Enhancing word signing in hearing students with reading disorders using computer-based learning trials.

Multiple-baseline-across-word-sets designs were used to determine whether a computer-based intervention would enhance accurate word signing with four participants. Each participant was a hearing college student with reading disorders. Learning trials included 3 s to observe printed words on the screen and a video model performing the sign twice (i.e., simultaneous prompting), 3 s to make the sign, 3 s to observe the same clip, and 3 s to make the sign again. For each participant and word set, no words were accurately signed during baseline. After the intervention, all four participants increased their accurate word signing across all three word sets, providing 12 demonstrations of experimental control. For each participant, accurate word signing was maintained. Application of efficient, technology-based, simultaneous prompting interventions for enhancing American Sign Language learning and future research designed to investigate causal mechanisms and optimize intervention effects are discussed.

Enzymatic digestibility of lignocellulosic wood biomass: Effect of enzyme treatment in supercritical carbon dioxide and biomass pretreatment.

Energy and resource intensive mechanical and chemical pretreatment along with the use of hazardous chemicals are major bottlenecks in widespread lignocellulosic biomass utilization. Herein, the study investigated different pretreatment methods on spruce wood namely supercritical CO2 (scCO2) pretreatment, ultrasound-assisted alkaline pretreatment, and acetosolv pulping-alkaline hydrogen peroxide bleaching, to enhance the enzymatic digestibility of wood using optimized enzyme cocktail. Also, the effect of scCO2 pretreatment on enzyme cocktail was investigated after optimizing the concentration and temperature of cellulolytic enzymes. The impact of scCO2 and ultrasound-assisted alkaline pretreatments of wood were insignificant for the enzymatic digestibility, and acetosolv pulping-alkaline hydrogen peroxide bleaching was the most effective pretreatment that showed the release of total reducing sugar yield (TRS) of ∼95.0 wt% of total hydrolyzable sugars (THS) in enzymatic hydrolysis. The optimized enzyme cocktail showed higher yield than individual enzymes with degree of synergism 1.34 among the enzymes, and scCO2 pretreatment of cocktail for 0.5-1.0 h at 10.0-22.0 MPa and 38.0-54.0 °C had insignificant effect on the enzyme's primary and global secondary structure of cocktail and its activity.

Identifying Predictors of Undertriage in Injured Older Adults After Implementation of Statewide Geriatric Trauma Triage Criteria.

OBJECTIVES: The objective was to identify factors associated with transport of injured older adults meeting statewide geriatric trauma triage criteria to a trauma center. METHODS: An observational retrospective cohort study using the 2009 to 2011 Ohio Trauma Registry. Subjects were adults ≥ 70 years old who met Ohio's geriatric triage criteria for trauma center transport by emergency medical services. We created multivariable logistic regression models to identify predictors of initial and ultimate (e.g., interfacility transfer) transport to a Level I or II trauma center and to a Level I, II, or III center. RESULTS: Of 10,411 subjects, 47% were initially and 59% were ultimately transported to a Level I or II trauma center with rates of 66 and 74%, respectively, for transport to a Level I, II, or III center. For initial transport to a Level I or II center, age 80 to 89 (odds ratio [OR] = 0.89), age ≥ 90 (OR = 0.76), and either only a Level 3 (OR = 0.3) or no trauma center (OR = 0.11) in county of residence had decreased odds of transport, while male sex (OR = 1.38), black race (OR = 2.07), Injury Severity Score (ISS) 10-15 (OR = 1.99), ISS > 15 (OR = 2.85), and Glasgow Coma Scale score < 9 (OR = 2.11) had increased odds. Results were similar for ultimate transport to a Level I or II center. Analyzing transport to a Level I, II, or III center demonstrated similar results except a Level III trauma center in county of residence was associated with increased odds (OR = 2.00 for initial and 2.21 for ultimate) of transport to a Level I, II, or III center. CONCLUSIONS: We identified factors independently associated with failure to transport injured older adults to trauma centers in statewide data collected after adoption of geriatric triage criteria. Lack of a trauma center in the county of residence remained a factor even in analyses that included ultimate transport.

