Incidence of False Positive Rotator Cuff Pathology in MRIs of Patients with Adhesive Capsulitis.
The purpose of this study was to compare the incidence of presumed rotator cuff pathology based on radiologist and surgeon interpretation of preoperative magnetic resonance images (MRIs) with actual rotator cuff pathology found intraoperatively in patients undergoing arthroscopic capsular release for adhesive capsulitis.The medical records of 38 consecutive patients who underwent arthroscopic glenohumeral capsular release for adhesive capsulitis between September 2001 and May 2007 were retrospectively reviewed. Radiologist and surgeon predicted status of the rotator cuff by prospective MRI interpretation was compared to the actual status of the rotator cuff intraoperatively. Radiologists' preoperative MRI interpretations predicted a 57.9% incidence of rotator cuff pathology, while operative findings revealed a true incidence of only 13.2% (P<.0001). Radiologists accurately predicted the absence or presence of a rotator cuff tear in 19 of 38 cases (50%), compared to the surgeon, who correctly interpreted 29 of 38 MRIs (76.3%).Interpretations of shoulder MRIs in patients with adhesive capsulitis may provide misleading information regarding rotator cuff pathology. The actual findings of shoulder MRI scans may lead to the appearance of false rotator cuff pathology in this population, and a high percentage of false positive MRI reports of rotator cuff tears was observed in these patients. If MRI is chosen as a diagnostic adjunct in this patient population, careful consideration should be given to its interpretation to avoid unnecessary or possibly aggravating surgical intervention.


Corpus callosum abnormalities in Wilson's disease.
Wilson's disease (WD) with neurological presentation is associated with brain lesions classically localised in globus pallidus, putamen, thalamus, mesencephalon, pons and dentate nucleus. Lesions of corpus callosum (CC) have not been studied in a broad population of patients with WD. Evaluation of the frequency of CC lesions in patients with neurological symptoms related to WD. The authors included all patients with neurological expression of WD, followed in the French national centre for WD who had a brain MRI between March 2006 and December 2008. The localisation of brain lesions was analysed and the frequency of lesions in CC evaluated. All patients were assessed using the Unified Wilson's Disease Rating Scale. For patients with abnormalities located in CC, a clinical dysconnexion syndrome was investigated. Among 81 patients (45 men, mean age: 34.8 years, from 12 to 74 years) with neurological expression, 42% had white-matter lesions on fluid-attenuated inversion recovery MRI. 23.4% of patients presented CC lesions, limited to the posterior part (splenium). The severity of disability estimated by Unified Wilson's Disease Rating Scale was correlated with the presence of CC lesions on MRI. Abnormalities in CC are not unusual (23.4%). Together with lesions of basal ganglia, CC signal changes should suggest the diagnosis of WD.


Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis.
Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs 145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.


Can physical activity interventions for adults with type 2 diabetes be translated into practice settings? A systematic review using the RE-AIM framework.
Despite the strong evidence base for the efficacy of physical activity in the management of type 2 diabetes, a limited number of physical activity interventions have been translated and evaluated in everyday practice. This systematic review aimed to report the findings of studies in which an intervention, containing physical activity promotion as a component, has been delivered within routine diabetes care. A comprehensive search was conducted for articles reporting process data relating to components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and/or Maintenance) framework. Twelve studies met the selection criteria. Of the nine studies which measured physical activity as an outcome, eight reported an increase in physical activity levels, five of which were significant. Tailoring recruitment, resources and intervention delivery to the target population played a positive role, in addition to the use of external organisations and staff training. Many interventions were of short duration and lacked long-term follow-up data. Findings revealed limited and inconsistent reporting of useful process data.


Parametric laser pulse shortening.
We report simultaneous laser pulse shortening and wavelength conversion based on spectral-temporal correlation in high-gain optical parametric generation (OPG). By spectrally filtering the off-peak signal energy, we shortened a 560 ps pump pulse at 1064 nm to an 80 ps signal pulse at 1.5 μm from a 45 mm long PPLN optical parametric generator with 60 μJ pump energy from a passively Q-switched Nd:YAG laser. Using the same technique, we further demonstrated a 3.6 time shortened laser pulse at 1072 nm from noncollinearly phase matched OPG in a 44 mm long lithium niobate crystal with 3 mJ amplified pump energy from the same Nd:YAG laser.


When and how to treat an IMRT patient on a second accelerator without replanning?
When a linear accelerator is unavailable for treatment, a clinical decision is imminent regarding whether a patient should be treated on a linear accelerator other than the machine the patient was scheduled on, or whether treatment should be postponed until the original Linac becomes available. This work investigates the feasibility of switching patients to different accelerators for intensity-modulated radiation therapy (IMRT). We have performed Monte Carlo simulations of photon beams from different Linac models and vendors. Prostate and head and neck (H&N) treatment plans for Siemens Primus, Primart, and Varian 21EX accelerators are studied in this work. Dose distributions for given plans are recalculated using different beam data with the same nominal energy from different Linacs. We have compared dose-volume histograms (DVHs) and the maximum, the minimum, and the mean doses to the target and critical structures because of switching accelerators. In the process of switching a treatment plan to a different accelerator, issues exist, including optimum penumbra compensation, dose distribution at the boundary of target and critical structures, and multileaf collimator (MLC) leaf-width effects, which need to be considered and verified with measurements. Our Monte Carlo simulation results confirm that, for the cases we tested, the dose received by 95% of the planning target volume differs by 0.2% to 1.5% between Siemens Primus and Varian 21EX Linacs. The discrepancy is within our clinical acceptance criteria of 3% for IMRT treatments. In making the final decision on whether to switch machines or not, the tumor control probabilities (TCPs) based on a linear-quadratic model are compared. Based on the analyses performed in this work, it is therapeutically more beneficial to switch a patient to a different machine than to postpone a treatment until the original machine is available, especially for fast-growing tumors such as H&N cancers.


Utility of DNA sequencing for direct identification of invasive fungi from fresh and formalin-fixed specimens.
To describe and discuss the utility and potential pitfalls of ribosomal RNA locus sequencing for direct identification of invasive fungi from fresh and formalin-fixed, paraffin-embedded specimens. DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue and subjected to real-time polymerase chain reaction (PCR) targeting ITS2 and D2 regions of fungal ribosomal RNA locus. Cycle sequencing was performed on PCR products, and the identity of sequences was determined using a public database. Four clinical cases of invasive fungal infection are presented to illustrate the utility of DNA sequencing for determining etiology when microbiological culture is negative, for shortening the time to identification of slow-growing fungi, for guiding antifungal therapy, and for shedding light on the pathogenesis of disseminated fungal infection. Fungal ribosomal RNA locus sequencing from fresh or formalin-fixed, paraffin-embedded specimens is a powerful tool for rapid and accurate diagnosis of patients with culture-negative or uncultured invasive mycosis.


Evaluating the travel, physical activity and carbon impacts of a 'natural experiment' in the provision of new walking and cycling infrastructure: methods for the core module of the iConnect study.
Improving infrastructure to support walking and cycling is often regarded as fundamental to encouraging their widespread uptake. However, there is little evidence that specific provision of this kind has led to a significant increase in walking or cycling in practice, let alone wider impacts such as changes in overall physical activity or carbon emissions. Connect2 is a major new project that aims to promote walking and cycling in the UK by improving local pedestrian and cycle routes. It therefore provides a useful opportunity to contribute new evidence in this field by means of a natural experimental study. iConnect is an independent study that aims to integrate the perspectives of public health and transport research on the measurement and evaluation of the travel, physical activity and carbon impacts of the Connect2 programme. In this paper, the authors report the study design and methods for the iConnect core module. This comprised a cohort study of residents living within 5 km of three case study Connect2 projects in Cardiff, Kenilworth and Southampton, supported by a programme of qualitative interviews with key informants about the projects. Participants were asked to complete postal questionnaires, repeated before and after the opening of the new infrastructure, which collected data on demographic and socioeconomic characteristics, travel, car fuel purchasing and physical activity, and potential psychosocial and environmental correlates and mediators of those behaviours. In the absence of suitable no-intervention control groups, the study design drew on heterogeneity in exposure both within and between case study samples to provide for a counterfactual. The study was approved by the University of Southampton Research Ethics Committee. The findings will be disseminated through academic presentations, peer-reviewed publications and the study website (http://www.iconnect.ac.uk) and by means of a national seminar at the end of the study.


