bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’ Expectations on Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Qualitative Exploration
Authors: Henssen Dylan J.H.A. , Scheepers Nicole , Kurt Erkan , Arnts Inge , Steegers Monique , Vissers Kris , van Dongen Robert , Engels Yvonne
Published: July 2017

Background

Spinal cord stimulation (SCS) is an effective therapy to reduce pain in patients who suffer from failed back surgery syndrome (FBSS). In order to inform patients optimally prior to this therapy, knowing their expectations is crucial.

Methods

Thirteen patients suffering from FBSS and scheduled for SCS were interviewed using a semistructured protocol. Patients were interviewed either at home or at their treating hospital. Data from these interviews were analyzed using directed content analysis. In addition to the qualitative interviews, an adjusted Brief Pain Inventory questionnaire was used to quantify expectations.

Results

The expectations of patients with regard to SCS could be subdivided into 13 categories, which could be grouped into 6 general themes: (1) physical well‐being, (2) social well‐being, (3) material well‐being, (4) emotional well‐being, (5) development and activity, and (6) constraints of the procedure of SCS. These findings confirm patients’ expectations about the improvement of their quality of life by SCS for FBSS. This indicates that assessing pain relief is not enough to adequately evaluate the effects of SCS. The small diversity within the studied population and the lack of patient‐to‐patient education are 2 possible limitations of this study.

Conclusions

To improve education for patients prior to SCS surgery and to evaluate the effects of SCS, a multidimensional approach needs to be implemented. Possible disadvantages of SCS need to be discussed prior to the treatment.
The avidity of tumor‐specific T cells amplified by a plasmacytoid dendritic cell‐based assay can predict the clinical evolution of melanoma patients
Authors: Charles Julie , Chaperot Laurence , Revol Bruno , Baudin Marine , Mouret Stephane , Hamon Agnes , Leccia Marie‐Therese , Plumas Joel , Aspord Caroline
Published: July 2017

The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that allows eliciting highly efficient antitumor T‐cell responses. We used it to investigate antitumor T‐cell functionality in peripheral blood mononuclear cells and tumor‐infiltrating lymphocytes from melanoma patients. The pDCs elicited tumor‐specific T cells in different proportions and displaying diverse functional features, dependent upon the stage of the disease, but independent of the histological parameters at diagnosis. Strikingly, the avidity of the MelA‐specific T cells triggered by the pDCs was found to predict patient relapse time and overall survival. Our findings highlighted unexplored aspects of antitumor T‐cell responsiveness in melanoma, and revealed for the first time the structural avidity of tumor‐specific T cells as a crucial feature for predicting clinical evolution.
Genetic architecture of adult plant resistance to leaf rust in a wheat association mapping panel
Authors: Gerard G. S. , Kobiljski B. , Lohwasser U. , Börner A. , Simón M. R.
Published: July 2017

Leaf rust caused by Puccina triticina is one of the most destructive fungal diseases of wheat (Triticum aestivum). Adult plant resistance (APR) is an effective strategy to achieve long‐term protection from the disease. In this study, findings are reported from a genome‐wide association study (GWAS) using a panel of 96 wheat cultivars genotyped with 874 Diversity Arrays Technology (DArT) markers and tested for adult leaf rust response in six field trials. A total of 13 quantitative trait loci (QTL) conferring APR to leaf rust were identified on chromosome arms 1BL, 1DS, 2AS, 2BL, 2DS, 3BS, 3BL, 4AL, 6BS (two), 7DS, 5BL/7BS and 6AL/6BS. Of these, seven QTLs mapped close to known resistance genes and QTLs, while the remaining six are novel and can be used as additional sources of resistance. Accessions with a greater number of combined QTLs for APR showed lower levels of disease severity, demonstrating additive and significant pyramiding effects. All QTLs had stable main effects and they did not exhibit a significant interaction with the experiments. These findings could help to achieve adequate levels of durable resistance through marker‐assisted selection and pyramiding resistance QTLs in local germplasm.
How to analyze technology lifecycle from the perspective of patent characteristics? the cases of DVDs and hard drives
Authors: Su Hsin‐Ning
Published: July 2017

This study aims to analyze the technology lifecycle from the perspective of the dynamics of patent characteristics; the dynamics of patent characteristics are proposed as an approach for characterizing technology lifecycle in this study. DVD and hard drive technologies, which have already experienced their complete technology lifecycles, were selected for analyzing their patent characteristics as a function of the different stages of their technology lifecycles to thus obtain the objective of this research. The results obtained in this study provide a channel to assess the nature of firms’ innovation strategies along technology lifecycles. It can be observed that (1) patents attempt to cite more prior patent or non‐patent references at the latter stages to find more technological or scientific sources that can contribute to technological innovation, (2) most litigated patents are granted in the Growth stage, so it is expected that patents in the Growth stage should be more important and, thus, more relevant to dominant design than the patents granted in other stages.
Clustered Multistate Models with Observation Level Random Effects, Mover–Stayer Effects and Dynamic Covariates: Modelling Transition Intensities and Sojourn Times in a Study of Psoriatic Arthritis
Authors: Yiu Sean , Farewell Vernon T. , Tom Brian D. M.
Published: July 2017

