 51% provided counselling on an opportunistic basis. Rural/remote practitioners were most likely to find counselling feasible. The majority (69%) utilised appropriate guidelines and addressed lifestyle modifications including smoking (81%), weight management (79%), and change medications appropriately such as ceasing ACE inhibitors (69%). Fewer (40%) prescribed the recommended dose of folate (5mg) or felt comfortable recommending delaying pregnancy to achieve optimal preconception glucose control (42%). Themes identified as barriers to care included the complexity of care setting and infrequent preconception consultations. There was a focus on motivation of women to make informed choices about conception, including birth spacing, timing and contraception. Preconception care enablers included cross-cultural communication, a multi-disciplinary care team and strong client-based relationships. Health practitioners are keen to provide preconception counselling and reported knowledge of evidence-based guidelines. Improvements are needed in recommending high dose folate and optimising glucose control. Cross-cultural communication and team-based care were reported as fundamental to successful preconception care in women with T2DM. Continued education and policy changes are required to support practitioners in opportunities to enhance pregnancy planning.


CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory.
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are an approved treatment for hormone receptor-positive breast cancer and are currently under evaluation across hundreds of clinical trials for other cancer types. The clinical success of these inhibitors is largely attributed to well-defined tumor-intrinsic cytostatic mechanisms, whereas their emerging role as immunomodulatory agents is less understood. Using integrated epigenomic, transcriptomic, and proteomic analyses, we demonstrated a novel action of CDK4/6 inhibitors in promoting the phenotypic and functional acquisition of immunologic T-cell memory. Short-term priming with a CDK4/6 inhibitor promoted long-term endogenous antitumor T-cell immunity in mice, enhanced the persistence and therapeutic efficacy of chimeric antigen receptor T cells, and induced a retinoblastoma-dependent T-cell phenotype supportive of favorable responses to immune checkpoint blockade in patients with melanoma. Together, these mechanistic insights significantly broaden the prospective utility of CDK4/6 inhibitors as clinical tools to boost antitumor T-cell immunity. SIGNIFICANCE: Immunologic memory is critical for sustained antitumor immunity. Our discovery that CDK4/6 inhibitors drive T-cell memory fate commitment sheds new light on their clinical activity, which is essential for the design of clinical trial protocols incorporating these agents, particularly in combination with immunotherapy, for the treatment of cancer.This article is highlighted in the In This Issue feature, p. 2355.


Eighteen-year follow up after Hancock II bioprosthesis insertion.
The long-term (18 years) results after aortic (AVR), mitral (MVR) and double (aortic/mitral, DVR) valve replacement with Hancock II bioprosthesis were investigated. Between 1978 and 1996, 279 Hancock II bioprostheses were implanted in 269 patients (166 males, 113 females; mean age 61.8+/-13.3 years). There were 135 AVR (48.4%), 122 MVR (43.8%) and 22 DVR (7.8%). Preoperatively, 208 patients (77.3%) were in NYHA functional class III/IV, 53 (19.7%) had previous cardiac surgery, and 19 (7.1%) underwent concomitant coronary artery bypass. Follow up (mean seven years) was 96% complete, with a total of 1,857 patient-years. There were 20 early (7.3%), and 78 (29.0%) late deaths. At the last follow up, 68.3% of patients were in NYHA functional class I/II. The actuarial survival rate of patients at 10 and 18 years after discharge was 67.7+/-5.0% and 44.7+/-8.8% after AVR and 64.5+/-5.6% and 32.7+/-11.5% after MVR, respectively; survival after DVR was 74.0+/-11.2% at 12 years. At 10 and 18 years, actuarial freedom from thromboembolism was 83.5+/-4.5% and 73.1+/-10.5% after AVR and 82.1+/-4.3% and 73.2+/-7.3% after MVR; it was 78.4+/-15.0% after DVR at 12 years. At these times, actuarial freedom from hemorrhage was 88.7+/-3.8% and 83.5+/-6.2% after AVR and 79.0+/-4.9% and 32.6+/-23.3% after MVR; freedom after DVR was 36.2+/-26.6%. Probability of freedom from endocarditis at 10 and >15 years was 93.4+/-3.5% and 85.9+/-7.8% after AVR and 97.0+/-2.1% and 97.0+/-2.1% for MVR, respectively; freedom at 10 years after DVR was 75.0+/-21.6%. Freedom from structural deterioration at 10 and 18 years was 77.9+/-5.3% and 18.7+/-14.6% after AVR and 78.3+/-6.0% and 32.1+/-10.2% after MVR; freedom at 10 and 12 years after DVR was 64.0+/-17.5% and 32.0+/-24.2%. A low incidence of structural valve deterioration was found in AVR patients aged >65 years (p = 0.0478). Hemorrhage and paravalvular leak were more frequent in MVR (p = 0.0296 and 0.0309, respectively). No difference was seen in thromboembolism after anticoagulation for one or three months after AVR. Actuarial freedom from explantation at 10 and 18 years was 73.1+/-5.9% and 15.9+/-13.5% after AVR and 77.1+/-6.1% and 37.3+/-9.7% after MVR; freedom at 10 and 12 years after DVR was 72.0+/-17.8% and 24.0+/-20.4%. Over an 18-year follow up, the Hancock II bioprosthesis has shown satisfactory results, with a low incidence of valve-related complications, especially in elderly patients in the aortic position.


