bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative
Authors: Jazuli Farah , Lynd Terence , Mah Jordan , Klowak Michael , Jechel Dale , Klowak Stefanie , Ovens Howard , Sabbah Sam , Boggild Andrea K
Published: July 2016

Background

Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting.

Methods

Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria includePlasmodium falciparummalaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence.

Results

From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%).

Conclusions

In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.
Pharmacological interventions to improve sleep in hospitalised adults: a systematic review
Authors: Kanji Salmaan , Mera Alexandru , Hutton Brian , Burry Lisa , Rosenberg Erin , MacDonald Erika , Luks Vanessa
Published: July 2016

Objectives

Patients often suffer from disturbed sleep in hospital. Poor-quality sleep in hospitalised patients has been associated with significant morbidity and pharmacological sleep aids are often prescribed. The objective of this systematic review is to evaluate the comparative efficacy and safety of pharmacological interventions used for sleep in hospitalised patients.

Setting/participants

We searched MEDLINE, Embase, the Cochrane database and grey literature for prospective studies that evaluated sleep in hospitalised adults after a pharmacological intervention.

Primary and secondary outcome measures

Two reviewers assessed studies for inclusion and extracted data for efficacy outcomes, including sleep efficiency, sleep latency, sleep fragmentation and objectively measured sleep stage distribution. Risk of bias was assessed and meta-analyses were planned contingent upon homogeneity of the included studies.

Results

After screening 1920 citations, 15 studies involving 861 patients were included. Medications studied included benzodiazepines, nonbenzodiazepine sedatives, melatonin, propofol and dexmedetomidine. Five studies were deemed to be of high quality. Heterogeneity and variable outcome reporting precluded meta-analysis in most cases. No consistent trends with respect to sleep efficiency, quality or interruptions were observed identifying a drug or drug class as superior to another or no treatment. Benzodiazepines appeared to be better than no treatment with respect to sleep latency, but this was not consistently demonstrated across all studies. Sleep stage distribution shows that sleep in hospital is dominated by stages N1 and N2.

Conclusions

There is insufficient evidence to suggest that pharmacotherapy improves the quality or quantity of sleep in hospitalised patients suffering from poor sleep. No drug class or specific drug was identified as superior even when compared to placebo or no treatment. Although 15 studies were included, the quality of evidence was limited by their quality and size. Larger, better-designed trials in hospitalised adults are needed.
Out-of-hospital cardiac arrest attended by ambulance services in Ireland: first 2 years’ results from a nationwide registry
Authors: Masterson Siobhán , Cullinan John , McNally Bryan , Deasy Conor , Murphy Andrew , Wright Peter , O'Reilly Martin , Vellinga Akke
Published: August 2016

Background

National data collection provides information on out-of-hospital cardiac arrest (OHCA) incidence, management and outcomes that may not be generalisable from smaller studies. This retrospective cohort study describes the first 2 years' results from the Irish National Out-of-Hospital Cardiac Arrest Register (OHCAR).

Methods

Data on OHCAs attended by emergency medical services (EMS) where resuscitation was attempted (EMS-treated) were collected from ambulance services and entered onto OHCAR. Descriptive analysis of the study population was performed, and regression analysis was performed on the subgroup of adult patients with a bystander-witnessed event of presumed cardiac aetiology and an initial shockable rhythm (Utstein group).

Results

3701 EMS-treated OHCAs were recorded for the study period (1 January 2012–31 December 2013). Incidence was 39/100 000 population/year. In the Utstein group (n=577), compared with the overall group, there was a higher proportion of male patients, public event location, bystander cardiopulmonary resuscitation (CPR) and early defibrillation. Median EMS call–response interval was similar in both groups. A higher proportion of patients in the Utstein group achieved return of spontaneous circulation (35% vs 17%) and survival to hospital discharge (22% vs 6%). After multivariate adjustment for the Utstein group, the following variables were found to be independent predictors of the outcome survival to hospital discharge: public event location (OR 3.1 (95% CI 1.9 to 5.0)); bystander CPR (2.4 (95% CI 1.2 to 4.9)); EMS response of 8 min or less (2.2 (95% CI 1.3 to 3.6)).

