bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of central venous catheter‐related bloodstream infections in haematooncological patients
Authors: Rabensteiner Jasmin , Theiler Georg , Duettmann Wiebke , Zollner‐Schwetz Ines , Hoenigl Martin , Valentin Thomas , Leitner Eva , Luxner Josefa , Grisold Andrea , Valentin Angelika , Neumeister Peter , Krause Robert
Published: June 2015

Background

Catheter‐related bloodstream infections (CRBSIs) are currently detected in patients with clinically suspicion. The aim of our study was to evaluate whether CRBSIs could be anticipated and detected in a subclinical stage by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) using universal hybridization probes or acridine orange leucocyte cytospin (AOLC) tests in haematooncological patients with central venous catheters (CVCs) in situ.

Materials and methods

Peptide nucleic acid fluorescence in situ hybridization and AOLC tests using blood samples from one CVC lumen/port chamber in haematooncological patients were continuously performed. These results were compared to those obtained from routinely performed CRBSI diagnostic tests.

Results

One hundred and eighty‐two patients with 342 catheter periods were investigated. Seventeen CRBSI cases were detected in 6466 CVC days by routine measures resulting in a CRBSI rate of 2·6/1000 catheter days. Two of 17 showed positive PNA FISH tests, and five positive AOLC test results before the diagnosis were established with routine measures. The screening revealed further seven patients with positive universal PNA FISH tests and 10 positive AOLC tests without symptoms indicative for infection and were therefore considered not to have CRBSI.

Conclusions

Sampling of only one CVC lumen/port chamber screening for CRBSI in haematooncological patients seems not to be a useful tool for anticipative diagnosis of CRBSI. Reasons for false‐negative results might include origin of CRBSIs from the other CVC lumina not sampled for screening, and false‐positive results might origin from catheter colonization without subsequent spread of micro‐organisms into the peripheral bloodstream.
Alteration of heme metabolism in a cellular model of Diamond–Blackfan anemia
Authors: Mercurio Sonia , Aspesi Anna , Silengo Lorenzo , Altruda Fiorella , Dianzani Irma , Chiabrando Deborah
Published: June 2015

Diamond–Blackfan anemia (DBA) is a congenital pure red cell aplasia often associated with skeletal malformations. Mutations in ribosomal protein coding genes, mainly in RPS19, account for the majority of DBA cases. The molecular mechanisms underlying DBA pathogenesis are still not completely understood. Alternative spliced isoforms of FLVCR1 (feline leukemia virus subgroup C receptor 1) transcript coding for non‐functional proteins have been reported in some DBA patients. Consistently, a phenotype very close to DBA has been described in animal models of FLVCR1 deficiency. FLVCR1 gene codes for two proteins: the plasma membrane heme exporter FLVCR1a and the mitochondrial heme exporter FLVCR1b. The coordinated expression of both FLVCR1 isoforms regulates an intracellular heme pool, necessary for proper expansion and differentiation of erythroid precursors. Here, we investigate the role of FLVCR1 isoforms in a cellular model of DBA. RPS19‐downregulated TF1 cells show reduced FLVCR1a and FLVCR1b mRNA levels associated with heme overload. The downregulation of FLVCR1 isoforms affects cell cycle progression and apoptosis in differentiating K562 cells, a phenotype similar to DBA. Taken together, these data suggest that alteration of heme metabolism could play a role in the pathogenesis of DBA.
Environmental enrichment rescues the degraded auditory temporal resolution of cortical neurons induced by early noise exposure
Authors: Jiang Cuiping , Xu Xiaoxiao , Yu Liping , Xu Jinghong , Zhang Jiping
Published: June 2015

The accurate processing of sound temporal information is crucial to human speech perception and other species‐specific communication. During postnatal development, the auditory cortex shows environmental and experience‐dependent plasticity. However, how the postnatal environment affects cortical processing of sound temporal information is not fully understood. The aim of the present study was to determine whether postnatal noise exposure impairs neural temporal resolution in the auditory cortex, and, if so, whether environmental enrichment can rescue this degraded neural temporal acuity. Using the neural gap detection threshold determined in anesthetized rats as an index of temporal acuity, we found that exposure of juvenile rats to moderate‐level noise induced much higher neural gap detection thresholds in adulthood than exposure of adult rats to the same noise. Environmental enrichment did not affect cortical neural gap detection thresholds in normally developing rats. However, rearing of rats with early noise exposure in an enriched environment promoted recovery from the noise‐induced degraded neural temporal resolution. In addition, the tonal stimuli in the enriched environment contributed to only a portion of the recovery. These results provide evidence for noise‐induced developmental impairment in neural gap detection thresholds in the auditory cortex, and suggest a therapeutic potential for environmental enrichment as a non‐invasive approach to rescue developmentally degraded auditory temporal processing.
The Effects of Liquidity Shocks on Corporate Investments and Cash Holdings: Evidence from Actuarial Pension Gains/Losses
Authors: Sasaki Takafumi
Published: June 2015