Development of a microsurgery training system.
Surgeons require significant training to acquire sufficient dexterity and hand-eye coordination to manipulate objects skillfully under the microscope. This paper presents a computer-based real-time simulation of microsurgery as well as the hardware setup. It presents a realistic physics-based elastic suture and blood vessel model, fast collision detection techniques, suture insertion process and novel approach of a haptic forceps. The simulation environment demonstrates a complete vascular suturing system to train skills such as grasping, suture placement, needle insertion and knot-tying running at 500 Hz, sufficient for physical realism.


Interaction between disinhibition and restraint: Implications for body weight and eating disturbance.
An increase in obesity is usually accompanied by an increase in eating disturbances. Susceptibility to these states may arise from different combinations of underlying traits: Three Factor Eating Questionnaire (TFEQ) Restraint and Disinhibition. Two studies were conducted to examine the interaction between these traits; one on-line study (n=351) and one laboratory-based study (n=120). Participants completed a battery of questionnaires and provided self-report measures of body weight and physical activity. A combination of high Disinhibition and high Restraint was associated with a problematic eating behaviour profile (EAT-26), and a higher rate of smoking and alcohol consumption. A combination of high Disinhibition and low Restraint was associated with a higher susceptibility to weight gain and a higher sedentary behaviour. These data show that different combinations of Disinhibition and Restraint are associated with distinct weight and behaviour outcomes.


A one-year study of human milk oligosaccharide profiles in the milk of healthy UK mothers and their relationship to maternal FUT2 genotype.
Human milk oligosaccharides (HMOs) are indigestible carbohydrates with prebiotic, pathogen decoy and immunomodulatory activities that are theorized to substantially impact infant health. The objective of this study was to monitor HMO concentrations over 1 year to develop a long-term longitudinal dataset. HMO concentrations in the breast milk of healthy lactating mothers of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) were measured at birth, 2 weeks, 6 weeks, 3 months, 6 months and 12 months postpartum. HMO quantification was conducted by high-performance anion-exchange chromatography with pulsed amperometric detection using a newly validated "dilute-and-shoot" method. This technique minimizes sample losses and expedites throughput, making it particularly suitable for the analysis of large sample sets. Varying patterns of individual HMO concentrations were observed with changes in lactation timepoint and maternal secretor status, with the most prominent temporal changes occurring during the first 3 months. These data provide valuable information for the development of human milk banks in view of targeted distribution of donor milk based on infant age. Maternal FUT2 genotype was determined based on identification at single-nucleotide polymorphism rs516246 and compared with the genotype expected based on phenotypic markers in the HMO profile. Surprisingly, two mothers genotyped as secretors produced milk that displayed very low levels of 2'-fucosylated moieties. This unexpected discrepancy between genotype and phenotype suggests that differential enzyme expression may cause substantial variation in HMO profiles between genotypically similar mothers, and current genotypic methods of secretor status determination may require validation with HMO markers from milk analysis.


Alcohol use among older adults: SABE cohort study, São Paulo, Brazil.
In recent years, Brazil has demonstrated a new demographic pattern characterized by a reduction in both birth and mortality rates and a significant increase in the number of older adults. The purpose of the present study was to describe the frequency of alcohol intake in a representative sample community of older adults in the city of São Paulo, Brazil, followed over a six-year period. A prospective Saúde, Bem-Estar e Envelhecimento (SABE [Health, Wellbeing and Aging]) cohort study conducted in 2000 and 2006 in City of São Paulo, Brazil. 2,143 individuals aged 60 years or older selected through multi-stage sampling in the year 2000 (41.4% male and 58.6% women) and 1,115 individuals belonging to the follow-up cohort evaluated in 2006. The frequency of alcohol intake in the previous three months was obtained through self-reports of interviewees. The results demonstrate that in 2000, alcohol consumption was less than one day a week among 79.7% of the sample, one to three days a week among 13.0% and four or more days a week among 7.3%. In agreement with findings on other populations, consumption four or more days a week was more frequent among the male gender as well as those with greater schooling and income and good self-rated health (p<0.05). The longitudinal analysis demonstrated an increase in the frequency of alcohol consumption one to three times a week among the individuals in the 2006 follow-up study. In the present population-based sample, alcohol intake was low and the frequency of moderate alcohol consumption increased over the years. The present study can assist understanding the changes in alcohol intake among older adults throughout time and the ageing process.


Selection of an infectious bursal disease virus mutant with increased immunogenicity following passage under humoral immune pressure.
It is generally known that the pathogenicity of infectious bursal disease virus (IBDV) strains decreases following passage in cell culture. However, there is no information about the effect of passage under immune pressure on the phenotypic and molecular properties of IBDV. In the present study, a small plaque mutant virus with poor neutralization capability, but showing similar growth characteristics as the parental virus strain, QC2, was isolated after serial passage in Vero cells in presence of IBDV serotype 1 chicken polyclonal antiserum. This mutant virus showed reduced pathogenicity but enhanced immunogenicity compared to the parental virus. Sequence analysis of the non-coding regions of the genome revealed 4 and 3 nucleotide changes in the 3' non-coding regions of segments A and B, respectively, and none in the 5' non-coding regions. Restriction enzyme analysis of selected coding regions of the IBDV genome in both viruses revealed a loss of the PstI site in the VP2 region of the mutant virus. Selection of such mutant viruses by passaging under immune pressure may offer an improved method for developing safer and more effective attenuated vaccine strains against infectious bursal disease of chickens.


Daxx is a predominately nuclear protein that does not translocate to the cytoplasm in response to cell stress.
The intracellular translocation of Daxx to the cytoplasm is a phenomenon often attributed to cells undergoing stress, opposite to predominant nuclear localization of this protein under normal homeostatic conditions. Moreover, a number of reports have suggested that export to the cytosol upon several stress conditions, including oxidative stress, glucose deprivation and beta-amyloid peptide treatment, is indispensable for the proper execution of Daxx-induced apoptosis. On the contrary, other studies have described translocation of Daxx from cytoplasm to nucleus upon stress application. Here, we examined cellular distribution of Daxx by sub-cellular fractionation and immunofluorescent localization of endogenous protein, using SH-SY5Y neuroblastoma cell line previously reported to exhibit cytoplasmic translocation of Daxx after oxidative stress and beta-amyloid exposure. In control conditions, Daxx is an exclusively nuclear protein in SH-SY5Y cells. Short treatment by either H(2)O(2) or beta-amyloid did not show any significant change in nuclear localization of Daxx. Prolonged exposure of cells to stress compounds did not alter the intracellular deposition of Daxx that remains exclusively in the nucleus. A cohort of other cell lines, including human prostate cancer cell line DU-145, previously reported to exhibit stress-induced cytosol translocation was examined for Daxx distribution and none were confirmed to show re-localization of Daxx to the cytoplasm after either short or long stress. Time-lapse visualization of Daxx-GFP upon H(2)O(2) treatment or glucose deprivation did not show cytoplasmic translocation either. Thus, while several Daxx-dependent apoptotic mechanisms have been described, the cytosolic association and function of this protein is questionable in light of these findings.


Reagent pencils: a new technique for solvent-free deposition of reagents onto paper-based microfluidic devices.
Custom-made pencils containing reagents dispersed in a solid matrix were developed to enable rapid and solvent-free deposition of reagents onto membrane-based fluidic devices. The technique is as simple as drawing with the reagent pencils on a device. When aqueous samples are added to the device, the reagents dissolve from the pencil matrix and become available to react with analytes in the sample. Colorimetric glucose assays conducted on devices prepared using reagent pencils had comparable accuracy and precision to assays conducted on conventional devices prepared with reagents deposited from solution. Most importantly, sensitive reagents, such as enzymes, are stable in the pencils under ambient conditions, and no significant decrease in the activity of the enzyme horseradish peroxidase stored in a pencil was observed after 63 days. Reagent pencils offer a new option for preparing and customizing diagnostic tests at the point of care without the need for specialized equipment.


Bio-oil deoxygenation by catalytic pyrolysis: new catalysts for the conversion of biomass into densified and deoxygenated bio-oil.
This work proposes an innovative catalytic pyrolysis process that converts bio-refinery residues, such as spent grains, into intermediate bio-oil with improved properties compared to traditional bio-oils, which allows the use of existing crude-oil refinery settings for bio-oil upgrading into fuels. The integration of bio-oil into a crude-oil refinery would decrease the economic disadvantage of biomass compared to fossil fuels. The catalytic pyrolysis was able to produce bio-oil with a lower O and N content and high levels of aliphatics and H by using activated serpentine and olivine at 430-460 °C. The activated materials seem to be beneficial to the bio-oil energy content by increasing it from less than 20 MJ kg(-1) in the original biomass to 26 MJ kg(-1). Approximately 70-74 % of the starting energy remains in the bio-oil using activated olivine (ACOL) and activated serpentine (ACSE) at 430 °C, whereas only 52 % is retained using alumina (ALU) at the same temperature. There was a strong reduction of the O content in the bio-oils, and the deoxygenation power decreased in the following order: ACOL>ACSE>ALU. In particular, ACOL at 430-460 °C was able to reduce the O content of the bio-oil by 40 %. The oxygenated bio-oil macromolecules interact in the catalyst's active sites with the naturally present metallic species and undergo decarboxylation with the formation of C(5)-C(6) O-depleted species.