In psoriatic arthritis, it is important to understand the joint activity (represented by swelling and pain) and damage processes because both are related to severe physical disability. The paper aims to provide a comprehensive investigation into both processes occurring over time, in particular their relationship, by specifying a joint multistate model at the individual hand joint level, which also accounts for many of their important features. As there are multiple hand joints, such an analysis will be based on the use of clustered multistate models. Here we consider an observation level random-effects structure with dynamic covariates and allow for the possibility that a subpopulation of patients is at minimal risk of damage. Such an analysis is found to provide further understanding of the activity–damage relationship beyond that provided by previous analyses. Consideration is also given to the modelling of mean sojourn times and jump probabilities. In particular, a novel model parameterization which allows easily interpretable covariate effects to act on these quantities is proposed.
The Effects of Regional and Distance Education on the Supply of Qualified Teachers in Rural Iceland
Authors: Bjarnason Thoroddur , Thorarinsdottir Brynhildur
Published: July 2017

Difficulties in recruiting qualified teachers have been traced to insufficient services and amenities in rural areas, an urban emphasis in teacher education, few local students becoming teachers and a lack of teacher mobility. This study maps the mobility of recently graduated teachers in urban, exurban, micropolitan and other rural areas of Iceland. The graduation rate of teachers was found to be higher in rural than urban areas, yet rural teachers are less likely to remain after graduation. Relatively few rural teachers return from on‐campus studies in the either the capital area or the northern regional centre. Rural distance students are however almost equally likely as urban on‐campus students to stay in their home areas after graduation, and they are the majority of teachers in rural areas. From a policy perspective, distance education appears more effective than regional campuses in increasing the supply of qualified teachers in rural and remote areas.
Does real exchange rate depreciation increase productivity? Analysis using Korean firm‐level data
Authors: Choi Bo‐Young , Pyun Ju Hyun
Published: July 2017

We examine the effects of real exchange rate (RER) depreciation shocks on firm productivity. Using the firm‐level data of Korean manufacturing industries for 2006–13, we distinguish between yearly RER movement and persistent RER depreciation during 2007–09 and analyse how each affects productivity. We find the positive effect of RER depreciation on productivity among exporters, and this positive effect increases with higher export exposure. However, the positive productivity gain disappears when the depreciation persists. Our findings suggest that while immediate depreciation leads to productivity upgrade via price competitiveness and scale expansion, persistent depreciation nullifies the productivity gain by slackening the innovation effort.
Linac‐based stereotactic radiation therapy for canine non‐lymphomatous nasal tumours: 29 cases (2013‐2016)
Authors: Gieger T. L. , Nolan M. W.
Published: July 2017

Twenty‐nine dogs were treated with linac‐based stereotactic radiation therapy (SRT) for non‐lymphomatous nasal tumours. Only dogs with a follow‐up time >365 days were included in this retrospective analysis. No dogs had evidence of distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3 daily 10 Gy fractions was delivered using intensity‐modulation, cone‐beamCT‐based image guidance and a robotic treatment couch. Clinical signs improved in all cases. Nineteen dogs hadCTscans 3‐4 months post‐SRTand all had partial or complete tumour response. Minimal acute toxicities were detected. Clinically significant late toxicities included oronasal or nasocutaneous fistulas (N = 3) and biopsy‐confirmed fungal rhinitis with no evidence of tumour progression (N = 2). The median progression‐free survival (PFS) was 354 days, with 49% and 39% progression‐free at 1 and 2 years post‐SRT, respectively. The median survival time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post‐SRT, respectively. Neither the clinical parameters evaluated (modified Adams’ stage, histopathology, presence of intracranial extension of the tumour) nor dosimetric data were predictive forPFSorST. ThisSRTprotocol appears to be well tolerated, andPFIandSTare comparable or superior to those reported in other definitive‐intent radiotherapy protocols.
Hazardous Area Classification for Surface Well Testing Equipment
Authors: Gupta Ashish
Published: July 2017

Hazardous area classification or zoning is a method of analyzing and classifying the environment in which explosive gas atmospheres may occur to facilitate the proper selection and installation of equipment to be used safely in that environment. In several oil and gas companies, hazardous area classification is carried out as an integral step of the risk assessment exercise to identify areas where controls over ignition sources are required on the rigs. In this paper, one example of such an exercise is presented. The recommendations from the exercise were used in updating the company’s guidelines on zoning and eventually improving the fire safety of its operations.