This paper investigates how anticipated liquidity shocks affect corporate investment and cash holdings by examining the impacts of actuarial pension gains/losses that do not reduce current internal resources but will reduce those available in the future. Using a sample from Japanese manufacturing firms in which pension deficits had a huge impact on the internal resources of sponsoring firms, I show that pension losses significantly decrease the capital expenditures of sponsoring firms. Pension losses also increase corporate cash holdings, suggesting precautionary demands for cash prepared for future pension contributions. Overall, the results indicate that managers consider anticipated liquidity shocks in determining current investment and cash‐saving policies.
Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin‐10 in cervical neoplastic lesions
Authors: Prata Thiago Theodoro Martins , Bonin Camila Mareti , Ferreira Alda Maria Teixeira , Padovani Cacilda Tezelli Junqueira , Fernandes Carlos Eurico dos Santos , Machado Ana Paula , Tozetti Inês Aparecida
Published: June 2015

A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high‐risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL‐10). This production of IL‐10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL‐10‐producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL‐10 production by keratinocytes, macrophages and Langerhans cells in high‐grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high‐risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL‐10‐producing cellular phenotypes in cervical cancer samples, and samples classified as high‐grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.
The Incidence of Audible Steam Pops Is Increased and Unpredictable With the ThermoCool® Surround Flow Catheter During Left Atrial Catheter Ablation: A Prospective Observational Study
Authors: THEIS CATHRIN , ROSTOCK THOMAS , MOLLNAU HANKE , SONNENSCHEIN SEBASTIAN , HIMMRICH EWALD , KÄMPFNER DENISE , OCETE BLANCA QUESADA , BOCK KARSTEN , MÜNZEL THOMAS , KONRAD TORSTEN
Published: June 2015

Audible Steam Pops During Left Atrial Catheter Ablation

Introduction

Open irrigated radiofrequency (RF) ablation catheters with a porous tip (56 holes, TC‐SF) permit delivering RF energy in a temperature‐controlled mode without temperature rise. This prospective observational study investigated the association of different catheter parameters on the occurrence of audible steam pops during left atrial (LA) ablation.

Methods and Results

A total of 226 patients underwent TC‐SF catheter ablation for atrial fibrillation. RF power delivery, impedance and catheter tip temperature were continually recorded throughout the ablation. Pulmonary vein isolation was performed with a maximum of 27 W and LA electrogram‐guided or linear ablation with a maximum of 30 W. A total of 59 audible steam pops occurred, 2 of them resulting in pericardial tamponade. In the initial 89 patients, with an irrigation flow rate of 10 mL/min, 18 steam pops with one tamponade occurred in 12 (14%) patients. Subsequently, the irrigation flow rate was increased to 20 mL/min in the following 137 patients, resulting in the occurrence of 41 steam pops including one case of tamponade in a total of 30 (22%) patients. The maximal power was significantly higher in RF applications associated with a pop than those that did not. In only 12 (20%) steam pops, a significant impedance change occurred immediately before pop occurrence (4 [7%] impedance rise >10 ohm, 8 [13%] impedance drop >15 ohm).

Conclusions

The TC‐SF catheter does not provide sufficient feedback from the ablated tissue to prevent steam popping.
Characterising flash flood response to intense rainfall and impacts using historical information and gauged data in Britain
Authors: Archer D.R. , Fowler H.J.
Published: June 2015

We analyse chronologies of historical flash floods derived from searches of newspaper archives and other sources commencing before 1800 and recent gauged rainfall and stream flow data. Five key examples are chosen to illustrate specific features of flash floods. Pluvial flash floods arise from rainfall before it reaches a watercourse and may cause severe flooding of land and properties far from rivers. River flash floods, like pluvial floods, have the characteristic of rapid speed of response, a principal source of risk to life. Intense rainfall can generate ‘walls of water’ in river courses which can propagate long distances downstream and steepen, without upstream structural failure. Steeply rising wavefronts more commonly occur on steep upland catchments but, where intensities of extreme short period rainfall are sufficient, such wavefronts can also occur on lowland catchments. A definition of flash floods from intense rainfall, relevant to British landscape and climate, is proposed.
Revisiting the membrane interaction mechanism of a membrane‐damaging β‐barrel pore‐forming toxin Vibrio cholerae cytolysin
Authors: Rai Anand Kumar , Chattopadhyay Kausik
Published: June 2015

