bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving saltland revegetation through understanding the “recruitment niche”: potential lessons for ecological restoration in extreme environments
Authors: Barrett‐Lennard Edward G. , Norman Hayley C. , Dixon Kingsley
Published: March 2016

Germination and emergence are often the most precarious stage in a plant's lifecycle: plants are particularly vulnerable to environmental stress at this time. Despite these constraints, plants colonize much of the planet including extreme environments. We argue that for many species, establishment in extreme situations is not because seed is adapted to germinate in extreme environments but because it falls into, and is spatially and temporally nurtured within, more benign “recruitment niches.” This principle has importance for revegetation in extreme environments such as the world's drylands. Using examples from ground‐breaking experiments conducted by CV Malcolm and colleagues between 1976 and 1982 on saltland revegetation with halophytes, we show that recruitment niches can be constructed based on an understanding of the key requirements that seeds need in their immediate environment to establish. As part of their studies, Malcolm's team developed a “niche seeder” capable of distributing and precisely placing fruits of Atriplex species in an elevated “V”‐shaped mound (to decrease waterlogging), covering the fruits with vermiculite (to decrease capillarity and therefore salinity at the soil surface), and spraying the placements with black paint (to increase soil temperatures). Subsequent studies in arid environments showed that the establishment of woody plants was also improved using stones on the soil surface to develop appropriate recruitment niches. Malcolm's identification of the “recruitment niche” is an important principle of broader relevance to the revegetation of degraded landscapes in extreme environments. In addition, the development of the niche seeder is an important case study in ecological restoration.
Multivariate Covariance Generalized Linear Models
Authors: Bonat Wagner Hugo , Jørgensen Bent
Published: March 2016

We propose a general framework for non-normal multivariate data analysis called multivariate covariance generalized linear models, designed to handle multivariate response variables, along with a wide range of temporal and spatial correlation structures defined in terms of a covariance link function combined with a matrix linear predictor involving known matrices. The method is motivated by three data examples that are not easily handled by existing methods. The first example concerns multivariate count data, the second involves response variables of mixed types, combined with repeated measures and longitudinal structures, and the third involves a spatiotemporal analysis of rainfall data. The models take non-normality into account in the conventional way by means of a variance function, and the mean structure is modelled by means of a link function and a linear predictor. The models are fitted by using an efficient Newton scoring algorithm based on quasi-likelihood and Pearson estimating functions, using only second-moment assumptions. This provides a unified approach to a wide variety of types of response variables and covariance structures, including multivariate extensions of repeated measures, time series, longitudinal, spatial and spatiotemporal structures.
The acute effect of match play on hamstring strength and lower limb flexibility in elite youth football players
Authors: Wollin M. , Thorborg K. , Pizzari T.
Published: March 2016

The aim of this study was to investigate the effect of competitive football match play on hamstring strength and lower limb flexibility. Fifteen male international youth football players were included. Hamstring strength and associated pain ratings, ankle dorsiflexion, hip extension, knee extension and flexion range of motion were evaluated immediately post‐match and at intervals of 24, 48, and 72 h post‐match. Strength significantly reduced post‐match (P < 0.01), mean difference −0.43 (CI95: −0.56, −0.30) and 24 h post (P < 0.05) mean difference −0.12 Nm/kg (CI95: −0.20, −0.04). The associated pain scores significantly increased at the post‐match (P < 0.01, ES = 0.61) and 24 h (P < 0.01, ES = 0.55) time intervals. At the 48 and 72 h post‐match tests no significant difference was found for strength or pain ratings. No significant differences were detected for any of the range of motion measures. Competitive football match play has a significant acute and transient effect on isometric hamstring strength and associated pain levels during resisted knee flexion in male international youth players. Range of motion measures appear to remain relatively unaffected by match play. Isometric hamstring strength testing and associated pain levels might be considered for inclusion in‐season to monitor player's post‐match hamstring recovery characteristics.
Different visual stimuli affect body reorientation strategies during sidestepping
Authors: Lee M. J. C. , Lloyd D. G. , Lay B. S. , Bourke P. D. , Alderson J. A.
Published: March 2016

Sidestepping in response to unplanned stimuli is a high‐risk maneuver for anterior cruciate ligament (ACL) injuries. Yet, differences in body reorientation strategies between high‐ and low‐level soccer players prior to sidestepping in response to quasi‐game‐realistic vs non‐game‐realistic stimuli, remain unknown. Fifteen high‐level (semi‐professional) and 15 low‐level (amateur) soccer players responded to a quasi‐game‐realistic one‐defender scenario (1DS) and two‐defender scenario (2DS), and non‐game‐realistic arrow‐planned condition (AP) and arrow‐unplanned condition (AUNP). The AP, 1DS, 2DS to AUNP represented increasing time constraints to sidestep. Selected biomechanics from the penultimate step to foot‐off were assessed using a mixed‐model (stimuli × skill) ANOVA (P < 0.05). Step length decreased in the defender scenarios compared with the arrow conditions. Support foot placement increased laterally, away from mid‐pelvis, with increasing temporal constraints. Greater trunk lateral flexion in the 1DS, 2DS, and AUNP has been associated with ACL injury onsets. Higher level players pushed off closer to their pelvic midline at initial foot contact in the 2DS especially. Higher level perception of game‐realistic visual information could have contributed to this safer neuromuscular strategy that, when understood better, could potentially be trained in lower level players to reduce ACL injury risk associated with dangerous sidestepping postures.
Issue Competence and its Influence on Voting Behavior in the Swiss 2015 Elections
Authors: Lutz Georg , Sciarini Pascal
Published: March 2016

