bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling of a mechanism of resistance to colistin in Klebsiella pneumoniae using atomic force microscopy
Authors: Formosa C. , Herold M. , Vidaillac C. , Duval R. E. , Dague E. 
Published: May 2015

Abstract

Objectives
In this study we focused on the mechanism of colistin resistance in Klebsiella pneumoniae.

Methods
We used two strains of K. pneumoniae: a colistin-susceptible strain (K. pneumoniae ATCC 700603, KpATCC) and its colistin-resistant derivative (KpATCCm, MIC of colistin 16 mg/L). We performed a genotypic analysis based on the expression of genes involved in LPS synthesis and L-Ara4N moiety addition. We also explored the status of the mgrB gene. Then, a phenotypic analysis was performed using atomic force microscopy (AFM). The Young modulus was extracted from force curves fitted using the Hertz model, and stiffness values were extracted from force curves fitted using the Hooke model.

Results
We failed to observe any variation in the expression of genes implicated in LPS synthesis or L-Ara4N moiety addition in KpATCCm, in the absence of colistin or under colistin pressure (versus KpATCC). This led us to identify an insertional inactivation/mutation in the mgrB gene of KpATCCm. In addition, morphology results obtained by AFM showed that colistin removed the capsule from the susceptible strain, but not from the resistant strain. Nanomechanical data on the resistant strain showed that colistin increased the Young modulus of the capsule. Extend force curves recorded on top of the cells allowed us to make the following hypothesis about the nanoarchitecture of the capsule of the two strains: KpATCC has a soft capsule consisting of one layer, whereas the KpATCCm capsule is harder and organized in several layers.

Conclusions
We hypothesize that capsular polysaccharides might be implicated in the mechanism of colistin resistance in K. pneumoniae, depending on its genotype.
Price Coherence and Excessive Intermediation
*
Authors: Edelman Benjamin , Wright Julian 
Published: May 2015

Abstract
Suppose an intermediary provides a benefit to buyers when they purchase from sellers using the intermediary’s technology. We develop a model to show that the intermediary would want to restrict sellers from charging buyers more for transactions it intermediates. With this restriction an intermediary can profitably raise demand for its services by eliminating any extra price buyers face for purchasing through the intermediary. We show that this leads to inflated retail prices, excessive adoption of the intermediaries’ services, over-investment in benefits to buyers, and a reduction in consumer surplus and sometimes welfare. Competition among intermediaries intensifies these problems by increasing the magnitude of their effects and broadening the circumstances in which they arise. We discuss applications to payment card systems, travel reservation systems, rebate services, and various other intermediaries.
Degenerative Cervical Disc Disease: Long-term Changes in Sagittal Alignment and Their Clinical Implications After Cervical Interbody Fusion Cage Subsidence
Authors: Tomé-Bermejo Félix , Morales-Valencia Julián A. , Moreno-Pérez Javier , Marfil-Pérez Juan , Díaz-Dominguez Elena , Piñera Angel R. , Alvarez Luis 
Published: May 2015

Study Design:
A retrospective, observational study of prospectively collected outcomes.

Objective:
To investigate the long-term clinical course of anterior cervical discectomy and fusion with interbody fusion cages (ACDF-IFC) with lordotic tantalum implants and to correlate the radiologic findings with the clinical outcomes, with special emphasis on the significance and the influence of implant subsidence.

Summary of Background Data:
Cage subsidence is the most frequently reported complication after ACDF-IFC. However, most reports fail to correlate cage subsidence with lower fusion rates or with unsatisfactory clinical results.

Methods:
Forty-one consecutive patients with symptomatic degenerative cervical disk disease with failure of conservative treatment were included. All patients underwent 1-/2-level ACDF-IFC with lordotic tantalum implants. The mean follow-up was 4.91 years.

