Prognostic performance of preoperative cardiac troponin and perioperative changes in cardiac troponin for the prediction of major adverse cardiac events and mortality in noncardiac surgery: A systematic review and meta-analysis.
Increased postoperative cardiac troponin (cTn) independently predicts short-term mortality. Previous studies suggest that preoperative cTn also predicts major adverse cardiovascular events (MACE) and mortality after noncardiac surgery. The value of preoperative and perioperative changes in cTn as a prognostic tool for adverse outcomes has been sparsely investigated. A systematic review and meta-analysis of the prognostic value of cTns for adverse outcome was conducted. Adverse outcome was defined as short-term (in-hospital or <30 days) and long-term (>30 days) MACE and/or all-cause mortality, in adult patients undergoing noncardiac surgery. The study protocol (CRD42018094773) was registered with an international prospective register of systematic reviews (PROSPERO). Preoperative cTn was a predictor of short- (OR 4.3, 95% CI 2.9-6.5, p<0.001, adjusted OR 5.87, 95% CI 3.24-10.65, p<0.001) and long-term adverse outcome (OR 4.2, 95% CI 1.0-17.3, p = 0.05, adjusted HR 2.0, 95% CI 1.4-3.0, p<0.001). Perioperative change in cTn was a predictor of short-term adverse outcome (OR 10.1, 95% CI 3.2-32.3, p<0.001). It was not possible to conduct pooled analyses for adjusted estimates of perioperative change in cTn as predictor of short- (a single study identified) and long-term (no studies identified) adverse outcome. Further, it was not possible to conduct pooled analyses for unadjusted estimates of perioperative change in cTn as predictor of long-term adverse outcome, since only one study was identified. Bivariate analysis of sensitivities and specificities were performed, and overall prognostic performance was summarized using summary receiver operating characteristic (SROC) curves. The pooled sensitivity and specificity for preoperative cTn and short-term adverse outcome was 0.43 and 0.86 respectively (area under the SROC curve of 0.68). There were insufficient studies to construct SROCs for perioperative changes in cTn and for long-term adverse outcome. Our study indicates that although preoperative cTn and perioperative change in cTn might be valuable predictors of MACE and/or all-cause mortality in adult noncardiac surgical patients, its overall prognostic performance remains uncertain. Future large, representative, high-quality studies are needed to establish the potential role of cTns in perioperative cardiac risk stratification.


Genes, behavior and next-generation RNA sequencing.
Advances in next-generation sequencing suggest that RNA-Seq is poised to supplant microarray-based approaches for transcriptome analysis. This article briefly reviews the use of microarrays in the brain-behavior context and then illustrates why RNA-Seq is a superior strategy. Compared with microarrays, RNA-Seq has a greater dynamic range, detects both coding and noncoding RNAs, is superior for gene network construction, detects alternative spliced transcripts, detects allele specific expression and can be used to extract genotype information, e.g. nonsynonymous coding single nucleotide polymorphisms. Examples of where RNA-Seq has been used to assess brain gene expression are provided. Despite the advantages of RNA-Seq, some disadvantages remain. These include the high cost of RNA-Seq and the computational complexities associated with data analysis. RNA-Seq embraces the complexity of the transcriptome and provides a mechanism to understand the underlying regulatory code; the potential to inform the brain-behavior relationship is substantial.


Effects of Grazing by Flagellates on Competition for Ammonium between Nitrifying and Heterotrophic Bacteria in Soil Columns.
The enhanced mineralization of immobilized nitrogen by bacteriophagous protozoa has been thought to favor the nitrification process in soils in which nitrifying bacteria must compete with heterotrophic bacteria for the available ammonium. To obtain more insight into this process, the influence of grazing by the flagellate Adriamonas peritocrescens on the competition for ammonium between the chemolithotrophic species Nitrosomonas europaea and the heterotrophic species Arthrobacter globiformis in the presence of Nitrobacter winogradskyi was studied in soil columns, which were continuously percolated with media containing 5 mM ammonium and different amounts of glucose at a dilution rate of 0.007 h (liquid volumes). A. globiformis won the competition for ammonium. The grazing activities of the flagellates had two prominent effects on the competition between N. europaea and A. globiformis. First, the distribution of ammonium over the profile of the soil columns was more uniform in the presence of flagellates than in their absence. In the absence of flagellates, relatively high amounts of ammonium accumulated in the upper layer (0 to 3 cm), whereas in the underlying layers the ammonium concentrations were low. In the presence of flagellates, however, considerable amounts of ammonium were found in the lower layers, whereas less ammonium accumulated in the upper layer. Second, the potential ammonium-oxidizing activity of N. europaea was stimulated in the presence of flagellates. The numbers of N. europaea at different glucose concentrations in the presence of flagellates were comparable to those in the absence of protozoa. However, in the presence of flagellates, the potential ammonium-oxidizing activities were four to five times greater than those in the absence of protozoa.


TOX4 and NOVA1 proteins are partners of the LEDGF PWWP domain and affect HIV-1 replication.
PWWP domains are involved in the chromatin attachment of several proteins. They bind to both DNA and proteins and their interaction with specific histone methylation marks define them as a new class of histone code readers. The lens epithelium derived growth factor (LEDGF/p75) contains an N-terminal PWWP domain necessary for its interaction with chromatin but also a C-terminal domain which interacts with several proteins, such as lentiviral integrases. These two domains confer a chromatin-tethering function to LEDGF/p75 and in the case of lentiviral integrases, this tethering participates in the efficiency and site selectivity of integration. Although proteins interacting with LEDGF/p75 C-terminal domain have been extensively studied, no data exist about partners of its PWWP domain regulating its interaction with chromatin. In this study, we report the identification by yeast-two-hybrid of thirteen potential partners of the LEDGF PWWP domain. Five of these interactions were confirmed in mammalian cells, using both a protein complementation assay and co-immunoprecipitation approaches. Three of these partners interact with full length LEDGF/p75, they are specific for PWWP domains of the HDGF family and they require PWWP amino acids essential for the interaction with chromatin. Among them, the transcription activator TOX4 and the splicing cofactor NOVA1 were selected for a more extensive study. These two proteins or their PWWP interacting regions (PIR) colocalize with LEDGF/p75 in Hela cells and interact in vitro in the presence of DNA. Finally, single round VSV-G pseudotyped HIV-1 but not MLV infection is inhibited in cells overexpressing these two PIRs. The observed inhibition of infection can be attributed to a defect in the integration step. Our data suggest that a regulation of LEDGF interaction with chromatin by cellular partners of its PWWP domain could be involved in several processes linked to LEDGF tethering properties, such as lentiviral integration, DNA repair or transcriptional regulation.


Solid-phase enrichment and analysis of electrophilic natural products.
In search for new natural products, which may lead to the development of new drugs for all kind of applications, novel methods are needed. Here we describe the identification of electrophilic natural products in crude extracts via their reactivity against azide as a nucleophile followed by their subsequent enrichment using a cleavable azide-reactive resin (CARR). Using this approach, natural products carrying epoxides and α,β-unsaturated enones as well as several unknown compounds were identified in crude extracts from entomopathogenic Photorhabdus bacteria.


Evaluating the tuberculosis hazard posed to cattle from wildlife across Europe.
Tuberculosis (TB) caused by infection with Mycobacterium bovis (M. bovis) and other closely related members of the M. tuberculosis complex (MTC) infects many domestic and wildlife species across Europe. Transmission from wildlife species to cattle complicates the control of disease in cattle. By determining the level of TB hazard for which a given wildlife species is responsible, the potential for transmission to the cattle population can be evaluated. We undertook a quantitative review of TB hazard across Europe on a country-by-country basis for cattle and five widely-distributed wildlife species. Cattle posed the greatest current and potential TB hazard other cattle for the majority of countries in Europe. Wild boar posed the greatest hazard of all the wildlife species, indicating that wild boar have the greatest ability to transmit the disease to cattle. The most common host systems for TB hazards in Europe are the cattle-deer-wild boar ones. The cattle-roe deer-wild boar system is found in 10 countries, and the cattle-red deer-wild boar system is found in five countries. The dominance of cattle with respect to the hazards in many regions confirms that intensive surveillance of cattle for TB should play an important role in any TB control programme. The significant contribution that wildlife can make to the TB hazard to cattle is also of concern, given current population and distribution increases of some susceptible wildlife species, especially wild boar and deer, and the paucity of wildlife TB surveillance programmes.


Defining priorities in prognostication research: results of a consensus workshop.
To establish consensus among palliative care researchers on the priorities for prognostication research. A nominal group technique was employed involving palliative care researchers attending a workshop within a scientific meeting on prognostication. Participants worked in small facilitated groups to generate future research questions which were amalgamated and rated according to importance. Twenty-five meeting delegates took part in the workshop including 10 palliative care physicians and four nurses, one dietician, and 10 academic researchers, all of whom had experience and/or interest in prognosis research. A total of 40 research questions were generated and after prioritization ratings, the top five questions were: (1) How valid are prognostic tools? (=2) Can we use prognostic criteria as entry criteria for research? (=2) How do we judge the impact of a prognostic score in clinical practice? (4) What is the best way of presenting survival data to patients? (5) What is the most user-friendly validated tool? Although a wide range of research questions relating to prognostication were identified, the strongest priority to emerge from the consensus data concerned the validity of prognostic tools. Further research to validate existing tools is essential to ensure their clinical value.