Conclusions

This study highlights the role of nationwide registries in quantifying, monitoring and benchmarking OHCA incidence and outcome, providing baseline data upon which service improvement effects can be measured.
SURFACTANT INDUCED INTERFACIAL ANCHORING TRANSITIONS IN NEMATIC LIQUID CRYSTAL DROPLETS ON GLASS SURFACES
Authors: KULKARNI SIDDHARTH , THAREJA PRACHI
Published: August 2016

The interfacial adsorption of surfactants at planar nematic liquid crystal (NLC)–water interface induces an ordering transition from a tilted to perpendicular anchoring with the increase in surfactant concentration at [Formula: see text], where [Formula: see text] is the Critical Micelle Concentration of surfactants in water. In this study, we show that depending upon the surfactant structure a tilted to perpendicular NLC anchoring transition is observed at [Formula: see text] in 5CB droplets of size 50–70[Formula: see text][Formula: see text]m. Micrometer sized 5CB droplets are deposited on glass surfaces using flow coating of 5CB-in-ethanol solutions. When placed on 5CB drop decorated glass surfaces, the aqueous surfactant solutions of aliphatic chain surfactants (SDS, CTAB and CPBr) at [Formula: see text], result in an optical transition to a bright-cross texture attributed to the tilted anchoring of 5CB molecules at 5CB–water interface. At [Formula: see text], perpendicular anchoring of 5CB molecules at 5CB–water interface results in a droplet texture with a hedgehog defect. In contrast, aqueous solutions of SDBS lead to 5CB droplets with a bright-cross texture regardless of the surfactant concentration in the aqueous phase. These results indicate that the orientation of 5CB molecules is independent of the nature of the surfactant headgroup. In addition, 5CB droplet decorated OTS treated glass substrates show a hedgehog texture which disappears completely on exposure to organic vapors with the response time-dependent on the polarity of the vapor molecules.
Intrinsic Comparative Statics of a Nash Bargaining Solution
Authors: Caputo Michael R.
Published: August 2016

A generalization of the class of bargaining problems examined by Engwerda and Douven [(2008) On the sensitivity matrix of the Nash bargaining solution, Int. J. Game Theory 37, 265–279] is studied. The generalized class consists of nonconvex bargaining problems in which the feasible set satisfies the requirement that the set of weak Pareto-optimal solutions can be described by a smooth function. The intrinsic comparative statics of the aforesaid class are derived and shown to be characterized by a symmetric and positive semidefinite matrix, and an upper bound to the rank of the matrix is established. A corollary to this basic result is that a Nash bargaining solution is intrinsically a locally nondecreasing function of its own disagreement point. Other heretofore unknown results are similarly deduced from the basic result.
The Need for Permission, the Power to Enforce, and Duality in Cooperative Games with a Hierarchy
Authors: Huettner Frank , Wiese Harald
Published: August 2016

A cooperative game with transferable utility (TU game) captures a situation in which players can achieve certain payoffs by cooperating. We assume that the players are part of a hierarchy. In the literature, this invokes the assumption that subordinates cannot cooperate without the permission of their superiors. Instead, we assume that superiors can force their subordinates to cooperate. We show how both notions correspond to each other by means of dual TU games. This way, we capture the idea that a superiors’ ability to enforce cooperation can be seen as the ability to neutralize her subordinate’s threat to abstain from cooperation. Moreover, we introduce the coercion value for games with a hierarchy and provide characterizations thereof that reveal the similarity to the permission value.
Implosive graphs: Square-free monomials on symbolic Rees algebras
Authors: Flores-Méndez A. , Gitler I. , Reyes E.
Published: August 2016

Let [Formula: see text] be the edge monomial ideal of a graph [Formula: see text], whose vertex set is [Formula: see text]. [Formula: see text] is implosive if the symbolic Rees algebra [Formula: see text] of [Formula: see text] has a minimal system of generators [Formula: see text] where [Formula: see text] are square-free monomials. We give some structural properties of implosive graphs and we prove that they are closed under clique-sums and odd subdivisions. Furthermore, we prove that universally signable graphs are implosive. We show that odd holes, odd antiholes and some Truemper configurations (prisms, thetas and even wheels) are implosive. Moreover, we study excluded families of subgraphs for the class of implosive graphs. In particular, we characterize which Truemper configurations and extensions of odd holes and antiholes are minimal nonimplosive.
Optimizing Personalized Touristic Itineraries by a Multiobjective Evolutionary Algorithm
Authors: De Falco Ivanoe , Scafuri Umberto , Tarantino Ernesto
Published: August 2016

The paper presents an electronic tourist guide, relying on an evolutionary optimizer, able to plan personalized multiple-day itineraries by considering several contrasting objectives. Since the itinerary planning can be modeled as an extension of the NP-complete team orienteering problem with time windows, a multiobjective evolutionary optimizer is proposed to find in reasonable times near-optimal solutions to such an extension. This optimizer automatically designs the itinerary by aiming at maximizing the tourists’ satisfaction as a function of their personal preferences and environmental constraints, such as operating hours, visiting times and accessibility of the points of interests, and weather forecasting. Experimental evaluations have demonstrated that the proposed optimizer is effective in different simulated operating conditions.
Alignment of time-resolved data from high throughput experiments
Authors: Abidi Nada , Franke Raimo , Findeisen Peter , Klawonn Frank
Published: August 2016