Method development for the determination of elements in Hypericum perforatum L. (St John's wort) herb and preparations using inductively coupled plasma-optical emission spectroscopy and microwave digestion.

OBJECTIVES: A method was developed to analyze St John's wort (Hypericum perforatum L.) herb and preparations using inductively coupled plasma-optical emission spectroscopy (ICP-OES) to determine the quantity of 11 elements (Al, B, Ba, Ca, Cu, Fe, Mg, Mn, Ni, Sr and Zn). METHODS: This study includes the evaluation of digestion acids and calibration methods, as well as instrumental parameters such as choice of nebulizer and emission wavelength. KEY FINDINGS: Two nebulizers (Conikal and SeaSpray) performed similarly for most elements, and two optimum wavelengths were determined for each element. Five acids were evaluated for the digestion of the Polish Certified Reference Material Tea Leaves (INCT-TL-1), while three were taken forward to use for the different St John's wort formulations (i.e. herb, capsule and tablet). A simple protocol using 5 ml HNO3 was sufficient in most cases; however, variability was observed for elements often bound in silicates (e.g. Al, Fe and Zn). An external weighted calibration was also found to be preferential over unweighted, and the use of standard addition affected some concentration values up to 20%. CONCLUSIONS: Therefore, this paper presents the development and optimized method parameters to be used with ICP-OES that will allow the analysis of 11 key elements present in St John's wort herb and preparations.

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.

Genetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. By leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection, we systematically evaluated the potential role of PMMs in autism risk. Initial re-evaluation of published single-nucleotide variant (SNV) de novo mutations showed evidence consistent with putative PMMs for 11% of mutations. We developed a robust and sensitive SNV PMM calling approach integrating complementary callers, logistic regression modeling, and additional heuristics. In our high-confidence call set, we identified 470 PMMs in children, increasing the proportion of mosaic SNVs to 22%. Probands have a significant burden of synonymous PMMs and these mutations are enriched for computationally predicted impacts on splicing. Evidence of increased missense PMM burden was not seen in the full cohort. However, missense burden signal increased in subcohorts of families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mutations. Parental mosaic mutations that were transmitted account for 6.8% of the presumed de novo mutations in the children. PMMs were identified in previously implicated high-confidence neurodevelopmental disorder risk genes, such as CHD2, CTNNB1, SCN2A, and SYNGAP1, as well as candidate risk genes with predicted functions in chromatin remodeling or neurodevelopment, including ACTL6B, BAZ2B, COL5A3, SSRP1, and UNC79. We estimate that PMMs potentially contribute risk to 3%-4% of simplex ASD case subjects and future studies of PMMs in ASD and related disorders are warranted.

Tea and Recurrent Clostridium difficile Infection.

Background and Aims. Studies have shown effects of diet on gut microbiota. We aimed to identify foods associated with recurrent Clostridium difficile infection (CDI). Methods. In this cross-sectional survey, consecutive patients diagnosed with CDI were identified by electronic medical records. Colitis symptoms and positive Clostridium difficile assay were confirmed. Health-care onset-health-care facility associated CDI was excluded. Food surveys were mailed to 411 patients. Survey responses served as the primary outcome measure. Spearman's rank correlation identified risk factors for CDI recurrence. Results. Surveys were returned by 68 patients. Nineteen patients experienced CDI recurrence. Compared to patients without CDI recurrence, patients with CDI recurrence had more antibiotics prescribed preceding their infection (p = 0.003). Greater numbers of the latter also listed tea (p = 0.002), coffee (p = 0.013), and eggs (p = 0.013), on their 24-hour food recall. Logistic regression identified tea as the only food risk factor for CDI recurrence (adjusted OR: 5.71; 95% CI: 1.26-25.89). Conclusion. The present results indicate a possible association between tea and CDI recurrence. Additional studies are needed to characterize and confirm this association.

Elemental fingerprinting of Hypericum perforatum (St John's Wort) herb and preparations using ICP-OES and chemometrics.