Results:
The final follow-up fusion rate was 96.96% (32/33). The interspace height (IH) at the affected levels was significantly incremented after implant insertion, and despite a gradual loss in the height over time, the final follow-up IH was significantly higher than that measured preoperatively (P<0.0001). Anterior IH and posterior IH lost 55.8% and 76.2% of the initially incremented height, respectively, with a final increase of 72% in the AIH-PIH height differential. Implant subsidence (>3 mm) occurred in 11 disk spaces (26.82%). Preoperative and postoperative IH were significantly higher in subsidence patients; however, there was no difference in the final follow-up IH (P>0.05). Patients with ≥3 years of follow-up (n=29) did not demonstrate further significant subsidence beyond the second year. Regarding C1–C7 lordosis, the segmental Cobb angle, the cervical Visual Analogue Scale, and Neck Disability Index questionnaires, no difference between patients with or without final follow-up endplate subsidence was encountered.

Conclusions:
Until fusion occurs, tantalum cage settlement into the vertebral body is to be expected. Further subsidence could be the result of segmental adaptative changes. Graft subsidence did not affect the clinical outcome in any of our patients during long-term follow-up. The occurrence of dynamical implant subsidence had a positive effect on cervical lordosis, especially at the posterior IH.
A Model to Predict the Feasibility of Concurrent Chemoradiotherapy With Temozolomide in Glioblastoma Multiforme Patients Over Age 65
Authors: Putz Florian , Knippen Stefan , Lahmer Godehard , Fietkau Rainer , Semrau Sabine 
Published: May 2015

Objectives:
It is controversial whether concurrent chemoradiotherapy (CRT) with temozolomide is feasible and beneficial in elderly patients with glioblastoma.

Materials and Methods:
Retrospective analysis of 74 elderly glioblastoma patients (65 y and above) treated with concurrent CRT with temozolomide. Factors influencing prognosis and feasibility of CRT were investigated.

Results:
The median overall survival was 11.3 months. Univariate analysis showed a significant difference in median overall survival for cumulative dose of concurrent temozolomide (optimal cutoff, 2655 mg/m2; 13.9 mo for >2655 mg/m2 vs. 4.9 mo for ≤2655 mg/m2; P=0.0216, adjusted for multiple testing). Furthermore, cumulative dose of concurrent temozolomide >2655 mg/m2 was a significant independent prognostic parameter in multivariate analysis (hazard ratio, 0.33; P=0.002). Hematotoxicity was the most common cause of treatment interruption or discontinuation in patients with an insufficient cumulative temozolomide dose. Prognostic factors for successful performance of CRT with a cumulative dose of concurrent temozolomide >2655 mg/m2 were female sex (odds ratio [OR], 0.174; P=0.006), age (OR, 0.826 per year; P=0.017), and pretreatment platelet count (OR, 1.013 per 1000 platelets/µL; P=0.001). For easy clinical application of the model an online calculator was developed, which is available at http://www.OldTMZ.com.

Conclusions:
The probability of successful performance of concurrent CRT with temozolomide can be estimated based on the patient’s age, sex, and pretreatment platelet count using the model developed in this study. Thus, a subgroup of elderly glioblastoma patients suitable for chemoradiation with temozolomide can be identified.
The Degradation of Mitomycin C Under Various Storage Methods
Authors: Kinast Robert M. , Akula Kiran K. , DeBarber Andrea E. , Barker Gordon T. , Gardiner Stuart K. , Whitson Emily , Mansberger Steve L. 
Published: May 2015

Purpose:
To compare the effects of common pharmacy preparation and storage conditions on the stability of mitomycin C (MMC) in solution.

Methods:
We used C18 reversed-phase high-performance liquid chromatography to determine the stability of 0.4 mg/mL MMC solutions, and liquid chromatography-electrospray ionization-mass spectrometry to identify degradation products. Conditions compared were: compounding and storage by refrigeration (1 and 2 wk), freezing (23 d), shipment “on-ice” (1 mo frozen followed by 1-wk refrigeration), and immediately compounding dry powder (Mitosol; Mobius Therapeutics LLC). We tested 3 samples for each storage method when samples reached room temperature (time 0), and then 1, 4, and 24 hours later. We used MMC peak area as a percentage of total (MMC plus degradants) area detected with high-performance liquid chromatography as a measure of stability.