Surgical treatment for distal clavicle fracture with coracoclavicular ligament disruption.
Surgical reconstruction is usually indicated for distal clavicle fractures with coracoclavicular ligament disruption due to a high rate of nonunion and delayed union. We report the outcome of a surgical technique for this type of fracture. The procedures consist of coracoclavicular reconstruction with a Mersilene tape, repair of torn coracoclavicular ligament, and wire fixation of the fracture fragments. From 1993 through 1998, this technique has been used on 13 patients with distal clavicle fracture and associated coracoclavicular ligament disruption. Eleven patients with at least 18 months of complete postoperative follow-up were included for functional and radiographic evaluation. After 18 to 48 months' follow-up, the clinical outcome has been encouraging. Solid union of the fracture could be achieved at 3 months after operation in 10 patients. The remaining one fracture achieved bony union at 6 months. Ten patients could return to the same or a higher level of preinjury activity. Good and excellent results were obtained in 10 patients. The advantages of this technique include that the disrupted coracoclavicular articulation is rigidly restored and then the fracture site can be easily reduced and fixed with a wire. This technique allows for stable fixation with early mobilization and early return to work and sports.


Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system.
The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.


Genetic variability in a genomic region with long-range linkage disequilibrium reveals traces of a bottleneck in the history of the European population.
The inference of the demographic history of populations from genetic variability data is not only of academic interest. It also provides background information for the identification of genes which may have played a role in human evolution or in the aetiology of human disease. To obtain a clear picture of this background, it is necessary to compare data obtained from a number of genomic loci. Due to its very low recombination rate, the NF1 gene region can be regarded as a further suitable locus. A combined resequencing and SNP typing project in a European population disclosed the presence of only two well separated subgroups of NF1 sequences. Statistical analysis revealed a bimodal distribution of the pairwise differences, a positive value of Tajima's D and a TMRCA of 700,000 years for the whole sample, and pairwise differences indicative for a growing population and TMRCAs of 130,000 to 150,000 years for the subgroups. Together, the data lead to a model that the recent European population went through a bottleneck during the last 150,000 years of its history. Regarding the given timeframe, this bottleneck could either reflect a speciation event which led to the anatomically modern human (AMH), or a severe reduction of the population size during the emigration of AMHs out of Africa or the immigration into Europe.


Do the genetic or environmental determinants of anxiety and depression change with age? A longitudinal study of Australian twins.
Because the determinants of anxiety and depression in late adolescence and early adulthood may differ from those in later life, we investigated the temporal stability and magnitude of genetic and environmental correlates of symptoms of anxiety and depression across the life span. Data were collected from a population-based Australian sample of 4364 complete twin pairs and 777 singletons aged 20 to 96 years who were followed-up over three studies between 1980 and 1996. Each study contained the 14-item self-report DSSI/sAD scale which was used to measure recently experienced symptoms of anxiety and depression. Symptom scores were then divided and assigned to age intervals according to each subject's age at time of participation. We fitted genetic simplex models to take into account the longitudinal nature of the data. For male anxiety and depression, the best fitting simplex models comprised a single genetic innovation at age 20 which was transmitted, and explained genetic variation in anxiety and depression at ages 30, 40, 50 and 60. Most of the lifetime genetic variation in female anxiety and depression could also be explained by innovations at age 20 which were transmitted to all other ages; however, there were also smaller age-dependent genetic innovations at 30 for anxiety and at 40 and 70 for depression. Although the genetic determinants of anxiety and depression appear relatively stable across the lifespan for males and females, there is some evidence to support additional mid-life and late age gene action in females for depression. The fact that midlife onset for anxiety occurs one decade before depression is also consistent with a causal relationship (anxiety leading to depression) between these conditions. These findings have significance for large scale depression prevention projects.


Secondary overtriage in pediatric trauma: can unnecessary patient transfers be avoided?
In an era of wide regionalization of pediatric trauma systems, interhospital patient transfer is common. Decisions regarding the location of definitive trauma care depend on prehospital destination criteria (primary triage) and interfacility transfers (secondary triage). Secondary overtriage can occur in any resource-limited setting but is not well characterized in pediatric trauma. The National Trauma Data Bank from 2008 to 2011 was queried to identify patients 15 years or younger who were transferred to pediatric trauma centers. Secondary overtriage was defined as meeting all 4 of the following criteria: injury severity score (ISS) less than 9, no need for surgical procedure, no critical care admission, and length of stay of less than 24 hours. All other transfers were deemed appropriate triage. Our definition of secondary overtriage was met in 32,318 patients out of 144,420 transfers (22.4%). Within this group, 37.5% were discharged directly from the emergency department of the receiving hospital without hospital admission. Appropriately triaged patients required a therapeutic procedure in 43.5% of cases. Differences in age, sex, mechanism of injury, and payer status were modest. Secondary overtriage is prevalent in pediatric trauma systems nationwide and is not associated with any particular patient characteristics. Because clinical outcomes and healthcare spending are increasingly scrutinized, secondary overtriage may reflect unnecessary patient transfer and a source of potential cost savings. Development of better guidelines for secondary triage of pediatric trauma patients may enable timely assessment and treatment of children who require a higher level of care while also preventing inefficient use of available resources.


Three-dimensional direct imaging of structural relaxation near the colloidal glass transition
Confocal microscopy was used to directly observe three-dimensional dynamics of particles in colloidal supercooled fluids and colloidal glasses. The fastest particles moved cooperatively; connected clusters of these mobile particles could be identified; and the cluster size distribution, structure, and dynamics were investigated. The characteristic cluster size grew markedly in the supercooled fluid as the glass transition was approached, in agreement with computer simulations; at the glass transition, however, there was a sudden drop in their size. The clusters of fast-moving particles were largest near the alpha-relaxation time scale for supercooled colloidal fluids, but were also present, albeit with a markedly different nature, at shorter beta-relaxation time scales, in both supercooled fluid and glass colloidal phases.


[CYP2C19 gene polymorphism in patients with myocardial infarction who use clopidogrel].
One of the foundations of the modern treatment of myocardial infarction (MI) is a combination antiplatelet therapy consisting of acetylsalicylic acid (ASA) and clopidogrel. Pharmacodynamic and clinical studies have demonstrated that the polymorphism CYP2C19 (CYP2C19*2 allele) is associated with a reduced antiplatelet effect of clopidogrel and an increase in the incidence of severe cardiovascular complications. The study included 97 patients with MI. Coronary angiography was performed with subsequent standard treatment of MI, including stenting of the infarct-related coronary artery. CYP2C19 polymorphism was determined by polymerase chain reaction. At 6months, outcomes were determined. The frequency of allele CYP2C19*2 was 22.7%. We found statistically insignificant differences in the prevalence of CYP2C19 gene polymorphism in different forms of myocardial infarction. In contrast to the authors, who previously published data on the effect of CYP2C19 gene polymorphism on cardiovascular complications, we found no differences according to genotype. CYP2C19 gene polymorphism does not influence the prognosis for the next six months, if to patient follow medical recommendations, including the regular use of clopidogrel.


Nearly two decades using the check-type to prevent ABO incompatible transfusions: one institution's experience.
To detect miscollected (wrong blood in tube [WBIT]) samples, our institution requires a second independently drawn sample (check-type [CT]) on previously untyped, non-group O patients who are likely to require transfusion. During the 17-year period addressed by this report, 94 WBIT errors were detected: 57% by comparison with a historic blood type, 7% by the CT, and 35% by other means. The CT averted 5 potential ABO-incompatible transfusions. Our corrected WBIT error rate is 1 in 3,713 for verified samples tested between 2000 and 2003, the period for which actual number of CTs performed was available. The estimated rate of WBIT for the 17-year period is 1 in 2,262 samples. ABO-incompatible transfusions due to WBIT-type errors are avoided by comparison of current blood type results with a historic type, and the CT is an effective way to create a historic type.


Mutation analysis of the SLC26A4 gene in three Chinese families.
In order to investigate the genetic causes of hearing loss in a Chinese proband (in Family A) with enlarged vestibular aqueduct (EVA) and to investigate the genotype of two Chinese probands with SLC26A4 singe-allelic mutation and normal hearing (in Families B and C, respectively), the three probands and their parents were clinically and genetically evaluated. Twenty exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations via amplification with PCR and bidirectional sequencing. As controls, a group of 400 healthy newborns from the same ethnic background underwent SLC26A4 gene screening using the same method. The three probands all harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. The genotypes of mutations in Families A, B, and C are c.1211C>A/c.919-2A>G, c.1729G>A/c.919-2A>G, and c.1286C>A/c.919-2A>G, respectively. The missense mutations c.1211C>A (p.T430Q) in exon 10 and c.1729G>A (p.V577I) in exon 16 are both reported for the first time and were absent in 400 healthy newborns. c.1211C>A has Glutamine (Gln) at amino acid 430 instead of Threonine (Thr), and c.1729G>A has Isoleucine (Ile) at amino acid 577 instead of Valine (Val). c.1286C>A, a mutation previously reported in DVD and HGMD, was associated with Mondini deformity, but a proband with the c.1286C>A mutation in this study was normal. This study has demonstrated that the novel missense mutation c.1211C>A in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is likely to be the cause of deafness in Family A. A novel variant, c.1729G>A, was identified and is likely benign. The pathogenicity of the c.1286C>A mutation warrants more in-depth study. These findings will broaden the spectrum of known SLC26A4 mutations in the Chinese population, providing more information for genetic counseling and diagnosis of hearing loss with EVA.


