Relationship between bone and muscles of mastication in hemifacial microsomia.
The relationship between the bone and muscles of mastication in hemifacial microsomia was studied using three-dimensional volumetric computed tomography scans and image processing techniques. High resolution head computed tomography scans were obtained from 31 patients with unilateral hemifacial microsomia and eight normal patients. Using three-dimensional volume renderings of bone, mandibular deformities in patients with hemifacial microsomia were classified using the Pruzansky system. For each patient, specific craniofacial bones (temporal bone, maxilla mandible) and the muscles of mastication (masseter, temporalis and lateral and medial pterygoid) were segmented bilaterally from the image volume for independent display and volume measurement. Volumes were expressed as the ratio of the affected: unaffected sides. For the masseter and temporalis, the relationship between muscular hypoplasia and osseous hypoplasia in its origin and insertion was studied by plotting affected:unaffected bone volume as a function of affected:unaffected muscle volume for each muscle, bone of origin, bone of insertion triplet. The volumes of the pterygoid muscles were compared with hemimandibular volumes. The precision of object segmentations was examined by repetitive definition tasks, whereas the accuracy of volume measurement was tested by scanning custom-made phantom objects and comparing digital to physical object volume measurements. Volume measurements performed using these techniques were both accurate and precise. In hemifacial microsomia, the extent of hypoplasia of specific muscles of mastication predicted the extent of dysplasia in their osseous origin and insertion. However, the reverse was not true. The extent of hypoplasia of the facial bones did not necessarily predict the extent of hypoplasia in the attached muscles of mastication. Pruzansky grade of the mandible described the degree of mandibular hypoplasia on the affected side, but was inconsistent in its prediction of volume decrease of the other facial bones.


Evaluating the impact of varied compliance to lung cancer screening recommendations using a microsimulation model.
The US preventive services task force (USPSTF) recently recommended that individuals aged 55-80 with heavy smoking history be annually screened by low-dose computed tomography (LDCT), thereby extending the stopping age from 74 to 80 compared to the national lung screening trial (NLST) entry criterion. This decision was made partly with model-based analyses from cancer intervention and surveillance modeling network (CISNET), which assumed perfect compliance to screening. As part of CISNET, we developed a microsimulation model for lung cancer (LC) screening and calibrated and validated it using data from NLST and the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO), respectively. We evaluated population-level outcomes of the lifetime screening program recommended by the USPSTF by varying screening compliance levels. Validation using PLCO shows that our model reproduces observed PLCO outcomes, predicting 884 LC cases [Expected(E)/Observed(O) = 0.99; CI 0.92-1.06] and 563 LC deaths (E/O = 0.94 CI 0.87-1.03) in the screening arm that has an average compliance rate of 87.9% over four annual screening rounds. We predict that perfect compliance to the USPSTF recommendation saves 501 LC deaths per 100,000 persons in the 1950 U.S. birth cohort; however, assuming that compliance behaviors extrapolated and varied from PLCO reduces the number of LC deaths avoided to 258, 230, and 175 as the average compliance rate over 26 annual screening rounds changes from 100 to 46, 39, and 29%, respectively. The implementation of the USPSTF recommendation is expected to contribute to a reduction in LC deaths, but the magnitude of the reduction will likely be heavily influenced by screening compliance.


The role of cytogenetic abnormalities as a prognostic marker in primary myelofibrosis: applicability at the time of diagnosis and later during disease course.
Although cytogenetic abnormalities are important prognostic factors in myeloid malignancies, they are not included in current prognostic scores for primary myelofibrosis (PMF). To determine their relevance in PMF, we retrospectively examined the impact of cytogenetic abnormalities and karyotypic evolution on the outcome of 256 patients. Baseline cytogenetic status impacted significantly on survival: patients with favorable abnormalities (sole deletions in 13q or 20q, or trisomy 9 +/- one other abnormality) had survivals similar to those with normal diploid karyotypes (median, 63 and 46 months, respectively), whereas patients with unfavorable abnormalities (rearrangement of chromosome 5 or 7, or > or = 3 abnormalities) had a poor median survival of 15 months. Patients with abnormalities of chromosome 17 had a median survival of only 5 months. A model containing karyotypic abnormalities, hemoglobin, platelet count, and performance status effectively risk-stratified patients at initial evaluation. Among 73 patients assessable for clonal evolution during stable chronic phase, those who developed unfavorable or chromosome 17 abnormalities had median survivals of 18 and 9 months, respectively, suggesting the potential role of cytogenetics as a risk factor applicable at any time in the disease course. Dynamic prognostic significance of cytogenetic abnormalities in PMF should be further prospectively evaluated.


Brain responses strongly correlate with Weibull image statistics when processing natural images.
The visual appearance of natural scenes is governed by a surprisingly simple hidden structure. The distributions of contrast values in natural images generally follow a Weibull distribution, with beta and gamma as free parameters. Beta and gamma seem to structure the space of natural images in an ecologically meaningful way, in particular with respect to the fragmentation and texture similarity within an image. Since it is often assumed that the brain exploits structural regularities in natural image statistics to efficiently encode and analyze visual input, we here ask ourselves whether the brain approximates the beta and gamma values underlying the contrast distributions of natural images. We present a model that shows that beta and gamma can be easily estimated from the outputs of X-cells and Y-cells. In addition, we covaried the EEG responses of subjects viewing natural images with the beta and gamma values of those images. We show that beta and gamma explain up to 71% of the variance of the early ERP signal, substantially outperforming other tested contrast measurements. This suggests that the brain is strongly tuned to the image's beta and gamma values, potentially providing the visual system with an efficient way to rapidly classify incoming images on the basis of omnipresent low-level natural image statistics.


Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.
Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.


The cyclic AMP phenotype of fragile X and autism.
Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.


Transcriptomic resilience to global warming in the seagrass Zostera marina, a marine foundation species.
Large-scale transcription profiling via direct cDNA sequencing provides important insights as to how foundation species cope with increasing climatic extremes predicted under global warming. Species distributed along a thermal cline, such as the ecologically important seagrass Zostera marina, provide an opportunity to assess temperature effects on gene expression as a function of their long-term adaptation to heat stress. We exposed a southern and northern European population of Zostera marina from contrasting thermal environments to a realistic heat wave in a common-stress garden. In a fully crossed experiment, eight cDNA libraries, each comprising ~125 000 reads, were obtained during and after a simulated heat wave, along with nonstressed control treatments. Although gene-expression patterns during stress were similar in both populations and were dominated by classical heat-shock proteins, transcription profiles diverged after the heat wave. Gene-expression patterns in southern genotypes returned to control values immediately, but genotypes from the northern site failed to recover and revealed the induction of genes involved in protein degradation, indicating failed metabolic compensation to high sea-surface temperature. We conclude that the return of gene-expression patterns during recovery provides critical information on thermal adaptation in aquatic habitats under climatic stress. As a unifying concept for ecological genomics, we propose transcriptomic resilience, analogous to ecological resilience, as an important measure to predict the tolerance of individuals and hence the fate of local populations in the face of global warming.


Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers.
Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetaminophen and phenylephrine. A series of four randomised, open-label, crossover studies investigating phenylephrine and acetaminophen combination pharmacokinetics were undertaken (n = 28, 30, 6 and 26) using standard non-compartmental analyses. Time-concentration observations from these four studies were pooled to examine the interaction between these two compounds. Data were analysed using non-linear mixed effects models. Non-compartmental analyses showed an approximate doubling of phenylephrine plasma concentration when the standard 10-mg dose was administered in combination with acetaminophen. Population analysis was based on data from 90 subjects with 2050 observations. The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone. The relative bioavailability of phenylephrine was increased when co-administered with acetaminophen.


The alpha-glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth.
The development of drugs that target the tumor neovasculature may hold promise in inhibiting tumor growth. Experiments in vivo with castanospermine, an inhibitor of the glucosidases that convert protein N-linked high mannose carbohydrates to complex oligosaccharides, resulted in significant inhibition of tumor growth in nude mice. Angiogenesis to basic fibroblast growth factor in castanospermine-treated C57/BL mice was similarly reduced. Endothelial cell proliferation, invasion of basement membrane, and differentiation are crucial steps during neovascularization. In vitro differentiation models using Matrigel and postconfluent cultures of endothelial cells were used to study the effects of glycosidase inhibitors on endothelial cell behavior. FACS analysis of cell surface oligosaccharides using either Concanavalin A or L-phytohemagglutinin lectins confirmed an increase in high mannose groups and a decrease in tri- and tetra antennary beta-linked galactose-N-acetylglucosamine on mannose residues of Asn-linked oligosaccharides upon drug treatment. Castanospermine and the glucosidase inhibitor N-methyldeoxynojirimycin prevented the morphological differentiation of endothelial cells in vitro. These compounds did not alter the proliferation of cultured endothelial cells or their ability to attach to various extracellular matrix molecules. However, the cells showed a reduced ability to migrate and to invade basement membrane gels in vitro and an increased tendency to form aggregates that was inhibitable by D-mannose. These studies suggest that certain cell surface oligosaccharides are required for angiogenesis and that glucosidase inhibitors that alter these structures on endothelial cells are able to inhibit tumor growth.


