Oxygen transfer during aerobic exercise in a varanid lizard Varanus mertensi is limited by the circulation

Oxygen transfer during sustained maximal exercise while locomoting on a treadmill at 0.33 m s(-1) was examined in a varanid lizard Varanus mertensi at 35degreesC. The rate of oxygen consumption ((V)over dot (O 2)) increased with locomotion from 3.49+/-0.75 (mean+/-S.D.) to 14.0+/-4.0 ml O-2 kg(-1) min(-1). Ventilation (V-E) increased, aided by increases in both tidal volume and frequency, in direct proportion to (V)over dot(O 2). The air convection requirement ((V)over dot(E)/(V)over dot(O 2)=27) was therefore maintained, together with arterial Pa-CO 2 and Pa-O 2. The alveolar-arterial P-O 2 difference (PA(O 2)-Pa-O 2) also remained unchanged during exercise from its value at rest, which was approximately 20 mmHg. Pulmonary diffusion for carbon monoxide (0.116+/-0.027 ml kg(-1) min(-1) mmHg(-1)) was double the value previously reported in V. exanthematicus and remained unchanged with exercise. Furthermore, exercise was associated with an increase in the arterial-venous O-2 content difference (Ca-O2-Cv(O 2)), which was assisted by a marked Bohr shift in the hemoglobin saturation curve and further unloading of venous O-2. During exercise the increase in cardiac output ((Q)over dot(tot)) did not match the increase in (V)over dot(O2) such that the blood convection requirement ((Q)over dot(tot)/(V)over dot (O 2)) decreased from the pre-exercise value of approximately 35 to 16 during exercise. Together, the results suggest that ventilation and O-2 transfer across the lung are adequate to meet the aerobic needs of V. mertensi during exercise, but the decrease in the blood convection requirement in the presence of a large arterial-venous O-2 content difference suggests that a limit in the transport of O-2 is imposed by the circulation

What causes the irregular cycle of the atmospheric tape recorder signal in HCN?

Variations in the mixing ratio of long-lived trace gases entering the stratosphere in the tropics are carried upward with the rising air with the signal being observable throughout the tropical lower stratosphere. This phenomenon, referred to as "atmospheric tape recorder" has previously been observed for water vapor, CO2, and CO which exhibit an annual cycle. Recently, based on Microwave Limb Sounder (MLS) and the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) satellite measurements, the tape recorder signal has been observed for hydrogen cyanide (HCN) but with an approximately two-year period. Here we report on a model simulation of the HCN tape recorder for the time period 2002-2008 using the Chemical Lagrangian Model of the Stratosphere (CLaMS). The model can reproduce the observed pattern of the HCN tape recorder signal if time-resolved emissions from fires in Indonesia are used as lower boundary condition. This finding indicates that inter-annual variations in biomass burning in Indonesia, which are strongly influenced by El Nino events, control the HCN tape recorder signal. A longer time series of tropical HCN data will probably exhibit an irregular cycle rather than a regular biannual cycle. Citation: Pommrich, R., R. Muller, J.-U. Grooss, G. Gunther, P. Konopka, M. Riese, A. Heil, M. Schultz, H.-C. Pumphrey, and K. A. Walker (2010), What causes the irregular cycle of the atmospheric tape recorder signal in HCN?, Geophys. Res. Lett., 37, L16805, doi:10.1029/2010GL044056

Hybrid Titanium/Biodegradable Polymer Implants with an Hierarchical Pore Structure as a Means to Control Selective Cell Movement

UNLABELLED: In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. METHODOLOGY/PRINCIPAL FINDINGS: A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 µm vs. 36.7±11.4 µm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. CONCLUSIONS: In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure

A Political Winner’s Curse: Why Preventive Policies Pass Parliament so Narrowly

Preventive policy measures such as bailouts often pass parliament very narrowly. We present a model of asymmetric information between politicians and voters which rationalizes this narrow parliamentary outcome. A successful preventive policy impedes the verification of its own necessity. When policy intervention is necessary but voters disagree ex-ante, individual politicians have an incentive to loose the vote in parliament in order to be rewarded by voters ex-post. Comfortable vote margins induce incentives to move to the loosing fraction to avoid this winner's curse. In equilibrium, parliamentary elections over preventive policies are thus likely to end at very narrow margins.Politikmaßnahmen zur Prävention einer drohenden Krise wie Bankenrettungen oder Finanzhilfen an notleidende Staaten erhalten häufig nur eine knappe Mehrheit im Parlament. Im vorliegenden Beitrag wird ein polit-ökonomisches Modell asymmetrischer Informationen zwischen Politikern und Wählern vorgestellt, aus dem sich diese knappen Parlamentsabstimmungen erklären lassen. Annahmegemäß haben die Politiker im Vorfeld der Parlamentsabstimmung (ex-ante) einen Informationsvorsprung gegenüber den Wählern was die Notwendigkeit der präventiven Politikmaßnahme betrifft. Selbst nach der Entscheidung über die Durchsetzung der Maßnahme (ex-post) erfahren die Wähler nur dann, ob die Maßnahme notwendig war, wenn sie nicht durchgesetzt wurde und die Folgen der ausbleibenden Krisenprävention sichtbar werden. Sofern die präventive Politik tatsächlich notwendig ist, um Schaden abzuwenden, die Wähler dies ex-ante aber nicht glauben, ergibt sich eine interessante Konstellation: Folgen die Politiker dem ex-ante-Willen der Wähler und wird dementsprechend die Politik nicht umgesetzt, tritt der volkswirtschaftliche Schaden auf. Dies wird ex-post offenkundig und die Wähler strafen die Politiker für ihre fehlerhafte Politik bei der nachfolgendenden Wahl ab. Entscheiden sich die Politiker hingegen dafür, die Politik zur Krisenprävention durchzusetzen, kann der Schaden abgewendet werden. Allerdings bleiben die Wähler ex-post im Unklaren darüber, ob die Politikmaßnahme tatsächlich notwendig war und somit bei ihrer ex-ante-Einstellung. Auch dann werden die Politiker für ihre als fehlerhaft erachtete Politik abgestraft. Hieraus ergibt sich für einen einzelnen Politiker im Parlament eine Situation, die im Aufsatz als Winner's Curse bezeichnet wird: Er erhält nur dann die Zustimmung der Wähler, wenn die Politik im Parlament durchgesetzt wird, er aber dagegen gestimmt hat, oder die Politik keine Mehrheit im Parlament erhält, er aber dafür gestimmt hat. Im Falle eines eindeutigen Mehrheitsverhältnisses entstehen somit individuelle Anreize, zur Minderheit abzuweichen. Die Wahrscheinlichkeit eines knappen Wahlausgangs steigt durch diese Anreize zur Abweichung

