Probiotics for prevention of necrotizing enterocolitis in preterm infants.
Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth.


Prematch salivary secretory immunoglobulin a in soccer players from the 2014 World Cup qualifying campaign.
To monitor resting salivary secretory immunoglobulin A (SIgA) levels in international soccer players during the short-term training period that precedes international match play. In a repeated-measure design, saliva samples were obtained from 13 outfield soccer players who participated in the training camps preceding 7 games (5 home and 2 away) of the 2014 FIFA World Cup qualifying campaign. Samples were obtained daily for 4 d preceding each game (and analyzed for SIgA using the IPRO oral-fluid-collection system) at match day minus 1 (MD-1), minus 2 (MD-2), minus 3 (MD-3), and minus 4 (MD-4). SIgA displayed a progressive decline (P = .01) during the 4-d training period (MD-4, 365 ± 127 μg/mL; MD-3, 348 ± 154 μg/mL; MD-2, 290 ± 138 μg/mL; MD-1, 256 ± 90 μg/mL) such that MD-1 values were significantly lower (P = .01) than both MD-4 and MD-3. The 95% confidence intervals for the differences between MD-1 and MD-4 were -191 to -26 and between MD-1 and MD-3 were -155 to -28. Data demonstrate that a short-term soccer-training camp in preparation for international competition induces detectable perturbations to mucosal immunity. Future studies should monitor SIgA (as a practical and noninvasive measure of immunity) alongside internal and external measures of training load in an attempt to strategically individualize training and nutritional strategies that may support optimal preparation for high-level competition.


Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and glycolytic mechanisms.
Pancreatic islets of Langerhans display complex intracellular calcium changes in response to glucose that include fast (seconds), slow ( approximately 5 min), and mixed fast/slow oscillations; the slow and mixed oscillations are likely responsible for the pulses of plasma insulin observed in vivo. To better understand the mechanisms underlying these diverse patterns, we systematically analyzed the effects of glucose on period, amplitude, and plateau fraction (the fraction of time spent in the active phase) of the various regimes of calcium oscillations. We found that in both fast and slow islets, increasing glucose had limited effects on amplitude and period, but increased plateau fraction. In some islets, however, glucose caused a major shift in the amplitude and period of oscillations, which we attribute to a conversion between ionic and glycolytic modes (i.e., regime change). Raising glucose increased the plateau fraction equally in fast, slow, and regime-changing islets. A mathematical model of the pancreatic islet consisting of an ionic subsystem interacting with a slower metabolic oscillatory subsystem can account for these complex islet calcium oscillations by modifying the relative contributions of oscillatory metabolism and oscillatory ionic mechanisms to electrical activity, with coupling occurring via K(ATP) channels.


In vivo time-dependent gene expression of cationic lipid-based emulsion as a stable and biocompatible non-viral gene carrier.
To make stable and biocompatible non-viral gene carriers for therapeutic gene therapy, we developed a cationic lipid-based emulsion (CLE) prepared by an oil-in-water (O/W) emulsion method, wherein squalene oil was used as an oil core and the cationic lipid, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP), was employed as an emulsifier. To evaluate in vivo characteristics such as toxicity and time-dependent gene expression, a bioluminescence reporter gene in pCMV-luc plasmid DNA was simply mixed with CLE in aqueous condition, resulting in a CLE/DNA complex. The CLE/DNA complex was optimized to form a compact and stable nano-sized particle by adding different amounts of plasmid DNA, and an optimal cationic lipid-to-DNA (C/D) weight ratio of 4 was identified. Freshly prepared CLE/DNA complex, with a C/D of 4, showed a high transfection efficiency and minimal cytotoxicity in vitro, compared to controls of a liposome (DOTAP)/DNA complex and a branched poly(ethyleneimine) (Mw=25 kDa) (bPEI)/DNA complex, respectively. The in vivo characteristics of the CLE/DNA complex were evaluated after intravenous injection into Balb/c mice. Time-dependent gene expression data in vivo were obtained using a non-invasive, whole animal bioluminescence imaging system. These data showed that the CLE/DNA complex offered prolonged high-level gene expression for 1 week, particularly in the liver and spleen. On the other hand, the controls of DOTAP/DNA complex and bPEI/DNA complex showed a relatively lower gene expression, because of the unstable and toxic properties of the control carriers. Our in vivo gene expression data demonstrate the potential of the CLE/DNA complex as a non-viral gene carrier for in vivo gene delivery.


Direct costs of inequalities in health care utilization in Germany 1994 to 2009: a top-down projection.
Social inequalities in health are a characteristic of almost all European Welfare States. It has been estimated, that this is associated with annual costs that amount to approximately 9% of total member state GDP. We investigated the influence of inequalities in German health care utilization on direct medical costs. We used longitudinal data from a representative panel study (German Socio-Economic Panel Study) covering 1994 to 2010. The sample consisted of respondents aged 18 years or older. We used additional data from the German Health Interview and Examination Survey for Children and Adolescents, conducted between 2003 and 2006, to report utilization for male and female participants aged from 0 to 17 years. We analyzed inequalities in health care using negative binomial regression models and top-down cost estimates. Men in the lowest income group (less than 60% of median income) had a 1.3-fold (95% CI: 1.2-1.4) increased number of doctor visits and a 2.2-fold (95% CI: 1.9-2.6) increased number of hospital days per year, when compared with the highest income group; the corresponding differences were 1.1 (95% CI: 1.0-1.1) and 1.3 (95% CI: 1.2-1.5) for women. Depending on the underlying scenario used, direct costs for health care due to health inequalities were increased by approximately 2 billion to 25 billion euros per year. The best case scenario (the whole population is as healthy and uses an equivalent amount of resources as the well-off) would have hypothetically reduced the costs of health care by 16 to 25 billion euros per year. Our findings indicate that inequalities and inequities in health care utilization exist in Germany, with respect to income position, and are associated with considerable direct costs. Additional research is needed to analyze the indirect costs of health inequalities and to replicate the current findings using different methodologies.


Level and determinants of county health system technical efficiency in Kenya: two stage data envelopment analysis.
Improving health system efficiency is a key strategy to increase health system performance and accelerate progress towards Universal Health Coverage. In 2013, Kenya transitioned into a devolved system of government granting county governments autonomy over budgets and priorities. We assessed the level and determinants of technical efficiency of the 47 county health systems in Kenya. We carried out a two-stage data envelopment analysis (DEA) using Simar and Wilson's double bootstrap method using data from all the 47 counties in Kenya. In the first stage, we derived the bootstrapped DEA scores using an output orientation. We used three input variables (Public county health expenditure, Private county health expenditure, number of healthcare facilities), and one outcome variable (Disability Adjusted Life Years) using 2018 data. In the second stage, the bias corrected technical inefficiency scores were regressed against 14 exogenous factors using a bootstrapped truncated regression. The mean bias-corrected technical efficiency score of the 47 counties was 69.72% (95% CI 66.41-73.01%), indicating that on average, county health systems could increase their outputs by 30.28% at the same level of inputs. County technical efficiency scores ranged from 42.69% (95% CI 38.11-45.26%) to 91.99% (95% CI 83.78-98.95%). Higher HIV prevalence was associated with greater technical inefficiency of county health systems, while higher population density, county absorption of development budgets, and quality of care provided by healthcare facilities were associated with lower county health system inefficiency. The findings from this analysis highlight the need for county health departments to consider ways to improve the efficiency of county health systems. Approaches could include prioritizing resources to interventions that will reduce high chronic disease burden, filling structural quality gaps, implementing interventions to improve process quality, identifying the challenges to absorption rates and reforming public finance management systems to enhance their efficiency.


Identification and Antimicrobial Resistance of Bacteria Isolated from Probiotic Products Used in Shrimp Culture.
Probiotics are increasingly used in aquaculture to control diseases and improve feed digestion and pond water quality; however, little is known about the antimicrobial resistance properties of such probiotic bacteria and to what extent they may contribute to the development of bacterial resistance in aquaculture ponds. Concerns have been raised that the declared information on probiotic product labels are incorrect and information on bacterial composition are often missing. We therefore evaluated seven probiotics commonly used in Vietnamese shrimp culture for their bacterial species content, phenotypic antimicrobial resistance and associated transferable resistance genes. The bacterial species was established by 16S rRNA sequence analysis of 125 representative bacterial isolates. MIC testing was done for a range of antimicrobials and whole genome sequencing of six multiple antimicrobial resistant Bacillus spp. used to identify resistance genes and genetic elements associated with horizontal gene transfer. Thirteen bacterial species declared on the probiotic products could not be identified and 11 non-declared Bacillus spp. were identified. Although our culture-based isolation and identification may have missed a few bacterial species present in the tested products this would represent minor bias, but future studies may apply culture independent identification methods like pyro sequencing. Only 6/60 isolates were resistant to more than four antimicrobials and whole genome sequencing showed that they contained macrolide (ermD), tetracycline (tetL), phenicol (fexA) and trimethoprim (dfrD, dfrG and dfrK) resistance genes, but not known structures associated with horizontal gene transfer. Probiotic bacterial strains used in Vietnamese shrimp culture seem to contribute with very limited types and numbers of resistance genes compared to the naturally occurring bacterial species in aquaculture environments. Approval procedures of probiotic products must be strengthened through scientific-based efficacy trials and product labels should allow identification of individual bacterial strains and inform the farmer on specific purpose, dosage and correct application measures.