The paper discusses these factors and their impact on zoning.
Ultradeep electron cyclotron resonance plasma etching of GaN
Authors: Harrison Sara E. , Voss Lars F. , Torres Andrea M. , Frye Clint D. , Shao Qinghui , Nikolić Rebecca J.
Published: July 2017

Ultradeep (≥5 μm) electron cyclotron resonance plasma etching of GaN micropillars was investigated. Parametric studies on the influence of the applied radio-frequency power, chlorine content in a Cl2/Ar etch plasma, and operating pressure on the etch depth, GaN-to-SiO2 selectivity, and surface morphology were performed. Etch depths of >10 μm were achieved over a wide range of parameters. Etch rates and sidewall roughness were found to be most sensitive to variations in RF power and % Cl2 in the etch plasma. Selectivities of >20:1 GaN:SiO2 were achieved under several chemically driven etch conditions where a maximum selectivity of ∼39:1 was obtained using a 100% Cl2 plasma. The etch profile and (0001) surface morphology were significantly influenced by operating pressure and the chlorine content in the plasma. Optimized etch conditions yielded >10 μm tall micropillars with nanometer-scale sidewall roughness, high GaN:SiO2 selectivity, and nearly vertical etch profiles. These results provide a promising route for the fabrication of ultradeep GaN microstructures for use in electronic and optoelectronic device applications. In addition, dry etch induced preferential crystallographic etching in GaN microstructures is also demonstrated, which may be of great interest for applications requiring access to non- or semipolar GaN surfaces.
Teaching a Holistic, Harmonious and Internal Motivational Concept of Excellence to Promote Olympic Ideals, Health and Well-Being for All
Authors: Papaioannou Athanasios G.
Published: July 2017

Based on recent trends in positive psychology, on ancient Greek sport literature and particularly on Aristotle’s philosophy, the holistic, harmonious and internal motivational components of excellence and their implications for students’ motivation for physical activity, health and well-being are presented. While modern motivational theories and research have partly addressed the holistic and internal motivational components of excellence, they have yet to address its harmonious part. In this article it is explained why all three components of excellence are required to promote eudaimonic well-being, which is the ultimate aim of Olympism. It is argued also that the conceptualization of hedonic-eudaimonic well-being should be primarily based on the “me” versus “us” meaning. While current physical activity experiences more often reflect a hedonistic perspective, to promote health and well-being for all, an eudaimonic perspective in teaching in physical education and youth sport is needed. This should primarily focus on the promotion of Olympic ideals, such as excellence, friendship, and respect. These three ideals and well-being are all very much interconnected, when all three components of excellence exist in excess. To promote excellence, Olympic ideals, and well-being, the core ideas of an educational philosophy promoting excellence in physical education and youth sport are presented.
Attitude Research in Physical Education: A Review
Authors: Silverman Stephen
Published: July 2017

This paper provides a comprehensive review of attitude research in physical education. The first section, reviews theoretical models that are prevalent in attitude research. Then, the next section describes the methods that were used to locate the research used in the remainder of the paper. The third section discusses measurement issues in attitude research, focusing on issues of score reliability. The final section reviews the results of research on attitude of physical education students and teachers. Critiques and analyses occur throughout the review.
Structural Insights into the TLA-3 Extended-Spectrum β-Lactamase and Its Inhibition by Avibactam and OP0595
Authors: Jin Wanchun , Wachino Jun-ichi , Yamaguchi Yoshihiro , Kimura Kouji , Kumar Anupriya , Yamada Mototsugu , Morinaka Akihiro , Sakamaki Yoshiaki , Yonezawa Minoru , Kurosaki Hiromasa , Arakawa Yoshichika
Published: July 2017

The development of effective inhibitors that block extended-spectrum β-lactamases (ESBLs) and restore the action of β-lactams represents an effective strategy against ESBL-producing
Enterobacteriaceae
. We evaluated the inhibitory effects of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL that we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent inhibitor constants (

K
i

app
) of 1.71 ± 0.10 and 1.49 ± 0.05 μM, respectively, and could restore susceptibility to cephalosporins in the TLA-3-producing
Escherichia coli
strain. The value of the second-order acylation rate constant (
k
2
/
K
, where
k
2
is the acylation rate constant and
K
is the equilibrium constant) of avibactam [(3.25 ± 0.03) × 10
3
M
−1
· s
−1
] was closer to that of class C and D β-lactamases (
k
2
/
K
, <10
4
M
−1
· s
−1
) than that of class A β-lactamases (
k
2
/
K
, >10
4
M
−1
· s
−1
). In addition, we determined the structure of TLA-3 and that of TLA-3 complexed with avibactam or OP0595 at resolutions of 1.6, 1.6, and 2.0 Å, respectively. TLA-3 contains an inverted Ω loop and an extended loop between the β5 and β6 strands (insertion after Ser237), which appear only in PER-type class A β-lactamases. These structures might favor the accommodation of cephalosporins harboring bulky R1 side chains. TLA-3 presented a high catalytic efficiency (
k
cat
/