Vitamin K intake and atherosclerotic cardiovascular disease in the Danish diet cancer and health study

Background Dietary vitamin K (K1 and K2) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food‐frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K1 and vitamin K2 were estimated from the food‐frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52–60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17–22) years of follow‐up. Compared with participants with the lowest vitamin K1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD‐related hospitalization (hazard ratio, 0.79; 95% CI: 0.74–0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K2, the risk of an ASCVD‐related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K2 intake (hazard ratio, 0.86; 95% CI, 0.81–0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K1 or K2. The similar inverse associations with both vitamin K1 and K2, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention

Ventromedial Prefrontal Cortex Activation Is Associated with Memory Formation for Predictable Rewards

During reinforcement learning, dopamine release shifts from the moment of reward consumption to the time point when the reward can be predicted. Previous studies provide consistent evidence that reward-predicting cues enhance long-term memory (LTM) formation of these items via dopaminergic projections to the ventral striatum. However, it is less clear whether memory for items that do not precede a reward but are directly associated with reward consumption is also facilitated. Here, we investigated this question in an fMRI paradigm in which LTM for reward-predicting and neutral cues was compared to LTM for items presented during consumption of reliably predictable as compared to less predictable rewards. We observed activation of the ventral striatum and enhanced memory formation during reward anticipation. During processing of less predictable as compared to reliably predictable rewards, the ventral striatum was activated as well, but items associated with less predictable outcomes were remembered worse than items associated with reliably predictable outcomes. Processing of reliably predictable rewards activated the ventromedial prefrontal cortex (vmPFC), and vmPFC BOLD responses were associated with successful memory formation of these items. Taken together, these findings show that consumption of reliably predictable rewards facilitates LTM formation and is associated with activation of the vmPFC

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B

Tracing North Atlantic volcanism and seaway connectivity across the Paleocene–Eocene Thermal Maximum (PETM)

Abstract. There is a temporal correlation between the peak activity of the North Atlantic Igneous Province (NAIP) and the Paleocene–Eocene Thermal Maximum (PETM), suggesting that the NAIP may have initiated and/or prolonged this extreme warming event. However, corroborating a causal relationship is hampered by a scarcity of expanded sedimentary records that contain both climatic and volcanic proxies. One locality hosting such a record is the island of Fur in Denmark, where an expanded pre- to post-PETM succession containing hundreds of NAIP ash layers is exceptionally well preserved. We compiled a range of environmental proxies, including mercury (Hg) anomalies, paleotemperature proxies, and lithium (Li) and osmium (Os) isotopes, to trace NAIP activity, hydrological changes, weathering, and seawater connectivity across this interval. Volcanic proxies suggest that NAIP activity was elevated before the PETM and appears to have peaked during the body of the δ13C excursion but decreased considerably during the PETM recovery. This suggests that the acme in NAIP activity, dominated by flood basalt volcanism and thermogenic degassing from contact metamorphism, was likely confined to just ∼ 200 kyr (ca. 56.0–55.8 Ma). The hundreds of thick (> 1 cm) basaltic ashes in the post-PETM strata likely represent a change from effusive to explosive activity, rather than an increase in NAIP activity. Detrital δ7Li values and clay abundances suggest that volcanic ash production increased the basaltic reactive surface area, likely enhancing silicate weathering and atmospheric carbon sequestration in the early Eocene. Signals in lipid biomarkers and Os isotopes, traditionally used to trace paleotemperature and weathering changes, are used here to track seaway connectivity. These proxies indicate that the North Sea was rapidly cut off from the North Atlantic in under 12 kyr during the PETM recovery due to NAIP thermal uplift. Our findings reinforce the hypothesis that the emplacement of the NAIP had a profound and complex impact on Paleocene–Eocene climate, both directly through volcanic and thermogenic degassing and indirectly by driving regional uplift and changing seaway connectivity

Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS