Random breath testing in Queensland and Western Australia: examination of how the random breath testing rate influences alcohol related traffic crash rates.
In this paper we explore the relationship between monthly random breath testing (RBT) rates (per 1000 licensed drivers) and alcohol-related traffic crash (ARTC) rates over time, across two Australian states: Queensland and Western Australia. We analyse the RBT, ARTC and licensed driver rates across 12 years; however, due to administrative restrictions, we model ARTC rates against RBT rates for the period July 2004 to June 2009. The Queensland data reveals that the monthly ARTC rate is almost flat over the five year period. Based on the results of the analysis, an average of 5.5 ARTCs per 100,000 licensed drivers are observed across the study period. For the same period, the monthly rate of RBTs per 1000 licensed drivers is observed to be decreasing across the study with the results of the analysis revealing no significant variations in the data. The comparison between Western Australia and Queensland shows that Queensland's ARTC monthly percent change (MPC) is 0.014 compared to the MPC of 0.47 for Western Australia. While Queensland maintains a relatively flat ARTC rate, the ARTC rate in Western Australia is increasing. Our analysis reveals an inverse relationship between ARTC RBT rates, that for every 10% increase in the percentage of RBTs to licensed driver there is a 0.15 decrease in the rate of ARTCs per 100,000 licenced drivers. Moreover, in Western Australia, if the 2011 ratio of 1:2 (RBTs to annual number of licensed drivers) were to double to a ratio of 1:1, we estimate the number of monthly ARTCs would reduce by approximately 15. Based on these findings we believe that as the number of RBTs conducted increases the number of drivers willing to risk being detected for drinking driving decreases, because the perceived risk of being detected is considered greater. This is turn results in the number of ARTCs diminishing. The results of this study provide an important evidence base for policy decisions for RBT operations.


Familial nonmedullary thyroid cancer: screening, clinical, molecular and genetic findings.
Thyroid cancer, the commonest of endocrine malignancies, continues increasing in incidence being the 5th more prevalent cancer among women in the United States in 2012. Familial thyroid cancer has become a well-recognized, unique, clinical entity in patients with thyroid cancer originating from follicular cells, that is, nonmedullary thyroid carcinoma. Hereditary nonmedullary thyroid cancer may occur as a minor component of familial cancer syndromes (familial adenomatous polyposis, Gardner's syndrome, Cowden's disease, Carney's complex type 1, Werner's syndrome, and papillary renal neoplasia) or as a primary feature (familial nonmedullary thyroid cancer [FNMTC]). Although there is some controversy, some epidemiologic and clinical kindred studies have shown that FNMTC is associated with more aggressive disease than sporadic cases, with higher rates of multicentric tumours, lymph node metastasis, extrathyroidal invasion, and shorter disease-free survival. This way, preventing screening will allow earlier detection, more timely intervention, and hopefully improved outcomes for patients and their families. On the other hand, in the last years, an important number of genetic studies on FNMTC have been published, trying to determine its genetic contribution. However, the genetic inheritance of FNMTC remains unclear; but it is believed to be autosomal dominant with incomplete penetrance and variable expressivity. This paper provides an extensive overview of FNMTC from several points of view. Firstly, the impact of early detection on prognosis, secondly, the management and follow-up of FNMTC patients, and finally, the role of susceptibility loci, microRNAs (miRNAs) and telomerases in recently identified isolated cases of FNMTC.


Light Inhibition of Shoot Regeneration Is Regulated by Endogenous Abscisic Acid Level in Calli Derived from Immature Barley Embryos.
Shoot regeneration in calli derived from immature barley embryos is regulated by light conditions during the callus-induction period. Barley cultivars Kanto Nijo-5 (KN5) and K-3 (K3) showed lower efficiency of shoot regeneration in a 16-h photoperiod during callus-induction than those in continuous darkness, whereas shoot regeneration was enhanced in cultures under a 16-h photoperiod in Golden Promise (GP) and Lenins (LN). These cultivars were classified as photo-inhibition type (KN5 and K3) or photo-induction type (GP and LN) according to their response to light. Contents of endogenous plant hormones were determined in calli cultured under a 16-h photoperiod and continuous darkness. In photo-inhibition type, higher accumulation of abscisic acid (ABA) was detected in calli cultured under a 16-h photoperiod, whereas calli showed lower levels of endogenous ABA in continuous darkness. However, cultivars of photo-induction type showed lower levels of ABA in calli cultured under both light conditions, similarly to photo-inhibition type in continuous darkness. Exogenous ABA inhibited the callus growth and shoot regeneration independent of light conditions in all cultivars. In photo-inhibition type, lower levels of endogenous ABA induced by ABA biosynthesis inhibitor, fluridone, reduced the photo-inhibition of shoot regeneration. Expression of ABA biosynthesis gene, HvNCED1, in calli was regulated by the light conditions. Higher expression was observed in calli cultured under a 16-h photoperiod. These results indicate that ABA biosynthesis could be activated through the higher expression of HvNCED1 in a 16-h photoperiod and that the higher accumulations of ABA inhibit shoot regeneration in the photo-inhibition type cultivars.


A multidimensional approach to apathy after traumatic brain injury.
Apathy is commonly described following traumatic brain injury (TBI) and is associated with serious consequences, notably for patients' participation in rehabilitation, family life and later social reintegration. There is strong evidence in the literature of the multidimensional nature of apathy (behavioural, cognitive and emotional), but the processes underlying each dimension are still unclear. The purpose of this article is first, to provide a critical review of the current definitions and instruments used to measure apathy in neurological and psychiatric disorders, and second, to review the prevalence, characteristics, neuroanatomical correlates, relationships with other neurobehavioural disorders and mechanisms of apathy in the TBI population. In this context, we propose a new multidimensional framework that takes into account the various mechanisms at play in the facets of apathy, including not only cognitive factors, especially executive, but also affective factors (e.g., negative mood), motivational variables (e.g., anticipatory pleasure) and aspects related to personal identity (e.g., self-esteem). Future investigations that consider these various factors will help improve the understanding of apathy. This theoretical framework opens up relevant prospects for better clinical assessment and rehabilitation of these frequently described motivational disorders in patients with brain injury.


Hair color and hearing loss: a survey in a group of military men.
It has been shown that low levels of pigmentation increase susceptibility to noise-induced hearing loss in humans. For this reason, white populations develop more pronounced noise- induced hearing loss in comparison to black populations. Similarly, blue-eyed individuals exhibit greater temporary threshold shift than brown-eyed subjects; still, no strong correlation has been verified between the lightness of hair color and susceptibility to noise-induced hearing loss. This study was performed with the purpose of investigating a possible association between hair color and the degree of hearing loss due to firing noise. Prospective observational study. A tertiary referral center with an accredited otorhinolaryngology-head & neck surgery department. A total of 57 military recruits were divided into two groups; light-colored (blond and light brown) and dark-colored hair (dark brown and black). The two groups were matched based on history of firing noise exposure (number of rounds; type of weapon) and the level of hearing loss at 2, 3, 4, 6 and 8 kHz sound frequencies was compared between them. The results showed that the mean level of hearing loss of light-colored hair individuals (20.5±17dB) was significantly greater than that of dark-haired subjects (13.5±11dB), (P=0.023). The results indicate that hair color (blond versus black) can be used as an index for predicting susceptibility to noise-induced hearing loss in military environments. Therefore, based on the individual's hair color, upgraded hearing conservation programs are highly recommended.


Formalizing Neurath's ship: Approximate algorithms for online causal learning.
Higher-level cognition depends on the ability to learn models of the world. We can characterize this at the computational level as a structure-learning problem with the goal of best identifying the prevailing causal relationships among a set of relata. However, the computational cost of performing exact Bayesian inference over causal models grows rapidly as the number of relata increases. This implies that the cognitive processes underlying causal learning must be substantially approximate. A powerful class of approximations that focuses on the sequential absorption of successive inputs is captured by the Neurath's ship metaphor in philosophy of science, where theory change is cast as a stochastic and gradual process shaped as much by people's limited willingness to abandon their current theory when considering alternatives as by the ground truth they hope to approach. Inspired by this metaphor and by algorithms for approximating Bayesian inference in machine learning, we propose an algorithmic-level model of causal structure learning under which learners represent only a single global hypothesis that they update locally as they gather evidence. We propose a related scheme for understanding how, under these limitations, learners choose informative interventions that manipulate the causal system to help elucidate its workings. We find support for our approach in the analysis of 3 experiments. (PsycINFO Database Record


Why is real-world visual object recognition hard?
Progress in understanding the brain mechanisms underlying vision requires the construction of computational models that not only emulate the brain's anatomy and physiology, but ultimately match its performance on visual tasks. In recent years, "natural" images have become popular in the study of vision and have been used to show apparently impressive progress in building such models. Here, we challenge the use of uncontrolled "natural" images in guiding that progress. In particular, we show that a simple V1-like model--a neuroscientist's "null" model, which should perform poorly at real-world visual object recognition tasks--outperforms state-of-the-art object recognition systems (biologically inspired and otherwise) on a standard, ostensibly natural image recognition test. As a counterpoint, we designed a "simpler" recognition test to better span the real-world variation in object pose, position, and scale, and we show that this test correctly exposes the inadequacy of the V1-like model. Taken together, these results demonstrate that tests based on uncontrolled natural images can be seriously misleading, potentially guiding progress in the wrong direction. Instead, we reexamine what it means for images to be natural and argue for a renewed focus on the core problem of object recognition--real-world image variation.


