Ecallantide for the treatment of acute attacks in hereditary angioedema.
Hereditary angioedema is a rare genetic disorder characterized by acute, intermittent, and potentially life-threatening attacks of edema of the skin and mucosa. We evaluated ecallantide, a newly developed recombinant plasma kallikrein inhibitor, for the treatment of acute attacks of angioedema. In this double-blind, placebo-controlled trial, patients with hereditary angioedema presenting with an acute attack were randomly assigned, in a 1:1 ratio, to receive subcutaneous ecallantide, at a dose of 30 mg, or placebo. Two measures of patient-reported outcomes were used to assess the response: treatment outcome scores, which range from +100 (designated in the protocol as significant improvement in symptoms) to -100 (significant worsening of symptoms), and the change from baseline in the mean symptom complex severity score, which range from +2 (representing a change from mild symptoms at baseline to severe symptoms after) to -3 (representing a change from severe symptoms at baseline to no symptoms after). The primary end point was the treatment outcome score 4 hours after study-drug administration. Secondary end points included the change from baseline in the mean symptom complex severity score at 4 hours and the time to significant improvement. A total of 71 of the 72 patients completed the trial. The median treatment outcome score at 4 hours was 50.0 in the ecallantide group and 0.0 in the placebo group (interquartile range [IQR], 0.0 to 100.0 in both groups; P=0.004). The median change in the mean symptom complex severity score at 4 hours was -1.00 (IQR, -1.50 to 0.00) with ecallantide, versus -0.50 (IQR, -1.00 to 0.00) with placebo (P=0.01). The estimated time to significant improvement was 165 minutes with ecallantide versus more than 240 minutes with placebo (P=0.14). There were no deaths, treatment-related serious adverse events, or withdrawals owing to adverse events. Four hours after administration of ecallantide or placebo for acute attacks of angioedema in patients with hereditary angioedema, patient-reported treatment outcome scores and mean symptom complex severity scores were significantly better with ecallantide than with placebo. (Funded by Dyax; ClinicalTrials.gov number, NCT00262080.)


Identification and characterization of two consistent osteoarthritis subtypes by transcriptome and clinical data integration.
To identify OA subtypes based on cartilage transcriptomic data in cartilage tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics. This study includes n = 66 primary OA patients (41 knees and 25 hips), who underwent a joint replacement surgery, from which macroscopically unaffected (preserved, n = 56) and lesioned (n = 45) OA articular cartilage were collected [Research Arthritis and Articular Cartilage (RAAK) study]. Unsupervised hierarchical clustering analysis on preserved cartilage transcriptome followed by clinical data integration was performed. Protein-protein interaction (PPI) followed by pathway enrichment analysis were done for genes significant differentially expressed between subgroups with interactions in the PPI network. Analysis of preserved samples (n = 56) resulted in two OA subtypes with n = 41 (cluster A) and n = 15 (cluster B) patients. The transcriptomic profile of cluster B cartilage, relative to cluster A (DE-AB genes) showed among others a pronounced upregulation of multiple genes involved in chemokine pathways. Nevertheless, upon investigating the OA pathophysiology in cluster B patients as reflected by differentially expressed genes between preserved and lesioned OA cartilage (DE-OA-B genes), the chemokine genes were significantly downregulated with OA pathophysiology. Upon integrating radiographic OA data, we showed that the OA phenotype among cluster B patients, relative to cluster A, may be characterized by higher joint space narrowing (JSN) scores and low osteophyte (OP) scores. Based on whole-transcriptome profiling, we identified two robust OA subtypes characterized by unique OA, pathophysiological processes in cartilage as well as a clinical phenotype. We advocate that further characterization, confirmation and clinical data integration is a prerequisite to allow for development of treatments towards personalized care with concurrently more effective treatment response.


Determinants of patient satisfaction after severe lower-extremity injuries.
In health care, increased emphasis has been placed on patient-centered care, but to our knowledge little work has been conducted to understand the influences on patient satisfaction after surgery for the treatment of severe lower-extremity injury. Our purpose was to analyze how the patient's satisfaction with the outcome correlates with other measures of outcome (clinical, functional, physical impairment, psychological impairment, and pain) and with the sociodemographic characteristics of the patient, the nature of the injury, and the treatment decisions. Four hundred and sixty-three patients treated for limb-threatening lower-extremity injuries at eight level-I trauma centers were followed prospectively. Multivariate regression techniques were used to identify factors correlating with variation in patient self-reported satisfaction at two years after the injury. The outcomes that were tested in the model were pain, range of motion, muscle strength, self-selected walking speed, depression, anxiety, the physical and psychosocial scores of the Sickness Impact Profile (SIP), return to work, and the number of major complications. The patient characteristics that were tested in the model were age, sex, education, poverty status, insurance status, occupation, race, personality profile, and medical comorbidities. Injury severity was tested in the model with use of both the Injury Severity Score and a score reflecting the probability of amputation. The treatment decisions that were tested were amputation versus reconstruction and time to treatment. No patient demographic, treatment, or injury characteristics were found to correlate with patient satisfaction. Only measures of physical function, psychological distress, clinical recovery, and return to work correlated with patient satisfaction at two years. Five of these outcome measures accounted for >35% of the overall variation in patient satisfaction; these were return to work (p < 0.05), depression (p < 0.05), the physical functioning component of the SIP (p < 0.01), self-selected walking speed (p < 0.001), and pain intensity (p < 0.001). The absence of major complications and less anxiety were marginally significant (p < 0.1). Patient satisfaction after surgical treatment of lower-extremity injury is predicted more by function, pain, and the presence of depression at two years than by any underlying characteristic of the patient, injury, or treatment.


Discussions with physicians about hospice among patients with metastatic lung cancer.
Many terminally ill patients enroll in hospice only in the final days before death or not at all. Discussing hospice with a health care provider could increase awareness of hospice and possibly result in earlier use. We used data on 1517 patients diagnosed as having stage IV lung cancer from a multiregional study. We estimated logistic regression models for the probability that a patient discussed hospice with a physician or other health care provider before an interview 4 to 7 months after diagnosis as reported by either the patient or surrogate or documented in the medical record. Half (53%) of the patients had discussed hospice with a provider. Patients who were black, Hispanic, non-English speaking, married or living with a partner, Medicaid beneficiaries, or had received chemotherapy were less likely to have discussed hospice. Only 53% of individuals who died within 2 months after the interview had discussed hospice, and rates were lower among those who lived longer. Patients who reported that they expected to live less than 2 years had much higher rates of discussion than those expecting to live longer. Patients reporting the most severe pain or dyspnea were no more likely to have discussed hospice than those reporting less severe or no symptoms. A third of patients who reported discussing do-not-resuscitate preferences with a physician had also discussed hospice. Many patients diagnosed as having metastatic lung cancer had not discussed hospice with a provider within 4 to 7 months after diagnosis. Increased communication with physicians could address patients' lack of awareness about hospice and misunderstandings about prognosis.


Ultrasonographic inferior vena cava collapsibility and distensibility indices for detecting the volume status of critically ill pediatric patients.
Especially in recent years, the use of point-of-care ultrasound by non-radiologist clinicians has become widespread. Point-of-care ultrasound provides rapid responses to the problems of critically ill patients at the bedside. This technique has many important advantages, including being non-invasive, cheap, repeatable, painless, and radiation-free. Numerous studies have revealed the most important clinical benefits of point-of-care ultrasound use by pediatric intensive care providers. The inferior vena cava is a vessel that is highly sensitive to fluid changes. The inferior vena cava diameter can be measured by a point-of-care ultrasound, and represents a critical parameter in assessing the patient's fluid status. The inferior vena cava collapsibility index (in spontaneously breathing patients) and the inferior vena cava distensibility index (in mechanically ventilated patients) are calculated by determined formulas by using maximum and minimum diameters of the inferior vena cava. The indices are important guides for pediatric intensive care providers for managing their patients' fluid treatment. Although some authors claim it is not a reliable method, the technique is coming to fore in intensive care units day by day, and has an increasing trend among pediatric intensive care specialists. Here, we aim to give detailed information on the ultrasonographic inferior vena cava diameter measurement methods, and calculations of the inferior vena cava collapsibility index and inferior vena cava distensibility index, and emphasize the importance of a noninvasive, bedside, and objective method of detecting the volume status of critically ill patients for pediatric intensive care specialists according to the published literature.