[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma].
In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology. Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied. The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices. The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.


Combining motion analysis and microfluidics--a novel approach for detecting whole-animal responses to test substances.
Small, early life stages, such as zebrafish embryos are increasingly used to assess the biological effects of chemical compounds in vivo. However, behavioural screens of such organisms are challenging in terms of both data collection (culture techniques, drug delivery and imaging) and data evaluation (very large data sets), restricting the use of high throughput systems compared to in vitro assays. Here, we combine the use of a microfluidic flow-through culture system, or BioWell plate, with a novel motion analysis technique, (sparse optic flow - SOF) followed by spectral analysis (discrete Fourier transformation - DFT), as a first step towards automating data extraction and analysis for such screenings. Replicate zebrafish embryos housed in a BioWell plate within a custom-built imaging system were subject to a chemical exposure (1.5% ethanol). Embryo movement was videoed before (30 min), during (60 min) and after (60 min) exposure and SOF was then used to extract data on movement (angles of rotation and angular changes to the centre of mass of embryos). DFT was subsequently used to quantify the movement patterns exhibited during these periods and Multidimensional Scaling and ANOSIM were used to test for differences. Motion analysis revealed that zebrafish had significantly altered movements during both the second half of the alcohol exposure period and also the second half of the recovery period compared to their pre-treatment movements. Manual quantification of tail flicking revealed the same differences between exposure-periods as detected using the automated approach. However, the automated approach also incorporates other movements visible in the organism such as blood flow and heart beat, and has greater power to discern environmentally-driven changes in the behaviour and physiology of organisms. We suggest that combining these technologies could provide a highly efficient, high throughput assay, for assessing whole embryo responses to various drugs and chemicals.


THE RELATION BETWEEN THE THYROID AND PARATHYROID GLANDS.
The following conclusions may be drawn from the experiments presented in this article. 1. Excessive meat diet develops hypertrophy of the thyroid gland. A definite hypertrophy of the parathyroid gland under the same conditions has not been established. A meat diet does not develop hypertrophy of the thyroid gland when insufficiency of the parathyroid gland exists at the same time, even if no clinical symptoms are present. Where a pronounced hypertrophy caused by a meat diet has already developed, the hypertrophy disappears and the gland assumes its ordinary appearance after extirpation of a sufficiently large number of parathyroid glands. 2. After parathyroidectomy no hypertrophy of the thyroid gland takes place. In chronic tetany the thyroid gland seems, on the contrary, to atrophy in spite of a meat diet. 3. After complete extirpation of the thyroid gland, the parathyroid gland does not change its structure, even in cases where the cachexia lasts for several years. Small remaining parts of the thyroid gland may through hypertrophy develop into compact tissue and thereby seemingly present some points of resemblance to the parathyroid gland. 4. When the parathyroid gland hypertrophies, as in some forms of chronic tetany, this hypertrophy is characterized by the development of large, transparent, sharply defined cells, with large nuclei rich in chromatin. 5. The parathyroid and thyroid glands are independent organs, each having specific functions. This, however, does not exclude the occurrence of a direct or indirect interaction in the functions of the two systems. 6. There is reason to believe that an insufficiency of the parathyroid gland checks to some extent the function of the thyroid gland. No proof of the existence of a vicarious cooperation between the two glands has been established.


Surface markers of human embryonic stem cells: a meta analysis of membrane proteomics reports.
Human embryonic stem cells (hESCs) have unique biological features and attributes that make them attractive in various areas of biomedical research. With heightened applications, there is an ever increasing need for advancement of proteome analysis. Membrane proteins are one of the most important subset of hESC proteins as they can be used as surface markers. Areas covered: This review discusses commonly used surface markers of hESCs, and provides in-depth analysis of available hESC membrane proteome reports and the existence of these markers in many other cell types, especially cancer cells. Appreciating, existing ambiguity in the definition of a membrane protein, we have attempted a meta analysis of the published membrane protein reports of hESCs by using a combination of protein databases and prediction tools to find the most confident plasma membrane proteins in hESCs. Furthermore, responsiveness of plasma membrane proteins to differentiation has been discussed based on available transcriptome profiling data bank. Expert commentary: Combined transcriptome and membrane proteome analysis highlighted additional proteins that may eventually find utility as new cell surface markers.


Actinidia callosa peel (kiwi fruit) ethanol extracts protected neural cells apoptosis induced by methylglyoxal through Nrf2 activation.
Methylglyoxal (MG) is a reactive dicarbonyl compound generated as an intermediate of glycolysis during the physical glycation in the diabetic condition. MG itself has been commonly implicated in the development of diabetic neuropathy. Several active compounds in Actinidia callosa have been found to inhibit glycation and MG-protein reaction. This study investigated the protective effects of A. callosa (kiwi fruits) peel ethanol extracts (ACE) on MG-induced Neuro-2A cell apoptosis. The Neuro-2A cells pre-treated by ACE (50-200 μg/mL) or allyl-isothiocyanate (AITC) (50 μM) for 6 h, in turn, the cells were treated with MG (250 μM) for 24 h. ACE or AITC treatment markedly inhibited the generation of reactive oxygen species (ROS) and the elevation of caspase-3 and capase-9 levels induced by MG in Neuro-2A cells. ACE and AITC elevated Bcl2 and inhibited Bax expressions in MG-induced Neuro-2A cells. ACE elevated Nrf2 transcriptional activity and nuclear translocation in MG-induced Neuro-2A cells. Nrf2 down-stream molecules including HO-1 and GCL were elevated by ACE or AITC treatment in MG-induced Neuro-2A cells. The protective effects of ACE on MG-induced Neuro-2A apoptosis were attenuated while Nrf2 knockdown. We established the first evidence that ACE might contribute to the prevention of the development of diabetic neuropathy by blocking the MG-mediated intracellular glycation system.


STX2171, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, is efficacious in vivo in a novel hormone-dependent prostate cancer model.
17β-Hydroxysteroid dehydrogenases (17β-HSDs) catalyse the 17-position reduction/oxidation of steroids. 17β-HSD type 3 (17β-HSD3) catalyses the reduction of the weakly androgenic androstenedione (adione) to testosterone, suggesting that specific inhibitors of 17β-HSD3 may have a role in the treatment of hormone-dependent prostate cancer and benign prostate hyperplasia. STX2171 is a novel selective non-steroidal 17β-HSD3 inhibitor with an IC(50) of ∼200 nM in a whole-cell assay. It inhibits adione-stimulated proliferation of 17β-HSD3-expressing androgen receptor-positive LNCaP(HSD3) prostate cancer cells in vitro. An androgen-stimulated LNCaP(HSD3) xenograft proof-of-concept model was developed to study the efficacies of STX2171 and a more established 17β-HSD3 inhibitor, STX1383 (SCH-451659, Schering-Plough), in vivo. Castrated male MF-1 mice were inoculated s.c. with 1×10(7) cells 24 h after an initial daily dose of testosterone propionate (TP) or vehicle. After 4 weeks, tumours had not developed in vehicle-dosed mice, but were present in 50% of those mice given TP. One week after switching the stimulus to adione, mice were dosed additionally with the vehicle or inhibitor for a further 4 weeks. Both TP and adione efficiently stimulated tumour growth and increased plasma testosterone levels; however, in the presence of either 17β-HSD3 inhibitor, adione-dependent tumour growth was significantly inhibited and plasma testosterone levels reduced. Mouse body weights were unaffected. Both inhibitors also significantly lowered plasma testosterone levels in intact mice. In conclusion, STX2171 and STX1383 significantly lower plasma testosterone levels and inhibit androgen-dependent tumour growth in vivo, indicating that 17β-HSD3 inhibitors may have application in the treatment of hormone-dependent prostate cancer.