St. John's wort (SJW) (Hypericum perforatum) is a herbal remedy commonly used to treat mild depression. The elemental profiles of 54 samples (i.e., dry herbs, tablets and capsules) were evaluated by monitoring 25 elements using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The major elemental constituents in the SJW samples were Ca (300-199,000µg/g), Mg (410-3,530µg/g), Al (4.4-900µg/g), Fe (1.154-760µg/g), Mn (2.4-261µg/g), Sr (0.88-83.6µg/g), and Zn (7-64µg/g). For the sixteen elements that could be reliably quantified, principal component analysis (PCA) was used to investigate underlying patterns in the data. PCA models identified 7 key elements (i.e., Ba, Ca, Cd, Mg, Mo, Ni and Y), which described 85% of the variance in the dataset in the first three principal components. The PCA approach resulted in a general delineation between the three different formulations and provides a basis for monitoring product quality in this manner.

Factors that Influence Trajectories of Delinquency Throughout Adolescence.

Given that one of the most powerful predictors of adult crime is the presence of behavior problems in childhood and adolescence, there is a need to further understand factors that determine behavior patterns during this developmental stage. This study focuses on stressful life experiences such as exposure to delinquent peers, racial discrimination, as well as family characteristics such as parenting style and family transitions. Data come from four waves of the Family and Community Health Survey, an African-American sample. The present study investigates 354 males from this dataset. We utilize a group-based trajectory model to estimate the number and type of trajectories of delinquency. We then estimate multinomial regression models to predict trajectory group membership. The results indicated that there were four distinct groups of offenders (negligible delinquents; early starter/declining; late starter; and early starter/chronic offenders). We predicted group membership using both early predictors and measures of change in these predictors across the study period. The results indicated that individuals who experience greater racial discrimination (both early in childhood and throughout adolescence) are more likely to be in trajectory groups that begin offending early and persist through adolescence. Additionally, those respondents who reported having friends with greater delinquent behavior were more likely to be in groups that began their offending early in life and persisted when compared to groups who started later or desisted as they entered adulthood. The results contribute to developmental research and provide information that may be helpful in preventing adolescents from persisting in antisocial behavior as they enter adulthood.

Position statement on visiting in adult critical care units in the UK.

To provide nurses with an evidence-based Position Statement on the standards patients and visitors should expect when visiting an adult critical care unit in the 21st century in the UK. The British Association of Critical Care Nurses (BACCN) is a leading organization for critical care nursing in the UK and regularly receives enquiries about best practice regarding visiting policies. Therefore, in keeping with the BACCN's commitment to provide evidence-based guidance for nurses, a Position Statement on visiting practices in adult critical care units was commissioned. This brought together experts from the field of critical care nursing and representatives from patient and relatives' groups to review visiting practices and the literature and produce a Position Statement. An extensive search of the literature was undertaken using the following databases: Blackwell Synergy, CINAHL, Medline, Swetswise, Cochrane Data Base of Systematic Reviews, National Electronic Library for Health, Institute for Healthcare Improvement and Google Scholar. After obtaining selected articles, the references from these articles were then evaluated for their relevance to this Position Statement and were retrieved. The evidence suggests a disparity between what nurses believe is best practice and what patients and visitors actually want. Historically, visitors have been perceived as being responsible for increasing noise, taking up space, taking up nursing time, hindering nursing care and spreading infection. The evidence reviewed for this Position Statement suggests there are many benefits to patients and nurses from visitors. There was no evidence to suggest that visitors pose a direct infection risk to patients. Clear visiting policies based on evidence will negate arbitrary decisions by nurses regarding who can visit and will lessen confusion and dispel myths which can only bring benefits to patients, staff and organizations. To make nurses aware of the physical and psychological benefits of visiting to patients. Visitors bring a positive energy to patients and can act as advocates. They can supply nurses with vital information about patients which will enable the nurse to provide more individualized care. Being cognizant of the evidence will help nurses develop policies on visiting which are up to date for the 21st century.

The effect of corporal punishment and verbal abuse on delinquency: mediating mechanisms.