Smoking status and its relationship to demographic and clinical characteristics in first episode psychosis.
Elevated rates of cigarette smoking are observed prior to the onset of psychosis and remain stable early in the illness. Cannabis use frequently co-occurs with cigarette smoking and is independently associated with distinct clinical outcomes. However, past research has not controlled for cannabis use in cigarette smokers with first episode psychosis (FEP), limiting conclusions on the unique relationship of cigarette smoking to the demographic and clinical profiles of these patients. The present study therefore aimed to: (1) Determine the prevalence and patterns of cigarette smoking and its co-use with cannabis in FEP, and (2) Examine the demographic, clinical, cognitive, and functional characteristics associated with cigarette smoking status, after adjusting for frequency of cannabis use. Patients entering specialized treatment for FEP (N = 140) were divided into groups according to their current smoking status: 66 non-smokers (0 cigarettes/day), 47 light/moderate smokers (1-19 cigarettes/day; M = 9.81, SD = 3.93), and 27 heavy smokers (≥20 cigarettes/day; M = 26.39, SD = 6.31). The prevalence of cigarette smoking was 53% and smoking status was highly associated with frequency of cannabis use. After adjusting for cannabis use, significant between-group differences emerged. Heavy smokers were older at program entry and had a later age of onset of psychosis than light/moderate and non-smokers. Non-smokers had more education, better neurocognitive performance, and higher levels of functioning than light/moderate and heavy smokers. Prospective, longitudinal studies are needed to better understand the clinical significance of tobacco use and factors that contribute to the initiation and continuation of smoking behaviours in FEP.


Rhesus monkeys behave as if they perceive the Duncker Illusion.
The visual system uses the pattern of motion on the retina to analyze the motion of objects in the world, and the motion of the observer him/herself. Distinguishing between retinal motion evoked by movement of the retina in space and retinal motion evoked by movement of objects in the environment is computationally difficult, and the human visual system frequently misinterprets the meaning of retinal motion. In this study, we demonstrate that the visual system of the Rhesus monkey also misinterprets retinal motion. We show that monkeys erroneously report the trajectories of pursuit targets or their own pursuit eye movements during an epoch of smooth pursuit across an orthogonally moving background. Furthermore, when they make saccades to the spatial location of stimuli that flashed early in an epoch of smooth pursuit or fixation, they make large errors that appear to take into account the erroneous smooth eye movement that they report in the first experiment, and not the eye movement that they actually make.


Mapping the Free Energy Landscape of PKA Inhibition and Activation: A Double-Conformational Selection Model for the Tandem cAMP-Binding Domains of PKA RIα.
Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. cAMP binds to two tandem cAMP-binding domains (CBD-A and -B) within the regulatory subunit of PKA (R), unleashing the activity of the catalytic subunit (C). While CBD-A in RIα is required for PKA inhibition and activation, CBD-B functions as a "gatekeeper" domain that modulates the control exerted by CBD-A. Preliminary evidence suggests that CBD-B dynamics are critical for its gatekeeper function. To test this hypothesis, here we investigate by Nuclear Magnetic Resonance (NMR) the two-domain construct RIα (91-379) in its apo, cAMP2, and C-bound forms. Our comparative NMR analyses lead to a double conformational selection model in which each apo CBD dynamically samples both active and inactive states independently of the adjacent CBD within a nearly degenerate free energy landscape. Such degeneracy is critical to explain the sensitivity of CBD-B to weak interactions with C and its high affinity for cAMP. Binding of cAMP eliminates this degeneracy, as it selectively stabilizes the active conformation within each CBD and inter-CBD contacts, which require both cAMP and W260. The latter is contributed by CBD-B and mediates capping of the cAMP bound to CBD-A. The inter-CBD interface is dispensable for intra-CBD conformational selection, but is indispensable for full activation of PKA as it occludes C-subunit recognition sites within CBD-A. In addition, the two structurally homologous cAMP-bound CBDs exhibit marked differences in their residual dynamics profiles, supporting the notion that conservation of structure does not necessarily imply conservation of dynamics.


Investigation of uranium interactions with calcium phosphate-binding proteins using ICP/MS and CE-ICP/MS.
During long-term exposure, uranium accumulates in bone. Since uranium in U(vi) complexes shares similar coordination properties to calcium, this toxicant is assumed to be exchanged with calcium ions at the surfaces of bone mineral crystals. Recently, two proteins involved in bone turnover, fetuin A and osteopontin, were shown to exhibit a high affinity for U(vi). A common biochemical feature of both fetuin A and osteopontin is their inhibiting role in calcium phosphate precipitation. Therefore it is conceivable that complexation of U(vi) with these proteins may alter their interaction with calcium and/or calcium phosphate. Quantitative analyses of calcium, phosphorus and uranium performed using inductively coupled plasma/mass spectrometry (ICP/MS) demonstrated the inhibition of the precipitation of calcium phosphate by fetuin A and osteopontin for 2 h. In addition, the presence of U(vi) did not seem to alter the duration of this process. However, dynamic light scattering studies revealed that the size of the colloidal particles formed with osteopontin was altered by the presence of U(vi) in a concentration-dependent manner. Finally, using hyphenated capillary electrophoresis-ICP/MS (CE-ICP/MS), we showed that in these systems, at a low concentration of U(vi) (protein : U(vi) 8 : 1), U(vi) might remain in solution by forming a complex with proteins and not by sequestration of a precipitate of either autunite or uranyl orthophosphate.


Economic and health burden of brucellosis in Kazakhstan.
Brucellosis is a widespread zoonotic disease considered as an emerging and re-emerging disease with a resulting threat of public health and animal health. Official reports document an animal incidence in Kazakhstan of about 0.6% per year, and the country still registers high number of human cases annually . The main objective of this paper was to evaluate the distribution and economic impact of brucellosis in Kazakhstan. We analysed human disease incidence data obtained from the Government Sanitary & Epidemiological Service with the aim to estimate the burden of disease in terms of disability-adjusted life years (DALYs). We also estimated the economic impact in terms of monetary losses. Additionally, we mapped the geographical distribution of the disease throughout Kazakhstan. In total, 1,334 human cases of brucellosis were registered in 2015 in Kazakhstan that resulted in 713 DALYs. Around $21 million was spent on compensation for animals that had to be slaughtered due to brucellosis, and an additional $24 million was spent on testing animals. Animal brucellosis and human brucellosis occur throughout the whole country, some trends of which are reviewed in this paper. We estimated the burden of the disease and explored possible explanation for high human incidence rates. This paper is the first to estimate the human burden of disease and the economic costs in Kazakhstan. Both of these are substantial.


External cavity beam combining of 21 semiconductor lasers using SPGD.
Active coherent beam combining of laser oscillators is an attractive way to achieve high output power in a diffraction limited beam. Here we describe an active beam combining system used to coherently combine 21 semiconductor laser elements with an 81% beam combining efficiency in an external cavity configuration compared with an upper limit of 90% efficiency in the particular configuration of the experiment. Our beam combining system utilizes a stochastic parallel gradient descent (SPGD) algorithm for active phase control. This work demonstrates that active beam combining is not subject to the scaling limits imposed on passive-phasing systems.


Methods for estimating medical expenditures attributable to intimate partner violence.
This article compares three methods for estimating the medical cost burden of intimate partner violence against U.S. adult women (18 years and older), 1 year postvictimization. To compute the estimates, prevalence data from the National Violence Against Women Survey are combined with cost data from the Medical Expenditure Panel Survey, the Medicare 5% sample, and published studies and with relative risk estimates from published studies. Results are compared and reasons for difference are explored, including the advantages and disadvantages of each approach. Estimates of the medical cost burden of intimate partner violence within the first 12 months after victimization range from USD 2.3 billion to USD 7.0 billion, depending on the method used. Although limited to women victimized in the last year, each method reveals that intimate partner violence imposes a substantial burden on the health care system. Among the approaches, there is no clear gold standard nor any evidence of bias.


Opioid Antagonists and the A118G Polymorphism in the μ-Opioid Receptor Gene: Effects of GSK1521498 and Naltrexone in Healthy Drinkers Stratified by OPRM1 Genotype.
The A118G single-nucleotide polymorphism (SNP rs1799971) in the μ-opioid receptor gene, OPRM1, has been much studied in relation to alcohol use disorders. The reported effects of allelic variation at this SNP on alcohol-related behaviors, and on opioid receptor antagonist treatments, have been inconsistent. We investigated the pharmacogenetic interaction between A118G variation and the effects of two μ-opioid receptor antagonists in a clinical lab setting. Fifty-six overweight and moderate-heavy drinkers were prospectively stratified by genotype (29 AA homozygotes, 27 carriers of at least 1 G allele) in a double-blind placebo-controlled, three-period crossover design with naltrexone (NTX; 25 mg OD for 2 days, then 50 mg OD for 3 days) and GSK1521498 (10 mg OD for 5 days). The primary end point was regional brain activation by the contrast between alcohol and neutral tastes measured using functional magnetic resonance imaging (fMRI). Secondary end points included other fMRI contrasts, subjective responses to intravenous alcohol challenge, and food intake. GSK1521498 (but not NTX) significantly attenuated fMRI activation by appetitive tastes in the midbrain and amygdala. GSK1521498 (and NTX to a lesser extent) significantly affected self-reported responses to alcohol infusion. Both drugs reduced food intake. Across all end points, there was less robust evidence for significant effects of OPRM1 allelic variation, or for pharmacogenetic interactions between genotype and drug treatment. These results do not support strong modulatory effects of OPRM1 genetic variation on opioid receptor antagonist attenuation of alcohol- and food-related behaviors. However, they do support further investigation of GSK1521498 as a potential therapeutic for alcohol use and eating disorders.


