Empirical Classification of Trajectory Data: An Opportunity for the Use of Machine Learning in Molecular Dynamics.
Classical Hamiltonian trajectories are initiated at random points in phase space on a fixed energy shell of a model two degrees of freedom potential, consisting of two interacting minima in an otherwise flat energy plane of infinite extent. Below the energy of the plane, the dynamics are demonstrably chaotic. However, most of the work in this paper involves trajectories at a fixed energy that is 1% above that of the plane, in which regime the dynamics exhibit behavior characteristic of chaotic scattering. The trajectories are analyzed without reference to the potential, as if they had been generated in a typical direct molecular dynamics simulation. The questions addressed are whether one can recover useful information about the structures controlling the dynamics in phase space from the trajectory data alone, and whether, despite the at least partially chaotic nature of the dynamics, one can make statistically meaningful predictions of trajectory outcomes from initial conditions. It is found that key unstable periodic orbits, which can be identified on the analytical potential, appear by simple classification of the trajectories, and that the specific roles of these periodic orbits in controlling the dynamics are also readily discerned from the trajectory data alone. Two different approaches to predicting trajectory outcomes from initial conditions are evaluated, and it is shown that the more successful of them has ∼90% success. The results are compared with those from a simple neural network, which has higher predictive success (97%) but requires the information obtained from the "by-hand" analysis to achieve that level. Finally, the dynamics, which occur partly on the very flat region of the potential, show characteristics of the much-studied phenomenon called "roaming." On this potential, it is found that roaming trajectories are effectively "failed" periodic orbits and that angular momentum can be identified as a key controlling factor, despite the fact that it is not a strictly conserved quantity. It is also noteworthy that roaming on this potential occurs in the absence of a "roaming saddle," which has previously been hypothesized to be a necessary feature for roaming to occur.


Anxiety impacts rheumatoid arthritis symptoms and health-related quality of life even at low levels.
We explored the burden of symptoms of anxiety and depression on health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA). Adults with RA participating in an observational cohort completed PROMIS tests of depression, anxiety, fatigue, physical function (PF), pain interference (PI), sleep disturbance, and participation in social roles and activities at the baseline visit. Clinical measures of disease status were also obtained. We used ANOVA and partial correlation adjusting for the swollen joint count (SJC) to examine associations of anxiety and depression with other aspects of HRQL. Mild and moderate-severe anxiety were defined as T-scores ≥55.4 and ≥ 62.3 and mild and moderate-severe depression was defined as ≥52.5 and ≥58.6 based on previous validated clinical thresholds. Multivariable linear regression (MVR) was used to identify predictors of emotional distress with a subset analysis of those in remission/low disease activity. Of 196 RA participants, 18% had mild anxiety, 9% had moderate-severe anxiety, 18% had mild depression, and 14% had moderate-severe depression symptoms. Anxiety and depression scores were associated with significantly worse mean scores across HRQL domains (p <0.05). In MVR, depression (β=0.75, p<0.001), PF (β=0.14, p=0.024) and fatigue (β=0.15, p=0.015) predicted higher anxiety levels, whereas only anxiety predicted higher depression levels (β=0.70, p=<0.001). In subset analysis, PF no longer predicted higher anxiety levels. Emotional distress is common in RA, even when disease is well controlled, with considerable impacts on other aspects of HRQL even at mild levels.


Outcomes in females hospitalised with community-acquired pneumonia are worse than in males.
There is little recent information on sex-specific outcomes of patients with community-acquired pneumonia (CAP). The objective of this study was to determine whether female sex is associated with better clinical outcomes in hospitalised patients with CAP. A secondary analysis was conducted by the Community Acquired Pneumonia Organization regarding male and female patients with CAP from 80 hospitals in 17 countries from June 1, 2001 to August 2, 2011. Outcomes were time to clinical stability, length of stay and in-hospital and 28-day mortality. Propensity-adjusted, multivariate regression models were used to predict the probability of occurrence of each of the study outcomes. There were 6718 patients in this study, of whom 40% were female. The adjusted hazard ratio (HR) for time to clinical stability was 0.91 (95% CI 0.85-0.97; p=0.005). The adjusted HR for length of stay was 0.94 (95% CI 0.88-1.01; p=0.089). The adjusted risk ratio for in-hospital mortality was 1.04 (95% CI 0.86-1.24; p=0.717), and for 28-day mortality was 1.15 (95% CI 1.02-1.30; p=0.018). This study demonstrates that the epidemiology of CAP may be changing, and that females have worse outcomes for CAP than males. They are more likely to take longer to reach clinical stability, have longer hospital stays and are 15% more likely to have died after 28 days. Current pneumonia scoring systems may need to be revised regarding female mortality risk.


General Transduction in Vibrio cholerae.
Evidence was obtained for general transduction in Vibrio cholerae. Transduction of three amino acid markers and three antibiotic resistance characters was demonstrated using strains of biotype eltor and biotype cholerae. Some of the genetic characters were transduced from a biotype eltor donor (and its mutant derivatives) to biotype cholerae and eltor recipients. For the genetic traits examined, the frequencies of transduction ranged between 10(-5) and 10(-8). Maximal frequencies were obtained with transducing phage lysates that were irradiated with ultraviolet light. The development of a system of general transduction will now aid in fine structure analysis and detailed mapping of the chromosome of V. cholerae.


CT-guided transforaminal epidural injections with local anesthetic, steroid, and tramadol for the treatment of persistent lumbar radicular pain.
A substantial number of patients with persistent lumbar radicular pain are treated with a multimodal spectrum of conservative therapies without lasting effect. The duration of pain is certainly a risk factor for chronification. There is evidence that guided periradicular infiltrations are a valid option in the treatment of radiculopathies. Usually a combination of local anesthetic and/or corticosteroid is injected. Tramadol is being used for perioperative analgesia and has been shown to provide effective, long-lasting pain relief after epidural administration. The aim of this pilot study was to evaluate the efficacy of serial CT-guided transforaminal nerve root infiltrations with a supplement of tramadol for patients with persistent, radicular pain. Interventional cohort study. Outpatient department for interdisciplinary pain medicine. 37 patients who had radicular leg pain for over 9 weeks received up to 3 CT-guided transforaminal nerve root infiltrations at intervals of 2 weeks as long as their level of pain was over 3 on a numerical rating scale from 0 to 10. 50 mg of Tramadol were added to a combination of local anesthetic (Ropivacain, 2 mg) and corticosteroid (Triamcinolon, 40 mg). Evaluations were carried out 24 hours after the Infiltration as well as 2 weeks, 3 and 6 months after the treatment series. The intensity of their radicular pain was measured by a numerical rating scale (NRS). Pain reduction of at least 50% was defined as successful outcome. In total, 65 infiltrations were carried out with pain relief in more than 90% of the patients within 24 hours and an average pain reduction of 64%. Six months post-injection 23 of 34 patients available for follow-up (67.6%) had a successful pain reduction of 84% on average. No adverse effects ascribable to the use of tramadol were noted. Due to the lack of a control group we cannot make any statement if tramadol improves short-term pain reduction. Fast and lasting pain relief is the key to optimize rehabilitation for patients with radicular pain. There is a physiological rationale that the opioid receptors at the spinal level could be used to optimize the analgetic effect of guided periradicular injections. In our case series, serial CT-guided selective nerve root infiltrations with the supplement of tramadol were found to be highly effective in the treatment of persistant radiculopathies. Randomized controlled trials will be necessary to clarify the possible benefit of the supplement of an opioid.


Prediction of functional regions of the maize streak virus replication-associated proteins by protein-protein interaction analysis.
The replication of the geminiviruses depends on the viral encoded early (complementary-sense) proteins and on host genome encoded factors. Additionally, some of the early proteins (the AL2 protein of subgroup III, and the RepA (formerly known as C1) or Rep (C1:C2) proteins of subgroup I geminiviruses) can function as transcriptional activators of virion- (V-)sense gene expression. The yeast two-hybrid system has allowed us to predict some of the functionally important regions of the maize streak virus (MSV) early proteins RepA and Rep. Defined domains of these proteins were shown to act as transactivators in yeast cells. We detected the association of the RepA and Rep proteins, and their subfragments, with the maize retinoblastoma protein (ZmRb1) which is likely to be one of the interacting host proteins. We showed the self-association capability of the MSV proteins and suggest that homo- or hetero-oligomerization may play an important role in virus replication. These results provide new insights into the role of different regions of the MSV proteins in relation to transcriptional activation and regulation of viral DNA replication.


Reaching to multiple targets when standing: the spatial organization of feedforward postural adjustments.
We examined the spatial organization of feedforward postural adjustments produced prior to and during voluntary arm reaching movements executed while standing. We sought to investigate whether the activity of postural muscles before and during reaching was directionally tuned and whether a strategy of horizontal force constraint could be observed. To this end, eight human subjects executed self-paced reach-to-point movements on the random illumination of one of 13 light targets placed within a 180 degrees array centered along the midline of the body. Analysis was divided into two periods: a first corresponding to the 250 ms preceding the onset of the reaching movements (termed pPA period) and a second 250-ms period immediately preceding target attainment (the aPA period). For both periods, electromyographic activity of the lower limb muscles revealed a clear directional tuning, with groups of muscles being activated for similar directions of reach. Analysis of horizontal ground reaction forces supported the existence of a force constraint strategy only for the pPA period, however, with those in the aPA period being more widely dispersed. We suggest that the strategy adopted for feedforward pPAs is one where the tuned muscle synergies constrain the forces diagonally away from the center of mass (CoM) to move it within the support base. However, the need to control for final finger and body position for each target during the aPA phase resulted in a distribution of vectors across reaching directions. Overall, our results would support the idea that endpoint limb force during postural tasks depends on the use of functional muscle synergies, which are used to displace the CoM or decelerate the body at the end of the reach.