Assessment of the Relation Between SNP in MxA Gene and the Responsiveness of Egyptian HCV Genotype 4 Patients to Pegylated Interferon and Ribavirin Treatment.
Pegylated interferon (PegIFN) is used in the treatment of chronic hepatitis C virus (HCV) patients especially in resource limited countries. Treatment with PegIFN stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-A (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promoter region that affects the expression of MxA gene protein and was suggested to affect the treatment outcome. The aim of the work was to assess the relation between the SNP in the MxA gene and its impact on treatment of chronic HCV patients with PegIFN and ribavirin. We therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and 40 healthy controls. G allele was the prevalent one in both HCV patients group (105, 74.5%) and control group (66, 82.5%), while T allele was less expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is no correlation between genotypes and response to IFN-alpha therapy: GG (OR: 0.958, 95% CI: 0.541 - 1.698, P = 0.884), GT (OR: 0.667, 95% CI: 0.188 - 2.362, P = 0.530), and TT (OR: 0.300, 95% CI: 0.083 - 1.090, P = 0.067). MxA nt-88 SNP did not affect the sustained virological response (SVR) rates after PegIFN and ribavirin combined treatment and did not act as a biological marker to potentially identify responders and non-responders to treatment. Our results call for additional large studies and/or meta-analysis of all currently available data to examine the role of MxA nt-88 SNP in predicting response to PegIFN and ribavirin in patients with IFN-alpha naive HCV genotype 4.


Phosphorescent soft salt for ratiometric and lifetime imaging of intracellular pH variations.
In contrast to traditional short-lived fluorescent probes, long-lived phosphorescent probes based on transition-metal complexes can effectively eliminate unwanted background interference by using time-resolved luminescence imaging techniques, such as photoluminescence lifetime imaging microscopy. Hence, phosphorescent probes have become one of the most attractive candidates for investigating biological events in living systems. However, most of them are based on single emission intensity changes, which might be affected by a variety of intracellular environmental factors. Ratiometric measurement allows simultaneous recording of two separated wavelengths instead of measuring mere intensity changes and thus offers built-in correction for environmental effects. Herein, for the first time, a soft salt based phosphorescent probe has been developed for ratiometric and lifetime imaging of intracellular pH variations in real time. Specifically, a pH sensitive cationic complex (C1) and a pH insensitive anionic complex (A1) are directly connected through electrostatic interaction to form a soft salt based probe (S1), which exhibits a ratiometric phosphorescent response to pH with two well-resolved emission peaks separated by about 150 nm (from 475 to 625 nm). This novel probe was then successfully applied for ratiometric and lifetime imaging of intracellular pH variations. Moreover, quantitative measurements of intracellular pH fluctuations caused by oxidative stress have been performed for S1 based on the pH-dependent calibration curve.


Creating a protein-based element of inheritance.
Proteins capable of self-perpetuating changes in conformation and function (known as prions) can serve as genetic elements. To test whether novel prions could be created by recombinant methods, a yeast prion determinant was fused to the rat glucocorticoid receptor. The fusion protein existed in different heritable functional states, switched between states at a low spontaneous rate, and could be induced to switch by experimental manipulations. The complete change in phenotype achieved by transferring a prion determinant from one protein to another confirms the protein-only nature of prion inheritance and establishes a mechanism for engineering heritable changes in phenotype that should be broadly applicable.