Results:
We assessed MMC stability for 5 preparation and storage methods at 4 timepoints (with n=3 per timepoint). At time 0, we found similar stabilities for MMC (F=0.72, P=0.599) between all 5 storage methods: 1-week refrigerated (97.9±0.2%), dry powder (97.5±0.3%), 2-week refrigerated (96.9±0.2%), 23-day frozen (96.7±3.1%), and shipment on-ice (96.0±1.2%). However, MMC demonstrated significant degradation over a 24-hour period with 2-week refrigeration (95.7±0.3%, β=−0.1%/h, P<0.001) and shipment on-ice (93.1±1.8%, β=−0.1%/h, P=0.013). We identified small amounts (<3.2%) of 2 degradants, cis-hydroxymitosene and trans-hydroxymitosene, across all samples.

Conclusions:
The different preparation and storage methods of MMC showed similar stability when used immediately upon reaching room temperature. However, degradation of MMC occurred with further storage at room temperature. The clinical implication of small amounts of MMC degradants is unclear.
Dynamics of an Expanding Black Rhinoceros (Diceros Bicornis Minor) Population
Authors: Law Peter R , Fike Brad , Lent Peter C. 
Published: May 2015

AbstractPopulation dynamics is a central component of demography and critical for meta-population management, especially of endangered species. We employed complete individual life records to construct census data for a reintroduced black rhinoceros population over 22 years from its founding and investigated that population’s dynamics to inform black rhinoceros meta-population management practice and, more generally, megaherbivore ecology. Akaike’s information criterion applied to scalar models of population growth based on the generalized logistic unambiguously selected an exponential growth model (r= 0.102 ± 0.017), indicating a highly successful reintroduction, but yielding no evidence of density dependence. This result is consistent with, but does not confirm, the threshold model of density dependence that has influenced black rhinoceros meta-population management. Our analysis did support previous work contending that the generalized logistic is unreliable when fit to data that do not sample the entire range of possible population sizes. A stage-based matrix model of the exponential population dynamics exhibited mild transient behaviour. We found no evidence of environmental stochasticity, consistent with our previous studies of this population that found no influence of rainfall on demographic parameters. Process noise derived from demographic stochasticity, principally reflected in annual sex-specific recruitment numbers that differed from deterministic predictions of the matrix model. Demographically driven process noise should be assumed to be a component of megaherbivore population dynamics, as these populations are typically relatively small, and should be considered in managed removals and introductions. We suggest that an extended period of exponential growth is common for megaherbivore populations growing from small size and that an increase in age at first reproduction with increasing population size, manifest in the study population, may provide a warning of density feedback prior to detectable slowing of population growth rate for megaherbivores.
Targeted modification of gene function exploiting homology-directed repair of TALEN-mediated double strand breaks in barley
Authors: Budhagatapalli Nagaveni , Rutten Twan , Gurushidze Maia , Kumlehn Jochen , Hensel Goetz 
Published: May 2015

ABSTRACTTranscription activator-like effector nucleases (TALENs) open up new opportunities for targeted mutagenesis in eukaryotic genomes. Similar to zinc-finger nucleases, sequence-specific DNA-binding domains can be fused with effector domains like the nucleolytically active part of FokI in order to induce double strand breaks (DSBs) and thereby modify the host genome on a predefined target site via non-homologous end joining. More sophisticated applications of programmable endonucleases involve the use of a DNA repair template facilitating homology-directed repair (HDR) so as to create predefined rather than random DNA sequence modifications. The aim of this study was to demonstrate the feasibility of editing the barley genome by precisely modifying a defined target DNA sequence resulting in a predicted alteration of gene function. We usedgfp-specific TALENs along with a repair template that, via HDR, facilitates conversion ofgfpintoyfpwhich is associated with a single amino acid exchange in the gene product. As a result of co-bombardment of leaf epidermis, we detected YFP accumulation in about 3 out of 100 mutated cells. The creation of a functionalyfpgene via HDR was unambiguously confirmed by sequencing of the respective genomic site. Predictable genetic modifications comprising only a few genomic base pairs rather than entire genes are of particular practical relevance, because they might not fall under the European regulation of genetically engineered organisms. In addition to the allele conversion accomplishedin planta,a readily screenable marker system is introduced that might be useful for optimization approaches in the field of genome editing.
Deconvolution of gene expression noise into physical dynamics of cognate promoters
Authors: Goñi-Moreno Ángel , Benedetti Ilaria , Kim Juhyun , Lorenzo Víctor de 
Published: May 2015