Kinetic analyses of the magnesium chelatase provide insights into the mechanism, structure, and formation of the complex.
The metabolic pathway known as (bacterio)chlorophyll biosynthesis is initiated by magnesium chelatase (BchI, BchD, BchH). This first step involves insertion of magnesium into protoporphyrin IX (proto), a process requiring ATP hydrolysis. Structural information shows that the BchI and BchD subunits form a double hexameric enzyme complex, whereas BchH binds proto and can be purified as BchH-proto. We utilized the Rhodobacter capsulatus magnesium chelatase subunits using continuous magnesium chelatase assays and treated the BchD subunit as the enzyme with both BchI and BchH-proto as substrates. Michaelis-Menten kinetics was observed with the BchI subunit, whereas the BchH subunit exhibited sigmoidal kinetics (Hill coefficient of 1.85). The BchI.BchD complex had intrinsic ATPase activity, and addition of BchH greatly increased ATPase activity. This was concentration-dependent and gave sigmoidal kinetics, indicating there is more than one binding site for the BchH subunit on the BchI.BchD complex. ATPase activity was approximately 40-fold higher than magnesium chelatase activity and continued despite cessation of magnesium chelation, implying one or more secondary roles for ATP hydrolysis and possibly an as yet unknown switch required to terminate ATPase activity. One of the secondary roles for BchH-stimulated ATP hydrolysis by a BchI.BchD complex is priming of BchH to facilitate correct binding of proto to BchH in a form capable of participating in magnesium chelation. This porphyrin binding is the rate-limiting step in catalysis. These data suggest that ATP hydrolysis by the BchI.BchD complex causes a series of conformational changes in BchH to effect substrate binding, magnesium chelation, and product release.


Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients.
Hypernatraemia is common in intensive care patients and may present an independent risk factor of mortality. Several formulae have been proposed to guide infusion therapy for correction of serum sodium. Unfortunately, these formulae have never been validated comparatively. We assessed the predictive potential of four different formulae (Adrogué-Madias, Barsoum-Levine, Kurtz-Nguyen and a simple formula based on electrolyte-free water clearance) in correction and maintenance of serum sodium in 66 hyper- and normonatraemic ICU patients. With daily measurements of sodium/potassium and fluid/electrolyte balances, a day-to-day prediction of serum sodium levels was calculated using the four formulae. This was compared to the measured changes in serum sodium. Six hundred and eighty-one patient-days (194 hypernatraemic) in 66 patients were available for calculations. Prediction of serum sodium levels using all four formulae correlated significantly (P < 0.05) with measured changes in serum sodium. Individual variations were extreme, and the mean differences (+/-SD) for predicted versus measured serum sodium were within the range of 3.4-4.5 (+/-4.4-4.7) mmol/l similar for the Adrogué-Madias, Barsoum-Levine and Nguyen-Kurtz formulae. In comparison, our proposed formula underestimated the changes of serum sodium (mean +/- SD -1.5 +/- 5.3). During hypernatraemia, the differences between predicted and measured values were even greater (mean +/- SD 5.0-6.7 +/- 3.9-4.3) using the published formulae compared to our formula (mean +/- SD 0.2 +/- 4.0). Currently available formulae to guide infusion therapy in hyper- and normonatraemic states do not accurately predict changes of serum sodium in the individual ICU patient. In clinical practice, infusion therapy should be based on the reasons for hypernatraemia and serial measurements of serum sodium to avoid evolution of derangements.


The role of platelet serotonin and depression in the acute coronary syndrome population.
Platelet serotonin has been associated with depression and coronary artery disease. Understanding the association between platelet serotonin and depressive symptoms during acute coronary syndrome (ACS) may explain some of the ACS events seen in depressed individuals. The objectives were to evaluate whether levels of platelet serotonin during an ACS event differ between individuals who screen positive or negative for depressive symptoms and to determine if a linear relationship exists. In this cross-sectional study, data were collected on 51 patients with ACS. Multiple linear regression models were examined. Platelet serotonin levels were not significantly different between the depressed and non-depressed groups (β = -4.093 and p = .293); a linear relationship was not found (β = -.254 and p = .250). In conclusion, a relationship between platelet serotonin and depressive symptoms was not found. It remains unclear if an association exists between platelet serotonin levels and depressive symptoms during hospitalization for ACS.


Balance Control and Peripheral Muscle Function in Aging: A Comparison Between Individuals with Acromegaly and Healthy Subjects.
Advances in the knowledge of acromegaly are leading to an increase in the survival rate of acromegalic subjects. This study was conducted to evaluate balance control, risk of falls, and peripheral muscle function in acromegalic older adults. Seventeen older subjects with acromegaly (67 [63-73] years) and 20 paired control subjects were evaluated with balance scales, force platform, and knee isokinetic dynamometry tests. There were significant differences between the groups on several balance and gait scales, with a worse performance and greater risk of falls in the acromegalic older adults. Acromegalic older adults had lower values for peak torque, maximum repetition of the total work, and total work during extension at 240°/s. The acromegalic older adults had higher values in the medial-lateral range. Acromegaly subjects had lateral instability that compromises their body balance and increases the risk of falls. Moreover, there was a propensity for muscle fatigue in these individuals.


Presentation of a modified dispersion model (MDM) for hepatic drug extraction and a new methodology for the prediction of the rate-limiting step in hepatic metabolic clearance.
The main objectives were to investigate the roles of and interplay between determinants of hepatic clearance (CL(H)) in humans, to develop a methodology and reference system for the evaluation and prediction of the rate-limiting step in CL(H), and to update the dispersion model and compare it with traditionally used liver extraction models. The new methodology enables predictions of the hepatic uptake and CL(H), dissociation, and rate-limiting step. In general, absorption, dissociation and diffusion are comparably rapid processes, and metabolism is rate-limiting. The liver appears to have a high passive uptake capacity. The Modified Dispersion Model (MDM) has a dispersion number of 0.5 and a distribution factor (df = 0.87) for the correction of a longer hepatic transit time of unbound molecules and the exclusion of the hidden unbound fraction within erythrocytes. Liver models are functionally equivalent at low CL(H), but differ for highly extracted compounds. Well-stirred and parallel-tube models demonstrate the greatest difference in performance, for example, 6- and 800,000-fold differences in the estimated in vivo intrinsic CL(H) and predicted oral bioavailability of the high CL(H) drug naloxone, respectively. The roles of and interplay between determinants of CL(H) have been further clarified and can now be better predicted. Apparent advantages with the MDM include its scientific rationale and intermediate/ balanced performance.


Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide.
The extent to which proteins aggregate into distinct structures ranging from prefibrillar oligomers to amyloid fibrils is key to the pathogenesis of many age-related degenerative diseases. We describe here for the Alzheimer's disease-related amyloid beta peptide (Abeta) an investigation of the sequence-based determinants of the balance between the formation of prefibrillar aggregates and amyloid fibrils. We show that by introducing single-point mutations, it is possible to convert the normally harmless Abeta40 peptide into a pathogenic species by increasing its relative propensity to form prefibrillar but not fibrillar aggregates, and, conversely, to abolish the pathogenicity of the highly neurotoxic E22G Abeta42 peptide by reducing its relative propensity to form prefibrillar species rather than mature fibrillar ones. This observation can be rationalized by the demonstration that whereas regions of the sequence of high aggregation propensity dominate the overall tendency to aggregate, regions with low intrinsic aggregation propensities exert significant control over the balance of the prefibrillar and fibrillar species formed, and therefore play a major role in determining the neurotoxicity of the Abeta peptide.


Validation of CHA₂DS₂-VASc and HAS-BLED scores in Japanese patients with nonvalvular atrial fibrillation: an analysis of the J-RHYTHM Registry.
Recent European guidelines recommended the CHA2DS2-VASc score for thromboembolic and the HAS-BLED score for bleeding risk stratifications. We validated these scores in 7,384 Japanese patients with nonvalvular atrial fibrillation (NVAF) enrolled in the J-RHYTHM Registry. Of the study cohort, 6,387 patients taking warfarin and the other 997 not taking warfarin were prospectively examined for 2 years. Thromboembolic and major bleeding risks were stratified by modified CHA2DS2-VASc (mCHA2DS2-VASc) and HAS-BLED (mHAS-BLED) scores, respectively. Of the patients with mCHA2DS2-VASc score 0, 1, and ≥2, thromboembolism occurred in 2/141 (0.7%/year), 4/233 (0.9%/year), and 24/623 (1.9%/year), respectively, in the non-warfarin group, and in 1/346 (0.1%/year, P=0.19 vs. non-warfarin), 4/912 (0.2%/year, P=0.05), and 92/5,129 (0.9%/year, P=0.0005), respectively, in the warfarin group. When female sex was excluded from the score, thromboembolism occurred in 2/180 patients (0.6%/year), 5/245 (1.0%/year), and 23/572 (1.6%/year), respectively, in the non-warfarin group, and in 1/422 (0.1%/year, P=0.20 vs. non-warfarin), 5/1,096 (0.2%/year, P=0.02), and 91/4,869 (0.9%/year, P=0.0005), respectively, in the warfarin group. Patients with mHAS-BLED scores ≥3 were at high risk for major bleeding irrespective of warfarin treatment (1.3 and 2.6%/year in the non-warfarin and warfarin groups, respectively). In Japanese NVAF patients, the mCHA2DS2-VASc score is useful for identifying patients at truly low risk of thromboembolism. Female sex may be excluded as a risk from the score. mHAS-BLED score ≥3 is useful for identifying patients at high risk of major bleeding.


The historiography of Swedish sociology and the bounding of disciplinary identity.
Bounding a scientific discipline is a way of regulating its cognitive direction as well as its relations to neighboring disciplines and extra-academic authorities. In this process of identity making, disciplinary history often is a crucial element. In this article, focusing on the historiography of Swedish sociology and the reception of Gustaf Steffen, Sweden's first professional sociologist, it is argued that Steffen's marginalized role in the traditional accounts should be understood not only with reference to his supposed theoretical shortcomings, but also in the historical context of the early postwar reestablishment of sociology as an academic discipline and its prevalent need for a new disciplinary identity, strategically adjusted to the contemporary institutional and political settings.


[Use of Diacarb to attain hypotension in preoperative treatment of patients with different cataract etiology].
The authors assess the efficacy of preoperative decrease of intraocular pressure by diacarb in 130 patients (134 eyes) with senile and complicated cataracts and cataracts combined with primary open-angle glaucoma. Diacarb administered after the proposed protocols helps notably decrease the initial intraocular pressure, thus preventing intraoperative complications in the course of extracapsular cataract extraction with implantation of intraocular lenses.