Cervical cytologic screening among females with nongynecologic hospital admissions.
Routine vaginal cytologic screening in nongynecologic admissions to Tygerberg Hospital revealed a detection rate for pelvic neoplasia of 9.3/1000 patients. Of these, 22 (16%) did not derive any benefit from this program because of the severity of the primary extrapelvic disease. However, 57% of those detected were still in the in situ stage and should have a 100% 5-year survival. The treatment was considered to be complete in 54.4% of the cases. As this service is performed by nursing personnel as part of their daily duty, this program seems to be a sound economic proposition.


Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol.
We previously showed that macrophages from macrophage-specific ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1(-M/-M)) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1(-M/-M) macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1(-M/-M) vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1(-M/-M) and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1(-M/-M) macrophages. Abca1(-M/-M) macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specific agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts.


Dried blood spot analysis: an easy and reliable tool to monitor the biochemical effect of hematopoietic stem cell transplantation in hurler syndrome patients.
Hurler syndrome (HS), the most severe phenotype in the spectrum of mucopolysaccharidosis type I, is caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase (IDUA). At present, hematopoietic stem cell transplantation (HSCT) is the only treatment able to prevent disease progression in the central nervous system, and therefore considered the treatment of choice in HS patients. Because IDUA enzyme activities after HSCT have been suggested to influence the prognosis of HS patients, monitoring these activities after HSCT remains highly important. The use of dried blood spots (DBS) for enzyme analysis can be a useful alternative to the conventional leukocyte assay. Importantly, this method allows for convenient worldwide shipment, and can therefore be applied to monitor patients from larger areas of the world, or during large-scale international studies. Furthermore, this method requires only a minimal amount of blood. From 13 HS patients receiving HSCT, 36 paired whole blood and DBS samples were analyzed to assess leukocyte and DBS IDUA activities, respectively. To correct for potential interfering factors, simultaneous assay of the alpha-Galactosidase-A (AGA) activity was performed in the DBS samples and an IDUA/AGA ratio was calculated. A strong linear correlation was demonstrated between the DBS IDUA/AGA ratio and the leukocyte IDUA activity (r(2) = .875, P < .001). This correlation was applicable to all enzyme activities, including the activities measured early after HSCT as well as heterozygous activities because of mixed chimerism or the use of a carrier donor. These results demonstrate that the DBS method is reliable to monitor the biochemical effect of HSCT in HS patients.


Critical Appraisal of the Quality of Clinical Practice Guidelines for Stress Ulcer Prophylaxis.
Inappropriate use of stress ulcer prophylaxis (SUP) is common in many hospitals. High-quality clinical practice guidelines (CPGs) produce better patient outcomes and promote cost-effective clinical care. Thus, the objective of this study was to evaluate the quality of CPGs for SUP. A search was conducted for SUP CPGs using PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM), guideline websites and Google (until March 1, 2015). The quality of CPGs was independently assessed by two assessors using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument, and the specific recommendations in the CPGs were summarized and evaluated. A total of 7 CPGs for SUP were included. The highest median scores were in the clarity of presentation domain (89%), and the lowest median scores were in the editorial independence domain (0%). The rigor of development, stakeholder involvement, and applicability domains all scored below 40%. The specific recommendations for SUP varied, and the recommendations were inconsistent with the supporting evidence. The overall quality of CPGs for SUP was relatively low, and no specific SUP CPG can be recommended. Not only should the AGREE II instrument be used to determine the quality of CPGs, but also the recommendations should be appraised based on supporting evidence, which would contribute to the development of high-quality CPGs.


Positive intravenous line tip cultures as predictors of bacteraemia.
Intravenous line tip cultures provide valuable information when taken in conjunction with blood culture, but in practice are often performed in isolation. This retrospective study has evaluated: (1) the frequency of isolated line tip culture; and (2) whether the species of microorganism isolated from line tip culture, using the Maki semi-quantitative culture method, is predictive of bacteraemia. Of 2753 line tip culture episodes in 1659 patients between May 1993 and August 1995, 2230 were performed in isolation (81%). Evaluation of 792 positive line tip culture episodes in 654 patients where blood cultures were performed in the period from 48 h before, to 24 h after tip culture, identified 825 line tip isolates. Of these, 194 were associated with a blood culture positive for the same species. The rate of positive blood culture, according to species, ranged from 10-72%. The highest rate was seen for methicillin-susceptible Staphylococcus aureus where 70 of 97 line tip episodes (72%) were associated with positive blood culture. This compared with a rate of 17% for coagulase-negative staphylococci (P < 0.0001). Patients with line tip cultures positive for S. aureus should be considered to be at high risk of bacteraemia.


Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. an integral model.
A growing body of evidence indicates that aberrant activation of alveolar epithelial cells and fibroblasts in an aging lung plays a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the biopathological processes linking aging with IPF and the mechanisms responsible for the abnormal activation of epithelial cells and fibroblasts have not been elucidated. Many of the hallmarks of aging (e.g., genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, and cellular senescence) have been proposed as essential mechanisms for the development of IPF; however, these disturbances are not restricted to IPF and also occur in other aging-related lung disorders, primarily chronic obstructive pulmonary disease (COPD). Therefore, an unanswered question is why a current/former smoker of about 60 years of age with shorter telomeres, alveolar epithelial senescence, excessive oxidative stress, and mitochondrial dysfunction develops IPF and not COPD; in other words, what makes old lungs specifically susceptible to develop IPF? In this Perspective, we propose an integral model in which the combination of some gene variants and/or gene expression in the aging lung results in the loss of epithelial integrity and consequently in the failure of the alveoli to correctly respond to injury and to face the stress associated with mechanical stretch. Afterward, a distinctive epigenetic "reprogramming" that affects both epithelial cells and fibroblasts provokes, among others, the recapitulation of developmental pathways and the aberrant activation and miscommunication between both cell types, resulting in the exaggerated production and accumulation of extracellular matrix and the subsequent destruction of the lung architecture.


Inducing articular cartilage phenotype in costochondral cells.
Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties. Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1. Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage.


Bird embryos perceive vibratory cues of predation risk from clutch mates.
During development in fluctuating environments, phenotypes can be adjusted to the conditions that individuals will probably encounter later in life. As developing embryos have a limited capacity to fully capture environmental information, theory predicts that they should integrate relevant information from all reliable sources, including the social environment. In many oviparous species, embryos are able to perceive cues of predator presence in some circumstances, but whether this information is socially transmitted among clutch mates-promoting phenotypic adjustments in the whole clutch-is unknown. Here, using an experimental design for which we modified the exposure to some, but not all, embryos of the same clutch to cues of predator presence (that is, alarm calls), we show that exposed embryos of the yellow-legged gull (Larus michahellis) and their unexposed clutch mates showed similar developmental changes that were absent in embryos from control clutches. Compared with the control broods, both embryos that were exposed to alarm calls and their unexposed clutch mates showed altered prenatal and postnatal behaviours, higher levels of DNA methylation and stress hormones, and reduced growth and numbers of mitochondria (which may be indicative of the capacity for energy production of cells). These results strongly suggest that gull embryos are able to acquire relevant environmental information from their siblings. Together, our results highlight the importance of socially acquired information during the prenatal stage as a non-genetic mechanism promoting developmental plasticity.