Immunoglobulin G4: an odd antibody.
Despite its well-known association with IgE-mediated allergy, IgG4 antibodies still have several poorly understood characteristics. IgG4 is a very dynamic antibody: the antibody is involved in a continuous process of half-molecules (i.e. a heavy and attached light-chain) exchange. This process, also referred to as 'Fab-arm exchange', results usually in asymmetric antibodies with two different antigen-combining sites. While these antibodies are hetero- bivalent, they will behave as monovalent antibodies in most situations. Another aspect of IgG4, still poorly understood, is its tendency to mimic IgG rheumatoid factor (RF) activity by interacting with IgG on a solid support. In contrast to conventional RF, which binds via its variable domains, the activity of IgG4 is located in its constant domains. This is potentially a source of false positives in IgG4 antibody assay results. Because regulation of IgG4 production is dependent on help by T-helper type 2 (Th2) cells, the IgG4 response is largely restricted to non-microbial antigens. This Th2-dependency associates the IgG4 and IgE responses. Another typical feature in the immune regulation of IgG4 is its tendency to appear only after prolonged immunization. In the context of IgE-mediated allergy, the appearance of IgG4 antibodies is usually associated with a decrease in symptoms. This is likely to be due, at least in part, to an allergen-blocking effect at the mast cell level and/or at the level of the antigen-presenting cell (preventing IgE-facilitated activation of T cells). In addition, the favourable association reflects the enhanced production of IL-10 and other anti-inflammatory cytokines, which drive the production of IgG4. While in general, IgG4 is being associated with non-activating characteristics, in some situations IgG4 antibodies have an association with pathology. Two striking examples are pemphigoid diseases and sclerosing diseases such as autoimmune pancreatitis. The mechanistic basis for the association of IgG4 with these diseases is still enigmatic. However, the association with sclerosing diseases may reflect an excessive production of anti-inflammatory cytokines triggering an overwhelming expansion of IgG4-producing plasma cells. The bottom line for allergy diagnosis: IgG4 by itself is unlikely to be a cause of allergic symptoms. In general, the presence of allergen-specific IgG4 indicates that anti-inflammatory, tolerance-inducing mechanisms have been activated. The existence of the IgG4 subclass, its up-regulation by anti-inflammatory factors and its own anti-inflammatory characteristics may help the immune system to dampen inappropriate inflammatory reactions.


Effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') on the jaw-opening reflex and on the alpha-adrenoceptors which regulate this reflex in the anesthetized rat.
Bruxism, principally jaw clenching, is frequently observed in users of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA). It has been suggested that during bruxism a reduction of the activity of oral protective reflexes occurs. In this study we investigated the effects of intravenously administered MDMA on the digastric electromyographic responses elicited by orofacial electrical stimulation in the rat. We also assessed the effects of either the administration of a single dose (20 mg kg(-1), s.c.) or repeated doses of MDMA (same dose, twice a day, for 4 d) on the jaw-opening reflex (JOR) and on the sensitivity of the alpha(2)-adrenoceptors which, in an inhibitory way, regulate it. Increasing doses of MDMA (1-29440 micro g kg(-1)) induced an incomplete inhibition of JOR and 50% inhibition (ED(50)) at 2550 micro g kg(-1); maximal inhibition was 88%. The repeated treatment with MDMA led to an enhancement of the inhibition of JOR induced by the alpha(2)-agonist, clonidine (ED(50) was reduced by 77%), indicating an increased sensitivity of the alpha(2)-adrenoceptors. This study shows that the intravenous administration of MDMA reduces the JOR while repeated doses of the drug enhance the inhibitory noradrenergic mechanisms which regulate the reflex. The results also allow speculation that a reduction of JOR may underlie the occurrence of episodes of bruxism in MDMA users.


Differential expression of odorant-binding proteins in the mandibular glands of the honey bee according to caste and age.
Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) mediate both perception and release of chemical stimuli in insects. The genome of the honey bee contains 21 genes encoding OBPs and 6 encoding CSPs. Using a proteomic approach, we have investigated the expression of OBPs and CSPs in the mandibular glands of adult honey bees in relation to caste and age. OBP13 is mostly expressed in young individuals and in virgin queens, while OBP21 is abundant in older bees and is prevalent in mated queens. OBP14, which had been found in larvae, is produced in hive workers' glands. Quite unexpectedly, the mandibular glands of drones also contain OBPs, mainly OBP18 and OBP21. We have expressed three of the most represented OBPs and studied their binding properties. OBP13 binds with good specificity oleic acid and some structurally related compounds, OBP14 is better tuned to monoterpenoid structures, while OBP21 binds the main components of queen mandibular pheromone as well as farnesol, a compound used as a trail pheromone in the honey bee and other hymenopterans. The high expression of different OBPs in the mandibular glands suggests that such proteins could be involved in solubilization and release of semiochemicals.


Gravity measured at the apollo 14 lading site.
The gravity at the Apollo 14 landing site has been determined from the accelerometer data that were telemetered from the lunar module. The values for the lunar gravity measured at the Apollo 11, 12, and 14 sites were reduced to a common elevation and were then compared between sites. A theoretical gravity, based on the assumption of a spherical moon, was computed for each landing site and compared with the observed value. The observed gravity was also used to compute the lunar radius at each landing site.


Individual patient data meta-analysis of trials of self-monitoring of blood glucose in non-insulin treated type 2 diabetes: protocol for a systematic review.
Recent trials have provided differing estimates of the benefits of self-monitoring of blood glucose (SMBG) for non-insulin treated patients with type 2 diabetes. Designing and conducting randomised trials to demonstrate the efficacy of complex interventions is challenging. Variations in the components of the intervention delivered, target population selected, and reporting methods used have limited the conclusions drawn in recent systematic reviews. We will systematically examine these factors within the trials of SMBG to enable further investigation of the data through an individual patient data analysis (IPD). The IPD analysis will include data from randomised trials comparing blood glucose self-monitoring and decisions about self-management versus a control group with standardised or routine care. The data requested for each trial will include outcomes (HbA1c, blood glucose and quality of life), potential moderators of effect (e.g. demographic variables, clinical data and psychosocial factors) and intervention descriptors. The primary outcome of interest will be HbA1c. Secondary outcomes include alternative measures of glycaemia, cardiovascular risk factors, persistence with monitoring, and measures of health status, quality of life and psychosocial factors. Analysis of patient sub-groups defined by age at randomisation, gender, prior use of monitoring and health status will be carried out. An intention to treat analysis will be performed and assessed for clinical and statistical heterogeneity. With current uncertainty about the extent of benefit from SMBG for non-insulin treated patients with type 2 diabetes, this study will provide the best estimates to date of overall effectiveness, effectiveness within potential target populations, and optimal components of the intervention.


Gastroesophageal Reflux Frequency, Severity, Age of Onset, Family History and Acid Suppressive Therapy Predict Barrett Esophagus in a Large Population.
To identify risk factors associated with Barrett esophagus (BE) for potential improved surveillance and risk reduction. Gastroesophageal reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma, but the ability of GERD symptom frequency and severity to predict presence of its putative precursor lesion, BE, is less well-defined in large, community-based populations. We conducted a case-control study within the Kaiser Permanente Northern California population. Cases had new diagnoses of BE. To identify risk factors in the general population, we contrasted cases with population controls; to identify risk factors only among patients with GERD, we contrasted cases with GERD patients who lacked BE. We interviewed 953 patients; 320 patients with BE, 316 patients with GERD who lacked BE and 317 population controls. Compared with population controls, BE risk was highest among patients with the most frequent and severe GERD symptoms [odds ratio (OR), 27.00; 95% confidence interval (CI), 14.52-50.21], nocturnal symptoms (OR, 5.40; 95% CI, 3.81-7.72), and family history of GERD (OR, 2.55; 95% CI, 1.80-3.62) or BE (OR, 10.08; 95% CI, 2.83-35.84). Although at least weekly proton pump inhibitor (PPI) use was a risk factor for BE (OR, 9.85; 95% CI, 6.54-14.84), among PPI users in the general population, GERD symptoms were not strongly associated with the risk of BE. Compared with GERD controls, cases were more likely to have onset of GERD symptoms before 30 years of age (OR, 1.93; 95% CI, 1.15-3.22) and a family history of BE (OR, 3.64; 95% CI, 1.50-8.83). Severe and frequent GERD symptoms are strongly associated with increased risk of BE in the general population, especially in the absence of frequent PPI use. Among people with GERD, family history of BE and early age of symptom onset were stronger predictors of BE. These findings may improve identification of patients at highest risk for BE.