Vibrio cholerae cytolysin (VCC) permeabilizes target cell membranes by forming transmembrane oligomeric β‐barrel pores. VCC has been shown to associate with the target membranes via amphipathicity‐driven spontaneous partitioning into the membrane environment. More specific interaction(s) of VCC with the membrane components have also been documented. In particular, specific binding of VCC with the membrane lipid components is believed to play a crucial role in determining the efficacy of the pore‐formation process. However, the structural basis and the functional implications of the VCC interaction with the membrane lipids remain unclear. Here we show that the distinct loop sequences within the membrane‐proximal region of VCC play critical roles to determine the functional interactions of the toxin with the membrane lipids. Alterations of the loop sequences via structure‐guided mutagenesis allow amphipathicity‐driven partitioning of VCC to the membrane lipid bilayer. Alterations of the loop sequences, however, block specific interactions of VCC with the membrane lipids and abort the oligomerization, membrane insertion, pore‐formation and cytotoxic activity of the toxin. Present study identifies the structural signatures in VCC implicated for its functional interactions with the membrane lipid components, a process that presumably acts to drive the subsequent steps of the oligomeric β‐barrel pore‐formation and cytotoxic responses.
Expressions of mRNA for innate immunity‐associated functional molecules in urinary sediment in immunoglobulin A nephropathy
Authors: Tsuruga Kazushi , Aizawa Tomomi , Watanabe Shojiro , Tsugawa Koji , Yoshida Hidemi , Imaizumi Tadaatsu , Ito Etsuro , Tanaka Hiroshi
Published: June 2015

Aim

It has been reported that the innate immune system plays a pivotal role in the pathogenesis of immunoglobulin A nephropathy (IgAN). To explore non‐invasive monitoring of disease activity in children with IgAN, we examined whether expressions of mRNA for innate immunity‐associated functional molecules: CC ligand chemokine 5 (CCL5), fractalkine/CX3CL1, interferon‐γ‐induced protein 10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), retinoic acid‐inducible gene‐I (RIG‐I), and toll‐like receptor 3 (TLR3) in urinary sediment from patients with IgAN correlate with histologic parameters.

Methods

Twenty consecutive children with IgAN and four children with thin basement membrane disease (serving as a non‐inflammatory control) were enrolled in this pilot study. Urinary mRNA expressions of target genes were examined real‐time quantitative polymerase chain reaction.

Results

The expressions of CCL5, fractalkine and RIG‐I were significantly increased in IgAN (all P < 0.05). Although no significant correlation was observed between mRNA expressions of these three molecules and clinical parameters, such as levels of urinary protein excretion, degrees of occult blood in urine and serum albumin, the expression of fractalkine was significantly correlated with the histological activity index (P = 0.022) and the chronicity index (P = 0.005). Furthermore, intense glomerular immune activity of fractalkine was observed in biopsy specimens in patients with moderately to severe proliferative IgAN.

Conclusion

Regional expression of fractalkine may be involved in the pathogenesis of childhood IgAN. Although our present findings remain preliminary, measurement of mRNA expression of fractalkine in urinary sediment could be used as a non‐invasive method for predicting histologic severity in IgAN in children. Further studies of this issue are needed.
Impulse Balance and Multiple‐Period Feedback in the Newsvendor Game
Authors: Ockenfels Axel , Selten Reinhard
Published: June 2015

Human subjects in the newsvendor game place suboptimal orders: orders are typically between the expected profit‐maximizing quantity and mean demand (“pull‐to‐center bias”). In previous work, we have shown that impulse balance equilibrium (IBE), which is based on a simple ex post rationality principle along with an equilibrium condition, can predict ordering decisions in the laboratory. In this study, we extend IBE to standing orders and multiple‐period feedback and show that it predicts—in line with previous findings—that constraining newsvendors to make a standing order for a sequence of periods moves the average of submitted orders toward the optimum.
How Costs and Heterogeneous Consumer Price Sensitivity Interact with Add‐On Pricing
Authors: Geng Xianjun , Shulman Jeffrey D.
Published: June 2015

Firms often cite cost savings as a reason why they charge separately for add‐ons. Firms also often face situations where consumers' price sensitivity is correlated with their valuation of add‐ons. While cost savings may directly translate into profit gains in some scenarios, this study examines the strategic implications of add‐on pricing and is the first to suggest that cost savings from add‐on pricing may in fact result in profit loss for firms when consumers are heterogeneous in price sensitivity. This is because add‐on pricing can trigger a revenue loss that exceeds any cost savings, thus leading to a negative net profit change for competing firms. Even if firms have the capability to pre‐commit to not adopting add‐on pricing, we show that competing firms can be locked in a prisoner's dilemma where all choose to adopt add‐on pricing and lose profits (as compared to none adopting add‐on pricing). We further show the possibility that the greater the cost of providing the add‐on (and the greater the cost savings generated from add‐on pricing), the worse this profit loss gets.
Optimal Choice for Appointment Scheduling Window under Patient No‐Show Behavior
Authors: Liu Nan
Published: June 2015

