bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Fetal Monitoring and Cesarean Birth: A Scoping Review
Authors: Paterno Mary T. , McElroy Kathleen , Regan Mary
Published: August 2016

Background

In many United States hospitals, electronic fetal monitoring (EFM) is used continuously during labor for all patients regardless of risk status. Application of EFM, particularly at labor admission, may trigger a chain of interventions resulting in increased risk for cesarean birth among low‐risk women. The goal of this review was to summarize evidence on use of EFM during low‐risk labors and identify gaps in research.

Methods

We conducted a scoping review of studies published in English since 1996 that addressed the relationship between EFM use and cesarean among low‐risk women. We screened 57 full‐text articles for appropriateness. Seven articles were included in the final review.

Results

The largest study demonstrated an 81 percent increased risk of primary cesarean birth when EFM was used in labor, but did not differentiate between high‐ and low‐risk pregnancies. Four randomized controlled trials examined the association of admission EFM with obstetric outcomes; only one considered cesarean birth as a primary outcome and found a 23 percent increase in operative birth when EFM lasted more than 1 hour. A study examining application of continuous EFM before and after 4 centimeters dilatation found no differences between groups.

Conclusions

In general, the research on this topic suggests an association between the use of EFM and cesarean birth; however, more well‐designed studies are needed to examine benefits of EFM versus auscultation, determine if EFM is associated with use of other technologies that could cumulatively increase risk of cesarean birth, and understand provider motivation to use EFM over auscultation.
Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization
Authors: Elbadawy Hossein Mostafa , Mirabelli Pierfrancesco , Xeroudaki Maria , Parekh Mohit , Bertolin Marina , Breda Claudia , Cagini Carlo , Ponzin Diego , Lagali Neil , Ferrari Stefano
Published: August 2016

Background and Purpose

The connexin 43 (Cx43) mimetic peptide Gap27 was designed to transiently block the function of this gap junction. This study was undertaken to investigate the effect of Gap27 on corneal healing, inflammation and neovascularization.

Experimental Approach

The effect of Gap27 on wound healing, inflammation and vascularization was assessed in primary human corneal epithelial cells (HCEC)in vitroand whole human corneasex vivo, and in anin vivorat wound healing model.

Key Results

Gap27 enhanced the wound closure of HCECin vitroand accelerated wound closure and stratification of epithelium in human corneasex vivo, but did not suppress the corneal release of inflammatory mediators IL‐6 or TNF‐αin vivo. In human corneasex vivo, F4/80 positive macrophages were observed around the wound site.In vivo, topical Gap27 treatment enhanced the speed and density of early granulocyte infiltration into rat corneas. After 7 days, the expressions of TNF‐α and TGFβ1 were elevated and correlated with inflammatory cell accumulation in the tissue. Additionally, Gap27 did not suppress VEGF release in organotypic culture, nor did it suppress early or late VEGFA expression or neovascularizationin vivo.

Conclusions and Implications

Gap27 can be effective in promoting the healing of superficial epithelial wounds, but in deep stromal wounds it has the potential to promote inflammatory cell migration and accumulation in the tissue and does not suppress the subsequent neovascularization response. These results support the proposal that Gap27 acts as a healing agent in the transient, early stages of corneal epithelial wounding.
Protection from interferon‐β‐induced neuronal apoptosis through stimulation of muscarinic acetylcholine receptors coupled to ERK1/2 activation
Authors: Olianas Maria C , Dedoni Simona , Onali Pierluigi
Published: August 2016

Background and Purpose

Although clinically useful for their immunomodulatory, antiproliferative and antiviral properties, type I interferons (IFNs) are involved in the pathogenesis of several neurodegenerative/neuroinflammatory diseases. In the present study, we investigated the ability of cholinergic stimulation to protect from IFN‐β‐induced neuronal apoptosis.

Experimental Approach

The effects of the ACh receptor agonist carbachol (CCh) on IFN‐β‐induced apoptosis of human SH‐SY5Y neuroblastoma cells were examined by using western blots, immunofluorescence and cytofluorimetry. The involvement of muscarinic acetylcholine receptors (mAChRs) was assessed by using selective antagonists and siRNA transfection. Pharmacological inhibitors and overexpression of ERK2 and an ERK2 constitutively active form (ERK2‐CA) were employed to study ERK1/2 signalling. The effects of oxotremorine‐M (Oxo‐M) on IFN‐β‐induced apoptosis of mouse hippocampal neurons were examined by measuring cleaved caspase 3 expression.