To better understand the dynamics of the underlying processes in cells, it is necessary to take measurements over a time course. Modern high-throughput technologies are often used for this purpose to measure the behavior of cell products like metabolites, peptides, proteins, [Formula: see text]RNA or mRNA at different points in time. Compared to classical time series, the number of time points is usually very limited and the measurements are taken at irregular time intervals. The main reasons for this are the costs of the experiments and the fact that the dynamic behavior usually shows a strong reaction and fast changes shortly after a stimulus and then slowly converges to a certain stable state. Another reason might simply be missing values. It is common to repeat the experiments and to have replicates in order to carry out a more reliable analysis. The ideal assumptions that the initial stimulus really started exactly at the same time for all replicates and that the replicates are perfectly synchronized are seldom satisfied. Therefore, there is a need to first adjust or align the time-resolved data before further analysis is carried out. Dynamic time warping (DTW) is considered as one of the common alignment techniques for time series data with equidistant time points. In this paper, we modified the DTW algorithm so that it can align sequences with measurements at different, non-equidistant time points with large gaps in between. This type of data is usually known as time-resolved data characterized by irregular time intervals between measurements as well as non-identical time points for different replicates. This new algorithm can be easily used to align time-resolved data from high-throughput experiments and to come across existing problems such as time scarcity and existing noise in the measurements. We propose a modified method of DTW to adapt requirements imposed by time-resolved data by use of monotone cubic interpolation splines. Our presented approach provides a nonlinear alignment of two sequences that neither need to have equi-distant time points nor measurements at identical time points. The proposed method is evaluated with artificial as well as real data. The software is available as an R package tra (Time-Resolved data Alignment) which is freely available at: http://public.ostfalia.de/klawonn/tra.zip .
Microwave-Assisted Fabrication of Recyclable CdS/Fe3O4/rGO Photocatalysts to Improve the Photocatalytic Performance Under Visible Light
Authors: Liu Xinlin , Qin Yingying , Zhou Mingjun , Yan Yongsheng
Published: August 2016

A unique CdS/Fe3O4/rGO composite photocatalyst is successfully synthesized by the microwave method. It displays promising photocatalytic activity towards the photo-degrading of tetracycline (TC) in aqueous solution, the degradation rate of TC is 69% with adding 0.1[Formula: see text]g CdS/Fe3O4/rGO photocatalyst into 20[Formula: see text]mg/L tetracycline for 2[Formula: see text]h under visible light irradiation. Furthermore, the mechanism was systematically investigated by active species trapping experiment. It can be known that [Formula: see text] the major active species in the photodegradation process and the possible process of charge transfer for CdS/Fe3O4/rGO was proposed based on the experimental results. The as-prepared samples were carefully evaluated by XRD, TEM, XPS, VSM, PL spectra, Raman spectrometer.
Nilpotent elements and nil-Armendariz property of skew generalized power series rings
Authors: Paykan Kamal , Moussavi Ahmad
Published: August 2016

Let [Formula: see text] be a ring, [Formula: see text] a strictly ordered monoid, and [Formula: see text] a monoid homomorphism. The skew generalized power series ring [Formula: see text] is a common generalization of (skew) polynomial rings, (skew) power series rings, (skew) Laurent polynomial rings, (skew) group rings, and Mal’cev–Neumann Laurent series rings. In this paper, we introduce and study the [Formula: see text]-nil-Armendariz condition on [Formula: see text], a generalization of the standard nil-Armendariz condition from polynomials to skew generalized power series. We resolve the structure of [Formula: see text]-nil-Armendariz rings and obtain various necessary or sufficient conditions for a ring to be [Formula: see text]-nil-Armendariz. The [Formula: see text]-nil-Armendariz condition is connected to the question of whether or not a skew generalized power series ring [Formula: see text] over a nil ring [Formula: see text] is nil, which is related to a question of Amitsur [Algebras over infinite fields, Proc. Amer. Math. Soc. 7 (1956) 35–48]. As particular cases of our general results we obtain several new theorems on the nil-Armendariz condition. Our results extend and unify many existing results.
Evaluation of Various Channel Shapes of a Microchannel Heat Sink
Authors: Khan Aatif Ali , Kim Kwang-Yong
Published: August 2016

