bluuebunny/crossref_metadata_2025 huggingface dataset:
A Model‐Adaptive Test for Parametric Single‐Index Time Series Models
Authors: Xia Qiang , He Kejun , Niu Cuizhen
Published: August 2017

In this paper, based on certain residual‐marked empirical processes, we study the model test to validate the composite structure with a given link function for parametric single‐index time series models. To extend an existing directional test that avoids the curse of dimensionality to an omnibus test, a model‐adaptive dimension‐reduction test procedure is proposed. Moreover, to fully utilize the dimension‐reduction structure under the null hypothesis, the test is designed for adapting both the null and alternative hypotheses, which can improve the power for a more general alternative. Simulation results and a real data example show that the proposed method can perform effectively in checking parametric single‐index time series models.
Bacterial infection‐triggered acute‐on‐chronic liver failure is associated with increased mortality
Authors: Mücke Marcus M. , Rumyantseva Tatiana , Mücke Victoria T. , Schwarzkopf Katharina , Joshi Sabrina , Kempf Volkhard A. J. , Welsch Christoph , Zeuzem Stefan , Lange Christian M.
Published: August 2017

Background & Aims

Acute‐on‐chronic liver failure (ACLF) is characterized by an acute deterioration of liver function in patients with cirrhosis in combination with recently defined organ failures. Our aim was to independently validate the prognostic value of the recently established EASL‐CLIF‐Consortium definition of ACLF and to identify new predictors of short‐term mortality.

Methods

Patients with cirrhosis and the International Classification of Diseases, Tenth Revision diagnosis of (sub)acute liver failure were retrospectively categorized according to the EASL‐CLIF‐Consortium definition. Logistic regression analyses were performed to identify clinical and epidemiological predictors of 30‐ and 90‐day mortality.

Results

From 2008 to 2015, 257 patients were included. Overall, 173 (67%) patients met the EASL criteria for ACLF (grade 1: n = 43 [25%], grade 2: n = 52 [30%], grade 3: n = 79 [45%]). Mortality within 30 days in patients without ACLF was 3.6%, and 18.6%, 37.3% and 62.0% in patients with ACLF grades 1, 2 and 3 respectively. Outcome of patients with bacterial infection‐triggered ACLF was distinct from non‐infection‐triggered ACLF (71.6% vs 33.8% 30‐day survival, P < .001), and infection‐triggered ACLF was independently associated with increased mortality (odds ratio [OR] = 4.28, P < .001). Pneumonia was a particularly frequent infection and burdened with high mortality. In addition, infections with multidrug‐resistant organisms were frequent and independently associated with mortality (P = .030, OR = 4.41), as was glycopeptide antibiotic therapy as initial empirical antibiotic therapy (P = .005).

Conclusions

This study confirmed the EASL‐CLIF‐Consortium definition of ACLF as strong predictor of mortality in patients with acute decompensation of cirrhosis. However, we have observed a remarkably higher mortality in infection‐triggered ACLF compared to other precipitating events.
Telomere length is reflected by plumage coloration and predicts seasonal reproductive success in the barn swallow
Authors: Parolini Marco , Romano Andrea , Costanzo Alessandra , Khoriauli Lela , Santagostino Marco , Nergadze Solomon G. , Canova Luca , Rubolini Diego , Giulotto Elena , Saino Nicola
Published: August 2017

Individuals differ in realized fitness but the genetic/phenotypic traits that underpin such variation are often unknown. Telomere dynamics may be a major source of variation in fitness traits because physiological telomere shortening depends on environmental and genetic factors and may impair individual performance. Here, we showed that, in a population of a socially monogamous, biparental passerine bird, the barn swallow (Hirundo rustica), breeding in northern Italy, telomere length (TL) of both adult males and females positively correlated with seasonal reproductive and fledging success, as expected because long telomeres are supposed to boost performance. Telomere length was correlated with sexually dimorphic coloration in both sexes, showing for the first time in any species that coloration reliably reflectsTLand may mediate mutual mate choice, leading to the observed positive assortative mating forTLin the barn swallow. Thus,TLappears to be associated with variation in a major fitness trait and may be an ultimate target of mate choice, as individuals of both sexes can use coloration to adaptively choose high‐quality mates that possess long telomeres.
Barriers to families' regaining control in ICU: Disconnectedness
Authors: Wong Pauline , Liamputtong Pranee , Koch Susan , Rawson Helen
Published: August 2017

Background

The nature of interactions between health care professionals and families may have a significant impact on families' experience and outcomes of critical illness. The value of encouraging positive relationships with families is well documented; however, it is argued that the lack of theoretical frameworks to guide practice in this area may be a barrier to improving patient‐ and family‐centred care.

Aims

The study on which this paper is based aimed to understand families' experiences of their interactions when a relative is admitted unexpectedly to an Australian intensive care unit and to generate a substantive theory that represents families' interactions that can be used to guide critical care nursing practice when caring for patients' families in this context.

Design and Methods

A grounded theory methodology was adopted for the study. Data were collected between 2009 and 2013 using in‐depth interviews with 25 family members of 21 critically ill patients admitted to a metropolitan, tertiary‐level intensive care unit (ICU) in Australia.