The Liberal Radical party and – even more so – the Swiss People's party are the two winners of the Swiss 2015 election. In this contribution, we evaluate whether and to what extent issue ownership voting may help to account for the electoral success of these two parties. To that end, we distinguish the two dimensions – the associative and the competence dimension – of the concept and we rely on data from the on‐line, four‐wave panel survey carried out in the context of the Swiss election studies. Our results highlight the stability of issue ownership perceptions during the course of the campaign on the aggregate level, but they also show the substantial importance of issue ownership voting, on the individual level. More specifically, in line with earlier studies we find that competence issue ownership has a direct impact on the vote choice, whereas the impact of associative issue ownership is far more limited. For both parties under study, being seen as the most competent party on two important issues (migration and the economy) significantly contributes to the explanation of the vote choice.
The Health Penalty of the GED: Testing the Role of Noncognitive Skills, Health Behaviors, and Economic Factors*
Authors: Zajacova Anna , Montez Jennifer Karas
Published: March 2016

Objectives

The general educational development (GED) diploma is intended to be equivalent to a high school (HS) credential; however, recent evidence finds that GED recipients have worse health than HS graduates. This study aims to explain the health disadvantage, focusing on three domains: noncognitive skills, health behaviors, and economic factors.

Methods

We analyze data on 3,119 HS graduates and GED recipients in the NLSY79 who reported their health status at the age of 40. Logistic and ordinal regression models examine whether the three domains account for the GED health disadvantage.

Results

The GED health disadvantage was jointly explained by lower noncognitive skills, unhealthy behaviors, and adverse economic circumstances, with the latter being particularly important.

Conclusions

A multipronged approach may be necessary to reduce the GED health disadvantage, including improving noncognitive skills during K–12 education, expanding opportunities for employment and living wage for low‐skill workers, and continued focus on improving health behaviors.
The golden ark: arsenopyrite crystal plasticity and the retention of gold through high strain and metamorphism
Authors: Fougerouse Denis , Micklethwaite Steven , Halfpenny Angela , Reddy Steven M. , Cliff John B. , Martin Laure A. J. , Kilburn Matt , Guagliardo Paul , Ulrich Stanislav
Published: March 2016

Quantitative electron backscatter diffraction analysis and ion microprobe imaging of gold‐rich arsenopyrites provide the first insights into the crystal plasticity and element mobility behaviour of arsenopyrites through metamorphism (340°–460° and 2 kbar). Remarkably, the gold‐rich arsenopyrites remained structurally and chemically robust during high strain deformation. It was only during a superimposed lower strain deformation event, at a high angle to the preferred orientation of the arsenopyrites, that small amounts of crystal plasticity affected the arsenopyrites. During the low strain event, a dissolution–reprecipitation reaction resulted in loss of gold from the crystal lattice, facilitated by localised domains of recrystallisation, most likely due to fluid percolation along sub‐ and new grain boundaries. We suggest that the abundance and rheologically robust nature of gold‐rich arsenopyrite in giant gold deposits, affected by greenschist–amphibolite metamorphism, is actually critical in the preservation of those deposits.
Survival of seeds from perennial biomass species during commercial‐scale anaerobic digestion
Authors: Baute K A , Robinson D E , Van Eerd L L , Edson M , Sikkema P H , Gilroyed B H
Published: March 2016

Tall perennial grass species can be utilised as bioenergy feedstocks, but some are considered invasive species. Using biomass from such species as feedstocks for anaerobic digestion (AD) may introduce the risk of disseminating viable seeds onto agricultural lands during digestate application. To evaluate this risk, we investigated the survival rates of perennial grass seeds obtained from biomass species during AD. After removal from the digester, seeds were germinated and stained with tetrazolium chloride to determine viability. During three experimental runs, batches of 100 seeds from four species were exposed to 0, 2, 6, 12, 24, 48, 72 and 168 h of mesophilic (38°C) AD within a commercial‐scale digester. Seed viability of Phalaris arundinacea, Phragmites australis, Panicum virgatum and Solanum lycopersicum was reduced by 95% (LT95) after 29, 52, 98 and 105 h of AD respectively. Commercial digesters that utilise perennial grasses as a feedstock typically have retention times ranging from 240 to 1480 h, which greatly exceeds the LT95 values found in this study. Anaerobic digestion resulted in the rapid death of seeds in all species tested, suggesting unwanted dissemination of perennial grass species via digestate application to agricultural land is unlikely.
First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Chapter 2b: genetically modified source pigs
Authors: Cowan Peter J. , Ayares David , Wolf Eckhard , Cooper David K. C.
Published: March 2016