Enhancing Literacy in Cardiovascular Genetics: A Scientific Statement From the American Heart Association.
Advances in genomics are enhancing our understanding of the genetic basis of cardiovascular diseases, both congenital and acquired, and stroke. These advances include finding genes that cause or increase the risk for childhood and adult-onset diseases, finding genes that influence how patients respond to medications, and the development of genetics-guided therapies for diseases. However, the ability of cardiovascular and stroke clinicians to fully understand and apply this knowledge to the care of their patients has lagged. This statement addresses what the specialist caring for patients with cardiovascular diseases and stroke should know about genetics; how they can gain this knowledge; how they can keep up-to-date with advances in genetics, genomics, and pharmacogenetics; and how they can apply this knowledge to improve the care of patients and families with cardiovascular diseases and stroke.


MnSOD overexpression reduces fibrosis and pro-apoptotic signaling in the aging mouse heart.
Contractility of the heart is impaired with advancing age via mechanical remodeling, as myocytes are lost through apoptosis and collagenous fibers accumulate. Exercise training confers protection against fibrosis and apoptosis in the aging heart, but the mechanisms remain poorly understood. We recently reported that exercise training elevates Mn isoform of superoxide dismutase (MnSOD) in the aging heart, concomitant with reduction in oxidative stress and fibrosis. Here, we tested the hypothesis that overexpression of MnSOD would be causal in protection against fibrosis and apoptosis in the aging heart. Hearts were extracted from young (8 months) wild-type, young mice overexpressing the Sod2 (MnSOD) gene, old (28 months) wild-type, and old transgenic mice. Left ventricle MnSOD protein levels were elevated in young mice overexpressing the Sod2 (MnSOD) gene and old transgenic mice. MnSODTg mice exhibited lower oxidative stress (total hydroperoxides, 4-hydroxynonenal, and 8-isoprostane) in the old group. Age-related cardiac remodeling and fibrosis was mitigated in MnSOD Tg mice with reductions in extramyocyte space (-65%), collagen-I, and transforming growth factor-β. Pro-apoptotic markers Bax (-38%) and caspase-3 cleavage (-41%) were reduced and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei, DNA laddering) was mitigated in MnSOD Tg hearts compared with old wild-type. We conclude that MnSOD elevation is indeed protective against oxidative stress, fibrosis, and apoptosis in the aging heart.


A phosphoglycoprotein associated with taxol resistance in J774.2 cells.
Taxol is an inhibitor of cell replication that promotes the assembly of microtubules in vitro and in cells. In the murine macrophage-like cell line J774.2, a taxol-resistant subline (J7/TAX-50) has been developed in vitro by growing the cells in increasing drug concentrations. These cells, which are approximately 800-fold resistant to taxol, display some cross-resistance to colchicine, vinblastine, puromycin, doxorubicin, and actinomycin D but remain sensitive to bleomycin. Binding of radiolabeled drug to the resistant cells is reduced by approximately 90%. Resistant cells grown in the absence of drug for 10 days (J7/TAX-0D10), 1 month (J7/TAX-0D30), and 8 months (J7/TAX-0D240) regain a major portion (27, 92, and 99%, respectively) of their sensitivity to the drug. However, binding of the drug to the J7/TAX-0D30 and J7/TAX-0D240 cells is increased to only 20 and 70%, respectively, of that measured with sensitive cells. Analysis of plasma membranes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining reveals the presence of a prominent protein with an approximate molecular weight of 135,000 in the resistant line that is essentially absent from the parental line and from both of the J7/TAX-0D30 and J7/TAX-0D240 lines. Although this protein can be seen in J7/TAX-0D10, its quantity is diminished. The Mr 135,000 protein is also observed in the resistant cells when they are labeled with [3H]leucine, [35S]methionine, [3H]glucosamine, or [32P]orthophosphate. Plasma membranes from colchicine- or vinblastine-resistant J774.2 cells also contain prominent phosphoglycoproteins, with approximate molecular weights of 145,000 and 150,000, respectively. Partial purification of the Mr 135,000 glycoprotein by agarose-bound ricinus communis agglutinin I-agarose affinity chromatography indicates that it accounts for approximately 4 to 5% of total membrane protein. A Mr 100,000 phosphoglycoprotein, present in the membranes of J774.2 cells is essentially absent in J7/TAX-50 cells after labeling with [3H]glucosamine or [32P]orthophosphate. Phosphoamino acid analysis of the Mr 135,000 and 100,000 phosphoglycoproteins reveals that the phosphorylation sites are serine and threonine residues. There appears to be a good correlation between the presence of the Mr 135,000 phosphoglycoprotein in plasma membranes and resistance to taxol.


It's early: event-related potential evidence for initial interaction of syntax and prosody in speech comprehension.
Psycholinguistic theories assume an interaction between prosody and syntax during language processing. Based on studies using mostly off-line methods, it is unclear whether an interaction occurs at later or initial processing stages. Using event-related potentials, the present study provides neurophysiological evidence for a prosody and syntax interaction in initial processing. The sentence material contained mere prosodic and syntactic as well as combined prosodic-syntactic violations. For the syntax violation, the critical word appeared after a preposition. The suffix of the critical word either indicated a noun fulfilling the syntactic requirements of the preceding preposition or a verb causing a word category violation. For the prosodic manipulation, congruent critical words were normally intonated (signaling sentence continuation) while prosodically incongruent critical words signaled sentence end. For the mere prosodic incongruity, a broadly distributed negativity was observed at the critical word-stem (300-500 msec aligned to word onset). In response to a mere syntactic error, a left temporal negativity was elicited in an early time window (200-400 msec aligned to suffix onset), taken to reflect initial phrase structure building processes. In contrast, in response to the combined prosodic-syntactic violation, an early temporal negativity showed up bilaterally at the suffix in the same time window. Our interpretation is that the process of initial structure building as reflected in the early left anterior negativity recruits additional right hemispheric neural resources when the critical word contains both syntactic and prosodic violations. This suggests the immediate influence of phrasal prosody during the initial parsing stage in speech processing.


Growth, Viability, and Death of Planktonic and Biofilm Sphingomonas desiccabilis in Simulated Martian Brines.
Aqueous solutions on Mars are theorized to contain very different ion compositions than those on Earth. To determine the effect of such solutions on typical environmental micro-organisms, which could be released from robotic spacecraft or human exploration activity, we investigated the resistance of Sphingomonas desiccabilis to brines that simulate the composition of martian aqueous environments. S. desiccabilis is a desiccation-resistant, biofilm-forming microbe found in desert crusts. The viability of cells in both planktonic and biofilm forms was measured after exposure to simulated martian brines. Planktonic cells showed a loss of viability over the course of several hours in almost all of the seven brines tested. Biofilms conferred greater resistance to all the brines, including those with low water activity and pH, but even cells in biofilms showed a complete loss of viability in <6 h in the harsher brines and in <2 days in the less harsh brines. One brine, however, allowed the microbes to maintain viability over several days, despite having a water activity and pH lower and ionic strength higher than brines that reduced viability over the same timescales, suggesting important ion-specific effects. These data show that biofilm-forming cells have a greater capacity to resist martian aqueous extremes, but that evaporative or deliquescent brines are likely to be destructive to many organisms over relatively short timescales, with implications for the habitability of Mars and for micro-organisms dispersed by robotic or human explorers.


MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation.
MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as beta-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and beta-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.


Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease.
Treatment of patients with Parkinson's disease with levodopa has profound effects on both movement and the pattern of movement-related reactivity in the subthalamic nucleus (STN), as reflected in the local field potential (LFP). The most striking change is the promotion of reactivity in the gamma frequency band, but it remains unclear whether the latter is itself a pathological feature, possibly associated with levodopa induced dyskinesias, or is primarily physiological. Gamma band reactivity in the cerebral cortex of humans without Parkinson's disease occurs contralateral to movement, so we posited that lateralization of subcortical gamma reactivity should occur following levodopa if the latter restores a more physiological pattern in patients with Parkinson's disease. Accordingly, we studied movement-related changes in STN LFP activity in 11 Parkinson's disease patients (age 59 +/- 2.7 years, three females) while they performed ipsi- and contralateral self-paced joystick movements ON and OFF levodopa. A bilaterally symmetrical gamma band power increase occurred around movement onset in the OFF state. Following levodopa this feature became significantly more pronounced in the subthalamic region contralateral to movement. The physiological nature of this asymmetric pattern of gamma reactivity was confirmed in the STN of two tremor patients without Parkinson's disease. Although levodopa treatment in the Parkinson's disease patients did not lead to lateralization of power suppression at lower frequencies (8-30 Hz), it did increase the degree of power suppression. These findings suggest that dopaminergic therapy restores a more physiological pattern of reactivity in the STN of patients with Parkinson's disease.


Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s) linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial derived factor (PEDF) in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ), a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice. MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo. We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and progression to CNV in smoker patients with dry AMD.


Holmium:YAG laser angioplasty. Experimental ablation of vascular tissue via flexible ring catheters.
This experimental study was designed to define the potential value of a mid-infrared holmium laser in the free running mode for angioplasty. Immediately after removal, fresh normal and diseased human cadaveric arteries were irradiated under saline with a Ho:YAG laser (wavelength 2.13 microns). The laser was pulsed at 3 Hz, 250 microseconds pulse width and fluences of 10 to 40 J/cm2. The laser beam was coupled to ring catheters with multiple low-OH quartz fibers. The tip of the delivery device was held in direct contact with the vessel surface with the laser beam oriented perpendicularly. Ablation of atherosclerotic plaque was accomplished at an ablation threshold of 10 J/cm2. The ablation rate was 2.1 to 8.3 microns/pulse. Removal of calcified plaque was only partially effective. There were marked thermal effects with vacuolizations extending up to 1505 +/- 178 microns into the adjacent tissue. Laser light at the mid-infrared wavelength of 2.13 microns is supposed to be attractive as it is readily absorbed in water and can easily be transmitted through optical fibers. However, Q-switching seems to be essential to minimize thermal side effects and to make effective ablation of calcium possible.


A retrospective analysis of boarding times for adolescents in psychiatric crisis.
The boarding of children and adolescents with identified psychiatric conditions at medical facilities has numerous negative effects on the patients and the systems that treat them. Efforts to minimize boarding times serves to increase patients' access to appropriate levels of care, redirect medical resources to patients who need them most, and reduce safety risks to people and property. This study explores the role Clinical Social Workers can play in facilitation of care and highlights the advantages of a coordinated data collection process facilitated by the effective use of the Electronic Medical Record. A retrospective chart analysis of 100 patients admitted to the Emergency department at a pediatric hospital in Central Florida was conducted for patients seen between 1 January 2015 and 30 June 2016. The data suggest key correlates that may impact the boarding times of pediatric patients presenting in a psychiatric crisis and the average duration of boarding time in hours (M = 5.11, SD = 2.07) was found to be significantly lower than prior published studies in the adult and pediatric literature. Discussion of these data implications on behavioral health practice is discussed.


Assessment of endotracheal cuff pressure by continuous monitoring: a pilot study.
Endotracheal tube cuff pressure must be maintained within a narrow therapeutic range to prevent complications. Cuff pressure is measured and adjusted intermittently. To assess the accuracy and feasibility of continuous monitoring of cuff pressure, describe changes in cuff pressure over time, and identify clinical factors that influence cuff pressure. In a pilot study, data were collected for a mean of 9.3 hours on 10 patients who were orally intubated and receiving mechanical ventilation. Sixty percent of the patients were white, mean age was 55 years, and mean intubation time was 2.8 days. The initial cuff pressure was adjusted to a minimum of 20 cm H2O. The pilot balloon of the endotracheal tube was connected to a transducer and a pressure monitor. Cuff pressure was recorded every 0.008 seconds during a typical 12-hour shift and was reduced to 1-minute means. Patient care activities and interventions were recorded on a personal digital assistant. Values obtained with the cufflator-manometer and the transducer were congruent. Only 54% of cuff pressure measurements were within the recommended range of 20 to 30 cm H2O. The cuff pressure was high in 16% of measurements and low in 30%. No statistically significant changes over time were noted. Endotracheal suctioning, coughing, and positioning affected cuff pressure. Continuous monitoring of cuff pressure is feasible, accurate, and safe. Cuff pressures vary widely among patients.


A case-control analysis on the association between erectile dysfunction and sudden sensorineural hearing loss in Taiwan.
Although the cause of sudden sensorineural hearing loss (SSNHL) is yet to be elucidated, many theories have been proposed regarding potentially contributory etiologies. One increasingly well-supported theory purports an underlying vascular pathomechanism. If this is the case, SSNHL may also associate with conditions comorbid with vascular diseases, such as erectile dysfunction (ED). However, no studies to date have investigated the association between ED and SSNHL. This study set out to estimate a putative association between ED and having been previously diagnosed with SSNHL using a population-based dataset with a case-control design. This study used administrative claim data from the Taiwan National Health Insurance program. We identified 4,504 patients with ED as the study group and randomly selected 22,520 patients as the comparison group. Conditional logistic regression was used to examine the association between ED and having previously received a diagnosis of SSNHL. The prevalence and risk of SSNHL between cases and controls were calculated. Of the sampled patients, 41 (0.15%) had been diagnosed with SSNHL before the index date; 22 (0.49% of the cases) were from the study group and 19 (0.08% of controls) were from the control group. Conditional logistic regression analysis revealed that after adjusting for the patient's monthly income, geographic location, hypertension, diabetes, hyperlipidemia, coronary heart disease, obesity, and alcohol abuse/alcohol dependence syndrome status, patients with ED were more likely than controls to have been diagnosed with SSNHL before the index date (odds ratio = 6.06, 95% confidence interval = 3.25-11.29). There was an association between ED and prior SSNHL. The results of this study add to the evidence supporting an underlying vascular pathomechanism regarding the development of SSNHL and highlight a need for clinicians dealing with SSNHL patients to be alert to the development of ED.


Polarity and patterning in the neural tube: the origin and function of the floor plate.
Little is known about the cellular and molecular mechanisms that determine neuronal cell fate and the patterning of neuronal connections in the vertebrate central nervous system. In this paper we summarize evidence which indicates that some aspects of neuronal differentiation and axon guidance are regulated by specialized epithelial cells that occupy the medial region of the neural plate and, later, the ventral midline of the spinal cord. This cell group, termed the notoplate/floor plate appears to constitute a distinct compartment within the neural plate that is more closely related in lineage and perhaps also in function to axial mesodermal cells of the underlying notochord than to other neural plate cells. Cells of the notoplate exhibit specialized mechanical and adhesive properties that may contribute to neurulation. At later stages of development, the floor plate appears to guide developing axons in the embryonic spinal cord by releasing a diffusible chemoattractant factor and by virtue of its specialized cell surface properties. The floor plate may also play a role in the determination of cell identity and patterning at earlier stages of neural tube development.


Slow component-a of axonal transport, nerve myo-inositol, and aldose reductase inhibition in streptozocin-diabetic rats.
This study measured sugars and polyols, weight/unit length, and slow component-a of axonal transport (SCa) in dorsal root afferents of the sciatic nerves of control rats and rats with streptozocin (STZ)-induced diabetes of 4-wk duration. The effects of two treatments--aldose reductase inhibition [Statil ("Statil" is a trademark; the property of Imperial Chemical Industries PLC.) ICI 128436 at 25 mg/kg/day, p.o.] and myo-inositol supplementation (650 mg/kg/day, p.o.)--were studied in control and diabetic groups. Inclusion of untreated controls and diabetics gave a total of six groups for the study. The treatments were begun on the day after injection of STZ and were maintained throughout the protocol. The sciatic nerves of the diabetic (untreated) rats showed accumulation of sorbitol and fructose, depletion of myo-inositol, and an 8% increase in weight/unit length. All of these abnormalities were prevented by treatment with Statil. Treatment of diabetic rats with myo-inositol prevented its depletion in the sciatic nerve, but did not affect the accumulation of sorbitol and fructose nor the increase in weight/unit length. Neither treatment exerted any apparent effect on body weight, blood glucose, nerve weight, or nerve sugars and polyols in the control rats. The diabetic rats showed a retardation of the wave of transported-labeled protein (shown as increased leftward skewness of the wave) and a reduction in mean transport velocity (calculated as the mean velocity for all segments contributing to the transport wave: 0.96 +/- 0.09 mm/day in diabetics versus 1.15 +/- 0.07 mm/day in controls).(ABSTRACT TRUNCATED AT 250 WORDS)


Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents.
Bioscavengers are molecules able to neutralize neurotoxic organophosphorus compounds (OP) before they can reach their biological target. Human butyrylcholinesterase (hBChE) is a natural bioscavenger each molecule of enzyme neutralizing one molecule of OP. The amount of natural enzyme is insufficient to achieve good protection. Thus, different strategies have been envisioned. The most straightforward consists in injecting a large dose of highly purified natural hBChE to increase the amount of bioscavenger in the bloodstream. This proved to be successful for protection against lethal doses of soman and VX but remains expensive. An improved strategy is to regenerate prophylactic cholinesterases (ChE) by administration of reactivators after exposure. But broad-spectrum efficient reactivators are still lacking, especially for inhibited hBChE. Cholinesterase mutants capable of reactivating spontaneously are another option. The G117H hBChE mutant has been a prototype. We present here the Y124H/Y72D mutant of human acetylcholinesterase; its spontaneous reactivation rate after V-agent inhibition is increased up to 110 fold. Catalytic bioscavengers, enzymes capable of hydrolyzing OP, present the best alternative. Mesophilic bacterial phosphotriesterase (PTE) is a candidate with good catalytic efficiency. Its enantioselectivity has been enhanced against the most potent OP isomers by rational design. We show that PEGylation of this enzyme improves its mean residence time in the rat blood stream 24-fold and its bioavailability 120-fold. Immunogenic issues remain to be solved. Human paraoxonase 1 (hPON1) is another promising candidate. However, its main drawback is that its phosphotriesterase activity is highly dependent on its environment. Recent progress has been made using a mammalian chimera of PON1, but we provide here additional data showing that this chimera is biochemically different from hPON1. Besides, the chimera is expected to suffer from immunogenic issues. Thus, we stress that interest for hPON1 must not fade away, and in particular, the 3D structure of the hPON1 eventually in complex with OP has to be solved.


Weight, physical activity, diet, and prognosis in breast and gynecologic cancers.
Diet, physical activity, and weight may affect prognosis among women who are diagnosed with breast or gynecologic cancer. Observational studies show associations between being overweight or obese and weight gain with several measures of reduced prognosis in women with breast cancer and some suggestion of poor prognosis in underweight women. Observational studies have shown an association between higher levels of physical activity and improved breast cancer-specific and all-cause mortality, although a dose-response relationship has not been established. One large randomized controlled trial reported increased disease-free survival after a mean of 5 years in patients with breast cancer randomly assigned to a low-fat diet versus control. However, another trial of similar size found no effect from a high vegetable/fruit, low-fat diet on breast cancer prognosis. The few reported studies suggest that obesity negatively affects endometrial cancer survival, while the limited data are mixed for associations of weight with ovarian cancer prognosis. Insufficient data exist for assessing associations of weight, physical activity, or diet with prognosis in other gynecologic cancers. Associations of particular micronutrient intake and alcohol use with prognosis are not defined for any of these cancers. The effects of dietary weight loss and increase in physical activity on survival or recurrence in breast and gynecologic cancers are not yet established, and randomized controlled trials are needed for definitive data.


Health disparities and children in immigrant families: a research agenda.
Children in immigrant families now comprise 1 in 5 children in the United States. Eighty percent of them are US citizens, and 53% live in mixed-citizenship families. Their families are among the poorest, least educated, least insured, and least able to access health care. Nonetheless, these children demonstrate better-than-expected health status, a finding termed "the immigrant paradox" and one suggesting that cultural health behaviors among immigrant families might be protective in some areas of health. In this article the strength of the immigrant paradox, the effect of acculturation on health, and the relationships of acculturation, enculturation, language, and literacy skills to health disparities are reviewed. The current public policy issues that affect the health disparities of children of immigrant families are presented, and a research agenda for improving our knowledge about children in immigrant families to develop effective interventions and public policies that will reduce their health disparities is set forth.


Large-mode-area fibers operating near single-mode regime.
Lower NA in large-mode-area fibers enables better single-mode operation and larger core diameters. Fiber NA has traditionally been limited to 0.06, mostly due to the control tolerance in the fabrication process. It has been recognized recently that transverse mode instability is a major limit to average power scaling in fiber lasers. One effective method to mitigate this limit is to operate nearer to the single-mode regime. Lower fiber NA is critical in this since it allows relatively larger core diameters which is the key to mitigate the limits imposed by nonlinear effects. We have developed a fabrication process of ytterbium-doped silica glass which is capable of highly accurate refractive index control and sufficient uniformity for LMA fibers. This process is also capable of large-volume production. It is based on a significant amount of post-processing once the fiber preforms are made. We have demonstrated 30/400 and 40/400 LMA fibers with a NA of ~0.028 operating very close to the single-mode regime. The second-order mode cuts off at ~1.2μm and ~1.55µm respectively. We have also studied issues related to bend losses due to the low NA and further optimization of LMA fibers.


A Robust Actin Filaments Image Analysis Framework.
The cytoskeleton is a highly dynamical protein network that plays a central role in numerous cellular physiological processes, and is traditionally divided into three components according to its chemical composition, i.e. actin, tubulin and intermediate filament cytoskeletons. Understanding the cytoskeleton dynamics is of prime importance to unveil mechanisms involved in cell adaptation to any stress type. Fluorescence imaging of cytoskeleton structures allows analyzing the impact of mechanical stimulation in the cytoskeleton, but it also imposes additional challenges in the image processing stage, such as the presence of imaging-related artifacts and heavy blurring introduced by (high-throughput) automated scans. However, although there exists a considerable number of image-based analytical tools to address the image processing and analysis, most of them are unfit to cope with the aforementioned challenges. Filamentous structures in images can be considered as a piecewise composition of quasi-straight segments (at least in some finer or coarser scale). Based on this observation, we propose a three-steps actin filaments extraction methodology: (i) first the input image is decomposed into a 'cartoon' part corresponding to the filament structures in the image, and a noise/texture part, (ii) on the 'cartoon' image, we apply a multi-scale line detector coupled with a (iii) quasi-straight filaments merging algorithm for fiber extraction. The proposed robust actin filaments image analysis framework allows extracting individual filaments in the presence of noise, artifacts and heavy blurring. Moreover, it provides numerous parameters such as filaments orientation, position and length, useful for further analysis. Cell image decomposition is relatively under-exploited in biological images processing, and our study shows the benefits it provides when addressing such tasks. Experimental validation was conducted using publicly available datasets, and in osteoblasts grown in two different conditions: static (control) and fluid shear stress. The proposed methodology exhibited higher sensitivity values and similar accuracy compared to state-of-the-art methods.


Flavobacterium daejeonense sp. nov. and Flavobacterium suncheonense sp. nov., isolated from greenhouse soils in Korea.
Two yellow-pigmented, Gram-negative, rod-shaped bacterial strains, GH1-10(T) and GH29-5(T), were isolated from greenhouse soils in Korea. 16S rRNA gene sequence analysis indicated that these strains were related to members of the genus Flavobacterium. Strain GH1-10(T) was most closely related to Flavobacterium psychrolimnae and Flavobacterium denitrificans, with sequence similarities of 95.9 and 95.2 %, respectively. Strain GH29-5(T) was most closely related to "Flavobacterium saliodium", F. denitrificans and Flavobacterium frigoris, with sequence similarities of 94.3, 92.5 and 92.5 %, respectively. The major cellular fatty acids of GH1-10(T) were iso-C(15 : 0), summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c) and iso-C(17 : 0) 3-OH, and those of GH29-5(T) were iso-C(15 : 0), iso-C(17 : 0) 3-OH, iso-C(15 : 1) G and iso-C(15 : 0) 3-OH. Both strains contained menaquinone with six isoprene units (MK-6) as the sole quinone. The DNA G+C contents of GH1-10(T) and GH29-5(T) were 35 and 39 mol%, respectively. Based on the phylogenetic and phenotypic data presented, it is concluded that the two bacteria represent two separate novel species of the genus Flavobacterium. The names proposed to accommodate these organisms are Flavobacterium daejeonense sp. nov., with type strain GH1-10(T) (=KACC 11422(T)=DSM 17708(T)), and Flavobacterium suncheonense sp. nov., with type strain GH29-5(T) (=KACC 11423(T)=DSM 17707(T)).


