Showing papers by "Saint Louis University published in 2014"

Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection

Abstract: Background Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. Methods We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir–sofosbuvir plus ribavirin for 12 weeks, ledipasvir–sofosbuvir for 24 weeks, or ledipasvir–sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Results Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of ...

Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis

Abstract: BACKGROUND High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. METHODS In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir–sofosbuvir) for 8 weeks, ledipasvir–sofosbuvir plus ribavirin for 8 weeks, or ledipasvir–sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. RESULTS The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir–sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir–sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir–sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir–sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, −4 to 6) and the rate in the group that received 8 weeks of ledipasvir–sofosbuvir with ribavirin was 1 percentage point lower (95% CI, −6 to 4); these results indicated noninferiority of the 8-week ledipas vir–sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir–sofosbuvir discontinued treatment owing to adverse events. CONCLUSIONS Ledipasvir–sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.)

Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study

Abstract: Summary Background In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF V600 mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF V600E and BRAF V600K mutation subgroups. Methods Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF V600 mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m 2 of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980. Findings 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7–16·0) on vemurafenib and 9·5 months (3·1–14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months [95% CI 12·0–15·2] vs 9·7 months [7·9–12·8]; hazard ratio [HR] 0·70 [95% CI 0·57–0·87]; p=0·0008), as was median progression-free survival (6·9 months [95% CI 6·1–7·0] vs 1·6 months [1·6–2·1]; HR 0·38 [95% CI 0·32–0·46]; p BRAF V600E disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9–14·9) compared with 10·0 months (8·0–14·0) in the dacarbazine group (HR 0·75 [95% CI 0·60–0·93]; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2–7·0) and 1·6 months (1·6–2·1), respectively (HR 0·39 [95% CI 0·33–0·47]; p BRAF V600K disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2–not estimable) compared with 7·6 months (6·1–16·6) in the dacarbazine group (HR 0·43 [95% CI 0·21–0·90]; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4–9·0) and 1·7 months (1·4–2·9), respectively (HR 0·30 [95% CI 0·16–0·56]; p Interpretation Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF V600E mutation and in patients with the less common BRAF V600K mutation. Funding F Hoffmann-La Roche-Genentech.

Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials.

Abstract: Importance Reducing early ( Objective To synthesize the evidence of the efficacy of interventions to reduce early hospital readmissions and identify intervention features—including their impact on treatment burden and on patients’ capacity to enact postdischarge self-care—that might explain their varying effects. Data Sources We searched PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus (1990 until April 1, 2013), contacted experts, and reviewed bibliographies. Study Selection Randomized trials that assessed the effect of interventions on all-cause or unplanned readmissions within 30 days of discharge in adult patients hospitalized for a medical or surgical cause for more than 24 hours and discharged to home. Data Extraction and Synthesis Reviewer pairs extracted trial characteristics and used an activity-based coding strategy to characterize the interventions; fidelity was confirmed with authors. Blinded to trial outcomes, reviewers noted the extent to which interventions placed additional work on patients after discharge or supported their capacity for self-care in accordance with the cumulative complexity model. Main Outcomes and Measures Relative risk of all-cause or unplanned readmission with or without out-of-hospital deaths at 30 days postdischarge. Results In 42 trials, the tested interventions prevented early readmissions (pooled random-effects relative risk, 0.82 [95% CI, 0.73-0.91]; P I 2 = 31%), a finding that was consistent across patient subgroups. Trials published before 2002 reported interventions that were 1.6 times more effective than those tested later (interaction P = .01). In exploratory subgroup analyses, interventions with many components (interaction P = .001), involving more individuals in care delivery (interaction P = .05), and supporting patient capacity for self-care (interaction P = .04) were 1.4, 1.3, and 1.3 times more effective than other interventions, respectively. A post hoc regression model showed incremental value in providing comprehensive, postdischarge support to patients and caregivers. Conclusions and Relevance Tested interventions are effective at reducing readmissions, but more effective interventions are complex and support patient capacity for self-care. Interventions tested more recently are less effective.

Forecasting the Equity Risk Premium: The Role of Technical Indicators

Abstract: Academic research relies extensively on macroeconomic variables to forecast the U.S. equity risk premium, with relatively little attention paid to the technical indicators widely employed by practitioners. Our paper fills this gap by comparing the predictive ability of technical indicators with that of macroeconomic variables. Technical indicators display statistically and economically significant in-sample and out-of-sample predictive power, matching or exceeding that of macroeconomic variables. Furthermore, technical indicators and macroeconomic variables provide complementary information over the business cycle: technical indicators better detect the typical decline in the equity risk premium near business-cycle peaks, whereas macroeconomic variables more readily pick up the typical rise in the equity risk premium near cyclical troughs. Consistent with this behavior, we show that combining information from both technical indicators and macroeconomic variables significantly improves equity risk premium forecasts versus using either type of information alone. Overall, the substantial countercyclical fluctuations in the equity risk premium appear well captured by the combined information in technical indicators and macroeconomic variables. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2013.1838 . This paper was accepted by Wei Jiang, finance.

Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009

Abstract: Background The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. Methods We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Results Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infect...

Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology—update 2014

Abstract: Sarcopenia is now defined as a decline in walking speed or grip strength associated with low muscle mass Sarcopenia leads to loss of mobility and function, falls, and mortality Sarcopenia is a major cause of frailty, but either condition can occur without the other being present Sarcopenia is present in about 5 to 10 % of persons over 65 years of age It has multiple causes including disease, decreased caloric intake, poor blood flow to muscle, mitochondrial dysfunction, a decline in anabolic hormones, and an increase in proinflammatory cytokines Basic therapy includes resistance exercise and protein and vitamin D supplementation There is now a simple screening test available for sarcopenia—SARC-F All persons 60 years and older should be screened for sarcopenia and treated when appropriate

REV-ERB and ROR nuclear receptors as drug targets

Abstract: This Review highlights recent progress in the development of ligands to target two classes of nuclear receptors — the REV-ERBs and retinoic acid receptor-related orphan receptors (RORs) — and describes how such ligands might be useful for treating disorders related to metabolism, immune function and the circadian rhythm.

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

Abstract: Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vectors are engineered to replicate preferentially in cancer cells and to destroy cancer cells through the natural process of lytic virus replication. Many clinical trials indicate that replication-defective and replication-competent adenovirus vectors are safe and have therapeutic activity.

Understanding Employee Responses to Stressful Information Security Requirements: A Coping Perspective

Abstract: We use coping theory to explore an underlying relationship between employee stress caused by burdensome, complex, and ambiguous information security requirements (termed "security-related stress" or SRS) and deliberate information security policy (ISP) violations. Results from a survey of 539 employee users suggest that SRS engenders an emotion-focused coping response in the form of moral disengagement from ISP violations, which in turn increases one's susceptibility to this behavior. Our multidimensional view of SRS—comprised of security-related overload, complexity, and uncertainty—offers a new perspective on the workplace environment factors that foster noncompliant user behavior and inspire cognitive rationalizations of such behavior. The study extends technostress research to the information systems security domain and provides a theoretical framework for the influence of SRS on user behavior. For practitioners, the results highlight the incidence of SRS in organizations and suggest potential mechani...

Effects of green space spatial pattern on land surface temperature: Implications for sustainable urban planning and climate change adaptation

Abstract: The urban heat island (UHI) refers to the phenomenon of higher atmospheric and surface temperatures occurring in urban areas than in the surrounding rural areas. Mitigation of the UHI effects via the configuration of green spaces and sustainable design of urban environments has become an issue of increasing concern under changing climate. In this paper, the effects of the composition and configuration of green space on land surface temperatures (LST) were explored using landscape metrics including percentage of landscape (PLAND), edge density (ED) and patch density (PD). An oasis city of Aksu in Northwestern China was used as a case study. The metrics were calculated by moving window method based on a green space map derived from Landsat Thematic Mapper (TM) imagery, and LST data were retrieved from Landsat TM thermal band. A normalized mutual information measure was employed to investigate the relationship between LST and the spatial pattern of green space. The results showed that while the PLAND is the most important variable that elicits LST dynamics, spatial configuration of green space also has significant effect on LST. Though, the highest normalized mutual information measure was with the PLAND (0.71), it was found that the ED and PD combination is the most deterministic factors of LST than the unique effects of a single variable or the joint effects of PLAND and PD or PLAND and ED. Normalized mutual information measure estimations between LST and PLAND and ED, PLAND and PD and ED and PD were 0.7679, 0.7650 and 0.7832, respectively. A combination of the three factors PLAND, PD and ED explained much of the variance of LST with a normalized mutual information measure of 0.8694. Results from this study can expand our understanding of the relationship between LST and street trees and vegetation, and provide insights for sustainable urban planning and management under changing climate.

Medical student mental health 3.0: improving student wellness through curricular changes.

Abstract: Medical education can have significant negative effects on the well-being of medical students. To date, efforts to improve student mental health have focused largely on improving access to mental health providers, reducing the stigma and other barriers to mental health treatment, and implementing ancillary wellness programs. Still, new and innovative models that build on these efforts by directly addressing the root causes of stress that lie within the curriculum itself are needed to properly promote student wellness. In this article, the authors present a new paradigm for improving medical student mental health, by describing an integrated, multifaceted, preclinical curricular change program implemented through the Office of Curricular Affairs at the Saint Louis University School of Medicine starting in the 2009–2010 academic year. The authors found that significant but efficient changes to course content, contact hours, scheduling, grading, electives, learning communities, and required resilience/mindfulness experiences were associated with significantly lower levels of depression symptoms, anxiety symptoms, and stress, and significantly higher levels of community cohesion, in medical students who participated in the expanded wellness program compared with those who preceded its implementation. The authors discuss the utility and relevance of such curricular changes as an overlooked component of change models for improving medical student mental health.