Thermal and hydraulic performances of various geometric shapes of a microchannel heat sink were evaluated numerically using Navier–Stokes equations. A heat sink comprised of a [Formula: see text][Formula: see text]cm2 silicon wafer was investigated with water as the cooling fluid. The performances of seven microchannel shapes were compared at the same microchannel hydraulic diameter and the same average height of the bottom silicon substrate. The thermal resistance, friction coefficient, and Nusselt number were calculated for a Reynolds number range of 50 to 500. The results show that an inverse trapezoidal shape gives the lowest thermal resistance for a Reynolds number up to 300. The values of [Formula: see text]Re are almost similar for all the shapes because of the constant hydraulic diameter.
Right ventricular end-diastolic stiffness heralds right ventricular failure in monocrotaline-induced pulmonary hypertension
Authors: Alaa Mohamed , Abdellatif Mahmoud , Tavares-Silva Marta , Oliveira-Pinto José , Lopes Lucas , Leite Sara , Leite-Moreira Adelino F. , Lourenço André P.
Published: July 2016

Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups ( n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24–34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (βi), end-systolic elastance (Eesi), arterial elastance for indexed volumes (Eai), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Eaiwas the strongest determinant of CI, alongside βibut not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher βi, along with low end-diastolic pressure (EDP) and stroke volume index (SVi) STF gain, denoting impaired preload reserve. On multivariate analysis βiand not Eesicorrelated with EDP-SViSTF gain ( P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SViSTF gain showed an area under curve of 0.84 for βiprediction ( P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SVi, which may constitute a prognostic tool in PH.
Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis
Authors: O'Dwyer David N. , Ashley Shanna L. , Moore Bethany B.
Published: July 2016

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies.
Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications
Authors: McClure Michelle L. , Barnes Stephen , Brodsky Jeffrey L. , Sorscher Eric J.
Published: July 2016

Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR PTMs may suggest novel treatment strategies for CF and perhaps other protein conformational diseases. This review provides a comprehensive summary of co- and posttranslational CFTR modifications and their significance with regard to protein biogenesis.
Motor outcomes of feedback delays and implicit/explicit strategy use: experimental considerations and clinical implications
Authors: Oswald Kaitlin , Campbell Rebecca , Wright Morgan
Published: August 2016

Sensorimotor adaptation requires integration of internal models of motor control with feedback from the external environment. As highlighted by Brudner, Kethidi, Graeupner, Ivry, and Taylor ( J Neurophysiol 115: 1499–1511, 2016), feedback characteristics, error or outcome based, as well as temporal constraints can impact motor learning and adaptation strategies. These findings provide novel insight into the underlying components of motor control, which can be applied to future clinical and experimental research on motor processes.
Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function
Authors: Elbers Frank , Woite Claudia , Antoni Valentina , Stein Sara , Funakoshi Hiroshi , Nakamura Toshikazu , Schares Gereon , Däubener Walter , Eller Silvia K.
Published: August 2016

Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO) provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO-mediated broad-spectrum effector functions have never been observed under hypoxiain vitro, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO andex vivomurine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites) and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occurin vivo. This might be detrimental for the appropriate host immune response towards relevant pathogens.
Asymptotic Distribution of Isolated Nodes in Secure Wireless Sensor Networks under Transmission Constraints
Authors: Tang Y. , Li Q. L.
Published: August 2016

The Eschenauer-Gligor (EG) key predistribution is regarded as a typical approach to secure communication in wireless sensor networks (WSNs). In this paper, we establish asymptotic results about the distribution of isolated nodes and the vanishing small impact of the boundary effect on the number of isolated nodes in WSNs with the EG scheme under transmission constraints. In such networks, nodes are distributed either Poissonly or uniformly over a unit square. The results reported here strengthen recent work by Yi et al.
Coordinating a Supply Chain with a Loss-Averse Retailer under Yield and Demand Uncertainties
Authors: Luo Weiwei , Shao Dongguo , Liu Wei , Wang Zhuomin
Published: August 2016

This paper investigates the channel coordination of a supply chain (SC) consisting of a loss-averse retailer and a risk-neutral supplier under yield and demand uncertainties. Three existing contracts are analyzed. Our results demonstrate that the buyback (BB) and quantity flexibility (QF) contracts can not only coordinate the supply chain but also lead to Pareto improvement for each player, while the wholesale price (WP) contract fails to coordinate the chain due to the effects of double marginalization and risk preference. For comparison, a chain with a risk-neutral retailer is also analyzed. Furthermore, numerical examples are provided to demonstrate the effectiveness of the coordination contracts, and the impacts of loss aversion and random yield on the decision-making behaviors and system performance are then discussed.
Wedelolactone, an Anti-inflammatory Botanical, Interrupts c-Myc Oncogenic Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer Cells
Authors: Sarveswaran Sivalokanathan , Ghosh Ritisha , Parikh Rujul , Ghosh Jagadananda
Published: July 2016