Regional Inequalities in Maternal and Neonatal Health Services in Iraq and Syria From 2000 to 2011.
We analyze regional inequalities in access to maternal and neonatal health services in Iraq and Syria during the period 2000-2011, before the rise of the Islamic State in Iraq and Syria, ISIS. Utilizing nationally representative survey data (Iraq 2000, 2006, 2011; Syria 2006, 2009), we examine changes in the rate of babies weighed at birth and women delivering at home. We calculate 4 regional inequality indicators: (1) extremal quotient, (2) interquartile quotient, (3) coefficient of variation, and (4) systematic component of variation. Despite national improvements in both countries over time, indicators show increasing regional inequalities in access to maternal and neonatal health services, particularly in Syria between 2006 and 2009. Spatial regression results indicate that these inequalities associate with inequalities in maternal education, rurality, and wealth. Regions where women experienced deteriorating access over time, reflecting overall inequalities, are those that fell under the control of ISIS. Inequalities in access to basic services (education and health) deserve more attention in understanding social and political change in the Arab region.


Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945.
We tested the hypothesis that first-trimester exposure to acute food deprivation is a risk factor for schizophrenia. A sharp and time-limited decline in the food intake of the Dutch population following a Nazi blockade in 1944 to 1945 created a unique if tragic natural experiment to test this hypothesis in three regions of Holland (west, north, and south). In the west, or famine region, birth cohorts exposed to severe food deprivation (an average daily ration under 4200 kJ) during the first trimester showed a substantial increase in hospitalized schizophrenia for women but not for men. Relative risks for women were 2.17 for "broad" and 2.56 for "restricted" schizophrenia. Moderate food deprivation during the first trimester (average daily ration under 6300 kJ) was not associated with increased risk of schizophrenia in the famine region. In the north and south regions, numbers were smaller and there was no exposure to severe famine. Birth cohorts exposed to moderate food deprivation during the first trimester showed a trend toward increased risk of schizophrenia for women. These findings give plausibility to the proposition that early prenatal nutrition can have a gender-specific effect on the risk of schizophrenia.


Prevalence of the rheumatic diseases in urban Vietnam: a WHO-ILAR COPCORD study.
To determine the prevalence rates of musculoskeletal disorders in an urban Vietnamese population. The Community Oriented Program for Control of Rheumatic Disease (COPCORD) Stage I study was carried out in 16 groups in the Trung Liet Commune, Dong Da District, Hanoi City, Vietnam. Phase 1: the WHO ILAR COPCORD Core Questionnaire was applied by primary health care workers to 2119 urban subjects aged 16 years and over. Phase 2: 276 positive responders who had musculoskeletal complaints were interviewed by nurses and examined one week later. Phase 3: 261 positive responders in phase II were examined by 3 rheumatologists and 38% of these subjects required radiographic and blood tests to classify rheumatic disease categories. The response rates were 94.4%, 86.2%, and 94.6% in phases 1, 2, and 3, respectively. The prevalence of musculoskeletal pain was 14.9%. The most common musculoskeletal complaints were knee pain 18.2%, low back pain 11.2%, and soft tissue disorder 15.4%. Functional disability was reported in 6.04% of the survey population. The prevalence of rheumatic diseases was OA 4.1%, rheumatoid arthritis 0.28%, osteoporosis 0.47%, connective tissue disease 0.09%, and gout 0.14%. The prevalence of musculoskeletal pain in 2119 adults in an urban population in Vietnam was 14.5%, and osteoarthritis was the most commonly found arthritis.


Relationship Dynamics and Partner Beliefs About Viral Suppression: A Longitudinal Study of Male Couples Living with HIV/AIDS (The Duo Project).
Accurate beliefs about partners' viral suppression are important for HIV prevention and care. We fit multilevel mixed effects logistic regression models to examine associations between partners' viral suppression beliefs and objective HIV RNA viral load tests, and whether relationship dynamics were associated with accurate viral suppression beliefs over time. Male couples (N = 266 couples) with at least one HIV-positive partner on antiretroviral therapy completed five assessments over 2 years. Half of the 407 HIV-positive partners were virally suppressed. Of the 40 % who had inaccurate viral load beliefs, 80 % assumed their partner was suppressed. The odds of having accurate viral load beliefs decreased over time (OR = 0.83; p = 0.042). Within-couple differences in dyadic adjustment (OR = 0.66; p < 0.01) and commitment (OR = 0.82; p = 0.022) were negatively associated with accurate viral load beliefs. Beliefs about a partner's viral load may factor into sexual decision-making and social support. Couple-based approaches are warranted to improve knowledge of partners' viral load.


Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts.
In mammalian cells inhibition of the cdc2 function results in arrest in the G2-phase of the cell cycle. Several cdc2-related gene products have been identified recently and it has been hypothesized that they control earlier cell cycle events. Here we have studied the relationship between activation of one of these cdc2 homologs, the cdk2 protein kinase, and the progression through the cell cycle in cultured human fibroblasts. We found that cdk2 was activated and specifically localized to the nucleus during S phase and G2. Microinjection of affinity-purified anti-cdk2 antibodies but not of affinity-purified anti-cdc2 antibodies, during G1, inhibited entry into S phase. The specificity of these effects was demonstrated by the fact that a plasmid-driven cdk2 overexpression counteracted the inhibition. These results demonstrate that the cdk2 protein kinase is involved in the activation of DNA synthesis.


Spatial and temporal variability of soil N2 O and CH4 fluxes along a degradation gradient in a palm swamp peat forest in the Peruvian Amazon.
Mauritia flexuosa palm swamp, the prevailing Peruvian Amazon peatland ecosystem, is extensively threatened by degradation. The unsustainable practice of cutting whole palms for fruit extraction modifies forest's structure and composition and eventually alters peat-derived greenhouse gas (GHG) emissions. We evaluated the spatiotemporal variability of soil N2 O and CH4 fluxes and environmental controls along a palm swamp degradation gradient formed by one undegraded site (Intact), one moderately degraded site (mDeg) and one heavily degraded site (hDeg). Microscale variability differentiated hummocks supporting live or cut palms from surrounding hollows. Macroscale analysis considered structural changes in vegetation and soil microtopography as impacted by degradation. Variables were monitored monthly over 3 years to evaluate intra- and inter-annual variability. Degradation induced microscale changes in N2 O and CH4 emission trends and controls. Site-scale average annual CH4 emissions were similar along the degradation gradient (225.6 ± 50.7, 160.5 ± 65.9 and 169.4 ± 20.7 kg C ha-1 year-1 at the Intact, mDeg and hDeg sites, respectively). Site-scale average annual N2 O emissions (kg N ha-1 year-1 ) were lower at the mDeg site (0.5 ± 0.1) than at the Intact (1.3 ± 0.6) and hDeg sites (1.1 ± 0.4), but the difference seemed linked to heterogeneous fluctuations in soil water-filled pore space (WFPS) along the forest complex rather than to degradation. Monthly and annual emissions were mainly controlled by variations in WFPS, water table level (WT) and net nitrification for N2 O; WT, air temperature and net nitrification for CH4 . Site-scale N2 O emissions remained steady over years, whereas CH4 emissions rose exponentially with increased precipitation. While the minor impact of degradation on palm swamp peatland N2 O and CH4 fluxes should be tested elsewhere, the evidenced large and variable CH4 emissions and significant N2 O emissions call for improved modeling of GHG dynamics in tropical peatlands to test their response to climate changes.


Prostate cancer risk and exposure to pesticides in British Columbia farmers.
Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. Our aim was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides. A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants' lifetime cumulative exposure to approximately 180 active compounds in pesticides. Conditional logistic regression was used to assess prostate cancer risk, adjusting for potential confounding variables and effect modifiers. These include age, ethnicity, alcohol consumption, smoking, education, and proxy respondent. The significant association between prostate cancer risk and exposure to DDT (OR = 1.68; 95% CI: 1.04-2.70 for high exposure), simazine (OR = 1.89; 95% CI: 1.08-3.33 for high exposure), and lindane (OR = 2.02; 95% CI: 1.15-3.55 for high exposure) is in keeping with those previously reported in the literature. We also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in our study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.


Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha.
Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a growth factor for granulocytes and macrophages, is an activator of cells of the monocyte/macrophage lineage and induces HLA class II expression and cytokine synthesis in these target cells. Macrophage activation and class II expression are prominent features in rheumatoid arthritis (RA) joints, but the mechanism of their stimulation is not understood, since interferon-gamma, the major stimulus of class II expression, is not usually detectable at the protein level in synovial cell culture supernatants. We have, therefore, studied GM-CSF expression in cultures of cells derived from joints affected by RA and osteoarthritis (OA), and show that GM-CSF is produced spontaneously both by RA synovial cells and to a lesser extent by OA synovial cells in the absence of extrinsic stimuli. GM-CSF production continues for the 5-day duration of the culture period. Using neutralizing antibodies to tumor necrosis factor (TNF)-alpha we demonstrated that GM-CSF production in RA synovial cell cultures is dependent on the continued presence of active TNF-alpha. This result supports our concept that continued activation of the cytokine network is a marked feature of RA, and that TNF-alpha plays a pivotal role in this network, by regulating the production of other pro-inflammatory cytokines, such as interleukin 1, as demonstrated previously, and GM-CSF.