The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARγ in retinal neuroprotection.
It has been shown that peroxisome proliferators-activated receptor gamma (PPARγ) is beneficial for central nervous system injury. However its role on optic nerve injury remains unknown. In the present study, we examined the change of PPARγ expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio), a PPARγ agonist, on retinal ganglion cells (RGCs) neuroprotection using a rat optic nerve crush (ONC) model. Our results showed that PPARγ mRNA and protein levels were increased after ONC, and most of PPARγ-immunoreactive cells colocalized with Müller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARγ antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Müller cell activation after ONC. These results indicate that PPARγ appears to protect RGCs from ONC possibly via the reduction of Müller glial activation. It provides evidence that activation of PPARγ may be a potential alternative treatment for RGCs neuroprotection.


Intra-endodermal interactions are required for pancreatic beta cell induction.
The cellular origin of signals that regulate pancreatic beta cell induction is not clearly defined. Here, we investigate the seeming paradox that Hedgehog/Smoothened signaling functions during gastrulation to promote pancreatic beta cell development in zebrafish, yet has an inhibitory role during later stages of pancreas development in amniotes. Our cell transplantation experiments reveal that in zebrafish, Smoothened function is not required in beta cell precursors. At early somitogenesis stages, when the zebrafish endoderm first forms a sheet, pancreatic beta cell precursors lie closest to the midline; however, the requirement for Smoothened lies in their lateral neighbors, which ultimately give rise to the exocrine pancreas and intestine. Thus, pancreatic beta cell induction requires Smoothened function cell-nonautonomously during gastrulation, to allow subsequent intra-endodermal interactions. These results clarify the function of Hedgehog signaling in pancreas development, identify an unexpected cellular source of factors that regulate beta cell specification, and uncover complex patterning and signaling interactions within the endoderm.


Carbon Density Is an Indicator of Mass Accommodation Coefficient of Water on Organic-Coated Water Surface.
The condensational growth of a water droplet follows water vapor accommodation and is described by the mass accommodation coefficient, α. To determine α for droplets coated by straight chain and branched alcohols, we perform molecular dynamics simulations with umbrella sampling and direct impinging. The free energy profiles of water from gas phase to bulk water coated by organic are estimated by the former method. These free energy profiles exhibit a barrier to accommodation in the monolayers containing alcohols with zero and one-level of branching. However, the barrier is not observed for monolayers containing alcohols with two-levels of branching. These profiles and friction coefficients estimated from simulation are used to calculate α from the transition state and Grote-Hynes theory. Results are compared with sticking probabilities estimated from direct impinging simulations, and their differences are interpreted through processes included in each theory. At a low surface coverage of these surface active molecules, the underlying bulk solution is exposed and the resistance to vapor accommodation is reduced. We estimate the carbon density in water surfaces coated by straight-chain alcohols, branched alcohols, and straight-chain fatty acids used in study by Takahama and Russell,1 and show that this quantity is related monotonically to the mass accommodation coefficient.


Access survival amongst hemodialysis patients referred for preventive angiography and percutaneous transluminal angioplasty.
Referring hemodialysis patients for elective access angiography and percutaneous transluminal angioplasty (PTA) is commonly done to prevent access failure, yet the effectiveness of this procedure remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASURES: An observational matched cohort analysis among 40,132 Medicare beneficiaries receiving hemodialysis with a fistula or graft was performed. Cox regression was used to determine whether access intervention was associated with improved 1-year access survival. Nonsurgical access intervention was found to be frequent at a rate of 20.9 procedures per 100 access years. In the 1-year period after intervention using angiography and PTA, the overall access failure rate was 53.7 per 100 access years in the intervention group and 49.6 in the nonintervention group (HR = 1.02; 95% CI, 0.96 to 1.08). Similar findings were also seen when the analysis was repeated in only fistulas (HR = 1.06; 95% CI, 0.98 to 1.15) and grafts (HR = 0.95; 95% CI, 0.86 to 1.05). In patients with a low intra-access flow rate (HR = 0.86; 95% CI, 0.75 to 0.99) or a new access (HR = 0.79; 95% CI, 0.71 to 0.89), angiography and PTA significantly increased access survival when compared with nonintervention (P for interaction was <0.0001). Angiography-PTA-related upper-extremity hematoma, vessel injury, or embolism-thrombosis occurred in 1.1% of all patients. Access characteristics significantly modify the survival benefits of angiography and PTA intervention where the benefits of these interventions are most seen in newer accesses or accesses with insufficient flow.


The electronic health record audit file: the patient is waiting.
We describe how electronic health record (EHR) audit files can be used to understand how time is spent in primary care (PC). We used audit file data from the Geisinger Clinic to quantify elements of the clinical workflow and to determine how these times vary by patient and encounter factors. We randomly selected audit file records representing 36 437 PC encounters across 26 clinic locations. Audit file data were used to estimate duration and variance of: (1) time in the waiting room, (2) nurse time with the patient, (3) time in the exam room without a nurse or physician, and (4) physician time with the patient. Multivariate modeling was used to test for differences by patient and by encounter features. On average, a PC encounter took 54.6 minutes, with 5 minutes of nurse time, 15.5 minutes of physician time, and the remaining 62% of the time spent waiting to see a clinician or check out. Older age, female sex, and chronic disease were associated with longer wait times and longer time with clinicians. Level of service and numbers of medications, procedures, and lab orders were associated with longer time with clinicians. Late check-in and same-day visits were associated with shorter wait time and clinician time. This study provides insights on uses of audit file data for workflow analysis during PC encounters. Scalable ways to quantify clinical encounter workflow elements may provide the means to develop more efficient approaches to care and improve the patient experience.


Short-term effect of different teaching methods on nasopharyngeal carcinoma for general practitioners in Jakarta, Indonesia.
In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p<0.0001). GPs attending the PHCC course recorded a greater increase in correct symptoms than those attending the symposium (3.8 vs. 2.8; p = 0.01). After a two week period the knowledge levels had declined slightly from 5.5 correctly identified symptoms to 4.2 (p = 0.25). These results confirm our findings regarding GPs insufficient knowledge of NPC. Lectures in the PHCC and a symposium have both been proven to be effective training tools in the education of GPs.


Designing Configurable Arm Rehabilitation Games: How Do Different Game Elements Affect User Motion Trajectories?
For successful rehabilitation of a patient after a stroke or traumatic brain injury, it is crucial that rehabilitation activities are motivating, provide feedback and have a high rate of repetitions. Advancements in recent technologies provide solutions to address these aspects where needed. Additionally, through the use of gamification, we are able to increase the motivation for participants. However, many of these systems require complex set-ups, which can be a big challenge when conducting rehabilitation in a home-based setting. To address the lack of simple rehabilitation tools for arm function for a home-based application, we previously developed a system, Cellulo for rehabilitation, that is comprised of paper-supported tangible robots that are orchestrated by applications deployed on consumer tablets. These components enable different features that allow for gamification, easy setup, portability, and scalability. To support the configuration of game elements to patients' level of motor skills and strategies, their motor trajectories need to be classified. In this paper, we investigate the classification of different motor trajectories and how game elements impact these in unimpaired, healthy participants. We show that the manipulation of certain game elements do have an impact on motor trajectories, which might indicate that it is possible to adapt the arm remediation of patients by configuring game elements. These results provide a first step towards providing adaptive rehabilitation based upon patients' measured trajectories.


Testosterone replacement does not normalize carcass composition in chronically decerebrate male rats.
Chronically decerebrate (CD) rats, in which the forebrain and its descending projections are completely neurally isolated from hindbrain and rostral projections, gain substantial amounts of body fat, lose lean tissue, and have low circulating testosterone concentrations. We tested whether testosterone replacement would normalize body composition of male CD rats. Five groups of rats were used: CD placebo, CD testosterone, control placebo, castrate placebo, and castrate testosterone. Testosterone replacement was initiated at the first stage of CD surgery in both CDs and castrate controls. The second stage of CD surgery occurred 8 days later, and the study ended 15 days later. Testosterone implants produced 10-fold normal circulating concentrations. Food intake was fixed for all rats by tube feeding. CD rats had substantially more body fat and less lean tissue than neurally intact rats. Testosterone replacement did not affect adiposity of CD rats but did increase carcass water content. Energy expenditure of CD rats was significantly lower than that of control placebo and castrated rats. Testosterone lowered respiratory equivalency ratio and ameliorated a fall in energy expenditure late in the intermeal interval in CD rats. Castration increased, and testosterone decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH) in neurally intact controls. LH was undetectable, and FSH was equivalent to neurally intact controls in CD rats, and neither was affected by testosterone. Collectively, low testosterone did not explain obesity or decreased lean body mass of CD rats, although CD rats exhibited abnormal levels of circulating reproductive hormones and disrupted testosterone negative feedback.


