Dobutamine stress MRI in pulmonary hypertension: relationships between stress pulmonary artery relative area change, RV performance, and 10-year survival

In pulmonary hypertension (PH), right ventricular (RV) performance determines survival. Pulmonary artery (PA) stiffening is an important biomechanical event in PH and also predicts survival based on the PA relative area change (RAC) measured at rest using magnetic resonance imaging (MRI). In this exploratory study, we sought to generate novel hypotheses regarding the influence of stress RAC on PH prognosis and the interaction between PA stiffening, RV performance and survival. Fifteen PH patients underwent dobutamine stress-MRI (ds-MRI) and right heart catheterization. RACREST, RACSTRESS, and ΔRAC (RAC STRESS – RAC REST) were correlated against resting invasive hemodynamics and ds-MRI data regarding RV performance and RV-PA coupling efficiency (n’vv [RV stroke volume/RV end-systolic volume]). The impact of RAC, RV data, and n’vv on ten-year survival were determined using Kaplan–Meier analysis. PH patients with a low ΔRAC (<−2.6%) had a worse long-term survival (log-rank P = 0.045, HR for death = 4.46 [95% CI = 1.08–24.5]) than those with ΔRAC ≥ −2.6%. Given the small sample, these data should be interpreted with caution; however, low ΔRAC was associated with an increase in stress diastolic PA area indicating proximal PA stiffening. Associations of borderline significance were observed between low RACSTRESS and low n’vvSTRESS, Δη’VV, and ΔRVEF. Further studies are required to validate the potential prognostic impact of ΔRAC and the biomechanics potentially connecting low ΔRAC to shorter survival. Such studies may facilitate development of novel PH therapies targeted to the proximal PA

Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization

Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry–based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. α- and β-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A–TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation

Functional nanostructures by NiCCo-PISA of helical poly(aryl isocyanide) copolymers

Herein, we present a straightforward and versatile methodology to achieve functional polymeric nano-objects that contain helical cores. Nickel-catalysed coordination polymerisation-induced self-assembly (NiCCo-PISA) of helical poly(aryl isocyanide) amphiphilic diblock copolymers was..

Epidemiology of patients presenting to the emergency centre of Princess Marina Hospital in Gaborone, Botswana

Emergency medicine is a newly recognized specialty in Botswana and the country launched an emergency medicine residency in January 2011. Data regarding the practice of emergency medicine in Botswana are limited. This study reviewed 1 year of patient presentations to the emergency centre of Princess Marina Hospital, the country’s main referral hospital located in the capital city, Gaborone. Methods: Epidemiologic data of all patients presenting to the emergency centre between May 2010 and April 2011 were extracted into a database. The diagnoses of a random sample of patient presentations were coded using the categories outlined by the Clinical Classifications Software (CCS) for ICD-10. For ease of analysis, several CCS categories were grouped together for subsequent analysis. Results: 24,905 patient encounters were recorded during the study period. A large proportion of patients were aged between 25 and 50 years old. 20% of patients presented with a traumatic injury. The most common diagnoses across all ages included trauma, pregnancy complications, gastrointestinal disorders, and pneumonia. Conclusion: These results can inform the development of emergency medicine education and acute care systems in Botswana

Different Psychophysiological Responses to a High-intensity Repetition Session Performed Alone or in a Group by Elite Middle-distance Runners

Internal training load refers to the degree of disturbance in psychophysiological homeostasis provoked by a training session and has been traditionally measured through session-RPE, which is the product of the session Rate of Perceived Exertion (RPE) and the duration. External training load refers to the actual physical work completed, and depends on session volume, intensity, frequency and density. Drafting, which is achieved by running closely behind another runner has been demonstrated to reduce the energy cost of running at a fixed speed and to improve performance. Therefore, it is hypothesized that psychophysiological responses might reflect different levels of internal load if training is performed individually or collectively. 16 elite middle-distance runners performed two high-intensity training sessions consisting of 4 repetitions of 500 m separated by 3 minutes of active recovery. Sessions were performed individually and collectively. Times for each repetition, RPE, core affect (valence and felt arousal) and blood lactate concentrations [BLa] were measured after each repetition. Main time effect was significant and increased across repetitions for [BLa] and RPE (p <0.001), and decreased for valence (p =0.001). Main group effect was significant and values were higher when training individually for [BLa] (p =0.003) and RPE (p =0.001), and lower for valence (p =0.001). No differential responses were found between conditions in terms of repeat time or felt arousal. Findings demonstrate that elite middle-distance athletes running collectively display lower levels of internal training load compared to running alone, despite external training load being similar