Microcontact Imprinted Plasmonic Nanosensors: Powerful Tools in the Detection of Salmonella paratyphi.
Identification of pathogenic microorganisms by traditional methods is slow and cumbersome. Therefore, the focus today is on developing new and quicker analytical methods. In this study, a Surface Plasmon Resonance (SPR) sensor with a microcontact imprinted sensor chip was developed for detecting Salmonella paratyphi. For this purpose, the stamps of the target microorganism were prepared and then, microcontact S. paratyphi-imprinted SPR chips were prepared with the functional monomer N-methacryloyl-L-histidine methyl ester (MAH). Characterization studies of the SPR chips were carried out with ellipsometry and scanning electron microscopy (SEM). The real-time Salmonella paratyphi detection was performed within the range of 2.5 × 10⁶-15 × 10⁶ CFU/mL. Selectivity of the prepared sensors was examined by using competing bacterial strains such as Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The imprinting efficiency of the prepared sensor system was determined by evaluating the responses of the SPR chips prepared with both molecularly imprinted polymers (MIPs) and non-imprinted polymers (NIPs). Real sample experiments were performed with apple juice. The recognition of Salmonella paratyphi was achieved using these SPR sensor with a detection limit of 1.4 × 10⁶ CFU/mL. In conclusion, SPR sensor has the potential to serve as an excellent candidate for monitoring Salmonella paratyphi in food supplies or contaminated water and clearly makes it possible to develop rapid and appropriate control strategies.


GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment.
General control nonderepressible 2 (GCN2) is an environmental sensor controlling transcription and translation in response to nutrient availability. Although GCN2 is a putative therapeutic target for immuno-oncology, its role in shaping the immune response to tumors is poorly understood. Here, we used mass cytometry, transcriptomics, and transcription factor-binding analysis to determine the functional impact of GCN2 on the myeloid phenotype and immune responses in melanoma. We found that myeloid-lineage deletion of GCN2 drives a shift in the phenotype of tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs) that promotes antitumor immunity. Time-of-flight mass cytometry (CyTOF) and single-cell RNA sequencing showed that this was due to changes in the immune microenvironment with increased proinflammatory activation of macrophages and MDSCs and interferon-γ expression in intratumoral CD8+ T cells. Mechanistically, GCN2 altered myeloid function by promoting increased translation of the transcription factor CREB-2/ATF4, which was required for maturation and polarization of macrophages and MDSCs in both mice and humans, whereas targeting Atf4 by small interfering RNA knockdown reduced tumor growth. Last, analysis of patients with cutaneous melanoma showed that GCN2-dependent transcriptional signatures correlated with macrophage polarization, T cell infiltrates, and overall survival. Thus, these data reveal a previously unknown dependence of tumors on myeloid GCN2 signals for protection from immune attack.


Reporting of diagnostic and laboratory tests by general hospitals as an indication of access to diagnostic laboratory services in Kenya.
Information on laboratory test availability and current testing scope among general hospitals in Kenya is not readily available. We sought to explore the reporting trends and test availability within clinical laboratories in Kenya over a 24-months period through analysis of the laboratory data reported in the District Health Information System (DHIS2). Monthly hospital laboratory testing data were extracted from the Kenyan DHIS2 between January 2018 and December 2019. We used the national laboratory testing summary tool (MoH 706) to identify the tests of interest among 204 general hospitals in Kenya. A local practitioner panel consisting of individuals with laboratory expertise was used to classify the tests as common and uncommon. We compared the tests on the MoH 706 template with the Essential Diagnostic List (EDL) of the World Health Organisation and further reclassified them into test categories based on the EDL for generalisability of our findings. Evaluation of the number of monthly test types reported in each facility and the largest number of tests ever reported in any of the 24 months were used to assess test availability and testing scope, respectively. Out of the 204 general hospitals assessed, 179 (179/204) reported at least one of the 80 tests of interest in any of the 24 months. Only 41% (74/179) of the reporting hospitals submitted all their monthly DHIS2 laboratory reports for the entire 24 months. The median testing capacity across the hospitals was 40% with a wide variation in testing scope from one hospital laboratory to another (% IQR: 33.8-51.9). Testing scope was inconsistent within facilities as indicated by often large monthly fluctuations in the total number of recommended and EDL tests reported. Tests of anatomical pathology and cancer were the least reported with 4 counties' hospitals not reporting any cancer or anatomical pathology tests for the entire 24 months. The current reporting of laboratory testing information in DHIS2 is poor. Monitoring access and utilisation of laboratory testing across the country would require significant improvements in consistency and coverage of routine laboratory test reporting in DHIS2. Nonetheless, the available data suggest unequal and intermittent population access to laboratory testing provided by general hospitals in Kenya.


Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification.
Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for fracture repair, but inefficient fibrinolysis decreases endochondral angiogenesis and ossification, thereby inhibiting fracture repair.


Functional assembly of intrinsic coagulation proteases on monocytes and platelets. Comparison between cofactor activities induced by thrombin and factor Xa.
Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of factor VIII to VIIIa. In the present studies, autocatalytic regulatory pathways operating on monocyte and platelet membranes were investigated by comparing the cofactor function of thrombin-activated factor VIII to that of factor Xa-activated factor VIII. Reciprocal functional titrations with purified human factor VIII and factor IXa were performed at fixed concentrations of human monocytes, CaCl2, factor X, and either factor IXa or factor VIII. Factor VIII was preactivated with either thrombin or factor Xa, and reactions were initiated by addition of factor X. Rates of factor X activation were measured using chromogenic substrate specific for factor Xa. The K1/2 values, i.e., concentration of factor VIIIa at which rates were half maximal, were 0.96 nM with thrombin-activated factor VIII and 1.1 nM with factor Xa-activated factor VIII. These values are close to factor VIII concentration in plasma. The Vsat, i.e., rates at saturating concentrations of factor VIII, were 33.3 and 13.6 nM factor Xa/min, respectively. The K1/2 and Vsat values obtained in titrations with factor IXa were not significantly different from those obtained with factor VIII. In titrations with factor X, the values of Michaelis-Menten coefficients (Km) were 31.7 nM with thrombin-activated factor VIII, and 14.2 nM with factor Xa-activated factor VIII. Maximal rates were 23.4 and 4.9 nM factor Xa/min, respectively. The apparent catalytic efficiency was similar with either form of factor VIIIa. Kinetic profiles obtained with platelets as a source of membrane were comparable to those obtained with monocytes. These kinetic profiles are consistent with a 1:1 stoichiometry for the functional interaction between cofactor and enzyme on the surface of monocytes and platelets. Taken together, these results indicate that autocatalytic pathways connecting the extrinsic, intrinsic, and common coagulation pathways can operate efficiently on the monocyte membrane.


Is treating anal furunculosis with 5 mg/kg ciclosporin once daily the optimal dosing schedule?
Critically Appraised Topics (CATs) are a standardised, succinct summary of research evidence organised around a clinical question, and a form of evidence synthesis used in the practice of evidence-based medicine (EBM) and evidence-based veterinary medicine (EBVM). Access to CATs enables clinicians to incorporate evidence from the scientific literature into clinical practice and they have been used to teach EBVM at the University of Bristol's School of Veterinary Sciences since 2011. CATs from Bristol university will be regularly published in the Clinical Decision Making section of Veterinary Record. The first CAT was published in VR, January 30, 2016, vol 178, pp 118-119.


Business model configuration and dynamics for technology commercialization in mature markets.
The food industry is a well-established and complex industry. New entrants attempting to penetrate it via the commercialization of a new technological innovation could face high uncertainty and constraints. The capability to innovate through collaboration and to identify suitable strategies and innovative business models (BMs) can be particularly important for bringing a technological innovation to this market. However, although the potential for these capabilities has been advocated, we still lack a complete understanding of how new ventures could support the technology commercialization process via the development of BMs. The paper aims to discuss these issues. To address this gap, this paper builds a conceptual framework that knits together the different bodies of extant literature (i.e. entrepreneurship, strategy and innovation) to analyze the BM innovation processes associated with the exploitation of emerging technologies; determines the suitability of the framework using data from the exploratory case study of IT IS 3D - a firm which has started to exploit 3D printing in the food industry; and improves the initial conceptual framework with the findings that emerged in the case study. From this analysis it emerged that: companies could use more than one BM at a time; hence, BM innovation processes could co-exist and be run in parallel; the facing of high uncertainty might lead firms to choose a closed and/or a familiar BM, while explorative strategies could be pursued with open BMs; significant changes in strategies during the technology commercialization process are not necessarily reflected in a radical change in the BM; and firms could deliberately adopt interim strategies and BMs as means to identify the more suitable ones to reach the market. This case study illustrates how firms could innovate the processes of their BM development to face the uncertainties linked with the entry into a mature and highly conservative industry (food).