Observing that patients with longer appointment delays tend to have higher no‐show rates, many providers place a limit on how far into the future that an appointment can be scheduled. This article studies how the choice of appointment scheduling window affects a provider's operational efficiency. We use a single server queue to model the registered appointments in a provider's work schedule, and the capacity of the queue serves as a proxy of the size of the appointment window. The provider chooses a common appointment window for all patients to maximize her long‐run average net reward, which depends on the rewards collected from patients served and the “penalty” paid for those who cannot be scheduled. Using a stylized M/M/1/K queueing model, we provide an analytical characterization for the optimal appointment queue capacity K, and study how it should be adjusted in response to changes in other model parameters. In particular, we find that simply increasing appointment window could be counterproductive when patients become more likely to show up. Patient sensitivity to incremental delays, rather than the magnitudes of no‐show probabilities, plays a more important role in determining the optimal appointment window. Via extensive numerical experiments, we confirm that our analytical results obtained under the M/M/1/K model continue to hold in more realistic settings. Our numerical study also reveals substantial efficiency gains resulted from adopting an optimal appointment scheduling window when the provider has no other operational levers available to deal with patient no‐shows. However, when the provider can adjust panel size and overbooking level, limiting the appointment window serves more as a substitute strategy, rather than a complement.
Endogenous Progesterone Concentrations Affect Progesterone Release from Intravaginal Devices Used for Oestrous Synchronization in Cattle
Authors: Neri HL , Palhao MP , Costa DS , Viana JHM , Fernandes CAC
Published: June 2015

Contents

Intravaginal progesterone‐releasing devices are largely used both as contraceptives in humans and as a component of oestrous synchronization protocols in cattle. To reduce costs in large‐scale timed artificial insemination, the reuse of these releasing devices is common. Passive hormone diffusion, however, depends on the concentration gradient, which could affect the amount of residual progesterone present in these devices after a first use. To evaluate the effect of the presence of a corpus luteum in the release of progesterone from intravaginal devices, three synchronization protocols were designed to simulate the effects of inserting the device in the early dioestrus, late dioestrus or anoestrus. Holstein‐Zebu cross‐bred heifers were randomly allocated into one of these three treatments, and a series of blood samples was taken to evaluate the plasma progesterone concentrations. After 8 days, the intravaginal devices were removed and underwent a previously validated alcoholic extraction technique to measure the residual progesterone. Non‐used devices were used as controls. As expected, the simultaneous presence of the intravaginal device and a corpus luteum resulted in increased plasma progesterone concentrations. Conversely, the amount of residual progesterone in the devices after use was inversely proportional to the plasma progesterone concentration. These results demonstrate that the release rate of progesterone from intravaginal devices is affected by the endogenous concentration of this hormone; consequently, the strategy for reuse should account for the category and expected luteal cyclic activity of the animals undergoing synchronization protocols.
The Arabidopsis root stele transporter NPF2.3 contributes to nitrate translocation to shoots under salt stress
Authors: Taochy Christelle , Gaillard Isabelle , Ipotesi Emilie , Oomen Ronald , Leonhardt Nathalie , Zimmermann Sabine , Peltier Jean‐Benoît , Szponarski Wojciech , Simonneau Thierry , Sentenac Hervé , Gibrat Rémy , Boyer Jean‐Christophe
Published: June 2015

In most plants,constitutes the major source of nitrogen, and its assimilation into amino acids is mainly achieved in shoots. Furthermore, recent reports have revealed that reduction oftranslocation from roots to shoots is involved in plant acclimation to abiotic stress. NPF2.3, a member of the NAXT (nitrate excretion transporter) sub‐group of the NRT1/PTR family (NPF) from Arabidopsis, is expressed in root pericycle cells, where it is targeted to the plasma membrane. Transport assays using NPF2.3‐enrichedLactococcus lactismembranes showed that this protein is endowed withtransport activity, displaying a strong selectivity foragainst Cl−. In response to salt stress,translocation to shoots is reduced, at least partly because expression of the root steletransporter geneNPF7.3is decreased. In contrast,NPF2.3expression was maintained under these conditions. A loss‐of‐function mutation inNPF2.3resulted in decreased root‐to‐shoottranslocation and reduced shootcontent in plants grown under salt stress. Also, the mutant displayed impaired shoot biomass production when plants were grown under mild salt stress. These mutant phenotypes were dependent on the presence of Na+in the external medium. Our data indicate that NPF2.3 is a constitutively expressed transporter whose contribution totranslocation to the shoots is quantitatively and physiologically significant under salinity.
Competition Nutrition Practices of Elite Ultramarathon Runners
Authors: Stellingwerff Trent
Published: June 2015