AbstractWhen facing recalcitrant pollutants, soil bacteria exploit noise of catabolic promoters for deploying environmentally beneficial phenotypes such as metabolic bet-hedging an/or division of biochemical labor. While the origin of such noise in terms of upstream promoter-regulator interplay is hardly understood, its dynamics has to be somehow encrypted in the patterns of flow-cytometry data delivered by transcriptional reporter fusions. On this background, we have examined the behaviour of thePmpromoter of the environmental bacteriumPseudomonas putidaand its cognate 3-methylbenzoate-responsive regulator XylS under different conditions by following expression ofPm-GFP fusions in single cells. Using mathematical modeling and computational simulations we elucidated the kinetic properties of the system and use them as a baseline code to interpret the observed fluorescence output in terms of upstream regulator variability. Transcriptional noise was predicted to depend on the intracellular physical distance between the regulator source (where the e.g. XylS is being produced in the cells) and the target promoter. Experiments with engineered bacteria where this distance is either minimized or enlarged proved the effects of proximity on noise patterns as predicted by the model. This approach not only allowed deconvolution of cytometry data into mechanistic information on the gene expression flow. But it also provided a mechanistic basis for selecting a given level of noise in engineered regulatory nodes e.g. in Synthetic Biology constructs.
Bottleneck detection for improvement of Emergency Department efficiency
Authors: Zhao Yuancheng , Peng Qingjin , Strome Trevor , Weldon Erin , Zhang Michael , Chochinov Alecs 
Published: May 2015

Purpose
– The purpose of this paper is to introduce a method of the bottleneck detection for Emergency Department (ED) improvement using benchmarking and design of experiments (DOE) in simulation model.

Design/methodology/approach
– Four procedures of treatments are used to represent ED activities of the patient flow. Simulation modeling is applied as a cost-effective tool to analyze the ED operation. Benchmarking provides the achievable goal for the improvement. DOE speeds up the process of bottleneck search.

Findings
– It is identified that the long waiting time is accumulated by previous arrival patients waiting for treatment in the ED. Comparing the processing time of each treatment procedure with the benchmark reveals that increasing the treatment time mainly happens in treatment in progress and emergency room holding (ERH) procedures. It also indicates that the to be admitted time caused by the transfer delay is a common case.

Research limitations/implications
– The current research is conducted in the ED only. Activities in the ERH require a close cooperation of several medical teams to complete patients’ condition evaluations. The current model may be extended to the related medical units to improve the model detail.

Practical implications
– ED overcrowding is an increasingly significant public healthcare problem. Bottlenecks that affect ED overcrowding have to be detected to improve the patient flow.

Originality/value
– Integration of benchmarking and DOE in simulation modeling proposed in this research shows the promise in time-saving for bottleneck detection of ED operations.
Constraint-based reasoning on declarative process execution with the logics workbench
Authors: Lam Vitus 
Published: May 2015

Purpose
– An integral part of declarative process modelling is to guarantee that the execution of a declarative workflow is compliant with the respective business rules. The purpose of this paper is to establish a formal framework for representing business rules and determining whether any business rules are violated during the executions of declarative process models.