Mutagenicity of radiations and chemical mutagens in Sorghum.
A comparative study on the relative mutagenicity of radiations (X-and gamma rays) and chemical mutagens (EMS, MMS, dES and NEU) in inducing chlorophyll, viable and total mutations was made on three cultivated varieties (Co. 11, Co. 12 and Co. 18) of Eu-Sorghum. A critical comparison of the chlorophyll, viable and total mutations shows that the mutation rate increased with an increase in dose up to a certain dose level beyond which the saturation effect was observed. EMS was found to be the most potent mutagen in inducing chlorophyll, viable and total mutations. The treatments with NEU (viable mutations) and dES (viable and total mutations) also proved to be effective. In a large number of cases the relationship between chlorophyll and total mutations was more close than that of viable to total mutation rates.


Implementing the EffTox dose-finding design in the Matchpoint trial.
The Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial. EffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed. We arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity. EffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design. Matchpoint was added to the European Clinical Trials Database ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB ) on 2013-12-30.


Desiccation sensitivity and cryopreservation of excised embryonic axes of Citrus suhuiensis cv. limau madu, Citrumelo [Citrus paradisi macf. × Poncirus trifoliata (l.) raf.] and Fortunella polyandra.
Excised embryonic axes from seeds of three taxa, namely, Citrus suhuiensis cv. limau madu, Citrumelo (Citrus paradisi x Poncirus trifoliate) and Fortunella polyandra, were desiccated in a laminar airflow, over silica gel, and ultra-rapidly. Desiccation sensitivity (WC50) was estimated for each taxon using the quantal response model. High desiccation tolerance (WC50 = 0.11 g water per g dry mass. g/gdw) was observed for limau madu embryonic axes desiccated in a laminar airflow and ultra-rapidly (WC50 =0.10 g/gdw). Desiccation tolerance was substantially lower (WC50 = 0.19 g/gdw) for silica gel dehydration. Similarly, high desiccation tolerance (WC50 = 0.15 g/gdw) was associated with F. polyandra embryonic axes when desiccated in a laminar airflow, while a lower desiccation tolerance (WC50 = 0.17 g/gdw) was observed with silica gel dehydration. Ultra-rapid desiccation led to the highest desiccation tolerance (WC50 = 0.14 g/gdw). The dehydration rate, however, had no influence on desiccation tolerance (WC50 ~ 0.14 g/gdw) for Citrumelo embryonic axes. After each desiccation period, embryonic axes were directly immersed in liquid nitrogen (LN) followed by rapid rewarming. Normal seedling recovery of 80 to 83% for excised embryonic axes of limau madu was observed for laminar airflow and ultra-rapid dehydration, but for silica gel dehydration, 57% recovery was obtained. Similarly, for Citrumelo, high recoveries of 100% and 97% were obtained from axes desiccated in a laminar airflow and using ultra-rapid dehydration, respectively, whereas a lower value was associated with silica gel dehydration (80%). For F. polyandra, 50% recovery was obtained both for laminar airflow and ultra-rapid dehydration, while much lower recovery (43%) was associated with silica gel dehydration. Regardless of the drying method employed, axis survival percentages following exposure to LN were commensurate with the desiccation sensitivity pattern.


Don't wear me out--the public's knowledge of and attitudes to antibiotic use.
To assess the public's knowledge and attitudes to antibiotics, their reported antibiotic use and the relationship between them. A questionnaire was included in the face-to-face Office for National Statistics Omnibus Household Survey in Britain in 2003. Of 10 981 randomly selected adults from England, Scotland and Wales, 7120 (65%) completed the questionnaire. Although 79% of respondents were aware that 'antibiotic resistance is a problem in British hospitals', 38% of respondents did not know that antibiotics do not work against most coughs or colds and 43% did not know that 'antibiotics can kill the bacteria that normally live on the skin and in the gut'. Respondents with lower educational qualifications were less knowledgeable about antibiotics. In a multivariable analysis, better knowledge of antibiotics was not associated with being less likely to be prescribed any in the last year, but was independently associated with being more likely to finish a course of antibiotic as prescribed. Knowledge was also associated with being more likely to take antibiotics without being told to do so. In women, better knowledge was associated with being more likely to give an antibiotic to someone else that was not prescribed for them. We have shown that there is no simple relationship between increased knowledge and more prudent antibiotic use. Future national antibiotic campaigns should have a defined audience and aims in order to facilitate prudent antibiotic use by clinicians and public.


Validity and sensitivity to change of patient-reported pain and disability measures for elbow pathologies.
Prospective cohort study. To evaluate the internal consistency, concurrent construct validity, longitudinal validity, sensitivity to change, and factor structure of the Patient-Rated Elbow Evaluation form (PREE), the patient-reported form of the American Shoulder and Elbow Surgeons Elbow Questionnaire (pASES-e), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) in a diverse group of patients who had surgery for various elbow pathologies. Measuring functional outcomes after surgical procedures of the elbow requires valid patient-reported pain and disability questionnaires. The PREE, the pASES-e, and the DASH are commonly used questionnaires. There is, however, insufficient evidence available concerning their validity and sensitivity to change. Data were prospectively collected from 128 patients (mean ± SD age, 46.5 ± 12.8 years) post-elbow surgery. Patients completed the PREE, the pASES-e, the DASH, and the Medical Outcomes Study 36-Item Short-Form Health Survey at baseline (first visit after surgery) and 6 months postsurgery. Concurrent construct validity, longitudinal validity, sensitivity to change, and factor structure were analyzed. Concurrent construct validity was demonstrated by confirmation of expected relationships; the strongest correlations were observed between the PREE pain score, the PREE total score, the pASES-e pain score, and the DASH score (r = 0.73-0.87). The pASES-e function score correlated the least with other constructs. Longitudinal validity demonstrated similar findings: the pASES-e pain change score and PREE change score were most strongly correlated, and the pASES-e function change score and DASH change score were moderately to weakly correlated. All 3 patient-reported questionnaires demonstrated a large effect size and standardized response means greater than 1.0. Structural validity was supported for the PREE (R2 = 77.2%, 4 factors) and the pASES-e (R2 = 74.4%, 4 factors), but not for the DASH (R2 = 71.3%, 5 factors). The PREE, the pASES-e, and the DASH have acceptable validity and sensitivity to change. The pASES-e function subscale is the least sensitive to change and is less correlated to other measures.


Mortality implications and factors associated with nonengagement in a public epilepsy care initiative in a transient population.
Community-based, public care programs are a requisite to close the epilepsy treatment gap in disadvantaged communities in low- and middle-income countries (LMICs). Potential beneficiaries may, however, choose not to engage in these programs. The aim of the study was to describe factors associated with and mortality consequences of nonacceptance of a public epilepsy care initiative. In this cross-sectional study, we contacted 207 (36%) people out of 575 who screened positive for epilepsy during a population-based survey of 59,509 people. They were invited for neurological evaluation and care provision (including antiseizure medications (ASMs)) but chose not to engage. Structured questionnaires and qualitative interviews were conducted to determine reason for their nonengagement. Factors associated with nonengagement were evaluated by univariate and multivariate analysis. We conducted verbal autopsies for those who had died. Ten (5%) of the 207 individuals died since the initial screening; six with epilepsy-related causes. Of those who could be contacted (n = 48), 40 (19%) were confirmed to have epilepsy. Nonengaging individuals were likely to be older (odds ratio (OR): 1.02; 95% confidence interval (CI), 1.01, 1.11), locals (OR: 4.32; 95% CI, 1.55, 12.03), and earn less than US$ 78/month (OR: 3.6; 95% CI, 1.62, 8.06). Reasons for not engaging included a belief that epilepsy is inconsequential, loss of daily wages owing to healthcare facility visit and physical infirmity. Nonacceptance of a community-based public epilepsy care initiative is associated with high premature mortality, mostly attributed to epilepsy-related causes. Older age, ethnic status, and economic deprivation are factors associated with nonacceptance, though the underlying reasons may be varied.


Characterization of hollow fibers for the transmission of infrared radiation.
Plastic hollow fibers were made from plastic tubes covered on the internal wall with a metal layer (a-type) or a metal layer and dielectric layer on top of it (b-type). The CO(2) laser energy transmission through the hollow fiber was measured as a function of the radius of curvature and the coupling lens (focal length at a constant fiber length). The yield of the transmission decreased in subtle curvatures (radius of curvature up to 100 cm) and remained almost constant as the curvature became sharper (down to radius of curvature of 13 cm). For the a-type fibers, the characteristics of attenuation depended on the focal length of the coupling lenses. The energy distribution at the output was measured and mapped. The experimental results showed that the maximum of the energy distribution is asymetrically positioned relative to the center and closer to the internal wall at a smaller bending radius. This was predicted in our previous theoretical calculation. The value of transmitted power attenuation was up to 1.4 dB/m. Maximum power at the output was 30 W, for a fiber of 50-cm length and a cross-sectional diameter of 1.9 mm. These types of hollow fiber have already been used in surgical experiments on dogs.


Spontaneous rupture of a giant hemangioma of the liver.
Hemangiomas are frequent benign tumors of the liver. Symptoms (abdominal pain and fullness) are mostly seen in giant lesions. Rupture is the most severe complication, can occur spontaneously, with intraperitoneal bleeding, in 1-4% of hemangiomas and has been described in about 30 cases in the international literature with a high mortality (about 60%). This complication is the principal indication for surgery. Although spiral CAT scan and MR are actually the most efficacious imaging methods for study of liver hemangiomas, after Echography, emergency techniques that allows a simultaneous therapeutic approach--as is angiography--are preferable. Trans-arterial embolization (TAE) is in fact useful to stop bleeding and then to perform a safer surgery. A successful embolization can delay the surgical resection of the hemangioma for the time necessary to recover from the hemodynamic distress. Aside from the success of angiographic approach, surgery remains mandatory, effective in stopping the bleeding and in preventing re-bleeding or other complications of TAE such as abscess, fever, etc.. Intraoperative echography currently is the best method to identify vasculo- biliary anatomy and to perform a correct resection. The absence of risk factors for spontaneous rupture of liver hemangiomas, makes this event unpredictable. The best treatment for non-ruptured hemangiomas is still controversial but surgery is usually limited to symptomatic tumors larger than 10 cm.