K
m

) against cephalosporins, including cephalothin, cefuroxime, and cefotaxime. Avibactam and OP0595 bound covalently to TLA-3 via the Ser70 residue and made contacts with residues Ser130, Thr235, and Ser237, which are conserved in ESBLs. Additionally, the sulfate group of the inhibitors formed polar contacts with amino acid residues in a positively charged pocket of TLA-3. Our findings provide a structural template for designing improved diazabicyclooctane-based inhibitors that are effective against ESBL-producing
Enterobacteriaceae
.
Assessment of Bactericidal Drug Activity and Treatment Outcome in a Mouse Tuberculosis Model Using a Clinical Beijing Strain
Authors: Mourik Bas C. , de Knegt Gerjo J. , Verbon Annelies , Mouton Johan W. , Bax Hannelore I. , de Steenwinkel Jurriaan E. M.
Published: July 2017

Mycobacterium tuberculosis
Beijing strains are associated with lower treatment success rates in tuberculosis (TB) patients. In contrast, laboratory strains such as H37Rv are often used in preclinical tuberculosis models. Therefore, we explored the impact of using a clinical Beijing strain on treatment outcome in our mouse tuberculosis model. Additionally, the predictive value of bactericidal activity on treatment outcome was assessed. BALB/c mice were infected with a Beijing strain and treated with one of 10 different combinations of conventional anti-TB drugs. Bactericidal activity was assessed by determining reductions in mycobacterial load after 7, 14, and 28 days and after 2, 3, and 6 months of treatment. Treatment outcome was evaluated after a 6-month treatment course and was based on lung culture status 3 months posttreatment. None of the anti-TB drug regimens tested could achieve 100% treatment success. Treatment outcome depended critically on rifampin. Four non-rifampin-containing regimens showed 0% treatment success compared to success rates between 81 and 95% for six rifampin-containing regimens. Bactericidal activity was predictive only for treatment outcome after 3 months of treatment. Our data advocate the use of multiple mycobacterial strains, including a Beijing strain, to increase the translational value of mouse TB models evaluating treatment outcome. Additionally, our findings support the notion that bactericidal activity in the first 2 months of treatment, as measured in clinical phase IIa/b trials, has limited predictive value for tuberculosis treatment outcome, thus emphasizing the need for better parameters to guide future phase IIII trials.
In Vitro
Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China
Authors: Pang Yu , Zong Zhaojing , Huo Fengmin , Jing Wei , Ma Yifeng , Dong Lingling , Li Yunxu , Zhao Liping , Fu Yuhong , Huang Hairong
Published: July 2017

Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the
in vitro
susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the
gyrA
gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (
P
< 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the
fbiC
gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent
in vitro
activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.
Resistance to Ceftazidime-Avibactam Is Due to Transposition of KPC in a Porin-Deficient Strain of Klebsiella pneumoniae with Increased Efflux Activity
Authors: Nelson Kirk , Hemarajata Peera , Sun Dongxu , Rubio-Aparicio Debora , Tsivkovski Ruslan , Yang Shangxin , Sebra Robert , Kasarskis Andrew , Nguyen Hoan , Hanson Blake M. , Leopold Shana , Weinstock George , Lomovskaya Olga , Humphries Romney M.
Published: July 2017

Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including
Klebsiella pneumoniae
carbapenemase (KPC). Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258
Klebsiella pneumoniae
that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a nonfunctional OmpK35, whereas we demonstrate that a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced the activity of this porin and impacted ceftazidime-avibactam susceptibility. In addition, we demonstrate that the increased expression of
bla
KPC-3
and
bla
SHV-12
observed in the ceftazidime-avibactam-resistant isolate was due to transposition of the Tn
4401
transposon harboring
bla
KPC-3
into a second plasmid, pIncX3, which also harbored
bla
SHV-12
, ultimately resulting in a higher copy number of