Nonlinear bouncing of nonlocal spatial solitons at the boundaries.
We investigate, both experimentally and theoretically, the interaction of (2D+1) spatial solitons with the boundaries of a nonlinear medium in the presence of nonlocality. We demonstrate power-dependent nonlinear repulsion at the boundaries, in quantitative agreement with the model predictions.


Rapid turnover of functional sequence in human and other genomes.
The amount of a genome's sequence that is functional has been surprisingly difficult to estimate accurately. This has severely hindered analyses asking whether the amount of functional genomic sequence correlates with organismal complexity. Most studies estimate these amounts by considering nucleotide substitution rates within aligned sequences. These approaches show reduced power to identify sequence that is aligned, functional, and constrained only within narrowly defined phyla. The neutral indel model exploits insertions or deletions (indels) rather than substitutions in predicting functional sequence. Surprisingly, this method indicates that half of all functional sequence is specific to individual eutherian lineages. This review considers the rates at which coding or noncoding and functional or nonfunctional sequence changes among mammalian genomes. In contrast to the slow rate at which protein-coding sequence changes, functional noncoding sequence appears to change or be turned over at rapid rates in mammals.


Moire fringes by evolute gratings.
Analytical expressions describing the moire fringes formed by two periodic structures consisting of the evolutes of a circle are derived. The circular and radial moire patterns can be formed by contact and noncontact superimposition of the structures. In the latter case the self-imaging phenomenon is used. Experimental verification and proposals for use are given.


Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin.
Survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) family that inhibits caspases and blocks cell death is highly expressed in cancer and is associated with a poorer clinical outcome. Functioning simultaneously during cell division and apoptosis inhibition, survivin plays a pivotal role in determining cell survival. Survivin has consistently been identified by molecular profiling analysis to be associated with higher tumor grade, more advanced disease, abbreviated survival, accelerated rates of recurrence, and chemotherapy and radiation resistance. Survivin's differential expression in cancer compared to normal tissue and its role as a nodal protein in a number of cellular pathways make it a highly flexible therapeutic target, suitable for small-molecule inhibitiors, molecular antagonists, and vaccination-based therapies. By targeting survivin it is hoped that multiple tumor signaling circuitries may be simultaneously disabled. This effect may be applicable to many tumor histologies irrespective of specific genetic makeup. To date, survivin inhibitors have shown modest activity as single agents, but it is anticipated that when given in combination with cytotoxic chemotherapy or monoclonal antibodies they may exhibit enhanced efficacy. This review discusses the complex circuitry of survivin in human cancers and highlights clinical trials involving novel agents that target this important protein.


Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.
Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.


Spectrin promotes the association of F-actin with the cytoplasmic surface of the human erythrocyte membrane.
We studied the binding of actin to the erythrocyte membrane by a novel application of falling ball viscometry. Our approach is based on the notion that if membranes have multiple binding sites for F-actin they will be able to cross-link and increase the viscosity of actin. Spectrin- and actin-depleted inside-out vesicles reconstituted with purified spectrin dimer or tetramer induce large increases in the viscosity of actin. Comparable concentrations of spectrin alone, inside-out vesicles alone, inside-out vesicles plus heat-denatured spectrin dimmer or tetramer induce large increases in the viscosity of actin. Comparable concentrations of spectrin alone, inside-out vesicles alone, inside-out plus heat denatured spectrin, ghosts, or ghosts plus spectrin have no effect on the viscosity of actin. Centrifugation experiments show that the amount of actin bound to the inside-out vesicles is enhanced in the presence of spectrin. The interactions detected by low-shear viscometry reflect actin interaction with membrane- bound spectrin because (a) prior removal of band 4.1 and ankyrin (band 2.1, the high- affinity membrane attachment site for spectrin) reduces both spectrin binding to the inside-out vesicles and their capacity to stimulate increase in viscosity of actin in the presence of spectrin + actin are inhibited by the addition of the water-soluble 72,000- dalton fragment of ankyrin, which is known to inhibit spectrin reassociation to the membrane. The increases in viscosity of actin induced by inside-out vesicles reconstituted with purified spectrin dimer or tetramer are not observed when samples are incubated at 0 degrees C. This temperature dependence may be related to the temperature-dependent associations we observe in solution studies with purified proteins: addition of ankyrin inhibits actin cross-linking by spectrin tetramer plus band 4.1 at 0 degrees C, and enhances it at 32 degrees C. We conclude (a) that falling ball viscometry can be used to assay actin binding to membranes and (b) that spectrin is involved in attaching actin filaments or oligomers to the cytoplasmic surface of the erythrocyte membrane.


Intraocular pressure homeostasis: maintaining balance in a high-pressure environment.
Although glaucoma is a relatively common blinding disease, most people do not develop glaucoma. A robust intraocular pressure (IOP) homeostatic mechanism keeps ocular pressures within relatively narrow acceptable bounds throughout most peoples' lives. The trabecular meshwork and/or Schlemm's canal inner wall cells respond to sustained IOP elevation and adjust the aqueous humor outflow resistance to restore IOP to acceptable levels. It appears that the cells sense IOP elevations as mechanical stretch or distortion of the actual outflow resistance and respond by initiating a complex extracellular matrix (ECM) turnover process that takes several days to complete. Although considerable information pertinent to this process is available, many aspects of the IOP homeostatic process remain to be elucidated. Components and mechanisms beyond ECM turnover could also be relevant to IOP homeostasis, but will not be addressed in detail here. Known aspects of the IOP homeostasis process as well as possible ways that it might function and impact glaucoma are discussed.


Factors influencing ambulatory care education in the U.S. Department of Veterans Affairs.
The Department of Veterans Affairs (VA) is undergoing change in the way it delivers health care. Forces underlying this change include demographics of its population, new fiscal constraints, and the requirements of its academic affiliates. The benefit to the medical school affiliates will be the availability of patients in a structure useful for outpatient teaching of medical students and houseofficers. Barriers to effective delivery of ambulatory health care and education in VA facilities are (1) the historic focus on episodic, inpatient care, (2) continuous changes in eligibility requirements, (3) increases in patient care responsibilities for affiliated faculty, and (4) concomitant withdrawal of resources from the VA at a time when costs of health care and education are increasing. The VA medical centers will be increasingly forced to investigate innovative models for patient care delivery and education in the ambulatory setting.


Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.
An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.


Calgary Shunt Protocol, an adaptation of the Hydrocephalus Clinical Research Network shunt protocol, reduces shunt infections in children.
OBJECTIVEThe shunt protocol developed by the Hydrocephalus Clinical Research Network (HCRN) was shown to significantly reduce shunt infections in children. However, its effectiveness had not been validated in a non-HCRN, small- to medium-volume pediatric neurosurgery center. The present study evaluated whether the 9-step Calgary Shunt Protocol, closely adapted from the HCRN shunt protocol, reduced shunt infections in children.METHODSThe Calgary Shunt Protocol was prospectively applied at Alberta Children's Hospital from May 23, 2013, to all children undergoing any shunt procedure. The control cohort consisted of children undergoing shunt surgery between January 1, 2009, and the implementation of the Calgary Shunt Protocol. The primary outcome was the strict HCRN definition of shunt infection. Univariate analyses of the protocol, individual elements within, and known confounders were performed using Student t-test for measured variables and chi-square tests for categorical variables. Multivariable logistic regression was performed using stepwise analysis.RESULTSTwo-hundred sixty-eight shunt procedures were performed. The median age of patients was 14 months (IQR 3-61), and 148 (55.2%) were male. There was a significant absolute risk reduction of 10.0% (95% CI 3.9%-15.9%) in shunt infections (12.7% vs 2.7%, p = 0.004) after implementation of the Calgary Shunt Protocol. In univariate analyses, chlorhexidine was associated with fewer shunt infections than iodine-based skin preparation solution (4.1% vs 12.3%, p = 0.02). Waiting ≥ 20 minutes between receiving preoperative antibiotics and skin incision was also associated with a reduction in shunt infection (4.5% vs 14.2%, p = 0.007). In the multivariable analysis, only the overall protocol independently reduced shunt infections (OR 0.19 [95% CI 0.06-0.67], p = 0.009), while age, etiology, procedure type, ventricular catheter type, skin preparation solution, and time from preoperative antibiotics to skin incision were not significant.CONCLUSIONSThis study externally validates the published HCRN protocol for reducing shunt infection in an independent, non-HCRN, and small- to medium-volume pediatric neurosurgery setting. Implementation of the Calgary Shunt Protocol independently reduced shunt infection risk. Chlorhexidine skin preparation and waiting ≥ 20 minutes between administration of preoperative antibiotic and skin incision may have contributed to the protocol's quality improvement success.