Key Results

In SH‐SY5Y cells, CCh inhibited IFN‐β‐induced mitochondrial cytochrome c release, activation of caspases 9, 7 and 3, PARP cleavage and DNA fragmentation. The anti‐apoptotic effect of CCh was mediated by M3 receptors, blocked by Gq/11 antagonist YM254890 and PKC inhibitor Go 6983, impaired by inhibition of ERK1/2 pathway, potentiated by overexpression of ERK2 and mimicked by ERK2‐CA. Blockade of JNK activation enhanced the CCh anti‐apoptotic response. IFN‐β inhibited JNK activation and up‐regulated CCh‐induced ERK1/2 signalling. In hippocampal neurons, Oxo‐M reduced IFN‐β‐induced apoptosis; this effect was antagonized by blockade of M1/M3 receptors and ERK1/2.

Conclusions and Implications

Stimulation of mAChRs counteracted IFN‐β‐induced neuronal apoptosis through the activation of ERK1/2 signalling. The data indicate that activation of ERK1/2‐coupled mAChRs may be an effective strategy for preventing IFNs neurotoxicity.
Synthesis, biological evaluation, and molecular docking studies of new pyrazol‐3‐one derivatives with aromatase inhibition activities
Authors: Yi Xue‐Jing , El‐Idreesy Tamer T. , Eldebss Taha M. A. , Farag Ahmad M. , Abdulla Mohamed M. , Hassan Shaimaa A. , Mabkhot Yahia N.
Published: August 2016

A new series derived from 4‐(2‐chloroacetyl)‐1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3H‐pyrazol‐3‐one was synthesized, characterized and its pharmacological activity toward aromatase enzyme inhibition was screened and compared to the reference native ligand letrozole. The most active compound of the series was 16, showing IC50 value of 0.0023 ± 0.0002 μm compared to letrozole with IC50 of 0.0028 ± 0.0006 μm. In addition, compounds 26 and 36 exhibit good inhibition activities close to letrozole with IC50 values 0.0033 ± 0.0001 and 0.0032 ± 0.0003 μm, respectively. Moreover, molecular docking studies were conducted to support the findings.
1‐[(Imidazolidin‐2‐yl)imino]‐1H‐indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies
Authors: Kornicka Anita , Wasilewska Aleksandra , Sączewski Jarosław , Hudson Alan L. , Boblewski Konrad , Lehmann Artur , Gzella Karol , Belka Mariusz , Sączewski Franciszek , Gdaniec Maria , Rybczyńska Apolonia , Bączek Tomasz
Published: August 2016

A series of 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indole analogues of hypotensive α2‐AR agonists, 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indazoles, was synthesized and tested in vitro for their activities at α1‐ and α2‐adrenoceptors as well as imidazoline I1 and I2 receptors. The most active 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indoles displayed high or moderate affinities for α1‐ and α2‐adrenoceptors and substantial selectivity for α2‐adrenoceptors over imidazoline‐I1 binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C‐7 position of the indole ring may result in compounds with high cardiovascular activity. Among them, 7‐fluoro congener 3g showed the most pronounced hypotensive and bradycardic activities in this experiment at a dose as low as 10 μg/kg i.v. Metabolic stability of the selected compounds of type 3 was determined using both in vitro and in silico approaches. The results indicated that these compounds are not vulnerable to rapid first‐phase oxidative metabolism.
THE EFFECT OF THE BUSINESS CYCLE ON FRESHMAN FINANCIAL AID
Authors: Clelan Elizabeth B. , Kofoed Michael S.
Published: August 2016

When the economy slips into recession, more needy students enroll in college, increasing the need for financial aid while resources for aid become more scarce. We use “Freshman Survey” data from the Higher Education Research Institute to observe changes in financial aid composition from 1980 to 2000. We use state‐level tax revenues, unemployment rates, and personal income growth as macroeconomic indicators. During recessions, we find that the burden of financing a student's college education shifts from states and institutions to families and federal programs. We also show that these macroeconomic fluctuations are increasingly volatile for underrepresented minorities. (JEL I22, H52, E32)
RELATIVE TEACHER SALARIES AND THE DECISION TO TEACH
Authors: Rickman Dan S. , Wang Hongbo , Winters John V.
Published: August 2016