Role of intracellular and extracellular pH in the chemosensitive response of rat locus coeruleus neurones.
The chemosensitive response of locus coeruleus (LC) neurones to changes in intracellular pH (pH(i)), extracellular pH (pH(o)) and molecular CO(2) were investigated using neonatal rat brainstem slices. A new technique was developed that involves the use of perforated patch recordings in combination with fluorescence imaging microscopy to simultaneously measure pH(i) and membrane potential (V(m)). Hypercapnic acidosis (15 % CO(2), pH(o) 6.8) resulted in a maintained fall in pH(i) of 0.31 pH units and a 93 % increase in the firing rate of LC neurones. On the other hand, isohydric hypercapnia (15 % CO(2), 77 mM HCO(3)(-), pH(o) 7.45) resulted in a smaller and transient fall in pH(i) of about 0.17 pH units and an increase in firing rate of 76 %. Acidified Hepes (N-2-hydroxyethylpiperazine-N'-2- ethanesulfonic acid)-buffered medium (pH(o) 6.8) resulted in a progressive fall in pH(i) of over 0.43 pH units and an increase in firing rate of 126 %. Isosmotic addition of 50 mM propionate to the standard HCO(3)(-)-buffered medium (5 % CO(2), 26 mM HCO(3)(-), pH(o) 7.45) resulted in a transient fall in pH(i) of 0.18 pH units but little increase in firing rate. Isocapnic acidosis (5 % CO(2), 7 mM HCO(3)(-), pH(o) 6.8) resulted in a slow intracellular acidification to a maximum fall of about 0.26 pH units and a 72 % increase in firing rate. For all treatments, the changes in pH(i) preceded or occurred simultaneously with the changes in firing rate and were considerably slower than the changes in pH(o). In conclusion, an increased firing rate of LC neurones in response to acid challenges was best correlated with the magnitude and the rate of fall in pH(i), indicating that a decrease in pH(i) is a major part of the intracellular signalling pathway that transduces an acid challenge into an increased firing rate in LC neurones.


Weight Status as a Mediator of the Association Between Preschool Extraversion and Adolescent Restrained Eating.
To determine the longitudinal association between preschool extraversion and weight/dieting outcomes in adolescence. Children (N = 180) were recruited as part of a longitudinal study, with child temperament assessed in preschool (age 5.25 years), weight assessed in 2nd grade and early adolescence, and eating outcomes assessed in early adolescence (mean age = 12.02 years). Preschoolers high in extraversion were significantly more likely to have higher body mass index z-scores (zBMI) and more restrained eating behaviors in adolescence. zBMI was found to mediate the relationship between extraversion and restrained eating, such that children with high levels of extraversion were more likely to have higher zBMI in adolescence and, owing to this higher weight status, to engage in more restrained eating. Temperament is an important predictor of later maladaptive weight/dieting outcomes in adolescence, making it a potentially important early factor to consider in weight management interventions.


Probing metagenomics by rapid cluster analysis of very large datasets.
The scale and diversity of metagenomic sequencing projects challenge both our technical and conceptual approaches in gene and genome annotations. The recent Sorcerer II Global Ocean Sampling (GOS) expedition yielded millions of predicted protein sequences, which significantly altered the landscape of known protein space by more than doubling its size and adding thousands of new families (Yooseph et al., 2007 PLoS Biol 5, e16). Such datasets, not only by their sheer size, but also by many other features, defy conventional analysis and annotation methods. In this study, we describe an approach for rapid analysis of the sequence diversity and the internal structure of such very large datasets by advanced clustering strategies using the newly modified CD-HIT algorithm. We performed a hierarchical clustering analysis on the 17.4 million Open Reading Frames (ORFs) identified from the GOS study and found over 33 thousand large predicted protein clusters comprising nearly 6 million sequences. Twenty percent of these clusters did not match known protein families by sequence similarity search and might represent novel protein families. Distributions of the large clusters were illustrated on organism composition, functional class, and sample locations. Our clustering took about two orders of magnitude less computational effort than the similar protein family analysis of original GOS study. This approach will help to analyze other large metagenomic datasets in the future. A Web server with our clustering results and annotations of predicted protein clusters is available online at http://tools.camera.calit2.net/gos under the CAMERA project.


Pitfalls in the assessment of disability in individuals with low-grade gliomas.
In this study, the presence of motor and cognitive disability is described in a cohort of patients with low-grade glioma recruited from a geographical area with a well-defined population located in the middle of Sweden. The study group consisted of 35 patients, of which 24 were evaluated by both a neurologist and a neuropsychologist, and 11 only by a neurologist. The test battery according to EFIT (Edinburgh Functional Impairment Test) was used by the neurologist to measure impairments of limb function, memory and speech. Patients were asked to self-evaluate their deficits in motor function and cognition by responding to a specific questionnaire. In addition, a neuropsychological test battery was used by an experienced neuropsychologist who had no previous contact with the patients. In general, motor impairment was mild and predominantly found in the upper limb. Neuropsychological assessment revealed moderate or severe cognitive impairment in more than half of the patients. This impairment was not detected by neurological examination, and only to some extent reported by the patients them selves. The results show statistical differences in cognitive function, memory and language as recorded by the three assessors. In conclusion, this study demonstrates the usefulness of neuropsychological assessment as a complement to neurological examination to detect cognitive dysfunction in patients with low-grade gliomas.


Biodistribution of the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker. Comparison with other radioiodination methods.
We have evaluated the applicability of the [(4-isothiocyanatobenzylammonio)undecahydro-closo-dodecaborate (1-)] (DABI) linker molecule for antibody radiohalogenation and compared it to radiohalogenation using the linker N-succinimidyl 4-iodobenzoate (PIB) and to direct radiohalogenation using Chloramine T. These studies were performed to assess the potential of DABI conjugates and to optimize the biological properties of halogen-labeled cMAb U36. The three conjugates were evaluated in vitro for their specificity and affinity and in vivo for their biodistribution patterns in normal mice at 1.5, 6, 24, and 96 h pi. Labeling efficiencies of direct CAT labeling, indirect PIB labeling, and indirect DABI labeling were 90-95%, 60%, and 68%, respectively. This resulted in a PIB:cMAb U36 molar ratio of 1.8-2.5 and a DABI:cMAb U36 molar ratio of 4.1. The in vitro data demonstrated specific binding for all conjugates and similar affinities with values around 1 x 10(8) M(-)(1). However, the in vivo data revealed accumulation of the radioiodine uptake in thyroid for the directly labeled conjugate, with a value 10 times higher than the indirectly labeled conjugates 96 h pi. Both the (125)I-PIB-cMAb U36 and (125)I-DABI-cMAb U36 conjugates yielded a low thyroid uptake with no accumulation, indicating different catabolites for these conjugates. This may favor the use of the indirectly labeled conjugates for future studies. Apart from the specific results obtained, these findings also demonstrate how the right linker molecule will provide additional opportunities to further improve the properties of an antibody-radionuclide conjugate.


Socio-Emotional Competencies and School Performance in Adolescence: What Role for School Adjustment?
There is growing evidence in the literature of positive relationships between socio-emotional competencies and school performance. Several hypotheses have been used to explain how these variables may be related to school performance. In this paper, we explored the role of various school adjustment variables in the relationship between interpersonal socio-emotional competencies and school grades, using a weighted network approach. This network approach allowed us to analyze the structure of interrelations between each variable, pointing to both central and mediatory school and socio-emotional variables within the network. Self-reported data from around 3,400 French vocational high school students were examined. This data included a set of interpersonal socio-emotional competencies (cognitive and affective empathy, socio-emotional behaviors and collective orientation), school adjustment measures (adaptation to the institution, school anxiety, self-regulation at school, and self-perceived competence at school) as well as grades in mathematics and French language. The results showed that self-regulation at school weighted the most strongly on the whole network, and was the most important mediatory pathway. More specifically, self-regulation mediated the relationships between interpersonal socio-emotional competencies and school grades.


Effect of UV irradiation on transduction by coliphage T1.
Lysates of the virulent coliphage T1 transduce seven markers between strains of Escherichia coli with reproducilble efficiencies which range from 10(-7) to 10(-5). The ability of a UV-irradiated lysate to transduce Arg(+), Str(R), Trp(+), Lac(+), and Pro(+) is 90% and Bio(+) is 99% inactivated by doses which inactivate plaque formation of T1 by six orders of magnitude. A dose of irradiation which causes a 1- to 2-log drop in the titer of T1 stimulated Gal(+) transduction by two- to three-fold; no other marker tested was stimulated. Irradiation causes dislinkage of some co-transducible markers but not others.