The Ideological-Conflict Hypothesis: Intolerance Among Both Liberals and Conservatives

Abstract: Decades of research in social and political psychology have demonstrated that political conservatives appear more intolerant toward a variety of groups than do political liberals. Recent work from our three independent labs has challenged this conventional wisdom by suggesting that some of the psychological underpinnings of intolerance are not exclusive to people on either end of the political spectrum. These studies have demonstrated that liberals and conservatives express similar levels of intolerance toward ideologically dissimilar and threatening groups. We suggest directions for future research and discuss the psychological and political implications of our conclusions.

CMIP5 climate model analyses: Climate extremes in the United States

Abstract: This is the fourth in a series of four articles on historical and projected climate extremes in the United States. Here, we examine the results of historical and future climate model experiments from the phase 5 of the Coupled Model Intercomparison Project (CMIP5) based on work presented at the World Climate Research Programme (WCRP) Workshop on CMIP5 Climate Model Analyses held in March 2012. Our analyses assess the ability of CMIP5 models to capture observed trends, and we also evaluate the projected future changes in extreme events over the contiguous Unites States. Consistent with the previous articles, here we focus on model-simulated historical trends and projections for temperature extremes, heavy precipitation, large-scale drivers of precipitation variability and drought, and extratropical storms. Comparing new CMIP5 model results with earlier CMIP3 simulations shows that in general CMIP5 simulations give similar patterns and magnitudes of future temperature and precipitation extremes in the Unite...

A comparison of four frailty models

Abstract: Frailty is a condition that places older persons at risk of poor outcomes when exposed to stressful events.1 Frailty is present in approximately 5% of the population aged 60 and older.2 Numerous studies have suggested that frailty is a predictor of functional deterioration and mortality.3–5 Models of frailty have been developed using three different domains: functional, deficit accumulation, and biological.6–11 The Frailty Index (FI) was developed based on the concept that deficit accumulation—a combination of symptoms, diseases, conditions, and disability—can predict frailty.9 A biological model of frailty based on five components—weight loss, exhaustion, low energy expenditure, slowness, and weakness—is known as the Cardiovascular Health Study (CHS) scale.12 The Study of Osteoporotic Fractures (SOF) scale included one functional and two biological factors in its frailty index—inability to rise from a chair five times without using the arms, weight loss, and reduced energy level.13 The CHS and FI measures are not practical for use in a busy clinic. The CHS scale requires measured performance (walking speed, grip strength) and is scored based on relative values in a population. The FI includes numerous items, typically 40 or more, and may include measured performance (e.g., cognition, physical performance). The SOF scale is brief and easy to administer in a clinic but requires measured performance (chair stands). The FRAIL scale was recently developed as a simple measure that combines components of functional, deficit accumulation, and biological frailty models.14,15 The FRAIL scale was constructed to include only interview questions and require minimal administration time so that physicians and other health professionals can easily use it in clinical practice. Initial studies have shown that the FRAIL scale predicts adverse health outcomes,16–18 but research directly comparing different models of frailty is limited,19,20 and these studies have not included the FRAIL scale. African Americans have a higher level of functional impairment and disability than do Caucasians21 and have been shown to have a higher prevalence of frailty than Caucasians using the CHS model.22 Thus there is a need for a brief frailty tool that can be used to identify African Americans at risk of disability and mortality so that early interventions can be developed. African American Health (AAH) is a population-based study of late middle-aged African Americans from two socioeconomically diverse areas of St. Louis. The AAH population has been demonstrated to have excess disability21 and represents a population that could benefit greatly from early frailty identification by clinicians. The objective of this study was to investigate how well the interview-based, clinic-friendly FRAIL scale predicts future disability and mortality compared with the clinic-friendly SOF scale, the phenotype-based CHS scale, and the comprehensive FI in the AAH cohort. It was hypothesized that the FRAIL, CHS, and SOF measures and the FI would have predictive validity for disability and mortality and that the predictive validity of the FRAIL scale for disability and mortality would be similar to that of the SOF and CHS scales and the FI using receiver operating characteristic (ROC) contrasts.

Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis

Abstract: Background IL-23 expression is increased in psoriatic lesions and might regulate T H 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.