Genetic modification of the source pig offers the opportunity to improve the engraftment and survival of islet xenografts. The type of modification can be tailored to the transplant setting; for example, intraportal islet xenografts have been shown to benefit from the expression of anticoagulant and anti‐inflammatory transgenes, whereas cytoprotective transgenes are probably more relevant for encapsulated islets. The rapid development of pig genetic engineering, particularly with the introduction of genome editing techniques such as CRISPR‐Cas, has accelerated the generation of new pig lines with multiple modifications. With pre‐clinical testing in progress, it is an opportune time to consider any implications of genetic modification for the conditions for undertaking clinical trials. Obviously, the stringent requirements to fulfill designated pathogen‐free status that are applied to wild‐type pigs will apply equally to genetically modified (GM) source pigs. In addition, it is important from a safety perspective that the genetic modifications are characterized at the molecular level (e.g., integration site, absence of off‐target mutations), the phenotypic level (e.g., durability and stability of transgene expression), and the functional level (e.g., protection of islets in vitro or in vivo, absence of detrimental effects on insulin secretion). The assessment of clinical trial protocols using GM pig islets will need to be performed on a case‐by‐case basis, taking into account a range of factors including the particular genetic modification(s) and the site and method of delivery.
Fetal in vivo continuous cardiovascular function during chronic hypoxia
Authors: Allison B. J. , Brain K. L. , Niu Y. , Kane A. D. , Herrera E. A. , Thakor A. S. , Botting K. J. , Cross C. M. , Itani N. , Skeffington K. L. , Beck C. , Giussani D. A.
Published: March 2016

Key points

The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.

We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.

This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.

The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism.

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l−1, P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase‐derived reactive oxygen species.
Large Eddy Simulation of an Enclosed Turbulent Reacting Methane Jet With the Tabulated Premixed Conditional Moment Closure Method
Authors: Velez Carlos , Martin Scott , Jemcov Aleksander , Vasu Subith
Published: March 2016

The tabulated premixed conditional moment closure (T-PCMC) method has been shown to provide the capability to model turbulent, premixed methane flames with detailed chemistry and reasonable runtimes in Reynolds-averaged Navier–Stokes (RANS) environment by Martin et al. (2013, “Modeling an Enclosed, Turbulent Reacting Methane Jet With the Premixed Conditional Moment Closure Method,” ASME Paper No. GT2013-95092). Here, the premixed conditional moment closure (PCMC) method is extended to large eddy simulation (LES). The new model is validated with the turbulent, enclosed reacting methane backward facing step data from El Banhawy et al. (1983, “Premixed, Turbulent Combustion of a Sudden-Expansion Flow,” Combust. Flame, 50, pp. 153–165). The experimental data have a rectangular test section at atmospheric pressure and temperature with an inlet velocity of 10.5 m/s and an equivalence ratio of 0.9 for two different step heights. Contours of major species, velocity, and temperature are provided. The T-PCMC model falls into the class of table lookup turbulent combustion models in which the combustion model is solved offline over a range of conditions and stored in a table that is accessed by the computational fluid dynamic (CFD) code using three controlling variables: the reaction progress variable (RPV), variance, and local scalar dissipation rate. The local scalar dissipation rate is used to account for the affects of the small-scale mixing on the reaction rates. A presumed shape beta function probability density function (PDF) is used to account for the effects of subgrid scale (SGS) turbulence on the reactions. SGS models are incorporated for the scalar dissipation and variance. The open source CFD code OpenFOAM is used with the compressible Smagorinsky LES model. Velocity, temperature, and major species are compared to the experimental data. Once validated, this low “runtime” CFD turbulent combustion model will have great utility for designing the next generation of lean premixed (LPM) gas turbine combustors.
Cylindrical Borehole Failure in a Poroelastic Medium
Authors: Gao Yue , Liu Zhanli , Zhuang Zhuo , Hwang Keh-Chih , Wang Yonghui , Yang Lifeng , Yang Henglin
Published: March 2016

Drilling a cylindrical borehole is the first and important step in oil mining. Borehole design and strength check are big problems of utmost importance. Biot introduced a poroelastic constitutive theory for porous rock with freely moving fluid inside. In this paper, by using Biot poroelastic model, we analyze a borehole with drilling fluid in an infinite porous rock with three-dimensional in situ stresses and obtain whole domain solutions for instantaneous, short-time, and long-time stress distributions. Maximum and minimum allowable drilling pressures are given for tensile failure and shear failure criterions, and allowable drilling pressure regions are drawn in the space of in situ hydrostatic stress P0, deviatoric stress S0, and pore pressure p0. By comparing with classical elastic constitutive relations, or Hooke's model, the necessity of Biot poroelastic constitutive relations is shown.
Hierarchical Structure Enhances and Tunes the Damping Behavior of Load-Bearing Biological Materials
Authors: Qwamizadeh Mahan , Liu Pan , Zhang Zuoqi , Zhou Kun , Wei Zhang Yong
Published: March 2016

One of the most crucial functionalities of load-bearing biological materials such as shell and bone is to protect their interior organs from damage and fracture arising from external dynamic impacts. However, how this class of materials effectively damp stress waves traveling through their structure is still largely unknown. With a self-similar hierarchical model, a theoretical approach was established to investigate the damping properties of load-bearing biological materials in relation to the biopolymer viscous characteristics, the loading frequency, the geometrical parameters of reinforcements, as well as the hierarchy number. It was found that the damping behavior originates from the viscous characteristics of the organic (biopolymer) constituents and is greatly tuned and enhanced by the staggered and hierarchical organization of the organic and inorganic constituents. For verification purpose, numerical experiments via finite-element method (FEM) have also been conducted and shown results consistent with the theoretical predictions. Furthermore, the results suggest that for the self-similar hierarchical design, there is an optimal aspect ratio of reinforcements for a specific loading frequency and a peak loading frequency for a specific aspect ratio of reinforcements, at which the damping capacity of the composite is maximized. Our findings not only add valuable insights into the stress wave damping mechanisms of load-bearing biological materials, but also provide useful guidelines for designing bioinspired synthetic composites for protective applications.
On the Reduction of Combustion Noise by a Close-Coupled Pilot Injection in a Small-Bore Direct-Injection Diesel Engine
Authors: Busch Stephen , Zha Kan , Warey Alok , Pesce Francesco , Peterson Richard
Published: March 2016

For a pilot–main injection strategy in a single-cylinder light-duty diesel engine, the dwell between the pilot- and main-injection events can significantly impact combustion noise. As the solenoid energizing dwell decreases below 200 μs, combustion noise decreases by approximately 3 dB and then increases again at shorter dwells. A zero-dimensional thermodynamic model has been developed to capture the combustion noise reduction mechanism; heat release (HR) profiles are the primary simulation input and approximating them as top-hat shapes preserves the noise reduction effect. A decomposition of the terms of the underlying thermodynamic equation reveals that the direct influence of HR on the temporal variation of cylinder pressure is primarily responsible for the trend in combustion noise. Fourier analyses reveal the mechanism responsible for the reduction in combustion noise as a destructive interference in the frequency range between approximately 1 kHz and 3 kHz. This interference is dependent on the timing of increases in cylinder pressure during pilot HR relative to those during main HR. The mechanism by which combustion noise is attenuated is fundamentally different from the traditional noise reduction that occurs with the use of long-dwell pilot injections, for which noise is reduced primarily by shortening the ignition delay of the main injection. Band-pass filtering of measured cylinder pressure traces provides evidence of this noise reduction mechanism in the real engine. When this close-coupled pilot noise reduction mechanism is active, metrics derived from cylinder pressure such as the location of 50% HR, peak HR rates, and peak rates of pressure rise cannot be used reliably to predict trends in combustion noise. The quantity and peak value of the pilot HR affect the combustion noise reduction mechanism, and maximum noise reduction is achieved when the height and steepness of the pilot HR profile are similar to the initial rise of the main HR event. A variation of the initial rise rate of the main HR event reveals trends in combustion noise that are the opposite of what would happen in the absence of a close-coupled pilot. The noise reduction mechanism shown in this work may be a powerful tool to improve the tradeoffs among fuel efficiency, pollutant emissions, and combustion noise.
A Robotic Ankle–Foot Prosthesis With Active Alignment
Authors: Kennedy LaPrè Andrew , Umberger Brian R. , Sup Frank C.
Published: March 2016

An ankle–foot prosthesis designed to mimic the missing physiological limb generates a large sagittal moment during push off which must be transferred to the residual limb through the socket connection. The large moment is correlated with high internal socket pressures that are often a source of discomfort for the person with amputation, limiting prosthesis use. In this paper, the concept of active alignment is developed. Active alignment realigns the affected residual limb toward the center of pressure (CoP) during stance. During gait, the prosthesis configuration changes to shorten the moment arm between the ground reaction force (GRF) and the residual limb. This reduces the peak moment transferred through the socket interface during late stance. A tethered robotic ankle prosthesis has been developed, and evaluation results are presented for active alignment during normal walking in a laboratory setting. Preliminary testing was performed with a subject without amputation walking with able-bodied adapters at a constant speed. The results show a 33% reduction in the peak resultant moment transferred at the socket limb interface.
An Evaluation of Combustion and Emissions Performance With Low Cetane Naphtha Fuels in a Multicylinder Heavy-Duty Diesel Engine
Authors: Zhang Yu , Voice Alexander , Tzanetakis Tom , Traver Michael , Cleary David
Published: March 2016

Future projections in global transportation fuel use show a demand shift toward diesel and away from gasoline. At the same time, greenhouse gas regulations will drive higher vehicle fuel efficiency and lower well-to-wheel CO2 production. Naphtha, a contributor to the gasoline stream and requiring less processing at the refinery level, is an attractive candidate to mitigate this demand shift while lowering the overall greenhouse gas impact. This study investigates the combustion and emissions performance of two naphtha fuels (Naphtha 1: RON59 and Naphtha 2: RON69) and one ultra-low sulfur diesel (ULSD) in a model year (MY) 2013, six-cylinder, heavy-duty diesel engine. Engine testing was focused on the heavy-duty supplemental emissions test (SET) “B” speed over a load sweep from 5 to 15 bar BMEP (brake-specific mean pressure). At each operating point, NOx sweeps were conducted over wide ranges. At 10–15 bar BMEP, mixing-controlled combustion dominates the engine combustion process. Under a compression ratio of 18.9, cylinder pressure and temperature at these load conditions are sufficiently high to suppress the reactivity difference between ULSD and the two naphtha fuels. As a result, the three test fuels showed similar ignition delay (ID). Nevertheless, naphtha fuels still exhibited notable soot reduction compared to ULSD. Under mixing-controlled combustion, this is likely due to their lower aromatic content and higher volatility. At 10 bar BMEP, Naphtha 1 generated less soot than Naphtha 2 since it contains less aromatics and is more volatile. When operated at light load, in a less reactive thermal environment, the lower reactivity naphtha fuels lead to longer IDs than ULSD. As a result, the soot benefit of naphtha fuels was enhanced. Utilizing the soot benefit of the naphtha fuels, engine-out NOx was calibrated from the production level of 3–4 g/hp-hr down to 2–2.5 g/hp-hr over the 12 nonidle SET steady-state modes. At this reduced NOx level, naphtha fuels were still able to maintain a soot advantage over ULSD and remain “soot-free” while achieving diesel-equivalent fuel efficiency. Finally, low-temperature combustion (LTC) operation (NOx ≤ 0.2 g/hp-hr and smoke ≤ 0.2 FSN) was achieved with both of the naphtha fuels at 5 bar BMEP through a late injection approach with high injection pressure. Under high exhaust gas recirculation (EGR) dilution, Naphtha 2 showed an appreciably longer ID than Naphtha 1, resulting in a soot reduction benefit.
Advances in Medical Physics
Authors: Winey Brian
Published: March 2016

Advances in Medical Physics. 5th ed Editors: Devon J. Godfrey, Shiva K. Das, and Anthony B. Wolbarst. Medical Physics Publishing, Madison, WI, 2014. 289 pp. Price: $95.00. ISBN: 978‐1‐930524‐63‐7 (hardcover).
Properly dividing with YAP
Authors: Pfeifer Gerd P.
Published: March 2016

YAP helps to define where cells undergoing mitosis separate.
Pain in the joint
Authors: VanHook Annalisa M.
Published: March 2016

Lipids activate an acid-sensing channel to produce pain signals.
Relationship between Adherence to Oral Antibiotics and Postdischarge Clinical Outcomes among Patients Hospitalized with Staphylococcus aureus Skin Infections
Authors: Eells Samantha J. , Nguyen Megan , Jung Jina , Macias-Gil Raul , May Larissa , Miller Loren G.
Published: March 2016

Skin and soft tissue infections are common and frequently recur. Poor adherence to antibiotic therapy may lead to suboptimal clinical outcomes. However, adherence to oral antibiotic therapy for skin and soft tissue infections and its relationship to clinical outcomes have not been examined. We enrolled adult patients hospitalized with uncomplicated skin and soft tissue infections caused by
Staphylococcus aureus
who were being discharged with oral antibiotics to complete therapy. We fit the participants' pill bottles with an electronic bottle cap that recorded each pill bottle opening, administered an in-person standardized questionnaire at enrollment, 14 days, and 30 days, and reviewed the participants' medical records to determine outcomes. Our primary outcome was poor clinical response, defined as a change in antibiotic therapy, new incision-and-drainage procedure, or new skin infection within 30 days of hospital discharge. Of our 188 participants, 87 had complete data available for analysis. Among these participants, 40 (46%) had a poor clinical response at 30 days. The mean electronically measured adherence to antibiotic therapy was significantly different than the self-reported adherence (57% versus 96%;
P
< 0.0001). In a multivariable model, poor clinical response at 30 days was associated with patients having lower adherence, being nondiabetic, and reporting a lack of illicit drug use within the previous 12 months (
P
< 0.05). In conclusion, we found that patient adherence to oral antibiotic therapy for a skin and soft tissue infection after hospital discharge was low (57%) and associated with poor clinical outcome. Patients commonly overstate their medication adherence, which may make identification of patients at risk for nonadherence and poor outcomes challenging. Further studies are needed to improve postdischarge antibiotic adherence after skin and soft tissue infections.
In Vitro
Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014)
Authors: de Jonge Boudewijn L. M. , Karlowsky James A. , Kazmierczak Krystyna M. , Biedenbach Douglas J. , Sahm Daniel F. , Nichols Wright W.
Published: March 2016