Anecdotal claims have suggested that an increasing number of ultramarathoners purposely undertake chronic low-carbohydrate (CHO) ketogenic diets while training, and race with very low CHO intakes, as a way to maximize fat oxidation and improve performance. However, very little empirical evidence exists on specific fueling strategies that elite ultramarathoners undertake to maximize race performance. The study’s purpose was to characterize race nutrition habits of elite ultramarathon runners. Three veteran male ultrarunners (M ± SD; age 35 ± 2 years; mass 59.5 ± 1.7 kg; 16.7 ± 2.5 hr 100-mi. best times) agreed to complete a competition-specific nutrition intake questionnaire for 100-mi. races. Verbal and visual instructions were used to instruct the athletes on portion sizes and confirm dietary intake. Throughout 2014, the athletes competed in 16 ultramarathons with a total of 8 wins, including the prestigious Western States Endurance Run 100-miler (14.9 hr). The average prerace breakfast contained 70 ± 16 g CHO, 29 ± 20 g protein, and 21 ± 8 g fat. Athletes consumed an average of 1,162 ± 250 g of CHO (71 ± 20g/hr), with minor fat and protein intakes, resulting in caloric intakes totaling 5,530 ± 1,673 kcals (333 ± 105 kcals/hr) with 93% of calories coming from commercial products. Athletes also reported consuming 912 ± 322 mg of caffeine and 6.9 ± 2.4 g of sodium. Despite having limited professional nutritional input into their fueling approaches, all athletes practiced fueling strategies that maximize CHO intake and are congruent with contemporary evidence-based recommendations.
Coaching and Coach Development in New Zealand
Authors: Kidman Lynn , Keelty David
Published: June 2015

The purpose of this article is to provide an overview of coaching and coach development in New Zealand. For a small country with a population of 4.47 million (Statistics New Zealand, 2015), New Zealand achieves great success on the world sporting stage. One of the many contributors to this success is New Zealand’s commitment to developing coaches with an emphasis on continuous improvement through the provision of ongoing learning opportunities for coaches (SPARC, 2006). Interestingly the International Sport Coaching Framework’s recommendations aligns itself to such an emphasis that they refer to as lifelong learning (ICCE, 2013). To achieve this focus, and based on a Ministerial Taskforce findings that, “Coaching is in urgent need of support and development” (Ministerial Taskforce, 2001, p.10) Sport and Recreation New Zealand (SPARC) established a consultancy group to review and redevelop coaching. An outcome of this consultation was the production of the New Zealand Coaching Strategy (SPARC, 2004). Based on robust discussion on many issues of how people learn and coaching development philosophies, the Coach Development Framework (CDF) was established in 2006. Since its establishment, the CDF has been guiding coach development in New Zealand, placing the responsibility for this development on the National Sporting Organisations (NSOs).
“Older and Faster”: Exploring Elite Masters Cyclists’ Involvement in Competitive Sport
Authors: Appleby Karen M. , Dieffenbach Kristen
Published: June 2015

The purpose of this study was to investigate elite masters cyclists’ involvement in competitive sport. Using a descriptive, qualitative approach, the researchers interviewed ten elite-level masters cyclists. Data analysis revealed the following salient themes relevant to participants’ experiences: (a) athletic identity, (b) motivational factors, and (c) life balance. These findings suggest that participation as an elite-level masters athlete reflects a high degree of continuity for athletic identity that can be positive in relation to self-esteem and social validation and challenging in relation to transition and maintaining social relationships out of cycling settings.
Novel variant of EATL evolving from mucosal γδ-T-cells in a patient with type I RCD
Authors: van Wanrooij R L J , de Jong D , Langerak A W , Ylstra B , van Essen H F , Heideman D A M , Bontkes H J , Mulder C J J , Bouma G
Published: June 2015

Objectives

Enteropathy associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma that may complicate coeliac disease and typically occurs in patients with refractoriness to the gluten-free diet. The majority of these patients harbour a clonal expansion of intraepithelial lymphocytes (IELs) with an aberrant phenotype in the small intestine which are thus considered as the ‘precursor’ lymphoma cells. We describe a 51-year-old female patient with refractory coeliac disease (RCD) who developed an EATL with manifestations in the proximal small intestine and in a mesenteric lymph node that did not evolve from regular type ‘aberrant’ αβ-T-cells but rather from a clonal expansion of γδ-T-cells.

Methods

Duodenal biopsies and lymphoma tissue from a patient with refractory coeliac disease whom developed an EATL were extensively studied by immunophenotypical, T-cell receptor immunogenetic and chromosomal analysis.

Results

Flow cytometric analysis of duodenal IELs revealed an unusual large clonal expansion of CD30 negative γδ-T-cells in a patient with RCD. When the patient clinically deteriorated 18 months later, a substantial part (30%) of this cell population did express CD30. In addition, identical immunogenetic aberrancies had developed in a prehepatic lymph node.

Conclusions

We here report on a case of extraintestinal EATL that originated from a clonal γδ-IEL population rather than from aberrant IEL. This EATL displayed a distinctive pattern of immunophenotypical, T-cell receptor immunogenetic and chromosomal aberrancies as compared to classical EATL, defining this lymphoma as a novel variant of EATL.
Expanding the scope of Critical Care Rapid Response Teams: a feasible approach to identify adverse events. A prospective observational cohort
Authors: Amaral Andre Carlos Kajdacsy-Balla , McDonald Andrew , Coburn Natalie G , Xiong Wei , Shojania Kaveh G , Fowler Robert A , Chapman Martin , Adhikari Neill K J
Published: June 2015

Introduction

Adverse events (AEs) affect 3–12% of hospitalised patients. These are estimates from a labour-intensive chart review process,which is not feasible outside research. Clinical deterioration on the wards triggers a rapid response teams (RRTs) consult and can be used to identify an AE prospectively.