The c-Myc gene encodes an oncoprotein transcription factor that is frequently upregulated in almost all cancer types and is the subject of intense investigation for management of cancer because of its pleiotropic effects controlling a spectrum of cellular functions. However, due of its nonenzymatic nature, development of suitable strategies to block its protein–protein or protein–DNA interaction is challenging. Thus, c-Myc has been recognized as an elusive molecular target for cancer control, and various approaches are in development to inhibit c-Myc transcriptional activity. We observed that wedelolactone (WDL), an anti-inflammatory botanical compound, severely downregulates the expression of c-Myc mRNA in prostate cancer cells. Moreover, WDL dramatically decreases the protein level, nuclear accumulation, DNA-binding, and transcriptional activities of c-Myc. c-Myc is a transforming oncogene widely expressed in prostate cancer cells and is critical for maintaining their transformed phenotype. Interestingly, WDL was found to strongly affect the viability of Myc-activated prostate cancer cells and completely block their invasion as well as soft agar colony formation in vitro. WDL was also found to downregulate c-Myc in vivo in nude mice xenografts. Moreover, WDL synergizes with enzalutamide to decrease the viability of androgen-sensitive prostate cancer cells via induction of apoptosis. These findings reveal a novel anticancer mechanism of the natural compound WDL, and suggest that the oncogenic function of c-Myc in prostate cancer cells can be effectively downregulated by WDL for the development of a new therapeutic strategy against Myc-driven prostate cancer. Mol Cancer Ther; 15(11); 2791–801. ©2016 AACR.
Peptidomimetic Targeting of Ca
v
β2 Overcomes Dysregulation of the L-Type Calcium Channel Density and Recovers Cardiac Function
Authors: Rusconi Francesca , Ceriotti Paola , Miragoli Michele , Carullo Pierluigi , Salvarani Nicolò , Rocchetti Marcella , Di Pasquale Elisa , Rossi Stefano , Tessari Maddalena , Caprari Silvia , Cazade Magali , Kunderfranco Paolo , Chemin Jean , Bang Marie-Louise , Polticelli Fabio , Zaza Antonio , Faggian Giuseppe , Condorelli Gianluigi , Catalucci Daniele
Published: August 2016

Background:

L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease.

Methods:

Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Ca
v
β2 chaperone regulates channel density at the plasma membrane.

Results:

On the basis of our previous results, we found a direct linear correlation between the total amount of the LTCC pore-forming Ca
v
α1.2 and the Akt-dependent phosphorylation status of Ca
v
β2 both in a mouse model of diabetic cardiac disease and in 6 diabetic and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic valve replacement. Mechanistically, we demonstrate that a conformational change in Ca
v
β2 triggered by Akt phosphorylation increases LTCC density at the cardiac plasma membrane, and thus the inward calcium current, through a complex pathway involving reduction of Ca
v
α1.2 retrograde trafficking and protein degradation through the prevention of dynamin-mediated LTCC endocytosis; promotion of Ca
v
α1.2 anterograde trafficking by blocking Kir/Gem-dependent sequestration of Ca
v
β2, thus facilitating the chaperoning of Ca
v
α1.2; and promotion of Ca
v
α1.2 transcription by the prevention of Kir/Gem-mediated shuttling of Ca
v
β2 to the nucleus, where it limits the transcription of Ca
v
α1.2 through recruitment of the heterochromatin protein 1γ epigenetic repressor to the
Cacna1c
promoter. On the basis of this mechanism, we developed a novel mimetic peptide that, through targeting of Ca
v
β2, corrects LTCC life-cycle alterations, facilitating the proper function of cardiac cells. Delivery of mimetic peptide into a mouse model of diabetic cardiac disease associated with LTCC abnormalities restored impaired calcium balance and recovered cardiac function.

Conclusions:

We have uncovered novel mechanisms modulating LTCC trafficking and life cycle and provide proof of concept for the use of Ca
v
β2 mimetic peptide as a novel therapeutic tool for the improvement of cardiac conditions correlated with alterations in LTCC levels and function.
Mitogen‐Activated Protein Kinase and Intracellular Polyamine Signaling Is Involved in TRPV1 Activation–Induced Cardiac Hypertrophy
Authors: Chen Mai , Xin Jiajia , Liu Baohui , Luo Liyang , Li Jiayi , Yin Wen , Li Mingkai
Published: July 2016

Background

The transient receptor potential vanilloid type 1 (
TRPV
1) is expressed in the cardiovascular system, and increased
TRPV
1 expression has been associated with cardiac hypertrophy. Nevertheless, the role of
TRPV
1 in the pathogenesis of cardiac hypertrophy and the underlying molecular mechanisms remain unclear.