The meaning of skilled care providers' relationships with stroke and aphasia patients.
Little is known about the reciprocal influence of communication difficulties on the care relationship. To illuminate care providers' lived experiences of relationships with stroke and aphasia patients, narrative interviews were conducted with providers particularly successful at communicating with patients. A phenomenological hermeneutic analysis of the narratives revealed three themes: Calling forth responsibility through fragility, restoring the patient's dignity, and being in a state of understanding. The analysis disclosed caring with regard to the patient's desire, which has its starting point in intersubjective relationship and interplay, in which nonverbal communication is essential--that is, open participation while meeting the patient as a presence. Thus, care providers prepare for deep fellowship, or communion, by being available. They described an equality with patients, interpreted as fraternity and reciprocity, that is a necessary element in presence as communion. The works of Marcel, Hegel, Stern, and Ricoeur provided the theoretical framework for the interpretation.


Pulmonary cavitary sarcoidosis: clinico-radiologic characteristics and natural history of a rare form of sarcoidosis.
Pulmonary cavitary lesions in the absence of concomitant comorbidities are an uncommon and often confusing manifestation of sarcoidosis. We retrospectively reviewed the clinical and high-resolution computed tomography (HRCT) characteristics and the natural history of a series of 23 patients with pulmonary cavitary lesions found on HRCT extracted from a large cohort of patients with pulmonary sarcoidosis. The estimated prevalence of cavitary sarcoidosis was 2.2%. Cavitary lesions developed in patients with severe and active sarcoidosis (serum angiotensin-converting enzyme [SACE] > or =2 times the upper limit of normal range: 63.6%). Twelve (52.2%) patients had evidence of radiographic stage IV, 9 of whom (75%) had persistently increased SACE. As found on HRCT, cavitary lesions were multiple in 21 patients (91.3%), including 5 patients with 10 or more cavities. The size of cavitary lesions was variable, with a median diameter of 20 mm (range, 11-100 mm). Follow-up was available for 20 patients with a median follow-up of 6.25 years (range, 6 months to 15 years). Seven patients (35%) experienced some type of complication related to cavitary lesions, including 6 episodes of hemoptysis in 5 patients and aspergilloma occurrence in 3 patients. As seen on HRCT, the evolution of the number and size of cavitary lesions was variable, with a complete resolution of the largest cavitary lesion in only 5 patients (25%). During follow-up, wall thickening was always associated with a further infectious complication. In summary, cavitary lesions are rare in pulmonary sarcoidosis and usually occur in active and severe sarcoidosis. Their evolution is unpredictable, and complications are frequent.


SU-E-J-119: Comparative Evaluation of Respiratory Motion-Corrected Cone-Beam CT Images Derived from Treatment-Day Vs. Simulation-Day Respiration-Correlated CT Scans.
Respiration-induced motion artifacts in cone-beam CT (CBCT) can be corrected using a model of patient motion obtained from respiration-correlated CT (RCCT). This approach assumes that respiration-induced organ deformations at simulation, when RCCT scans are normally acquired, are still valid at treatment. The purpose of this study is to compare lung tumor image quality in motion-corrected CBCT images derived from treatment-day RCCT(tx) to simulation-day RCCT(sim) patient images. In an IRB-approved study, lung cancer patients receive an RCCT at simulation, and an RCCT, gated CBCT and 1-minute CBCT at one treatment session. CBCT projections from the 1-minute scan are sorted according to breathing amplitude from an external monitor and reconstructed and warped to obtain a motion-corrected MC-CBCT at end expiration. Motion correction uses a model adapted from either RCCT(tx) or RCCT(sim), thus obtaining MC-CBCT(tx) and MC-CBCT(sim) images respectively. A gated CBCT, in which gantry rotation and projection acquisition occur within a gate at end expiration, serves as ground truth for comparison. Quality of MC-CBCT images is evaluated from tumor-to-background contrast ratio (TBCR) values measured by delineating the tumor and annular volume around it on the gated CBCT then transferring the contours and aligning them to each MC-CBCT. TBCR is found tobe lower in MC-CBCT(sim) images, relative to MC-CBCT(tx), in four out of five patients with mean 21% reduction in a range 9-39%. In the remaining case, where there was no change in TBCR, tumor motion observed in the RCCT was small (2mm). Tumor motion extent relative to diaphragm is observed to change between RCCT(tx) and RCCT(sim) scans. Preliminary results indicate that deformation patterns in lung do change between simulation and treatment. Such variations may reduce the validity of using simulation data for motion-corrected CBCT at treatment. The findings require confirmation with larger numbers of patients. NIH/NCI award R01 CA126993, research grant from Varian Medical Systems.


Surgical outcomes after trauma pneumonectomy: Revisited.
Trauma pneumonectomy has been historically associated with an exceedingly high morbidity and mortality. The recent advent of standardized reporting and data-collecting measures has facilitated large volume data analysis on predictors and outcomes of trauma pneumonectomy. The purpose of this study is to describe patient characteristics and outcomes of the patients who underwent trauma pneumonectomy in the modern era and identify clinical factors associated with postoperative mortality. Data between 2007 and 2014 from the National Trauma Data Bank were used for analysis, which included patients with both blunt and penetrating trauma who underwent pneumonectomy within 24 hours after admission. Patient characteristics, injury data, and outcomes were analyzed. Postoperative survival was estimated using the Kaplan-Meier method. Multivariate logistic regression analysis was performed to identify variables associated with postoperative mortality. A total of 261 patients were included for analysis. Of those, 163 (62.5%) patients sustained penetrating trauma. Less invasive lung resections were performed before pneumonectomy in 12.6% of patients. First 24-hour and in-hospital mortality were significantly higher in blunt trauma patients compared with penetrating trauma patients (54.1% vs. 34.1% and 77.6% vs. 49.1%, respectively; p < 0.01). In our multivariate logistic regression analysis, an admission Glasgow Coma Scale of less than 9 (odds ratio [OR], 2.16, 95% CI: 1.24-3.77, p < 0.01) and associated brain injury (OR, 2.11, 95% CI: 1.01-4.42, p = 0.048) were significantly associated with in-hospital death, whereas penetrating mechanism (OR, 0.36, 95% CI 0.19-0.70, p < 0.01) and less invasive lung resections before pneumonectomy (OR, 0.39, 95% CI: 0.17-0.87, p = 0.02) were significantly associated with survival to hospital discharge. Trauma pneumonectomy remains a highly morbid procedure even in the modern era and should be reserved for carefully selected patients. Prognostic study, level IV.


Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes.
Vascular cell adhesion molecule-1 (VCAM-1), an inducible cell-cell recognition protein on the endothelial cell surface (EC), has been associated with early stages of atherosclerosis. In view of the accelerated vascular disease observed in patients with diabetes, and the enhanced expression of VCAM-1 in diabetic rabbits, we examined whether irreversible advanced glycation endproducts (AGEs), could mediate VCAM-1 expression by interacting with their endothelial cell receptor (receptor for AGE, RAGE). Exposure of cultured human ECs to AGEs induced expression of VCAM-1, increased adhesivity of the monolayer for Molt-4 cells, and was associated with increased levels of VCAM-1 transcripts. The inhibitory effect of anti-RAGE IgG, a truncated form of the receptor (soluble RAGE) or N-acetylcysteine on VCAM-1 expression indicated that AGE-RAGE-induced oxidant stress was central to VCAM-1 induction. Electrophoretic mobility shift assays on nuclear extracts from AGE-treated ECs showed induction of specific DNA binding activity for NF-kB in the VCAM-1 promoter, which was blocked by anti-RAGE IgG or N-acetylcysteine. Soluble VCAM-1 antigen was elevated in human diabetic plasma. These data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes.


Psychopathology and its risk and protective factors in hearing-impaired children and adolescents: a systematic review.
Pediatric hearing impairment is a chronic handicap that can potentially lead to the development of psychopathology. Yet, for hearing-impaired children and adolescents, the exact occurrence of various forms of psychopathology and its causes are unclear, while this knowledge is essential to enable targeted screenings and interventions. To investigate the level of psychopathological symptoms in hearing-impaired children and adolescents as compared with normally hearing peers. Second, the influence of type of hearing device and possible risk and protective factors on psychopathology were examined. A systematic literature search was performed covering relevant databases, including PubMed, Embase, and Web of Science. Two independent researchers identified the relevant articles. The final search was performed on May 2, 2013, and resulted in a total of 35 articles. Literature consistently demonstrated that hearing-impaired children and adolescents were more prone to developing depression, aggression, oppositional defiant disorder, conduct disorder, and psychopathy than their normally hearing peers. Levels of anxiety, somatization, and delinquency were elevated in some, but not all, hearing-impaired participants, for reasons related to sex, age, and type of school. Divergent results were obtained for the level of attention-deficit/hyperactivity disorder and the influence of type of hearing device on psychopathology. Possible risk and protective factors were identified, including age at detection and intervention of hearing loss, additional disabilities, communication skills, intelligence, type of school, and number of siblings. Literature on psychopathology in hearing-impaired children and adolescents is scarce and sometimes inconsistent. To define a more precise occurrence of psychopathology, more studies are needed. These studies should have a longitudinal design to draw firmer conclusions on causality. Hopefully, this will lead to more knowledge in the future to help and support each hearing-impaired individual.