Objectives

To demonstrate the feasibility of using RRT to detect AEs and compare this methodology to the rates reported using an electronic safety reporting system.

Methods

Prospective observational cohort of RRT consults. Three independent physicians reviewed all cases for the occurrence of an AE and its preventability. We summarise AEs as rates per 1000 patient-days, and compared the rates between RRT and the safety reporting system using a Poisson model.

Results

There were 8713 hospital admissions, with 531 RRT consults and 247 (2.8%) cases included. Forty-four (17.8%) and 35 cases (14.2%) were judged as AEs and preventable AEs, respectively. RRT identified 0.52 AE/1000 patient-days, compared with 0.21 AE/1000 patient-days detected through the electronic safety reporting system (rate ratio 2.4, 95% CI 1.4 to 4.2, p=0.0014). Patients in surgical wards had more AEs (0.83/1000 vs 0.36/1000, p<0.01) and preventable AEs (0.70 vs 0.21, p<0.01) than patients in medical wards. Agreement for AE (κ 0.46, 95% CI 0.39 to 0.53) and preventable AE (κ 0.47, 95% CI 0.40 to 0.53) was moderate among reviewers.

Conclusions

Reviewing RRT consults identified a high proportion of AEs and preventable AEs. This methodology detected twice as many AEs as the hospital's safety reporting system. RRT clinicians provide a complementary and more sensitive mechanism than traditional safety reporting systems to identify possible AEs in hospitals.
Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages
Authors: Almzaiel Anwar J. , Billington Richard , Smerdon Gary , Moody A. John
Published: June 2015

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.
Seasonal variation in water sources of the riparian tree species Acer negundo and Betula nigra, southern Appalachian foothills, USA
Authors: White Joseph C. , Smith William K.
Published: June 2015

Determining which water sources a plant accesses throughout a year is an important step in understanding how changes in source characteristics affect utilization by plants. Water sources of Acer negundo L. and Betula nigra L. of the foothills of the southern Appalachians Mountains were examined during one full year, including the phenological stages of leaf bolt, flowering, and leaf senescence and abscission. Source utilization was monitored, comparing the isotopic composition of water samples from woody tissue with those of possible water sources at the site. Species used deep ground and shallow soil water, with a greater reliance on deeper sources during the late growing season. Betula nigra was typically more depleted in δ2H than all water sources measured, while values from A. negundo were more variable throughout the study. Intraspecifically, isotopic values did not vary monthly or seasonally for either species (P > 0.56), while interspecific values were different for December, January, and July samplings (P < 0.02). Positive relationships occurred between air temperature and isotopic values of both species (P < 0.04), and may reflect increased evaporation from the upper soil layers at warmer temperatures, which both species appeared to use. An inability to sample all sources prevented the application of mixing models and may weaken conclusions.
Phylogenomic grouping of Listeria monocytogenes
Authors: Doijad Swapnil , Weigel Markus , Barbuddhe Sukhadeo , Blom Jochen , Goesmann Alexander , Hain Torsten , Chakraborty Trinad
Published: June 2015

The precise delineation of lineages and clonal groups are a prerequisite to examine within-species genetic variations, particularly with respect to pathogenic potential. A whole-genome-based approach was used to subtype and subgroup isolates of Listeria monocytogenes. Core-genome typing was performed, employing 3 different approaches: total core genes (CG), high-scoring segment pairs (HSPs), and average nucleotide identity (ANI). Examination of 113 L. monocytogenes genomes available in-house and in public domains revealed 33 phylogenomic groups (PGs). Each PG could be differentiated into a number of genomic types (GTs), depending on the approach used: HSPs (n = 57 GTs), CG (n = 71 GTs), and ANI (n = 83 GTs). Demarcation of the PGs was concordant with the 4 known lineages and led to the identification of sublineages in the lineage groups I, II, and III. In addition, PG assignments had discriminatory power similar to multi-virulence-locus sequence typing types and clonal complexes of multilocus sequence typing. Clustering of genomically highly similar isolates from different countries, sources, and isolation dates using whole-genome-based PG suggested that dispersion of phylogenomic clones of L. monocytogenes preceded their subsequent evolution. Classification according to PG may act as a guideline for future epidemiological studies.
Stock-Based Compensation and Earnings Management Behaviors
Authors: Chen Yu-Cheng , Lee Chia-Hao , Chou Pei-I
Published: June 2015