The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles.
The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR) γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS) and their influence on lipid and lipoprotein profiles of patients. The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran). The PPARγ Pro12Ala and PPARγ C161T polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS), serum triglycerides (TG), cholesterol, low density lipoprotein- cholesterol (LDL-C), high density lipoproteincholesterol (HDL-C) and estradiol levels were measured. The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG) genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T) was 21% in patients and 17.2% in controls with no significant difference (P=0.52). In all studied individuals, the PPARγ CG genotype was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype. Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.


Mapping photothermally induced gene expression in living cells and tissues by nanorod-locked nucleic acid complexes.
The photothermal effect of plasmonic nanostructures has numerous applications, such as cancer therapy, photonic gene circuit, large cargo delivery, and nanostructure-enhanced laser tweezers. The photothermal operation can also induce unwanted physical and biochemical effects, which potentially alter the cell behaviors. However, there is a lack of techniques for characterizing the dynamic cell responses near the site of photothermal operation with high spatiotemporal resolution. In this work, we show that the incorporation of locked nucleic acid probes with gold nanorods allows photothermal manipulation and real-time monitoring of gene expression near the area of irradiation in living cells and animal tissues. The multimodal gold nanorod serves as an endocytic delivery reagent to transport the probes into the cells, a fluorescence quencher and a binding competitor to detect intracellular mRNA, and a plasmonic photothermal transducer to induce cell ablation. We demonstrate the ability of the gold nanorod-locked nucleic acid complex for detecting the spatiotemporal gene expression in viable cells and tissues and inducing photothermal ablation of single cells. Using the gold nanorod-locked nucleic acid complex, we systematically characterize the dynamic cellular heat shock responses near the site of photothermal operation. The gold nanorod-locked nucleic acid complex enables mapping of intracellular gene expressions and analyzes the photothermal effects of nanostructures toward various biomedical applications.


Clinical history of HIV infection may be misleading in cytopathology.
Human immunodeficiency virus (HIV)-infected patients are at an increased risk for developing opportunistic infections, reactive conditions and neoplasms. As a result, a broad range of conditions are frequently included in the differential diagnosis of HIV-related lesions. The clinical history of HIV infection may, however, be misleading in some cases. Illustrative cases are presented in which knowledge of a patient's HIV status proved to be misleading and increased the degree of complexity of the cytologic evaluation. Case 1 involved the fine needle aspiration (FNA) of a painful 3 cm unilateral neck mass in a 38-year-old female with generalized lymphadenopathy. Her aspirate revealed a spindle cell proliferation devoid of mycobacteria that was immunoreactive for S-100 and macrophage markers (KP-1, PGM1). Multiple noncontributory repeat procedures were performed until a final excision revealed a schwannoma. Case 2 was a CT-guided FNA of a positron emission tomography positive lung mass in a 53-year-old man. The acellular aspirate in this case contained structures resembling fungal spore forms that were negative for mucicarmine and GMS stains, as well as cryptococcal antigen immunocytochemistry. A Von Kossa stain confirmed that these pseudo-fungal structures were calcified debris. Follow up revealed multiple calcified lung and hilar node based granulomata. Case 3 involved the cytologic evaluation of pleural fluid from a 47-year-old man with Kaposi sarcoma and recurrent chylous pleural effusions. Large atypical cells identified in his effusion were concerning for primary effusion lymphoma. Subsequent pleural biopsy revealed extramedullary hematopoiesis, documenting these atypical cells as megakaryocytes. These cases demonstrate that knowledge of a patient's HIV status can be misleading in the evaluation of cytology specimens, with potential for misdiagnosis and/or multiple procedures. To avoid this pitfall in the setting of HIV infection, common entities unrelated to HIV infection and artifacts should always be included in the differential diagnosis.


Multiwavelength depth encoding method for 3D range geometry compression.
This paper presents a novel method for representing three-dimensional (3D) range data within regular two-dimensional (2D) images using multiwavelength encoding. These 2D images can then be further compressed using traditional lossless (e.g., PNG) or lossy (e.g., JPEG) image compression techniques. Current 3D range data compression methods require significant filtering to reduce lossy compression artifacts. The nature of the proposed encoding, however, offers a significant level of robustness to such artifacts brought about by high levels of JPEG compression. This enables extremely high compression ratios while maintaining a very low reconstruction error percentage with little to no filtering required to remove compression artifacts. For example, when encoding 3D geometry with the proposed method and storing the resulting 2D image with Matlab R2014a JPEG80 image compression, compression ratios of approximately 935:1 versus the OBJ format can be achieved at an error rate of approximately 0.027% without any filtering.


Specialized insulin is used for chemical warfare by fish-hunting cone snails.
More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail's distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.


Amino acids, monoamines and audiogenic seizures in genetically epilepsy-prone rats: effects of aspartame.
It has been suggested that aspartame facilitates seizures in man and animals because phenylalanine, one of its major metabolites, interferes with brain transport of neurotransmitter precursors and alters the synthesis of monoamine neurotransmitters such as norepinephrine, dopamine and/or serotonin. This facilitation is purportedly more likely in subjects predisposed to seizures. One test of this hypothesis would be to administer a wide range of aspartame doses to subjects whose seizure predisposition is dependent on abnormalities in monoaminergic function. Genetically epilepsy-prone rats (GEPRs) have a broadly based seizure predisposition that is based, in part, on widespread central nervous system noradrenergic and serotonergic deficits. Further reductions in the functional state of these neurotransmitters increases seizure severity in GEPRs. Thus, GEPRs appear ideally suited for testing the hypothesis that aspartame facilitates seizures by interfering with central nervous system monoamines. Oral administration of acute (50-2000 mg/kg) or sub-chronic (up to 863 mg/kg/day for 28 days) doses of aspartame did not alter seizure severity in either of two types of GEPRs. Not surprisingly, acute aspartame doses produced dramatic changes in plasma and brain amino acid concentrations. Hypothesized alterations in monoamine neurotransmitter systems were largely absent. Indeed, increases in norepinephrine concentration, rather than the hypothesized decreases, were the most evident alterations in these neurotransmitter systems. We conclude that aspartame does not facilitate seizures in GEPRs and that convincing evidence of seizure facilitation in any species is lacking.


Use of inter-proton nuclear Overhauser effects to assign the nuclear magnetic resonance spectra of oligodeoxynucleotide and hybrid duplexes in aqueous solution.
Inter-proton nuclear Overhauser enhancements (NOEs) have been used to assign the aromatic, anomeric and 2' resonances in the 1H nuclear magnetic resonance spectrum of the duplex formed between d(T-C-A-C-A-T) and d(A-T-G-T-G-A). The same techniques have been applied to assignments in the hybrid duplex formed by d(T-C-A-C-A-T) with r(A-U-G-U-G-A). Comparison of intra-residue with inter-residue NOEs yields structural information which suggests that the conformations of both duplexes are similar. The NOEs are consistent with inter-proton distances measured from models of B-form DNA. Circular dichroic results confirm these deductions.


Cancer evolution and individual susceptibility.
Cancer susceptibility is due to interactions between inherited genetic factors and exposure to environmental carcinogens. The genetic component is constituted mainly by weakly acting low-penetrance genetic variants that interact among themselves, as well as with the environment. These low susceptibility genes can be categorized into two main groups: one includes those that control intrinsic tumor cell activities (i.e. apoptosis, proliferation or DNA repair), and the other contains those that modulate the function of extrinsic tumor cell compartments (i.e. stroma, angiogenesis, or endocrine and immune systems). Genome-Wide Association Studies (GWAS) of human populations have identified numerous genetic loci linked with cancer risk and behavior, but nevertheless the major component of cancer heritability remains to be explained. One reason may be that GWAS cannot readily capture gene-gene or gene-environment interactions. Mouse model approaches offer an alternative or complementary strategy, because of our ability to control both the genetic and environmental components of risk. Recently developed genetic tools, including high-throughput technologies such as SNP, CGH and gene expression microarrays, have led to more powerful strategies for refining quantitative trait loci (QTL) and identifying the critical genes. In particular, the cross-species approaches will help to refine locations of QTLs, and reveal their genetic and environmental interactions. The identification of human tumor susceptibility genes and discovery of their roles in carcinogenesis will ultimately be important for the development of methods for prediction of risk, diagnosis, prevention and therapy for human cancers.