Genome Sequence Resource for Ilyonectria mors-panacis, Causing Rusty Root Rot of Panax notoginseng.
Ilyonectria mors-panacis is the cause of a serious disease hampering the production of Panax notoginseng, an important Chinese medicinal herb, widely used for its anti-inflammatory, antifatigue, hepato-protective, and coronary heart disease prevention effects. Here, we report the first Illumina-Pacbio hybrid sequenced draft genome assembly of I. mors-panacis strain G3B and its annotation. The availability of this genome sequence not only represents an important tool toward understanding the genetics behind the infection mechanism of I. mors-panacis strain G3B but also will help illuminate the complexities of the taxonomy of this species.


Anderson localization of light in PT-symmetric optical lattices.
Anderson localization (AL) of light is investigated numerically in a disordered parity-time (PT)-symmetric potential, in the form of an optical lattice. The lattice is recorded in a nonlinear medium with Kerr nonlinearity. We demonstrate enhancement of light localization in a PT-symmetric lattice, as compared to the localization in the corresponding real lattice. The effect of strength of the gain-loss component in the PT lattice on various regimes of AL is also discussed. It is found that the localization exists and is further enhanced above the threshold strength of the imaginary part of the potential. The influence of nonlinearity and disorder level on the transverse localization of light in such a complex-valued potential is addressed.


pH-dependent reduction potentials and proton-coupled electron transfer mechanisms in hydrogen-producing nickel molecular electrocatalysts.
The nickel-based P2(Ph)N2(Bn) electrocatalysts comprised of a nickel atom and two 1,5-dibenzyl-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane ligands catalyze H2 production in acetonitrile. Recent electrochemical experiments revealed a linear dependence of the Ni(II/I) reduction potential on pH with a slope of 57 mV/pH unit, implicating a proton-coupled electron transfer (PCET) process with the same number of electrons and protons transferred. The combined theoretical and experimental studies herein provide an explanation for this pH dependence in the context of the overall proposed catalytic mechanism. In the proposed mechanisms, the catalytic cycle begins with a series of intermolecular proton transfers from an acid to the pendant amine ligand and electrochemical electron transfers to the nickel center to produce the doubly protonated Ni(0) species, a precursor to H2 evolution. The calculated Ni(II/I) reduction potentials of the doubly protonated species are in excellent agreement with the experimentally observed reduction potential in the presence of strong acid, suggesting that the catalytically active species leading to the peak observed in these cyclic voltammetry (CV) experiments is doubly protonated. The Ni(I/0) reduction potential was found to be slightly more positive than the Ni(II/I) reduction potential, indicating that the Ni(I/0) reduction occurs spontaneously after the Ni(II/I) reduction, as implied by the experimental observation of a single CV peak. These results suggest that the PCET process observed in the CV experiments is a two-electron/two-proton process corresponding to an initial double protonation followed by two reductions. On the basis of the experimental and theoretical data, the complete thermodynamic scheme and the Pourbaix diagram were generated for this catalyst. The Pourbaix diagram, which identifies the most thermodynamically stable species at each reduction potential and pH value, illustrates that this catalyst undergoes different types of PCET processes for various pH ranges. These thermodynamic insights will aid in the design of more effective molecular catalysts for H2 production.


Effect of lengthening rate on angiogenesis during distraction osteogenesis.
This study investigated the angiogenic response to four varying rates (0.3, 0.7, 1.3, and 2.7 mm/day) of distraction in a rabbit model of leg-lengthening. Immunostaining was performed with use of specific antibodies to type-IV collagen and endothelial cell antigen to examine semiquantitatively the presence of blood vessels in the developing tissues. With use of the Chalkley counting method, the greatest number of positive-staining blood vessel cells was found in the central fibrous zone of the groups that underwent lengthening at 0.7 and 1.3 mm/day compared with any other zone in any group (p < 0.05, t test). There were no statistical differences in the positive labeling indices in the mineralization front and the new bone zone adjacent to the mineralization front in any of the groups. However, the decrease in the number of positive-staining blood vessel cells in the new bone zone distant to the mineralization front compared with any other zone in any group was statistically significant. The results suggest that during distraction osteogenesis, the precursor cells of new capillaries were present in abundance within the fibrous interzone. These cells connected into the capillary network at the junction of the mineralization front and the fibrous zone. The angiogenic response was weaker in the more mature regions within the new bone zones. A slow rate of distraction (0.3 mm/day) did not maximally stimulate angiogenesis in the central fibrous zone, whereas high rates (2.7 mm/day) appeared to impair this response. In this model of distraction osteogenesis, the vascularization process in the central fibrous zone was maximally stimulated at distraction rates of 0.7 and 1.3 mm/day.


Drive-through delivery: where are the "savings"?
Using a natural experiment, this study estimates the effects of Medicaid managed care on total hospital costs of a birth. The authors study 5,585 vaginal deliveries from 1993 through 1995. Hospital length of stay for maternity care has been reduced by 21 percent after the introduction of managed care. The resultant program saving, however, is $280 in total hospital cost per delivery, 12 percent of the total hospital costs before managed care. Furthermore, when the full costs of an earlier discharge, including costs to patients and their families, are taken into account, the savings associated with a shortened hospital stay may be even smaller.


Recording from two neurons: second-order stimulus reconstruction from spike trains and population coding.
We study the reconstruction of visual stimuli from spike trains, representing the reconstructed stimulus by a Volterra series up to second order. We illustrate this procedure in a prominent example of spiking neurons, recording simultaneously from the two H1 neurons located in the lobula plate of the fly Chrysomya megacephala. The fly views two types of stimuli, corresponding to rotational and translational displacements. Second-order reconstructions require the manipulation of potentially very large matrices, which obstructs the use of this approach when there are many neurons. We avoid the computation and inversion of these matrices using a convenient set of basis functions to expand our variables in. This requires approximating the spike train four-point functions by combinations of two-point functions similar to relations, which would be true for gaussian stochastic processes. In our test case, this approximation does not reduce the quality of the reconstruction. The overall contribution to stimulus reconstruction of the second-order kernels, measured by the mean squared error, is only about 5% of the first-order contribution. Yet at specific stimulus-dependent instants, the addition of second-order kernels represents up to 100% improvement, but only for rotational stimuli. We present a perturbative scheme to facilitate the application of our method to weakly correlated neurons.


The value of machine perfusion perfusate biomarkers for predicting kidney transplant outcome.
Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl-β-D-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) measured during kidney machine perfusion (MP) could have predictive value for posttransplant outcome. However, these data may be biased due to organ discard based on biomarker measurements, and previous analyses were not adjusted for likely confounding factors. No reliable prospective evidence has been available so far. Nevertheless, some centers already use these biomarkers to aid decisions on accepting or discarding a donor kidney. From 306 deceased-donor kidneys donated after brain death or controlled cardiac death and included in an international randomized controlled trial, these six biomarkers were measured in the MP perfusate. In this unselected prospective data set, we tested whether concentrations were associated with delayed graft function, primary nonfunction, and graft survival. Multivariate regression models investigated whether the biomarkers remained independent predictors when adjusted for relevant confounding factors. GST, NAG, and H-FABP were independent predictors of delayed graft function but not of primary nonfunction and graft survival. Lactate dehydrogenase, aspartate aminotransferase, and alanine-aminopeptidase had no independent prognostic potential for any of the endpoints. Perfusate biomarker concentrations had no relevant correlation with cold ischemic time or renal vascular resistance on the pump. Increased GST, NAG, or H-FABP concentrations during MP are an indication to adjust posttransplant recipient management. However, this study shows for the first time that perfusate biomarker measurements should not lead to kidney discard.


Comparative study of the dissociative ionization of 1,1,1-trichloroethane using nanosecond and femtosecond laser pulses.
Changes in the laser induced molecular dissociation of 1,1,1-trichloroethane (TCE) were studied using a range of intensities and standard laser wavelengths with nanosecond and femtosecond pulse durations. TCE contains C-H, C-C and C-Cl bonds and selective bond breakage of one or more of these bonds is of scientific interest. Using laser ionization time of flight mass spectrometry, it was found that considerable variation of fragment ion peak heights as well as changes in relative peak ratios is possible by varying the laser intensity (by attenuation), wavelength and pulse duration using standard laser sources. The nanosecond laser dissociation seems to occur via C-Cl bond breakage, with significant fragmentation and only a few large mass ion peaks observed. In contrast, femtosecond laser dissociative ionization results in many large mass ion peaks. Evidence is found for various competing dissociation and ionization pathways. Variation of the nanosecond laser intensity does not change the fragmentation pattern, while at high femtosecond intensities large changes are observed in relative ion peak sizes. The total ionization yield and fragmentation ratios are presented for a range of wavelengths and intensities, and compared to the changes observed due to a linear chirp variation.