Recovery of protective activity in rabies virus vaccines concentrated and purified by four different methods.
Rabies vaccines concentrated by ultrafiltration, zinc acetate precipitation, ammonium sulfate precipitation, or aluminum phosphate gel adsorption were compared with respect to recovery of protective activity and purity, as measured by protective activity per mg of protein. Vaccine obtained by ammonium sulfate precipitation had a better recovery rate and a higher purity than those prepared by the other methods. Potent vaccines were also obtained by the zinc acetate precipitation and aluminum phosphate gel adsorption methods, whereas ultrafiltration was the least satisfactory method from the standpoint of vaccine purity. Chromatography of virus concentrated by ultrafiltration on a cellulose ion exchange column reduced the level of nonviral proteins. The protective activity data obtained for the vaccines examined in these experiments were found to correlate with the vaccine's complement fixation titer per mg of protein.


Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia.
Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with chronic myelomonocytic leukemia (CMML); however, few data exist regarding prognostic factors and transplantation outcomes. We performed this retrospective study to identify prognostic factors for post-transplantation outcomes. The CMML-specific prognostic scoring system (CPSS) has been validated in subjects receiving nontransplantation therapy and was included in our study. From 2001 to 2012, 209 adult subjects who received HCT for CMML were reported to the Center for International Blood and Marrow Transplant Research. The median age at transplantation was 57 years (range, 23 to 74). Median follow-up was 51 months (range, 3 to 122). On multivariate analyses, CPSS scores, Karnofsky performance status (KPS), and graft source were significant predictors of survival (P = .004, P = .01, P = .01, respectively). Higher CPSS scores were not associated with disease-free survival, relapse, or transplantation-related mortality. In a restricted analysis of subjects with relapse after HCT, those with intermediate-2/high risk had a nearly 2-fold increased risk of death after relapse compared to those with low/intermediate-1 CPSS scores. Respective 1-year, 3-year, and 5-year survival rates for low/intermediate-1 risk subjects were 61% (95% confidence interval [CI], 52% to 72%), 48% (95% CI, 37% to 59%), and 44% (95% CI, 33% to 55%), and for intermediate-2/high risk subjects were 38% (95% CI, 28% to 49%), 32% (95% CI, 21% to 42%), and 19% (95% CI, 8% to 29%). We conclude that higher CPSS score at time of transplantation, lower KPS, and a bone marrow graft are associated with inferior survival after HCT. Further investigation of CMML disease-related biology may provide insights into other risk factors predictive of post-transplantation outcomes.


Breaking the Myth That Relay Swimming Is Faster Than Individual Swimming.
To investigate if swimming performance is better in a relay race than in the corresponding individual race. The authors analyzed 166 elite male swimmers from 15 nations in the same competition (downloaded from www.swimrankings.net). Of 778 observed races, 144 were Olympic Games performances (2000, 2004, 2012), with the remaining 634 performed in national or international competitions. The races were 100-m (n = 436) and 200-m (n = 342) freestyle events. Relay performance times for the 2nd-4th swimmers were adjusted (+ 0.73 s) to allow for the "flying start." Without any adjustment, mean individual relay performances were significantly faster for the first 50 m and overall time in the 100-m events. Furthermore, the first 100 m of the 200-m relay was significantly faster (P > .001). During relays, swimmers competing in 1st position did not show any difference compared with their corresponding individual performance (P > .16). However, swimmers competing in 2nd-4th relay-team positions demonstrated significantly faster times in the 100-m (P < .001) and first half of the 200-m relays than in their individual events (P < .001, ES: 0.28-1.77). However, when finishing times for 2nd-4th relay team positions were adjusted for the flying start no differences were detected between relay and individual race performance for any event or split time (P > .17). Highly trained swimmers do not swim (or turn) faster in relay events than in their individual races. Relay exchange times account for the difference observed in individual vs relay performance.


Dental anxiety among patients visiting a dental institute in Faridabad, India.
Despite advances in dentistry, anxiety about dental treatment and the fear of pain remains widespread among patients and is a significant barrier to dental treatment. This study would therefore provide information so as to minimize levels of anxiety and aid in planning stress-free treatment. The cross-sectional study utilizing a self-reported questionnaire based on Modified Corah's Dental Anxiety Scale (MDAS) framed in Hindi (local language) was performed on 1032 patients (aged 14-68 years). Around 1004 questionnaires were returned (response rate--97.3%). Overall, prevalence of dental anxiety was high (50.2%), but severe anxiety (phobia) was low (4.38%). The prevalence of anxiety was seen mostly in the 20-30-year age group (37.3%). Anxiety was also seen to be significantly higher in females (mean - 11.79) than in males [mean - 9.47] (p < 0.0000). Patients anxious about dental procedures are often more difficult to treat. Anxious patients should be identified and managed appropriately by behavioural/pharmacological measures.


The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation.
Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction.


Everyday ethics of suicide care: Survey of mental health care providers' perspectives and support needs.
Suicide occurs in people of all ages and backgrounds, which negatively affects families, communities, and the health care providers (HCPs) who care for them. The objective of this study was to better understand HCPs' perspectives of everyday ethical issues related to caring for suicidal patients, and their perceived needs for training and/or support to address these issues. We conducted a mixed methods survey among HCPs working in mental health in Québec, Canada. Survey questions addressed their perspectives and experiences of everyday ethical challenges they encounter in their practice with people who are suicidal, and their perceived needs for training and/or support therein. 477 HCPs completed the survey. Most participants mentioned encountering ethical issues when caring for people who are suicidal. The challenges HCPs encounter in their practice with people who are suicidal are numerous, including issues related to maintaining privacy, confidentiality, freedom and the therapeutic relationship. The lack of time, resources and professional support to address these issues was emphasized. Most HCPs reported that the training or education they have received does not allow them to address everyday ethical issues related to suicide care. In sum, there is a clear reported need for better training and support for HCPs who are offering care to people who are suicidal in relation to everyday ethical issues they encounter. Implications for practice include providing greater access to training, including access to specialists in ethics to address specific issues. This additional support could alleviate morally distressing situations for HCPs.


CH stretching excitation promotes its cleavage in the F + CHD3(ν1 = 1) → HF + CD3 reaction at low collision energies.
The effects of CH stretching excitation on the reactivity of the F + CHD3 → HF + CD3 reaction were studied experimentally using crossed-beam and time-sliced velocity map imaging techniques over the collision energy range of 1.21 to 9.00 kcal mol-1. The experimental results showed that the CH stretching excitation promoted its cleavage and enhanced the title reaction at low collision energies. This enhancement dropped with an increase of the collision energy. And at high collision energies, CH stretching excitation appeared to lower the reactivity of the above reaction, in contrast to the case at low collision energies. This decreasing trend in the enhancement of reactivity was in agreement with previous theoretical studies. The vibrationally excited reaction was further compared with the ground-state reaction at a same total reagent energy of 9.80 kcal mol-1, and similar reactivities were derived.


Twelve-Month-Old Infants' Encoding of Goal and Source Paths in Agentive and Non-Agentive Motion Events.
Across languages and event types (agentive and non-agentive motion, transfer, change of state, attach/detach), goal paths are privileged over source paths in the linguistic encoding of events. Furthermore, some linguistic analyses suggest that goal paths are more central than source paths in the semantic and syntactic structure of motion verbs. However, in the non-linguistic memory of children and adults, a goal bias shows up only for events involving intentional, goal-directed, action. Three experiments explored infants' non-linguistic representations of goals and sources in motion events. The findings revealed that 12-month-old infants privilege goals over sources only when the event involves action of an agent. Thus, unlike language (but similar to the memory of children and adults), an endpoint bias in infant thought may be restricted to events involving goal-directed motion by an agent. These results raise the question of how children later learn to collapse over conceptual domains for purposes of coding paths in language.


A computational model for epidural electrical stimulation of spinal sensorimotor circuits.
Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.