Selective mode excitation of graded index optical fibers.
A method is described permitting excitation of a small number of modes in graded index fibers, the order of the launched mode being easily varied and determined. Using this launching technique, it is possible to determine the index profile and index difference of graded core fibers; results are compared with those obtained by other techniques. Other important fiber parameters, such as the differential attenuation and the differential propagation delay time as a function of the mode parameter, are also obtained, giving an insight into the fundamental propagation characteristics of the fiber.


[Endothelin system and heart failure: a potential therapeutic target].
Neurohormonal activation is a marker and one of the most important pathophysiologic aspects of heart failure. The hyperactivation and participation of the endothelin system in several manifestations of this syndrome have been widely documented in the last few years. These data support attempts to view the endothelin system as a potential pharmacological target in order to reduce the high morbidity and mortality associated with heart failure. This is a short review of the main aspects of endothelin biology, its mechanisms of action, including those at the molecular level, and its pathophysiological role in heart failure. Finally, the potential benefits of the pharmacological manipulation of the endothelin system as well as some results of clinical trials in this context will be presented.


p204-initiated innate antiviral response in mouse Leydig cells.
The mammalian testis is an immunoprivileged organ where local tissue-specific cells acquire an effective innate immune function against invading microbial pathogens. The present study demonstrated that mouse Leydig cells had innate antiviral activities in response to viral DNA challenge through p204 activation. The DNA sensor p204 and its signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in Leydig cells. Synthetic herpes simplex virus DNA analog (HSV60), a p204 agonist, induced the expression of type I IFNs and various antiviral proteins, including IFN-stimulating gene 15, 2'5'-oligoadenylate synthetase, and Mx glutamyl transpeptidase 1, in Leydig cells. The HSV60-induced innate antiviral response in Leydig cells was significantly reduced by inhibiting p204 signaling using specific small interfering RNAs targeting p204 and Sting. The antiviral response did not affect steroidogenesis in Leydig cells. These results indicated a novel mechanism underlying the testicular innate antiviral response.


The Gap Study (GapS) interview--developing a process to determine the meaning and determinants of quality of life in children with arthritis and rheumatic disease.
Quality of Life (QOL) is a ubiquitous yet rarely precisely defined term. QOL may be determined by the differences (gaps) between our current situation and our expectations. Contemporary methods of measuring QOL often do not take these gaps into consideration. We performed this study to develop items and methods for measuring and valuing these gaps in order to better determine individual QOL for children with rheumatic diseases. We generated items from literature review, other QOL measures and interviews with pediatric rheumatology patients and their families. Gap-scales to measure the discrepancy between a child's current state and the expected or desired state were designed and tested iteratively in pilot interviews. Thirty-one children (mean age=13.5 years, age range=6-17 years) and 22 parents were recruited through pediatric rheumatology clinics. The process of item generation, reduction and preliminary formatting yielded a list of 72 items. We developed a 3-point categorical scale of importance and a vertical visual analog scale (VAS) to determine individual valuation of items. 5 gap-scales were developed to reflect different aspects of the discrepancy between the child's current and expected or desired states for different QOL items. We have developed a QOL interview based on theory that we can now test to see if it will enrich our understanding of the determinants of QOL in pediatric rheumatology patients and other chronically ill children.


Deferred Warping.
We introduce deferred warping, a novel approach for real-time deformation of 3D objects attached to an animated or manipulated surface. Our target application is virtual prototyping of garments where 2D pattern modeling is combined with 3D garment simulation which allows an immediate validation of the design. The technique works in two steps: First, the surface deformation of the target object is determined and the resulting transformation field is stored as a matrix texture. Then the matrix texture is used as look-up table to transform a given geometry onto a deformed surface. Splitting the process in two steps yields a large flexibility since different attachment types can be realized by simply defining specific mapping functions. Our technique can directly handle complex topology changes within the surface. We demonstrate a fast implementation in the vertex shading stage allowing the use of highly decorated surfaces with millions of triangles in real-time.


Disordered hyperuniformity in two-dimensional amorphous silica.
Disordered hyperuniformity (DHU) is a recently proposed new state of matter, which has been observed in a variety of classical and quantum many-body systems. DHU systems are characterized by vanishing infinite-wavelength normalized density fluctuations and are endowed with unique novel physical properties. Here, we report the discovery of disordered hyperuniformity in atomic-scale two-dimensional materials, i.e., amorphous silica composed of a single layer of atoms, based on spectral-density analysis of high-resolution transmission electron microscopy images. Moreover, we show via large-scale density functional theory calculations that DHU leads to almost complete closure of the electronic bandgap compared to the crystalline counterpart, making the material effectively a metal. This is in contrast to the conventional wisdom that disorder generally diminishes electronic transport and is due to the unique electron wave localization induced by the topological defects in the DHU state.


Reorienting women's health in low- and middle-income countries: the case of depression and Type 2 diabetes.
Women's health in low- and middle-income countries (LMICs) has historically focused on sexual and reproductive health. However, understanding how women acquire, experience, and treat non-reproductive health conditions, such as non-communicable diseases, has become a fundamental public health concern. Special attention to the social determinants of LMIC women's health can provide socially and culturally relevant knowledge for implementation of policies and programs for women increasingly confronting these 'New Challenge Diseases'. This article uses the example of depression and Type 2 diabetes comorbidity to illustrate how attending to the social determinants of mental and physical health beyond the reproductive years contributes to a more holistic agenda for women's health. For instance, we must address the plurality of experiences that shape women's health from social determinants of depression, such as gendered subjugation within the home and public sphere, to the structural determinants of obesity and diabetes, such as poor access to healthy foods and health care. Attending to the complexities of health and social well-being beyond the reproductive years helps the women's global health agenda capture the full spectrum of health concerns, particularly the chronic and non-communicable conditions that emerge as life expectancy increases.


4-NN-dimethylaminoazobenzene 4'-isothiocyanate, a new chromophoric reagent for protein sequence analysis.
4-NN-Dimethylaminoazobenzene 4'-isothiocyanate was synthesized for the purpose of improving the ease and sensitivity of peptide sequence analysis. The method of 4-NN-dimethylaminoazobenzene 4'-isothiocyanate synthesis, the preparation of 24 4-NN-dimethylaminoazobenzene-4'-thiohydantoins of amino acids and their t.l.c. separation are described. All the thiohydantoins, except those of leucine and isoleucine, could be satisfactorily separated by chromatography on a two-dimensional polyamide sheet. The sensitive azo group permits the detection of 4-NN-dimethylaminoazobenzene-4'-thiohydantoins of amino acids as red spots down to pmol amounts directly on the sheet. A simple sensitive method for sequencing dipeptides and the first two or three N-terminal amino acids of proteins is also reported. The colour change of the spots from purple to blue to red after being exposed to HCl vapour, corresponding to the chemical change from 4-NN-dimethylaminoazobenzene-4' isothiocyanate to the 4-NN-dimethylaminoazobenzene-4'-thiocarbamoyl amino acid derivative to the 4-NN-dimethylaminoazobenzene-4'-thiohydantoin amino acid derivative, reveals a very interesting and valuable feature of this reagent.


Evaluation of age-appropriate firearm safety interventions.
The purpose of this study was to determine if firearm safety training increased the knowledge of school-age children about gun safety. It was predicted that children's knowledge, attitudes, and feelings about firearm safety would be impacted by the method used to teach the key firearm safety constructs. The specific aim was to test the effects of 3 levels of firearm safety training on school-age children's knowledge about gun safety. The hypothesis was that children who attended a firearm injury prevention program that used a scripted discussion, psychomotor exercise, and a role-playing exercise about firearm safety would have greater knowledge about firearm safety. A quasi-experimental pretest-posttest randomized complete block design was used. There were 57 participants, 58% were male and the mean age was 5.89 years. A pictorial tool was used to assess kindergarten and first-grade students' baseline and postintervention knowledge of firearm safety. Knowledge increased in all of the intervention groups [F(3,53) = 6.69, P = 0.001]. The greatest increase in knowledge occurred in the scripted discussion/psychomotor exercise group which exhibited an 81% increase in knowledge from the pretest to the posttest. There was no change in the control group's knowledge from pretest to posttest (P = 0.3). This study provides evidence that children do retain firearm safety training. The long-term objective of this research is to reduce the incidence of firearm injuries during childhood by teaching children how to be safe around guns.


The influence of dentures on nasalance values in speech.
The purpose of this study was to investigate the effects of maxillary dentures on nasalance values in normal elderly individuals. A three-factor within-subjects experimental design was employed to analyze the nasalance scores obtained. Twenty English-speaking women aged 61 to 81 years, who wore complete maxillary dentures, participated in the study. A Nasometer was used to collect nasalance data. Participants read three standard passages aloud, three times each, in two conditions: with and without their maxillary dentures. Results revealed that nasalance values were significantly lower with the maxillary dentures removed (p<.01), although the difference in nasalance between the two denture conditions averaged no more than 2%. Nasalance scores obtained both with and without maxillary dentures fell within one standard deviation of the mean for a reference group of comparably aged English-speaking women. The results suggest that the existing collection of normal reference data for nasalance may be safely used for elderly individuals regardless of their status with respect to natural or prosthetic maxillary dentition.


Quantitative studies on concanavalin A-induced, TCGF-reactive T cells. I. Correlation between proliferation and lectin-dependent cytolytic activity.
A limiting dilution assay was used to determine the frequencies of T cells that could be induced to proliferate and kill by Con A and TCGF. The frequency of proliferating cells was 1 in 5 nylon wool-purified spleen cells and 1 in 7 normal lymph node cells. The frequencies in the same cell populations of lectin-dependent killer cell precursors were 1 in 5 and 1 in 9, respectively. Even at limiting numbers of T cells seeded per culture, very few cultures proliferated without showing cytotoxic activity. Thus, under these conditions Con A and TCGF, preferentially if not exclusively, activate T cells that will kill in the presence of PHA. This experimental system can be used for estimating the repertoires of specific CTL-precursors activated by Con A and expanded in TCGF.