Personal solar UV exposure measurements employing modified polysulphone with an extended dynamic range.
Polysulphone dosimeters using a simple to use filter have been developed and tested to provide an extended dynamic measurement range of personal solar UV exposures over an extended period (3 to 6 days). At a Southern Hemisphere subtropical site (27.6 degrees S, 151.9 degrees E), the dynamic range of the filtered polysulphone allowed measurements of erythemal exposures to approximately 100 minimum erythemal dose (MED) for a change in optical absorbance at 330 nm (deltaA330) of 0.35. In comparison, unfiltered polysulphone dosimeters were exposed to approximately 8 MED for the same deltaA330. The error associated with the use of the filtered polysulphone dosimeters is of the order of +/-15%, compared with +/-10% of the unfiltered variety. The developed filtered polysulphone dosimeter system allowed the measurement of erythemal UV exposures over 3 to 6 days at a subtropical site without the need to replace the dosimeters because of saturation. The results show that longer-term measurement programs of personal solar UV have been made more feasible with the use of these polysulphone dosimeters with an extended dynamic range compared with unfiltered polysulphone dosimeters.


Mixed permian-triassic fauna, guryul ravine, kashmir.
At Guryul Ravine near Srinagar, Kashmir, a varied fauna of productid brachiopods, including Spinomarginifera, is associated in approximately 15 feet (about 4 meters) of strata with the typical Scythian (Lower Triassic) pelecypod Claraia. These faunas are interpreted as true associations of surviving "Permian" and Lower Triassic faunal elements. Similar mixed associations have previously been identified in the lowest Triassic strata of the Salt Range and Surghar Range of West Pakistan.


The association between proximity to animal feeding operations and community health: a systematic review.
A systematic review was conducted for the association between animal feeding operations (AFOs) and the health of individuals living near AFOs. The review was restricted to studies reporting respiratory, gastrointestinal and mental health outcomes in individuals living near AFOs in North America, European Union, United Kingdom, and Scandinavia. From June to September 2008 searches were conducted in PUBMED, CAB, Web-of-Science, and Agricola with no restrictions. Hand searching of narrative reviews was also used. Two reviewers independently evaluated the role of chance, confounding, information, selection and analytic bias on the study outcome. Nine relevant studies were identified. The studies were heterogeneous with respect to outcomes and exposures assessed. Few studies reported an association between surrogate clinical outcomes and AFO proximity. A negative association was reported when odor was the measure of exposure to AFOs and self-reported disease, the measure of outcome. There was evidence of an association between self-reported disease and proximity to AFO in individuals annoyed by AFO odor. There was inconsistent evidence of a weak association between self-reported disease in people with allergies or familial history of allergies. No consistent dose response relationship between exposure and disease was observable.


Cerebral palsy: why we must plan for survival.
The survival of children in the South East Thames region, born between 1970 and 1979 and diagnosed as having some form of cerebral palsy was investigated. Of the 732 children studied, 651 (90%) are still alive, and hence cerebral palsy must be regarded as a condition with which people live rather than a condition of which they die. Survival varies considerably among the different diagnostic groups: those suffering from spasic quadriplegia, dyskinetic and 'mixed' cerebral palsy are most severely affected. Our evidence suggests that, though immobility and severe mental subnormality are the strongest predictors of mortality in children with cerebral palsy, the majority of even the most severely affected patients survive to adulthood. It is therefore appropriate to plan for their survival by funding and evaluating programmes to maximise health, independence, and quality of life.


Color vision deficiency in a middle-aged population: the Shahroud Eye Study.
The aim of this study was to determine the prevalence of color vision defects in the middle-age population of Shahroud, Iran. We selected 6,311 people from the 40- to 64-year-old population through random cluster sampling. Color vision testing was performed with the Farnsworth D-15. Cases with similar and symmetric results in both eyes were classified as hereditary, and those with asymmetric results were considered acquired. Cases that did not conform to standard patterns were classified as unknown category. Of 5,190 respondents (response rate 82.2 %), 5,102 participants underwent the color vision test. Of these, 14.7 % (95 % confidence interval 13.7-15.6) had some type of color vision deficiency. Of the 2,157 male participants, 6.2 % were hereditary and 10.2 % were acquired and of the 2,945 female participants, 3.1 % were hereditary and 10 % were acquired. Hereditary color deficiencies were mostly of the deutan form (63.8 %), and acquired deficiencies were mostly tritan (66.1 %). The prevalence of hereditary and acquired color vision deficiency, as well as different types of red-green and blue-yellow color vision defects significantly increased with age (p < 0.001). In conclusion, the pattern of color vision defects among the middle-aged population of Shahroud was significantly different from that seen in the younger population. This could be due to changes associated with age, gender, medical and ocular conditions, and differences in race and environment. Thus, results of previous examinations and the overall health status should be considered before making any judgment about the status of color vision in middle-aged people.


Transition Path Sampling Study of the Reaction Catalyzed by Purine Nucleoside Phosphorylase.
The Transition Path Sampling (TPS) method is a powerful technique for studying rare events in complex systems, that allows description of reactive events in atomic detail without prior knowledge of reaction coordinates and transition states. We have applied TPS in combination with a hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) method to study the enzyme human purine nucleoside phosphorylase (hPNP). This enzyme catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to generate the corresponding purine base and (deoxy)ribose 1-phosphate. Hundreds of reactive trajectories were generated. Analysis of this transition path ensembles provides insight into the detailed mechanistic dynamics of reaction in the enzyme. Our studies have indicated a reaction mechanism involving the cleavage of the N-ribosidic bond to form transition states with substantial ribooxacarbenium ion character, that is then followed by conformational changes in the enzyme and the ribosyl group leading to migration of the anomeric carbon of the ribosyl group toward phosphate to form the product ribose 1-phosphate. This latter process is crucial in PNP, because several strong H-bonds form between active site residues in order to capture and align the phosphate nucleophile. Calculations of the commitment probability along reactive paths demonstrated the presence of a broad energy barrier at the transition state. Analysis of these transition state structures showed that bond-breaking and bond-forming distances are not a good choice for the reaction coordinate, but that the pseudorotational phase of the ribose ring is also a significant variable.


Helmet use and associated factors among Thai motorcyclists during Songkran festival.
The aim of this study was to assess helmet use and associated factors among motorcycle riders during Songkran festival in Thailand. A cross-sectional survey was conducted to determine the prevalence of helmet use among Thai motorcycle riders (sample size = 18,998) during four days of the Songkran festival. For this sample, the population of motorcycle riders was consecutively selected using quota sampling from 12 petrol stations in four provinces from each of the four main geographical regions of Thailand. The study was conducted at petrol stations at roads in town, outside town and highway at different time intervals when trained field staff administered a structured questionnaire and performed an observation checklist. Results indicate that 44.2% of the motorcycle riders and 72.5% of the motorcycle passengers had not been using a helmet. In multivariable analysis demographics, environmental factors, helmet use experiences and attitudes and recalling a lower exposure to road safety awareness (RSA) campaign were associated with non-helmet use among motorcyclists. It appears that the RSA campaign may have some positive effect on reducing non-helmet use among motorcycle riders during the Songkran festival.


Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.
Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10-4) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10-10). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, PCDHA2, PCDHA3 and PCDHA5, were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia.


Relationship of pregnancy to human papillomavirus among human immunodeficiency virus-infected women.
Because parity is a reported risk factor for cervical cancer, we sought to estimate the effects of pregnancy on the prevalence, incident detection, and copy number of human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women, patients at high risk for cervical cancer. Human immunodeficiency virus-infected women who had a pregnancy in the Women's Interagency HIV Study (n = 178) and the Women and Infants Transmission Study (n = 450) underwent serial type-specific HPV DNA testing using MY09/MY11 polymerase chain reaction. During pregnancy and during the prepregnancy and postpregnancy periods, we assessed HPV prevalence, incident detection, and HPV copy number (estimated using hybridization signal strength) of both oncogenic and nononcogenic HPV. All binary-regression analyses incorporated generalized estimating equations to address the repeated observations of the same women over time, and were further adjusted for parity, gestational age, smoking, antiretroviral use, number of lifetime sexual partners, and oral contraceptive use. The prevalence and copy number of oncogenic and nononcogenic HPV did not significantly differ between pregnancy and either the prepregnancy or postpregnancy periods. Incident HPV detection was significantly lower for both oncogenic and nononcogenic HPV during pregnancy compared with the postpregnancy period (relative risk 0.534, 95% confidence interval 0.390-0.732, P < .001 and relative risk 0.577, 95% confidence interval 0.428-0.779, P < .001, respectively), but not compared with the prepregnancy period Among HIV-infected women, the incident detection of HPV is lower during pregnancy compared with postpregnancy, while prevalence and copy number do no differ between pregnancy and either prepregnancy or postpregnancy. II-3.