Respiratory health and lung function in Chinese restaurant kitchen workers.
To measure air pollutant concentrations in Chinese restaurant kitchens using different stove types and assess their influence on workers' respiratory health. 393 kitchen workers from 53 Chinese restaurants were surveyed over 16 months: 115 workers from 21 restaurants using only electric stoves and 278 workers from 32 restaurants using only gas stoves. Workers were interviewed about their respiratory symptoms and had their lung function tested. Concentrations of nitric oxide (NO), nitrogen dioxide (NO(2)), carbon monoxide (CO), carbon dioxide (CO(2)), methane (CH(4)), non-methane hydrocarbons (NMHC), total volatile organic compounds (TVOC) and fine particulate matter (PM(2.5)) were measured using portable monitors and air-bag sampling. Temperature and noise levels were assessed. Median concentrations of NO, NO(2) and CO were 7.4, 1.5 and 1.6 times higher in gas-fuelled kitchens than in electric ones and average concentrations of PM(2.5) and TVOC were 81% and 78% higher, respectively. Differences were smaller for CH(4) and NMHC. Electricity-run kitchens were 4.5°C cooler and 9 dBA less noisy than gas-fuelled ones. Workers using electric cookers had significantly better lung function than their gas-using counterparts and their mean FEV(1) and FVC values were 5.4% and 3.8% higher, respectively, after adjustment for confounders. Wheeze, phlegm, cough and sore throat were more prevalent in workers using gas. The adjusted OR for having phlegm regularly was significantly higher. The poorer lung function and higher prevalence of respiratory symptoms among workers in gas-fuelled kitchens compared to those in electricity-powered kitchens may be associated with exposure to higher concentrations of toxic air pollutants generated during gas cooking.


Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients.
Tuberculosis (TB) is a significant opportunistic infection in solid organ transplant recipients (SOTR). There are limited data on TB incidence in transplantation from low prevalence countries as well as on long-term TB-specific immune responses. We performed a single-center retrospective review of SOTR diagnosed with active TB between 2000 and 2015 and further contacted the available patients for a study of long-term T-cell responses using an interferon-gamma (IFN-γ) release assay and a flow cytometry-based assay. We identified 31 SOTR with active TB for an incidence of 62 cases/100 000 patient-years. Nineteen (61.3%) of 31 patients were diagnosed within the first year after transplant. Nineteen (61.3%) were born in countries with high TB prevalence and disseminated disease occurred in 22.6%. No patient had been screened for latent TB infection pretransplant. The majority of patients received isoniazid and a rifamycin as part of multidrug regimen. In addition, 13 (44.8%) of 29 patients received quinolones. One-year mortality in this population was 19.4%. Eight patients were available for long-term immune responses. Of these, all had detectable IFN-γ response by IFN-γ release assay testing and 7 of 8 had detectable TB-specific T cells, primarily central and effector T-cell responses in the CD4 compartment and terminally differentiated T cells in the CD8 compartment. TB has high incidence in SOTR even in low-prevalence regions but especially targets patients who originated from TB-endemic countries. Long-term TB-specific T-cell responses were found in the majority of patients.


Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment.


Comprehensive re-analysis of archived herring gull eggs reconstructs historical temporal trends in chlorinated hydrocarbon contamination in Lake Ontario and Green Bay, Lake Michigan, 1971-1982.
Herring gull egg homogenates collected between 1971 and 1982 from a colony in central Lake Ontario (Scotch Bonnet Island) and from a colony in central Green Bay, Lake Michigan (Big Sister Island) were archived in the Canadian Wildlife Service Specimen Bank. Pooled samples (N = 10) were exhaustively analyzed in 1993 for a wide range of individual chlorinated hydrocarbon contaminant (CHC) compounds: DDT, mirex and chlordane compounds and metabolites, chlorobenzenes (CBzs), dieldrin, chlorostyrenes (CSs), hexachlorocyclohexanes (HCHs), polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and 87 PCB congeners, including the TCDD-like non-ortho and mono-ortho congeners. PCBs and DDTs were the dominant residues in eggs from both Lake Ontario (31-242 mg kg(-1) and 9-64 mg kg(-1)) and Green Bay (34-133 mg kg(-1) and 14-91 mg kg(-1)). SigmaPCBs declined by a factor of 4-5 and DDTs a factor of 4-7 at both colonies between 1971 and 1982. Lake Ontario eggs had significantly higher residues of 2,3,7,8-TCDD (0.2-2.0 microg kg(-1)), HCBz (0.1-4.7 mg kg(-1)), OCS (0.03-0.45 mg kg(-1)), three HpCSs (0.13-0.97 mg kg(-1)), mirex and mirex photodegradation products (2.1-9.2 mg kg(-1)) than Green Bay eggs. HCBz levels in Lake Ontario eggs declined a factor of 40, TCDD and chlorostyrenes a factor of 8-10, and mirex a factor of 4 between 1971-1978. Green Bay eggs had slightly higher levels of chlordane-related compounds, dieldrin and beta-HCH than Lake Ontario eggs. There were no consistent or strong trends in residue levels of these pesticides, PCDDs (except TCDD) and PCDFs in either lake, indicating that rates of input and removal of these CHCs in the lakes were much closer in the early 1970s than was the case for the other compounds.