Reintervention rates following bioprosthetic surgical aortic valve replacement-a Danish Nationwide Cohort Study.
Updated European guidelines recommend annual echocardiographic evaluation after bioprosthetic surgical aortic valve replacement (bio-SAVR). Given the increased demand on health care resources, only clinically relevant controls can be prioritized. We therefore aimed to explore reintervention rates following bio-SAVR. From the nationwide Danish Register of Surgical Procedures, we identified all patients ≥40 years with isolated bio-SAVR ± concomitant coronary artery bypass graft surgery (CABG) during 2000-2016. In 90-day reintervention-free survivors, we assessed aortic valve reintervention rates (primary outcome) and all-cause mortality rates (secondary outcome) at 1, 3 and 5 years with total follow-up until 31 December 2017 and further estimated annual theoretical echocardiographic control visits. In 10 518 patients with bio-SAVR (+CABG 39.7%), we observed low reintervention rates at 1, 3 and 5 years, but with high rates of all-cause mortality; i.e. 5-year reintervention rate of 3.7/1000 person-years (≤1.5%) and 5-year mortality rate of 21.7/1000 person-years. Accounting for the competing risk of death, 5-year rates were inversely related to age group and remained relatively low across all age categories but increased gradually in the long term. A significant proportion of reinterventions were presumed due to infectious endocarditis (48% at 3 years, 37% at 5 years). With annual transthoracic echocardiography, the theoretical ratio of echocardiographies per reintervention in the first 5 years was 248, and 425 when endocarditis events were excluded. Reintervention rates within the first 5 years following bio-SAVR were relatively rare, and with a substantial number due to endocarditis.


Breastfeeding Practices Among Mothers of Children With Orofacial Clefts in an African Cohort.
To carry out a survey of breastfeeding practices and related challenges among mothers with orofacial cleft babies attending the cleft clinic of a tertiary health institution. This was a cross-sectional descriptive study using an interviewer-administered questionnaire. Sample population was all mothers of babies aged between 1 and 18 months with nonsyndromic orofacial clefts attending the cleft clinic of a tertiary health institution in Nigeria. A total of 65 mothers participated in the study. Initiation of breastfeeding was reported by the majority (83%, n = 54) of the mothers, and only 18.5% (n = 10) of this proportion continued exclusive breastfeeding. Inability of the babies to suck was reported by 46% (n = 30) of the mothers as being the most important challenge in breastfeeding. There was a significant correlation between the type of cleft and challenge in breastfeeding (Fisher exact P = .001). Sixty-three percent (n = 41) of the mothers reported they received no counseling on overcoming challenges associated with feeding their babies with a cleft at the facility where they delivered. Sixty-nine percent (n = 45) reported they first received nutritional information from the cleft clinic at presentation. The most adopted substitute for breastfeeding was the use of regular feeding bottles (n = 24, 43.6%). Rate of initiation of breastfeeding for children with orofacial clefts in this African cohort is higher than reported in other populations despite the low level of nutritional counseling of the mothers after delivery.


Is the U.S. Environmental Protection Agency brownfields assessment pilot program environmentally just?
In the early 1990s, the U.S. Environmental Protection Agency (U.S. EPA) started a grant program to assist communities redevelop brownfields, which are abandoned or underutilized sites that have real or perceived contamination. In addition to determining if the communities receiving the grants were the most distressed cities in the United States, we also evaluate the U.S. EPA program in terms of environmental justice at the macro scale. Using 1990 U.S. Census of Housing and Population data and a matched-cities methodology, we compared the brownfields pilot cities to other communities in the United States. We found that regardless of intent, the U.S. EPA program is environmentally just by disproportionately awarding grants to the most economically distressed cities. We also found that the cities that received funding in the early years of the program were more economically distressed than cities receiving the funding more recently.


Steroid-induced short term diabetes in chick embryo: reversible effects of insulin on metabolic changes and cataract formation.
To determine the reversible effect of insulin on glucocorticoid (GC)-induced cataract formation in relation to systemic metabolic changes in the developing chick embryo. Hydrocortisone sodium succinate (HC; 0.25 micromoles) was administered to 15-day-old embryos followed by administration of long-acting recombinant human insulin, 4 and 28 hours later. At the indicated time after HC administration, the incidence of cataractous lenses and any changes in the components of the lenses, liver, and blood were determined. At 48 hours after HC administration, the following observations were made: opacification of lenses; an elevation of glucose and lipids in the blood and lenses; an increase in lipid peroxide (LPO) in the blood, liver, and lenses; a decrease in glutathione (GSH) in the lens and liver (at 24 hours after HC administration); and a depletion of adenosine triphosphate (ATP) in the liver. These changes in response to HC administration were reversed by a double application of insulin. Insulin antagonizes GC-induced gluconeogenesis, stimulates glycolysis, and ultimately leads to recovery of decreased activity in the citric acid cycle. The restoration of ATP by the recovered citric acid cycle may facilitate de novo synthesis of GSH, which in turn may diminish GC-induced elevation of LPO in the liver. Thus, the metabolic changes in response to HC-accelerated gluconeogenesis in the liver, which can be reversed by insulin, are likely to produce oxidative stress that leads to cataract formation. GC-induced metabolic changes in the liver, which are antagonized by insulin, may relate to production of one of the risk factors for cataract formation.


The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer.
The purpose of the study was to investigate the prognostic value and clinicopathological correlate of tumor p53, p16 and Rb protein expression in patients with locally advanced urinary bladder cancer. Sixty-five patients (44 men and 21 women; 40 to 84 yrs old) with locally advanced urinary bladder cancer (21 pT2, 27pT3, 17pT4) undergoing radical cystectomy and bilateral pelvic lymph node dissection were followed up for 2 to 116 months (mean +/- SD: 30.02 +/- 6.46 months). Immunohistochemical staining for p53, Rb and p16 proteins were performed on surgically obtained, formalin fixed and paraffin embedded tissue sections. Thirty of the tumors (46.2%) were p53+, 52 of the tumors (80%) were p16- and 41 (63%) were Rb-. Only 5 of the tumors (7.7%) had normal expression of all three proteins. The tumor expression status of p53 could not be correlated with p16 (P = 1.000) or Rb (P = 1.000). Only a marginal inverse relationship was found between the expression of p16 and Rb (P = 0.056). Higher grade tumors had significantly lower percentage of p16 abnormality (P = 0.05), while higher grade (not higher stage) tumors had higher percentage of Rb abnormality (P = 0.0245). Univariate analysis showed that tumor expression of Rb or p16, alone or combined, had no predictive value on progression-free and disease-specific survival. It did, however, show a significant correlation between progression-free survival and tumor p53 and LN status (P = 0.032 and P = 0.0304) and a significant correlation between tumor stage disease-specific survival (P = 0.042). Multivariate analysis showed tumor stage and nodal status to be two significant independent indicators for progression-free survival (P = 0.0038 and P = 0.0049) and disease-specific survival (P = 0.0066 and P = 0.0484). It was also noteworthy that, after receiving postoperative adjuvant systemic M-VEC chemotherapy, patients with node-positive p53-normal tumors had significantly better progression-free and disease-specific survivals than those with node-positive p53-abnormal tumors (P = 0.036 and P = 0.0479, respectively). This study has found tumor expression of p53, p16 and Rb proteins in locally advanced bladder cancer to be frequently abnormal. Although multivariate analysis showed tumor stage and nodal status to be the only two statistically significant parameters, p53 may also serve as an additional prognostic predictor of the outcome of postoperative adjuvant systemic chemotherapy in patients with regional lymph node tumor involvement. Such patients with p53-normal tumors experienced significantly better progression-free and disease-specific survivals than those with p53-abnormal tumors.


Developmental trajectories for children with dyslexia and low IQ poor readers.
Reading difficulties are found in children with both high and low IQ and it is now clear that both groups exhibit difficulties in phonological processing. Here, we apply the developmental trajectories approach, a new methodology developed for studying language and cognitive impairments in developmental disorders, to both poor reader groups. The trajectory methodology enables identification of atypical versus delayed development in datasets gathered using group matching designs. Regarding the cognitive predictors of reading, which here are phonological awareness, phonological short-term memory (PSTM) and rapid automatized naming (RAN), the method showed that trajectories for the two groups diverged markedly. Children with dyslexia showed atypical development in phonological awareness, while low IQ poor readers showed developmental delay. Low IQ poor readers showed atypical PSTM and RAN development, but children with dyslexia showed developmental delay. These divergent trajectories may have important ramifications for supporting each type of poor reader, although all poor readers showed weakness in all areas. Regarding auditory processing, the developmental trajectories were very similar for the two poor reader groups. However, children with dyslexia demonstrated developmental delay for auditory discrimination of Duration, while the low IQ children showed atypical development on this measure. The data show that, regardless of IQ, poor readers have developmental trajectories that differ from typically developing children. The trajectories approach enables differences in trajectory classification to be identified across poor reader group, as well as specifying the individual nature of these trajectories. (PsycINFO Database Record


Lichen sclerosus: a review of literature and a case of an atypic surgical treatment.
Lichen sclerosus is a chronic immuno-mediated skin disease of the genital region in men and women. The treatment may be pharmacological or surgical, the choice depending on the extension of the involved area, the histological pattern and the level of functional disease complained by the patient. If the biopsy is negative for neoplastic degeneration the treatment may be pharmacological only. In our paper, we describe the case of a patient with vulvar disease and labial fusion, burial of the clitoris and severe introital stenosis. In this case, the treatment was surgical.


Perioperative surgery- and anaesthesia-related risks of laparoscopic Roux-en-Y gastric bypass - a single centre, retrospective data analysis.
Conservative obesity treatment often leads to limited results. Bariatric surgery is highly efficient, but the candidates are at risk of developing perioperative complications. Bariatric outcomes have been well described in the past, but there are only few reports of perioperative outcomes. The aim of this study was to evaluate the incidence of anaesthetic and surgical complications of Roux-en-Y bypass. Data of all adult patients, who underwent primary Roux-en-Y gastric bypass surgery between 1/2006 and 12/2013 at the University Hospital Zurich were analysed. Using our clinical database, anaesthetic and surgical complications during the first 30 days after surgery were analysed and risk factors determined by multivariate analysis. Seven hundred eleven patients (72% female, median age 40 years) were analysed. Overall, surgical complications occurred in 34% patient, while complications attributable to anaesthesia occurred in 37%. Post-operative nausea and vomiting (PONV) were observed in 34%, intubation-related complications in 4%, and delayed extubation in 2% of our patients. Within the first 30 days after surgery, 22% of the patients presented with an infection. Gastrointestinal complications were found in 8%, and bleeding complications in 3%. Anaesthesia complications were less common in older patients and in patients anaesthetized with a volatile anaesthetic. Severe complications were more common in patients with a lower body mass index (BMI) and with longer surgery. The risk to develop a postoperative infection was higher in diabetic patients. Roux-en-Y bariatric surgery has few anaesthetic complications, the most common is PONV. PONV is more common in younger patients and not more common with volatile anaesthetics. Major complications are overall rare and occur in patients with lower BMI and longer surgery, likely reflecting more difficult procedures.