The fallacy of the Principle of Procreative Beneficence.
The claim that we have a moral obligation, where a choice can be made, to bring to birth the 'best' child possible, has been highly controversial for a number of decades. More recently Savulescu has labelled this claim the Principle of Procreative Beneficence. It has been argued that this Principle is problematic in both its reasoning and its implications, most notably in that it places lower moral value on the disabled. Relentless criticism of this proposed moral obligation, however, has been unable, thus far, to discredit this Principle convincingly and as a result its influence shows no sign of abating. I will argue that while criticisms of the implications and detail of the reasoning behind it are well founded, they are unlikely to produce an argument that will ultimately discredit the obligation that the Principle of Procreative Beneficence represents. I believe that what is needed finally and convincingly to reveal the fallacy of this Principle is a critique of its ultimate theoretical foundation, the notion of impersonal harm. In this paper I argue that while the notion of impersonal harm is intuitively very appealing, its plausibility is based entirely on this intuitive appeal and not on sound moral reasoning. I show that there is another plausible explanation for our intuitive response and I believe that this, in conjunction with the other theoretical criticisms that I and others have levelled at this Principle, shows that the Principle of Procreative Beneficence should be rejected.


Beneficial impact of exercise and obesity interventions on erectile function and its risk factors.
Erectile dysfunction (ED) is a multifaceted disease involving cardiovascular, metabolic, and hormonal factors and affects over 100 million men worldwide. ED has been shown to be a harbinger of underlying cardiovascular diseases (CVD), as there are common risk factors (aging, hypertension, obesity) and mechanistic basis. To provide an update on clinical and experimental evidence regarding the impact of lifestyle modifications, such as exercise and diet, with respect to changes in erectile function. Published evidence regarding the impact of aging, hypertension, and obesity on ED and CVD, as well as new experimental data linking obesity and diminished erectile responses. We reviewed the literature regarding common risk factors of ED and CVD, particularly involving obesity, as well as performed new analysis on the findings of other experimental studies involving diet and exercise interventions. Physical inactivity negatively impacts on erectile function, and experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Mediterranean-style diets and a reduction in caloric intake have been found to improve erectile function in men with the aspects of the metabolic syndrome. In addition, both clinical and experimental studies have confirmed that combining the two interventions provides additional benefit to erectile function, likely via reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (e.g., increased endothelial function). Lifestyle modifications provide significant benefits to vascular health and erectile function in a population that is increasingly aged and more obese.


Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system.
Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever, are endemic in tropical and temperate parts of the world. The flavivirus nonstructural protein 1 (NS1) functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. We report crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses. The NS1 hexamer in crystal structures is similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 binds to lipid bilayers and remodels large liposomes into lipoprotein nanoparticles. The NS1 structures reveal distinct domains for membrane association of the dimer and interactions with the immune system and are a basis for elucidating the molecular mechanism of NS1 function.


Comparison of Government and Non-Government Alcohol and Other Drug (AOD) Treatment Service Delivery for the Lesbian, Gay, Bisexual, and Transgender (LGBT) Community.
Lesbian, gay, bisexual, and transgender (LGBT) populations are more likely to misuse alcohol and other drugs (AOD), compared to the general population. However, LGBT engagement with AOD treatment is often precluded by insensitivity and misunderstanding of LGBT issues. These treatment barriers may be a consequence of either worker attitudes, organizational factors or a combination of both. Few studies have compared service context as an impediment to AOD treatment. This pilot study sought to examine and compare staff attitudes, knowledge and awareness of LGBT issues in two state-wide AOD services within Australia. One organization was a government service, whilst the other was faith based. A cross-sectional study of a convenience sample (N = 130) of workers employed in a state-wide government AOD service (n = 65), and a state-wide non-government service (n = 65) was conducted. Participants self-completed a questionnaire comprising tools previously used to assess staff attitudes, knowledge and awareness of LGBT issues. Few significant differences in attitudes and awareness of LGBT issues between government and non-government respondents were found. Nearly all respondents were supportive of LGBT persons irrespective of organizational context, with a small number of negative views. Although most respondents demonstrated awareness of organizational policies and practices relating to LGBT clients, many were "unsure" or "neutral" of what these might be. It is confirming that the majority of staff report supportive attitudes towards LGBT clients. Findings suggest that organizations need to continue to take leadership to strengthen organizational training and capacity to deliver LGBT friendly AOD treatment practices.


Neuroanatomy of memory and amnesia: a case for multiple memory systems.
Several different dissociable memory systems are considered in terms of their known or putative sites of pathology. In man, short-term memory can be selectively impaired by left hemisphere lesions near the acoustic projection area. There may be other modality-specific deficits. Long-term memory is considered in terms of a) knowledge systems, b) stable associative memory; c) priming, and d) event memory, with special reference to the amnesic syndrome. For each of these categories, clinical neuropathological and relevant animal evidence is reviewed. It is concluded that "memory" is not holistic, and the anatomical bases must be considered independently for each of the several dissociable (but normally interacting) systems. Some are likely to involve virtually all levels of the nervous system, while others are highly specific.


Congenital disorder of glycosylation (CDG) type Ie. A new patient.
CDG Ie is caused by a deficiency of dolichol-phosphate-mannose synthase 1 (DPM1), an enzyme involved in N-glycan assembly in the endoplasmic reticulum. Three proteins are known to be part of the synthase complex: DPM 1, DPM2 and DPM3. Only mutations in DPM1, the catalytic subunit, have been described in three families. One was homozygous for the c274C>G (R92G) mutation in DPM1 and two others were compound heterozygous for R92G and a c628delC deletion or a c331-343del13, respectively. Clinical features were a severe infantile encephalopathy, early intractable seizures, acquired microcephaly, and some dysmorphic features. We report a patient with milder symptoms: microcephaly, dysmorphic features, developmental delay, optic atrophy, and cerebellar dysfunction without cerebellar atrophy. The patient is homozygous for a new mutation in exon 9 of the DPM1 gene (c742T>C (S248P)). Our findings extend the spectrum of CDG Ie.


The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene.
To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials. International, multicenter, retrospective cohort study. Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families. Medical records were reviewed for medical history, best-corrected visual acuity (BCVA), ophthalmoscopy, visual fields, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain OCT [SD-OCT], fundus autofluorescence). Age of onset, evolution of BCVA, genotype-phenotype correlations, anatomic characteristics on funduscopy, and multimodal imaging. Fourteen patients with autosomal recessive LCA and 68 with autosomal dominant CORD were included. The median follow-up times were 5.2 years (interquartile range [IQR] 2.6-8.8 years) for LCA and 7.2 years (IQR 2.2-14.2 years) for CORD. Generally, LCA presented in the first year of life. The BCVA in patients with LCA ranged from no light perception to 1.00 logarithm of the minimum angle of resolution (logMAR) and remained relatively stable during follow-up. Imaging for LCA was limited but showed little to no structural degeneration. In patients with CORD, progressive vision loss started around the second decade of life. The BCVA declined annually by 0.022 logMAR (P < 0.001) with no difference between patients with the c.2513G>A and the c.2512C>T GUCY2D variants (P = 0.798). At the age of 40 years, the probability of being blind or severely visually impaired was 32%. The integrity of the ellipsoid zone (EZ) and that of the external limiting membrane (ELM) on SD-OCT correlated significantly with BCVA (Spearman ρ = 0.744, P = 0.001, and ρ = 0.712, P < 0.001, respectively) in those with CORD. Leber congenital amaurosis associated with GUCY2D caused severe congenital visual impairment with relatively intact macular anatomy on funduscopy and available imaging, suggesting long preservation of photoreceptors. Despite large variability, GUCY2D-associated CORD generally presented during adolescence, with a progressive loss of vision, and culminated in severe visual impairment during mid-to-late adulthood. The integrity of the ELM and EZ may be suitable structural end points for therapeutic studies of GUCY2D-associated CORD.


Differential growth on sutures of tendon cells derived from torn human rotator cuff.
Rotator cuff tendon pathology is proposed to account for 30-70% of all shoulder pain and surgical repair with a nonabsorbable suture is the common option for painful rotator cuff tears that have failed conservative treatment. A number of studies have suggested the beneficial effect of augmenting the repair with implants constructed from polymers used for sutures. Thus, it was of interest to investigate the affinity of tendon-derived fibroblasts, often thought to be the repairing agents of torn tendons, to commonly used sutures. The aim of this comparative study was to evaluate the suitability of these sutures for the construction of a patch by measuring cell survival, proliferation, and migration of human tendon-derived fibroblasts on different sutures. To ensure relevance to the target tissue, cells used in this study were obtained from torn human supraspinatus tendons. An initial comparison of cell proliferation on suture mats showed an overall positive proliferation on polyester (Ethibond) and polydioxanone (PDSII) mats and a reduction of proliferation on vicryl (polyglactin 910) compared to day one. The results also showed that the degradation products of vicryl had a negative effect on cell growth over 10 weeks. Of the commercial sutures selected and tested, Ethibond showed the best performance in terms of cell attachment and increase in biomass. The degradable PDSII also showed good interaction with cells in vitro, but relatively poor cell adhesion. This study provides useful and clinically relevant information, which could help to guide future considerations for candidate materials from which to construct tissue repair patches.