While the link between parenting and delinquency is well established, there is less consensus among scholars with regards to the processes that account for this link. The current study had two objectives. The first was to disentangle the effects of African American parents' use of corporal punishment and verbal abuse on the conduct problems of their preteen children. The second was to investigate the mechanisms that explain this relationship, such as having low self-control or a hostile view of relationships, whereby these harsh parenting practices increase a youth's involvement in problem behavior. Further, we are interested in specifically addressing how these mechanisms may operate differently for males versus females. Analyses utilized structural equation modeling and longitudinal data spanning approximately 2.5 years from a sample of 704 (54.2 % female) African American children ages 10-12. The results indicated that verbal abuse was a more important predictor of conduct problems than corporal punishment. Additionally, we found that the mechanisms that mediated the impact of verbal abuse and corporal punishment on conduct problems varied by gender. For males, most of the effect of verbal abuse was mediated by low self-control, whereas anger/frustration was the primary mediator for females. Implications of these results and directions for future study are also discussed.

An activating transcription factor 5-mediated survival pathway as a target for cancer therapy?

Genes that are highly expressed in cancer cells and are essential for their viability are attractive targets for the development of novel cancer therapeutics. Activating transcription factor 5 (ATF5) is an anti-apoptotic protein that is highly expressed in malignant glioma but not normal brain tissues, and is essential for glioma cell survival. Recent work has revealed an essential survival pathway mediated by ATF5 in malignant glioma; pharmacological inhibition of this pathway leads to tumor regression in mice. ATF5 is also highly expressed in a variety of other cancers, and preliminary studies have shown that the ATF5-mediated survival pathway is active in diverse human cancer cell lines. Targeting this pathway may therefore have therapeutic implications for the treatment of a wide range of cancers. In this perspective, we summarize recent advances in ATF5 research, focusing on its role in promoting cancer and its potential as a target for cancer therapy.

Seasonal blood-feeding behavior of Culex tarsalis (Diptera: Culicidae) in Weld County, Colorado, 2007.

Studies on Culex tarsalis Coquillett in Colorado have shown marked seasonal variation in the proportion of blood meals from birds and mammals. However, limitations in the specificity of antibodies used in the precipitin test and lack of vertebrate host availability data warrant revisiting Cx. tarsalis blood feeding behavior in the context of West Nile virus (WNV) transmission. We characterized the host preference of Cx. tarsalis during peak WNV transmission season in eastern Colorado and estimated the relative contribution of different avian species to WNV transmission. Cx. tarsalis preferred birds to mammals each month, although the proportion of blood meals from mammals increased in July and August. The distribution of blood meals differed significantly across months, in part because of changes in the proportion of blood meals from American robins, a preferred host. The estimated proportion of WNV-infectious vectors derived from American robins declined from 60 to 1% between June and August. The majority of avian blood meals came from doves, preferred hosts that contributed 25-40% of the WNV-infectious mosquitoes each month. Active WNV transmission was observed in association with a large house sparrow communal roost. These data show how seasonal patterns in Cx. tarsalis blood feeding behavior relate to WNV transmission in eastern Colorado, with the American robin contributing greatly to early-season virus transmission and a communal roost of sparrows serving as a focus for late-season amplification.

Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome.

The p53 tumor suppressor protein has long been recognized as the central factor protecting humans from cancer. It has been famously dubbed "the guardian of the genome" due to its ability to respond to genotoxic stress, such as DNA damage and other stress signals, and to protect the genome by inducing a variety of biological responses including DNA repair, cell cycle arrest, and apoptosis. However, the tumor suppressive effects of p53 go far beyond its roles in mediating these three processes. There is growing evidence that p53 also exerts its effects on multiple aspects of tumor formation, including suppression of metastasis and, as summarized in this review, inhibition of new blood vessel development (angiogenesis). The p53 protein has been shown to limit angiogenesis by at least three mechanisms: (1) interfering with central regulators of hypoxia that mediate angiogenesis, (2) inhibiting production of proangiogenic factors, and (3) directly increasing the production of endogenous angiogenesis inhibitors. The combination of these effects allows p53 to efficiently shut down the angiogenic potential of cancer cells. Inactivation of p53, which occurs in approximately half of all tumors, reverses these effects; as a consequence, tumors carrying p53 mutations appear more vascularized and are often more aggressive and correlate with poor prognosis for treatment. Thus, the loss of functional p53 during tumorigenesis likely represents an essential step in the switch to an angiogenic phenotype that is displayed by aggressive tumors.