Unrecognized impact of a biocontrol agent on the spread rate of an invasive thistle.
Herbivores may significantly reduce plant populations by reducing seed set; however, we know little of their impact on seed movement. We show for the first time that the receptacle-feeding weevil Rhinocyllus conicus not only reduces seed production by the invasive thistle Carduus nutans but also inhibits release and subsequent wind dispersal of seeds. These effects generate large, though different, impacts on spatial spread and local abundance in two populations with differing demography, located in the United States and New Zealand. Furthermore, the mechanism is context dependent, with the largest effects through increased terminal velocity in the United States but through reduced seed production in New Zealand. Our results show that the benefit of biocontrol programs may have been underestimated; screenings of potential biocontrol agents should examine effects on pest dispersal and spread, as well as on abundance.


Genome and polypeptides characterization of Tellina virus 1 reveals a fifth genetic cluster in the Birnaviridae family.
We characterized tellina virus 1 (TV-1), a birnavirus isolated from the marine bivalve mollusk Tellina tenuis. Genome sequence analysis established that TV-1 is representative of a viral cluster distant from other birnaviruses. The maturation process of the polyprotein encoded by the genomic segment A was delineated with the identification of the N-termini of the viral protease VP4 and the ribonucleoprotein VP3, and the characterization of peptides deriving from the processing of pVP2, the VP2 capsid protein precursor. One of these peptides was shown to possess a membrane-disrupting domain. Like the blotched snakehead virus, the polyprotein exhibits a non-structural polypeptide (named [X]) located between pVP2 and VP4. Mutagenesis analysis allowed the identification in VP4 of a catalytic Ser-Lys dyad that does not possess the common Gly-X-Ser signature of the serine hydrolases. The genomic segment B encodes the viral RNA-dependent RNA-polymerase VP1 with the unique sequence motif arrangement identified in other birnavirus VP1s.


Regulation of cancer metabolism by oncogenes and tumor suppressors.
Cell proliferation requires the coordination of multiple signaling pathways as well as the provision of metabolic substrates. Nutrients are required to generate such building blocks and their form of utilization differs to significant extents between malignant tissues and their nontransformed counterparts. Thus, oncogenes and tumor suppressor genes regulate the proliferation of cancer cells also by controlling their metabolism. Here, we discuss the central anabolic functions of the signaling pathways emanating from mammalian target of rapamycin, MYC, and hypoxia-inducible factor-1. Moreover, we analyze how oncogenic proteins like phosphoinositide-3-kinase, AKT, and RAS, tumor suppressors such as phosphatase and tensin homolog, retinoblastoma, and p53, as well as other factors associated with the proliferation or survival of cancer cells, such as NF-κB, regulate cellular metabolism.


[Discovery and electron microscopic observation on unusual intranuclear inclusion bodies of breast carcinoma].
Unusual intranuclear inclusion bodies in one case of breast carcinoma discovered and studied by electron microscope is reported. The ultrastructural feature of these inclusion bodies is very characteristic and has not been reported previously. They presented with unequal sizes, location at the margin of nuclei, and frequent separation from the nuclear chromatin by a single thin membrane. These inclusion bodies can be divided into two kinds: one with granular central portion surrounded by numerous radiating flagella-like filaments, the other assuming concentric laminated arrangements. There are transitional forms between them. The nature of these intranuclear inclusion bodies are discussed.


Serum vaspin level as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty.
This study is all about predicting the value of serum vaspin level in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty (LVBG). A total of 164 patients (from January 2012 to May 2015) with severe obesity were chosen and performed LVBG. Enzyme-linked immunosorbent assay was performed to detect the serum vaspin level. The patients were given a biochemical automatic analyzer to measure the biochemical indicators. Homeostasis model assessment (HOMA) helps in the calculation of fasting insulin level (FINS) and insulin resistance (IR). The changes in fatty liver were examined by computed tomography (CT). Receiver operating characteristic curve is used to increase the predictive value of serum vaspin level in the amelioration of liver function and disturbances in the metabolism. Weight, BMI, waist circumference, serum vaspin level, and triglyceride (TG) decreased, but CT value of liver increased at 4th, 7th, and 12th month after surgery. After the 7th and 12th month period of surgery, the alanine aminotransferase, aspartate aminotransferase, FINS, and HOMA-IR reduced in the patients (P <.005). The area under ROC curve (AUC) is about 0.871 ± 0.031 with 95%CI of 0.810-0.931 (P <.001). The sensitivity, specificity, and accuracy of serum vaspin level ≤0.9 were 87.80%, 78.05%, and 83.28%, respectively. BMI, FINS, and serum vaspin level ≤0.9 were the influencing factors of the amelioration of fatty liver and metabolic disturbance. This study proves that the serum vaspin level serves as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after LVBG.


Arterial stiffness in symptomatic smokers with normal lung function.
Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular morbidity and mortality. Arterial stiffness and endothelial dysfunction index are validated surrogate cardiovascular markers and are increased in subjects with COPD. We tested whether increased arterial stiffness and endothelial dysfunction occur in symptomatic smokers with no evidence of bronchial obstruction. Clinical and lung functional assessments were conducted in smoker subjects with chronic respiratory symptoms and in COPD patients. Pulse wave velocity (PWV), aortic augmentation index (AIx) and reactive hyperaemia index (RHI) were measured to estimate the cardiovascular risk. 48 smokers (male n=37, female n=11; mean age 70±8.4 years) were studied. Smokers with respiratory symptoms without bronchial obstruction (n=13) did not differ from COPD patients (n=35) in terms of mean±sd PWV (12±3.2 m·s-1versus 14±3.8 m·s-1; p=0.10), aortic AIx (25.2±11.8% versus 24.8±9.7%, p=0.89) and RHI (1.66±1.49 versus 1.62±1.43; p=0.79). The current investigation shows that the cardiovascular risk occurs in smokers with respiratory symptoms in the absence of bronchial obstruction. These findings need to be confirmed in larger populations in order to inform the design of intensive preventive programmes.


Development and evaluation of evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will fall: case-control and cohort studies.
To identify clinical characteristics of elderly inpatients that predict their chance of falling (phase 1) and to use these characteristics to derive a risk assessment tool and to evaluate its power in predicting falls (phases 2 and 3). Phase 1: a prospective case-control study. Phases 2 and 3: prospective evaluations of the derived risk assessment tool in predicting falls in two cohorts. Elderly care units of St Thomas's Hospital (phase 1 and 2) and Kent and Canterbury Hospital (phase 3). Elderly hospital inpatients (aged > or = 65 years): 116 cases and 116 controls in phase 1,217 patients in phase 2, and 331 in phase 3. 21 separate clinical characteristics were assessed in phase 1, including the abbreviated mental test score, modified Barthel index, a transfer and mobility score obtained by combining the transfer and mobility sections of the Barthel index, and several nursing judgements. In phase 1 five factors were independently associated with a higher risk of falls: fall as a presenting complaint (odds ratio 4.64 (95% confidence interval 2.59 to 8.33); a transfer and mobility score of 3 or 4 (2.10 (1.22 to 3.61)); and primary nurses' judgment that a patient was agitated (20.9 (9.62 to 45.62)), needed frequent toileting (2.48 (1.08 to 5.70)), and was visually impaired (3.56 (1.26 to 10.05)). A risk assessment score (range 0-5) was derived by scoring one point for each of these five factors. In phases 2 and 3 a risk assessment score > 2 was used to define high risk: the sensitivity and specificity of the score to predict falls during the following week was 93% and 88% respectively in phase 2 and 92% and 68% respectively in phase 3. This simple risk assessment tool predicted with clinically useful sensitivity and specificity a high percentage of falls among elderly hospital inpatients.


Radiographic evaluation of foot osteoarthritis: sensitivity of radiographic variables and relationship to symptoms.
To evaluate a radiographic atlas for grading foot osteoarthritis (OA) in relation to the relative sensitivity of different radiographic and views and features, and to examine the relationship between radiographic OA and foot symptoms. Weightbearing dorso-plantar (DP) and lateral foot radiographs were obtained from 197 people (126 women and 71 men) aged 62-94 years (mean age 75.9, standard deviation [SD] 6.6). The prevalence of OA in five joints (the first metatarsophalangeal joint [1st MPJ], the first cuneo-metatarsal joint [1st CMJ], the second cuneo-metatarsal joint [2nd CMJ], the navicular-first cuneiform joint [N1st CJ] and the talo-navicular joint [TNJ]) was then determined using both views in combination (as recommended in the atlas), or by using either view in isolation. Associations between radiographic OA in individual foot joints and symptoms were then explored. Joint-specific prevalence of OA using both DP and lateral views was 1st MPJ (42.4%), 1st CMJ (22.6%), 2nd CMJ (60.2%), N1st CJ (39.1%) and TNJ (32.7%). Using only the DP view detected almost all cases of 1st MPJ OA (94.6%), however, the sensitivity was lower for the other joints (31.0-60.7%). Using only the lateral view detected almost all cases of OA (83.8 to 86.9%), with the exception of the 1st MPJ and 1st CMJ (50.9% and 60.7%, respectively). Using either osteophytes (OP) alone or joint space narrowing (JSN) alone showed low sensitivity for all joints (14.3-63.0%), with the exception of OP alone in the DP view for the 1st MPJ and JSN in the lateral view for the 2nd CMJ (83.8% and 84.0%, respectively). Radiographic OA in individual foot joints and the total number of joints affected were both moderately associated with foot symptoms. Epidemiological and clinical studies should incorporate observation of both OP and JSN from both DP and lateral views to determine the presence of OA in the foot, as the number of cases detected is reduced if only one radiographic feature or view is used. Radiographic foot OA is common in older people and is moderately associated with foot symptoms.