Cancer-associated galactosyltransferase acceptor: inhibition of transformed cell and tumor growth.
A distinctive glycopeptide, which acts as an acceptor for a cancer-associated galactosyltransferase, has been detected in sera and effusions of patients with extensive carcinoma. Cancer-associated galactosyltransferase acceptor (CAGA) purified from human malignant effusions was tested for its effects on cell growth in vitro and in vivo. Addition of the glycopeptide to the media of cells growing in tissue culture significantly inhibited the attachment and growth of transformed cells but had minimal effect on nontransformed cells. Transformed hamster cells (BHKpy, BHKpygiv, Nilpy) and human malignant cells (BT-20 human breast, pancreatic and colonic carcinoma cells) were killed by the addition of as little as 0.5 microgram of acceptor (per ml of medium); whereas nontransformed counterparts did not show a significant change in growth or morphology. In vivo studies showed that the acceptor inhibited development and progression of tumors in hamsters inoculated with tumorigenic BHKpy cells and in nude mice inoculated with human carcinoma cells. Growth of tumors was inhibited 69--94% in animals given 20 micrograms of acceptor subcutaneously and 39--67% when acceptor was given intraperitoneally at the time of tumor cell inoculation. Administration of the acceptor after the development of palpable tumor (congruent to 0.5 cm) caused a 60--85% reduction in growth rate and, in some cases, actual reduction in size and disappearance of palpable tumor. These studies demonstrate that a galactosyltransferase glycopeptide acceptor purified from human malignant effusions produces selective inhibition of transformed cell growth in animal and tissue culture systems.


Body adiposity in later life and the incidence of dementia: the health in men study.
To determine if adiposity in later life increases dementia hazard. Cohort study of 12,047 men aged 65-84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease. Compared with men with BMI<25, participants with BMI between 25-30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70-0.95). The HR of dementia for men with BMI ≥ 30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67-1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR ≥ 0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69-0.98). We found a "J" shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR. Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR ≥ 0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.


Impact of interobserver disagreement on phenotype-genotype associations in Crohn's disease.
Nonvalidated definitions of disease-related parameters in inflammatory bowel disease cause variations in diagnosis and disease classification. We determined interobserver agreement on applications of definitions of the Vienna Classification variables and computed the potential influence of misclassification on genotype/phenotype associations. Ten records of patients with Crohn's disease (CD) were independently evaluated by 19 observers using a standardized inflammatory bowel disease documentation system, which included the Vienna Classification. Interobserver agreement (IOA) was calculated as a percentage of the observers' agreement with a predetermined reference observer and by Cohen's kappa. Randomized reclassifications were then computed with 10,000 simulation runs using the IOA results and published NOD2/CARD15 gene status. A chi-square independence test was calculated for each simulation run. IOA for location and behavior was 70% (K = 0.57) and 95% (K = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and for behavior from 91% to 97%. By including the results of histopathology into the evaluation of location, the overall IOA increased significantly, to 80% (P = 0.019). Assuming a true genotype/phenotype association, the proportion of studies with nonsignificant findings (P > 0.05) because of the observed misclassification of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%, depending on a study sample size of 500 or 150 patients respectively. We concluded that there is appreciable interobserver disagreement on the location of CD according to the original Vienna Classification that may obscure true genotype/phenotype associations. Definitions of disease parameters have to be validated before being used as the bases for classifications.


Variation in obesity among American secondary school students by school and school characteristics.
Body mass index (BMI) is known to vary by individual characteristics, but little is known about whether BMI varies by school and by school characteristics. Nationally representative samples of United States schools and students are used to determine the extent to which BMI and percent of students at or above the 85th percentile of BMI vary by school and by school characteristics. Data from the 1991-2004 Monitoring the Future (MTF) study were analyzed in 2006 and 2007. A relatively small proportion of variance in BMI lies between schools; intraclass correlations are on the order of 3%. Still, this is sufficient variation to provide very different environments for students attending schools that are low versus high in average BMI. There is some modest variation by school type (public, Catholic private, non-Catholic private); school size (number of students in the sampled grade); region of the country; and population density. There is more variation as a function of school socioeconomic status (SES) and racial/ethnic composition of the school. School SES in particular was negatively associated with BMI levels, even after controlling individual-level SES and racial/ethnic status. The residual differences in BMI by school suggest that some characteristic of the school and/or community environment--perhaps cultural factors or peer role modeling or differences in school food, beverage, or physical education policies--facilitate obesity in schools with a high concentration of lower socioeconomic students, beyond individual-level factors.


Driver injury severity related to inclement weather at highway-rail grade crossings in the United States.
Previous studies on crash modeling at highway-rail grade crossings were aimed at exploring the factors that are likely to increase the crash frequencies at highway-rail grade crossings. In recent years, modeling driver's injury severity at highway-rail grade crossings has received interest. Because there were substantial differences among different weather conditions for driver's injury severity, this study attempts to explore the impact of weather influence on driver injury at highway-rail grade crossing. Utilizing the most recent 10 years (2002-2011) of highway-rail grade crossing accident data, this study applied a mixed logit model to explore the determinants of driver injury severity under different weather conditions at highway-rail grade crossing. Analysis results indicate that drivers' injury severity at highway-rail grade crossings is strongly different for different weather conditions. It was found that the factors significantly impacting driver injury severity at highway-rail grade crossings include motor vehicle speed, train speed, driver's age, gender, area type, lighting condition, highway pavement, traffic volume, and time of day. The findings of this study indicate that crashes are more prevalent if vehicle drivers are driving at high speed or the oncoming trains are high speed. Hence, a reduction in speed limit during inclement weather conditions could be particularly effective in moderating injury severity, allowing more reaction time for last-minute maneuvering and braking in moments before impacts. In addition, inclement weather-related crashes were more likely to occur in open areas and highway-rail grade crossings without pavement and lighting. Paved highway-rail grade crossings with installation of lights could be particularly effective in moderating injury severity.


Prevalence of 3 sexually transmitted infections in a pediatric emergency department.
This study aimed to determine the prevalence of Chlamydia trachomatis, Neisseria gonorrheae, and Trichomonas vaginalis and to describe factors associated with sexually transmitted infection (STI) in a pediatric emergency department (ED). Adolescents aged 14 to 19 years presenting to a Midwestern pediatric ED were asked to provide urine for STI testing and complete a survey about previous sexual activity (PSA), high-risk behaviors, demographics, and visit reason (reproductive: genitourinary complaints, abdominal pain, or a female with vomiting). Comparisons between subgroups were analyzed using Χ test. Among 200 subjects (64% of approached), mean age was 15.6 years; 63% were female. Eleven subjects (6%; 95% confidence interval, 2.3-8.7) tested positive for 1 or more STIs: 10 for C. trachomatis (one denied PSA), 3 for T. vaginalis (all coinfected with C. trachomatis), and 1 for N. gonorrheae. Half reported PSA; of these, 71% reported 1 or more high-risk behaviors, most commonly first sex before the age of 15 years (51%) and no condom at last sex (42%). Among those with PSA and nonreproductive visit (n = 73), 11.0% had 1 or more STIs (95% confidence interval, 3.4-18.1). Two factors were associated with greater likelihood of positive STI test result, namely, reporting PSA versus no PSA (10% vs 1%, P = 0.005) and last sex within 1 month or less versus more than 1 month (20% vs 0%, P = 0.001). In this sample, none of the following characteristics were associated with STI: insurance, race, high-risk behaviors, age, or ED visit reason. Approximately 1 in 10 sexually active adolescent ED patients without reproductive complaints had 1 or more STIs. This suggests the need for strategies to increase STI testing for this population.


Can first cycle CBCs predict older patients at very low risk of neutropenia during further chemotherapy?
Elderly cancer patients with normal complete blood cell counts (CBCs) during the first course of (some types of) chemotherapy might be unlikely to experience grade 4 neutropenia during subsequent cycles. In this case, further weekly CBCs might be avoided. We used data of 223 cancer patients aged 70+ who were included in the CRASH (Chemotherapy Risk Assessment Score for High-age patients) trial between 2003 and 2007 in 7 cancer practices in the US. First cycle CBC values were compared to subsequent cycles. MAX2-score was used as a measure for toxicity of the chemotherapy regimen. Sixty-two patients (28%) experienced grade 4 neutropenia during subsequent cycles. Among patients who received chemotherapy with a MAX2-score lower than 0.20, only 4.6% of those without neutropenia during the first cycle experienced grade 4 neutropenia during subsequent cycles. Weekly CBC might be avoided in these patients receiving chemotherapy. Future prospective studies should confirm these results.


Minimally invasive direct repair of lumbar spondylolysis with a pedicle screw and hook construct.
Object Lumbar spondylolysis occurs in approximately 6% of the population and presents with localized mechanical back pain, often in young athletes. Surgical treatment may involve decompression, lumbar intersegmental fusion, or direct repair of pars defects. Although such open procedures may effectively resolve symptoms, minimal-access approaches may additionally decrease collateral damage to soft tissues, allowing young, active patients to resume athletic activities sooner. In this study, the authors review their experience repairing bilateral lumbar spondylolyses with screw and hook constructs placed via a minimal-access approach. Methods Five consecutive pediatric patients with bilateral L-5 spondylolysis were treated. Bilateral incisions (2.5 cm) were made over L-5. Exposure was maintained with bilateral expandable tubular retractor systems. Pedicle screws were placed in the L-5 pedicles and attached to hooks under the L-5 laminae. A direct repair was performed at the pars defect. Clinical characteristics, operative variables, and postoperative outcomes were collected. Results All 5 patients underwent surgery; 4 were male (80%) and 1 was female (20%), and the mean age was 15.8 years (range 15-17 years). The mean estimated blood loss and duration of surgery were 37 ml (range 15-75 ml) and 1.94 hours (range 1-3 hours), respectively. Postoperative hospital stays ranged from 1 to 3 days (mean 1.8 days). The only complication occurred in 1 patient who experienced minor superficial wound breakdown. All patients have experienced resolution of symptoms at this preliminary stage, which has continued over an 8-month follow-up period. Conclusions Lumbar spondylolysis can be adequately and safely treated via minimal-access surgical repair of the pars interarticularis by using pedicle screws and rod-hook constructs. This approach may decrease the collateral soft tissue damage common to open dissections, and may be ideal for young, active surgical candidates.