Transcriptional regulatory elements in the human genome.

The faithful execution of biological processes requires a precise and carefully orchestrated set of steps that depend on the proper spatial and temporal expression of genes. Here we review the various classes of transcriptional regulatory elements (core promoters, proximal promoters, distal enhancers, silencers, insulators/boundary elements, and locus control regions) and the molecular machinery (general transcription factors, activators, and coactivators) that interacts with the regulatory elements to mediate precisely controlled patterns of gene expression. The biological importance of transcriptional regulation is highlighted by examples of how alterations in these transcriptional components can lead to disease. Finally, we discuss the methods currently used to identify transcriptional regulatory elements, and the ability of these methods to be scaled up for the purpose of annotating the entire human genome.

Fluorescence resonance energy transfer as a method for dissecting in vivo mechanisms of transcriptional activation.

The first step in transcriptional activation of protein-coding genes involves the assembly on the promoter of a large PIC (pre-initiation complex) comprising RNA polymerase II and a suite of general transcription factors. Transcription is greatly enhanced by the action of promoter-specific activator proteins (activators) that function, at least in part, by increasing PIC formation. Activator-mediated stimulation of PIC assembly is thought to result from a direct interaction between the activator and one or more components of the transcription machinery, termed the 'target'. The unambiguous identification of direct, physiologically relevant in vivo targets of activators has been a considerable challenge in the transcription field. The major obstacle has been the lack appropriate experimental methods to measure direct interactions with activators in vivo. The development of spectral variants of green fluorescent protein has made it possible to perform FRET (fluorescence resonance energy transfer) analysis in living cells, thereby allowing the detection of direct protein-protein interactions in vivo. Here we discuss how FRET can be used to identify activator targets and to dissect in vivo mechanisms of transcriptional activation.

The Est1 subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance.

The telomerase-associated Est1 protein of Saccharomyces cerevisiae mediates enzyme access by bridging the interaction between the catalytic core of telomerase and the telomere-binding protein Cdc13. In addition to recruiting telomerase, Est1 may act as a positive regulator of telomerase once the enzyme has been brought to the telomere, as previously suggested by the inability of a Cdc13-Est2 fusion protein to promote extensive telomere elongation in an est1-Delta strain. We report here three classes of mutant Est1 proteins that retain association with the telomerase enzyme but confer different in vivo consequences. Class 1 mutants display a telomere replication defect but are capable of promoting extensive telomere elongation in the presence of a Cdc13-Est2 fusion protein, consistent with a defect in telomerase recruitment. Class 2 mutants fail to elongate telomeres even in the presence of the Cdc13-Est2 fusion, which is the phenotype predicted for a defect in the proposed second regulatory function of EST1. A third class of mutants impairs an activity of Est1 that is potentially required for the Ku-mediated pathway of telomere length maintenance. The isolation of mutations that perturb separate functions of Est1 demonstrates that a telomerase holoenzyme subunit can contribute multiple regulatory roles to telomere length maintenance.

Tiletamine-zolazepam, ketamine, and xylazine anesthesia of captive cheetah (Acinonyx jubatus).

Thirty-two anesthetic episodes used a combination of tiletamine-zolezepam (50 mg/ml each), ketamine (80 mg/ml), and xylazine (20 mg/ml) at various dosages for routine diagnostic and minor surgical procedures in 13 captive cheetahs (Acinonyx jubatus). The mean dosage (0.023 +/- 0.003 ml/kg) provided rapid induction with a single i.m. injection along with safe predictable working time, good muscle relaxation, and analgesia. Yohimbine administration subsequently accelerated smooth and rapid recovery.