Single versus two-incision arthroscopic anterior cruciate ligament reconstruction.
The purpose of this study was to compare single (endoscopic) versus two-incision arthroscopic anterior cruciate ligament reconstruction using bone-patellar tendon-bone in a population of young athletes. All patients followed a similar postoperative rehabilitation program. The Lysholm knee score, the International Knee Documentation Committee Score, KT-1000 arthrometric measurements, Lachman tests, pivot shift tests, isokinetic and functional testing, and perioperative complications were used to compare the two techniques. Anteroposterior and lateral radiographs were also evaluated and compared. Group I comprised 51 patients who underwent two-incision arthroscopic ACL reconstruction. The average age was 19.8 years, with a range of 18 to 22. The average follow-up in this group was 31 months (range, 24 to 43 months). Group II, the endoscopic group, consisted of 31 patients with an average age of 19.4 years (range, 18 to 22). The average follow-up was 25 months (range, 24 to 31 months). There were no significant differences between the two groups using subjective, objective, and functional criteria. There did appear to be a trend toward a residual pivot glide in the endoscopic group, but this did not achieve statistical significance. Radiographic analysis demonstrated an increased incidence of screw divergence in the endoscopic group. Intraoperative complications were more common with the endoscopic method.


Can HbA1c detect undiagnosed diabetes in acute medical hospital admissions?
To study hyperglycaemia in acute medical admissions to Irish regional hospital. From 2005 to 2007, 2061 white Caucasians, aged >18 years, were admitted by 1/7 physicians. Those with diabetes symptoms/complications but no previous record of hyperglycaemia (n=390), underwent OGTT with concurrent HbA1c in representative subgroup (n=148). Comparable data were obtained for 108 primary care patients at risk of diabetes. Diabetes was diagnosed immediately by routine practice in 1% (22/2061) [aged 36 (26-61) years (median IQ range)/55% (12/22) male] with pre-existing diabetes/dysglycaemia present in 19% (390/2061) [69 (58-80) years/60% (235/390) male]. Possible diabetes symptoms/complications were identified in 19% [70 (59-79) years/57% (223/390) male] with their HbA1c similar to primary care patients [54 (46-61) years], 5.7 (5.3-6.0)%/39 (34-42)mmol/mol (n=148) vs 5.7 (5.4-6.1)%/39 (36-43)mmol/mol, p=0.35, but lower than those diagnosed on admission, 10.2 (7.4-13.3)%/88 (57-122)mmol/mol, p<0.001. Their fasting plasma glucose (FPG) was similar to primary care patients, 5.2 (4.8-5.7) vs 5.2 (4.8-5.9) mmol/L, p=0.65, but 2hPG higher, 9.0 (7.3-11.4) vs 5.5 (4.4-7.5), p<0.001. HbA1c identified diabetes in 10% (15/148) with 14 confirmed on OGTT but overall 32% (48/148) were in diabetic range on OGTT. The specificity of HbA1c in 2061 admissions was similar to primary care, 99% vs 96%, p=0.20, but sensitivity lower, 38% vs 93%, p<0.001 (63% on FPG/23% on 2hPG, p=0.037, in those with possible symptoms/complications). HbA1c can play a diagnostic role in acute medicine as it diagnosed another 2% of admissions with diabetes but the discrepancy in sensitivity shows that it does not reflect transient/acute hyperglycaemia resulting from the acute medical event.


Oxygen dependence of mitochondrial function in isolated rat cardiac myocytes.
The O2 dependence of respiratory functions was studied in suspensions of isolated rat cardiac myocytes. Direct optical spectroscopy of the oxidation of cytochromes and oxygenation of Mb showed that cytochrome alpha 3 oxidation measured at 445-460 nm parallels Mb oxygenation; half-maximal values were at 8.0 and 8.5 microM, respectively. Thus there appears to be a close functional relationship between these components in the cells. The values are very high relative to comparable values for cytochrome alpha 3 oxidation in isolated rat heart mitochondria under state 3 conditions (0.43 microM) and isolated rat heart Mb (2.8 microM). Moreover, the measured values for half-maximal oxidation of cytochromes and oxygenation of Mb in the cells are sensitive to factors that alter the O2 consumption rate of the cells. These results indicate that mitochondrial respiration results in establishment of a gradient of O2 concentration from the suspending medium to the mitochondrial inner membrane. A portion of this gradient is between the suspending medium and the region occupied by Mb, and the remainder is between the region occupied by Mb and the inner mitochondrial membrane. The intracellular O2 gradient is an important factor in determining the O2 dependence of mitochondria in cells and hence may contribute to the O2 dependence of cardiac myocyte function in vivo.


Somatic lamins in germinal vesicles of goldfish (Carassius auratus) vitellogenic oocytes.
In fish and amphibians, B-type lamins are divided into somatic (B1, B2) and oocyte-type (B3) lamins. In this study, we purified nuclear lamins from rainbow trout erythrocytes, raised an anti-lamin monoclonal antibody (L-200) that recognizes goldfish somatic-lamins, and isolated cDNAs encoding goldfish B-type lamins (B1 and B2) from a goldfish cell culture cDNA library. Goldfish B-type lamins are structurally similar to lamins found in other vertebrates with minor amino acid substitutions in the conserved region. Western blot analysis showed that goldfish oocytes contained mainly GV-lamin B3 as well as some somatic lamins. Laser-confocal microscope observations revealed that lamin B3 was present only in GV nuclear lamina, whereas somatic lamins were present in dense fibrillar structures throughout nuclear gels of isolated GVs. Similar nuclear filamentous structures were also observed in GVs of paraffin embedded oocytes. Epitope mapping indicated that L-200 recognized a conserved region containing a short stretch of the alpha-helix coiled-coil rod domain (Y(E/Q)(Q/E)LL). A similar motif is also present in other cytoplasmic intermediate filaments (i.e., vimentin, desmin, peripherin and GFAP). Taken together, these findings suggest that lamins or lamin-related intermediate filaments are an important component of the interior architecture of goldfish vitellogenic oocyte nuclei (GVs).


Overexpression of sweet pepper glycerol-3-phosphate acyltransferase gene enhanced thermotolerance of photosynthetic apparatus in transgenic tobacco.
In order to investigate the relationship between the lipid composition in thylakoid membrane and thermostability of photosynthetic apparatus, tobacco transformed with sweet pepper sense glycerol-3-phosphate acyltransferase (GPAT) gene were used to analyze the lipid composition in thylakoid membrane, the net photosynthetic rate and chlorophyll fluorescence parameters under high temperature stress. The results showed that the saturated extent of monogalactosyldiacylglycerol (MGDG), sulfoquinovosyldiacylglycerol, digalactosyldiacylglycerol and phosphatidylglycerol in thylakoid membrane of transgenic tobacco T(1) lines increased generally. Particularly, the saturated extent in MGDG increased obviously by 16.2% and 12.0% in T(1)-2 and T(1)-1, respectively. With stress temperature elevating, the maximum efficiency of photosystem II (PSII) photochemistry (Fv/Fm), actual photochemical efficiency of PSII in the light (Phi(PSII)) and net photosynthetic rate (Pn) of the two lines and wild type tobacco plants decreased gradually, but those parameters decreased much less in transgenic plants. Even though the recovery process appeared differently in the donor and acceptor side of PSII in transgenic tobacco compared with wild-type plants, the entire capability of PSII recovered faster in transgenic tobacco, which was shown in the parameters of PI, Fv/Fm and Phi(PSII), as a result, the recovery of Pn was accelerated. Conclusively, we proposed that the increase in saturated extent of thylakoid membrane lipids in transgenic plants enhanced the stability of photosynthetic apparatus under high temperature stress.


An antisense RNA in a lytic cyanophage links psbA to a gene encoding a homing endonuclease.
Cyanophage genomes frequently possess the psbA gene, encoding the D1 polypeptide of photosystem II. This protein is believed to maintain host photosynthetic capacity during infection and enhance phage fitness under high-light conditions. Although the first documented cyanophage-encoded psbA gene contained a group I intron, this feature has not been widely reported since, despite a plethora of new sequences becoming available. In this study, we show that in cyanophage S-PM2, this intron is spliced during the entire infection cycle. Furthermore, we report the widespread occurrence of psbA introns in marine metagenomic libraries, and with psbA often adjacent to a homing endonuclease (HE). Bioinformatic analysis of the intergenic region between psbA and the adjacent HE gene F-CphI in S-PM2 showed the presence of an antisense RNA (asRNA) connecting these two separate genetic elements. The asRNA is co-regulated with psbA and F-CphI, suggesting its involvement with their expression. Analysis of scaffolds from global ocean survey datasets shows this asRNA to be commonly associated with the 3' end of cyanophage psbA genes, implying that this potential mechanism of regulating marine 'viral' photosynthesis is evolutionarily conserved. Although antisense transcription is commonly found in eukaryotic and increasingly also in prokaryotic organisms, there has been no indication for asRNAs in lytic phages so far. We propose that this asRNA also provides a means of preventing the formation of mobile group I introns within cyanophage psbA genes.


Are Kentuckians using advance medical directives?
Findings of a statewide survey indicate that only 9% of Kentucky adults are completing Living Wills and an equal percent are designating Health Care Surrogates. Designed to protect patient's rights of self-determination in treatment decisions and protect physicians and other health care professionals from liability in complying with patient wishes, only 37% of the state's residents know about Kentucky's Living Will and 24% known about the Designation of Health Care Surrogate. In view of the results, it is recommended that educational efforts be undertaken, changes in legislation occur to ease advance medical directive access and use, and that, following customary medical practice, legislation be enacted to provide authorization of family members to serve as substitute health care decision makers for incapacitated patients.