Findings

A core category of regaining control has been generated from our study. This paper focuses on Disconnectedness, which leads to increased emotional vulnerability and is also a barrier to families' regaining control. Families feel disconnected when staff emotionally and physically disengage from them, when staff interact insensitively and in a manner that offers families limited hope.

Conclusion

Our findings offer an in‐depth understanding of staff engagement with families and its impact on the families' ability to regain control. Although some themes have been previously identified in the literature in isolation, the interrelationships of the categories within a theoretical framework to represent family resilience in the context of an ICU situated in the Australian health care system are a novel finding.

Relevance to Clinical Practice

The findings can be used to support patient‐ and family‐centred care interventions in the ICU.
Bilateral sympathectomy for treatment of refractory ventricular tachycardia
Authors: Kopecky Kathleen , Afzal Aasim , Felius Joost , Hall Shelley A. , Mendez Jose C. , Assar Manish , Mason David P. , Bindra Amarinder S.
Published: August 2017

Ventricular tachycardia (VT) commonly occurs in patients with ischemic or nonischemic cardiomyopathy and requires antiarrhythmic drugs, ablation, or advanced circulatory support. However, life‐threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69‐year‐old man with nonischemic cardiomyopathy, life‐threatening VT, and hemodynamic instability with numerous ICD discharges, who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges.
A synthetic biology approach for consistent production of plant‐made recombinant polyclonal antibodies against snake venom toxins
Authors: Julve Parreño Jose Manuel , Huet Estefanía , Fernández‐del‐Carmen Asun , Segura Alvaro , Venturi Micol , Gandía Antoni , Pan Wei‐song , Albaladejo Irene , Forment Javier , Pla Davinia , Wigdorovitz Andrés , Calvete Juan J. , Gutiérrez Carlos , Gutiérrez José María , Granell Antonio , Orzáez Diego
Published: August 2017

Antivenoms developed from the plasma of hyperimmunized animals are the only effective treatment available against snakebite envenomation but shortage of supply contributes to the high morbidity and mortality toll of this tropical disease. We describe a synthetic biology approach to affordable and cost‐effective antivenom production based on plant‐made recombinant polyclonal antibodies (termed pluribodies). The strategy takes advantage of virus superinfection exclusion to induce the formation of somatic expression mosaics in agroinfiltrated plants, which enables the expression of complex antibody repertoires in a highly reproducible manner. Pluribodies developed using toxin‐binding genetic information captured from peripheral blood lymphocytes of hyperimmunized camels recapitulated the overall binding activity of the immune response. Furthermore, an improved plant‐made antivenom (plantivenom) was formulated using an in vitro selected pluribody against Bothrops asper snake venom toxins and has been shown to neutralize a wide range of toxin activities and provide protection against lethal venom doses in mice.
Activity of salivary glands in secreting honey‐elaborating enzymes in two subspecies of honeybee (Apis melliferaL)
Authors: Al‐Sherif Aliaa A. , Mazeed Adel M. , Ewis Mohamed A. , Nafea Emad A. , Hagag El‐Seid E. , Kamel Ahmed A.
Published: August 2017

The activity of invertase, glucose oxidase and amylase in the cephalic (post‐cerebral) and thoracic salivary glands is determined in Egyptian and Carniolan honeybees (Apis mellifera L). For this purpose, three ages of worker bees are selected for enzyme assays. The results show that the three target enzymes are detected in the two glands during the three worker ages, except invertase, which cannot be detected in the cephalic gland of newly emerged bees of both subspecies. In both glands, the secretion of invertase is highest, followed by amylase and then glucose oxidase. In Carniolan bees, invertase secretion of the cephalic and thoracic glands increases gradually with age. In Egyptian bees, invertase increases with age only in the cephalic gland, whereas, in the thoracic gland, the highest secretion activity is detected in 10–15‐day‐old bees. The highest amounts of glucose oxidase and amylase in the cephalic gland are detected in newly emerged individuals of both Egyptian and Carniolan bees. In the thoracic gland, however, the highest activity of both enzymes is recorded only in newly emerged Egyptian bees. The results are discussed in the light of bee management and biological aspects of the two subspecies.
Body size‐adjusted dose analysis of pirfenidone in patients with interstitial pneumonia
Authors: Uehara Masahiro , Enomoto Noriyuki , Oyama Yoshiyuki , Suzuki Yuzo , Kono Masato , Furuhashi Kazuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Suda Takafumi
Published: August 2017

ABSTRACT

Background and objective

Pirfenidone is an effective anti‐fibrotic agent for idiopathic pulmonary fibrosis (IPF). Although adverse events (AE) sometimes prevent patients from continuing treatment, current dose adjustment guidance does not consider patient body size or weight (BW). The aim of this study was to evaluate the importance of pirfenidone dose adjustment by body surface area (BSA) or BW for preventing AE and permitting continuous treatment in patients with interstitial pneumonia (IP).