bla
KPC

-3
in the resistant isolate. pIncX3 plasmid from the ceftazidime-avibactam resistant isolate, conjugated into a OmpK35/36-deficient
K. pneumoniae
background that harbored a mutation to the
ramR
regulator of the
acrAB
efflux operon recreated the ceftazidime-avibactam-resistant MIC of 32 μg/ml, confirming that this constellation of mutations is responsible for the resistance phenotype.
Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods
Authors: Espinel-Ingroff A. , Abreu D. P. B. , Almeida-Paes R. , Brilhante R. S. N. , Chakrabarti A. , Chowdhary A. , Hagen F. , Córdoba S. , Gonzalez G. M. , Govender N. P. , Guarro J. , Johnson E. M. , Kidd S. E. , Pereira S. A. , Rodrigues A. M. , Rozental S. , Szeszs M. W. , Ballesté Alaniz R. , Bonifaz A. , Bonfietti L. X. , Borba-Santos L. P. , Capilla J. , Colombo A. L. , Dolande M. , Isla M. G. , Melhem M. S. C. , Mesa-Arango A. C. , Oliveira M. M. E. , Panizo M. M. , Pires de Camargo Z. , Zancope-Oliveira R. M. , Meis J. F. , Turnidge J.
Published: July 2017

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenicSporothrixspecies to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates ofSporothrixschenckii sensu latoand some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents andSporothrixspecies and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301Sporothrix schenckii sensu stricto, 486S. brasiliensis, 75S. globosa, and 13S. mexicanamolecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs forS. schenckiiandS. brasiliensis, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs forS. brasiliensiswere 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs forS. schenckii, as well as ECVs forS. globosaandS. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.
Emergence of
mcr-1
in Raoultella ornithinolytica and Escherichia coli Isolates from Retail Vegetables in China
Authors: Luo Juan , Yao Xu , Lv Luchao , Doi Yohei , Huang Xiuyu , Huang Sicheng , Liu Jian-Hua
Published: July 2017

The presence of
mcr-1
among
Enterobacteriaceae
isolates collected from retail vegetables in China between 2015 and 2016 was investigated. Two
Raoultella ornithinolytica
and seven
Escherichia coli
strains recovered from lettuce and tomato samples were identified as MCR-1-producers. Similar to isolates from animals and humans, the
mcr-1
gene was located on the IncHI2/ST3, IncI2, or IncX4 plasmids. The presence of MCR-1-producing organisms in ready-to-eat food samples represents a serious risk for human health.
Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease
Authors: Choi Hayoung , Kim Su-Young , Kim Dae Hun , Huh Hee Jae , Ki Chang-Seok , Lee Nam Yong , Lee Seung-Heon , Shin Soyoun , Shin Sung Jae , Daley Charles L. , Koh Won-Jung
Published: July 2017

Macrolide antibiotics are mainstays in the treatment of lung disease due to the
Mycobacterium abscessus
complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant
Mycobacterium abscessus
subsp.
abscessus
. This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of
M. abscessus
subsp.
abscessus
. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant
M. abscessus
subsp.
abscessus
lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for
M. abscessus
subsp.
abscessus
, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (
n
= 10) or 2059 (
n
= 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with
M. abscessus
subsp.
abscessus
lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant
M. abscessus
subsp.
abscessus
lung disease.
Transfersomal Phage Cocktail Is an Effective Treatment against Methicillin-Resistant Staphylococcus aureus-Mediated Skin and Soft Tissue Infections
Authors: Chhibber Sanjay , Shukla Ashu , Kaur Sandeep
Published: July 2017

The emergence of drug resistance has rekindled interest in phage therapy as an alternative treatment option; its potency, safety, and proven efficacy are worth noting. However, phage therapy still suffers from issues of poor stability, narrow spectra, and poor pharmacokinetic profiles. Therefore, it is essential to look into the use of drug delivery systems for efficient delivery of lytic phagesin vivo. The present study evaluated the use of nanostructured lipid-based carriers, i.e., transfersomes, as transdermal delivery systems for encapsulating a methicillin-resistantStaphylococcus aureus(MRSA) phage cocktail. Furthermore, the therapeutic potential of the encapsulated phage cocktail in resolving experimental soft tissue infections in rats was studied. Results fromin vitrostability andin vivophage titer experiments indicated that the transfersome-entrapped phage cocktail showed better persistence and stability than did free phages. Rats treated with the transfersome-entrapped phage cocktail resolved the experimental thigh infections within a period of 7 days, unlike the 20-day period required for untreated animals. The findings of the present study support the use of transfersomes as delivery agents to enhance the stability andin vivopersistence of the encapsulated phages. In addition, this study highlights the advantages offered by transfersome-encapsulated phages in providing better therapeutic options than free phages for treating skin and soft tissue infections. The transfersome-entrapped phage cocktail was able to protect all test animals (with no deaths) even when administered with a delay of 12 h postinfection, unlike free phages, thus making this treatment option more suitable for clinical settings.
Interleukin-17A Aggravates Middle Ear Injury Induced by Streptococcus pneumoniae through the p38 Mitogen-Activated Protein Kinase Signaling Pathway
Authors: Wang Wei , Liu Wenbin , Liu Jiali , Wang Zimeng , Fan Fangmei , Ma Yurong , Jin Chunfang , Xiang Yun , Huang Yifei , Zhang Xuemei , Xu Wenchun , Yin Yibing , He Yujuan
Published: July 2017