Conflicting influences on UK mothers' decisions to introduce solid foods to their infants.
Adherence to recommendations to wait until 6 months to introduce solid foods into infants' diets is very poor. An in-depth understanding of the factors involved in this decision is essential if health practitioners are to offer suitable advice and health education. A cross-sectional electronic questionnaire study was conducted with 105 mothers recruited via UK-based Internet parenting discussion forums. Ratings of variables important in making the decision to introduce solid foods were analyzed using factor analysis and multiple regression. Open-ended questions were analyzed qualitatively using content analysis. In this sample of educated women, later weaning was found to be associated with a focus on the importance of the recommendations and a perception that health visitor advice and support was poor. Earlier weaning was associated with a focus on the importance of putative weaning signs from the baby. Qualitative analysis revealed a number of conflicting influences on the decision about when to give solid foods: recommendations, guidelines and advice, signs from the baby, beliefs about solids and maternal considerations. The conflict that some mothers experience in deciding when to give their babies solid food between the rigid recommendations, more tailored guidance from health professionals and their perceptions of putative weaning signs from their infants poses a particular problem for those attempting to provide clear and helpful health education information. Future research must assess the extent to which this conflict is prevalent in the general population, and investigate the salience and utility of different health education messages to promote good infant health.


Adenohypophysial transmembrane potentials: polarity reversal by elevated external potassium ion concentration.
Incubation of rat adenohypophyses in potassium ion of sufficient concentration to provoke the release of several of the adenohypophysial trophic hormones produces a reversed, positive transmembrane potential in more than half the cells. This finding is consistent with a process of "stimulus-secretion coupling" in which hypothalamic releasing factors act by selective depolarization of their "target" cells. The positive potentials may be due to a prolonged preferential permeability to calcium ions triggered by an initial depolarization of the cell membrane to a threshold value by increased external potassium ion.


PVP stabilized Pt nano particles catalyzed de-oxygenation of phenoxazine group by hydrazine in physiological buffer media: surfactant competes with reactants for the same surface sites.
PVP capped platinum nano particles (PNP) of 5 nm diameter were prepared and characterized as homogeneous and of spherical nature. At physiological pH range (6.0-8.0), these PNP catalyze the deoxygenation of phenoxazine group containing resazurin (1) by hydrazine. The observed rate constants (k(o)), increase linearly with [PNP] at constant [1] and [Hydrazine]; but first increase and then after reaching a maximum it decrease with increase in [1] as well as in [Hydrazine]. The k(o) values increase linearly with 1/[H(+)] indicating N(2)H(4) as the reducing species that generates from the PNP assisted deprotonation of N(2)H(5)(+). The kinetic observations suggest Langmuir-Hinshelwood type surface reaction mechanism where both 1 and hydrazine are adsorbed on nano particles surface and compete for the same sites. Interestingly, the surfactant molecules, polyvinylpyrrolidone (PVP), though do not take part into reduction reaction but having same type of functional groups as reactants, competes with them for the same surface sites. Adsorption on PNP with same type of functional group is further supported by the FTIR spectra of Pt-PVP and Pt-1. Thus on increasing [PVP], k(o) decreases linearly and only when [PVP] is held constant, the plot of k(o) vs. [PNP] passes through the origin indicating the insignificance of uncatalyzed reaction. The plot of ln k(o) vs. [1] or [Hydrazine] shows two different linear zones with different exponent values with respect to [1] and [Hydrazine]. This indicates that along with the complex heterogeneous surface adsorption processes, the mutual interactions between the reactants are also changing with the relative concentrations of reactants or, in general, with the molar ratio ([Hydrazine]/[1]).


Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury.
Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.


The Effect of Cold Treatment of Parboiled Rice with Lowered Glycaemic Potency on Consumer Liking and Acceptability.
A significant reduction in rice starch digestibility and subsequent postprandial blood glucose responses following extended cold treatment (at 4 °C for 24 h) have been demonstrated in both in vitro and in vivo studies, respectively. The impact of cold treatment was more significant for parboiled rice compared to other rice varieties. This study aimed to investigate consumer liking of sensory characteristics that may influence consumer acceptability of three available rice products in the Auckland region (medium grain white, medium grain brown and parboiled rice, which were either freshly boiled or cold-treated and reheated). The consumer liking of sensory characteristics (colour, taste, flavour, and texture) of each rice sample were accessed using visual analogue scales (VAS) in a randomized single blind setting. In the second stage, the participants evaluated their acceptability on VAS after the nutritional value and the characteristics of the rice samples were revealed. Sixty-four rice consumers reported higher likings of sensory characteristics of cold-treated parboiled rice and medium grain brown rice. The effect of cold treatment on the liking of sensory characteristics was more significant for parboiled rice (p < 0.05). Participants who are between 36 and 55 years old and consume rice domestically more than 10 times per month preferred cold-treated brown rice (73.8% of the participants' population (67.4%, 80.2%)) and parboiled rice (74.3% of the participants' population (67.9%, 80.7%)) (p < 0.001). As a result, cold-treated reheated parboiled rice received higher likings and acceptability and could be recommended and accepted as a healthier replacement of the daily staple meal.


Modulating dream experience: Noninvasive brain stimulation over the sensorimotor cortex reduces dream movement.
Recently, cortical correlates of specific dream contents have been reported, such as the activation of the sensorimotor cortex during dreamed hand clenching. Yet, despite a close resemblance of such activation patterns to those seen during the corresponding wakeful behaviour, the causal mechanisms underlying specific dream contents remain largely elusive. Here, we aimed to investigate the causal role of the sensorimotor cortex in generating movement and bodily sensations during REM sleep dreaming. Following bihemispheric transcranial direct current stimulation (tDCS) or sham stimulation, guided by functional mapping of the primary motor cortex, naive participants were awakened from REM sleep and responded to a questionnaire on bodily sensations in dreams. Electromyographic (EMG) and electroencephalographic (EEG) recordings were used to quantify physiological changes during the preceding REM period. We found that tDCS, compared to sham stimulation, significantly decreased reports of dream movement, especially of repetitive actions. Other types of bodily experiences, such as tactile or vestibular sensations, were not affected by tDCS, confirming the specificity of stimulation effects to movement sensations. In addition, tDCS reduced EEG interhemispheric coherence in parietal areas and affected the phasic EMG correlation between both arms. These findings show that a complex temporal reorganization of the motor network co-occurred with the reduction of dream movement, revealing a link between central and peripheral motor processes and movement sensations of the dream self. tDCS over the sensorimotor cortex interferes with dream movement during REM sleep, which is consistent with a causal contribution to dream experience and has broader implications for understanding the neural basis of self-experience in dreams.


An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel.
The amino acid sequence of proteins generally carries all the necessary information for acquisition of native conformations, but the vectorial nature of translation can additionally determine the folding outcome. Such consideration is particularly relevant in human diseases associated to inherited mutations leading to structural instability, aggregation, and degradation. Mutations in the KCNQ2 gene associated with human epilepsy have been suggested to cause misfolding of the encoded Kv7.2 channel. Although the effect on folding of mutations in some domains has been studied, little is known of the way pathogenic variants located in the calcium responsive domain (CRD) affect folding. Here, we explore how a Kv7.2 mutation (W344R) located in helix A of the CRD and associated with hereditary epilepsy interferes with channel function. We report that the epilepsy W344R mutation within the IQ motif of CRD decreases channel function, but contrary to other mutations at this site, it does not impair the interaction with Calmodulin (CaM) in vitro, as monitored by multiple in vitro binding assays. We find negligible impact of the mutation on the structure of the complex by molecular dynamic computations. In silico studies revealed two orientations of the side chain, which are differentially populated by WT and W344R variants. Binding to CaM is impaired when the mutated protein is produced in cellulo but not in vitro, suggesting that this mutation impedes proper folding during translation within the cell by forcing the nascent chain to follow a folding route that leads to a non-native configuration, and thereby generating non-functional ion channels that fail to traffic to proper neuronal compartments. Our data suggest that the key pathogenic mechanism of Kv7.2 W344R mutation involves the failure to adopt a configuration that can be recognized by CaM in vivo but not in vitro.