Methods

Sixty‐seven Japanese patients with IP including 46 patients with IPF treated with pirfenidone between 2009 and 2015 were retrospectively evaluated. Pirfenidone doses were adjusted by BSA or BW and were compared with clinical parameters.

Results

Forty‐two of 67 patients (62.7%) with IP showed AE, most commonly gastrointestinal symptoms (77.5%). Patients having AE received significantly higher adjusted doses of pirfenidone by both BSA and BW (P = 0.024 and P = 0.010, respectively), while unadjusted doses did not differ. BSA‐adjusted dose discriminated patients with AE from those without (area under the curve = 0.666 at 1085 mg/m2). Six of seven patients (85.7%) who discontinued pirfenidone due to AE took ≥1085 mg/m2 of pirfenidone. In a subgroup with IPF, patients taking a medium dose (median: 876 median–1085 mg/m2) showed a lower annual decline in % forced vital capacity than patients taking a lower dose (P = 0.025).

Conclusion

BSA‐adjusted pirfenidone dosing may be useful to prevent AE whilst achieving a long‐term treatment effect in patients with IP.
The spillover effects of innovative ideas on human capital
Authors: Alpaslan Barış , Ali Abdilahi
Published: August 2017

This paper extends a two‐period overlapping generations model of endogenous growth where the interactions between public infrastructure and human capital with research and development (R&D) activities and growth are studied. The paper makes two important contributions. First, it accounts for the spillover effect of the stock of ideas on learning, which in turn promotes the production of innovative technologies. In doing so, it brings to the fore a two‐way interaction between human capital and innovation. The paper then applies various econometric methods which confirm the above theoretical thesis. Second, the solutions of the model emphasize the important role public spending on infrastructure, human capital and R&D can play in promoting economic growth. However, the findings also show that trade‐offs in the allocation of public spending may inevitably emerge. In particular, investment in public infrastructure at the expense of spending on R&D is less likely to succeed in promoting economic growth, whereas it may be more effective to foster growth through an offsetting cut in another productive component, namely, education. In light of these potential trade‐offs, governments in low‐income countries need to use their limited budgets as part of holistic measures in order to achieve efficient outcomes.
Cognitive behavioural therapy and mindfulness for stress and burnout: a waiting list controlled pilot study comparing treatments for parents of children with chronic conditions
Authors: Anclair Malin , Lappalainen Raimo , Muotka Joona , Hiltunen Arto J.
Published: August 2017

Background

Parents of children with chronic conditions often experience a crisis with serious mental health problems for themselves as a consequence. The healthcare focus is on the children; however, the parents often worry about their children's health and future but are seldom offered any counselling or guidance.

Aim

The aim of this study was to investigate the effectiveness of two group‐based behavioural interventions on stress and burnout among parents of children with chronic conditions.

Design, participants and setting

After a waiting list control period (n = 28), parents were offered either a cognitive behavioural (CBT, n = 10) or a mindfulness program (MF, n = 9).

Results

Both interventions decreased significantly stress and burnout. The within‐group effect sizes were large in both interventions (CBT, g = 1.28–1.64; MF, g = 1.25–2.20).

Conclusions

Hence, the results of this pilot study show that treating a group using either CBT or mindfulness can be an efficient intervention for reducing stress levels and burnout in parents of children with chronic conditions.
The effects of nutritional guideline implementation on nursing home staff performance: a controlled trial
Authors: Törmä Johanna , Winblad Ulrika , Saletti Anja , Cederholm Tommy
Published: August 2017

Rationale

Suboptimal nutritional practices in elderly care settings may be resolved by an efficient introduction of nutritional guidelines.

Aims

To compare two different implementation strategies, external facilitation (EF) and educational outreach visits (EOVs), when introducing nutritional guidelines in nursing homes (NHs), and study the impact on staff performance.

Methodological design

A quasi‐experimental study with baseline and follow‐up measurements.

Outcome measures

The primary outcome was staff performance as a function of mealtime ambience and food service routines.

Interventions/research methods

TheEFstrategy was a 1‐year, multifaceted intervention that included support, guidance, practice audit and feedback in twoNHunits. TheEOVstrategy comprised one‐three‐hour lecture about nutritional guidelines in two otherNHunits. Both strategies were targeted to selectedNHteams, which consisted of a unit manager, a nurse and 5–10 care staff. Mealtime ambience was evaluated by 47 observations using a structured mealtime instrument. Food service routines were evaluated by 109 food records performed by the staff.

Results

Mealtime ambience was more strongly improved in theEFgroup than in theEOVgroup after the implementation. Factors improved were laying a table (p = 0.03), offering a choice of beverage (p = 0.02), the serving of the meal (p = 0.02), interactions between staff and residents (p = 0.02) and less noise from the kitchen (p = 0.01). Food service routines remained unchanged in both groups.

Conclusions

AnEFstrategy that included guidance, audit and feedback improved mealtime ambience when nutritional guidelines were introduced in a nursing home setting, whereas food service routines were unchanged by theEFstrategy.
Envisioning the future as expressed within family health conversations by families of persons suffering from stroke
Authors: Sundin Karin , Pusa Susanna , Jonsson Carin , Saveman Britt‐Inger , Östlund Ulrika
Published: August 2017

Background

The whole family is affected when a person suffers from stroke, but few studies have focused on families’ expectations following the stroke.