Acute otitis media (AOM) is one of the most common bacterial infectious diseases in children aged 2 to 7 years worldwide. We previously demonstrated that interleukin-17A (IL-17A) promotes an acute inflammatory response characterized by the influx of neutrophils into the middle ear cavity during
Streptococcus pneumoniae
-induced AOM. In general, the inflammatory response is viewed as an effector that frequently causes local tissue damage. However, little is known about the pathogenic effects of IL-17A in AOM. Here, we investigated the pathogenic effects of IL-17A by using wild-type (WT) and IL-17A knockout (KO) mouse models. The results showed that the pathogenic effects of AOM, including weight loss, histopathological changes, and proinflammatory cytokine production, were more severe in WT mice than in IL-17A KO mice, suggesting that IL-17A aggravates tissue damage in AOM. Furthermore, these pathogenic effects were found to be dependent on p38 mitogen-activated protein kinase (MAPK) and could be reversed in the presence of a p38 MAPK-specific inhibitor. It was also demonstrated that IL-17A promoted the production of neutrophil myeloperoxidase (MPO) through the p38 MAPK signaling pathway, which was responsible for the middle ear tissue injury. These data support the conclusion that IL-17A contributes to middle ear injury through the p38 MAPK signaling pathway.
Changing views on child mortality and economic sanctions in Iraq: a history of lies, damned lies and statistics
Authors: Dyson Tim , Cetorelli Valeria
Published: July 2017

In August 1990, Saddam Hussein’s army invaded Kuwait and consequently the United Nations imposed economic sanctions on Iraq. In 1991, an international military alliance expelled the Iraqi army from Kuwait during a short war. Nevertheless, the economic sanctions remained in place—their removal required that Iraq should destroy its weapons of mass destruction. Subsequent years saw reports of acute suffering in Iraq. The sanctions undoubtedly greatly reduced the country’s ability to import supplies of food and medicine. Particular concerns arose about the state of young children. These concerns crystalised in 1999 when, with cooperation from the Iraqi government, Unicef conducted a major demographic survey. The results of the survey indicated that the under-5 death rate in Iraq had increased hugely between 1990 and 1991 and had then continued at a very high level. The survey results were used both to challenge and support the case for the invasion of Iraq in 2003. And they were cited by Tony Blair in 2010 in his testimony to the Iraq Inquiry established by the British government. Indeed, the results of the 1999 Unicef/Government of Iraq survey are still cited. Since 2003, however, several more surveys dealing with child mortality have been undertaken. Their results show no sign of a huge and enduring rise in the under-5 death rate starting in 1991. It is therefore clear that Saddam Hussein’s government successfully manipulated the 1999 survey in order to convey a very false impression—something that is surely deserving of greater recognition.
A unified multi-level model approach to assessing patient responsiveness including; return to normal, minimally important differences and minimal clinically important improvement for patient reported outcome measures
Authors: Sayers Adrian , Wylde Vikki , Lenguerrand Erik , Gooberman-Hill Rachael , Dawson Jill , Beard David , Price Andrew , Blom Ashley W
Published: July 2017

Objective

This article reviews and compares four commonly used approaches to assess patient responsiveness with a treatment or therapy (return to normal (RTN), minimal important difference (MID), minimal clinically important improvement (MCII), OMERACT-OARSI [Outcome Measures in Rheumatology—Osteoarthris Reseach Society International] (OO)) and demonstrates how each of the methods can be formulated in a multilevel modelling (MLM) framework.

Design

Cohort study.

Setting

A cohort of patients undergoing total hip and knee replacement were recruited from a single UK National Health Service hospital.

Population

400 patients from the Arthroplasty Pain Experience cohort study undergoing total hip (n=210) and knee (n=190) replacement who completed the Intermittent and Constant Osteoarthritis Pain questionnaire prior to surgery and then at 3, 6 and 12 months after surgery.

Primary outcomes

The primary outcome was defined as a response to treatment following total hip or knee replacement. We compared baseline scores, change scores and proportion of individuals defined as ‘responders’ using traditional and MLM approaches with patient responsiveness.

Results

Using existing approaches, baseline and change scores are underestimated, and the variance of baseline and change scores overestimated in comparison with MLM approaches. MLM increases the proportion of individuals defined as responding in RTN, MID and OO criteria compared with existing approaches. Using MLM with the MCII criteria reduces the number of individuals identified as responders.