Using the 3‐year microdata sample of the American Community Survey for 2009–2011, we examine the effect of state‐level public school teacher salaries relative to those of other college graduates in the state not employed in education on the decision to teach. We find that relative teacher salaries in the state positively affect the share of education majors that are employed as public school teachers at the time of the survey. The effect for males majoring in math, science, and computer education is largest among all estimated effects. A statistically significant effect is also found among females majoring in elementary education. (JEL H75, I20, R23)
Papillary fibroelastoma: clinical and echocardiographic features and initial approach in 54 cases
Authors: Cianciulli Tomás Francisco , Soumoulou Juan Bautista , Lax Jorge Alberto , Saccheri María Cristina , Cozzarin Alberto , Beck Martín Alejandro , Ferreiro Daniel Ernesto , Prezioso Horacio Alberto
Published: August 2016

Introduction

Papillary fibroelastoma (PFE) is a benign cardiac tumor that is currently detected more often due to the technological improvements in echocardiography.

Objectives

To describe the echocardiographic features of PFE and correlate them with the clinical presentation and initial treatment.

Materials and Methods

A prospective analysis of patients with a diagnosis of PFE was conducted between 2000 and 2015. We assessed the clinical history, symptoms at the time of diagnosis, echocardiographic features, and initial treatment.

Results

Fifty‐four patients with a diagnosis of PFE by echocardiography were included. The incidence was 0.038%. Mean age was 62±16 years; 50% were male. Forty‐six percent of patients had symptoms at the time of diagnosis, the most frequent of which was transient ischemic accident (TIA). Embolic episodes occurred in 31% of patients, mainly to the brain. PFEs were valvular in 70.4% of cases and multiple in 13%. Mean maximum length was 1.18±0.58 cm, and 44% were mobile. PFEs >1.5 cm were most often found in the heart valves (56.8% vs 10.8%; P=.045). There was no significant relation between size, mobility, location and number of tumors, and the presence of embolism or symptoms. Most frequent treatment was oral anticoagulation in 48.6%, followed by simple tumor resection in 42.8% of cases.

Conclusions

PFE is a small tumor, predominantly valvular and benign, but entails a high incidence of cerebral embolism. The initial approach should be individualized according to clinical manifestations, comorbidities, and the experience of the surgical center.
Prolonged QT and myocardium recovery after primary PCI: a cMRI study
Authors: Ieva Riccardo , Casavecchia Graziapia , Gravina Matteo , Totaro Antonio , Ferraretti Armando , Macarini Luca , Di Biase Matteo , Brunetti Natale Daniele
Published: August 2016

Background

The presence of viable stunned myocardium recovering after primary angioplasty is not easy to identify in the early phase of acute myocardial infarction (AMI) by noninvasive bed‐side methods. We therefore aimed to assess whether a simple electrocardiogram parameter may be of help in identifying the presence of stunned viable myocardium recovering after reperfusion with primary angioplasty.

Materials and methods

A total of 14 consecutive patients with ST‐elevation AMI (STEMI) were enrolled in the study and underwent QT duration assessment after admission: the difference between QT corrected (QTc) in the ischaemic areas and QTc values in nonischaemic areas was therefore calculated and compared with the presence and the extension of viable stunned myocardium, assessed by comparing akinetic/dyskinetic areas at admission echocardiography with akinetic/dyskinetic areas and extension of scar at 6‐month cardiac magnetic resonance imaging (cMRI).

Results

In subjects with viable recovering myocardium, 75% had a QTc max > 440 ms (vs. 17%, P = 0·03); higher differential QTc values and smaller scar areas were found (33 ms vs. −17 ms, 14% vs. 27%, P = 0·03, 0·06 respectively). Differential QTc values > 0 were able to identify the presence of viable myocardium with an odds ratio of 35 (P < 0·05, sensitivity 88%, specificity 83%, positive predictive power 88%, negative predictive power of 83%). Differential QTc values were related to the extension of viable recovering myocardium (P < 0·001).