Activity and participation in home rehabilitation: older people's and family members' perspectives.
To explore the experiences of older people and their supporting family members in relation to home rehabilitation, with a focus on activity and participation. Qualitative interviews were carried out with 6 older people and 6 family members at 1 and 6 months after the older person's discharge to their home. Qualitative content analysis of the data was carried out. The International Classification of Functioning, Disability and Health provides a guiding framework for rehabilitation. Informants' experiences of home rehabilitation contributed to the formation of 6 categories: (i) living with a frail body; (ii) striving for well-being in daily life; (iii) being close at hand; (iv) feeling dependent in daily life; (v) struggling to carry on; and (vi) striving to be at home. Older people's goals were to return to daily routines and to perform meaningful activities without feeling dependent on other people. Family members' participation was crucial. Psychosocial support and autonomy were essential for facilitating activity and participation. Healthcare professionals should consider each individual's unique experiences along with the significance of being at home.


Drag reduction on laser-patterned hierarchical superhydrophobic surfaces.
Hierarchical laser-patterned surfaces were tested for their drag reduction abilities. A tertiary level of surface roughness which supports stable Cassie wetting was achieved on the patterned copper samples by laser-scanning multiple times. The laser-fabricated micro/nano structures sustained the shear stress in liquid flow. A rheometer setup was used to measure the drag reduction abilities in term of slip lengths on eight different samples. A considerable increase in slip length (111% on a grate sample) was observed on these surfaces compared to the slip length predictions from the theoretical and the experimental models for the non-hierarchical surfaces. The increase in slip lengths was correlated to the secondary level of roughness observed on the patterned samples. The drag reduction abilities of three different arrangements of the surface features were also compared: posts in a square lattice, parallel grates, and posts in a hexagonal lattice. Although the latter facilitates a stable Cassie state, it nevertheless resulted in a lower normalized slip length compared to the other two arrangements at a similar solid fraction. Furthermore, we coated the laser-patterned surfaces with a silane to test the effect of surface chemistry on drag reduction. While the contact angles were surprisingly similar for both the non-silanized and the silanized samples, we observed higher slip lengths on the latter, which we were able to explain by measuring the respective penetration depths of the liquid-vapour interface between surface features.


Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis.
During embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a primitive population of FLK1(+) mesodermal cells. Endoglin (ENG) is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors. However, the functional role of ENG during the transition of FLK1(+) mesoderm to hematopoietic cells is ill defined. To address this we used a murine embryonic stem cell model that has been shown to mirror the temporal emergence of these cells in the embryo. We noted that FLK1(+) mesodermal cells expressing ENG generated fewer blast colony-forming cells but had increased hemogenic potential when compared with ENG non-expressing cells. TIE2(+)/CD117(+) HE cells expressing ENG also showed increased hemogenic potential compared with non-expressing cells. To evaluate whether high ENG expression accelerates hematopoiesis, we generated an inducible ENG expressing ES cell line and forced expression in FLK1(+) mesodermal or TIE2(+)/CD117(+) HE cells. High ENG expression at both stages accelerated the emergence of CD45(+) definitive hematopoietic cells. High ENG expression was associated with increased pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken together, these data show that ENG potentiates the emergence of definitive hematopoietic cells by modulating TGF-β/pSMAD2 signalling and increasing eNOS/NO synthesis.