Conclusion

MLM improves the estimation of the SD of baseline and change scores by explicitly incorporating measurement error into the model and avoiding regression to the mean when making individual predictions. Using refined definitions of responsiveness may lead to a reduction in misclassification when attempting to predict who does and does not respond to an intervention and clarifies the similarities between existing methods.
Exploring the relationship between frequent internet use and health and social care resource use in a community-based cohort of older adults: an observational study in primary care
Authors: Clarke Caroline S , Round Jeff , Morris Stephen , Kharicha Kalpa , Ford John , Manthorpe Jill , Iliffe Steve , Goodman Claire , Walters Kate
Published: July 2017

Objectives

Given many countries’ ageing populations, policymakers must consider how to mitigate or reduce health problems associated with old age, within budgetary constraints. Evidence of use of digital technology in delaying the onset of illness and reducing healthcare service use is mixed, with no clear consensus as yet. Our aim was to investigate the relationship between frequent internet use and patterns of health or social care resource use in primary care attendees who took part in a study seeking to improve the health of older adults.

Methods

Participants recruited from primary care, aged >65 and living in semirural or urban areas in the south of England, were followed up at 3 and 6 months after completing a comprehensive questionnaire with personalised feedback on their health and well-being. We performed logistic regression analyses to investigate relationships between frequent internet use and patterns of service use, controlling for confounding factors, and clustering by general practitioner practice. Four categories of service use data were gathered: use of primary National Health Service (NHS) care; secondary NHS care; other community health and social care services; and assistance with washing, shopping and meals.

Results

Our results show, in this relatively healthy population, a positive relationship (OR 1.72, 95% CI 1.33 to 2.23) between frequent internet use and use of any other community-based health services (physiotherapist, osteopath/chiropractor, dentist, optician/optometrist, counselling service, smoking cessation service, chiropodist/podiatrist, emergency services, other non-specific health services) and no relationship with the other types of care. No causal relationship can be postulated due to the study’s design.

Conclusions

No observed relationship between frequent internet use and primary or secondary care use was found, suggesting that older adults without internet access are not disadvantaged regarding healthcare use. Further research should explore how older people use the internet to access healthcare and the impact on health.
A 3D navigation template for guiding a unilateral lumbar pedicle screw with contralateral translaminar facet screw fixation: a study protocol for multicentre randomised controlled trials
Authors: Shao Zhen-Xuan , He Wei , He Shao-Qi , Lin Sheng-Lei , Huang Zhe-Yu , Tang Hong-Chao , Ni Wen-Fei , Wang Xiang-Yang , Wu Ai-Min
Published: July 2017

Introduction

The incidence of lumbar disc degeneration disease has increased in recent years. Lumbar interbody fusion using two unilateral pedicle screws and a translaminar facet screw fixation has advantages of minimal invasiveness and lower costs compared with the traditional methods. Moreover, a method guided by a three-dimensional (3D) navigation template may help us improve the surgical accuracy and the success rate. This is the first randomised study using a 3D navigation template to guide a unilateral lumbar pedicle screw with contralateral translaminar facet screw fixation.

Methods and analysis

Patients who meet the criteria of the surgery will be randomly divided into experimental groups and control groups by a computer-generated randomisation schedule. We will preoperatively design an individual 3D navigation template using CATIA software and MeditoolCreate. The following primary outcomes will be collected: screw angles compared with the optimal screw trajectories in 3D digital images, length of the wound incision, operative time, intraoperative blood loss and complications. The following secondary outcomes will be collected: visual analogue scale (VAS) for back pain, VAS for leg pain and the Oswestry Disability Index. These parameters will be evaluated on day 1 and then 3, 6, 12 and 24 months postoperatively.

Ethics and dissemination

The study has been reviewed and approved by the institutional ethics review board of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University. The results will be presented at scientific communities and peer-reviewed journals.

Trial registration number

ChiCTR-IDR-17010466
Influences on university students’ intention to receive recommended vaccines: a cross-sectional survey
Authors: Landowska Kate , Waller Jo , Bedford Helen , Rockliffe Lauren , Forster Alice S
Published: July 2017

Objectives

To explore predictors of university students’ intention to receive a recommended vaccine and the main sources of vaccine-related information accessed by university students.

Setting

Participants were recruited from University College London (UK) in summer 2015.

Participants

177 university students participated. The majority of participants were female (58%), White (68%) and had no religion (58%). Participants were aged 18 to 42 (mean age=23.6).

Primary and secondary outcome measures

Primary outcome measures included vaccine attitude, perceived subjective norm, perceived behavioural control, perceived self-efficacy, past receipt of recommended childhood vaccines, perceived adverse reaction to past vaccination and needle fear. As a secondary outcome sources of vaccine-related information were assessed.