Suppressed expression of phenobarbital-inducible hepatic cytochrome P-450s in Eisai-hyperbilirubinuria rats (EHBR/Eis).
The differential induction of hepatic cytochrome P-450 (P450) was studied in Eisai-hyperbilirubinuria rats (EHBR/Eis). This rat is a mutant that has as high a concentration of bilirubin in the urine as in the plasma. A single administration of trans-stilbene oxide (TSO, 2 mmol/kg), a phenobarbital (PB)-type P450 inducer, did not increase total P450, the CYP2B1/2 or the CYP2C6 in EHBR/Eis liver. TSO was able to induce delta-aminolevulinic acid synthetase and heme oxygenase, rate-limiting enzymes in heme biosynthesis and degradation, respectively, in both EHBR/Eis and Sprague-Dawley rat (SDR), the strain from which EHBR/Eis is derived. TSO also produced similar effects on glutathione depletion and on the activities of other drug-metabolizing enzymes in both strains. A 23-fold increase in CYP2B1/2 mRNA in the SDR liver was observed 24 hr after TSO treatment. In the EHBR/Eis strain, however, TSO increased CYP2B1/2 mRNA only 2-fold. In addition, repeated injection of TSO failed to induce P450 isozymes, CYP2B1/2, CYP2C6 or CYP3A2 in EHBR/Eis. On the other hand, there was essentially no difference in the induced levels of CYP1A1/2 apoprotein and mRNA between twins of SDR and EHBR/Eis livers treated with 3-methylcholanthrene or 1-benzylimidazole. The increased levels of both CYP2B1/2 apoprotein and mRNA from EHBR/Eis liver treated with TSO and 1-benzylimidazole were much smaller (2.5- and 5-fold increases, respectively) than from the SDR liver (17.5- and 15-fold increases, respectively). Although PB expressed CYP2B1/2 apoprotein and mRNA to a similar extent in both homozygous and heterozygous EHBR/Eis livers, CYP3A2 and CYP2C6 were less responsive to PB in homozygous EHBR/Eis. Repeated treatment with TSO induced these isozymes in heterozygote but not in homozygote. These findings suggest that the suppressed expression of PB-inducible P450 isozyme genes in the EHBR/Eis liver may be a general phenomenon associated with PB-type inducers. Therefore, EHBR/Eis may be experimentally useful for studying the mechanism of P450 induction by PB and PB-type inducers.


Mesenchymal stem cells promote cardiac muscle repair via enhanced neovascularization.
Transplantation of bone-marrow derived stem/progenitor cells has an established therapeutic effect on cardiac muscle repair after injury. However, the exact mechanism that underlies this phenomenon is not completely understood. Here we transplanted mesenchymal stem cells (MSCs), a major population from the bone-marrow derived stem/progenitor cells, and studied its effects on cardiac muscle repair after injury. MSCs transplantation significantly improved cardiac muscle repair after injury. The grafted MSCs did not significantly differentiate into cardiac muscle cells themselves, but appeared to induce neovascularization in the injured heart. In a loss-of-function experiment, we further show that production and secretion of placental growth factor, but not vascular endothelial growth factor A in MSCs, were essential for the MSCs-induced neovasularization after cardiac muscle injury to facilitate cardiac muscle repair. Our study thus sheds light on an undescribed role of placental growth factor in cardiac muscle regeneration.


Five-second STEM dislocation tomography for 300 nm thick specimen assisted by deep-learning-based noise filtering.
Scanning transmission electron microscopy (STEM) is suitable for visualizing the inside of a relatively thick specimen than the conventional transmission electron microscopy, whose resolution is limited by the chromatic aberration of image forming lenses, and thus, the STEM mode has been employed frequently for computed electron tomography based three-dimensional (3D) structural characterization and combined with analytical methods such as annular dark field imaging or spectroscopies. However, the image quality of STEM is severely suffered by noise or artifacts especially when rapid imaging, in the order of millisecond per frame or faster, is pursued. Here we demonstrate a deep-learning-assisted rapid STEM tomography, which visualizes 3D dislocation arrangement only within five-second acquisition of all the tilt-series images even in a 300 nm thick steel specimen. The developed method offers a new platform for various in situ or operando 3D microanalyses in which dealing with relatively thick specimens or covering media like liquid cells are required.


Moesin is a glioma progression marker that induces proliferation and Wnt/β-catenin pathway activation via interaction with CD44.
Moesin is an ERM family protein that connects the actin cytoskeleton to transmembrane receptors. With the identification of the ERM family protein NF2 as a tumor suppressor in glioblastoma, we investigated roles for other ERM proteins in this malignancy. Here, we report that overexpression of moesin occurs generally in high-grade glioblastoma in a pattern correlated with the stem cell marker CD44. Unlike NF2, moesin acts as an oncogene by increasing cell proliferation and stem cell neurosphere formation, with its ectopic overexpression sufficient to shorten survival in an orthotopic mouse model of glioblastoma. Moesin was the major ERM member activated by phosphorylation in glioblastoma cells, where it interacted and colocalized with CD44 in membrane protrusions. Increasing the levels of moesin competitively displaced NF2 from CD44, increasing CD44 expression in a positive feedback loop driven by the Wnt/β-catenin signaling pathway. Therapeutic targeting of the moesin-CD44 interaction with the small-molecule inhibitor 7-cyanoquinocarcinol (DX-52-1) or with a CD44-mimetic peptide specifically reduced the proliferation of glioblastoma cells overexpressing moesin, where the Wnt/β-catenin pathway was activated. Our findings establish moesin and CD44 as progression markers and drugable targets in glioblastoma, relating their oncogenic effects to activation of the Wnt/β-catenin pathway.


Human islet amyloid polypeptide fibril binding to catalase: a transmission electron microscopy and microplate study.
The diabetes-associated human islet amyloid polypeptide (IAPP) is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-beta (A-beta) and prion protein (PrP) fibrils. Previous studies have shown that catalase binds to A-beta fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM)-based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KD of 0.77 nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu-like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, A-beta, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.


Individual Monitoring of Immune Response in Atlantic Salmon Salmo salar following Experimental Infection with Infectious Salmon Anaemia Virus (ISAV).
Monitoring the immune response in fish over the progression of a disease is traditionally carried out by experimental infection whereby animals are killed at regular intervals and samples taken. We describe here a novel approach to infectiology for salmonid fish where blood samples are collected repeatedly in a small group of PIT-tagged animals. This approach contributes to the reduction of animals used in research and to improved data quality. Two groups of 12 PIT-tagged Atlantic salmon (Salmo salar) were i.p infected with Infectious Salmon Anaemia Virus (ISAV) or culture medium and placed in 1 m3 tanks. Blood samples were collected at 0, 4, 8, 12, 16, 21 and 25 days post infection. The viral load, immune and stress response were determined in individual fish by real-time quantitative PCR (QPCR) on the blood cells, as well as the haematocrit used as an indicator of haemolysis, a clinical consequence of ISAV infection. "In-tank" anaesthesia was used in order to reduce the stress related to chase and netting prior to sampling. The data were analysed using a statistical approach which is novel with respect to its use in fish immunology. The repeated blood collection procedure did not induce stress response as measured by HSP70 and HSP90 gene expression in the un-infected animals. A strong increase in viraemia as well as a significant induction of Mx and γIP gene expression were observed in the infected group. Interleukin 10 was found induced at the later stage of the infection whereas no induction of CD8 or γ IFN could be detected. These results and the advantages of this approach are discussed.


Normal tissue studies in radiation oncology: A systematic review of highly cited articles and citation patterns.
Radiation therapy is one of the cornerstones of modern multidisciplinary cancer treatment. Normal tissue tolerance is critical as radiation-induced side effects may compromise organ function and quality of life. The importance of normal tissue research is reflected by the large number of scientific articles, which have been published between 2006 and 2010. The present study identified important areas of research as well as seminal publications. The article citation rate is among the potential indicators of scientific impact. Highly cited articles, arbitrarily defined as those with ≥15 citations, were identified via a systematic search of the citation database, Scopus. Up to 608 articles per year were published between 2006 and 2010, however, <10% of publications in each year accumulated ≥15 citations. This figure is notably low, when compared with other oncology studies. A large variety of preclinical and clinical topics, including toxicity prediction, the dose-volume relationship and radioprotectors, accumulated ≥15 citations. However, clinical prevention or mitigation studies were underrepresented. The following conclusion may be drawn from the present study; despite the improved technology that has resulted in superior dose distribution, clinical prevention or mitigation studies are critical and must receive higher priority, funding and attention.


The sensitivities of high-harmonic generation and strong-field ionization to coupled electronic and nuclear dynamics.
The sensitivities of high-harmonic generation (HHG) and strong-field ionization (SFI) to coupled electronic and nuclear dynamics are studied, using the nitric oxide (NO) molecule as an example. A coherent superposition of electronic and rotational states of NO is prepared by impulsive stimulated Raman scattering and probed by simultaneous detection of HHG and SFI yields. We observe a fourfold higher sensitivity of high-harmonic generation to electronic dynamics and attribute it to the presence of inelastic quantum paths connecting coherently related electronic states [Kraus et al., Phys. Rev. Lett.111, 243005 (2013)]. Whereas different harmonic orders display very different sensitivities to rotational or electronic dynamics, strong-field ionization is found to be most sensitive to electronic motion. We introduce a general theoretical formalism for high-harmonic generation from coupled nuclear-electronic wave packets. We show that the unequal sensitivities of different harmonic orders to electronic or rotational dynamics result from the angle dependence of the photorecombination matrix elements which encode several autoionizing and shape resonances in the photoionization continuum of NO. We further study the dependence of rotational and electronic coherences on the intensity of the excitation pulse and support the observations with calculations.