The Relation of Childhood Maltreatment to Psychotic Symptoms in Adolescents and Young Adults With Depression.
This study examined the relation between a history of maltreatment and the presence of psychotic symptoms in a community sample of adolescents and young adults with major depressive disorder. One hundred and twenty-nine depressed adolescents and young adults (M = 16.02 years, 77% female, 92% White) were recruited through community advertisement and clinician referral. Clinical diagnoses and psychotic symptoms (i.e., hallucinations and delusions) were assessed using a structured diagnostic interview. Childhood maltreatment was assessed using a contextual interview and standardized rating system. Logistic regression analyses examined the relation between childhood maltreatment and psychotic symptoms. As hypothesized, individuals with psychotic symptoms were significantly more likely to report a history of severe sexual maltreatment than those without psychotic symptoms (Wald = 5.44, odds ratio = 3.86, p = .020), 95% confidence interval [1.24, 12.01]. Further, those with psychotic symptoms were more likely to report being the victims of more than one type of maltreatment than those without, χ2(2) = 6.66, p = .036 (ϕ = .23; 40% vs. 16%). Results held upon adjusting for overall level of depression symptoms. A history of severe sexual maltreatment is related to a severe presentation of major depressive disorder even in the initial onset of the syndrome in adolescence and young adulthood. These findings underscore the importance of early assessment of both depression and maltreatment history to implement interventions that have the potential to prevent the emergence of psychotic psychopathology in young people at risk.


Lung epithelial CCAAT/enhancer-binding protein-β is necessary for the integrity of inflammatory responses to cigarette smoke.
Cigarette smoke is the major cause of chronic obstructive pulmonary disease and lung cancer. The mechanisms by which smoking induces pulmonary dysfunction are complex, involving stress from toxic components and inflammatory responses. Although CCCAAT/enhancer-binding protein (C/EBP)-β is known as a key intracellular regulator of inflammatory signaling, its role in pulmonary inflammation has not been established. To characterize the role of C/EBPβ in the airway epithelial response to cigarette smoke. mRNA expression in the airway epithelium of current, former, and never-smokers, and in in vitro cigarette smoke extract-treated primary human airway epithelial cells, was analyzed by microarray and quantitative real-time polymerase chain reaction, respectively. Mice with lung epithelial-specific inactivation of C/EBPβ were generated and exposed to cigarette smoke for 4 or 11 days. Lung histology, bronchoalveolar lavage cell differentials, and expression of inflammatory and innate immune mediators in the lungs were assessed. C/EBPβ was significantly down-regulated in the airway epithelium of both current and former smokers compared with never-smokers, and in cigarette smoke-treated primary human airway epithelial cells in vitro. Cigarette smoke-exposed mice with a lung epithelial-specific inactivation of C/EBPβ displayed blunted respiratory neutrophil influx and compromised induction of neutrophil chemoattractants growth-regulated oncogene-α, macrophage inflammatory protein-1γ, granulocyte colony-stimulating factor, and serum amyloid A 3 and proinflammatory cytokines tumor necrosis factor-α and interleukin-1β, compared with smoke-exposed controls. Inhibition of C/EBPβ in human airway cells in vitro caused a similarly compromised response to smoke. Our data suggest a previously unknown role for C/EBPβ and the airway epithelium in mediating inflammatory and innate immune responses to cigarette smoke.


Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model.
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8+ T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis. LTX-315 rapidly killed the cells in vitro with a lytic mode of action followed by the subsequent release of Danger-Associated Molecular Pattern (DAMP) molecules such as HMGB1, ATP and Cytochrome c. Together, our data demonstrate that LTX-315 represents a new approach to cancer immunotherapy, which has the potential as a novel immunotherapeutic agent.


Developing Research Collaborations in an Academic Clinical Setting: Challenges and Lessons Learned.
Research collaboration in "real world" practice settings may enhance the meaningfulness of the findings and reduce barriers to implementation of novel intervention strategies. This study describes an initiative to integrate research into a hospital-based outpatient psychiatric clinic within an academic medical center, focusing on collaborative processes across three research projects. We report on the varied outcomes of the projects and utilize data from two focus groups to identify the key elements that contributed to the challenges and successes. We identify barriers to practice-research collaborations that emerged even when the initial circumstances of the partnership were favorable. These barriers include the presence of varied agendas across clinicians and investigators, resource constraints, limited staff buy-in, and staff turnover. In highlighting the lessons learned in this collaborative process, we hope to facilitate successful partnerships in other clinical settings.


Defining hazard from the mine worker's perspective.
In the recent past, the mining industry has witnessed a substantial increase in the numbers of fatalities occurring at metal and nonmetal mine sites, but it is unclear why this is occurring. One possible explanation is that workers struggle with identifying worksite hazards and accurately assessing the associated risk. The purpose of this research was to explore this possibility within the mining industry and to more fully understand stone, sand and gravel (SSG) mine workers' thoughts, understandings and perceptions of worksite hazards and risks. Eight mine workers were interviewed and asked to identify common hazards they come across when doing their jobs and to then discuss their perceptions of the risks associated with those identified hazards. The results of this exploratory study indicate the importance of workers' job-related experience as it applies to hazard identification and risk perception, particularly their knowledge of or familiarity with a task, whether or not they had personal control over that task, and the frequency with which they perform that task.


Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.
Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.


[Treatment of 11 cases of pulmonary arteriovenous fistula].
We have experienced a total of 11 patients operated for pulmonary arteriovernous fistula (PAVF) from 1976 to 1993 consisting of three males and eight females with the average age of 35 years. To reserve the pulmonary function, limited resections were applied for all cases (partial resection in 8, fistula excision in 2, and segmentectomy in one case). The most recent case, a 36-year-old female who had two abnormal shadows on her routine chest X-ray, was diagnosed as PAVF by pulmonary arteriogram. She was treated by fistula excision in the right S8 lesion and embolization in the left S1 + 2 lesion. Because of its unsatisfactory natural course, PAVF should be treated aggressively by surgery and/or by embolization according to the size, shape and localization.


Frequency distribution of HLA alleles and haplotypes in Uyghur women with advanced squamous cell cervical cancer and relation to HPV status and clinical outcome.
This study aims to investigate the association of human leukocyte antigen (HLA) alleles and haplotypes in Uyghur women with advanced squamous cell cervical cancer (SCC). A total of 131 Uyghur patients with advanced SCC (IIb-IVa) and 91 healthy subjects from Xinjiang province were genotyped for HLA-I and II genes using Polymerase Chain Reaction Sequence Based Typing. The different frequencies of HLA alleles and haplotypes between patients and controls were compared and the correlations were analyzed between HLA distribution and HPV status and prognosis. (1) The frequencies of B*51:01, DRB1*07:01, DQB1*02:01, A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01, DRB1*07:01-DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in cancer group were higher than control group whereas the frequencies of B*44:02, B*58:01, C*05:01, DRB1*04:01, DRB1*12:01, DRB1*13:01, DQB1*02:02, DQB1*05:02, DRB1*03:01-DQB1*02:02 and DRB1*04:01-DQB1*03:02 in cancer group were lower than control group (P < 0.05). (2) The frequencies of A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01, DRB1*07:01-DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in HPV positive group were lower than HPV negative group, differences of which were statistically significant (P < 0.05). (3) B*44:02 and B*58:01 were associated with reduced disease-specific survival (DSS) (P = 0.010 and 0.007). (4) Multivariate Cox proportional hazard models revealed that age, International Federation of Gynaecology and Obstetrics (FIGO) stage, tumor differentiation and allele B*58:01 as independent predictors for DSS while FIGO stage and tumor differentiation as independent factors for DFS. In the development and progression of advanced SCC among Uyghur population, the HLA alleles and its haplotypes play an important role. B*58:01 allele may act as an independent predictor for DSS.