Design/methodology/approach
– In the approach, a business rule is phrased in terms of restricted English that is related to a constraint template. Linear temporal logic (LTL) is employed as a formalism for defining the set of constraint templates. By exploiting the theorem-proving feature of the Logics Workbench (LWB), business rule violations are then detected in an automatic manner.

Findings
– This study explored the viability of encoding: first, process executions by means of LTL and second, business rules in terms of restricted English that built upon pattern-oriented templates and LTL. The LWB was used for carrying out temporal reasoning through automated techniques. The applicability of the formal verification approach was exemplified by a case study concerning supply chain management. The findings showed that practical reasoning could be achieved by combining declarative process modelling, restricted English, pattern-oriented templates, LTL and LWB.

Originality/value
– First, new business rule templates are proposed; second, business rules are expressed in restricted English instead of graphical constructs; third, both finite execution trace and business rules are grounded in LTL. There is no need to deal with the semantic differences between different formalisms; and finally, the theorem prover LWB is used for the conformance checking of a finite execution trace against business rules.
Agile, a guiding principle for health care improvement?
Authors: Tolf Sara , Nyström Monica E. , Tishelman Carol , Brommels Mats , Hansson Johan 
Published: May 2015

Purpose
– The purpose of this paper is to contribute to increased understanding of the concept agile and its potential for hospital managers to optimize design of organizational structures and processes to combine internal efficiency and external effectiveness.

Design/methodology/approach
– An integrative review was conducted using the reSEARCH database. Articles met the following criteria: first, a definition of agility; second, descriptions of enablers of becoming an agile organization; and finally, discussions of agile on multiple organizational levels. In total, 60 articles qualified for the final analysis.

Findings
– Organizational agility rests on the assumption that the environment is uncertain, ranging from frequently changing to highly unpredictable. Proactive, reactive or embracive coping strategies were described as possible ways to handle such uncertain environments. Five organizational capacities were derived as necessary for hospitals to use the strategies optimally: transparent and transient inter-organizational links; market sensitivity and customer focus; management by support for self-organizing employees; organic structures that are elastic and responsive; flexible human and resource capacity for timely delivery. Agile is portrayed as either the “new paradigm” following lean, the needed development on top of a lean base, or as complementary to lean in distinct hybrid strategies.

Practical implications
– Environmental uncertainty needs to be matched with coping strategies and organizational capacities to design processes responsive to real needs of health care. This implies that lean and agile can be combined to optimize the design of hospitals, to meet different variations in demand and create good patient management.

Originality/value
– While considerable value has been paid to strategies to improve the internal efficiency within hospitals, this review raise the attention to the value of strategies of external effectiveness.
Service quality in contracted facilities
Authors: Rabbani Fauziah , Pradhan Nousheen Akber , Zaidi Shehla , Azam Syed Iqbal , Yousuf Farheen 
Published: May 2015

Purpose– The purpose of this paper is to explore the readiness of contracted and non-contracted first-level healthcare facilities in Pakistan to deliver quality maternal and neonatal health (MNH) care. A balanced scorecard (BSC) was used as the assessment framework.Design/methodology/approach– Using a cross-sectional study design, two rural health centers (RHCs) contracted out to Aga Khan Health Service, Pakistan were compared with four government managed RHCs. A BSC was designed to assess RHC readiness to deliver good quality MNH care. In total 20 indicators were developed, representing five BSC domains: health facility functionality, service provision, staff capacity, staff and patient satisfaction. Validated data collection tools were used to collect information. Pearsonχ2, Fisher’s Exact and the Mann-Whitney tests were applied as appropriate to detect significant service quality differences among the two facilities.Findings– Contracted facilities were generally found to be better than non-contracted facilities in all five BSC domains. Patients’ inclination for facility-based delivery at contracted facilities was, however, significantly higher than non-contracted facilities (80 percent contracted vs 43 percent non-contracted,p=0.006).Practical implications– The study shows that contracting out initiatives have the potential to improve MNH care.Originality/value– This is the first study to compare MNH service delivery quality across contracted and non-contracted facilities using BSC as the assessment framework.