The activity of ceftazidime-avibactam was assessed against 961 isolates of meropenem-nonsusceptible
Enterobacteriaceae
. Most meropenem-nonsusceptible metallo-β-lactamase (MBL)-negative isolates (97.7%) were susceptible to ceftazidime-avibactam. Isolates that carried KPC or OXA-48-like β-lactamases, both alone and in combination with extended-spectrum β-lactamases (ESBLs) and/or AmpC β-lactamases, were 98.7% and 98.5% susceptible to ceftazidime-avibactam, respectively. Meropenem-nonsusceptible, carbapenemase-negative isolates demonstrated 94.7% susceptibility to ceftazidime-avibactam. Ceftazidime-avibactam activity was compromised only in isolates for which carbapenem resistance was mediated through metallo-β-lactamases.
Tigecycline Is Highly Efficacious against Mycobacterium abscessus Pulmonary Disease
Authors: Ferro Beatriz E. , Srivastava Shashikant , Deshpande Devyani , Pasipanodya Jotam G. , van Soolingen Dick , Mouton Johan W. , van Ingen Jakko , Gumbo Tawanda
Published: March 2016

Mycobacterium abscessus
causes chronic pulmonary infections that are extremely difficult to cure. The currently recommended combination therapy is associated with high failure rates and relapse. Tigecycline has been explored in salvage regimens, with a response rate of 43% in those who received at least a month of therapy. We performed a dose-response study in a hollow-fiber system model of pulmonary
M. abscessus
infection in which we recapitulated tigecycline human pulmonary concentration-time profiles of 8 different doses for 21 days. We identified the maximal kill or efficacy in CFU per milliliter and the ratio of the 0- to 24-h area under the concentration-time curve to MIC (AUC/MIC) associated with 80% efficacy (EC
80
). The tigecycline efficacy was 5.38 ± 2.35 log
10
CFU/ml, and the drug achieved the unprecedented feat of a bacterial level of 1.0 log
10
CFU/ml below the pretreatment inoculum (1-log kill) of
M. abscessus
in the hollow-fiber system. The EC
80
AUC/MIC ratio was 36.65, while that for a 1-log kill was 44.6. Monte Carlo experiments with 10,000 patients were used to identify the clinical dose best able to achieve the EC
80
or 1-log kill. The standard dose of 100 mg/day had a cumulative fraction of response of 51% for the EC
80
and 46% for 1-log kill. For both the EC
80
target and 1-log kill, the optimal tigecycline clinical dose was identified as 200 mg/day. The susceptibility breakpoint was ≤0.5 mg/liter. Tigecycline is the most active single agent evaluated to date, and we propose that 200 mg/day be examined as the backbone of new combination therapy regimens to replace current treatment.
Haemophilus ducreyi Seeks Alternative Carbon Sources and Adapts to Nutrient Stress and Anaerobiosis during Experimental Infection of Human Volunteers
Authors: Gangaiah Dharanesh , Zhang Xinjun , Baker Beth , Fortney Kate R. , Gao Hongyu , Holley Concerta L. , Munson Robert S. , Liu Yunlong , Spinola Stanley M.
Published: March 2016

Haemophilus ducreyi
causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans,
H. ducreyi
resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014,
http://dx.doi.org/10.1128/mBio.01081-13
) suggested that
H. ducreyi
encounters growth conditions in human lesions resembling those found in stationary phase. However, how
H. ducreyi
transcriptionally responds to stress during human infection is unknown. Here, we determined the
H. ducreyi
transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the
in vivo
transcriptome is distinct from those of
in vitro
growth. Compared to the inoculum (mid-log-phase bacteria),
H. ducreyi
harvested from pustules differentially expressed ∼93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (
l
-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis.
H. ducreyi
upregulated few genes (
hgbA
,
flp-tad
, and
lspB-lspA2
) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed
in vivo
, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the
in vivo
transcriptome is distinct from those of
in vitro
growth and that adaptation to nutrient stress and anaerobiosis is crucial for
H. ducreyi
survival in humans.
FAD-I, a Fusobacterium nucleatum Cell Wall-Associated Diacylated Lipoprotein That Mediates Human Beta Defensin 2 Induction through Toll-Like Receptor-1/2 (TLR-1/2) and TLR-2/6
Authors: Bhattacharyya Sanghamitra , Ghosh Santosh K. , Shokeen Bhumika , Eapan Betty , Lux Renate , Kiselar Janna , Nithianantham Stanley , Young Andrew , Pandiyan Pushpa , McCormick Thomas S. , Weinberg Aaron
Published: March 2016