mHealth Assessment: Conceptualization of a Global Framework.
The mass availability and use of mobile health (mHealth) technologies offers the potential for these technologies to support or substitute medical advice. However, it is worrisome that most assessment initiatives are still not able to successfully evaluate all aspects of mHealth solutions. As a result, multiple strategies to assess mHealth solutions are being proposed by medical regulatory bodies and similar organizations. We aim to offer a collective description of a universally applicable description of mHealth assessment initiatives, given their current and, as we see it, potential impact. In doing so, we recommend a common foundation for the development or update of assessment initiatives by addressing the multistakeholder issues that mHealth technology adds to the traditional medical environment. Organized by the Mobile World Capital Barcelona Foundation, we represent a workgroup consisting of patient associations, developers, and health authority representatives, including medical practitioners, within Europe. Contributions from each group's diverse competencies has allowed us to create an overview of the complex yet similar approaches to mHealth evaluation that are being developed today, including common gaps in concepts and perspectives. In response, we summarize commonalities of existing initiatives and exemplify additional characteristics that we believe will strengthen and unify these efforts. As opposed to a universal standard or protocol in evaluating mHealth solutions, assessment frameworks should respect the needs and capacity of each medical system or country. Therefore, we expect that the medical system will specify the content, resources, and workflow of assessment protocols in order to ensure a sustainable plan for mHealth solutions within their respective countries. A common framework for all mHealth initiatives around the world will be useful in order to assess whatever mHealth solution is desirable in different areas, adapting it to the specifics of each context, to bridge the gap between health authorities, patients, and mHealth developers. We aim to foster a more trusting and collaborative environment to safeguard the well-being of patients and citizens while encouraging innovation of technology and policy.


The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines.
The ubiquitin-proteasome pathway plays a crucial role in many cellular processes by degrading substrates tagged by polyubiquitin chains, linked mostly through lysine 48 of ubiquitin. Although polymerization of ubiquitin via its six other lysine residues exists in vivo as part of various physiological pathways, the molecular mechanisms that determine the type of polyubiquitin chains remained largely unknown. We undertook a systematic, in vitro, approach to evaluate the role of E2 enzymes in determining the topology of polyubiquitin. Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized. Moreover, our findings are in complete agreement with prior analyses of lysine preference assigned to certain E2s in the context of E3 (in vitro and in vivo). Finally, our findings support the rising notion that the functional unit of E2 is a dimer. To our knowledge, this is the first systematic indication for the involvement of E2 enzymes in specifying polyubiquitin chain assembly.


Internet addiction and physical and psychosocial behavior problems among rural secondary school students.
The aim of this study was to determine secondary school students' levels of Internet addiction and the physical and psychosocial behavior problems they face while using the Internet. This descriptive study was conducted in three state secondary schools in a rural area in the western part of Turkey. This study's sample consisted of 549 students who agreed to participate, with the consent of their families, and who had an Internet connection at home. The data were evaluated using t-tests and variance analyses. In this study the students' score of Internet addiction was at medium level (mean addiction score 44.51 ± 17.90). There were significant differences between the students' Internet addiction scores and the presence of physical behavior problems (going to bed late, skipping meals, eating meals in front of the computer) and psychosocial behavior problems (suffering from conditions such as restlessness, anger, heart palpitations, or tremors when they could not connect to the Internet, decreased relationships with family and friends, feelings of anger, arguing with parents, and finding life boring and empty without an Internet connection).


Trends in incidence of oesophageal and gastric cancer according to morphology and anatomical location, in Switzerland 1982-2011.
This study aimed to evaluate trends in the incidence of oesophageal and gastric cancer by anatomical location and histology using nationally representative Swiss data. We included all oesophageal and gastric cancers recorded in 10 Swiss population-based cancer registries 1982-2011. We calculated age-standardised incidence rates (ASIRs) per 100 000 person-years (PY) (European standard) for both cancer sites stratified by sex, language region (German, French-Italian), morphology and anatomical location. To assess time trends, we estimated annual percentage changes (APCs) with 95% confidence intervals (95% CIs). ASIR of oesophageal adenocarcinoma increased in both sexes and language regions (p <0.001). The steepest increase occurred in males of the German-speaking region (APC 6.8%, 95% CI 5.8-7.8) with ASIRs of 0.8 per 100,000 PY in 1982-1987 and 3.9 per 100.000 PY in 2007-2011. Incidence of oesophageal squamous cell carcinoma decreased significantly in males of both language regions by around -1.5% per year. In contrast, a slight but significant increase (APC 1.4%, 95% CI 0.3-2.4]) of oesophageal squamous cell carcinoma was observed in females of the German-speaking region. We observed stable rates for cancer of the gastric cardia. The incidence of noncardia gastric cancer decreased substantially in both sexes and language regions (p <0.001). In Switzerland, the incidence of oesophageal adenocarcinoma has risen whereas incidence of noncardia gastric cancer has decreased substantially as observed in other developed countries.


Biological Effects of IL-26 on T Cell-Mediated Skin Inflammation, Including Psoriasis.
Psoriasis is a chronic inflammatory skin disease characterized mainly by epidermal hyperplasia, scaling, and erythema; T helper 17 cells have a role in its pathogenesis. Although IL-26, known as a T helper 17 cytokine, is upregulated in psoriatic skin lesions, its precise role is unclear. We investigated the role of IL-26 in the imiquimod-induced psoriasis-like murine model using human IL-26 transgenic mice. Erythema symptoms induced by daily applications of imiquimod increased dramatically in human IL-26 transgenic mice compared with controls. Vascularization and immune cell infiltration were prominent in skin lesions of human IL-26 transgenic mice. Levels of fibroblast growth factor (FGF) 1, FGF2, and FGF7 were significantly upregulated in the skin lesions of imiquimod-treated human IL-26 transgenic mice and psoriasis patients. In vitro analysis demonstrated that FGF1, FGF2, and FGF7 levels were elevated in human keratinocytes and vascular endothelial cells following IL-26 stimulation. Furthermore, IL-26 acted directly on vascular endothelial cells, promoting proliferation and tube formation, possibly through protein kinase B, extracellular signal-regulated kinase, and NF-κB pathways. Moreover, similar effects of IL-26 were observed in the murine contact hypersensitivity model, indicating that these effects are not restricted to psoriasis. Altogether, our data indicate that IL-26 may be a promising therapeutic target in T cell-mediated skin inflammation, including psoriasis.


Socioeconomic Risk and School Readiness: Longitudinal Mediation Through Children's Social Competence and Executive Function.
The association of socioeconomic status with academic readiness and school achievement is well established. However, the specific contributions of cognitive and social aspects of self-regulation, and potential reciprocal relations between them in the prediction of school readiness and early school achievement have not previously been examined. This study examined mediational processes involving children's executive function (EF) skills at 58 months and Grade 1 (G1) and social competence in Kindergarten (K) and G1, as potential pathways by which early-life poverty-related risks influence Grade 2 (G2) math and reading achievement. Data came from the Family Life Project, which is a prospective longitudinal study of 1,292 children and families followed from birth in primarily low-income, non-urban counties in Pennsylvania (PA) and North Carolina (NC). Autoregressive cross-lagged mediation analyses indicated that EF at 58 months through EF at G1 mediated negative associations between cumulative risk exposure and academic skills, with this pathway mediating 36% of the total effect. Furthermore, social competence at K through EF at G1 mediated negative associations between early-life cumulative socioeconomic risk and academic skills, mediating 16% of the total effect. These findings provide evidence that poverty-related risks can influence school readiness and academic achievement via EF. Additionally, these results provide preliminary support for the premise that social competence through EF is a pathway by which cumulative poverty-related risk predicts early academic competence. Our findings are consistent with studies demonstrating developmental associations between EF and social competence. Furthermore, our findings are consistent with prekindergarten programs for children in poverty that emphasize both cognitive and social aspects of self-regulation.


van der Waals force-induced loading of proangiogenic nanoparticles on microbubbles for enhanced neovascularization.
Nanoparticles emerged as carriers of promising diagnostic and therapeutic molecules due to their unique size, injectability, and potential to sustainably release molecular cargos. However, with local injection of particles into target tissue, the significant particle loss caused by external biomechanical forces is a great challenge yet to be resolved to date. We hypothesized that nanoparticles associated with tissue-adherent microbubbles in the form of core-shell particles due to van der Waals attractive forces would stably remain on an implanted site and significantly increase therapeutic efficacy of drug cargos. To examine this hypothesis, we used 100 nm diameter nanoparticles made of poly(lactide-co-glycolic acid) (PLGA) as a model nanoparticle and 50 μm diameter microbubbles made of poly(2-hydroxyethyl aspartamide) (PHEA) grafted with octadecyl chains, PHEA-g-C18, as a model microbubble. Simple mixing of PLGA nanoparticles and PHEA-g-C18 microbubbles resulted in the core-shell particles. Following implantation, the PHEA-g-C18 microbubbles acted as glue to minimize the displacement of PLGA nanoparticles, because of the association between the octadecyl chains on PHEA-g-C18 and the epithelium of the tissue. As a consequence, the core-shell particles prepared with Angiopoietin-1 (Ang1)-encapsulated PLGA nanoparticles significantly promoted vascularization in the implanted tissue. Overall, the results of this study provide a simple but advanced strategy for improving therapeutic efficacy of drug-carrying nanoparticles without altering their surface chemistry and potential.


Identifying the reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in California: the role of the western gray squirrel (Sciurus griseus).
We investigated the role of the western gray squirrel (Sciurus griseus) as a reservoir host of the Lyme disease spirochete Borrelia burgdorferi. A survey of 222 western gray squirrels in California showed an overall prevalence of B. burgdorferi infection of 30%, although at a county level, prevalence of infection ranged from 0% to 50% by polymerase chain reaction. Laboratory trials with wild-caught western gray squirrels indicated that squirrels were competent reservoir hosts of the Lyme disease bacterium and infected up to 86% of feeding Ixodes pacificus larvae. Infections were long-lasting (up to 14 months), which demonstrated that western gray squirrels can maintain B. burgdorferi trans-seasonally. Non-native eastern gray squirrels (Sciurus carolinensis) and fox squirrels (Sciurus niger) were infrequently infected with B. burgdorferi.


Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial.
IVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment.The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked. We will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture.Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power). There remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective. Australian and New Zealand Clinical Trial Registry ACTRN12611000226909.


Megacity development and the demise of coastal coral communities: Evidence from coral skeleton δ15 N records in the Pearl River estuary.
Historical coral skeleton (CS) δ18 O and δ15 N records were produced from samples recovered from sedimentary deposits, held in natural history museum collections, and cored into modern coral heads. These records were used to assess the influence of global warming and regional eutrophication, respectively, on the decline of coastal coral communities following the development of the Pearl River Delta (PRD) megacity, China. We find that, until 2007, ocean warming was not a major threat to coral communities in the Pearl River estuary; instead, nitrogen (N) inputs dominated impacts. The high but stable CS-δ15 N values (9‰-12‰ vs. air) observed from the mid-Holocene until 1980 indicate that soil and stream denitrification reduced and modulated the hydrologic inputs of N, blunting the rise in coastal N sources during the early phase of the Pearl River estuary urbanization. However, an unprecedented CS-δ15 N peak was observed from 1987 to 1993 (>13‰ vs. air), concomitant to an increase of NH4+ concentration, consistent with the rapid Pearl River estuary urbanization as the main cause for this eutrophication event. We suggest that widespread discharge of domestic sewage entered directly into the estuary, preventing removal by natural denitrification hotspots. We argue that this event caused the dramatic decline of the Pearl River estuary coral communities reported from 1980 to 2000. Subsequently, the coral record shows that the implementation of improved wastewater management policies succeeded in bringing down both CS-δ15 N and NH4+ concentrations in the early 2000s. This study points to the potential importance of eutrophication over ocean warming in coral decline along urbanized coastlines and in particular in the vicinity of megacities.


Gaming Preferences, Motivations, and Experiences of Pharmacy Students in Asia.
Serious games are becoming popular in various healthcare domains. However, they should be designed to cater toward learners' perspectives, needs, and specifications in order to be used to their full potential in education. This study investigated the gaming experiences, motivations, and preferences of pharmacy students. An anonymous self-administered survey obtained participant demographics, gaming experiences (enjoyment level of different game genres, years of experience, gaming frequency and duration, and motivations), and gaming preferences (on in-game rewards, settings, storylines, perspectives, and styles). Descriptive statistics, t tests, analysis of variance, chi-squared tests, and Fisher's exact tests were used for analysis. The response rate was 69.1 percent (465/673 undergraduates). Role-playing games (RPGs) (4.12 ± 1.07) and massively multiplayer online RPGs (MMORPGs) (3.81 ± 1.26) had the highest enjoyment ratings. Males enjoyed imagination games (e.g., RPGs, MMORPGs) more than females, whereas females enjoyed simulation games more. Top motivating factors for respondents were progressing to the next level (3.63 ± 1.19), excitement (3.33 ± 1.33), and a feeling of efficacy when playing (3.02 ± 1.16). Unlocking mechanisms (25.2 percent) and experience points (17.6 percent) were the most popular in-game reward systems. Most respondents preferred a fantasy/medieval/mythic setting (59.8 percent) and an adventurer storyline (41.3 percent), with similar proportions preferring competitive (35.3 percent), cooperative (33.3 percent), and collaborative (30.8 percent) game styles. Different groups of pharmacy students differ in their gaming experiences, motivating factors, and preferences. There is no "one size fits all" game that is suitable for all pharmacy education. Such differences should be considered when developing a pharmacy game in order to cater to the diverse student population.


Parent eReferral to Tobacco Quitline: A Pragmatic Randomized Trial in Pediatric Primary Care.
Quitlines are effective in helping smokers quit, but pediatrician quitline referral rates are low, and few parents who smoke use the service. This study compared enrollment of parents who smoke in the quitline using electronic referral with that using manual referral. The study was designed as a pragmatic RCT. Participants were recruited from one large, urban pediatric primary care site in Philadelphia, Pennsylvania with a high percentage of low-income families. Participants included adult parents who smoked and were present at their child's healthcare visit. Pediatricians screened for tobacco use; smokers were given brief advice to quit and, if interested in quitting, were referred to the quitline. The eReferral ("warm handoff") involved electronically sending parent information to the quitline (parent received a call within 24-48 hours). Control group procedures were identical to eReferral, except the quitline number was provided to the parent. Data were collected between March 2017 and February 2018 and analyzed in 2018. The primary outcome was the proportion of parents enrolled in quitline treatment. Secondary outcomes included parent factors (e.g., demographics, nicotine dependence, and quitting motivation) associated with successful enrollment. Number of quitline contacts was also explored. During the study period, in the eReferral group, 10.3% (24 of 233) of parents who smoked and were interested in quitting enrolled in the quitline, whereas only 2.0% (5 of 251) of them in the control group enrolled in the quitline-a difference of 8.3% (95% CI=4.0, 12.6). Parents aged ≥50 years enrolled in the quitline more frequently. Although more parents in the eReferral group connected to the quitline, among parents who had at least one quitline contact, there was no significant difference in the mean number of quitline contacts between eReferral and control groups (mean, 2.04 vs 2.40 calls; difference, 0.36 [95% CI=0.35, 1.06]). Smoking parent eReferral from pediatric primary care may increase quitline enrollment and could be adopted by practices interested in increasing rates of parent treatment. This study is registered at www.clinicaltrials.gov NCT02997735.


[Prevalence of the use of psychoactive medication to treat young persons with autism spectrum disorder in the province of Antwerp, Belgium].
Very little information is available concerning the prevalence of the use of medication for treatment of individuals with autism spectrum disorder (ASD), particularly in European countries. Earlier studies have shown that a large number of patients with ASD use at least one psychoactive drug and that the numbers are increasing. Even in the nineties, studies suggested that the frequent use of psychoactive medication was widespread, although at the time there were only limited grounds for this assumption. To assess the prevalence with which psychoactive medication and complementary and alternative medicine (CAM) are being used for treating young people with ASD, and also to investigate relations between medication use and a number of individual characteristics that are included in the Behavioral Model of Health Service Use. The study sample (0-17 years) in the province of Antwerp, Belgium, was recruited by various means. We used a questionnaire that had been previously used in North American studies and that had to be completed by the parents of the young persons involved in the study. We included data from 263 questionnaires. In our sample 42.6% of the young persons used one or more one psychoactive drug. More than 12.2% used more than one drug. The most frequently used psychoactive drugs were ADHD-medication (31.6%) and antipsychotics (16.7%). About 14% used at least one CAM. We found a positive relationship between the use of medication and psychiatric comorbidity and/or epilepsy, the severity of autism and the parents' living conditions. We found a relatively low use of antipsychotics, antidepressants, mood stabilisers and sedatives, the prevalence being lower that that reported in North American studies. Our findings appear to be in accordance with current clinical guidelines.