Promoting effect of tungsten carbide on the catalytic activity of Cu for CO2 reduction.
The adsorption of H, CO2, HCOO, O and CO on copper monolayers and submonolayers supported on hexagonal WC(0001) surfaces has been investigated. Calculations have been performed using density functional theory with the Perdew-Burke-Ernzerhof exchange correlation functional and D2 van der Waals corrections. In addition, dipole corrections were also included. The catalytic properties of supported Cu on both carbon- and metal-terminated WC(0001) surfaces were explored. On carbon-terminated WC(0001) surfaces, Cu tends to be oxidized, while on the metallic terminated surface, it gains charge. The results indicate that all studied Cu/WC(0001) surfaces bind all adsorbates stronger than the extended Cu(111). For CO, the binding energy is so large in some cases (1.6-2.2 eV) that it could potentially lead to catalyst deactivation. Nevertheless, surfaces with an adsorbed Cu monolayer, CuML, are less prone to this deactivation, since there are not WC surface atoms; and thus, the contribution of strong CO adsorption from the support does not play a role. Energy barriers for HCOO formation, relative to direct dissociation barriers of CO2, indicate that a hydrogen-assisted reduction path is more likely to occur on Cu/WC(0001) materials, with CuML/metallic termination being the most active system for this reaction path. On the other hand, CO2 adsorption on CuML surfaces is slightly weaker on a C-terminated surface than on a metal-terminated surface, although both surfaces have similar dissociation barriers. This fact together with the weaker CO adsorption on CuML/C-terminated WC(0001) than on metal-terminated WC(0001) suggests that the former system may be a better catalyst for CO2 reduction, due to the lower surface poisoning by the CO2 dissociation products. Possible deactivation of Cu/WC(0001) materials may be prevented by the introduction of hydrogen into the system, thus promoting the formation of HCOO and avoiding CO and O formation.


Antiparasitic and anticancer carvotacetone derivatives of Sphaeranthus bullatus.
The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 microg/mL) and chloroquine resistant W2 (IC50 15.0 microg/mL) strains of Plasmodium falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity of four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1), 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxy-carvotacetone (4); with antiplasmodial IC50 values of 1.40, 0.79, 0.60 and 3.40 microg/mL, respectively, against chloroquine sensitive D6 strains of P. falciparum; antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 microg/mL, respectively, against chloroquine resistant W2 strains of P. falciparum; antileishmanial IC50 values of 0.70, 3.00, 0.70 and 17.00 microg/mL, respectively, against the parasite L. donovanii promastigotes, and anticancer activity against human SK-MEL, KB, BT-549 and SK-OV-3 tumor cells, with IC50 values between <1.1 - 5.3 microg/mL for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11). The structures of carvotacetone derivatives were determined by 1D and 2D NMR spectroscopy; the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) was determined as 3R, 4R, 5S by circular dichroism, specific rotation, 1H NMR and 2D NMR ROESY and NOESY experiments.


Exploring gene expression data with class scores.
We address a commonly asked question about gene expression data sets: "What functional classes of genes are most interesting in the data?" In the methods we present, expression data is partitioned into classes based on existing annotation schemes. Each class is then given three separately derived "interest" scores. The first score is based on an assessment of the statistical significance of gene expression changes experienced by members of the class, in the context of the experimental design. The second is based on the co-expression of genes in the class. The third score is based on the learnability of the classification. We show that all three methods reveal significant classes in each of three different gene expression data sets. Many classes are identified by one method but not the others, indicating that the methods are complementary. The classes identified are in many cases of clear relevance to the experiment. Our results suggest that these class scoring methods are useful tools for exploring gene expression data.


Large radial graded-index polymer.
A very large radial graded-index (GRIN) polymer was successfully prepared for the first time, to the best of our knowledge, by two methods: the curved mold method and the diffusion copolymerization method. Both methods gave a radial GRIN polymer with a diameter of 70 mm and a ∆n value greater than 0.02. Ray tracing through these radial GRIN polymers was used to predict that such a GRIN polymer could be a promising candidate for thinner ophthalmic lenses with no spherical aberration or multifocusing characteristics.


Comparison of the remineralisation effect of a glass ionomer cement versus a resin composite on dentin of primary teeth.
The aim of this study was to investigate the interaction of a high viscosity glass ionomer cement (GIC) and a composite resin with caries affected dentin and to determine the remineralization levels. In a split mouth design 24 GIC and composite resin atraumatic restorative treatment restorations were made in vivo and the teeth were collected after 2 years and subsequently sectioned and examined using Vickers microhardness test; the latter was performed starting from the dentin surface adjacent to the restoration. Repeated Measure ANOVA and Bonferroni statistical methods were used for data analysis. The microhardness adjacent to the GIC restorative material resulted to be significantly higher. GIC resulted to be a better restorative material for the remineralization of caries affected dentin, though further studies are necessary for the corroboration of this finding. The GIC restored primary molar dentin had a higher level of remineralization and GIC could be the material of choice in pediatric dentistry.