Direct proof of a "more-than-single-layered" peptidoglycan architecture of Escherichia coli W7: a neutron small-angle scattering study.
A neutron small-angle scattering study was performed to determine the thickness and the scattering density profile of isolated peptidoglycan sacculi of Escherichia coli W7 in aqueous suspension (D2O). The maximum thickness (7 +/- 0.5 nm) of the sacculus from the exponential-phase cells was large enough to suggest the existence of a more-than-single-layered architecture. The experimental density profile across the thickness of the sacculus did not allow an unambiguous differentiation between a single-layered architecture characterized by completely extended peptide side chains projecting from the sugar strands or, alternatively, a partially triple layered structure. To resolve this ambiguity, sacculi were labeled with deuterated wall peptides. Comparison of the two experimental profiles indicated that the sacculus is more than single layered across its surface, with about 75 to 80% of its surface single layered and 20 to 25% triple layered.


Promoting patients' rights at the end of life in a geriatric setting in France: The healthcare professionals' level of knowledge about surrogate decision-makers and advance directives.
To assess levels of knowledge about patients' rights, surrogate decision-makers, and advance directives among healthcare professionals at three hospitals in France. A multicenter, cross-sectional study in three geriatric hospitals in the Paris area (France) in 2015. The participants' level of knowledge was assessed via an 18-item self-questionnaire on surrogate decision-makers, advance directives, and end-of-life decision-making. The characteristics associated with a good level of knowledge were assessed using logistic regression. Among the 301 healthcare professionals (median ± standard deviation age: 40.4 ± 10.2 years; women: 73.4 %), only 15.0 % (95 % confidence interval (CI): [19.7-29.5]) correctly answered at least 75 % of the questions on patients' rights. Respectively 24.6 % [19.7-29.5], 36.5 % [31.1-42.0] and 37.5 % [32.0-43.0] had sufficient knowledge regarding "surrogate decision-maker", "advance directives", and "decision-making at the end of life". In a multivariable analysis, the only factor significantly associated with a good level of knowledge about end-of-life policy was employment in a university hospital, with a non-significant trend for status as a physician. Our survey of staff working in geriatric care units highlighted the poor overall level of knowledge about healthcare surrogates and advance directives; the results suggest that additional training in these concepts is required. Continuing education of healthcare professionals on advance directives and surrogate decision-maker should be promoted to ensure rights of elderly patients at the end of life.


Technologies to minimize blood transfusion in cardiac and orthopedic surgery. Results of a practice variation survey in nine countries. International Study of Peri-operative Transfusion (ISPOT) Investigators.
Due to the discovery in the 1980s that blood transfusion can transmit HIV, there has been increased interest in technologies that reduce the amount of allogeneic blood used during and after surgery. These technologies include drugs (aprotinin, tranexamic acid, epsilon-aminocaproic acid, erythropoietin), devices (cell salvage), and techniques (acute hemodilution, predeposited autologous donation). The purpose of this study was to ascertain the degree of practice variation, if any, that exists for eight technologies in nine countries in orthopedic and cardiac surgery. In each country, either all hospitals or a random sample of hospitals with medical/surgical beds were surveyed between 1995 and 1997. Two instruments were used. The first instrument was a postcard that asked recipients whether the technologies were currently being used in their hospital for orthopedic and/or cardiac surgery to reduce perioperative allogeneic transfusion. The second questionnaire elicited information regarding the degree of use both in qualitative and quantitative terms. Data were collected, entered, and analyzed in each country, with summary results submitted to the Canadian coordinating center on a standardized data collection form. Pharmaceuticals were generally used in a much smaller proportion of hospitals in orthopedic than in cardiac surgery. Aprotinin and tranexamic acid were the drugs most frequently used in cardiac surgery. Nonpharmacological technologies were used to a greater degree than drugs in orthopedic surgery, although there was wide variation among technologies and countries. Acute hemodilution and cell salvage were used in a greater proportion of hospitals for cardiac surgery than orthopedic surgery. The results of this survey indicate that there is considerable practice variation in the use of technologies to minimize exposure to perioperative allogeneic transfusion within and between countries.


Enhanced structural and functional genome elucidation of the arsenite-oxidizing strain Herminiimonas arsenicoxydans by proteomics data.
The arsenite-oxidizing strain Herminiimonas arsenicoxydans proteome was investigated with gel electrophoresis and tandem mass spectrometry analyses. The comparison of experimental and theoretical M(r) and pI, as well as that of peptide sequences identified by MS and predicted protein sequences, allowed the correction of five protein annotations. More importantly, the functional analysis of SDS- and 2D-PAGE proteome maps obtained in the presence of arsenic, combined with partial transcriptomic results indicate that H. arsenicoxydans expressed genes and proteins required not only for arsenic detoxification or stress response but also involved in motility, exopolysaccharide synthesis, phosphate import or energetic metabolism. This study provides therefore new insights into the adaptation processes of H. arsenicoxydans in response to arsenic.


Effects of indomethacin on lymphokine-activated killer cell activities in cancer patients.
Prostaglandin E2 (PGE2) is known to downregulate the generation of lymphokine-activated killer (LAK) cell activity. Indomethacin, an inhibitor of cyclooxygenase catalyzing the biosynthesis of PGE2, has been shown to augment LAK cell activities generated from peripheral blood mononuclear cells of normal healthy individuals. This study was undertaken to examine whether or not this augmentation is also a common phenomenon in cancer patients. LAK cell activities generated in the presence and the absence of indomethacin were examined in 15 normal healthy individuals and in 83 cancer patients. Paired data analysis revealed that indomethacin exhibited a significant augmentation of LAK activity generated from healthy individuals. Indomethacin enhanced LAK activity in patients with no distant metastases (TxNxM0); but depressed LAK activity in patients with distant metastases (TxNxM1). In patients without distant metastases, indomethacin showed an upregulating effect on LAK activity in those with an early T stage (T1-2NxM0), and no such effect was detected in those with a late T stage (T3-4NxM0). Indomethacin also significantly enhanced LAK cell generation in cancer patients with an ECOG performance status of 1, but significantly inhibited LAK cell generation in patients with a performance status of 4. These results indicated that indomethacin inhibited generation of LAK cell activity in cancer patients with a poor performance status or with distant metastatic disease, who normally would be the subjects of adoptive immunotherapy. Further, PGE2 production in cultured LAK cell medium was suppressed by indomethacin in all 20 cancer patients that were examined, suggesting that other yet to be identified factors or mechanisms may be responsible for the paradoxical effects of indomethacin on LAK cell activity.


Tn5 Insertion Mutants of Pseudomonas fluorescens Defective in Adhesion to Soil and Seeds.
Tn5 insertion mutants of a soil isolate, Pseudomonas fluorescens Pf0-1, were selected for decreased ability to adhere to quartz sand in a column assay. Three adhesion-deficient mutants that differed in the location of the Tn5 insertion in the chromosome were isolated and compared with the wild-type strain. One mutant, Pf0-5, was described previously as an adhesion-defective, nonmobile, flagellumless mutant (M. F. DeFlaun, A. S. Tanzer, A. L. McAteer, B. Marshall, and S. B. Levy, Appl. Environ. Microbiol. 56:112-119, 1990). Another insertion mutant, Pf0-10, was also missing flagella and the 34-kDa outer membrane protein that was absent in Pf0-5 but present in the wild-type strain. The third mutant (Pf0-15) had increased amounts of this 34-kDa outer membrane protein and more flagella than the wild-type strain. These mutants also displayed decreased ability to adhere to sterile and natural (live) soil and to a variety of plant seeds. In kinetics studies, the wild-type strain showed an initial rapid binding to seeds followed by a later slow phase of binding. The mutant strains were defective in the initial stages of attachment but did show the later slow binding. The findings indicate that the same mutations that affect binding to sand and soil also affect adhesion to plant seeds.


In vitro and in vivo evaluation of doxycycline-chondroitin sulfate/PCLmicrospheres for intraarticular treatment of osteoarthritis.
Osteoarthritis (OA) is a degenerative joint disease, which has no complete treatment with medication yet. Intraarticular hyaluronan (HA) injection can decrease pain and modify the natural course of OA. This study was designed to provide long term delivery of an MMP (matrix-metalloproteinase) inhibitor agent-doxycycline, together with matrix regenerative agent-chondroitin sulfate for treating OA which progress with matrix degenerations. Doxycycline (D) and doxycycline-chondroitin sulfate (D-CS) loaded poly-ɛ-caprolactone (PCL) microspheres (MS) were prepared as intraarticular delivery systems. Bio-effectiveness of developed microspheres was first evaluated with three-dimensional in vitro model of OA where both MS showed significant reduction in MMP-13 levels compared to untreated OA-chondrocytes at 15 and 24 days. Significant decrease was observed in GAG release into the media for both D MS and D-CS MS treated groups at 15 and 24 days. Second, the microspheres were injected to rabbit knee in hyaluronan (HA) to evaluate the effectiveness of the treatment. Radiographic scores of D MS and D-CS MS groups improved after 8 weeks when compared to OA group. Mankin-Pitzker histological scores similarly showed improvement with D MS and D-CSMS groups when compared to OA group. Ex vivo hardness tests of cartilages demonstrated superior hardness values with both doses of D-CSMS compared to OA group. D MS showed promising improvement of OA in histology results. Although, both MS groups had similar effects on cells in the in vitro model, D-CSMS had a positive contribution on all in vivo treatment outcomes and showed potential as a new strategy for treatment when applied to OA knee joints.