We previously identified a cell wall-associated protein fromFusobacterium nucleatum, a Gram-negative bacterium of the oral cavity, that induces human beta defensin 2 (hBD-2) in primary human oral epithelial cells (HOECs) and designated it FAD-I (Fusobacterium-associateddefensininducer). Here, we report differential induction of hBD-2 by different strains ofF. nucleatum; ATCC 25586 and ATCC 23726 induce significantly more hBD-2 mRNA than ATCC 10953. Heterologous expression of plasmid-bornefadIfrom the highly hBD-2-inducing strains in a ΔfadImutant of ATCC 10953 resulted in hBD-2 induction to levels comparable to those of the highly inducing strains, indicating that FAD-I is the principalF. nucleatumagent for hBD-2 induction in HOECs. Moreover, anti-FAD-I antibodies blockedF. nucleatuminduction of hBD-2 by more than 80%. Recombinant FAD-I (rFAD-I) expressed inEscherichia colitriggered levels of hBD-2 transcription and peptide release in HOECs similar to those of native FAD-I (nFAD-I) isolated fromF. nucleatumATCC 25586. Tandem mass spectrometry revealed a diacylglycerol modification at the cysteine residue in position 16 for both nFAD-I and rFAD-I. Cysteine-to-alanine substitution abrogated FAD-I's ability to induce hBD-2. Finally, FAD-I activation of hBD-2 expression was mediated via both Toll-like receptor-1/2 (TLR-1/2) and TLR-2/6 heterodimerization. Microbial molecules like FAD-I may be utilized in novel therapeutic ways to bolster the host innate immune response at mucosal surfaces.
Vfr Directly Activates
exsA
Transcription To Regulate Expression of the Pseudomonas aeruginosa Type III Secretion System
Authors: Marsden Anne E. , Intile Peter J. , Schulmeyer Kayley H. , Simmons-Patterson Ethan R. , Urbanowski Mark L. , Wolfgang Matthew C. , Yahr Timothy L.
Published: March 2016

The
Pseudomonas aeruginosa
cyclic AMP (cAMP)-Vfr system (CVS) is a global regulator of virulence gene expression. Regulatory targets include type IV pili, secreted proteases, and the type III secretion system (T3SS). The mechanism by which CVS regulates T3SS gene expression remains undefined. Single-cell expression studies previously found that only a portion of the cells within a population express the T3SS under inducing conditions, a property known as bistability. We now report that bistability is altered in a
vfr
mutant, wherein a substantially smaller fraction of the cells express the T3SS relative to the parental strain. Since bistability usually involves positive-feedback loops, we tested the hypothesis that virulence factor regulator (Vfr) regulates the expression of
exsA
. ExsA is the central regulator of T3SS gene expression and autoregulates its own expression. Although
exsA
is the last gene of the
exsCEBA
polycistronic mRNA, we demonstrate that Vfr directly activates
exsA
transcription from a second promoter (P

exsA

) located immediately upstream of
exsA
. P

exsA

promoter activity is entirely Vfr dependent. Direct binding of Vfr to a P

exsA

promoter probe was demonstrated by electrophoretic mobility shift assays, and DNase I footprinting revealed an area of protection that coincides with a putative Vfr consensus-binding site. Mutagenesis of that site disrupted Vfr binding and P

exsA

promoter activity. We conclude that Vfr contributes to T3SS gene expression through activation of the P

exsA

promoter, which is internal to the previously characterized
exsCEBA
operon.

IMPORTANCE
Vfr is a cAMP-dependent DNA-binding protein that functions as a global regulator of virulence gene expression in
Pseudomonas aeruginosa
. Regulation by Vfr allows for the coordinate production of related virulence functions, such as type IV pili and type III secretion, required for adherence to and intoxication of host cells, respectively. Although the molecular mechanism of Vfr regulation has been defined for many target genes, a direct link between Vfr and T3SS gene expression had not been established. In the present study, we report that Vfr directly controls
exsA
transcription, the master regulator of T3SS gene expression, from a newly identified promoter located immediately upstream of
exsA
.
A Membrane-Embedded Amino Acid Couples the SpoIIQ Channel Protein to Anti-Sigma Factor Transcriptional Repression during Bacillus subtilis Sporulation
Authors: Flanagan Kelly A. , Comber Joseph D. , Mearls Elizabeth , Fenton Colleen , Wang Erickson Anna F. , Camp Amy H.
Published: March 2016