The purpose of this paper is to investigate whether a CEOs stock-based compensation incentive, that is one of the main corporate governance dimensions, has different impacts on accruals-based earnings management (AEM) and real activities earnings management (REM) which have different economic costs. Empirical results show that CEOs stock-based compensation incentive has a positive impact on AEM but a negative impact on REM, implying stock-based compensation incentive leads executives to use more AEM but less REM. Given that the SOX places additional compensation risk on executives, the stock-based compensation is an incentive to significantly encourage managers for using more AEM during the pre-SOX period and less REM during the post-SOX period. The evidence implies that managers change their risk perceptions for AEM and REM after the enactment of SOX, and then their earnings management behaviors indeed change for avoiding wealth-destroying pitfalls. These results bring a new insight into the ability to prevent managers from increasing personal wealth at shareholders' expense.
Defining a general hydrogeological model for Susak Island, Adriatic Sea, Croatia
Authors: Vlahović Tatjana , Šumanovac Franjo
Published: June 2015

The island of Susak differs from other Croatian islands in its geological and hydrogeological properties, because it is, for the most part, covered with fine-grained loess-type sands. At the outset of the research it was unclear whether the main aquifer lies within the superficial deposits or within the underlying carbonate rocks. This gave rise to two alternative conceptual models, depending on whether the interface between the superficial cover and the carbonates occurs above or below sea level. Hydrogeological and geophysical investigations were conducted. The primary objective of the geophysical exploration was to determine optimum positions for exploratory boreholes. The results showed that the main aquifer is contained within the carbonate rocks, and that this carbonate aquifer is overlain by a second, confined, aquifer within the superficial sandy deposits. Groundwater within the carbonate aquifer is hydraulically connected to the sea by fault zones. Measurement of electrical conductivity in boreholes established that the mixing zone of fresh and salt water is at depths from 22 to 30 m below ground level. It is necessary to ensure constant control of pumping quantities and control of the brackish water lens by monitoring of the groundwater salinity. For inclusion in public water supply, the groundwater should be treated by desalination.
Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure-overloaded hearts
Authors: Yamagami Kiyoshi , Oka Toru , Wang Qi , Ishizu Takamaru , Lee Jong-Kook , Miwa Keiko , Akazawa Hiroshi , Naito Atsuhiko T. , Sakata Yasushi , Komuro Issei
Published: June 2015

Although cardiac fibrosis causes heart failure, its molecular mechanisms remain elusive. In this study, we investigated the mechanisms of cardiac fibrosis and examined the effects of the antifibrotic drug pirfenidone (PFD) on chronic heart failure. To understand the responsible mechanisms, we generated an in vivo pressure-overloaded heart failure model via transverse aortic constriction (TAC) and examined the effects of PFD on chronic-phase cardiac fibrosis and function. In the vehicle group, contractile dysfunction and left ventricle fibrosis progressed further from 4 to 8 wk after TAC but were prevented by PFD treatment beginning 4 wk after TAC. We isolated cardiac fibroblasts and vascular endothelial cells from the left ventricles of adult male mice and investigated the cell-type-specific effects of PFD. Transforming growth factor-β induced upregulated collagen 1 expression via p38 phosphorylation and downregulated claudin 5 (Cldn5) expression in cardiac fibroblasts and endothelial cells, respectively; both processes were inhibited by PFD. Moreover, PFD inhibited changes in the collagen 1 and Cldn5 expression levels, resulting in reduced fibrosis and serum albumin leakage into the interstitial space during the chronic phase in TAC hearts. In conclusion, PFD inhibited cardiac fibrosis by suppressing both collagen expression and the increased vascular permeability induced by pressure overload.
Cardiac-specific ablation of theSTAT3gene in the subacute phase of myocardial infarction exacerbated cardiac remodeling
Authors: Enomoto Daichi , Obana Masanori , Miyawaki Akimitsu , Maeda Makiko , Nakayama Hiroyuki , Fujio Yasushi
Published: June 2015

STAT3 is a cardioprotective molecule against acute myocardial injury; however, recent studies have suggested that chronic STAT3 activation in genetically modified mice was detrimental after myocardial infarction (MI). In the present study, we assessed the biological significance of STAT3 activity in subacute MI using tamoxifen (TM)-inducible cardiac-specific STAT3 knockout (STAT3 iCKO) mice. After coronary ligation, STAT3 was rapidly activated in hearts, and its activation was sustained to the subacute phase. To make clear the pathophysiological roles of STAT3 activation specifically in subacute MI, MI was generated in STAT3 iCKO mice followed by TM treatment for 14 consecutive days beginning from day 11 after MI, which ablated the STAT3 gene in the subacute phase. Intriguingly, mortality was increased by TM treatment in STAT3 iCKO mice, accompanied by an increased heart weight-to-body weight ratio. Masson's trichrome staining demonstrated that cardiac fibrosis was dramatically exacerbated in STAT3 iCKO mice 24 days after MI (fibrotic circumference: 58.3 ± 6.7% in iCKO mice and 40.8 ± 9.3% in control mice), concomitant with increased expressions of fibrosis-related gene transcripts, including matrix metalloproteinase 9, procollagen 1, and procollagen 3. Echocardiography clarified that cardiac function was deteriorated in STAT3 iCKO mice (fractional shortening: 20.6 ± 4.1% in iCKO mice and 29.1 ± 6.0% in control mice). Dihydroethidium fluorescence analysis revealed that superoxide production was increased in STAT3 iCKO mice. Moreover, immunohistochemical analyses revealed that capillary density was decreased in STAT3 iCKO mice. Finally, STAT3 deletion in subacute MI evoked severe cardiac hypertrophy in the border zone. In conclusion, the intrinsic activity of STAT3 in the myocardium confers the resistance to cardiac remodeling in subacute MI.
Study of Phase Change Materials Applied to CPV Receivers
Authors: Shih Zun-Hao , Chain Ke-Jen , Hong Hwen-Fen
Published: June 2015