There and back again: The study of mental disorder and terrorist involvement.
For the past 40 years, researchers studied the relationship between mental disorder and terrorist involvement. The literature developed in 4 paradigms, each of which differs in terms of their empirical evidence, the specific mental disorders studied, and their conceptualizations of terrorist involvement. These paradigms have not, however, witnessed linear and incremental improvements upon 1 another. Although 1 paradigm has generally tended to dominate a temporal period, many false assumptions and incorrect interpretations of earlier work permeate into today's discourse. This article provides a history of the study of mental disorders and the terrorist. First, we briefly outline the core fundamental principles of the first 2 paradigms, The article then outlines the core arguments produced by the seminal reviews conducted in Paradigm 3. We highlight how these findings were consistently misinterpreted in subsequent citations. We then highlight recent innovations in the study of terrorism and mental disorder since the various influential literature reviews of 1997-2005. We conclude by outlining how future research in this area may improve in the coming years by broadening our understanding of both terrorist involvement and psychopathology away from simple dichotomous thinking. (PsycINFO Database Record


Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression.
Smoking is an independent risk factor for atherosclerosis, the primary pathogenesis of which is inflammation. We recently reported that cigarette smoke extract (CSE) causes cytosolic and extracellular accumulation of both nuclear (n) and mitochondrial (mt) DNA, which leads to inflammation in human umbilical vein endothelial cells (HUVECs). In this study, we examined whether inflammation induction depends more on cytosolic nDNA or mtDNA, and which chemical constituents of CSE are involved. Acrolein (ACR), methyl vinyl ketone (MVK), and 2-cyclopenten-1-one (CPO) were used in the experiments, as these are the major cytotoxic factors in CSE in various cell types. Stimulation with ACR, MVK, or CPO alone resulted in the accumulation of DNA double-strand breaks (DSBs), but not oxidative DNA damage, accumulation of cytosolic DNA, or increased expression of inflammatory cytokines. Simultaneous administration of all three constituents (ALL) resulted in oxidative DNA damage in both the nucleus and mitochondria, accumulation of DSBs, reduced mitochondrial membrane potential, induction of minority mitochondrial outer membrane permeabilization, accumulation of cytosolic free DNA, and increased expression of inflammatory cytokines such as IL-6 and IL-1α. Treatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, suppressed oxidative DNA damage and the increased expression of IL-6 and IL-1α induced by ALL or CSE. The ALL- or CSE-induced increase in IL-6 expression, but not that of IL-1α, was suppressed by mtDNA depletion. In conclusion, ACR, MVK, and CPO may strongly contribute to CSE-induced inflammation. More importantly, cytosolic free mtDNA is thought to play an important role in IL-6 expression, a central mediator of inflammation.


Evidence of the Elusive Gold-Induced Non-classical Hydrogen Bonding in Aqueous Environments.
The ability of a gold ion to act as a proton acceptor in hydrogen bonding continues to remain an open question. Heavy-atom effects and secondary competitive interactions in gold complexes make it challenging to precisely establish the identity of gold-ion-induced hydrogen bonding via experimental techniques. In such situations, computational chemistry may play an important role. Herein we have performed Born-Oppenheimer molecular dynamics simulations to study the behavior of [Au(CH3)2)]- in bulk and interfacial aqueous environments. The simulation results suggest that the [Au(CH3)2)]- complex forms one and two gold-ion-induced hydrogen bonds with the water molecules in interfacial and bulk environments, respectively. The calculated probabilities of key hydrogen-bonded configurations of [Au(CH3)2)]-, combined distribution functions, and diffusion coefficients further support this unusual hydrogen-bonding interaction. In summary, the present results suggest that gold-ion-induced hydrogen bonding in an actual solvent environment may be feasible. These results will improve our understanding about the role of weak interactions in transition metal complexes and, thus, will have implications in catalysis and supramolecular assemblies.


Gene set-based module discovery decodes cis-regulatory codes governing diverse gene expression across human multiple tissues.
Decoding transcriptional programs governing transcriptomic diversity across human multiple tissues is a major challenge in bioinformatics. To address this problem, a number of computational methods have focused on cis-regulatory codes driving overexpression or underexpression in a single tissue as compared to others. On the other hand, we recently proposed a different approach to mine cis-regulatory codes: starting from gene sets sharing common cis-regulatory motifs, the method screens for expression modules based on expression coherence. However, both approaches seem to be insufficient to capture transcriptional programs that control gene expression in a subset of all samples. Especially, this limitation would be serious when analyzing multiple tissue data. To overcome this limitation, we developed a new module discovery method termed BEEM (Biclusering-based Extraction of Expression Modules) in order to discover expression modules that are functional in a subset of tissues. We showed that, when applied to expression profiles of human multiple tissues, BEEM finds expression modules missed by two existing approaches that are based on the coherent expression and the single tissue-specific differential expression. From the BEEM results, we obtained new insights into transcriptional programs controlling transcriptomic diversity across various types of tissues. This study introduces BEEM as a powerful tool for decoding regulatory programs from a compendium of gene expression profiles.


Intrauterine volume in pregnancy.
Intrauterine volume, a three-dimensional measure of growth, was evaluated in pregnancy. The ultrasonic method for measurement of volume was investigated for its accuracy and error potentials and then used to collect information on the growth of three volume components, - total intrauterine, intra-amniotic and placental volume, in the latter half of normal pregnancy. Against reference standards from the normal population, two other main groups, a non-selected and a pre-selected high-risk group, were studied, to test the hypothesis that a small intrauterine volume would predict the presence of a small-for-dates and possibly compromised baby. In previous times main interest in uterine volume had centered on its possible role in parturition. More recently ultrasound had been used to measure intrauterine volume in early pregnancy and a simple ultrasonic method of calculating total intrauterine volume had been used for diagnosing the small-for-dates fetus. The study showed that in a phantom model situation, a method based on serial parallel planimetric area measurements was significantly more accurate than a linear measurement method that assumed the uterine shape to be like a prolate ellipsoid. With the former method 93.3% of measurements were within +/- 5% of the true volume with a mean error of -0.43%. When the method was evaluated for its accuracy in women undergoing midtrimester termination or in women delivering near term, there was good correlation between ultrasonically and directly/indirectly measured intra-amniotic volume suggesting that the same level of accuracy could be expected in pregnancy as found in the phantom models. Intra- and interobserver variation was small. The PPA method was used for all measurements in pregnancy because of its superior accuracy. Data from 115 healthy women with no pregnancy complications were evaluated longitudinally to study normal growth and derive reference standards. Median and mean values for total intrauterine volume increased from around 1,000 ml at 20 weeks to 4,500 ml at 40 weeks. The standard deviation was large at any stage of pregnancy, also for intra-amniotic and placental volume. The rate of volume increase was near constant for total intrauterine and intra-amniotic volumes, except during the period 30-35 weeks, when a faster rise was observed. Placental volume growth decreased after 30 weeks. With growth of total volume following a largely linear trend, a tendency for ranking of volume levels was observed, but predictability of one measurement on the basis of earlier ones weakened with increasing separation of time points.(ABSTRACT TRUNCATED AT 400 WORDS)


The source of nitrogen (NH4+ or NO3-) affects the concentration of oxalate in the shoots and the growth of Atriplex nummularia (oldman saltbush).
Atriplex nummularia Lindl. (oldman saltbush) is a halophytic shrub used widely as a forage for ruminant production in saline farming systems. However, it can contain high concentrations of oxalate in the leaves, which may cause calcium deficiency in grazing animals. We hypothesised that supplying NH4+ instead of NO3- to a clone of this species would decrease oxalate concentrations in the shoots, and also decrease plant growth. Oxalate concentrations were measured in plants in the field, and a glasshouse experiment was conducted in which plants were grown with 10mM NO3- or NH4+, with 50, 200 or 500mM NaCl. The field survey showed effects of site (P<0.001), with average oxalate concentrations in shoots varying between 2.4 and 6.4% dry mass (DM). In the glasshouse, oxalate concentrations and plant growth were both affected by N-source and salinity (P<0.001). Averaged across salinities, plants grown with NH4+ for 24 days had only 43% of the shoot DM but 25% of the oxalate concentration of plants grown with NO3-. We discuss the effects of N-source on oxalate concentrations, the implications of this for halophyte growth, and the opportunity to select halophytes with lower oxalate and higher nutritive value for livestock.


Highly selective hydrogenation of amides catalysed by a molybdenum pincer complex: scope and mechanism.
A series of molybdenum pincer complexes has been shown for the first time to be active in the catalytic hydrogenation of amides. Among the tested catalysts, Mo-1a proved to be particularly well suited for the selective C-N hydrogenolysis of N-methylated formanilides. Notably, high chemoselectivity was observed in the presence of certain reducible groups including even other amides. The general catalytic performance as well as selectivity issues could be rationalized taking an anionic Mo(0) as the active species. The interplay between the amide C[double bond, length as m-dash]O reduction and the catalyst poisoning by primary amides accounts for the selective hydrogenation of N-methylated formanilides. The catalyst resting state was found to be a Mo-alkoxo complex formed by reaction with the alcohol product. This species plays two opposed roles - it facilitates the protolytic cleavage of the C-N bond but it encumbers the activation of hydrogen.


"Telling tales out of court": a pilot study of experts' disclosures about opposing experts.
A pilot questionnaire surveyed forensic psychiatrists and psychologists about information they would feel it appropriate to disclose to their retaining attorneys about an opposing expert witness. A spectrum of hypothetical disclosures was offered, varying in their relevance to the case at hand and in their degree of "public" versus "personal" information. Respondents agreed significantly that "public" information could be disclosed to one's attorney, but responses about disclosing "personal" information varied widely. The findings and their implications are briefly discussed.


Contrast-Enhanced Ultrasound for Image-Guided Procedures.
Contrast-enhanced ultrasound (CEUS) uses intravenously injected gas microbubbles as a pure blood pool contrast agent to demonstrate blood flow and tissue perfusion at a much higher sensitivity than color Doppler and power Doppler ultrasound. CEUS has gained traction in abdominal diagnostic imaging for improved lesion detection and characterization and a complementary problem-solving tool to CT and MRI. In addition to its diagnostic applications, CEUS has also proven useful for pre-procedure planning, procedure guidance, and post-procedure evaluation. This review provides a practical overview and guides to the application of CEUS in percutaneous, ultrasound-guided, needle-driven procedures, focusing on 2 common procedures, which illustrate the many benefits of CEUS- core needle biopsy (CNB) and percutaneous hepatic lesion ablation.