Objective

The aim of this study was to illuminate what persons with stroke and their family members talk about in Family Health Conversations (FamHCs) with focus on the future and how nurses leading these conversations apprehended the families’ future shown in closing letters based on these conversations.

Method

In this study, seven families with a member ≤65 years who had suffered a stroke participated in FamHC in their homes after the person with stroke had been discharged from the rehabilitation clinic. The FamHC comprised a series of three conversations conducted every other week and a closing letter sent by the nurses to the family to conclude the series. In this study, the third conversations were recorded and they and the closing letters were transcribed and analysed using qualitative content analysis.

Result

The family members including the persons with stroke were found to be able to tell their stories and express their feelings, worries, losses, hopes and wishes for the future within the context of the Family Health Conversations. Support within the family was highlighted as essential to the satisfactory management of future situations.

Conclusion

The persons with stroke and their belonging family members’ vision of the future was reflected over in the light of theories about beliefs, possible selves, hope and suffering, and the findings highlight the need for broader use of family conversations to support persons with stroke and their families to manage the future.
Regulation of tapetum‐specific A9 promoter by transcription factors AtMYB80, AtMYB1 and AtMYB4 in Arabidopsis thaliana and Nicotiana tabacum
Authors: Verma Neetu , Burma Pradeep Kumar
Published: August 2017

Tapetum‐specific promoters have been successfully used for developing transgenic‐based pollination control systems. Although several tapetum‐specific promoters have been identified, in‐depth studies on regulation of such promoters are scarce. The present study analyzes the regulation of the A9 promoter, one of the first tapetum‐specific promoter identified in Arabidopsis thaliana. Transcription factors (TFs) AtMYB80, AtMYB1 (positive regulators) identified by in silico analysis were found to upregulate A9 promoter activity following the over‐expression of the TFs in transient and stable (transgenic) expression assays in both A. thaliana and tobacco. Furthermore, mutations of binding sites of these TFs in the A9 promoter led to loss of its activity. The role of a negative regulator AtMYB4 was also studied by analyzing the activity of A9 promoter following transient expression of RNAi against the TF and by mutating binding sites for AtMYB4 in the A9 promoter. While no changes were observed in case of A. thaliana, the A9 promoter was activated in the roots of transgenic tobacco plants, highlighting the role of these cis‐elements in keeping the A9 promoter repressed in the roots of tobacco.
Measurements and Characterization of Turbulence in the Tip Region of an Axial Compressor Rotor
Authors: Li Yuanchao , Chen Huang , Katz Joseph
Published: August 2017

Modeling of turbulent flows in axial turbomachines is challenging due to the high spatial and temporal variability in the distribution of the strain rate components, especially in the tip region of rotor blades. High-resolution stereo-particle image velocimetry (SPIV) measurements performed in a refractive index-matched facility in a series of closely spaced planes provide a comprehensive database for determining all the terms in the Reynolds stress and strain rate tensors. Results are also used for calculating the turbulent kinetic energy (TKE) production rate and transport terms by mean flow and turbulence. They elucidate some but not all of the observed phenomena, such as the high anisotropy, high turbulence levels in the vicinity of the tip leakage vortex (TLV) center, and in the shear layer connecting it to the blade suction side (SS) tip corner. The applicability of popular Reynolds stress models based on eddy viscosity is also evaluated by calculating it from the ratio between stress and strain rate components. Results vary substantially, depending on which components are involved, ranging from very large positive to negative values. In some areas, e.g., in the tip gap and around the TLV, the local stresses and strain rates do not appear to be correlated at all. In terms of effect on the mean flow, for most of the tip region, the mean advection terms are much higher than the Reynolds stress spatial gradients, i.e., the flow dynamics is dominated by pressure-driven transport. However, they are of similar magnitude in the shear layer, where modeling would be particularly challenging.
Growth and morphology of Pb phases on Ge(111)
Authors: Sato Yu , Chiang Shirley
Published: August 2017

Using low energy electron microscopy (LEEM), the authors investigated how various phases of the Pb overlayer on Ge(111) grow as the Pb coverage increases in the submonolayer range, for substrate temperatures between 200 and 300 °C during Pb deposition. The authors find that each of the three known Pb phases forms in a distinct manner. The low coverage (√3 × √3)R30°-α phase forms small islands less than 10 nm in size, which then coalesce and saturate the surface at 0.33 ML. During the formation of the α phase, Pb atoms replace Ge adatoms of the c(2 × 8) reconstructed structure of the Ge (111) substrate, and the released Ge atoms diffuse and form islands on terraces or attach to steps. The authors show that the size and density of the Ge islands can be controlled systematically by controlling the film deposition parameters. After the saturation of the α phase, the (1 × 1) phase starts to grow preferentially at the lower side of the step edges. LEEM data provide direct evidence of the (1 × 1) phase being a disordered phase, rather than a Pb-terminated unreconstructed Ge(111) surface, resolving the previous controversy. The (√3 × √3)R30°-β phase forms in a dramatic first-order transition from the (1 × 1) phase, with spontaneous domain switching occurring in the coexistence region of the two phases.
Potent β-Lactam Enhancer Activity of Zidebactam and WCK 5153 against Acinetobacter baumannii, Including Carbapenemase-Producing Clinical Isolates
Authors: Moya Bartolome , Barcelo Isabel M. , Bhagwat Sachin , Patel Mahesh , Bou German , Papp-Wallace Krisztina M. , Bonomo Robert A. , Oliver Antonio
Published: August 2017