Susceptibility to prosocial and antisocial influence in adolescence following mindfulness training.
Mindfulness training programmes have shown to encourage prosocial behaviours and reduce antisocial tendencies in adolescents. However, less is known about whether training affects susceptibility to prosocial and antisocial influence. The current study investigated the effect of mindfulness training (compared with an active control) on self-reported prosocial and antisocial tendencies and susceptibility to prosocial and antisocial influence. 465 adolescents aged 11-16 years were randomly allocated to one of two training programmes. Pre- and post-training, participants completed a social influence task. Self-reported likelihood of engaging in prosocial and antisocial behaviours did not change post-training, and regardless of training group, participants showed a higher propensity for prosocial influence than for antisocial influence. Finally, participants were less influenced by antisocial ratings following both training programmes.


Resource efficient single photon source based on active frequency multiplexing.
We propose a new, to the best of our knowledge, single photon source based on the principle of active multiplexing of heralded single photons, which, unlike previously reported architecture, requires a limited amount of physical resources. We discuss both its feasibility and the purity and indistinguishability of single photons as a function of the key parameters of a possible implementation.


Adsorption Behavior of Cellulose and Its Derivatives toward Ag(I) in Aqueous Medium: An AFM, Spectroscopic, and DFT Study.
The aim of this study was to develop a fundamental understanding of the adsorption behavior of metal ions on cellulose surfaces using experimental techniques supported by computational modeling, taking Ag(I) as an example. Force interactions among three types of cellulose microspheres (native cellulose and its derivatives with sulfate and phosphate groups) and the silica surface in AgNO3 solution were studied with atomic force microscopy (AFM) using the colloidal probe technique. The adhesion force between phosphate cellulose microspheres (PCM) and the silica surface in the aqueous AgNO3 medium increased significantly with increasing pH while the adhesion force slightly decreased for sulfate cellulose microspheres (SCM), and no clear adhesion force was observed for native cellulose microspheres (CM). The stronger adhesion enhancement for the PCM system is mainly attributed to the electrostatic attraction between Ag(I) and the negative silica surface. The observed force trends were in good agreement with the measured zeta potentials. The scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) analyses confirmed the presence of silver on the surface of cellulose microspheres after adsorption. This study showed that PCM with a high content of phosphate groups exhibited a larger amount of adsorbed Ag(I) than CM and SCM and possible clustering of Ag(I) to nanoparticles. The presence of the phosphate group and a wavenumber shift of the P-OH vibration caused by the adsorption of silver ions on the phosphate groups were further confirmed with computational studies using density functional theory (DFT), which gives support to the above findings regarding the adsorption and clustering of Ag(I) on the cellulose surface decorated with phosphate groups as well as IR spectra.


The use of virtual reality in craving assessment and cue-exposure therapy in substance use disorders.
Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity paradigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue-exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue-exposure therapy with virtual environment, however, reported mitigated success so far.


A Study of the Validity of Two Exposure Assessment Tools: Stoffenmanager and the Advanced REACH Tool.
The use of exposure modelling tools for estimating chemical airborne exposure has increased since the European Union's REACH legislation for safe use of industrial chemicals came into force. Two tools that European Chemicals Agency recommends are Stoffenmanager® and the Advanced REACH Tool (ART). The aim of this study was to investigate the validity of these two exposure modelling tools by comparing the lack of agreement between estimated and measured exposure. We examined the airborne chemical exposure at companies in seven different types of industries: wood, printing, foundry, spray painting, flour milling, chemical industry, and plastic moulding industry. The inhalable exposure of liquids or powders at two to three situations at each company was modelled with both tools and measured. To study the validity of the tools, the mean differences and precisions (lack of agreement) of exposures from both situations handling liquids and powders were calculated by using the 50th percentile outcome of the tools and the geometric mean of the measured exposure (all data were ln transformed). For Stoffenmanager, the mean difference and precision of the situations concerning liquids were 0.22 ± 1.0 and for powders -0.024 ± 0.66. It was also shown that Stoffenmanager overestimated low exposures and underestimated high exposures. Stoffenmanager showed higher agreement with the measured exposure in the wood and flour mill industries than in foundry and the plastic moulding industry. For ART, the mean difference and precision of liquids were -0.55 ± 0.88 and for powders -1.4 ± 1.6. ART showed lower agreement with the measured exposure in the wood industry.


An investigation into the statistical properties of TB episodes in a South African community with high HIV prevalence.
Continuous differential equations are often applied to small populations with little time spent on understanding uncertainty brought about by small-population effects. Despite large numbers of individuals being latently infected with Mycobacterium tuberculosis (TB), progression from latent infection to observable disease is a relatively rare event. For small communities, this means case counts are subject to stochasticity, and deterministic models may not be appropriate tools for interpreting transmission trends. Furthermore, the nonlinear nature of the underlying dynamics means that fluctuations are autocorrelated, which can invalidate standard statistical analyses which assume independent fluctuations. Here we extend recent work using a system of differential equations to study the HIV-TB epidemic in Masiphumelele, a community near Cape Town in South Africa [Bacaër, et al., J. Mol. Biol. 57(4), 557-593] by studying the statistical properties of active TB events. We apply van Kampen's system-size (or population-size) expansion technique to obtain an approximation to a master equation describing the dynamics. We use the resulting Fokker-Planck equation and point-process theory to derive two-time correlation functions for active TB events. This method can be used to gain insight into the temporal aspect of cluster identification, which currently relies on DNA classification only.


Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring.
Cerebral blood flow (CBF) during stepped hypercapnia was measured simultaneously in the rat brain using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeling MRI (ASL). DCS and ASL CBF values agree very well, with high correlation (R=0.86, p< 10(-9)), even when physiological instability perturbed the vascular response. A partial volume effect was evident in the smaller magnitude of the optical CBF response compared to the MRI values (averaged over the cortical area), primarily due to the inclusion of white matter in the optically sampled volume. The 8.2 and 11.7 mm mid-separation channels of the multi-distance optical probe had the lowest partial volume impact, reflecting ~75 % of the MR signal change. Using a multiplicative correction factor, the ASL CBF could be predicted with no more than 10% relative error, affording an opportunity for real-time relative cerebral metabolism monitoring in conjunction with MR measurement of cerebral blood volume using super paramagnetic contrast agents.


I lie, why don't you: Neural mechanisms of individual differences in self-serving lying.
People tend to lie in varying degrees. To advance our understanding of the underlying neural mechanisms of this heterogeneity, we investigated individual differences in self-serving lying. We performed a functional magnetic resonance imaging study in 37 participants and introduced a color-reporting game where lying about the color would in general lead to higher monetary payoffs but would also be punished if get caught. At the behavioral level, individuals lied to different extents. Besides, individuals who are more dishonest showed shorter lying response time, whereas no significant correlation was found between truth-telling response time and the degree of dishonesty. At the neural level, the left caudate, ventromedial prefrontal cortex (vmPFC), right inferior frontal gyrus (IFG), and left dorsolateral prefrontal cortex (dlPFC) were key regions reflecting individual differences in making dishonest decisions. The dishonesty associated activity in these regions decreased with increased dishonesty. Subsequent generalized psychophysiological interaction analyses showed that individual differences in self-serving lying were associated with the functional connectivity among the caudate, vmPFC, IFG, and dlPFC. More importantly, regardless of the decision types, the neural patterns of the left caudate and vmPFC during the decision-making phase could be used to predict individual degrees of dishonesty. The present study demonstrated that lying decisions differ substantially from person to person in the functional connectivity and neural activation patterns which can be used to predict individual degrees of dishonesty.


β2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies.
The β(2)-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD). We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p < 0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV(1) % pred and 6% and 1% reduced FEV(1)/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54-13.3) and 1.07 (95% CI 0.92-1.25), respectively. Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population.


Introducing a Supportive Care Team for Advance Directive Education in a Neurological and Neurosurgical Patient Population.
Patient-centered care includes delineation of patient treatment values (ie, advance care planning [ACP]). Advance care planning often includes advance directive (AD) completion and is underutilized, particularly among neurology and neurosurgery patients. Implementation of a supportive care team (SCT) in outpatient clinic settings may offer opportunities for AD education and completion. This study assesses the effectiveness of an integrative SCT composed of hospice volunteers and undergraduate quality improvement interns in their efforts to provide ACP education in neurological and neurosurgical outpatient clinics. Assessment includes a description of different types of SCT-patient encounters, as well as patient interest in and completion of ADs after interacting with the SCT. Across the data collection period, 2770 encounters were initiated. The majority of encounters resulted in patient ACP education. Some patients completed ADs during their SCT encounter (3.45%) or after their SCT encounter (10.18%). The SCT effectively enhances ACP education in this patient population. The utilization of trained interns to assist with ACP is beneficial and practical in clinic workflow.