Economic consequences of preterm birth: a systematic review of the recent literature (2009-2017).
Despite extensive knowledge on the functional, neurodevelopmental, behavioural and educational sequelae of preterm birth, relatively little is known about its economic consequences. To systematically review evidence around the economic consequences of preterm birth for the health services, for other sectors of the economy, for families and carers, and more broadly for society. Updating previous reviews, systematic searches of Medline, EconLit, Web of Science, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase and Scopus were performed using broad search terms, covering the literature from 1 January 2009 to 28 June 2017. Studies reporting economic consequences, published in the English language and conducted in a developed country were included. Economic consequences are presented in a descriptive manner according to study time horizon, cost category and differential denominators (live births or survivors). Of 4384 unique articles retrieved, 43 articles met the inclusion criteria. Of these, 27 reported resource use or cost estimates associated with the initial period of hospitalisation, while 26 reported resource use or costs incurred following the initial hospital discharge, 10 of which also reported resource use or costs associated with the initial period of hospitalisation. Only two studies reported resource use or costs incurred throughout the childhood years. Initial hospitalisation costs varied between $576 972 (range $111 152-$576 972) per infant born at 24 weeks' gestation and $930 (range $930-$7114) per infant born at term (US$, 2015 prices). The review also revealed a consistent inverse association between gestational age at birth and economic costs regardless of date of publication, country of publication, underpinning study design, follow-up period, age of assessment or costing approach, and a paucity of evidence on non-healthcare costs. Several categories of economic costs, such as additional costs borne by families as a result of modifications to their everyday activities, are largely overlooked by this body of literature. Moreover, the number and coverage of economic assessments have not increased in comparison with previous review periods. Evidence identified by this review can be used to inform clinical and budgetary service planning and act as data inputs into future economic evaluations of preventive or treatment interventions. Future research should focus particularly on valuing the economic consequences of preterm birth in adulthood.


The Family Time Squeeze: Perceived Family Time Adequacy Buffers Work Strain in Certified Nursing Assistants With Multiple Caregiving Roles.
This study examined how certified nursing assistants (CNAs) with unpaid family caregiving roles for children ("double-duty-child caregivers"), older adults ("double-duty-elder caregivers"), and both children and older adults ("triple-duty caregivers") differed from their nonfamily caregiving counterparts ("workplace-only caregivers") on four work strain indicators (emotional exhaustion, job satisfaction, turnover intentions, and work climate for family sacrifices). The moderating effects of perceived family time adequacy were also evaluated. Regression analyses were conducted on survey data from 972 CNAs working in U.S.-based nursing homes. Compared with workplace-only caregivers, double-and-triple-duty caregivers reported more emotional exhaustion and pressure to make family sacrifices for the sake of work. Triple-duty caregivers also reported less job satisfaction. Perceived family time adequacy buffered double-duty-child and triple-duty caregivers' emotional exhaustion and turnover intentions, as well as reversed triple-duty caregivers' negative perceptions of the work climate. Perceived family time adequacy constitutes a salient psychological resource for double-duty-child and triple-duty caregivers' family time squeezes. Amid an unprecedented demand for long-term care and severe direct-care workforce shortages, future research on workplace factors that increase double-and-triple-duty caregiving CNAs' perceived family time adequacy is warranted to inform long-term care organizations' development of targeted recruitment, retention, and engagement strategies.


Accuracy of three-dimensional simulation in the sizing of aortic endoluminal devices.
The purpose of this study is to examine the accuracy of a 3D simulation generated by inclusion of various intensity-selected portions of spiral CT data into a proprietary software program (Preview, Medical Media Systems, MMS) in preoperative and postoperative assessment of the anatomical features of abdominal aortic aneurysm (AAA). The accuracy of this software was measured against two other modalities-intravascular ultrasound (IVUS) and axial CT scan-using the IVUS as the reference. Eighty-five patients were included; 43 underwent AAA endovascular exclusion with Talent devices, and 42 with Aneurx devices. Measurement of proximal neck diameter was performed using IVUS, Preview software, and axial CT scan with manual calipers. Measurement of the AAA maximum diameter was performed using Preview software and axial CT scan; 253 measurements in the 85 patients were included. These measurements were compared by means of both linear regression and Bland-Altman agreement analysis. Our results showed that the 95% confidence interval between the Preview software and mean IVUS measurement of proximal AAA neck (3.1 and 2.5) is narrow enough for the software to be used in sizing AAA. This would be especially important for having the properly sized devices available preoperatively. The Preview software tended to be more accurate than CT scans although it was not statistically significant.


Facile synthesis of an ultra-stable metal-organic framework with excellent acid and base resistance.
A novel ultra-stable metal-organic framework, MCIF-1, [Cu2(DCI)2](MeCN), based on dicyanoimidazole and Cu(i), has been synthesized at room temperature successfully. MCIF-1 shows excellent water stability and can retain crystallinity after soaking in water for about one week. In addition, MCIF-1 also shows exceptional resistance under both acidic and basic conditions within a large pH range from 0 to 13.5. What is more, after modifying the synthesis procedure slightly, we can produce this material in a large scale during a very short time. Mild synthesis conditions, excellent stability and ease of large scale production give MCIF-1 great potential for practical use.


Narrative review of primary care point-of-care testing (POCT) and antibacterial use in respiratory tract infection (RTI).
Antimicrobial resistance is a global problem and is being addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) and procalcitonin, measurements to guide antibacterial prescribing in adult patients presenting to GP practices with symptoms of respiratory tract infection (RTI). Studies that were included were randomised controlled trials, controlled before and after studies, cohort studies and economic evaluations. Many studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces antibiotic prescribing by 23.3% to 36.16%. Procalcitonin is not currently available as a point-of-care testing (POCT), but has shown value for patients with RTI admitted to hospital. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. CRP POCT can better target antibacterial prescribing by GPs and contribute to national antimicrobial resistance strategies. Health services need to develop ways to ensure funding is transferred in order for POCT to be implemented.


Results of acoustic neuroma radiosurgery: an analysis of 5 years' experience using current methods.
The goal of this study was to define tumor control and complications of radiosurgery encountered using current treatment methods for the initial management of patients with unilateral acoustic neuroma. One hundred ninety patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent gamma knife radiosurgery between 1992 and 1997. The median follow-up period in these patients was 30 months (maximum 85 months). The marginal radiation doses were 11 to 18 Gy (median 13 Gy), the maximum doses were 22 to 36 Gy (median 26 Gy), and the treatment volumes were 0.1 to 33 cm3 (median 2.7 cm3). The actuarial 5-year clinical tumor-control rate (no requirement for surgical intervention) for the entire series was 97.1+/-1.9%. Five-year actuarial rates for any new facial weakness, facial numbness, hearing-level preservation, and preservation of testable speech discrimination were 1.1+/-0.8%, 2.6+/-1.2%, 71+/-4.7%, and 91+/-2.6%, respectively. Facial weakness did not develop in any patient who received a marginal dose of less than 15 Gy (163 patients). Hearing levels improved in 10 (7%) of 141 patients who exhibited decreased hearing (Gardner-Robertson Classes II-V) before undergoing radiosurgery. According to multivariate analysis, increasing marginal dose correlated with increased development of facial weakness (p = 0.0342) and decreased preservation of testable speech discrimination (p = 0.0122). Radiosurgery for acoustic neuroma performed using current procedures is associated with a continued high rate of tumor control and lower rates of posttreatment morbidity than those published in earlier reports.


Cdc45: the missing RecJ ortholog in eukaryotes?
DNA replication is one of the most ancient of cellular processes and functional similarities among its molecular machinery are apparent across all cellular life. Cdc45 is one of the essential components of the eukaryotic replication fork and is required for the initiation and elongation of DNA replication, but its molecular function is currently unknown. In order to trace its evolutionary history and to identify functional domains, we embarked on a computational sequence analysis of the Cdc45 protein family. Our findings reveal eukaryotic Cdc45 and prokaryotic RecJ to possess a common ancestry and Cdc45 to contain a catalytic site within a predicted exonuclease domain. The likely orthology between Cdc45 and RecJ reveals new lines of enquiry into DNA replication mechanisms in eukaryotes.


Decisional balance for immoderate drinking in college students.
Immoderate drinking in college is common and is associated with significant negative sequelae. In this study, measures of Decisional Balance for Immoderate Drinking were developed. This construct is proposed to represent the basic decision-making process that is used by students when deciding whether to drink at immoderate levels or not. Furthermore this construct is embedded in a larger model of behavior change, the Transtheoretical Model of Change, which has been shown to be effective in understanding many health-related behaviors across a wide variety of populations. A total of 629 college students were administered a 25-item decisional balance questionnaire in 1993-1994. Exploratory and confirmatory analyses suggested two different solutions, a two-factor solution and a three-factor solution, but did not provide clear evidence for the psychometric superiority of one over the other. The three-factor solution was chosen as it was seen as an elaboration of the two-factor solution, and validity evidence for this solution is presented. The three factors were labeled the Pros, the Cons-Actual, and the Cons-Potential of Immoderate Drinking. The Cons-Actual scale is a measure of negative affective states associated with current drinking whereas the Cons Potential measures the risk of more concrete negative effects of drinking. External validity was established by the significant and meaningful differences on a number of alcohol-related variables including consumption variables, three measures of negative sequelae of immoderate drinking, and Stage of Change, the organizing construct of the Transtheoretical Model of Change.


