Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

IntroductionCurrent evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice.AimThe aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics.MethodsA total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study.ResultsModel-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2(-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed.ConclusionIn conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.     

Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized,Comparator-Controlled,International Phase 3 Clinical Trial

Background

Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine.

Methods

This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included.The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.

Findings/Conclusions

The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity.     

The role of sponge-bacteria interactions: the sponge Aplysilla rosea challenged by its associated bacterium Streptomyces ACT-52A in a controlled aquarium system

Applied Microbiology and Biotechnology - Sponge-associated bacteria play a critical role in sponge biology, metabolism and ecology, but how they interact with their host sponges and the role of...     

The Predation Strategy of the Recluse Spider <Emphasis Type="Italic">Loxosceles rufipes</Emphasis> (Lucas, 1834) against four Prey Species

Generalist predators have to deal with prey with sometimes very different morphologies and defensive behaviors. Therefore, such predators are expected to express plasticity in their predation strategy. Here we investigated the predatory behavior of the recluse spider Loxosceles rufipes (Araneae, Sicariidae) when attacking prey with different morphologies and defensive mechanisms. We expected L. rufipes to show different prey capture strategies and variable acceptance towards each prey type. Potential prey species were collected directly from the web or in the surroundings of the web-building site of L. rufipes. We collected and used the following in our experiments: termite workers (Nasutitermes sp.), lepidopteran larvae (Eurema salome), ants (Camponotus sp.) and isopods (Tylidae). We paired these prey with L. rufipes and recorded their behavior in captivity, quantifying acceptance rate, immobilization time and the sequence of behaviors by the predator. The acceptance rate was lower for isopods but not different among other prey. The immobilization time was higher for isopods than for termites and similar for the other pairwise comparisons. The behavioral sequence was similar for all prey except for isopods, which were also bit more often. Our combined results show plasticity in the behavior of L. rufipes and also show it subdues a potentially dangerous prey (ant) and an armored prey (isopod).     

Tree growth,cambial phenology,and wood anatomy of limber pine at a Great Basin (USA) mountain observatory

Key message

Anatomical features of Pinus flexilis under warmer and drier conditions along an altitudinal transect revealed a shorter growing season and shifts in the timing of wood formation.

Abstract

Future climate change driven by greenhouse warming is expected to increase both frequency and severity of drought events and heat waves. Possible consequences for forest ecosystems include changes in foundation species and extended die-off phenomena. We investigated tree growth under the set of biotic and abiotic conditions, and their interactions, that are expected in a drier and warmer world using mountain observatories designed to capture elevation gradients in the Great Basin of North America. Stem cambial activity, wood anatomy, and radial growth of limber pine (Pinus flexilis) were examined at two different elevations using automated dendrometers and repeated histological microcores in 2013–2014. Mean annual temperature was 3.7° cooler at the higher site, which received 170 mm year^?1 of precipitation more than the lower site. Mean air temperature thresholds for xylogenesis computed using logistic regression were 7.7 and 12.0 °C at the higher and lower site, respectively. No differences in the onset date of cambial activity were found under such naturally contrasted conditions, with the global change analog provided by the lower site. Growing season was shortened by increasing drought stress at the lower site, thereby reducing xylem production. Stem expansion was only detectable by automated dendrometers at the higher site. Using elevation to simulate climatic changes and their realized ecosystem feedbacks, it was possible to express tree responses in terms of xylem phenology and anatomical adaptations.

     

Design‐to‐Device Approach Affords Panchromatic Co‐Sensitized Solar Cells

Data‐driven materials discovery has become increasingly important in identifying materials that exhibit specific, desirable properties from a vast chemical search space. Synergic prediction and experimental validation are needed to accelerate scientific advances related to critical societal applications. A design‐to‐device study that uses high‐throughput screens with algorithmic encodings of structure–property relationships is reported to identify new materials with panchromatic optical absorption, whose photovoltaic device applications are then experimentally verified. The data‐mining methods source 9431 dye candidates, which are auto‐generated from the literature using a custom text‐mining tool. These candidates are sifted via a data‐mining workflow that is tailored to identify optimal combinations of organic dyes that have complementary optical absorption properties such that they can harvest all available sunlight when acting as co‐sensitizers for dye‐sensitized solar cells (DSSCs). Six promising dye combinations are shortlisted for device testing, whereupon one dye combination yields co‐sensitized DSSCs with power conversion efficiencies comparable to those of the high‐performance, organometallic dye, N719. These results demonstrate how data‐driven molecular engineering can accelerate materials discovery for panchromatic photovoltaic or other applications.