Substance flow analysis as a tool for mitigating the impact of pharmaceuticals on the aquatic system.
Pharmaceuticals constitute an important environmental issue for receiving waters. A holistic approach, taking into consideration the sources of these compounds (hospitals, domestic use), discharges (wastewater effluent, combined sewer overflows) and related risks to the environment, is therefore needed to develop the best protection strategy. The substance flow analysis (SFA) approach, applied, for example, to the city of Lausanne, Switzerland, is an ideal tool to tackle these issues. Four substances were considered: one antibiotic (ciprofloxacin), an analgesic (diclofenac), and two anti-epileptics (carbamazepine and gabapentin). Consumption data for the main hospital of the city (916 beds) and for the population were available. Micropollutant concentrations were measured at different points of the system: wastewater inlet and outlet (WWTP), combined sewer overflows (CSO) and in the receiving waters (Vidy Bay, Lake Geneva). Measured and predicted concentrations were in agreement, except for diclofenac, for which analytical uncertainties were expected. Seven different scenarios were considered (supplementary treatment at the WWTP, at the hospital or at both places, etc.). Based on the results obtained, the supplementary treatment at the WWTP decreases the load of pharmaceuticals reaching surface water by a factor between 2 and 27, depending on the compound and on the technique. The treatment at the hospitals only influences the amount of ciprofloxacin reaching the environment and decreases the release by one third. The contribution of CSO to surface water pollution is low compared to that of the WWTP for the selected compounds. Regarding the risk for the receiving waters, ciprofloxacin was found to be the most problematic compound, with a risk quotient far above 1. In this particular case, a treatment at the WWTP is not sufficient to reduce the risk, and additional measures at the CSO or at the hospital should be considered. SFA is an ideal tool for developing the best strategy for pharmaceutical elimination, but its application depends on data availability and local conditions.


Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin's lymphoma.
Mitoxantrone (Novantrone, American Cyanamid Company; NO) and high-dose cytarabine (Ara-C; AC) have each been shown to be active in non-Hodgkin's lymphomas (NHL) in various studies. The studies reported here are sequential. The first study (NOAC I) combined high-dose cytarabine (3 g/m2/12 h as a 3 h infusion on day 1) with mitoxantrone (10 mg/m2/d on days 2 and 3). Of 31 patients with relapsed and refractory NHL, 7 achieved complete remission (CR) and 7, partial remission (PR). Myelosuppression was the major toxicity of this regimen. In the second study (NOAC II), the dosage of cytarabine was escalated to 3 g/m2/12 h on days 1 and 2 (4 doses) while mitoxantrone remained 10 mg/m2/d on days 2 and 3. The effects of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) were simultaneously studied. Twenty-three patients from five centers were treated with NOAC plus rhGM-CSF while 14 patients from four centers received NOAC II alone. A CR was achieved in 9 of 23 patients who received the additional rhGM-CSF and in 2 of 14 patients treated with NOAC alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nL) after chemotherapy was 8 days versus a median of 13 days without rhGM-CSF, while the duration of severe thrombocytopenia (less than 20/nL) was not significantly different. The rates of infection and mucositis were 25% and 17%, respectively, with rhGM-CSF compared to 53% and 60% without rhGM-CSF. Thus, this last nonrandomized pilot study indicates that administration of rhGM-CSF reduces the duration of chemotherapy-induced cytopenia and the rate of mucositis. This growth factor does not appear to result in stimulation of lymphoma cells. At present, a controlled randomized trial is being conducted using NOAC II with rhGM-CSF or placebo to establish the definitive role of this growth factor in the treatment of NHL.


The sociodemographic pattern of tobacco cessation in the 1980s: results from a panel study of living condition surveys in Sweden.
To analyse the factors that determined whether or not people were successful in quitting tobacco during the 1980s in Sweden. A logistic regression model was used for the analyses and included: education, marital status, socioeconomic group, social network, physical activities, cigarette consumption, and years spent smoking as independent variables. Men and women were analysed separately for smoking. A specific univariate analysis was also performed for men who used snuff. Sweden. A panel of 5104 randomised people aged 16-84 years was interviewed in 1980-81 and followed up in 1988-89 in the survey of living conditions undertaken by Statistics Sweden. The participation rate was 86%. The panel included 1546 men and women who were daily smokers. There were 418 daily users of snuff among the men, and 129 men both smoked and used snuff. Together 26% of women and 23% of men had quit smoking. Five percent in both groups were new smokers. Among men, 26% had quit using snuff and 5% had begun smoking. New snuff users among men were 5%. In the multivariate analysis, unmarried men kept smoking at significantly higher rates (OR 2.1; 95% CI 1.2,3.6), as did those men who smoked 11-20 cigarettes/day (OR 2.2; 95% CI 1.5, 3.4), or more than 20 cigarettes/day (OR 2.8; 95% CI 1.4,5.7). Among women, smoking 11-20 cigarettes/day was also a significant factor (OR 3.3; 95% CI 2.1,5.0). Men and women aged 25-44 were significantly more likely to continue smoking (OR = 2.1; 95% CI 1.1,3.7, and 2.2; 95% CI 1.2,4.4) as were those who had smoked for 20 years or more (OR 4.7; 95% CI 2.0,10.8 and OR 2.5; 95% CI 1.1,5.5, respectively). For women, low education (up to grade 9) was also a significant factor (OR = 2.5; 95% CI 1.2,5.1). Among men who had quit using snuff we did not find any values of significance. One in four smokers had quit during the 1980s and a few started smoking (5%). Some men quit smoking and started using snuff instead. For both sexes, the daily consumption of cigarettes, years spent smoking, and age were the most important determinants of successful quitting. In men, being married/ cohabiting was an important factor as was higher education in women.


Structuring polymers for delivery of DNA-based therapeutics: updated insights.
Gene therapy offers greater opportunities for treating numerous incurable diseases from genetic disorders, infections, and cancer. However, development of appropriate delivery systems could be one of the most important factors to overcome numerous biological barriers for delivery of various therapeutic molecules. A number of nonviral polymer-mediated vectors have been developed for DNA delivery and offer the potential to surmount the associated problems of their viral counterpart. To address the concerns associated with safety issues, a wide range of polymeric vectors are available and have been utilized successfully to deliver their therapeutics in vivo. Today's research is mainly focused on the various natural or synthetic polymer-based delivery carriers that protect the DNA molecule from degradation, which offer specific targeting to the desired cells after systemic administration, have transfection efficiencies equivalent to virus-mediated gene delivery, and have long-term gene expression through sustained-release mechanisms. This review explores an updated overview of different nonviral polymeric delivery system for delivery of DNA-based therapeutics. These polymeric carriers have been evaluated in vitro and in vivo and are being utilized in various stages of clinical evaluation. Continued research and understanding of the principles of polymer-based gene delivery systems will enable us to develop new and efficient delivery systems for the delivery of DNA-based therapeutics to achieve the goal of efficacious and specific gene therapy for a vast array of clinical disorders as the therapeutic solutions of tomorrow.


Neuromuscular electrical stimulation-assisted gait increases muscle strength and volume in children with unilateral spastic cerebral palsy.
To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP). Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control. At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14. Eight weeks of daily NMES-assisted gait increases muscle volume and strength of the stimulated ankle dorsiflexors in children with unilateral spastic CP. These changes are use-dependent and do not carry over after the 8-week treatment period. Gastrocnemius volume also increased post-treatment with carryover at week 14.


Infective causes of stroke in tropical regions.
Vascular diseases of the brain are the second reason of the death and the first cause of morbidity and disability worldwide. In tropical areas stroke has some particular features related to the nature of torrid zones. There are some special causes of the stroke, mainly infectious, although some of them are non-infectious. The most important etiologies are malaria, tuberculosis, cysticercosis, syphilis, and Chagas' disease. The mean age of the patients with stroke in tropical areas seems to be less than that in developed countries, and the disease is more prevalent in younger adults. Prevention and/or treatment of the classic risk factors as well as factors related to tropical zones are the mainstays of controlling the disease. It has to be mentioned that lack of human as well as financial resources makes it difficult to control and treat the disease properly. Herein, the etiologies and risk factors of the cerebrovascular diseases in tropical regions will be reviewd.