Multidrug-resistant
Acinetobacter baumannii
has rapidly spread worldwide, resulting in a serious threat to hospitalized patients. Zidebactam and WCK 5153 are novel non-β-lactam bicyclo-acyl hydrazide β-lactam enhancer antibiotics being developed to target multidrug-resistant
A. baumannii
. The objectives of this work were to determine the 50% inhibitory concentrations (IC
50
s) for penicillin-binding proteins (PBP), the OXA-23 inhibition profiles, and the antimicrobial activities of zidebactam and WCK 5153, alone and in combination with β-lactams, against multidrug-resistant
A. baumannii
. MICs and time-kill kinetics were determined for an
A. baumannii
clinical strain producing the carbapenemase OXA-23 and belonging to the widespread European clone II of sequence type 2 (ST2). Inhibition of the purified OXA-23 enzyme by zidebactam, WCK 5153, and comparators was assessed. All of the compounds tested displayed apparent

K
i

values of >100 μM, indicating poor OXA-23 β-lactamase inhibition. The IC
50
s of zidebactam, WCK 5153, cefepime, ceftazidime, meropenem, and sulbactam (range of concentrations tested, 0.02 to 2 μg/ml) for PBP were also determined. Zidebactam and WCK 5153 demonstrated specific high-affinity binding to PBP2 of
A. baumannii
(0.01 μg/ml for both of the compounds). The MICs of zidebactam and WCK 5153 were >1,024 μg/ml for wild-type and multidrug-resistant
Acinetobacter
strains. Importantly, combinations of cefepime with 8 μg/ml of zidebactam or WCK 5153 and sulbactam with 8 μg/ml of zidebactam or WCK 5153 led to 4- and 8-fold reductions of the MICs, respectively, and showed enhanced killing. Notably, several of the combinations resulted in full bacterial eradication at 24 h. We conclude that zidebactam and WCK 5153 are PBP2 inhibitors that show a potent β-lactam enhancer effect against
A. baumannii
, including a multidrug-resistant OXA-23-producing ST2 international clone.
Heterogeneous Genetic Location of
mcr-1
in Colistin-Resistant Escherichia coli Isolates from Humans and Retail Chicken Meat in Switzerland: Emergence of
mcr-1
-Carrying IncK2 Plasmids
Authors: Donà Valentina , Bernasconi Odette J. , Pires João , Collaud Alexandra , Overesch Gudrun , Ramette Alban , Perreten Vincent , Endimiani Andrea
Published: August 2017

We characterized the genetic environment of
mcr-1
in colistin-resistant
Escherichia coli
strains isolated in Switzerland during 2014 to 2016 from humans (
n
= 3) and chicken meat (
n
= 6). Whole-genome and plasmid sequencing identified the
mcr-1
gene integrated in IncX4 (of which, one strain carried the
mcr-1.2
variant), IncI2, IncHI2, and novel IncK2 plasmids (overall,
n
= 7), as well as in the bacterial chromosome (
n
= 2) in single or duplicate copies. Our study supports the easy mobilization of
mcr-1
across diverse genetic locations.
Translational Efficacy of Humanized Exposures of Cefepime, Ertapenem, and Levofloxacin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Murine Model of Complicated Urinary Tract Infection
Authors: Monogue Marguerite L. , Nicolau David P.
Published: August 2017

Validated animal models are required as bridging tools to assess the utility of novel therapies and potential microbiologic outcomes. Herein, we utilized uropathogenic extended-spectrum-β-lactamase (ESBL)-producing and non-ESBL-producing
Escherichia coli
in the neutropenic murine complicated urinary tract infection (cUTI) model with humanized exposures of cefepime, ertapenem, and levofloxacin to assess its translational value to human outcomes. Our data support the translational utility of this murine model to cUTI in humans as humanized exposures produced microbiologic outcomes consistent with the phenotypic profiles of the organisms.
Intracavitary and Systemic Daptomycin for Successful Treatment of a Postpneumonectomy Intrathoracic Infection
Authors: Sangro Paloma , Carmona-Torre Francisco , Mesa Miguel , Del Pozo Jose L. , Yuste Jose R.
Published: August 2017

Treatment of an infected postpneumonectomy cavity is very difficult. We present a patient with an infection of a postpneumonectomy cavity by
Staphylococcus epidermidis
treated with local daptomycin for different dwell times, maintaining high antibiotic levels above the MIC. Clinical and microbiological cure were achieved successfully.
Vaborbactam: Spectrum of Beta-Lactamase Inhibition and Impact of Resistance Mechanisms on Activity in Enterobacteriaceae
Authors: Lomovskaya Olga , Sun Dongxu , Rubio-Aparicio Debora , Nelson Kirk , Tsivkovski Ruslan , Griffith David C. , Dudley Michael N.
Published: August 2017

Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore. The spectrum of beta-lactamase inhibition by vaborbactam and the impact of bacterial efflux and permeability on its activity were determined using a panel of strains with beta-lactamases cloned from various classes and a panel of
Klebsiella pneumoniae
carbapenemase 3 (KPC-3)-producing isogenic strains with various combinations of efflux and porin mutations. Vaborbactam is a potent inhibitor of class A carbapenemases, such as KPC, as well as an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) beta-lactamases. Vaborbactam does not inhibit class D or class B carbapenemases. When combined with meropenem, vaborbactam had the highest potency compared to the potencies of vaborbactam in combination with other antibiotics against strains producing the KPC beta-lactamase. Consistent with broad-spectrum beta-lactamase inhibition, vaborbactam reduced the meropenem MICs for engineered isogenic strains of
K. pneumoniae
with increased meropenem MICs due to a combination of extended-spectrum beta-lactamase production, class C beta-lactamase production, and reduced permeability due to porin mutations. Vaborbactam crosses the outer membrane of
K. pneumoniae
using both OmpK35 and OmpK36, but OmpK36 is the preferred porin. Efflux by the multidrug resistance efflux pump AcrAB-TolC had a minimal impact on vaborbactam activity. Investigation of the vaborbactam concentration necessary for restoration of meropenem potency showed that vaborbactam at 8 μg/ml results in meropenem MICs of ≤2 μg/ml in the most resistant engineered strains containing multiple mutations. Vaborbactam is a highly active beta-lactamase inhibitor that restores the activity of meropenem and other beta-lactam antibiotics in beta-lactamase-producing bacteria, particularly KPC-producing carbapenem-resistant
Enterobacteriaceae
.
Otitis Media and Nasopharyngeal Colonization inccl3−/−Mice
Authors: Deniffel Dominik , Nuyen Brian , Pak Kwang , Suzukawa Keigo , Hung Jun , Kurabi Arwa , Wasserman Stephen I. , Ryan Allen F.
Published: August 2017

We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses ofccl3−/−mice to nontypeableHaemophilus influenzae(NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced inccl3−/−and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by anin vitroassay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline.ccl3−/−deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads inccl3−/−mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease.
Candida albicans and Pseudomonas aeruginosa Interact To Enhance Virulence of Mucosal Infection in Transparent Zebrafish
Authors: Bergeron Audrey C. , Seman Brittany G. , Hammond John H. , Archambault Linda S. , Hogan Deborah A. , Wheeler Robert T.
Published: August 2017

Polymicrobial infections often include both fungi and bacteria and can complicate patient treatment and resolution of infection. Cross-kingdom interactions among bacteria, fungi, and/or the immune system during infection can enhance or block virulence mechanisms and influence disease progression. The fungus
Candida albicans
and the bacterium
Pseudomonas aeruginosa
are coisolated in the context of polymicrobial infection at a variety of sites throughout the body, including mucosal tissues such as the lung.
In vitro
,
C. albicans
and
P. aeruginosa
have a bidirectional and largely antagonistic relationship. Their interactions
in vivo
remain poorly understood, specifically regarding host responses in mediating infection. In this study, we examine trikingdom interactions using a transparent juvenile zebrafish to model mucosal lung infection and show that
C. albicans
and
P. aeruginosa
are synergistically virulent. We find that high
C. albicans
burden, fungal epithelial invasion, swimbladder edema, and epithelial extrusion events serve as predictive factors for mortality in our infection model. Longitudinal analyses of fungal, bacterial, and immune dynamics during coinfection suggest that enhanced morbidity is associated with exacerbated
C. albicans
pathogenesis and elevated inflammation. The
P. aeruginosa
quorum-sensing-deficient Δ
lasR
mutant also enhances
C. albicans
pathogenicity in coinfection and induces extrusion of the swimbladder. Together, these observations suggest that
C. albicans-P. aeruginosa
cross talk
in vivo
can benefit both organisms to the detriment of the host.
The Essential Genome of Burkholderia cenocepacia H111
Authors: Higgins Steven , Sanchez-Contreras Maria , Gualdi Stefano , Pinto-Carbó Marta , Carlier Aurélien , Eberl Leo
Published: August 2017

The study of the minimum set of genes required to sustain life is a fundamental question in biological research. Recent studies on bacterial essential genes suggested that between 350 and 700 genes are essential to support autonomous bacterial cell growth. Essential genes are of interest as potential new antimicrobial drug targets; hence, our aim was to identify the essential genome of the cystic fibrosis (CF) isolate
Burkholderia cenocepacia
H111. Using a transposon sequencing (Tn-Seq) approach, we identified essential genes required for growth in rich medium under aerobic and microoxic conditions as well as in a defined minimal medium with citrate as a sole carbon source. Our analysis suggests that 398 genes are required for autonomous growth in rich medium, a number that represents only around 5% of the predicted genes of this bacterium. Five hundred twenty-six genes were required to support growth in minimal medium, and 434 genes were essential under microoxic conditions (0.5% O
2
). A comparison of these data sets identified 339 genes that represent the minimal set of essential genes required for growth under all conditions tested and can be considered the core essential genome of
B. cenocepacia
H111. The majority of essential genes were found to be located on chromosome 1, and few such genes were located on chromosome 2, where most of them were clustered in one region. This gene cluster is fully conserved in all
Burkholderia
species but is present on chromosome 1 in members of the closely related genus
Ralstonia
, suggesting that the transfer of these essential genes to chromosome 2 in a common ancestor contributed toward the separation of the two genera.