Collagen/β(1) integrin interaction is required for embryoid body formation during cardiogenesis from murine induced pluripotent stem cells.
The interactions between stem cells and extracellular matrix (ECM) mediated by integrins play important roles in the processes that determine stem cell fate. However, the role of ECM/integrin interaction in the formation of embryoid bodies (EBs) during cardiogenesis from murine induced pluripotent stem cells (miPSCs) remains unclear. In the present study, collagen type I and β(1) integrin were expressed and upregulated synergistically during the formation of miPSC-derived EBs, with a peak expression at day 3 of differentiation. The blockage of collagen/β(1) integrin interaction by β(1) integrin blocking antibody resulted in the production of defective EBs that were characterized by decreased size and the absence of a shell-like layer composed of primitive endoderm cells. The quantification of spontaneous beating activity, cardiac-specific gene expression and cardiac troponin T (cTnT) immunostaining showed that the cardiac differentiation of these defective miPSC-derived EBs was lower than that of control EBs. These findings indicate that collagen/β(1) integrin interaction is required for the growth and cardiac differentiation of miPSC-derived EBs and will be helpful in future engineering of the matrix microenvironment within EBs to efficiently direct the cardiac fate of pluripotent stem cells to promote cardiovascular regeneration.


Mild traumatic brain injuries: a 10-year follow-up.
Long-term consequences of mild traumatic brain injuries were investigated based on a 10-year follow-up of patients from a previously-published randomized controlled study of mild traumatic brain injuries. One aim was to describe changes over time after mild traumatic brain injuries in terms of the extent of persisting post-concussion symptoms, life satisfaction, perceived health, activities of daily living, changes in life roles and sick leave. Another aim was to identify differences between the intervention and control groups. The intervention group comprised 142 persons and the control group 56 persons. Postal questionnaires with a response rate of 56%. No differences over time were found for the intervention and control groups in terms of post-concussion symptoms. In the intervention group some variables in life satisfaction, perceived health and daily life were decreased. Some roles had changed over the years for both groups. No other differences between the intervention and control groups were found. However, in both groups sick leave decreased. Early individual intervention by a qualified rehabilitation team does not appear to impact on the long-term outcome for persons with symptoms related to mild traumatic brain injuries. The status after approximately 3 weeks is indicative of the status after 10 years.


Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process.


Cryo-EM structure of Escherichia coli σ70 RNA polymerase and promoter DNA complex revealed a role of σ non-conserved region during the open complex formation.
First step of gene expression is transcribing the genetic information stored in DNA to RNA by the transcription machinery including RNA polymerase (RNAP). In Escherichia coli, a primary σ70 factor forms the RNAP holoenzyme to express housekeeping genes. The σ70 contains a large insertion between the conserved regions 1.2 and 2.1, the σ non-conserved region (σNCR), but its function remains to be elucidated. In this study, we determined the cryo-EM structures of the E. coli RNAP σ70 holoenzyme and its complex with promoter DNA (open complex, RPo) at 4.2 and 5.75 Å resolutions, respectively, to reveal native conformations of RNAP and DNA. The RPo structure presented here found an interaction between the σNCR and promoter DNA just upstream of the -10 element, which was not observed in a previously determined E. coli RNAP transcription initiation complex (RPo plus short RNA) structure by X-ray crystallography because of restraint of crystal packing effects. Disruption of the σNCR and DNA interaction by the amino acid substitutions (R157A/R157E) influences the DNA opening around the transcription start site and therefore decreases the transcription activity of RNAP. We propose that the σNCR and DNA interaction is conserved in proteobacteria, and RNAP in other bacteria replaces its role with a transcription factor.


The product of the H19 gene may function as an RNA.
The mouse H19 gene was identified as an abundant hepatic fetal-specific mRNA under the transcriptional control of a trans-acting locus termed raf. The protein this gene encoded was not apparent from an analysis of its nucleotide sequence, since the mRNA contained multiple translation termination signals in all three reading frames. As a means of assessing which of the 35 small open reading frames might be important to the function of the gene, the human H19 gene was cloned and sequenced. Comparison of the two homologs revealed no conserved open reading frame. Cellular fractionation showed that H19 RNA is cytoplasmic but not associated with the translational machinery. Instead, it is located in a particle with a sedimentation coefficient of approximately 28S. Despite the fact that it is transcribed by RNA polymerase II and is spliced and polyadenylated, we suggest that the H19 RNA is not a classical mRNA. Instead, the product of this unusual gene may be an RNA molecule.


Implementation of evidence-based stroke care: enablers, barriers, and the role of facilitators.
A stroke care strategy was developed in 2007 to improve stroke services in Victoria, Australia. Eight stroke network facilitators (SNFs) were appointed in selected hospitals to enable the establishment of stroke units, develop thrombolysis services, and implement protocols. We aimed to explain the main issues being faced by clinicians in providing evidence-based stroke care, and to determine if the appointment of an SNF was perceived as an acceptable strategy to improve stroke care. Face-to-face semistructured interviews were used in a qualitative research design. Interview transcripts were verified by respondents prior to coding. Two researchers conducted thematic analysis of major themes and subthemes. Overall, 84 hospital staff participated in 33 interviews during 2008. The common factors found to impact on stroke care included staff and equipment availability, location of care, inconsistent use of clinical pathways, and professional beliefs. Other barriers included limited access to specialist clinicians and workload demands. The establishment of dedicated stroke units was considered essential to improve the quality of care. The SNF role was valued for identifying gaps in care and providing capacity to change clinical processes. This is the first large, qualitative multicenter study to describe issues associated with delivering high-quality stroke care and the potential benefits of SNFs to facilitate these improvements.


Is serial homicide really increasing?
Close examination of the available crime data reveals little scientific support for the widely held belief that serial homicide is frequent and increasing. The author argues that the dramatic changes in homicide clearance rates, incidence of murders with unknown motives, and victim gender data point to a likely increase, not in serial murder, but in contract murder. This type of killing appears to be having a significant impact on society; yet there has been a complete absence of forensic psychiatric study of this crime, a circumstance that needs to change.


Reducing confounding and suppression effects in TCGA data: an integrated analysis of chemotherapy response in ovarian cancer.
Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA) research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms. To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS) and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are detected subsequently using classical statistical approaches and enrichment analysis. The proposed procedure for the reduction of confounding and suppression effects and the semi-supervised clustering method are essential steps to identify genes associated with the chemotherapeutic response.


Drinking water quality monitoring using trend analysis.
One of the common quality parameters for drinking water is residual aluminium. High doses of residual aluminium in drinking water or water used in the food industry have been proved to be at least a minor health risk or even to increase the risk of more serious health effects, and cause economic losses to the water treatment plant. In this study, the trend index is developed from scaled measurement data to detect a warning of changes in residual aluminium level in drinking water. The scaling is based on monotonously increasing, non-linear functions, which are generated with generalized norms and moments. Triangular episodes are classified with the trend index and its derivative. The severity of the situations is evaluated by deviation indices. The trend episodes and the deviation indices provide good tools for detecting changes in water quality and for process control.


A nurse-led intervention study: Promoting compliance with Diskus Inhaler use in asthma patients.
To examine the impact of a nurse-led patient assessment and education programme in promoting compliance with inhaler use in asthma patients. A quasi-experimental pre-test and post-test design. A sample of asthmatic patients (N = 21) were recruited from the population of patients attending an asthma clinic. An Inhaler Proficiency Schedule (IPS) was developed and validated. At each visit, participants were requested to demonstrate their inhaler technique. The participants were investigated as to their confidence level with self-administration of their inhaler and adherence to prescribed doses. This information was recorded on a Patient-Reported Behaviour (PRB) questionnaire. Technique, compliance and patient confidence levels improved with nurse-led education repeated over three visits; this was sustained on measurement at 6 months following completion of the education programme.


Management of childhood craniopharyngioma: can the morbidity of radical surgery be predicted?
Seventy-five children treated for craniopharyngioma between 1973 and 1994 were studied to demonstrate which pre- and intraoperative factors were indicative of a poor outcome as defined by a quantitative assessment of morbidity. This involved a retrospective review of 65 patients and a prospective study of 10 patients focused on clinical details and cranial imaging and a follow-up "study assessment" of 66 survivors performed over the last 2 years. As part of the assessment, 63 patients underwent magnetic resonance imaging with a three-dimensional volume acquisition sequence 1.5 to 19.2 years after initial surgery. Predictors of high morbidity included severe hydrocephalus, intraoperative adverse events, and young age ( < or = 5 years) at presentation. Predictors of increased hypothalamic morbidity included symptoms of hypothalamic disturbance already established at diagnosis, greater height ( > or = 3.5 cm) of the tumor in the midline, and attempts to remove adherent tumor from the region of the hypothalamus at operation. Large tumor size, young age, and severe hydrocephalus were predictors of tumor recurrence, whereas complete tumor resection (as determined by postoperative neuroimaging) and radiotherapy given electively after subtotal excision were less likely to be associated with recurrent disease. Based on these findings, the authors propose an individualized, more flexible treatment approach whereby surgical strategies may be modified to provide long-term tumor control with the lowest morbidity.