Fearful but not happy expressions boost face detection in human infants.
Human adults show an attentional bias towards fearful faces, an adaptive behaviour that relies on amygdala function. This attentional bias emerges in infancy between 5 and 7 months, but the underlying developmental mechanism is unknown. To examine possible precursors, we investigated whether 3.5-, 6- and 12-month-old infants show facilitated detection of fearful faces in noise, compared to happy faces. Happy or fearful faces, mixed with noise, were presented to infants (N = 192), paired with pure noise. We applied multivariate pattern analyses to several measures of infant looking behaviour to derive a criterion-free, continuous measure of face detection evidence in each trial. Analyses of the resulting psychometric curves supported the hypothesis of a detection advantage for fearful faces compared to happy faces, from 3.5 months of age and across all age groups. Overall, our data show a readiness to detect fearful faces (compared to happy faces) in younger infants that developmentally precedes the previously documented attentional bias to fearful faces in older infants and adults.


Iron and other micronutrient deficiencies in low-birthweight infants.
Low birthweight (LBW), defined as birthweight <2,500 g, is a major global public health problem and is associated with lifelong cognitive and behavioral problems. Very LBW (VLBW) infants (<1,500 g) are at high risk of multiple macro- and micronutrient deficiencies, but most LBW infants are larger (1,500-2,500 g), and the most common nutritional problem of those infants is iron deficiency (ID). Globally, about 25% of pre-school children have ID anemia (IDA), the most severe form of ID, and there is good evidence that ID is associated with impaired brain development. However, adverse effects of excessive iron supplementation have been observed. Delayed umbilical cord clamping, which increases infant iron stores, should be recommended for all newborns. There is good evidence that intakes of 2 mg of dietary iron per kg daily prevents IDA in LBW infants without causing adverse effects. A recent study shows that this dose of iron supplementation also reduces the risk of behavioral problems at 3 years in infants with birthweights 2,000-2,500 g. VLBW infants need 2-3 mg/kg per day. To achieve these intakes, breastfed LBW infants should receive iron supplements, and formula-fed LBW infants should receive an iron-fortified infant formula.


Factors associated with the prescribing of high-dose opioids in primary care: a systematic review and meta-analysis.
The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. PROSPERO, CRD42018088057.


A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature.
Anaplastic pancreatic carcinomas are rare tumors, frequently displaying a variety of growth patterns. The literature lacks a comprehensive study of this tumor. Thirty-five cases of anaplastic carcinoma of the pancreas diagnosed between 1955 and 1997 were retrieved from the Endocrine Registry at the Armed Forces Institute of Pathology. Histology, immunophenotype, molecular analysis, and patient follow-up were analyzed. The tumors of 10 women and 25 men, aged 34 to 85 years (mean age at presentation, 62.5 years), were studied. Patients had vague symptoms (weight loss, pain, and fatigue, nausea, or vomiting), lasting an average of 13.2 weeks. The tumors, of an average size of 9.2 cm, were usually in the head or tail of the pancreas. The tumors were widely infiltrative, histomorphologically separated into predominantly large, pleomorphic cell, or spindle cell groups. Tumor phagocytosis and necrosis were noted. Immunohistochemical studies confirmed an epithelial origin with at least one epithelial marker in 78% of the tumors. K-ras mutations by sequence analysis were found in eight of 12 cases tested. Surgical biopsy/excision was used in all patients. Twenty-nine of 35 patients died of disease (average, 5.2 months), three died with no evidence of disease (average, 56.9 months), and three patients were alive at last follow-up (average, 94.0 months), one with residual disease. There was no statistically significant difference in survival between patients with and without a K-ras mutation. Anaplastic carcinoma of the pancreas usually occurs in the head of the pancreas in older men. The epithelial nature of the pleomorphic cells (giant or spindled) can usually be documented. Patients with K-ras mutations have a shorter survival time, even though the overall prognosis for all anaplastic carcinomas is fatal (93% fatality; average survival, 448 days). Ann Diagn Pathol 5: 129-140, 2001. This is a US government work. There are no restriction on its use.


Biochemical recurrence without PSA progression characterizes a subset of patients after radical prostatectomy. Prostate-specific antigen.
To characterize a subset of patients with biochemical recurrence after radical prostatectomy but with little, if any, subsequent rise in serum prostate-specific antigen (PSA) and no clinical progression during long-term follow-up. Of a series of 600 patients, 158 with biochemical recurrence after radical prostatectomy were examined. We identified a subset with measurable serum PSA levels during long-term follow-up, but with very low PSA velocity and no clinical recurrence. Serum PSA was measured with the ultrasensitive TOSOH assay with a PSA recurrence defined as a serum PSA of 0.07 ng/mL or greater. We identified 14 patients (8.8% of biochemical recurrences) with a detectable serum PSA level after radical prostatectomy yet without clinical or PSA progression at a mean follow-up after radical prostatectomy of 10.3 years. The mean time to PSA recurrence was 5.8 years, and the mean PSA velocity after recurrence was 0.028 ng/mL/yr. No clinical or pathologic features were found that could be used to identify this subset of patients. A subset of patients with biochemical recurrence after radical prostatectomy will not exhibit a progressive rise in serum PSA or clinical progression at 10 years follow-up. This suggests that serum PSA kinetics should be observed after biochemical recurrence before adjuvant hormonal therapy or radiotherapy.


Diseases, Injuries, and Risk Factors in Child and Adolescent Health, 1990 to 2017: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2017 Study.
Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. Being under the age of 20 years between 1990 and 2017. Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years.


Kaposiform hemangioendothelioma of infancy and childhood. An aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis.
We report the clinical and pathological features of nine distinctive, but relatively unknown, vascular tumors of infancy and childhood presenting as soft tissue masses often associated with locally aggressive disease, lymphangiomatosis and Kasabach-Merritt syndrome. The patients, four males and five females, were all in their first decade of life except for two (median, 2 years; range, 5 months to 19 years). These tumors involved deep soft tissues of the upper extremity (four cases), retroperitoneum (two cases), chest wall, scalp, and neck (one case each). Four patients also had Kasabach-Merritt syndrome, and three patients had lymphangiomatosis. Lymphangiomatosis consisted of diffusely infiltrating lymphangioma of soft tissue (three cases) and in two by the additional presence of bone lesions. In one of these three cases, lymphangiomatosis antedated the diagnosis of the vascular tumor, and in the remainder they were concurrently diagnosed. Tumors were characterized by infiltrating, interconnecting sheets or irregular nodules of slender endothelial cells lining crescentic or slit-like vessels and, less commonly, rounded capillary-type vessels. Within some tumors, nests of epithelioid endothelial cells with prominent eosinophilic cytoplasm containing finely granular hemosiderin, hyaline droplets, and cytoplasmic vacuoles were identified. Smaller amounts of hemosiderin were observed within the spindled endothelial cells and microthrombi could be seen occasionally within the tiny lumina. Nuclear atypia was minimal within these tumors and mitotic figures were infrequent, averaging 2 to 3/10 high-power fields (HPF) (range 0-7/10 HPF). Larger, well-formed feeding vessels were present at the periphery of the tumor. The endothelium of these vessels expressed factor VIII-AG, CD34, and bound Ulex europaeus, and contained an occasional perithelial cell expressing muscle-specific actin. In contrast, the spindled tumor cells expressed only CD34. Human papilloma virus (HPV)-16-like DNA transcripts, which have been identified in cases of Kaposi's sarcoma, were not detected by polymerase chain reaction in two cases. Follow-up information revealed that four patients were alive without disease after wide excision, multiple excision(s), or amputation (one case); three were alive with disease; and two died, one from lymphangiomatosis with respiratory compromise and the other from hemorrhage complicating Kasabach-Merritt syndrome. It appears that treatment should consist of wide local excision and supportive therapy for associated symptoms.


Analysis of the spatial sensitivity of conductance/admittance catheter ventricular volume estimation.
Conductance catheters are known to have a nonuniform spatial sensitivity due to the distribution of the electric field. The Geselowitz relation is applied to murine and multisegment conductance catheters using finite element models to determine the spatial sensitivity in a uniform medium and simplified left ventricle models. A new formulation is proposed that allows determination of the spatial sensitivity to admittance. Analysis of FEM numerical modeling results using the Geselowitz relation provides a true measure of parallel conductance in simplified left ventricle models for assessment of the admittance method and hypertonic saline techniques. The spatial sensitivity of blood conductance (Gb) is determined throughout the cardiac cycle. Gb is converted to volume using Wei's equation to determine if the presence of myocardium alters the nonlinear relationship through changes to the electric field. Results show that muscle conductance (Gm) from the admittance method matches results from the Geselowitz relation and that the relationship between Gb and volume is accurately fit using Wei's equation. Single-segment admittance measurements in large animals result in a more evenly distributed sensitivity to the LV blood pool. The hypertonic saline method overestimates parallel conductance throughout the cardiac cycle in both murine and multisegment conductance catheters.