IMPORTANCE
Transposon sequencing (Tn-Seq) is a powerful method used to identify genes that are essential for autonomous growth under various conditions. In this study, we have identified a set of “core essential genes” that are required for growth under multiple conditions, and these genes represent potential antimicrobial targets. We also identified genes specifically required for growth under low-oxygen and nutrient-limited environments. We generated conditional mutants to verify the results of our Tn-Seq analysis and demonstrate that one of the identified genes was not essential
per se
but was an artifact of the construction of the mutant library. We also present verified examples of genes that were not truly essential but, when inactivated, showed a growth defect. These examples have identified so-far-underestimated shortcomings of this powerful method.
Maintenance of Microbial Cooperation Mediated by Public Goods in Single- and Multiple-Trait Scenarios
Authors: Özkaya Özhan , Xavier Karina B. , Dionisio Francisco , Balbontín Roberto
Published: August 2017

Microbes often form densely populated communities, which favor competitive and cooperative interactions. Cooperation among bacteria often occurs through the production of metabolically costly molecules produced by certain individuals that become available to other neighboring individuals; such molecules are called public goods. This type of cooperation is susceptible to exploitation, since nonproducers of a public good can benefit from it while saving the cost of its production (cheating), gaining a fitness advantage over producers (cooperators). Thus, in mixed cultures, cheaters can increase in frequency in the population, relative to cooperators. Sometimes, and as predicted by simple game-theoretic arguments, such increases in the frequency of cheaters cause loss of the cooperative traits by exhaustion of the public goods, eventually leading to a collapse of the entire population. In other cases, however, both cooperators and cheaters remain in coexistence. This raises the question of how cooperation is maintained in microbial populations. Several strategies to prevent cheating have been studied in the context of a single trait and a unique environmental constraint. In this review, we describe current knowledge on the evolutionary stability of microbial cooperation and discuss recent discoveries describing the mechanisms operating in multiple-trait and multiple-constraint settings. We conclude with a consideration of the consequences of these complex interactions, and we briefly discuss the potential role of social interactions involving multiple traits and multiple environmental constraints in the evolution of specialization and division of labor in microbes.
Lifetime prevalence of traumatic brain injury with loss of consciousness
Authors: Corrigan John D , Yang Jingzhen , Singichetti Bhavna , Manchester Kara , Bogner Jennifer
Published: August 2017

Objective

To determine the prevalence of lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) among adult, non-institutionalised residents of Ohio.

Methods

We analysed data from 2014 Ohio Behavioral Risk Factor Surveillance System, which included a state-specific module designed to elicit lifetime history of TBI.

Results

Of non-institutionalised adults 18 years and over living in Ohio, 21.7% reported at least one lifetime TBI with LOC, 2.6% experienced at least one moderate or severe such injury, 9.1% experienced a TBI with LOC before age 15 years and 10.8% experienced either TBI with LOC before age 15 years or a moderate or severe injury. Males, those with lower incomes and those unable to work were more likely to have incurred at least one TBI with LOC, multiple TBIs with LOC, a moderate or severe TBI and a TBI with LOC before age15.

Conclusions

One in five adults experienced TBIs of sufficient severity to cause LOC; 3% experienced at least one moderate or severe TBI and almost 10% experienced a first TBI with LOC before the age of 15 years. The prevalence of lifetime TBI in the present study suggests that there may be a substantially greater burden of injury than concluded from previous prevalence estimates.
Comparison of the effectiveness of hands-on versus online education in child passenger safety
Authors: Mantha Anita , Beckworth Kristen L , Ansiaux John A , Chen Carol C , Hoffman Benjamin , Shenoi Rohit P
Published: August 2017

Background

Community paediatricians’ knowledge of appropriate child safety seat (CSS) use in vehicles may be inadequate. We compared the effectiveness of hands-on and online education in improving and retaining child passenger safety (CPS) knowledge and skills among paediatric trainees.

Methods

Paediatric trainees were randomised to receive hands-on skills training versus a 1-hour online module in CPS. CSS knowledge and installation skills were assessed using a validated 10-item/point questionnaire and an assessment tool respectively at baseline and after 6 months. Preintervention and postintervention knowledge improvement and CSS installation skills between groups were assessed using paired t-tests and effect size (d).