In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children and adolescents, with up to 5 % affected worldwide. Twin and family studies on ADHD show its high familiality with heritability estimated around 70 %, but, to date, no specific polymorphism or gene was found to be specifically affected. Psychostimulants (amphetamine, methylphenidate) and non-psychostimulants (atomoxetine) are used successfully in ADHD therapy, but many of their mechanisms of action and their adverse effects are not yet fully understood. Therefore, both genetic findings and therapeutic interventions should be further investigated. One easy platform for such studies is in vitro analyses, which encompass neuronal cell culture studies, transfections of genetic constructs, binding and electrophysiology analyses. In this review, different methods will be referred in particular to ADHD findings, and new techniques will be mentioned for future studies of drug or genetic effects in vitro.


Discrete unified gas kinetic scheme for all Knudsen number flows. IV. Strongly inhomogeneous fluids.
This work is an extension of the discrete unified gas kinetic scheme (DUGKS) from rarefied gas dynamics to strongly inhomogeneous dense fluid systems. The fluid molecular size can be ignored for dilute gases, while the nonlocal intermolecular collisions and the competition of solid-fluid and fluid-fluid interactions play an important role for surface-confined fluid flows at the nanometer scale. The nonequilibrium state induces strong fluid structural-confined inhomogeneity and anomalous fluid flow dynamics. According to the previous kinetic model [Guo et al., Phys. Rev. E 71, 035301(R) (2005)10.1103/PhysRevE.71.035301], the long-range intermolecular attraction is modeled by the mean-field approximation, and the volume exclusion effect is considered by the hard-sphere potential in the collision operator. The kinetic model is solved by the DUGKS, which has the characteristics of asymptotic preserving, low dissipation, second-order accuracy, and multidimensional nature. Both static fluid structure and dynamic flow behaviors are calculated and validated with Monte Carlo or molecular dynamics results. It is shown that the flow of dense fluid systems tends to that of rarefied gases as the dense degree decreases or the mean flow path increases. The DUGKS is proved to be applicable to simulate such nonequilibrium dense fluid systems.


Evaluation of the impact of a personalized postdonation short messaging service on the retention of whole blood donors.
Short messaging service (SMS) is routinely used by blood collection agencies to remind donors about appointments but has been applied less frequently in interventions to increase return behavior. This study aimed to investigate whether receipt of a personalized postdonation SMS promoted donor retention. A postdonation SMS was sent to 2605 whole blood donors who had donated at one of six donor centers in Australia from April to July 2015 and left without making a forward appointment. Once their donation was dispatched to a hospital or facility an SMS was sent informing the donor of the hospital or town to which their blood was dispatched. Donor's return behavior over 12 months was examined, comparing with a control group of donors who donated at the same donor centers but did not receive an SMS. Donors who received the SMS had increased odds of returning to donate within 12 months, with 70.3% of these donors returning (adjusted odds ratio, 1.49; 95% confidence interval, 1.30-1.71), compared with 62.6% of donors who did not receive the SMS. The SMS was effective in retaining first-time, novice, and established donors at 12 months, but had no effect on experienced donors. The timing of the receipt of the SMS postdonation had no impact on donor retention. This study highlights the potential of utilizing a postdonation SMS that informs donors where their blood has been dispatched as a cost-effective tool to increase retention, particularly among new donors, who are traditionally more difficult to retain.


Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia.
A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphate-buffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C(max)/MIC) and percent time that the serum concentration exceeded the MIC (%T > MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, beta-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.


Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington.
Predictors of outcome in pediatric submersion victims treated by Seattle and King County's prehospital emergency services were studied. Victims less than 20 years old were identified from hospital admissions and paramedic and medical examiners' reports. The proportion of fatal or severe outcomes in patients were compared with various risk factors. Of 135 patients, 45 died and 5 had severe neurologic impairment. A subset of 38 victims found in cardiopulmonary arrest had a 32% survival rate, with 67% of survivors unimpaired or only mildly impaired. The two risk factors that occurred most commonly in victims who died or were severely impaired were submersion duration greater than 9 minutes (28 patients) and cardiopulmonary resuscitation duration longer than 25 minutes (20 patients). Both factors were ascertained in the prehospital phase of care. Submersion duration was associated with a steadily increasing risk of severe or fatal outcomes: 10% risk (7/67) for 0 to 5 minutes, 56% risk (5/9) for 6 to 9 minutes, 88% risk (21/25) for 10 to 25 minutes, 100% risk (4/4) for greater than 25 minutes. None of 20 children receiving greater than 25 minutes of cardiopulmonary resuscitation escaped death or severe neurologic impairment. Our rates for saving all victims, particularly victims in cardiopulmonary arrest, are considerably higher than has been reported before the children. Prompt prehospital advanced cardiac life support is the most effective means of medical intervention for the pediatric submersion victim. Prehospital information provided the most valuable predictors of outcome.