Intercomparison of Satellite-Derived Snow-Cover Maps

In anticipation of the launch of the Earth Observing System (EOS) Terra, and the PM-1 spacecraft in 1999 and 2000, respectively, efforts are ongoing to determine errors of satellite-derived snow-cover maps. EOS Moderate Resolution Imaging Spectroradiometer (MODIS) and Advanced Microwave Scanning Radiometer-E (AMSR-E) snow-cover products will be produced. For this study we compare snow maps covering the same study area acquired from different sensors using different snow- mapping algorithms. Four locations are studied: 1) southern Saskatchewan; 2) a part of New England (New Hampshire, Vermont and Massachusetts) and eastern New York; 3) central Idaho and western Montana; and 4) parts of North and South Dakota. Snow maps were produced using a prototype MODIS snow-mapping algorithm used on Landsat Thematic Mapper (TM) scenes of each study area at 30-m and when the TM data were degraded to 1 -km resolution. National Operational Hydrologic Remote Sensing Center (NOHRSC) 1 -km resolution snow maps were also used, as were snow maps derived from 1/2 deg. x 1/2 deg. resolution Special Sensor Microwave Imager (SSM/1) data. A land-cover map derived from the International Geosphere-Biosphere Program (IGBP) land-cover map of North America was also registered to the scenes. The TM, NOHRSC and SSM/I snow maps, and land-cover maps were compared digitally. In most cases, TM-derived maps show less snow cover than the NOHRSC and SSM/I maps because areas of incomplete snow cover in forests (e.g., tree canopies, branches and trunks) are seen in the TM data, but not in the coarser-resolution maps. The snow maps generally agree with respect to the spatial variability of the snow cover. The 30-m resolution TM data provide the most accurate snow maps, and are thus used as the baseline for comparison with the other maps. Comparisons show that the percent change in amount of snow cover relative to the 3 0-m resolution TM maps is lowest using the TM I -km resolution maps, ranging from 0 to 40%. The highest percent change (less than 100%) is found in the New England study area, probably due to the presence of patchy snow cover. A scene with patchy snow cover is more difficult to map accurately than is a scene with a well-defined snowline such as is found on the North and South Dakota scene where the percent change ranged from 0 to 40%. There are also some important differences in the amount of snow mapped using the two different SSM/I algorithms because they utilize different channels

Pre-EDIT: protocol for a randomised feasibility trial of elastance-directed intrapleural catheter or talc pleurodesis (EDIT) in malignant pleural effusion

Introduction: Non-expansile lung (NEL) is a common cause of talc pleurodesis (TP) failure in malignant pleural effusion (MPE), but is often occult prior to drainage. Reliable detection of NEL would allow patients to be allocated between intrapleural catheter (IPC) and TP. High pleural elastance (PEL) has been associated with NEL in observational studies. Pre-EDIT is a randomised feasibility trial of elastance-directed IPC or TP (EDIT) management using a novel, purpose-built digital pleural manometer (Rocket Medical, UK). Methods and analysis: Consecutive patients with MPE without prior evidence of NEL or preference for IPC will be randomised 1:1 between EDIT management and standard care (an attempt at TP). The primary objective is to determine whether sufficient numbers of patients (defined as 30 within 12 months (or 15 over 6 months)) can be recruited and randomised to justify a subsequent phase III trial testing the efficacy of EDIT management. Secondary objectives include safety, technical feasibility and validation of study design elements, including the definition of PEL using 4D pleural MRI before and after fluid aspiration. EDIT involves PEL assessment during a large volume pleural fluid aspiration, followed by an attempt at TP or placement of an IPC within 24 hours. Patients will be allocated to IPC if the rolling average PEL sustained over at least 250 mL fluid aspirated (PEL250) is ≥ 14.5 cm H2O/L. Ethics and dissemination: Pre-EDIT was approved by the West of Scotland Regional Ethics Committee on 8 March 2017 (Ref: 17/WS/0042). Results will be presented at scientific meetings and published in peer-reviewed journals

Intelligence and ambition are distributed equally around the globe

The impact of freely accessible knowledge distribution platforms is briefly discussed

Heterogeneous models place the root of the placental mammal phylogeny

Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root