Identification and purification of two distinct complexes containing the five RAD51 paralogs.
Cells defective in any of the RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are sensitive to DNA cross-linking agents and to ionizing radiation. Because the paralogs are required for the assembly of DNA damage-induced RAD51 foci, and mutant cell lines are defective in homologous recombination and show genomic instability, their defect is thought to be caused by an inability to promote efficient recombinational repair. Here, we show that the five paralogs exist in two distinct complexes in human cells: one contains RAD51B, RAD51C, RAD51D, and XRCC2 (defined as BCDX2), whereas the other consists of RAD51C with XRCC3. Both protein complexes have been purified to homogeneity and their biochemical properties investigated. BCDX2 binds single-stranded DNA and single-stranded gaps in duplex DNA, in accord with the proposal that the paralogs play an early (pre-RAD51) role in recombinational repair. Moreover, BCDX2 complex binds specifically to nicks in duplex DNA. We suggest that the extreme sensitivity of paralog-defective cell lines to cross-linking agents is owing to defects in the processing of incised cross links and the consequential failure to initiate recombinational repair at these sites.


Cancer pharmacogenomics: early promise, but concerted effort needed.
The past decade has brought together substantial advances in human genome analysis and a maturation of understanding of tumor biology. Although there is much progress still to be made, there are now several prominent examples in which tumor-associated somatic mutations have been used to identify cellular signaling pathways in tumors. This in turn has led to the development of targeted therapies, with somatic mutations serving as genomic predictors of tumor response and providing new leads for drug development. There is also a realization that germline DNA variants can help optimize cancer drug dosing and predict the susceptibility of patients to the adverse side effects of these drugs-knowledge that ultimately can be used to improve the benefit:risk ratio of cancer treatment for individual patients.


Eliminating Health Care Disparities With Mandatory Clinical Decision Support: The Venous Thromboembolism (VTE) Example.
All hospitalized patients should be assessed for venous thromboembolism (VTE) risk factors and prescribed appropriate prophylaxis. To improve best-practice VTE prophylaxis prescription for all hospitalized patients, we implemented a mandatory computerized clinical decision support (CCDS) tool. The tool requires completion of checklists to evaluate VTE risk factors and contraindications to pharmacological prophylaxis, and then recommends the risk-appropriate VTE prophylaxis regimen. The objective of the study was to examine the effect of a quality improvement intervention on race-based and sex-based health care disparities across 2 distinct clinical services. This was a retrospective cohort study of a quality improvement intervention. The study included 1942 hospitalized medical patients and 1599 hospitalized adult trauma patients. In this study, the proportion of patients prescribed risk-appropriate, best-practice VTE prophylaxis was evaluated. Racial disparities existed in prescription of best-practice VTE prophylaxis in the preimplementation period between black and white patients on both the trauma (70.1% vs. 56.6%, P=0.025) and medicine (69.5% vs. 61.7%, P=0.015) services. After implementation of the CCDS tool, compliance improved for all patients, and disparities in best-practice prophylaxis prescription between black and white patients were eliminated on both services: trauma (84.5% vs. 85.5%, P=0.99) and medicine (91.8% vs. 88.0%, P=0.082). Similar findings were noted for sex disparities in the trauma cohort. Despite the fact that risk-appropriate prophylaxis should be prescribed equally to all hospitalized patients regardless of race and sex, practice varied widely before our quality improvement intervention. Our CCDS tool eliminated racial disparities in VTE prophylaxis prescription across 2 distinct clinical services. Health information technology approaches to care standardization are effective to eliminate health care disparities.


Preconditioning, organ preservation, and postconditioning to prevent ischemia-reperfusion injury to the liver.
Ischemia and reperfusion lead to injury of the liver. Ischemia-reperfusion injury is inevitable in liver transplantation and trauma and, to a great extent, in liver resection. This article gives an overview of the mechanisms involved in this type of injury and summarizes protective and treatment strategies in clinical use today. Intervention is possible at different time points: during harvesting, during the period of preservation, and during implantation. Liver preconditioning and postconditioning can be applied in the transplant setting and for liver resection. Graft optimization is merely possible in the period between the harvest and the implantation. Given that there are 3 stages in which a surgeon can intervene against ischemia-reperfusion injury, we have structured the review as follows. The first section reviews the approaches using surgical interventions, such as ischemic preconditioning, as well as pharmacological applications. In the second section, static organ preservation and machine perfusion are addressed. Finally, the possibility of treating the recipient or postconditioning is discussed.


Details of left ventricular radial wall motion supporting the ventricular theory of the third heart sound obtained by cardiac MR.
Obtaining new details of radial motion of left ventricular (LV) segments using velocity-encoding cardiac MRI. Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Cine images for navigator-gated phase contrast velocity mapping were acquired using a black blood segmented κ-space spoiled gradient echo sequence with a temporal resolution of 13.8 ms. Peak systolic and diastolic radial velocities as well as radial velocity curves were obtained for 16 ventricular segments. Significant differences among peak radial velocities of basal and mid-ventricular segments have been recorded. Particular patterns of segmental radial velocity curves were also noted. An additional wave of outward radial movement during the phase of rapid ventricular filling, corresponding to the expected timing of the third heart sound, appeared of particular interest. The technique has allowed visualization of new details of LV radial wall motion. In particular, higher peak systolic radial velocities of anterior and inferior segments are suggestive of a relatively higher dynamics of anteroposterior vs lateral radial motion in systole. Specific patterns of radial motion of other LV segments may provide additional insights into LV mechanics. The outward radial movement of LV segments impacted by the blood flow during rapid ventricular filling provides a potential substrate for the third heart sound. A biphasic radial expansion of the basal anteroseptal segment in early diastole is likely to be related to the simultaneous longitudinal LV displacement by the stretched great vessels following repolarization and their close apposition to this segment.


Pd-P nanoparticles supported on PxOy-incorporated carbon nanotubes for enhanced methanol oxidation in an alkaline medium.
Phosphorous oxide (PxOy)-incorporated carbon nanotubes (PCNTs) and nitric acid treated carbon nanotubes (OCNTs) are first synthesized, then phosphorous modified palladium nanoparticles (Pd-P NPs) supported on PCNTs (Pd-P/PCNTs) and OCNTs (Pd-P/OCNTs) are synthesized and employed as electrocatalysts in a methanol oxidation reaction. Pd-P/PCNTs show enhanced electrocatalytic activity and stability in comparison to Pd-P/OCNTs. Combining surface analysis and electrochemical performance, PxOy incorporated into CNTs could create anchoring sites for Pd ions and P precursors, which could facilitate the synthesis of Pd-P NPs in an aqueous solution containing Pd ions and sodium hypophosphite serving as a reducing agent and a P source. The electronic modification of embedded Pd-P NPs on PxOy-incorporated CNTs accounts for the enhanced electrochemical performance of Pd-P/PCNTs.


Social Inequalities in Young Children's Meal Skipping Behaviors: The Generation R Study.
Regular meal consumption is considered an important aspect of a healthy diet. While ample evidence shows social inequalities in breakfast skipping among adolescents, little is known about social inequalities in breakfast skipping and skipping of other meals among young school-aged children. Such information is crucial in targeting interventions aimed to promote a healthy diet in children. We examined data from 4704 ethnically diverse children participating in the Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Information on family socioeconomic position (SEP), ethnic background, and meal skipping behaviors was assessed by parent-reported questionnaire when the child was 6 years old. Multiple logistic regression analyses were performed to assess the associations of family SEP (educational level, household income, employment status, family composition) and ethnic background with meal skipping behaviors, using high SEP children and native Dutch children as reference groups. Meal skipping prevalence ranged from 3% (dinner) to 11% (lunch). The prevalence of meal skipping was higher among low SEP children and ethnic minority children. Maternal educational level was independently associated with breakfast skipping ([low maternal educational level] OR: 2.21; 95% CI: 1.24,3.94). Paternal educational level was independently associated with lunch skipping ([low paternal educational level] OR: 1.53; 95% CI: 1.06,2.20) and dinner skipping ([mid-high paternal educational level] OR: 0.39; 95% CI: 0.20,0.76). Household income was independently associated with breakfast skipping ([low income] OR: 2.43, 95% CI: 1.40,4.22) and dinner skipping ([low income] OR: 2.44; 95% CI: 1.22,4.91). In general, ethnic minority children were more likely to skip breakfast, lunch, and dinner compared with native Dutch children. Adjustment for family SEP attenuated the associations of ethnic minority background with meal skipping behaviors considerably. Low SEP children and ethnic minority children are at an increased risk of breakfast, lunch, and dinner skipping compared with high SEP children and native Dutch children, respectively. Given these inequalities, interventions aimed to promote regular meal consumption, breakfast consumption in particular, should target children from low socioeconomic groups and ethnic minority children. More qualitative research to investigate the pathways underlying social inequalities in children's meal skipping behaviors is warranted.