Results

Forty-eight students agreed to participate and were randomised. Thirty-nine completed training (hands-on: 23 and online: 15). At entry, no significant differences in learners’ demographics and prior CPS education existed. Baseline CPS knowledge scores did not differ significantly between groups (p=0.26). Postintervention, both groups demonstrated a significant increase in knowledge scores (hands-on=3.1 (95% CI 2.4 to 3.7), p<0.0001; online=2.6 (95% CI 1.9 to 3.3), p<0.0001), though the pre–post gain in knowledge scores were not significantly different between groups (p=0.35). At follow-up, both groups demonstrated a significant increase in knowledge scores (hands-on=1.8 (95% CI 1.2 to 2.4), p<0.0001; online=1.1 (95% CI 0.7 to 1.6), p<0.0001) with the hands-on group scores significantly better than the online group (p<0.02). The long-term gain in knowledge scores was not significantly different between groups (p=0.12).

Baseline CSS installation skill scores did not significantly differ between groups for forward-facing seats (p=0.16) and rear-facing seats (p=0.51). At follow-up, mean CSS installation skill scores significantly increased for the hands-on group (forward-facing seat: 0.8 (95% CI 0.16 to 1.44), p<0.02; rear-facing seat: 1.2 (95% CI 0.6 to 1.7), p<0.001) but not for the online group (forward-facing seat: 0.9 (95% CI −0.08 to 1.9), p=0.07); rear-facing seat: −0.2 (95% CI −1.1 to 0.7), p=0.6).

Conclusions

Among paediatric trainees, hands-on and online CPS education are both effective in improving long-term CPS knowledge. Long-term installation skills for forward-facing and rear-facing CSS persist for hands-on education but are inconclusive for online education.
Risk factors for redemption of feline neutering vouchers issued by welfare organisations
Authors: Kinsman Rachel H , Gruffydd‐Jones Tim J , Clements Jane , Murray Jane K
Published: August 2017

Animal welfare organisations in the UK invest substantial resources to fund subsidised neutering vouchers to increase feline neutering rates. Little evidence exists to quantify factors influencing voucher redemption. This cross‐sectional study assessed risk factors (including voucher value and expiry period) for redemption of neutering vouchers issued by staff of the feline welfare charity Cats Protection. Data were collected using telephone interview‐administered questionnaires of cat owners who were issued a neutering voucher(s) and from Cats Protection voucher payment records. During the four‐month study 2655 owners were issued 3935 vouchers. Multivariable logistic regression analysis revealed that owners of cats that had produced ≥1 litter before voucher request, owners eligible for a voucher due to receiving benefits and owners who rented their homes or lived with family were less likely to redeem vouchers than owners whose cats had not had a litter, were eligible for a voucher for other reasons and/or owners who owned their home, respectively.
Uncovering the fuzzy community structure accurately based on steepest descent projection
Authors: Fang Changjian , Mu Dejun , Deng Zhenghong , Yan Jiaqi
Published: August 2017

Uncovering the community structure in complex network is a hot research point in recent years. How to identify the community structure accurately in complex network is still an open question under research. There are lots of methods based on topological information, which have some good performances at the expense of longer runtimes. In this paper, we propose a new fuzzy algorithm which follows the line of fuzzy c-means algorithm. A steepest descent framework with projection by optimizing the quality function is presented under the generalized framework. The results of experiments on both real-world networks and synthetic networks show that the proposed method achieves the highest efficiency and is easy for detecting fuzzy community structure in large-scale complex networks.
Enhanced Sensitivity for Structural Damage Detection Using Incomplete Modal Data
Authors: Esfandiari Akbar , Vahedi Maryam
Published: August 2017

The necessity of detecting structural damages in an early stage has led to the development of various procedures for structural model updating. In this regard, sensitivity-based model updating methods utilizing mode shape data are known as effective tools. For this purpose, accurate estimation of the mode shape changes is desired to achieve successful model updating. In this paper, Wang’s method is improved by including measured natural frequencies of the damaged structure in derivation of the sensitivity equation. The sensitivity equation is then solved using an incomplete subset of mode shape data in evaluation of the changes of the structural parameters. A comparative study of the results obtained by the proposed method with those by the modal method for a truss and a frame model indicated that the former is significantly more effective for damage detection than the latter. Furthermore, the capability of the proposed method for model updating in the presence of measurement and mass modeling errors is investigated.
MARKET FLUCTUATIONS EXPLAINED BY DIVIDENDS AND INVESTOR NETWORKS
Authors: OLDHAM MATTHEW
Published: August 2017

The inability of investors and academics to consistently predict, and understand the behavior of financial markets has forced the search for alternative analytical frameworks. Analyzing financial markets as complex systems is a framework that has demonstrated great promises, with the use of agent-based models (ABMs) and the inclusion of network science playing an important role in increasing the relevance of the framework. Using an artificial stock market created via an ABM, this paper provides a significant insight into the mechanisms that drive the returns in financial markets, including periods of elevated prices and excess volatility. The paper demonstrates that the network topology that investors form and the dividend policy of firms significantly affect the behavior of the market. However, if investors have a bias to following their neighbors then the topology becomes redundant. By successfully addressing these issues this paper helps refine and shape a variety of additional research tasks for the use of ABMs in uncovering the dynamics of financial markets.