Staged gamma knife radiosurgery for large critically located benign meningiomas: evaluation of a series comprising 20 patients.
This study investigated the efficacy of staged radiosurgical treatment for intracranial meningiomas exceeding 3 cm in diameter. Between April 1992 and May 2008, staged gamma knife radiosurgery was performed in 20 patients with large benign meningiomas. 14 patients had undergone surgery at least once. The patients' ages ranged between 26 and 73 years (median 60.5). Tumour volumes measured between 13.6 and 79.8 cm(3) (median 33.3) and treatment volumes between 5.4 and 42.9 cm(3) (median 19.0). Of 41 treatments, the prescription dose at the tumour margin was 12 Gy for 33 treatments, 10 Gy for one treatment, 14 Gy for four treatments, 15 Gy for one treatment and 25 Gy for a further two treatments (median 12 Gy to a marginal isodose of 45%). Median follow-up was 7.5 years. Tumour control was achieved in 90% of our series (25% tumour regression, 65% stable size). Two patients (10%) experienced tumour progression outlying the planning target volumes treated by an additional radiosurgical procedure. Thereafter tumour volume decreased in one patient and remained stable in the second one. Clinically, nine patients (45%) improved within the time of follow-up and 11 (55%) remained unchanged. As a result of excellent tumour control at a low concomitant morbidity, staged radiosurgical treatment for meningiomas represents a safe treatment modality that can be recommended for meningiomas in critical locations either after incomplete surgery or as primary treatment for patients with significant comorbidity.


A cross-sectional, population-based study measuring comorbidity among people living with HIV in Ontario.
As people diagnosed with HIV and receiving combination antiretroviral therapy are now living longer, they are likely to acquire chronic conditions related to normal ageing and the effects of HIV and its treatment. Comordidities for people with HIV have not previously been described from a representative population perspective. We used linked health administrative data from Ontario, Canada. We applied a validated algorithm to identify people with HIV among all residents aged 18 years or older between April 1, 1992 and March 31, 2009. We randomly selected 5 Ontario adults who were not identified with HIV for each person with HIV for comparison. Previously validated case definitions were used to identify persons with mental health disorders and any of the following physical chronic diseases: diabetes, congestive heart failure, acute myocardial infarction, stroke, hypertension, asthma, chronic obstructive lung disease, peripheral vascular disease and end-stage renal failure. We examined multimorbidity prevalence as the presence of at least two physical chronic conditions, or as combined physical-mental health multimorbidity. Direct age-sex standardized rates were calculated for both cohorts for comparison. 34.4% (95% confidence interval (CI) 33.6% to 35.2%) of people with HIV had at least one other physical condition. Prevalence was especially high for mental health conditions (38.6%), hypertension (14.9%) and asthma (12.7%). After accounting for age and sex differences, people with HIV had significantly higher prevalence of all chronic conditions except myocardial infarction and hypertension, as well as substantially higher multimorbidity (prevalence ratio 1.30, 95% CI 1.18 to 1.44) and combined physical-mental health multimorbidity (1.79, 95% CI 1.65 to 1.94). Prevalence of multimorbidity among people with HIV increased with age. The difference in prevalence of multimorbidity between the two cohorts was more pronounced among women. People living with HIV in Ontario, especially women, had higher prevalence of comorbidity and multimorbidity than the general population. Quantifying this morbidity at the population level can help inform healthcare delivery requirements for this complex population.


A Statistical Analysis of IrisCode and Its Security Implications.
IrisCode has been used to gather iris data for 430 million people. Because of the huge impact of IrisCode, it is vital that it is completely understood. This paper first studies the relationship between bit probabilities and a mean of iris images (The mean of iris images is defined as the average of independent iris images.) and then uses the Chi-square statistic, the correlation coefficient and a resampling algorithm to detect statistical dependence between bits. The results show that the statistical dependence forms a graph with a sparse and structural adjacency matrix. A comparison of this graph with a graph whose edges are defined by the inner product of the Gabor filters that produce IrisCodes shows that partial statistical dependence is induced by the filters and propagates through the graph. Using this statistical information, the security risk associated with two patented template protection schemes that have been deployed in commercial systems for producing application-specific IrisCodes is analyzed. To retain high identification speed, they use the same key to lock all IrisCodes in a database. The belief has been that if the key is not compromised, the IrisCodes are secure. This study shows that even without the key, application-specific IrisCodes can be unlocked and that the key can be obtained through the statistical dependence detected.


A critical commentary on management science in relation to reforms after institutional National Health Service failures.
A discussion paper on the United Kingdom (UK) National Health Service (NHS) market reforms. NHS market reforms reliance on management science methods introduced a fundamental shift in measuring care for commissioning. A number of key reports are discussed in relation to NHS market reforms and management science. NHS market reforms were influenced through a close alliance between policy makers, the department of health, free market think tanks and management consultancies. The timing of reforms coincided with reports on NHS failings and the evolution of measurement methods to focus on finance. The balance in favour of measurement practises is of concern. Management science methods are criticised in the Francis Report yet promoted as the solution to some of the key findings; why may be explained by the close alliance. A return to principles of management involving consensus, trust and involvement to promote quality care and use management science methods to this end.


Commensal Bacteria Regulate Gene Expression and Differentiation in Vertebrate Olfactory Systems Through Transcription Factor REST.
Sensory systems such as the olfactory system detect chemical stimuli and thereby determine the relationships between the animal and its surroundings. Olfaction is one of the most conserved and ancient sensory systems in vertebrates. The vertebrate olfactory epithelium is colonized by complex microbial communities, but microbial contribution to host olfactory gene expression remains unknown. In this study, we show that colonization of germ-free zebrafish and mice with microbiota leads to widespread transcriptional responses in olfactory organs as measured in bulk tissue transcriptomics and RT-qPCR. Germ-free zebrafish olfactory epithelium showed defects in pseudostratification; however, the size of the olfactory pit and the length of the cilia were not different from that of colonized zebrafish. One of the mechanisms by which microbiota control host transcriptional programs is by differential expression and activity of specific transcription factors (TFs). REST (RE1 silencing transcription factor, also called NRSF) is a zinc finger TF that binds to the conserved motif repressor element 1 found in the promoter regions of many neuronal genes with functions in neuronal development and differentiation. Colonized zebrafish and mice showed increased nasal expression of REST, and genes with reduced expression in colonized animals were strongly enriched in REST-binding motifs. Nasal commensal bacteria promoted in vitro differentiation of Odora cells by regulating the kinetics of REST expression. REST knockdown resulted in decreased Odora cell differentiation in vitro. Our results identify a conserved mechanism by which microbiota regulate vertebrate olfactory transcriptional programs and reveal a new role for REST in sensory organs.


Structure and properties of silk from the African wild silkmoth Gonometa postica reared indoors.
African wild silkmoth, Gonometa postica Walker (Lepidoptera: Lasiocampidae), were reared indoors in order to examine the influence of rearing conditions on the structure and properties of silk cocoon shells and degummed fibers by using a scanning electron microscope, an Instron tensile tester, and a thermogravimetric analyzer. The cocoons reared indoors showed inferior quality in weight, length, width, and cocoon shell ratio compared to cocoons reared outdoors. There were no differences in cocoon shell and fiber surfaces and cross sectional structures. Cocoon shells were covered with calcium oxalate crystals with few visible fibers on their surface. Degummed fibers were smooth with minimum unfractured surfaces and globular to triangular cross sections. Indoor-reared cocoon shells had a significantly higher breaking strain, while the breaking stress was higher for cocoons reared outdoors. Fibers from indoor cocoons had a significantly higher breaking stress while outdoor fibers had higher breaking strain. Thermogravimetric analysis curves showed two main thermal reactions revealing the dehydration of water molecules and ir-reversible decomposition of the crystallites in both cocoons and fibers reared indoors and outdoors. Cocoon shells underwent additional peaks of decomposition with increased temperature. The total weight loss was higher for cocoon shells and degummed fibers from indoors. Rearing conditions (temperature and relative humidity), feeding method used, changes in total life span, days to molting, and spinning might have influenced the variation in the properties observed.The ecological and commercial significances of indoor rearing of G. posticaare discussed.


An international survey of gross anatomy courses in chiropractic colleges.
The purpose of this study is to provide the first comprehensive description of gross anatomy course design in chiropractic colleges internationally and to provide baseline data for future investigation, future comparison with other health care professions, and identification of trends. A 72-question cross-sectional electronic survey was sent to the anatomy department chair at 36 chiropractic colleges internationally using Zoomerang, a web-based survey instrument. To augment the survey response data, public sources of data also were collected. Forty-four percent of the electronic surveys were returned and information was gathered for 31 institutions from public sources. These results indicate (1) the most common degrees held by anatomy faculty were MS and PhD in anatomy, and DC degrees; (2) 75% of institutions utilized human cadavers and 75% presented laboratory anatomical demonstrations; (3) 62% used PowerPoint and 100% provided students with copies of lecture presentations; (4) 88% required attendance in laboratory and 50% in lecture; (5) 69% issued one grade for lecture and laboratory; (6) 100% of laboratory examinations were anatomical identification; and (7) 80% of written examinations were multiple-choice format. While individual variations existed, chiropractic institutions internationally have similar gross anatomy faculty, course design, delivery methods, and assessment methods.