Multi-generational persistence of traditions in neighbouring meerkat groups.
Reports of socially transmitted traditions based on behavioural differences between geographically separated groups of conspecifics are contentious because they cannot exclude genetic or environmental causes. Here, we report persistent differences between neighbouring groups of meerkats (Suricata suricatta) where extensive gene flow precludes genetic differentiation. Over 11 years, some groups consistently emerged later from their sleeping burrows in the morning than others, despite complete turnovers in group membership and the influx of immigrants. Group territories overlapped and, in many cases, the same sleeping burrows were used by different groups. Differences persisted even after accounting for effects of group size, weather and burrow characteristics, and were unrelated to food availability within territories. These results provide compelling evidence that the emergence times of meerkat groups represent conservative traditions.


A Large-Scale Study Indicates Increase in the Risk of Epilepsy in Patients With Different Risk Factors, Including Rheumatoid Arthritis.
Peripheral neuropathy and inflammatory reactions of the central nervous system may accompany rheumatoid arthritis (RA). Inflammatory processes play a critical role in epilepsy. Therefore, we conducted this study to determine the risk of epilepsy in patients with RA.The RA cohort comprised patients ages 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database. Patients without RA were frequency matched with an RA cohort at a 1:1 ratio according to age, sex, and year of RA diagnosis.The overall crude hazard ratio (HR) for epilepsy was 1.27-fold higher in the RA cohort compared with that in the controls. After adjustment for age, sex, comorbidities, and medications, the patients with RA were associated with an increased risk of epilepsy compared with those without RA (adjusted HR [aHR] = 1.52, 95% confidence interval [CI] = 1.12-2.07). Compared with the RA patients with ≤ 560 days of nonsteroidal anti-inflammatory drug (NSAID) use, the RA patients with 1181 to 2145 and >2145 days of NSAID use had a significantly lower risk of epilepsy (aHR = 0.35, 95% CI = 0.24-0.52 and aHR = 0.15, 95% CI = 0.09-0.24, respectively).This study provides compelling evidence of an increased risk of epilepsy in patients with RA. The period of NSAID treatment is negatively associated with the risk of epilepsy in RA patients.


Fronto-parietal connectivity changes following noxious stimulation during anesthesia.
The aim of our study was to assess the changes in the fronto-parietal connectivity estimated by the cross approximate entropy (XAppEn) during noxious stimulation while under chloral hydrate anaesthesia, in rats. A group of 11 Wistar rats chronically implanted with Ni-Cr electrodes, which were placed on the dura mater of the right hemisphere (over the olfactory cortex, the frontal and the parietal lobes), were used in the present study. Noxious stimuli of a mechanical and thermal nature were applied on the left hindpaw during chloral hydrate anesthesia. The anesthetic depth was estimated through median frequency computation, which in that instance was of 2-3 Hz. Fronto-parietal functional cortical connectivity was assessed by using XAppEn. After data processing and analysis we observed an increase of fronto-parietal functional connectivity during mechanical and thermal noxious stimulation. In addition, MEF increased both in frontal and parietal areas during the mechanical and thermal stimulation compared to baseline. Mechanical and thermal stimulation induces an increase in the fronto-parietal connectivity during chloral hydrate anesthesia in rats.


PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment.
Combination cancer therapy has emerged as crucial approach for achieving superior anti-cancer efficacy. In this study, we developed a strategy by localized co-delivery of PLK1shRNA/polylysine-modified polyethylenimine (PEI-Lys) complexes and doxorubicin (DOX) using biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for treatment of osteosarcoma. When incubated with osteosarcoma Saos-2 and MG-63 cells, the hydrogel containing PLK1shRNA/PEI-Lys and DOX displayed significant synergistic effects in promoting the apoptosis of osteosarcoma cells in vitro. After subcutaneous injection of the hydrogel containing PLK1shRNA/PEI-Lys and DOX beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts, the hydrogels exhibited superior antitumor efficacy in vivo compared to the hydrogels loaded with PLK1shRNA/PEI-Lys or DOX alone. It is noteworthy that the combination treatment in vivo led to almost complete suppression of tumor growth up to 16 days, significantly enhanced PLK1 silencing, higher apoptosis of tumor masses, as well as increased cell cycle regulation. Additionally, ex vivo histological analysis of major organs of the mice indicated that the localized treatments showed no obvious damage to the organs, suggesting lower systemic toxicity of the treatments. Therefore, the strategy of localized, sustained co-delivery of PLK1shRNA and DOX by using the biodegradable, injectable hydrogel may have potential for efficient clinical treatment of osteosarcoma.


Clonal haematopoiesis and risk of chronic liver disease.
Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.


Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus.
During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.


Designing Endocrine Disruption Out of the Next Generation of Chemicals.
A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health.


Therapy-related myelodysplastic syndrome following primary breast cancer.
Therapy-related myelodysplastic syndrome (t-MDS) is a serious clinical disease occurring after breast cancer treatment. A cohort of 11,684 invasive breast cancer (BC) patients from 1990-2014 were followed for incidence of t-MDS through institutional and the Surveillance, Epidemiology and End Results (SEER) Program registries. t-MDS cases were identified using ICD-O SEER registry codes, pathology and chart reports. Treatment, cytogenetics, and time from BC diagnosis to t-MDS and t-MDS diagnosis to last follow up or death were obtained. Incidence rate ratios were calculated using SEER national incidence rates for comparison. 27 cases of t-MDS post BC treatment were confirmed. 96% of cases were breast cancer stage I-II at diagnosis. All patients had received radiation treatment and 59% received adjuvant chemotherapy. Two patients were alive with no evidence of disease after treatment with stem cell transplantation (age 33 and 46). t-MDS incidence was 30 times the expected population rate among patients <55 years (RR 31.8, 95% CI 15.0, 60.8) with shorter time from t-MDS diagnosis to death (median survival time: <55: 8 months, 55-74: 26 months, 75+: 23 months). We found elevated t-MDS risk especially among younger BC patients with stem cell transplantation the only observed curative treatment.


[0.5% enantiomeric excess bupivacaine (S75-R25), 0.5% racemic bupivacaine, and 2%lidocaine for facial nerve block by the O'Brien technique: a comparative study.].
Enantiomeric mixtures of bupivacaine in different formulations, S75-R25 or S90-R10, were proposed aiming at reducing the cardiotoxicity and with a satisfactory motor blockade. The aim of this study was to compare the length of time until the appearance of the motor blockade and its degree using 50% enantiomeric excess 0.5% bupivacaine (S75-R25), 0.5% racemic bupivacaine, and 2% lidocaine for facial nerve block by the O'Brien technique. Forty-five patients, over 60 years old, scheduled for the surgical treatment of cataracts under retrobulbar block preceded by O'Brien paralysis participated in this study. Patients were randomly divided in three groups of 15 patients, according to the anesthetic used for the facial nerve block: Group L (Lidocaine), Group B (Bupivacaine), and Group M (S75-R25). Three milliliters of the solution were administered. The length of time for motor blockade to become apparent and the degree of the motor block (Grades 1, 2, and 3) were evaluated 15 seconds after the injection and every 15 seconds until it reached 180 seconds. The initial manifestations of the blockade were faster (15 s) in Group L. There were no differences between Groups B and M. Every patient in Group L showed Grade 3 motor block in up to 60 seconds, which was faster than Groups B and M (120 and 135 seconds, respectively). Groups B and M had similar behavior during the study, without any statistically significant difference. At 180 seconds, the incidence of Grade 3 motor block was similar in all three groups. The beginning of the motor blockade and its maximal degree were achieved faster with 2% lidocaine. The same degree was achieved by racemic bupivacaine and S75-R25, but it took longer. These two anesthetics showed the same behavior regarding the latency and the maximal degree of motor block, but at the end of 180 seconds there were no differences in the intensity of the blockade among the three groups.


Prostacyclin synthesis and stimulation of cyclic AMP production in ovine fetal vasculature: heterogeneity in pulmonary and systemic arteries.
Prostacyclin (PGI2) is an important local mediator of vasomotor tone in the fetus and newborn, acting via stimulation of cAMP production by vascular smooth muscle (VSM) adenylate cyclase. In this investigation PGI2 and prostaglandin (PG) E2 synthesis and stimulation of cAMP production were compared in vitro in ovine fetal pulmonary versus systemic (mesenteric) arteries. PGI2 synthesis was similar in the pulmonary and systemic arteries (2.4 +/- 0.2 and 2.6 +/- 0.3 ng/mg protein.h, respectively), as was PGE2 synthesis (1.9 +/- 0.2 and 1.5 +/- 0.2 ng/mg protein.h, respectively); synthesis was greater for PGI2 versus PGE2 in both artery types. 65-71% of PGI2 synthesis and 51-59% of PGE2 synthesis occurred in the endothelium. Basal (nonstimulated) cAMP production was fully attenuated by indomethacin, indicating that it is mediated exclusively by endogenous PG. Basal cAMP production was 3.8-fold less in pulmonary versus systemic arteries, and this was related to a 9.7-fold difference in responsiveness to PG. A 14.7-fold difference in the response to forskolin indicates that underlying mechanism may be a disparity in the quantity and/or function of the adenylate cyclase enzyme complex. Thus, prostacyclin and PGE2 synthesis are comparable in ovine fetal pulmonary versus systemic arteries, but the cAMP response to the prostanoids is markedly greater in the latter artery type due to differences in the activation of adenylate cyclase. This heterogeneity in VSM intracellular signalling may contribute to differential vasomotor tone and responses in the fetal pulmonary and systemic circulation.