Glucose-induced activation of the plasma membrane H(+)-ATPase in Fusarium oxysporum.
Addition of glucose and other sugars to derepressed cells of the fungus Fusarium oxysporum var. lini triggered activation of the plasma membrane H(+)-ATPase within 5 min. Glucose was the best activator while galactose and lactose had a lesser effect. The activation was not prevented by previous addition of cycloheximide and it was fully reversible when the glucose was removed. The activation process in vivo also caused changes in the kinetic properties of the enzyme. The non-activated enzyme had an apparent Km of about 3.2 mM for ATP whereas the activated enzyme showed an apparent Km of 0.26 mM. In addition, the pH optimum of the H(+)-ATPase changed from 6.0 to 7.5 upon activation. The activated enzyme was more sensitive to inhibition by vanadate. When F. oxysporum was cultivated in media containing glucose as the major carbon source, enhanced H(+)-ATPase activity was largely confined to the period corresponding to the lag phase, i.e. just before the start of acidification of the medium. This suggests that the activation process might play a role in the onset of extracellular acidification. Addition of glucose to F. oxysporum var. lini cells also caused an increase in the cAMP level. No reliable increase could be demonstrated for the other sugars. Addition of proton ionophores such as DNP and CCCP at pH 5.0 caused both a large increase in the intracellular level of cAMP and in the activity of the plasma membrane H(+)-ATPase. Inhibition of the DNP-induced increase in the cAMP level by acridine orange also resulted in inhibition of the activation of plasma membrane H(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)


An intracellular analysis of some intrinsic factors controlling neural output from inferior mesenteric ganglion of guinea pigs.
1. In vitro studies were conducted on neurons within the inferior mesenteric ganglion (IMG) of guinea pigs to investigate how intrinsic features of the spike-generating process interact with preganglionic inputs to produce the output firing patterns of these neurons. Intracellular-electrode techniques were used to monitor and control electrical activity of IMG neurons. Preganglionic inputs were activated either synchronously by stimulating an attached nerve trunk or asynchronously by leaving the ganglion attached to a segment of terminal colon and activating the colonic-IMG mechanosensory system. 2. Ninety-seven percent of the neurons studied demonstrated an afterspike hyperpolarization (ASH). The ASH process was activated only by the occurrence of a spike and did not have a synaptically induced component. Further activation of this process was produced by two or more spikes having interspike intervals less than the duration of an ASH following a single spike. An aftertrain hyperpolarization (ATH) resulted from this progressive activation. The amplitude of both the ASH and the ATH decreased when the resting membrane potential was hyperpolarized by current injection or by increasing the external potassium ion concentration. 3. Neuronal excitability was reduced during the ASH. From this observation it was concluded that when IMG neurons operate in the occasional-firing mode, the ASH process prevents output frequency from greatly exceeding the reciprocal of the ASH duration produced by a single spike. 4. Two types of synaptically induced slow depolarizations were observed: a slow, long-latency depolarization and a short-latency depolarization (SLD). These depolarizations differed in their latency, onset, and duration. Both were capable of converting synchronous, preganglionic input from subthreshold (non-spike-activating) to threshold (spike-activating) activity. 5. Neurons having resting potentials more positive than -60 mV were capable of firing in the rhythmic-firing mode; 40% of these neurons demonstrated tonic- and 60% phasic-firing behavior. Frequency-current relations for tonic-discharging neurons were linear from the rhythmic-firing threshold to current levels approximately 2.5 times the threshold value. Minimal frequency for tonic firing and the slope of the linear portion of the frequency-current relation were indirectly related to the duration of the ASH. 6. This study suggests that sympathetic, noradrenergic neurons of the IMG can operate in either the occasional- or rhythmic-firing mode. In the physiologic state in vivo, most IMG neurons probably do not produce action potentials in excess of 10-15 Hz because of their intrinsic properties which regulate firing in both modes of operation.


RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase.
The RAC guanine nucleotide binding proteins regulate multiple biological activities, including actin polymerization, activation of the Jun kinase (JNK) cascade, and cell proliferation. RAC effector loop mutants were identified that separate the ability of RAC to interact with different downstream effectors. One mutant of activated human RAC protein, RACV12H40 (with valine and histidine substituted at position 12 and 40, respectively), was defective in binding to PAK3, a Ste20-related p21-activated kinase (PAK), but bound to POR1, a RAC-binding protein. This mutant failed to stimulate PAK and JNK activity but still induced membrane ruffling and mediated transformation. A second mutant, RACV12L37 (with leucine substituted at position 37), which bound PAK but not POR1, induced JNK activation but was defective in inducing membrane ruffling and transformation. These results indicate that the effects of RAC on the JNK cascade and on actin polymerization and cell proliferation are mediated by distinct effector pathways that diverge at the level of RAC itself.


G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease.
Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34(+) cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34(+) monocytes in peripheral blood CD34(+) cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD.


What an ambulance nurse needs to know: a content analysis of curricula in the specialist nursing programme in prehospital emergency care.
In Sweden, ambulances must be staffed by at least one registered nurse. Twelve universities offer education in ambulance nursing. There is no national curriculum for detailed course content and there is a lack of knowledge about the educational content that deals with the ambulance nurse practical professional work. The aim of this study was to describe the content in course curricula for ambulance nurses. A descriptive qualitative research design with summative content analysis was used. Data were generated from 49 courses in nursing and medical science. The result shows that the course content can be described as medical, nursing and contextual knowledge with a certain imbalance with largest focus on medical knowledge. There is least focus on nursing, the registered nurses' main profession. This study clarifies how the content in the education for ambulance nurses in Sweden looks today but there are reasons to discuss the content distribution.


Financial aid policy: lessons from research.
In the nearly fifty years since the adoption of the Higher Education Act of 1965, financial aid programs have grown in scale, expanded in scope, and multiplied in form. As a result, financial aid has become the norm among college enrollees. Aid now flows not only to traditional college students but also to part-time students, older students, and students who never graduated from high school. Today aid is available not only to low-income students but also to middle- and even high-income families, in the form of grants, subsidized loans, and tax credits. The increasing size and complexity of the nation's student aid system has generated questions about effectiveness, heightened confusion among students and parents, and raised concerns about how program rules may interact. In this article, Susan Dynarski and Judith Scott-Clayton review what is known, and just as important, what is not known, about how well various student aid programs work. The evidence, the authors write, clearly shows that lowering costs can improve college access and completion. But this general rule is not without exception. First, they note, the complexity of program eligibility and delivery appears to moderate the impact of aid on college enrollment and persistence after enrollment. Second, for students who have already decided to enroll, grants that tie financial aid to academic achievement appear to boost college outcomes such as persistence more than do grants with no strings attached. Third, compared with grant aid, relatively little rigorous research has been conducted on the effectiveness of student loans. The paucity of evidence on student loans is particularly problematic both because they represent a large share of student aid overall and because their low cost (relative to grant aid) makes them an attractive option for policy makers. Future research is likely to focus on several issues: the importance of program design and delivery, whether there are unanticipated interactions between programs, and to what extent program effects vary across different types of students. The results of this evidence will be critical, the authors say, as politicians look for ways to control spending.


Association of urinary sodium/creatinine ratio with bone mineral density in postmenopausal women: KNHANES 2008-2011.
Accumulating evidence shows that high sodium chloride intake increases urinary calcium excretion and may be a risk factor for osteoporosis. However, the effect of oral sodium chloride intake on bone mineral density (BMD) and risk of osteoporosis has been inadequately researched. The aim of the present study was to determine whether urinary sodium excretion (reflecting oral sodium chloride intake) associates with BMD and prevalence of osteoporosis in postmenopausal women. This cross-sectional study involved a nationally representative sample consisting of 2,779 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys in 2008-2011. The association of urinary sodium/creatinine ratio with BMD and other osteoporosis risk factors was assessed. In addition, the prevalence of osteoporosis was assessed in four groups with different urinary sodium/creatinine ratios. Participants with osteoporosis had significantly higher urinary sodium/creatinine ratios than the participants without osteoporosis. After adjusting for multiple confounding factors, urinary sodium/creatinine ratio correlated inversely with lumbar spine BMD (P = 0.001). Similarly, when participants were divided into quartile groups according to urinary sodium/creatinine ratio, the average BMD dropped as the urinary sodium/creatinine ratio increased. Multiple logistic regression analysis revealed that compared to quartile 1, quartile 4 had a significantly increased prevalence of lumbar spine osteoporosis (odds ratios 1.346, P for trend = 0.044). High urinary sodium excretion was significantly associated with low BMD and high prevalence of osteoporosis in lumbar spine. These results suggest that high sodium chloride intake decreases lumbar spine BMD and increases the risk of osteoporosis in postmenopausal women.


Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype.
Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to sixfold and eight- to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2-3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research.