Mobile phone use and risk of uveal melanoma: results of the risk factors for uveal melanoma case-control study.
We recently reported an increased risk of uveal melanoma among mobile phone users. Here, we present the results of a case-control study that assessed the association between mobile phone use and risk of uveal melanoma. We recruited 459 uveal melanoma case patients at the University of Duisburg-Essen and matched 455 case patients with 827 population control subjects, 133 with 180 ophthalmologist control subjects, and 187 with 187 sibling control subjects. We used a questionnaire to assess mobile phone use and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) of risk for uveal melanoma using conditional logistic regression. Risk of uveal melanoma was not associated with regular mobile phone use (OR = 0.7, 95% CI = 0.5 to 1.0 vs population control subjects; OR = 1.1, 95% CI = 0.6 to 2.3 vs ophthalmologist control subjects; and OR = 1.2, 95% CI = 0.5 to 2.6 vs sibling control subjects), and we observed no trend for cumulative measures of exposure. We did not corroborate our previous results that showed an increased risk of uveal melanoma among regular mobile phone users.


Psychological variables underlying political orientations in an old and a new democracy: A comparative study between Sweden and Latvia.
This study examines in detail the psychological variables underlying ideological political orientation, and structure and contents of this orientation, in Sweden and Latvia. Individual political orientation is conceptualized on two dimensions: acceptance vs. rejection of social change and acceptance vs. rejection of inequality. Swedish (N = 320) and Latvian (N = 264) participants completed measures of political orientation, Social Dominance Orientation (SDO), Right Wing Authoritarianism (RWA), self vs. other orientation, tolerance for ambiguity, humanism and normativism, core political values, system justification, as well as moral foundations questionnaire and portrait values questionnaire. The results showed that the relation among the measured variables was similar in both samples. Swedish participants showed stronger endorsement of egalitarian attitudes and social values, whereas we found more self-enhancing and socially conservative values and attitudes among the Latvian participants.


Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group.
To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. Randomized, double-blind, placebo-controlled trial with 3-month follow-up. A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. Combined death and disability score (Barthel index <60) 3 months after the stroke. Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.


eNOS deficiency predisposes podocytes to injury in diabetes.
Endothelial nitric oxide synthase (eNOS) deficiency may contribute to the pathogenesis of diabetic nephropathy in both experimental models and humans, but the underlying mechanism is not fully understood. Here, we studied two common sequelae of endothelial dysfunction in diabetes: glomerular capillary growth and effects on neighboring podocytes. Streptozotocin-induced diabetes increased glomerular capillary volume in both C57BL/6 and eNOS(-/-) mice. Inhibiting the vascular endothelial growth factor receptor attenuated albuminuria in diabetic C57BL/6 mice but not in diabetic eNOS(-/-) mice, even though it inhibited glomerular capillary enlargement in both. In eNOS(-/-) mice, an acute podocytopathy and heavy albuminuria occurred as early as 2 weeks after inducing diabetes, but treatment with either captopril or losartan prevented these effects. In vitro, serum derived from diabetic eNOS(-/-) mice augmented actin filament rearrangement in cultured podocytes. Furthermore, conditioned medium derived from eNOS(-/-) glomerular endothelial cells exposed to both high glucose and angiotensin II activated podocyte RhoA. Taken together, these results suggest that the combined effects of eNOS deficiency and hyperglycemia contribute to podocyte injury, highlighting the importance of communication between endothelial cells and podocytes in diabetes. Identifying mediators of this communication may lead to the future development of therapies targeting endothelial dysfunction in albuminuric individuals with diabetes.


Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials.
To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR). This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61-78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57-82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68-91%)) and TRUFFLE (77% (95% CI, 70-84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80-89%)) (P < 0.01 for trend). This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment. GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.


Patterns of youth injury: a comparison across the northern territories and other parts of Canada.
Injury is the leading cause of death for young people in Canada. For those living in the northern territories (Yukon, Nunavut, and the Northwest Territories), injury represents an even greater problem, with higher rates of injury for people of all ages in northern areas compared with the rest of Canada; however, no such comparative studies have focussed specifically on non-fatal injury in youth. To profile and examine injuries and their potential causes among youth in the northern territories as compared with other parts of Canada. Cross-sectional data from the 2009/2010 Health Behaviour in School-aged Children survey (youth aged 11-15 years) were examined for the Canadian northern territories and the provinces (n=26,078). Individual survey records were linked to community-level data to profile injuries and then study possible determinants via multilevel regression modelling. The prevalence of injury reported by youth was similar in northern populations and other parts of Canada. There were some minimal differences by injury type: northern youth experienced a greater percentage of neighbourhood (p<0.001) and fighting (p=0.02) injuries; youth in the Canadian provinces had a greater proportion of sport-related injuries (p=0.01). Among northern youth, female sex (RR=0.87, 95% CI 0.81-0.94), average (RR=0.88, 95% CI 0.80-0.97) or above-average affluence (RR=0.84, 95% CI 0.76-0.91), not being drunk in the past 12 months (RR=0.77, 95% CI 0.69-0.85), not riding an all-terrain vehicle (RR=0.81, 95% CI 0.68-0.97) and not having permanent road access (RR=0.89, 95% CI 0.80-0.98) were protective against injury; sport participation increased risk (RR=1.45, 95% CI 1.33-1.59). Patterns of injury were similar across youth from the North and other parts of Canada. Given previous research, this was unexpected. When implementing injury prevention initiatives, individual and community-level risk factors are essential to understand; however, specific positive safety assets that might exist in different community contexts must also be considered.


The NeBoP score - a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe.
The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas.


Immunogenicity of human recombinant acetylcholine receptor alpha subunit: cytoplasmic epitopes dominate the antibody response in four mouse strains.
In mysathenia gravis (MG) autoantibodies directed against acetylcholine receptors (AChR), at the neuromuscular junction lead to muscle weakness. These antibodies are directed against extracellular determinants, predominantly on the AChR alpha subunits. Similar antibodies can be induced in animals by immunisation with purified AChR, but immunisation of mice with recombinant human alpha subunit or its extracellular domain has produced conflicting results. To study further the immunogenicity of the human alpha subunit we immunised four inbred stains (C57B1/6, SJL, BALB/c, SWR) with almost full-length recombinant alpha subunit, r37-429, and looked at B cell epitopes by mapping with smaller recombinant fragments and synthetic peptides. The majority of anti-r37-429 antibodies bound to sequences within a region thought to be cytoplasmic, alpha 325-368, and reacted with human AChR. In two C57B1/6 sera, only, most antibodies were directed against an extracellular region, alpha 138-167, but the r37-429 used for immunisation of these two mice appeared to have lost the integrity of its cytoplasmic domain during preparation. Our results suggest that the antigenicity of the cytoplasmic region of the recombinant alpha subunit dominates the immune response in each of the four strains, and may even suppress the formation of antibodies to the extracellular domain. Moreover, although C57B1/6 and SJL mice were able to produce antibodies to alpha 138-167, these antibodies did not react with intact AChR, and none of the mice became weak.


Risk of major adverse cardiovascular events among patients with rheumatoid arthritis after initial CT-based diagnosis and treatment.
Rheumatoid arthritis (RA) is a known risk factor for developing coronary artery disease (CAD). The influence of RA on the prognosis after initial CAD diagnosis and treatment is however largely unknown. We examined the risk of major cardiovascular events among RA and non-RA patients with chest pain referred to cardiac CT. This was a follow-up study, using data from the Western Denmark Heart Registry, containing data on CT angiography examinations (Cardiac CT). Information on RA diagnosis and covariates were identified through nationwide administrative registers. The primary outcome was a combined outcome including, myocardial infarction, ischaemic or unspecified stroke, coronary artery bypass grafting, percutaneous coronary intervention, and all-cause mortality. Median time until events or censoring was 3.5 years (min/max: 0.0: 9.2). Cox proportional hazard models were used to examine the association between RA/non-RA patients and outcomes. Among 42 257 patients, referred between 2008 and 2016, we identified 358 (0.8%) with RA. An increased risk was seen in RA compared with non-RA (adjusted HR 1.35, 95% CI 0.93 to 1.96). Among patients who had received flare treatment more than once prior to cardiac CT the adjusted HR 1.80 (95% CI 1.08 to 3.00), and among patients with seropositive RA the adjusted HR 1.42 (95% CI 0.93 to 2.16). In patients referred to cardiac CT due to chest pain, we found a trend of an association between RA and the combined primary outcome, supporting that RA per se, but in particular seropositive and active RA, may increase the risk of CAD even after initial CAD diagnosis and treatment.