Methods and Results

In cultured cardiomyocytes, activation of
TRPV
1 increased cell size and elevated expression of atrial natriuretic peptide
mRNA
and intracellular calcium level, which was reversed by
TRPV
1 antagonist capsazepine. Increased expression of phosphorylated calmodulin‐dependent protein kinase II
δ
and mitogen‐activated protein kinases were found in
TRPV
1 agonist capsaicin‐treated cardiomyocytes. Selective inhibitor of calmodulin‐dependent protein kinase II
δ
decreased phosphorylation of extracellular signal–regulated kinases and p38. Capsaicin induced an increase in expression of ornithine decarboxylase protein, which is the key enzyme in polyamine biosynthesis in cardiomyocytes. Nevertheless, there was no obvious change of ornithine decarboxylase expression in
TRPV
1 knockdown cells after capsaicin treatment, and specific inhibitors of calmodulin‐dependent protein kinase II
δ
or p38 downregulated the capsaicin‐induced expression of ornithine decarboxylase. Capsazepine alleviated the increase in cross‐sectional area of cardiomyocytes and the ratio of heart weight to body weight and improved cardiac function, including left ventricular internal end‐diastolic and ‐systolic dimensions and ejection fraction and fractional shortening percentages, in mice treated with transverse aorta constriction. Capsazepine also reduced expression of ornithine decarboxylase and cardiac polyamine levels. Transverse aorta constriction induced increases in phosphorylated calmodulin‐dependent protein kinase II
δ
and extracellular signal–regulated kinases, and p38 and Serca2a were attenuated by capsazepine treatment.

Conclusions

This study revealed that the mitogen‐activated protein kinase signaling pathway and intracellular polyamines are essential for
TRPV
1 activation–induced cardiac hypertrophy.
How precise can wood identification be? Wood anatomy’s role in support of the legal timber trade, especially cites
Authors: Gasson Peter
Published: July 2016

Traditional wood identification techniques using light microscopy are usually sufficient to identify a wood sample to the genus level. In some cases CITES legislation requires identification to species level, which is difficult or impossible using traditional light microscopy. This paper concentrates mainly on the identification challenges posed by CITES, particularly with ramin (Gonystylus spp.), Brazilian Rosewood (Dalbergia nigra) and Agarwood (Aquilaria and Gyrinops species). All the other CITES listed timbers and some other taxa that are traded or confused with protected species and might in the future be protected by legislation are also discussed. There are several new non-anatomical techniques being tried to make more accurate identifications and these are mentioned where appropriate.

There is a mismatch between legislation and the natural world, and the limitations of the identification process need to be better appreciated by enquirers, especially in relation to CITES enquiries, since species and genus concepts vary among biologists, and can be ambiguous.
Wood Anatomy of Cites-Listed tree species
Authors: Gasson Peter , Baas Pieter , Wheeler Elisabeth
Published: July 2016

The wood anatomy of all currently CITES-listed angiosperm and conifer tree taxa is illustrated with low- to high-power magnification light micrographs. Their diagnostic wood features are presented in numerical codes taken from the IAWA Hardwood (1989) and Softwood (2004) Lists of microscopic features for wood identification. Features used are summarized in two appendices. These descriptions and illustrations can be used for genus identification when carefully compared with look-alike non-CITES-listed timbers illustrated and described in the InsideWood web-database or present in reference wood collections.
Design and application of CITESwoodID Computer-aided identification and description of CITES-protected timbers
Authors: Koch Gerald , Richter Hans-Georg , Schmitt Uwe
Published: July 2016

Wood identification is of prime importance in enforcing CITES policies regarding protected species. A tool to facilitate wood identification based on macroscopic features, CITESwoodID, is available, developed in the DELTA-INTKEY-System. This database contains descriptions and an interactive identification system for 12 CITES-listed timbers (11 hardwoods, 1 softwood) known for their potential in the manufacture of lumber and downstream processing into products, and 44 trade timbers which can be easily mistaken for CITES-listed timbers due to a similar appearance and/or wood anatomical pattern. The database is primarily designed for institutions and persons involved in regulating import and export of wood and wood products controlled by CITES regulations. It is also used in primary and secondary educational facilities active in teaching wood anatomy and wood identification, and has been the basis of a number of training modules and short courses for government inspectors and students.
Pl@ntwood: A Computer-Assisted Identification Tool for 110 species of amazon trees based on wood Anatomical Features
Authors: Sarmiento Carolina , Détienne Pierre , Heinz Christine , Molino Jean-François , Grard Pierre , Bonnet Pierre
Published: July 2016

