Visualizing biological data in museums : Visitor learning with an interactive tree of life exhibit

In this study, we investigate museum visitor learning and engagement at an interactive visualization of an evolutionary tree of life consisting of over 70,000 species. The study was conducted at two natural history museums where visitors collaboratively explored the tree of life using direct touch gestures on a multi-touch tabletop display. In the study, 247 youth, aged 8-15 years, were randomly assigned in pairs to one of four conditions. In two of the conditions, pairs of youth interacted with different versions of the tree of life tabletop exhibit for a fixed duration of 10minutes. In a third condition, pairs watched a 10minute video on a similar topic. Individual responses on a 53-item exit interview were then compared to responses from a fourth, baseline condition. Contrasting with the baseline condition, visitors who interacted with the tabletop exhibits were significantly more likely to reason correctly about core evolutionary concepts, particularly common descent and shared ancestry. They were also more likely to correctly interpret phylogenetic tree diagrams. To investigate the factors influencing these learning outcomes, we used linear mixed models to analyze measures of dyads' verbal engagement and physical interaction with the exhibit. These models indicated that, while our verbal and physical measures were related, they accounted for significant portions of the variance on their own, independent of youth age, prior knowledge, and parental background. Our results provide evidence that multi-touch interactive exhibits that enable visitors to explore large scientific datasets can provide engaging and effective learning opportunities

Systemic Blood Pressure Trends and Antihypertensive Utilization Following Continuous-Flow Left Ventricular Assist Device Implantation: an Analysis of the Interagency Registry for Mechanically Assisted Circulatory Support

Background: Elevated systemic blood pressure (SBP) has been linked to complications in Continuous-flow left ventricular assist devices (CF-LVADs), including stroke and pump thrombosis. We queried Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to describe the response of SBP to CF-LVAD implantation and to delineate contemporary trends in antihypertensive (AH) utilization for patients with these pumps. Methods: We identified all CF-LVAD implantations in patients older than 18 years from 2006-2014, excluding those whose durations were less than 30 days. Pre-implant patient demographics and characteristics were obtained for each record. SBPs [i.e., mean arterial pressures (MAPs)], AH-use data, and vital status were tabulated, extending up to 5 years following implantation. Results: A total of 10,329 CF-LVAD implantations were included for study. Post-implant, SBPs increased rapidly during the first 3 months but plateaued thereafter; AH utilization mirrored this trend. By 6 months, mean MAPs climbed 12.2% from 77.6 mmHg (95% CI: 77.4-77.8) pre-implantation to 87.1 mmHg (95% CI: 86.7-87.4) and patients required a mean of 1.8 AH medications (95% CI: 1.75-1.78) -a 125% increase from AH use at 1-week post-implantation (0.8 AHs/patient, 95% CI: 0.81-0.83) but a 5.3% decrease from pre-implant utilization (1.9 AHs/patient, 95% CI: 1.90-1.92). Once medication changes stabilized, the most common AH regimens were lone beta blockade (15%, n=720) and a beta blocker plus an ACE inhibitor (14%, n=672). Conclusions: SBP rises rapidly after CF-LVAD implantation, stabilizing after 3 months, and is matched by concomitant changes in AH utilization; this AH use has increased over consecutive implant years

Rationale and design of a phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT

Background - Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH. Methods - ASA-STAT is a phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in 6 min at 6 months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups. Screening and enrollment - We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin. Conclusions - This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed

Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension

Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865)

Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension

Background—Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH. Methods and Results—We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at 4 centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was 6-minute walk distance at 6 months. Sixty-five subjects had been randomized when the trial was terminated by the Data Safety and Monitoring Board after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6-minute walk distance, there was no significant difference in the 6-minute walk distance at 6 months between aspirin (n=32) and placebo (n=33; placebo-corrected difference −0.5 m, 95% confidence interval −28.4 to 27.4 m; P=0.97) or between simvastatin (n=32) and placebo (n=33; placebo-corrected difference −27.6 m, 95% confidence interval −59.6 to 4.3 m; P=0.09). There tended to be more major bleeding episodes with aspirin than with placebo (4 events versus 1 event, respectively; P=0.17). Conclusions—Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications

Use of an electromagnetic colonoscope to assess maneuvers associated with cecal intubation

<p>Abstract</p> <p>Background</p> <p>Safe and effective colonoscopy is aided by the use of endoscopic techniques and maneuvers (ETM) during the examination including patient repositioning, stiffening of the endoscope and abdominal pressure.</p> <p>Aim</p> <p>To better understand the use and value of ETM during colonoscopy by using a device that allows real-time imaging of the colonoscope insertion shaft.</p> <p>Methods</p> <p>The use of ETM during colonoscopy and their success was recorded. Experienced colonoscopists and endoscopy assistants used a commercially available electromagnetic (EM) transmitter and a special adult variable stiffness instrument with 12 embedded sensors to examine 46 patients. In 5 of these a special EM probe passed through the instrument channel of a standard pediatric variable stiffness colonoscope was used instead of the EM colonoscope.</p> <p>Results</p> <p>Thirty-nine men and 7 women with a mean age of 64 years (range 33–90) were studied. The cecum was intubated in 93.5% (43/46). The mean time to reach the cecum was 10.6 minutes (range 3–25). ETM were used a total of 174 times in 41 of the patients to assist with cecal intubation. When ETM were required to reach the cecum, and the cecum was intubated, an average of 3.82 ETM/patient was used. While ETM were used most often when the tip of the colonoscope was in the left side of the colon (rectum 5.0%, sigmoid colon 20.7%, descending colon 5.0%, and splenic flexure 11.6%), when the instrument was in the transverse colon (14.8%), hepatic flexure (20.7%) and ascending colon (19.8%) the use of ETM was also required. When the colonoscope tip was in the transverse colon, hepatic flexure and ascending colon, ETM success rates were less (61.1%, 52.0%, and 41.7% respectively) compared to the left colon success rates (rectum 83.3%, sigmoid colon 84.0%, descending colon 100%, and splenic flexure 85.7%).</p> <p>Conclusion</p> <p>The EM colonoscope allows imaging of the insertion shaft without fluoroscopy and is a useful device for evaluating the efficacy of ETM. ETM are important tools of the colonoscopist and are used most often in the left colon where they are most effective.</p

Clinical risk factors for portopulmonary hypertension

Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dynes · second · cm−5, and pulmonary capillary wedge pressure ≤ 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio =2.90, 95% confidence interval 1.20-7.01, P = 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio = 4.02, 95% confidence interval 1.14-14.23, P = 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio =0.24, 95% confidence interval 0.09-0.65, P =0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension

The experimental power of FR900359 to study Gq-regulated biological processes.

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq

A Cell-Permeable Inhibitor to Trap Gαq Proteins in the Empty Pocket Conformation

In spite of the crucial role of heterotrimeric G proteins as molecular switches transmitting signals from G protein-coupled receptors, their selective manipulation with small molecule, cell-permeable inhibitors still remains an unmet challenge. Here, we report that the small molecule BIM-46187, previously classified as pan-G protein inhibitor, preferentially silences Gαq signaling in a cellular context-dependent manner. Investigations into its mode of action reveal that BIM traps Gαq in the empty pocket conformation by permitting GDP exit but interdicting GTP entry, a molecular mechanism not yet assigned to any other small molecule Gα inhibitor to date. Our data show that Gα proteins may be “frozen” pharmacologically in an intermediate conformation along their activation pathway and propose a pharmacological strategy to specifically silence Gα subclasses with cell-permeable inhibitors