Troponin-tropomyosin: an allosteric switch or a steric blocker?
The interaction of myosin subfragment 1 (S1) with actin-tropomyosin-troponin (regulated actin) is highly nucleotide dependent. The binding of S1 or S1-ADP (but not S1-ATP nor N,N'-rho-phenylenedimaleimide-modified S1-ATP) to regulated actin activates ATP hydrolysis even in the absence of Ca(2+). Investigations with S1 and S1-ADP have led to the idea that some actin sites are directly blocked toward the binding of S1 either by tropomyosin or troponin. The blocked state is thought to occur only at ionic strengths greater than 50 mM. The question is whether nonactivating S1 binding is blocked under the same conditions. We show that troponin inhibits binding of the nonactivating state, N,N'-rho-phenylenedimaleimide-S1-ATP, to actin but only when tropomyosin is absent. A lag in the rate of binding of activating S1 to actin (an indicator of the blocked state) occurs only in the presence of tropomyosin. Thus, tropomyosin inhibits binding of rigor S1 but not S1-ATP-like states. No evidence for an ionic strength-dependent change in the mechanism of regulation was observed either from measurements of the rate of activating S1 binding or from the equilibrium binding of nonactivating S1 to actin. At all conditions examined, N,N'-rho-phenylenedimaleimide-S1-ATP bound to regulated actin in the absence of Ca(2+). These results support the view of regulation in which tropomyosin movement is an allosteric switch that is modulated by activating myosin binding but that does not function solely by regulating myosin binding.


Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice.
Animal studies have shown that early postnatal propofol administration is involved in neurobehavioral alterations in adults. However, the underlying mechanism is not clear. We used c-Fos immunohistochemistry to identify activated neurons in brain regions of neonatal mice under propofol exposure and performed behavioral tests to observe the long-term consequences. Exposure to propofol (30g or 60 mg/kg) on P7 produced significant c-Fos expression in the deep layers of the piriform cortex on P8. Double immunofluorescence of c-Fos with interneuron markers in the piriform cortex revealed that c-Fos was specifically induced in calbindin (CB)-positive interneurons. Repeated propofol exposure from P7 to P9 induced behavioral deficits in adult mice, such as olfactory function deficit in a buried food test, decreased sociability in a three-chambered choice task, and impaired recognitive ability of learning and memory in novel object recognition tests. However, locomotor activity in the open-field test was not generally affected. Propofol treatment also significantly decreased the number of CB-positive interneurons in the piriform cortex of mice on P21 and adulthood. These results suggest that CB-positive interneurons in the piriform cortex are vulnerable to propofol exposure during the neonatal period, and these neurons are involved in the damage effects of propofol on behavior changes. These data provide a new target of propofol neurotoxicity and may elucidate the mechanism of neurobehavioral deficits in adulthood.


A high-resolution HPLC-QqTOF platform using parallel reaction monitoring for in-depth lipid discovery and rapid profiling.
Here, we developed a robust lipidomics workflow merging both targeted and untargeted approaches on a single liquid chromatography coupled to quadrupole-time of flight (LC-QqTOF) mass spectrometry platform with parallel reaction monitoring (PRM). PRM assays integrate both untargeted profiling from MS1 scans and targeted profiling obtained from MS/MS data. This workflow enabled the discovery of more than 2300 unidentified features and identification of more than 600 lipid species from 23 lipid classes at the level of fatty acid/long chain base/sterol composition in a barley root extracts. We detected the presence of 142 glycosyl inositol phosphorylceramides (GIPC) with HN(Ac)-HA as the core structure of the polar head, 12 cardiolipins and 17 glucuronosyl diacylglycerols (GlcADG) which have been rarely reported previously for cereal crops. Using a scheduled algorithm with up to 100 precursors multiplexed per duty cycle, the PRM assay was able to achieve a rapid profiling of 291 species based on MS/MS data by a single injection. We used this novel approach to demonstrate the applicability and efficiency of the workflow to study salt stress induced changes in the barley root lipidome. Results show that 221 targeted lipids and 888 unknown features were found to have changed significantly in response to salt stress. This combined targeted and untargeted single workflow approach provides novel applications of lipidomics addressing biological questions.


Depreissia decipiens, an enigmatic canopy spider from Borneo revisited (Araneae, Salticidae), with remarks on the distribution and diversity of canopy spiders in Sabah, Borneo.
Depreissia is a little known genus comprising two hymenopteran-mimicking species, one found in Central Africa and one in the north of Borneo. The male of Depreissia decipiens is redescribed, the female is described for the first time. The carapace is elongated, dorsally flattened and rhombus-shaped, the rear of the thorax laterally depressed and transformed, with a pair of deep pits; the pedicel is almost as long as the abdomen. The male palp is unusual, characterized by the transverse deeply split membranous tegulum separating a ventral part which bears a sclerotized tegular apophysis and a large dagger-like retrodirected median apophysis. The female epigyne consists of one pair of large adjacent spermathecae and very long copulatory ducts arising posteriorly and rising laterally alongside the spermathecae continuing in several vertical and horizontal coils over the anterior surface. Relationships within the Salticidae are discussed and an affinity with the Cocalodinae is suggested. Arguments are provided for a hypothesis that Depreissia decipiens is not ant-mimicking as was previously believed, but is a mimic of polistinine wasps. The species was found in the canopy in the Kinabalu area only, in primary and old secondary rainforest at 200-700 m.a.s.l. Overlap of canopy-dwelling spider species with those in the understorey are discussed and examples of species richness and endemism in the canopy are highlighted. Canopy fogging is a very efficient method of collecting for most arthropods. The canopy fauna adds an extra dimension to the known biodiversity of the tropical rainforest. In southeast Asia, canopy research has been neglected, inhibiting evaluation of comparative results of this canopy project with that from other regions. More use of fogging as a collecting method would greatly improve insight into the actual species richness and species distribution in general.


A pattern analysis of gene conversion literature.
Gene conversion is an important biological process that involves the transfer of genetic (sequence) information from one gene to another. This can have a variety of effects on an organism, both short-term and long-term and both positive and detrimental. In an effort to better understand this process, we searched through over 3,000 abstracts that contain research on gene conversions, tagging the important data and performing an analysis on what we extract. Through this we established trends that give a better insight into gene conversion research and genetic research in general. Our results show the importance of the process and the importance of continuing gene conversion research.


Prevention of adolescents' music-induced hearing loss due to discotheque attendance: a Delphi study.
Noise-induced hearing loss is a significant social and public health problem, which is found in increasing numbers of adolescents. Young people are particularly likely to expose themselves to potentially damaging loud sounds during leisure activities. Visiting discotheques is one of the most popular leisure activities of young people. Only a few minutes exposure to the sound levels played in discotheques can cause permanent hearing loss. Since little is known about what constitutes effective prevention strategies, we explored the opinions and ideas of 30 experts in a qualitative study consisting of a three-round web-based Delphi study. The main parties involved in the prevention of music-induced hearing loss due to discotheque attendance are as follows: the adolescents themselves, followed by the government, discotheque owners, decorators of discotheques and disk jockeys (DJs). None of the identified protective behaviors of adolescents was considered to be feasible. Five environmental interventions were identified as being both relevant and feasible; of these, the most important were that loudspeakers must be placed further away from the visitors and that discotheques have attractive, low-volume and clearly indicated 'chill-out rooms'. Effective prevention strategies to avoid music-induced hearing loss among adolescents due to discotheque attendance need to be taken primarily by discotheque owners and disk jockeys.


Body mass index and 25 hydroxyvitamin D status in patients with and without heart failure.
The purpose of this pilot study was to assess the association between 25-hydroxyvitamin D (25[OH]D) concentrations, vitamin D intake, and sunlight exposure in patients with heart failure (HF) compared with healthy volunteers. Fourteen healthy volunteers 50 and older were recruited to compare with 14 patients with HF. Healthy volunteers were compared with HF patients by serum 25(OH)D concentrations, dietary vitamin D intake, weekly sunlight exposure, and other covariates. Independent sample t tests and linear regression models were used to compare differences between healthy volunteers and patients with HF. The mean serum 25(OH)D concentration was not significantly different between groups (healthy volunteers 25.7 ± 11.1 ng/mL, patients with HF 20.4 ± 10.2 ng/mL; P=.2) and no group effect was found in any multivariable models. Body mass index regardless of group was found to be inversely associated with serum 25(OH)D concentrations (P=.025). There was no difference in the dietary intake of vitamin D or calcium between groups. The healthy volunteers had a significantly greater amount of sunlight exposure but this did not result in higher 25(OH)D when compared with those with HF. Our findings suggest that body mass index has an important relationship with 25(OH)D concentrations regardless of a person being healthy or having HF.