The lived experience of parenting a child with a life-limiting condition: a focus on the mental health realm.
As medical technology has improved, there has been a marked increase in the numbers of children with life-limiting conditions being managed in the community. Few studies have evaluated the life worlds of the parents of these children. However, there have been studies that have reported feelings of isolation and depression among mothers. This article reports a study that highlights the mental health implications of the lived experience of parenting a child with a life-limiting condition. Semistructured interviews were conducted with 10 parents of children with life-limiting conditions and analyzed using a phenomenological method. The essential meaning of the phenomenon "the lived experience of parenting a child with a life limiting condition" is understood as a full-time emotional struggle involving six continuous constituents: inner drive, feeling responsible, psychological effects, threatened self image, social withdrawal, and a fear of reaching the bottom line. Very little clinical attention is focused upon the wider issues that affect parents dealing with caring for a child with a life-limiting condition.


Ultra low concentration deltamethrin loaded patch development and evaluation of its repellency against dengue vector Aedes (S) albopictus.
Mosquito repellents and emanators confer protection against mosquito bites through spatial action of emanated vapours which are released into the adjoining environment. Synthetic insecticides released into the environment in ultra low volume vapour phase deter the mosquitoes from biting humans in a protected space. Formulation patches were prepared using the solvent evaporation method over a backing membrane and using Dibutylphthalate (DBT) as a plasticizer. The effect of formulation variables on the deltamethrin release from the patch matrices were studied under accelerated conditions, whereas, HPLC was used for quantitative estimation of deltamethrin. The prepared patch formulations were subjected to physicochemical studies, such as, deltamethrin content, thickness, weight variation, percent moisture content, moisture uptake, surface area and surface pH determination. Deltamethrin-polymer interaction and compatibility was ascertained using DSC and FT-IR, while surface morphology and deltamethrin distribution in the patch were studied using SEM technique. Repellent activity of the patch formulations was evaluated against Ae. albopictus mosquitoes. Blends of polymeric combinations of polyvinylpyrrolidone (PVP) and ethyl-cellulose (EC) with admixture of deltamethrin provided prolonged repellent activity against Ae. albopictus mosquitoes. Physicochemical characterisation indicated the suitability of deltamethrin patch formulation with the polymeric combinations of PVP and EC. Patches were very effective against laboratory reared Ae. albopictus mosquitoes. No significant difference was observed between the performance of test patches and commercially available repellent cream Mosqshield®. Deltamethrin loaded patches provided effective repellency against Ae. albopictus mosquitoes. The study emphasised that deltamethrin released to the environment in low concentration could be an excellent spatial repellent against hematophagous mosquitoes.


The simple advantage in perceptual and categorical generalization.
Recent research in relational learning has suggested that simple training instances may lead to better generalization than complex training instances. We examined the perceptual-encoding mechanisms that might undergird this "simple advantage" by testing category and perceptual learning in adults with simplified and traditional (more complex) Chinese scripts. In Experiment 1, participants learned Chinese characters and their English translations, performed a memorization test, and generalized their learning to the corresponding characters written in the other script. In Experiment 2, we removed the training phase and modified the tests to examine transfer based purely on the perceptual similarities between simplified and traditional characters. We found the simple advantage in both experiments. Training with simplified characters produced better generalization than training with traditional characters when generalization relied on either recognition memory or pure perceptual similarities. On the basis of the results of these two experiments, we propose a simple process model to explain the perceptual mechanism that might drive this simple advantage, and in Experiment 3 we tested novel predictions of this model by examining the effect of exposure duration on the simple advantage. We found support for our model that the simple advantage is driven primarily by differences in the perceptual encoding of the information available from simple and complex instances. These findings advance our understanding of how the perceptual features of a learning opportunity interact with domain-general mechanisms to prepare learners for transfer.


The effectiveness of physiotherapeutic interventions in treatment of frozen shoulder/adhesive capsulitis: a systematic review.
Frozen shoulder is a common condition, yet its treatment remains challenging. In this review, the current best evidence for the use of physical therapy interventions (PTI) is evaluated. MEDLINE, CINAHL, Cochrane, PEDro, ProQuest, Science Direct, and Sport Discus were searched for studies published in English since 2000. 39 articles describing the PTI were analyzed using Sackett's levels of evidence and were examined for scientific rigor. The PTI were given grades of recommendation that ranged from A to C. Therapeutic exercises and mobilization are strongly recommended for reducing pain, improving range of motion (ROM) and function in patients with stages 2 and 3 of frozen shoulder. Low-level laser therapy is strongly suggested for pain relief and moderately suggested for improving function but not recommended for improving ROM. Corticosteroid injections can be used for stage 1 frozen shoulder. Acupuncture with therapeutic exercises is moderately recommended for pain relief, improving ROM and function. Electro- therapy can help in providing short-term pain relief. Continuous passive motion is recommended for short-term pain relief but not for improving ROM or function. Deep heat can be used for pain relief and improving ROM. Ultrasound for pain relief, improving ROM or function is not recommended.


Broadband extraordinary terahertz transmission through super-aligned carbon nanotubes film.
We experimentally demonstrate the extraordinary transmission of THz waves through super-aligned multi-walled carbon nanotube (MWCNT) films with one-dimensional arrays of sub-wavelength rectangular gratings in the broad frequency range from 0.2 to 2.5 THz. To achieve this, two kinds of MWCNT films (1 μm and 3 μm in thickness) were fabricated by drawing from a sidewall of super-aligned nanotube arrays synthesized by low pressure chemical vapor deposition. The measured complex refraction index of the film exhibits highly anisotropic transmission of THz waves through the MWCNTs. The anisotropy depends not only on the polarization direction of the THz waves but also on the orientation of the MWCNT gratings. We found that the resonantly extraordinary THz transmission originated from the surface plasmon polaritons supported by periodically patterned carbon nanotube gratings. Our experimental results may provide important insights for emerging THz plasmonic devices based on carbon nanotubes.


Transport and release of chemicals from plastics to the environment and to wildlife.
Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2'-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g(-1) to microg g(-1). Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub microg l(-1) to mg l(-1) and were correlated with the level of economic development.


Metabolic stress-like condition can be induced by prolonged strenuous exercise in athletes.
Few studies have examined energy metabolism during prolonged, strenuous exercise. We wanted therefore to investigate energy metabolic consequences of a prolonged period of continuous strenuous work with very high energy expenditure. Twelve endurance-trained athletes (6 males and 6 females) were recruited. They performed a 7-h bike race on high work-load intensity. Physiological, biochemical, endocrinological, and anthropometric muscular compartment variables were monitored before, during, and after the race. The energy expenditure was high, being 5557 kcal. Work-load intensity (% of VO(2) peak) was higher in females (77.7%) than in men (69.9%). Muscular glycogen utilization was pronounced, especially in type I fibres (>90%). Additionally, muscular triglyceride lipolysis was considerably accelerated. Plasma glucose levels were increased concomitantly with an unchanged serum insulin concentration which might reflect an insulin resistance state in addition to proteolytic glyconeogenesis. Increased reactive oxygen species (malondialdehyde (MDA)) were additional signs of metabolic stress. MDA levels correlated with glycogen utilization rate. A relative deficiency of energy substrate on a cellular level was indicated by increased intracellular water of the leg muscle concomitantly with increased extracellular levels of the osmoregulatory amino acid taurine. A kindred nature of a presumed insulin-resistant state with less intracellular availability of glucose for erythrocytes was also indicated by the findings of decreased MCV together with increased MCHC (haemoconcentration) after the race. This strenuous energy-demanding work created a metabolic stress-like condition including signs of insulin resistance and deteriorated intracellular glucose availability leading to compromised fuelling of ion pumps, culminating in a disturbed cellular osmoregulation indicated by taurine efflux and cellular swelling.


[No reduced number of abortions despite easily available emergency contraceptive pills. Studies of women's knowledge, attitudes and experience of the method].
Despite the fact that emergency contraceptive pills (ECP) have become easily available across the country during recent years, abortion numbers continue to rise in Sweden, especially in the young age groups (< 25). In a series of studies, we have investigated knowledge, attitudes and experience of ECP among young women. Our results show that, whereas most women are aware of the method, many lack knowledge about the mechanism of action and time frames for best use, which could explain why ECPs are not used by more than a fraction of women who might have had benefit from their use. Since half of the women requesting a termination of pregnancy stated that they would have used ECP if they had had them available at home at the time of the unprotected intercourse which led to an unintended pregnancy, it seems reasonable to encourage women to keep ECPs at home, in case the need should arise. It is important that ECPs are available without prescription, but beyond that, much more information about ECP is necessary in order for the method to be widely accepted and used as a back-up after failure with other contraceptives.