Tuberculosis in the Caribbean: using spacer oligonucleotide typing to understand strain origin and transmission.
We used direct repeat (DR)-based spacer oligonucleotide typing (spoligotyping) (in association with double-repetitive element polymerase chain reaction, IS6110-restriction fragment length polymorphism [RFLP], and sometimes DR-RFLP and polymorphic GC-rich sequence-RFLP) to detect epidemiologic links and transmission patterns of Mycobacterium tuberculosis on Martinique, Guadeloupe, and French Guiana. In more than a third of the 218 strains we typed from this region, clusters and isolates shared genetic identity, which suggests epidemiologic links. However, because of limited epidemiologic information, only 14.2% of the strains could be directly linked. When spoligotyping patterns shared by two or more isolates were pooled with 392 spoligotypes from other parts of the world, new matches were detected, which suggests imported transmission. Persisting foci of endemic disease and increased active transmission due to high population flux and HIV-coinfection may be linked to the recent reemergence of tuberculosis in the Caribbean. We also found that several distinct families of spoligotypes are overrepresented in this region.


Temperature-modulated bioluminescence tomography.
It was recently reported that bioluminescent spectra can be significantly affected by temperature, which we recognize as a major opportunity to overcome the inherent illposedness of bioluminescence tomography (BLT). In this paper, we propose temperature-modulated bioluminescence tomography (TBT) to utilize the temperature dependence of bioluminescence for superior BLT performance. Specifically, we employ a focused ultrasound array to heat small volumes of interest (VOI) one at a time, and induce a detectable change in the optical signal on the body surface of a mouse. Based on this type of information, the BLT reconstruction can be stabilized and improved. Our numerical experiments clearly demonstrate the merits of our TBT with either noise-free or noisy datasets. Also, this idea is applicable in 2D bioluminescence imaging and computational optical biopsy (COB). We believe that our approach and technology represents a major step forward in the field of BLT, and has an important and immediate applicability in bioluminescence imaging of small animals in general.


Word Imageability Enhances Association-memory by Increasing Hippocampal Engagement.
The hippocampus is thought to support association-memory, particularly when tested with cued recall. One of the most well-known and studied factors that influences accuracy of verbal association-memory is imageability; participants remember pairs of high-imageability words better than pairs of low-imageability words. High-imageability words are also remembered better in tests of item-memory. However, we previously found that item-memory effects could not explain the enhancement in cued recall, suggesting that imageability enhances association-memory strength. Here we report an fMRI study designed to ask, what is the role of the hippocampus in the memory advantage for associations due to imageability? We tested two alternative hypotheses: (1) Recruitment Hypothesis: High-imageability pairs are remembered better because they recruit the underlying hippocampal association-memory function more effectively. Alternatively, (2) Bypassing Hypothesis: Imageability functions by making the association-forming process easier, enhancing memory in a way that bypasses the hippocampus, as has been found, for example, with explicit unitization imagery strategies. Results found, first, hippocampal BOLD signal was greater during study and recall of high- than low-imageability word pairs. Second, the difference in activity between recalled and forgotten pairs showed a main effect, but no significant interaction with imageability, challenging the bypassing hypothesis, but consistent with the predictions derived from the recruitment hypothesis. Our findings suggest that certain stimulus properties, like imageability, may leverage, rather than avoid, the associative function of the hippocampus to support superior association-memory.


Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies.
Although several in vitro and animal in vivo studies have suggested that soy or soy isoflavones may exert inhibitory effects on lung carcinogenesis, epidemiologic studies have reported inconclusive results on the association between soy intake and lung cancer. The aim of this meta-analysis was to investigate whether an association exists between soy and lung cancer in epidemiologic studies. We searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2011 for both case-control and cohort studies that assessed soy consumption and lung cancer risk. Study-specific risk estimates were combined by using fixed-effect or random-effect models. A total of 11 epidemiologic studies that consisted of 8 case-control and 3 prospective cohort studies were included. A significantly inverse association was shown between soy intake and lung cancer with an overall RR of 0.77 (95% CI: 0.65, 0.92). Findings were slightly different when analyses were restricted to 5 high-quality studies (RR: 0.70; 95% CI: 0.45, 0.99). In a subgroup meta-analysis, a statistically significant protective effect of soy consumption was observed in women (RR: 0.79; 95% CI: 0.67, 0.93), never smokers (RR: 0.62; 95% CI: 0.51, 0.76), and Asian populations (RR: 0.86; 95% CI: 0.74, 0.98). Our findings indicate that the consumption of soy food is associated with lower lung cancer risk. Because of different methods used to assess soy consumption across studies, more well-designed cohort studies or intervention studies that use unified measures of soy intake are needed to fully characterize such an association.


Recovery of waterborne oocysts of Cyclospora cayetanensis by Asian freshwater clams (Corbicula fluminea).
Asian freshwater clams (Corbicula fluminea) were exposed for 24 hr in 38 liters of water contaminated with 1.0 x 10(5) Cyclospora cayetanensis oocysts (2.6 x 10(3) oocysts/L). The hemolyph and gill smears of 30 clams were examined by acid-fast stain on days 1, 3, 5, 7, 10, 13, and 18 postexposure (PE). Since no oocysts were detected in the water 24 hr after contamination by the membrane filter-dissolution method, the oocyst retention rate was 4.6 X 10(2) oocysts/clam. The prevalence of oocyst-positive clams significantly decreased (P < 0.01) from 93% to 47% during 13 days PE. None of the clams contained oocysts on day 18 PE; no oocysts were detected in the clam feces. The numbers of oocysts recovered from six clam size classes varied and significantly decreased with smaller clam size (P < 0.01). The lowest prevalence values of oocyst-positive clams, 45% and 34%, were observed in the two lowest size classes: 12.1-14.0 mm and 14.1-16.0 mm, respectively. The prevalence values in the remaining four classes ranged from 84% to 100%. The sampling program demonstrated that the population of 180 clams examined during the study up to 13 day PE could be assessed for C. cayetanensis positivity by random testing of a minimum of 75 clams (42%). When the two lowest clam size classes are eliminated, the population of 114 clams could be assessed by sampling a minimum of 32 clams (28%). The results demonstrate that Corbicula fluminea can recover waterborne oocysts of C. cayetanensis, and could be used as biological indicators of contamination of water with C. cayetanensis oocysts.


Predictors for severe hemorrhage requiring angioembolization post percutaneous nephrolithotomy: A single-center experience over 3 years.
About 1% of the patients undergoing percutaneous nephrolithotomy (PCNL) have bleeding severe enough to require angioembolization. We identified factors which could predict severe bleeding post-PCNL and reviewed patients who underwent angioembolization for the same. This is a single-institutional, retrospective study over a period of 3 years. We retrospectively studied 583 patients undergoing PCNL at our institute from 2013 to 2016. We analyzed nine patients (three from our institute and six referred patients) who underwent angioembolization for severe bleeding post-PCNL. We analyzed the preoperative characteristics, intraoperative findings, and postoperative course of these patients and compared this with those patients who did not have a severe post-PCNL bleeding. Fischer's exact test and Chi-square test were used in univariate analysis. Logistic regression analysis was used in multivariate analysis with a value of P < 0.05 considered statistically significant. Three of the 583 patients (0.51%) who underwent PCNL at our institute required embolization to control bleeding. Preoperative characteristics that were significant risk factors for severe bleeding were a history of ipsilateral renal surgery (P = 0.0025) and increased stone complexity (P = 0.006), while significant intraoperative factors were injury to the pelvicalyceal system (P = 0.0005) and multiple access tracts (P = 0.022). Angiography revealed arteriovenous fistula in two patients and a pseudoaneurysm in seven patients. All patients underwent successful superselective angioembolization with preserved renal perfusion in six patients on control angiography postembolization. History of ipsilateral renal surgery, increased stone complexity, multiple access tracts, and injury to the pelvicalyceal system are risk factors predicting severe renal hemorrhage post-PCNL. Early angiography followed by angioembolization should be performed in patients with severe post-PCNL bleeding who fail to respond to conservative measures.


Single-shot photonic time-intensity integration based on a time-spectrum convolution system.
Real-time and single-shot ultra-fast photonic time-intensity integration of arbitrary temporal waveforms is proposed and demonstrated. The intensity-integration concept is based on a time-spectrum convolution system, where the use of a multi-wavelength laser with a flat envelope, employed as the incoherent broadband source, enables single-shot operation. The experimental implementation is based on optical intensity modulation of the multi-wavelength laser with the input waveform, followed by linear dispersion. In particular, photonic temporal intensity integration with a processing bandwidth of 36.8 GHz over an integration time window of 1.24 ns is verified by experimentally measuring the integration of an ultra-short microwave pulse and an arbitrary microwave waveform.