Patterns of physical activity among 11 to 16 year old British children.
To examine the patterns of physical activity among British schoolchildren aged 11 to 16 and to assess whether the children experience the intensity and duration of physical activity that are believed to stress the cardiopulmonary system appropriately. Cross sectional study of a sample of children drawn from a larger survey of coronary risk factors in children. Continuous monitoring of heart rate for 12 hour periods on three school days and one Saturday. Two communities in Devon. 266 Children (163 girls, 103 boys) aged 11 to 16 randomly selected from a sample of 707 children. Percentage of time and number of sustained periods in which heart rate was greater than 139 beats/min. Anthropometric measures and external assessment of sexual maturity with Tanner's indices. The boys had heart rates greater than 139 beats/min for a significantly higher percentage of time than the girls (p less than 0.01) during the weekday (6.2% v 4.3%) and the Saturday (5.6% v 2.6%). The boys had significantly more five and 10 minute periods with heart rates greater than 139 beats/min than the girls during the Saturday and weekdays and more 20 minute periods during the weekdays. 84 Girls and 37 boys had no 10 minute period with a heart rate greater than 139 beats/min during the three weekdays and 112 girls and 65 boys had no such 10 minute period during the Saturday. No significant relation was detected in either sex between the amount or habitual physical activity (heart rate) and skinfold thickness or maturity group. British children have surprisingly low levels of habitual physical activity, and many children seldom undertake the volume of physical activity believed to benefit the cardiopulmonary system. Boys are more active than girls. The pubertal stage of development or body fatness, or both, do not seem to be sensitive indicators of physical activity in either girls or boys.


The role of subgaleal suction drain placement in chronic subdural hematoma evacuation.
There is lack of uniformity about the preferred surgical treatment, role of drain, and type of drain among various surgeons in chronic subdural hematoma (CSDH). The present study is aimed to evaluate role of subgaleal drain. This was a prospective study of 260 patients of CSDH treated surgically. Burr-hole irrigation with and without suction drain was done in 140 and 120 patients, respectively. Out of 120 patients without suction drain 60 each were managed by single and two burr holes. Pre- and postoperative GCS was recorded. Recurrent hematomas, CSDH secondary to tumor, due to intracranial hypotension, coagulopathy, children below 18 years, and patients treated by twist drill craniostomy or craniotomy were excluded. Subgaleal closed-system drainage with low negative pressure was used. Age of the patients ranged from 18 to 75 years with mean age of 57 years. There were 9, 47, 204 patients in GCS of 3-8, 9-12, and 13-15, respectively. Both the groups were comparable in terms of age, etiology, gender, and neurological status. There was no difference in the mortality in both the group. The recurrence and postoperative pneumocephalus was significantly less in suction drain group as compared to without drain group. There was no infection or any other complication related to suction drainage. Subgaleal closed suction drainage was safe, simple, and effective in the management of CSDH. Recurrence rate was low in the suction drain group.


Adolescent exposure to food advertising on television.
Television viewing is hypothesized to contribute to obesity among children and adolescents through several mechanisms that include the displacement of physical activity, snacking while watching TV, and the influence of food advertising. This study drew on television ratings to examine the distribution of food advertising exposure among adolescents aged 12 through 17 based on 170 top-rated shows across network, cable and syndicated TV stations over the 9-month period from September 2003 to May 2004. A total of 238,353 30-second equivalent advertisements on the top-rated shows were assessed. Each advertisement was weighted by its rating to measure actual exposure to advertisements. The results showed that among total nonprogram content time, food-related products accounted for roughly one fifth of advertising exposure. Excluding TV promotions and public service announcements, as a proportion of all product advertising, total food-related advertising made up 26% of advertised products viewed by adolescents. By race, the proportion of advertising exposure to food products was 14% greater for African-American versus white adolescents and total exposure to food advertising would be even larger for African-American teens given that, on average, they watched more TV. Fast food was the most frequently viewed food product category comprising 23% of all food-related advertisements among adolescents. Food ads made up just over one quarter of TV ads viewed by adolescents with the most commonly viewed products of fast food, sweets, and beverage products well within the reach of their own purchasing power.