There are lots of factors which can directly affect output efficiency of photovoltaic device. One of them is high temperature which would cause adverse effect to solar cell. When solar cell is operated in high temperature, the cell’s output efficiency will become low. Therefore, improving thermal spreading of solar cell is an important issue. In this study, we focused on finding new materials to enhance the thermal dispreading and keep the temperature of solar cell as low as possible. The new materials are different from conventional metal ones; they are called “phase change materials (PCMs)” which are mainly applied to green buildings. We chose two kinds of PSMs to study their thermal dispreading ability and to compare them with traditional aluminum material. These two kinds of PCMs are wax and lauric acid. We made three aluminum‐based cuboids as heat sinking units and two of them were designed with hollow space to fill in the PCMs. We applied electric forward bias on solar cells to simulate the heat contributed from the concentrated sunlight. Then we observed the thermal distribution of these three kinds of thermal spreading materials. Two levels of forward biases were chosen to test the samples and analyze the experiment results.
Extranodal Rosai-Dorfman Disease Involving the Left Atrium: Cardiac MRI, CT, and PET Scan Findings
Authors: Daruwalla Vistasp J. , Parekh Keyur , Tahir Hassan , Collins Jeremy D. , Carr James
Published: June 2015

Rosai-Dorfman disease (RDD) is a rare entity that usually involves the lymph nodes but extranodal involvements have been seen in numerous cases, although RDD with cardiovascular involvement is extremely rare. We describe a case of a young male who presented with intermittent palpitations and was found to have a left atrium mass. Our case not only emphasizes the rarity of the above lesion but also highlights the importance of modern-day imaging like computed tomography, Cardiac Magnetic Resonance Imaging (CMRI), and PET scan in characterizing such nonspecific lesions and directing appropriate line of treatment. RDD should be considered as one of the differentials even for isolated cardiac lesions.
Erlotinib Pretreatment Improves Photodynamic Therapy of Non–Small Cell Lung Carcinoma Xenografts via Multiple Mechanisms
Authors: Gallagher-Colombo Shannon M. , Miller Joann , Cengel Keith A. , Putt Mary E. , Vinogradov Sergei A. , Busch Theresa M.
Published: June 2015

Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers, including non–small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. Although EGFR is currently a favorite molecular target for the treatment of these cancers, inhibition of the receptor with small-molecule inhibitors (i.e., erlotinib) or monoclonal antibodies (i.e., cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared with 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT. Cancer Res; 75(15); 3118–26. ©2015 AACR.
NF-κB2/p52:c-Myc:hnRNPA1 Pathway Regulates Expression of Androgen Receptor Splice Variants and Enzalutamide Sensitivity in Prostate Cancer
Authors: Nadiminty Nagalakshmi , Tummala Ramakumar , Liu Chengfei , Lou Wei , Evans Christopher P. , Gao Allen C.
Published: June 2015

Castration-resistant prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active, ligand-independent variants is one of the principal mechanisms that promote the development of resistance to next-generation antiandrogens such as enzalutamide. Here, we demonstrate that the splicing factor heterogeneous nuclear RNA-binding protein A1 (hnRNPA1) plays a pivotal role in the generation of AR splice variants such as AR-V7. hnRNPA1 is overexpressed in prostate tumors compared with benign prostates, and its expression is regulated by NF-κB2/p52 and c-Myc. CRPC cells resistant to enzalutamide exhibit higher levels of NF-κB2/p52, c-Myc, hnRNPA1, and AR-V7. Levels of hnRNPA1 and AR-V7 are positively correlated with each other in prostate cancer. The regulatory circuit involving NF-κB2/p52, c-Myc, and hnRNPA1 plays a central role in the generation of AR splice variants. Downregulation of hnRNPA1 and consequently of AR-V7 resensitizes enzalutamide-resistant cells to enzalutamide, indicating that enhanced expression of hnRNPA1 may confer resistance to AR-targeted therapies by promoting the generation of splice variants. These findings may provide a rationale for cotargeting these pathways to achieve better efficacy through AR blockade. Mol Cancer Ther; 14(8); 1884–95. ©2015 AACR.