Hominin teeth from the early Late Pleistocene site of Xujiayao, Northern China.
It is generally accepted that from the late Middle to the early Late Pleistocene (∼340-90 ka BP), Neanderthals were occupying Europe and Western Asia, whereas anatomically modern humans were present in the African continent. In contrast, the paucity of hominin fossil evidence from East Asia from this period impedes a complete evolutionary picture of the genus Homo, as well as assessment of the possible contribution of or interaction with Asian hominins in the evolution of Homo sapiens and Homo neanderthalensis. Here we present a comparative study of a hominin dental sample recovered from the Xujiayao site, in Northern China, attributed to the early Late Pleistocene (MIS 5 to 4). Our dental study reveals a mosaic of primitive and derived dental features for the Xujiayao hominins that can be summarized as follows: i) they are different from archaic and recent modern humans, ii) they present some features that are common but not exclusive to the Neanderthal lineage, and iii) they retain some primitive conformations classically found in East Asian Early and Middle Pleistocene hominins despite their young geological age. Thus, our study evinces the existence in China of a population of unclear taxonomic status with regard to other contemporary populations such as H. sapiens and H. neanderthalensis. The morphological and metric studies of the Xujiayao teeth expand the variability known for early Late Pleistocene hominin fossils and suggest the possibility that a primitive hominin lineage may have survived late into the Late Pleistocene in China.


Role of Orbital Ultrasound in the Assessment of Clinically Detected Papilledema.
Increased intracranial pressure (ICP) is frequently seen, and it is considered a serious problem that needs a careful assessment and management, especially by easy and least invasive modalities. The objective of the study is to assess the optic nerve sheath diameter (ONSD) using transorbital ultrasound (US) as a marker and indicator for diagnosing raised intracranial pressure. It is a prospective study that was carried out in Neurology and/or Ophthalmology Clinics, Baghdad Teaching Hospital in the Medical City Complex during the period from June 2016 to May 2017; in this study, 40 patients seeking medical help for other causes were considered to be a control group and the other 40 patients who were complaining of raised ICP symptoms and suggested of having optic disc swelling by ophthalmoscopy examination. All the patients and the control group were examined by transorbital US to measure the ONSD, and then, only the patients with symptoms of raised intracranial underwent a lumbar puncture (LP). Pearson's correlation test was used, demonstrating a very significant correlation between the ultrasonographic ONSD and the measurements of LP (R > 0.9) and (P < 0.001). Transorbital US yielded high sensitivity (91.6%) with modest specificity (75%) and high accuracy (90.0%) of ONSD was considered the normal the cutoff value of (5 mm) obtained from the control group. The US also showed the crescent sign and the optic disc bulging with lower sensitivity than the ONSD (61.1% and 41.6%, respectively) but with very high specificity (100%) for both. ONSD by transorbital ultrasonography is highly accurate, easily performed, and noninvasive procedure for the detection of raised ICP. Routine daily monitoring of ONSD could be of help in intensive care units when invasive ICP monitoring is not available or contraindicated; it also has a good role in early recognition of intracranial hypertension.


When Bigger Is Better: Household Size, Abuse Injuries, Neglect, and Family Response in Novosibirsk, Russia.
Although previous research has demonstrated larger households to be at higher risk of physical abuse and neglect of children, we argue that unilateral conceptualization of larger households as a risk factor is inappropriate. Application of resource dilution theory must capture the possibility that larger families may have more members with both the agency and will to intervene against child maltreatment. We hypothesized a negative interaction between household size and protective informal social control by family members in predicting abuse injuries and neglect. A three-stage probability proportional to size cluster sample representative of Novosibirsk, Russia, was collected from 306 cohabiting couples. One parent in each household was interviewed. A focal child was selected using most recent birthday. When responses limited to families with minor children (below age 18) were selected, 172 families remained in the data. Physical abuse and neglect were measured using the Conflict Tactics Scales (CTS). Protective informal social control by family members was measured using the Informal Social Control of Child Maltreatment (ISC_CM) Scale. Models were tested using random effects regression and logistic regression. Nearly 7% of focal children were injured in the last year, 10% were neglected. Consistent with previous research, protective informal social control was associated with lower odds of injury and fewer instances of neglect. The significant negative interaction between household size and protective control is consistent with the idea that larger households may be protective when adult family members intervene against maltreatment to protect children. Replication and further investigation of protective ISC_CM in Western populations is much needed. Future research should not conceptualize or measure household size as a unilateral risk factor.


Female oxytocin-deficient mice display enhanced anxiety-related behavior.
Previous studies have suggested that oxytocin (OT) may be anxiolytic in female laboratory rats and mice. The elevated plus-maze was used to compare anxiety-related behaviors of OT-deficient (OT-/-) and wild-type (OT+/+) mice. Female OT-/- mice displayed increased anxiety-related behavior compared with OT+/+ mice. The percentage of entries (P < 0.0002) and time spent (P < 0.003) in the open arms was less in female OT-/- than OT+/+ mice. Administration of synthetic OT, 2 ng by intracerebroventricular (icv) injection to female OT-/- mice, increased the percentage of entries (P < 0.003) and time spent (P < 0.004) in the open arms compared with artificial cerebrospinal fluid female OT-/- mice. Administration of an OT receptor antagonist (Atosiban, d[Dtyr(Et)(2), Thr(4)]ornithine vasotocin) 100 ng icv, to female OT+/+ mice increased anxiety-related behavior by decreasing the percentage of entries (P < 0.01) and time spent (P < 0.04) in the open arms compared with artificial cerebrospinal fluid-treated controls. Central infusion of an OT receptor antagonist, 100 ng icv, before administration of synthetic OT, 2 ng icv, in female OT-/- mice blocked the anxiolytic affect of OT. In contrast, male OT-/- mice displayed decreased anxiety-related behavior compared with male OT+/+ mice. The percentage of entries (P < 0.007) and time spent (P < 0.004) in the open arms was greater in male OT-/- vs. OT+/+ mice. Our findings indicate that OT pathways play a role in modulating anxiety in female mice of the C57BL/6 background, and the effect is mediated by the OT receptor.


Enzyme linked immuno-spot; a useful tool in the search for elusive immune markers in common pediatric immunological diseases.
In order to provide better therapy we strive to increase our knowledge of how the immune system behaves and communicates in common pediatric immunological diseases, such as type 1 diabetes, allergic and celiac diseases. However, when dealing with pediatric diseases, where study subjects are almost exclusively children, blood volumes available for immunological studies are limited and as such must be carefully handled and used to their full extent. Single immune markers can easily be detected by a traditional Enzyme Linked Immunosorbent Assay (ELISA), whereas multiple markers can be detected by a fluorochrome (Luminex) or electrochemiluminescence (MSD) technique. These techniques however are sometimes not sensitive enough to detect low levels of secreted immune markers in limited sample sizes. To detect immune markers at the single-cell level, an Enzyme Linked Immuno-spot (ELISPOT) can be used to pin-point elusive immune markers in common pediatric immunological diseases.


A neuronal network model for context-dependence of pitch change perception.
Many natural stimuli have perceptual ambiguities that can be cognitively resolved by the surrounding context. In audition, preceding context can bias the perception of speech and non-speech stimuli. Here, we develop a neuronal network model that can account for how context affects the perception of pitch change between a pair of successive complex tones. We focus especially on an ambiguous comparison-listeners experience opposite percepts (either ascending or descending) for an ambiguous tone pair depending on the spectral location of preceding context tones. We developed a recurrent, firing-rate network model, which detects frequency-change-direction of successively played stimuli and successfully accounts for the context-dependent perception demonstrated in behavioral experiments. The model consists of two tonotopically organized, excitatory populations, E up and E down, that respond preferentially to ascending or descending stimuli in pitch, respectively. These preferences are generated by an inhibitory population that provides inhibition asymmetric in frequency to the two populations; context dependence arises from slow facilitation of inhibition. We show that contextual influence depends on the spectral distribution of preceding tones and the tuning width of inhibitory neurons. Further, we demonstrate, using phase-space analysis, how the facilitated inhibition from previous stimuli and the waning inhibition from the just-preceding tone shape the competition between the E up and E down populations. In sum, our model accounts for contextual influences on the pitch change perception of an ambiguous tone pair by introducing a novel decoding strategy based on direction-selective units. The model's network architecture and slow facilitating inhibition emerge as predictions of neuronal mechanisms for these perceptual dynamics. Since the model structure does not depend on the specific stimuli, we show that it generalizes to other contextual effects and stimulus types.