Identifying gaps in the continuum of care for cardiovascular disease and diabetes in two communities in South Africa: Baseline findings from the HealthRise project.
The HealthRise initiative seeks to implement and evaluate innovative community-based strategies for diabetes, hypertension and hypercholesterolemia along the entire continuum of care (CoC)-from awareness and diagnosis, through treatment and control. In this study, we present baseline findings from HealthRise South Africa, identifying gaps in the CoC, as well as key barriers to care for non-communicable diseases (NCDs). This mixed-methods needs assessment utilized national household data, health facility surveys, focus group discussions, and key informant interviews in Umgungundlovu and Pixley ka Seme districts. Risk factor and disease prevalence were estimated from the South Africa National Health and Nutrition Examination Survey. Health facility surveys were conducted at 86 facilities, focusing on essential intervention, medications and standard treatment guidelines. Quantitative results are presented descriptively, and qualitative data was analyzed using a framework approach. 46.8% of the population in Umgungundlovu and 51.0% in Pixley ka Seme were hypertensive. Diabetes was present in 11.0% and 9.7% of the population in Umgungundlovu and Pixley ka Seme. Hypercholesterolemia was more common in Pixley ka Seme (17.3% vs. 11.1%). Women and those of Indian descent were more likely to have diabetes. More than half of the population was found to be overweight, and binge drinking, inactivity and smoking were all common. More than half of patients with hypertension were unaware of their disease status (51.6% in Pixley ka Seme and 51.3% in Umgungundlovu), while the largest gap in the diabetes CoC occurred between initiation of treatment and achieving disease control. Demand-side barriers included lack of transportation, concerns about confidentiality, perceived discrimination and long wait times. Supply-side barriers included limited availability of testing equipment, inadequate staffing, and pharmaceutical stock outs. In this baseline assessment of two South African health districts we found high rates of undiagnosed hypercholesterolemia and hypertension, and poor control of hypercholesterolemia, hypertension, and diabetes. The HealthRise Initiative will need to address key supply- and demand-side barriers in an effort to improve important NCD outcomes.


Possible mechanisms of switching in symmetrical two-ports based on 2D photonic crystals with magneto-optical resonators.
We analyze possible mechanisms of switching in two-ports based on 2D photonic crystals (PhCs) with a magneto-optical resonator. The input and output waveguides can be side or front coupled with the resonator. The resonator operates with a dipole mode. In the switch with front coupling in the nonmagnetic state the standing dipole mode provides equal nonzero wave amplitudes in the input and output waveguides and therefore transmission of the signal from the input to output waveguides. This is the state on. The applied magnetic field normal to the plane of the PhC rotates the standing dipole mode by 90° setting the nodes in the input and output waveguides. This corresponds to the state off. On the contrary, in the switch with side coupling and nonmagnetized resonator, the standing dipole mode excited by a wave in the input waveguide has its node in the output waveguide. Therefore, the signal is reflected from the input port. This corresponds to the state off of the switch. Magnetization by a DC magnetic field produces a rotating dipole pattern in the cavity. Due to this rotating, the mode signal passes from the input port to the output one and this is the state on.


Comparative cephalometric errors for orthodontic and surgical patients.
The aim of this study was to quantify and compare the reproducibility (intraexaminer method error) of cephalometric measurements in two groups of adult patients: one group with minor skeletal disharmonies and the other with severe skeletal disharmonies. It was hypothesized that errors were greater for subjects displaying severe morphologic deviations. The samples comprised two groups: 30 pretreatment cephalograms of patients planned for comprehensive orthodontic treatment and 30 cephalograms of patients additionally planned for orthognathic surgery. Two reference points and 28 cephalometric landmarks were defined and digitized by one examiner on two occasions 1 week apart. In total, 30 angles and 9 distances were studied. Reproducibility was expressed as the angular or linear differences between the two series of recordings. Two sample t tests were performed. In general, no significant differences in landmark location and measurement were found between the orthodontic and surgical patient groups. It was concluded that extreme variations in skeletal morphology do not effect the accuracy of cephalometric evaluation.