Sustainable management and conservation of tropical trees and forests require accurate identification of tree species. Reliable, user-friendly identification tools based on macroscopic morphological features have already been developed for various tree floras. Wood anatomical features provide also a considerable amount of information that can be used for timber traceability, certification and trade control. Yet, this information is still poorly used, and only a handful of experts are able to use it for plant species identification. Here, we present an interactive, user-friendly tool based on vector graphics, illustrating 99 states of 27 wood characters from 110 Amazonian tree species belonging to 34 families. Pl@ntWood is a graphical identification tool based on the IDAO system, a multimedia approach to plant identification. Wood anatomical characters were selected from the IAWA list of microscopic features for hardwood identification, which will enable us to easily extend this work to a larger number of species. A stand-alone application has been developed and an on-line version will be delivered in the near future. Besides allowing non-specialists to identify plants in a user-friendly interface, this system can be used with different purposes such as teaching, conservation, management, and selftraining in the wood anatomy of tropical species.
Petronymphe rara a new species of Oaxaca, Mexico and the rediscovery of P. decora (Asparagaceae: Brodiaeoideae)
Authors: GUTIÉRREZ JORGE , TERRAZAS TERESA , SOLANO ELOY
Published: August 2016

Petronymphe rara is described and illustrated as a new species, endemic to the state of Oaxaca, Mexico, which develops in gypsum soils in the tropical deciduous forest of the Oaxacan Mixteca Alta. This species differs from P. decora, the latter distributed in the state of Guerrero, Mexico, in leaf shape, floral tube size and color and stamen size. We also report the rediscovery of P. decora, a species not collected since 1949 and described in 1951 by Harold E. Moore, including a complete morphological description. In addition, we present an expanded genus description to accommodate the new species.
Disruption and deniable interventionism: explaining the appeal of covert action and Special Forces in contemporary British policy
Authors: Cormac Rory
Published: July 2016

The United Kingdom has long engaged in covert action. It continues to do so today. Owing to the secrecy involved, however, such activity has consistently been excluded from debates about Britain’s global role, foreign and security policy and military planning: an important lacuna given the controversy, risk, appeal and frequency of covert action. Examining when, how and why covert action is used, this article argues that contemporary covert action has emerged from, and is shaped by, a specific context. First, a gap exists between Britain’s perceived global responsibilities and its actual capabilities; policy elites see covert action as able to resolve, or at least conceal, this. Second, intelligence agencies can shape events proactively, especially at the tactical level, while flexible preventative operations are deemed well suited to the range of fluid threats currently faced. Third, existing Whitehall machinery makes covert action viable. However, current covert action is smaller scale and less provocative today than in the early Cold War; it revolves around ‘disruption’ operations. Despite being absent from the accompanying debates, this role was recognised in the 2015 Strategic Defence and Security Review, which placed intelligence actors at the heart of British thinking.
A Design-Based Approach to Improve External Validity in Welfare Policy Evaluations
Authors: Tipton Elizabeth , Peck Laura R.
Published: July 2016

Background:

Large-scale randomized experiments are important for determining how policy interventions change average outcomes. Researchers have begun developing methods to improve the external validity of these experiments. One new approach is a balanced sampling method for site selection, which does not require random sampling and takes into account the practicalities of site recruitment including high nonresponse.

Method:

The goal of balanced sampling is to develop a strategic sample selection plan that results in a sample that is compositionally similar to a well-defined inference population. To do so, a population frame is created and then divided into strata, which “focuses” recruiters on specific subpopulations. Units within these strata are then ranked, thus identifying “replacements” similar to sites that can be recruited when the ideal site refuses to participate in the experiment.

Result:

In this article, we consider how a balanced sample strategic site selection method might be implemented in a welfare policy evaluation.