SpoIIQ is an essential component of a channel connecting the developing forespore to the adjacent mother cell during
Bacillus subtilis
sporulation. This channel is generally required for late gene expression in the forespore, including that directed by the late-acting sigma factor σ
G
. Here, we present evidence that SpoIIQ also participates in a previously unknown gene regulatory circuit that specifically represses expression of the gene encoding the anti-sigma factor CsfB, a potent inhibitor of σ
G
. The
csfB
gene is ordinarily transcribed in the forespore only by the early-acting sigma factor σ
F
. However, in a mutant lacking the highly conserved SpoIIQ transmembrane amino acid Tyr-28,
csfB
was also aberrantly transcribed later by σ
G
, the very target of CsfB inhibition. This regulation of
csfB
by SpoIIQ Tyr-28 is specific, given that the expression of other σ
F
-dependent genes was unaffected. Moreover, we identified a conserved element within the
csfB
promoter region that is both necessary and sufficient for SpoIIQ Tyr-28-mediated inhibition. These results indicate that SpoIIQ is a bifunctional protein that not only generally promotes σ
G
activity in the forespore as a channel component but also specifically maximizes σ
G
activity as part of a gene regulatory circuit that represses σ
G
-dependent expression of its own inhibitor, CsfB. Finally, we demonstrate that SpoIIQ Tyr-28 is required for the proper localization and stability of the SpoIIE phosphatase, raising the possibility that these two multifunctional proteins cooperate to fine-tune developmental gene expression in the forespore at late times.

IMPORTANCE
Cellular development is orchestrated by gene regulatory networks that activate or repress developmental genes at the right time and place. Late gene expression in the developing
Bacillus subtilis
spore is directed by the alternative sigma factor σ
G
. The activity of σ
G
requires a channel apparatus through which the adjacent mother cell provides substrates that generally support gene expression. Here we report that the channel protein SpoIIQ also specifically maximizes σ
G
activity as part of a previously unknown regulatory circuit that prevents σ
G
from activating transcription of the gene encoding its own inhibitor, the anti-sigma factor CsfB. The discovery of this regulatory circuit significantly expands our understanding of the gene regulatory network controlling late gene expression in the developing
B. subtilis
spore.
A young male runner with a posterior knee mass—not just your typical Baker's cyst
Authors: Abid Ayesha , Kelley James Fitzhugh , Flemming Donald J , Silvis Matthew L
Published: March 2016

We present the case of a 28-year-old man with a growing mass in his right popliteal fossa causing pain on exertion. The differential diagnosis included Baker's cyst, entrapment syndrome of the popliteal artery, as well as a benign or malignant neoplasm. An ultrasound was non-specific. Follow-up MRI of the knee demonstrated cystic adventitial disease (CAD). With only about 500 cases reported in the literature since its discovery in 1947, CAD is a rare entity. The disease is characterised by mucinous or gelatinous cysts in the arterial or venous adventitia. The disease is predominantly seen in the popliteal artery and typically affects otherwise healthy males in the fourth to fifth decade of life. It presents clinically as intermittent exertional claudication. Examination of our case and a review of the literature will highlight the importance of considering CAD in patients who report of a popliteal mass and intermittent claudication.
Effect of obesity on cognition in adults with and without a mood disorder: study design and methods
Authors: Restivo Maria R , McKinnon Margaret C , Frey Benicio N , Hall Geoffrey B , Taylor Valerie H
Published: March 2016

Introduction

Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions. Individuals with mood disorders (bipolar disorder (BD) or major depressive disorder (MDD)) display an increased prevalence of both obesity and risk factors for cardiovascular diseases. Moreover, BD and MDD are associated with impairment in cognitive functioning across multiple domains. The independent contribution of obesity to cognitive decline in this population has not been explored. This study examines the impact of obesity on cognition by comparing neuropsychological performance in obese individuals, with or without a mood disorder before and after undergoing bariatric surgery.

Methods and analysis

This study compares measures of declarative memory, executive functioning and attention in obese individuals (body mass index >35 kg/m2) with BD or MDD, and 2 control populations (obese individuals without a psychiatric illness and healthy non-obese controls) prior to and following bariatric surgery. Participants (ages 18–60) receive a psychiatric diagnosis via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; SCID). Mood ratings, physical measurements, nutritional and health questionnaires are also administered. A standardised battery of neuropsychological tests aimed at establishing performance in areas of declarative memory, executive functioning and attention are administered. Warrington'sRecognition Memory Task(RMT) and an N-Back Task are performed in a 3 T functional MRI to investigate patterns of neural activation during cognitive performance. Additionally, anatomical MRI data are obtained to investigate potential changes in neural structures. Baseline data will be analysed for between-group differences and later compared with postsurgical data to investigate cognitive change.

Ethics and dissemination

This study has been approved by the Hamilton Integrated Research Ethics Board (09–3254). Results will be available in peer-reviewed scientific publications and scientific meetings presentations, and released in lay form to media.