3D printed microfluidic devices with integrated versatile and reusable electrodes

Abstract: We report two 3D printed devices that can be used for electrochemical detection In both cases, the electrode is housed in commercially available, polymer-based fittings so that the various electrode materials (platinum, platinum black, carbon, gold, silver) can be easily added to a threaded receiving port printed on the device; this enables a module-like approach to the experimental design, where the electrodes are removable and can be easily repolished for reuse after exposure to biological samples The first printed device represents a microfluidic platform with a 500 × 500 μm channel and a threaded receiving port to allow integration of either polyetheretherketone (PEEK) nut-encased glassy carbon or platinum black (Pt-black) electrodes for dopamine and nitric oxide (NO) detection, respectively The embedded 1 mm glassy carbon electrode had a limit of detection (LOD) of 500 nM for dopamine and a linear response (R2 = 099) for concentrations between 25–500 μM When the glassy carbon electrode was coated with 005% Nafion, significant exclusion of nitrite was observed when compared to signal obtained from equimolar injections of dopamine When using flow injection analysis with a Pt/Pt-black electrode and standards derived from NO gas, a linear correlation (R2 = 099) over a wide range of concentrations (76–190 μM) was obtained, with the LOD for NO being 1 μM The second application showcases a 3D printed fluidic device that allows collection of the biologically relevant analyte adenosine triphosphate (ATP) while simultaneously measuring the release stimulus (reduced oxygen concentration) The hypoxic sample (48 ± 05 ppm oxygen) released 24 ± 04 times more ATP than the normoxic sample (84 ± 06 ppm oxygen) Importantly, the results reported here verify the reproducible and transferable nature of using 3D printing as a fabrication technique, as devices and electrodes were moved between labs multiple times during completion of the study

North American Climate in CMIP5 Experiments: Part III: Assessment of Twenty-First-Century Projections*

Abstract: In part III of a three-part study on North American climate in phase 5 of the Coupled Model Intercomparison Project (CMIP5) models, the authors examine projections of twenty-first-century climate in the representative concentration pathway 8.5 (RCP8.5) emission experiments. This paper summarizes and synthesizes results from several coordinated studies by the authors. Aspects of North American climate change that are examined include changes in continental-scale temperature and the hydrologic cycle, extremes events, and storm tracks, as well as regional manifestations of these climate variables. The authors also examine changes in the eastern North Pacific and North Atlantic tropical cyclone activity and North American intraseasonal to decadal variability, including changes in teleconnections to other regions of the globe. Projected changes are generally consistent with those previously published for CMIP3, although CMIP5 model projections differ importantly from those of CMIP3 in some aspects, inc...

Diagnosis and management of Neuro-Behcet's disease: international consensus recommendations.

Abstract: Neuro-Behcet’s disease (NBD) is one of the more serious manifestations of Behcet’s disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments.

The common marmoset genome provides insight into primate biology and evolution

Abstract: Kim Worley and colleagues report the whole-genome sequence of the common marmoset, Callithrix jacchus, the first New World monkey to be sequenced.

Violence and Externalizing Behavior Among Youth in the United States: Is There a Severe 5%?

Abstract: Despite research demonstrating that approximately 5% of study populations are composed of severely antisocial persons who account for a disproportionate share of problem behaviors, there have been no nationally representative studies assessing this phenomenon among adolescents. Using a large nationally representative sample (N = 18,614), we identified a severe group (4.7% of respondents) characterized by involvement in varied and intensive externalizing behaviors, greater internalizing, lower academic achievement, and less parental involvement. The current study is the first nationally representative study of criminal careers/externalizing behaviors among adolescents in the United States, which is convergent with prior research and theory. Language: en

International Union of Basic and Clinical Pharmacology. XC. Multisite Pharmacology: Recommendations for the Nomenclature of Receptor Allosterism and Allosteric Ligands

Abstract: Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

Luminol-Based Chemiluminescent Signals: Clinical and Non-clinical Application and Future Uses

Abstract: Chemiluminescence (CL) is an important method for quantification and analysis of various macromolecules. A wide range of CL agents such as luminol, hydrogen peroxide, fluorescein, dioxetanes and derivatives of oxalate, and acridinium dyes are used according to their biological specificity and utility. This review describes the application of luminol chemiluminescence (LCL) in forensic, biomedical, and clinical sciences. LCL is a very useful detection method due to its selectivity, simplicity, low cost, and high sensitivity. LCL has a dynamic range of applications, including quantification and detection of macro and micromolecules such as proteins, carbohydrates, DNA, and RNA. Luminol-based methods are used in environmental monitoring as biosensors, in the pharmaceutical industry for cellular localization and as biological tracers, and in reporter gene-based assays and several other immunoassays. Here, we also provide information about different compounds that may enhance or inhibit the LCL along with the effect of pH and concentration on LCL. This review covers most of the significant information related to the applications of luminol in different fields.