Conclusion:

We find that simply developing a population frame can be challenging, with three possible and reasonable options arising in the welfare policy arena. Using relevant study-specific contextual variables, we craft a recruitment plan that considers nonresponse.
Appropriation, Activation and Acceleration: The Escalatory Logics of Capitalist Modernity and the Crises of Dynamic Stabilization
Authors: Rosa Hartmut , Dörre Klaus , Lessenich Stephan
Published: July 2016

The paper starts by identifying dynamic stabilization as a defining feature of modern societies. This term refers to the fact that such a society requires (material) growth, (technological) augmentation and high rates of (cultural) innovation in order to reproduce its structure and to preserve the socioeconomic and political status quo. The subsequent sections explore the mechanisms and consequences of this mode of social reproduction, proceeding in three steps. First, three key aspects or ‘motors’ of dynamization are identified, namely the mechanisms of (socio-economic) appropriation, (socio-cultural) acceleration and (socio-political) activation. In the second step, we argue that this ‘Triple-A-Mode’ of dynamic stabilization necessarily entails a logic of incessant escalation which eventually threatens to undermine itself, leading to a multifaceted process of destabilization. Unmistakable signs of this can be seen in the current financial, democratic, ecological and psychosocial crises. The third and last part briefly and very preliminarily sketches out the possible contours of a ‘post-growth’ society which could move beyond the current mode of dynamic stabilization.
Modelling approach to support design of new high nitrogen austenitic steel for wind turbines components
Authors: Ruffini Federico , Tassa Oriana , Guarnaschelli Claudio , Arcobello-Varlese Francesca , Holweger Walter , Blass Toni , Trojahn Werner
Published: July 2016

The alloy design of a new high nitrogen austenitic steel for bearing used in wind turbine gearboxes has been approached. The alloy design was based on a modelling approach to the different aspects of manufacturing routes. The mechanical strength was predicted by means of empirical models. Nitrogen solubility in liquid steel was estimated on the basis of Sievert’s law and Thermo-Calc calculations. Scheil calculations and models developed by Centro Sviluppo Materiali SpA (CSM) were used for estimating nitrogen solubility. The stability of austenite has been studied by thermodynamic calculations. The results show that amounts of at least N = 0.5% are required to fall in austenite domain approaching the required mechanical strength. Vacuum induction melting + pressure electroslag remelting is required to manufacture alloys with N ⩾ 0.6%, but the addition of elements as Mn can potentially allow to increase N amounts achievable with only vacuum induction melting route processing.
Defining Thresholds for the Patient Acceptable Symptom State for the IKDC Subjective Knee Form and KOOS for Patients Who Underwent ACL Reconstruction
Authors: Muller Bart , Yabroudi Mohammad A. , Lynch Andrew , Lai Chung-Liang , van Dijk C. Niek , Fu Freddie H. , Irrgang James J.
Published: July 2016

Background:

A clinically meaningful change in patient-reported outcome (PRO) may not be associated with an acceptable state that corresponds to “feeling well,” also known as the patient acceptable symptom state (PASS). The PASS thresholds for the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) and the Knee injury and Osteoarthritis Outcome Score (KOOS) have not been determined for individuals after anterior cruciate ligament (ACL) reconstruction.

Purpose:

To determine the PASS thresholds for the IKDC-SKF and KOOS in individuals at 1 to 5 years after ACL reconstruction.

Study Design:

Cohort study (diagnosis): Level of evidence, 2.

Methods:

Individuals 1 to 5 years after primary ACL reconstruction completed a survey that included the IKDC-SKF and KOOS. All subjects assessed satisfaction with their current state by answering the question, “Taking into account all the activity you have during your daily life, your level of pain, and also your activity limitations and participation restrictions, do you consider the current state of your knee satisfactory?”

Results:

A total of 251 participants (mean age ± SD, 26.1 ± 9.9 years) completed the survey at an average of 3.4 ± 1.3 years after ACL reconstruction. Of these, 223 (89.2%) individuals indicated that they were in an acceptable symptom state (PASS-Y). Analysis of the receiver operating characteristic curve revealed that the IKDC-SKF and each of the KOOS subscales (pain, symptoms, activities of daily living [ADL], sport and recreation [sport/rec], and quality of life [QoL]) were significantly better identifiers of PASS than chance as indicated by the significance of the area under the curves. The PASS threshold (sensitivity, specificity) was 75.9 (0.83, 0.96) for the IKDC-SKF, 88.9 (0.82, 0.81) for the KOOS pain, 57.1 (0.78, 0.67) for the KOOS symptoms, 100.0 (0.70, 0.89) for the KOOS ADL, 75.0 (0.87, 0.88) for the KOOS sport/rec, and 62.5 (0.82, 0.85) for the KOOS QoL. In addition, the difference between PASS-Y and PASS-N was statistically significant ( P < .001) for all PROs.

Conclusion:

To our knowledge, this is the first study to identify the PASS thresholds for the IKDC-SKF and the KOOS subscales for individuals 1 to 5 years after ACL reconstruction. By identifying threshold values for the PASS, this study provides additional information to facilitate interpretation of the IKDC-SKF and KOOS in daily practice and clinical research related to ACL reconstruction.