Results

Students classified as high intenders were more likely to have received all recommended childhood vaccines (OR 3.57; 95% CI 1.21 to 10.59; p=0.022), be less afraid of needles (OR 2.44; 95% CI 1.12 to 5.36; p=0.026) and to have lived in the UK until at least the age of 4 compared with those not living in the UK until at least the age of 4 (OR 0.39; 95% CI 0.18 to 0.83; p=0.015) and those who lived both in the UK and elsewhere (OR 0.42; 95% CI 0.04 to 4.06; p=0.424). The multivariable model explained 25.5% of variance in intention to receive a recommended vaccine. The internet was the most commonly reported source of vaccination information.

Conclusions

Findings provide an indication of the factors that may need to be addressed by interventions aiming to increase uptake of recommended vaccines in a university population. Future research is recommended using a prospective cohort design.
Canadian main track derailment trends, 2001 to 2014
Authors: Leishman Eric M. , Hendry Michael T. , Martin C. Derek
Published: July 2017

The Transportation Safety Board of Canada (TSB) maintains the Rail Occurrence Database System (RODS). This database contains information on all types of rail occurrences including derailments that must be reported by all Canadian railway operators. This paper analyzes the derailments that occurred on Canadian main track network between 2001 and 2014. The results from the analysis show that between 2001 and 2014 there was an overall decreasing trend in the number and intensity of main track derailments, derailments involving dangerous goods cars, and the number of derailments resulting in the release of dangerous goods. The RODS data was further analyzed to evaluate the frequency of the differing causes of derailments and the severity of the resulting incidents. The most common and severe derailment causes resulted from rail breaks, track geometry, and environmental conditions. Derailment velocity was also found to have an impact on the severity, with higher velocities resulting in a greater number of derailed rolling stock.
Numerical modeling of ice transport in channels with river restoration structures
Authors: Knack Ian M. , Shen Hung Tao
Published: July 2017

Cross vane structures aim to reduce near-bank shear and increase center channel flow intensity to retain flood flow and maintain sediment transport capacity in stream channels. These in-stream structures have been widely applied for river management, but how they interact with the local ice regime is poorly understood. This paper presents a numerical model study of the interaction of cross vane structures with sediment and ice using a two-dimensional coupled river ice-sediment dynamic model. The model was used to simulate a variety of ice and flow conditions to show how cross vanes affect sediment and ice processes. The study showed the design of cross vane structures in cold region rivers should consider the ice effects, especially the increasing potential of ice jam formation and related bed change.
Fruit and vegetable wash-water characterization, treatment feasibility study and decision matrices
Authors: Mundi Gurvinder S. , Zytner Richard G. , Warriner Keith
Published: July 2017

On average, it is estimated that up to 5 L of wastewater is generated per kilogram of produce in post-harvest processing of fruit, leafy greens, and root vegetables. The typical wastewater parameters vary in concentration (solids content, COD, BOD, nitrogen, phosphorus) based on the produce being processed. The challenge for producers and regulators is that the selection of the appropriate treatment technology is challenging, so decision matrices were developed to narrow down the treatment selections. Wash-waters for different types of fruit and vegetables from two different operation types, washing only versus washing and processing were investigated. Bench-scale treatments selected for testing included settling, coagulation and flocculation with settling, centrifuge, dissolved air flotation, electrocoagulation, screening, and hydrocyclone. The developed decision matrices summarize the removal effectiveness of the different treatments for typical wastewater parameters and serve as a reference tool in understanding wash-water treatment technologies and their effectiveness in treating various wash-waters.
Long-term growth trends in northern Wisconsin walleye populations under changing biotic and abiotic conditions
Authors: Pedersen Eric J. , Goto Daisuke , Gaeta Jereme W. , Hansen Gretchen J.A. , Sass Greg G. , Vander Zanden M. Jake , Cichosz Thomas A. , Rypel Andrew L.
Published: July 2017

Walleye (Sander vitreus) populations are declining in Wisconsin and neighboring regions, motivating broader interest in walleye biology amidst ecological change. In fishes, growth integrates variation in ecological drivers and provides a signal of changing ecological conditions. We used a 23-year data set of length-at-age from 353 walleye populations across Wisconsin to test whether walleye growth rates changed over time and what ecological factors best predicted these changes. Using hierarchical models, we tested whether spatiotemporal variation in walleye growth was related to adult walleye density (density-dependent effects), water temperature, and largemouth bass (Micropterus salmoides) catch per unit effort (CPUE; predator or competitor effects). The average length of young walleye increased over time, and as a result, time to reach harvestable size declined significantly. In contrast, average lengths of older walleye have remained relatively constant over time. Juvenile walleye length-at-age was positively correlated with largemouth bass CPUE and surface water temperatures, but negatively correlated with adult walleye density. Our finding of widespread and long-term changes in walleye growth rates provides additional insights into how inland fisheries are responding to environmental change.