Molecular Alterations in Patients with Pulmonary Adenocarcinoma Presenting with Malignant Pleural Effusion at the First Diagnosis.
The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression. We identified 18 patients (9 males and 9 females). Micropapillary and/or solid adenocarcinoma type features predominated among cytologic specimens (n = 15), while acinar patterns predominated in controls. Survival was not significantly different from that of the control group (mean 13.8 vs. 13.9 months, respectively; p = 0.61). Ten (55%) cases had mutations in EGFR (n = 6; 60%), KRAS (n = 3; 30%), or ALK translocation (n = 1; 10%). No mutations were identified in BRAF, AKT, ERBB2, NRAS, or PIK3CA (tested in 7 patients). Patients positive for the tested mutations had a better overall survival than patients negative for the mutations (mean survival 16.2 vs. 6.05 months, respectively; p = 0.006, log-rank test). Ten (84%) control patients were positive for mutations in EGFR (n = 5; 42%), KRAS (n = 4; 34%), or ALK translocation (n = 1; 8.4%). In our series, a micropapillary-like and solid-like morphology, common in cytologic specimens, and alterations in EGFR were the most frequent identifiable molecular changes.


Tolerability and Effectiveness of 17-α-Alkylated Androgen Therapy for Hereditary Angioedema: A Re-examination.
Hereditary angioedema (HAE) is a genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling. 17-α-Alkylated androgens (AA) have been used prophylactically to reduce HAE severity, but there are many questions about the efficacy and tolerability of AA. The objective of this study was to investigate the tolerability and effectiveness of AA therapy in a large cohort of patients with HAE. We performed a retrospective cross-sectional study on 650 subjects with HAE utilizing a one time, anonymous, web-based survey. Based on an initial questionnaire, patients were routed to one of the following questionnaires: currently using AA, previously used but discontinued AA, or never used AA. Statistical analysis revealed that androgens decreased attack frequency and severity in previous AA users (P < .0001) and current AA users (P < .0001). Substantial variability in the effectiveness was observed. Users who discontinued AA reported significantly lesser benefit. No dose effect was seen for the beneficial effect of AA; however, almost all users reported frequent side effects that were dose related and often severe. AA therapy is usually effective for the treatment of HAE although a substantial fraction of patients with HAE do not achieve adequate benefit. In contrast, the side effects of AA are seen in almost all subjects who take the medicines. If used, AA should only be recommended in the lowest effective and tolerated dose for carefully selected patients.


Cancer incidence in British vegetarians.
Few prospective studies have examined cancer incidence among vegetarians. We studied 61,566 British men and women, comprising 32,403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20,601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07-1.20) in fish eaters and 0.36 (0.16-0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18-0.77) in fish eaters and 0.69 (0.45-1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36-1.81) in fish eaters and 0.47 (0.25-0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56-1.29) in fish eaters and 0.55 (0.39-0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73-0.93) in fish eaters and 0.88 (0.81-0.96) in vegetarians (P for heterogeneity=0.001). The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.


Unified account of the variable effects of carbon dioxide on nerve cells.
When the abdominal ganglion of Aplysia californica is exposed to 5 percent carbon dioxide, certain neurons are depolarized, others hyperpolarized, and some are unaffected. The effect of increased carbon dioxide is due solely to the concomitant fall in extracellular pH, which causes an increase in membrane chloride conductance of responsive cells. The directional change of the membrane potential in different neurons is determined by the relative values of the chloride equilibrium and the resting potentials. The chloride equilibrium potentials are calculated after direct measurement of the intracellular chloride activity with a chloride microelectrode.


Development of a Couette-Taylor flow device with active minimization of secondary circulation.
A novel Taylor-Couette experiment has been developed to produce rotating shear flows for the study of hydrodynamic and magnetohydrodynamic instabilities which are believed to drive angular momentum transport in astrophysical accretion disks. High speed, concentric, corotating cylinders generate the flow where the height of the cylinders is twice the radial gap width. Ekman pumping is controlled and minimized by splitting the vertical boundaries into pairs of nested, differentially rotating rings. The end rings and cylinders comprise four independently driven rotating components which provide flexibility in developing flow profiles. The working fluids of the experiment are water, a water-glycerol mix, or a liquid gallium alloy. The mechanical complexity of the apparatus and large dynamic pressures generated by high speed operation with the gallium alloy presented unique challenges. The mechanical implementation of the experiment and some representative results obtained with laser Doppler velocimetry in water are discussed.


Diagnosis and treatment of rosacea.
Rosacea is a common skin disorder affecting middle-aged and older adults. Many patients mistakenly assume that early rosacea is normally aging skin and are not aware that effective treatments exist to prevent progression to permanent disfiguring skin changes. The medical literature was reviewed on the pathophysiology, diagnosis, and treatment of rosacea. MEDLINE was searched using the key search terms "rosacea," "rhinophyma," "metronidazole," "Helicobacter pylori," and "facial redness." Rosacea is easily diagnosed by physician observation, and physicians should initiate discussion of rosacea treatment with patients. Effective treatment of rosacea includes avoidance of triggers, topical and oral antibiotic therapy, both topical and oral retinoid therapy, topical vitamin C therapy, and cosmetic surgery.


The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis.
The Food and Drug Administration approval of ruxolitinib for treatment of myelofibrosis and polycythemia vera has changed the management of patients with myeloproliferative neoplasms. Yet the impact of this therapy on risk of thrombosis, a major cause of morbidity and mortality among these patients, remains unknown. The aim of this study was to evaluate the impact of ruxolitinib on the risk of thrombosis among patients with polycythemia vera or myelofibrosis. Following identification of randomized controlled trials comparing ruxolitinib to standard care or placebo, rates of thrombosis, including venous and arterial thrombosis, were analyzed using fixed effects models. Rates of thrombosis were significantly lower among patients treated with ruxolitinib [risk ratio 0.45, 95% confidence interval (CI) 0.23-0.88]. Subgroup analysis of venous and arterial thrombosis demonstrated similar risk ratios, which did not reach statistical significance (risk ratio 0.46, 95% CI 0.14-1.48 and RR 0.42, 95% CI 0.18-1.01, respectively). In conclusion, our analysis suggests that JAK2 inhibition with ruxolitinib decreases the risk of arterial and/or venous thrombosis in patients with polycythemia vera or myelofibrosis. These findings will require confirmation in a prospective study.


Dispersion Corrected Atom-Centered Potentials for Phosphorus.
Dispersion-corrected atom-centered potentials (DCACPs) for the element phosphorus were generated and tested for the BLYP, BP, and PBE generalized gradient approximations of the exchange-correlation functional. The accuracy and transferability of the DCACPs were tested by evaluating the interaction energy of different weakly bound molecular systems (P2, PH3, and PN dimers). These results were compared to reference CCSD(T) calculations and standard density functional theory (DFT). The DCACP were also tested in the case of condensed phase systems. Specifically, the density and cohesive energies of β-white and black phosphorus were estimated and compared to available experimental data. Our results show an overall strong improvement both at the qualitative and quantitative level, with respect to uncorrected generalized gradient approximation DFT results for all three functionals. In particular, BLYP-corrected results show the maximal transferability, reporting for all systems a deviation from CCSD(T) results of less than 1% in the predicted binding energies.


Facile synthesis and enhanced electrochemical properties of reduced graphene oxide/MoS2/polyaniline ternary composites.
In this study, ternary composites of reduced graphene oxide/molybdenum disulfide/polyaniline (rGEO/MoS2/PANI) were prepared via a two-stage facile synthesis including a hydrothermal reaction and polymerization at room temperature which makes the materials much easier for industrialization. The doping of reduced graphene oxide (rGEO) decreases the aggregation of MoS2 and enhances the electronic conductivities of MoS2, thus exhibiting better capacitance properties (531 F g-1 at 1 A g-1) and cycling stabilities (86.7% retained capacitance over 3000 cycles at 1 A g-1) of ternary composites than a uniform material (MoS2) or binary materials (MoS2/PANI). The combined effects between the three components make the composites obtain both pseudocapacitance and double-layer capacitance, which can be used to explain the improvement of electrochemical performances.


Disordered microstructure polymer optical fiber for stabilized coherent random fiber laser.
We have demonstrated the realization of a random polymer fiber laser (RPFL) based on laser dye Pyrromethene 597-doped one-dimensional disordered polymer optical fiber (POF). The stabilized coherent laser action for the disordered POF has been obtained by the weak optical multiple scattering of the polyhedral oligomeric silsesquioxanes nanoparticles in the core of the POF in situ formed during polymerization, which was enhanced by the waveguide confinement effect. Meanwhile, the threshold of our RPFL system is almost one order of magnitude lower than that of the liquid core random fiber laser reported previously, which promotes the development of random lasers.


A Feature-Based Approach to Big Data Analysis of Medical Images.
This paper proposes an inference method well-suited to large sets of medical images. The method is based upon a framework where distinctive 3D scale-invariant features are indexed efficiently to identify approximate nearest-neighbor (NN) feature matches-in O (log N) computational complexity in the number of images N. It thus scales well to large data sets, in contrast to methods based on pair-wise image registration or feature matching requiring O(N) complexity. Our theoretical contribution is a density estimator based on a generative model that generalizes kernel density estimation and K-nearest neighbor (KNN) methods.. The estimator can be used for on-the-fly queries, without requiring explicit parametric models or an off-line training phase. The method is validated on a large multi-site data set of 95,000,000 features extracted from 19,000 lung CT scans. Subject-level classification identifies all images of the same subjects across the entire data set despite deformation due to breathing state, including unintentional duplicate scans. State-of-the-art performance is achieved in predicting chronic pulmonary obstructive disorder (COPD) severity across the 5-category GOLD clinical rating, with an accuracy of 89% if both exact and one-off predictions are considered correct.