Conclusion

Viable myocardium recovering after primary angioplasty in STEMI may be predicted by the presence of increased QTc values in ischaemic areas in comparison with nonischaemic areas.
An electrophysiological marker of the desire to quit in smokers
Authors: Donohue Sarah E. , Harris Joseph A. , Heinze Hans‐Jochen , Woldorff Marty G. , Schoenfeld Mircea A.
Published: August 2016

For many smokers, the motivational state of craving is a central feature of their dependence on nicotine, and is often at odds with a general desire to quit. How this desire to quit may influence the craving for a cigarette, however, is unclear. In the current study, we manipulated the level of craving in 24 regular smokers, and recorded EEG measures of brain activity during a rare target detection task utilizing addiction‐unrelated stimuli. In response to the non‐targets, we observed that smokers wanting to quit showed an enhanced late frontal activation when they were craving vs. not craving, whereas smokers not wanting to quit showed the opposite pattern of activity. A dissociation was also present in the target‐related P300 response as a function of craving and desire to quit, with smokers who did not want to quit processing targets differentially between the states of craving and non‐craving. The data suggest that distinct top‐down control mechanisms during craving may be implemented by people who wish to quit smoking, as compared to those who do not wish to quit. This pattern of findings establishes this ERP activity as a potential biomarker that may help to differentiate people who want to quit their addiction from those who wish to continue to use their substance of choice.
Evolution‐informed modeling improves outcome prediction for cancers
Authors: Liu Li , Chang Yung , Yang Tao , Noren David P , Long Byron , Kornblau Steven , Qutub Amina , Ye Jieping
Published: August 2016

Despite wide applications of high‐throughput biotechnologies in cancer research, many biomarkers discovered by exploring large‐scale omics data do not provide satisfactory performance when used to predict cancer treatment outcomes. This problem is partly due to the overlooking of functional implications of molecular markers. Here, we present a novel computational method that uses evolutionary conservation as prior knowledge to discover bona fide biomarkers. Evolutionary selection at the molecular level is nature's test on functional consequences of genetic elements. By prioritizing genes that show significant statistical association and high functional impact, our new method reduces the chances of including spurious markers in the predictive model. When applied to predicting therapeutic responses for patients with acute myeloid leukemia and to predicting metastasis for patients with prostate cancers, the new method gave rise to evolution‐informed models that enjoyed low complexity and high accuracy. The identified genetic markers also have significant implications in tumor progression and embrace potential drug targets. Because evolutionary conservation can be estimated as a gene‐specific, position‐specific, or allele‐specific parameter on the nucleotide level and on the protein level, this new method can be extended to apply to miscellaneous “omics” data to accelerate biomarker discoveries.
Heritability and factors associated with number of harness race starts in the Spanish Trotter horse population
Authors: Solé M. , Valera M. , Gómez M.D. , Sölkner J. , Molina A. , Mészáros G.
Published: August 2016

Background

Longevity/durability is a relevant trait in racehorses. Genetic analysis and knowledge of factors that influence number of harness race starts would be advantageous for both horse welfare and the equine industry.

Objectives

To perform a genetic analysis on harness racing using number of races as a measure of longevity/durability and to identify factors associated with career length in Spanish Trotter Horses (STH).

Study design

Longitudinal study.

Methods

Performance data (n = 331,970) on the STH population for harness racing at national level between 1990 and 2014 were used. A grouped data model was fitted to assess factors influencing the risk of ending harness racing career and to estimate the heritability and breeding values for total number of harness races starts as an indicator of horses' longevity and durability. The model included sex, age at first race and first start earnings as time‐independent effects, and the calendar year, driver, trainer, racetrack category and season of competition as time‐dependent effects.

Results

Across the whole dataset, the average number of harness races horses achieved in Spain was 54.7 races, and this was associated with the horses' sex, age at first race and first start earnings, calendar year, driver, racetrack category, and season. The heritability estimated (0.17 ± 0.01) for number of harness race starts indicates that a beneficial response to direct genetic selection can be expected.

Main limitations

Data on horses' health status were not available.

Conclusions

Horses' total number of harness race starts is a promising tool for genetic analysis and the evaluation of racing longevity and durability. The estimated heritability provides evidence to support the application of genetic selection of total career number of races to improve longevity/durability of STH.
Owner reported diseases of working equids in central Ethiopia
Authors: Stringer A. P. , Christley R. M. , Bell C. E. , Gebreab F. , Tefera G. , Reed K. , Trawford A. , Pinchbeck G. L.
Published: August 2016

Reasons for performing study

Working horses, donkeys and mules suffer from numerous diseases and clinical problems. However, there is little information on what owners perceive as important health concerns in their working animals.

Objectives

To identify and prioritise with owners the diseases and other health concerns in working equids in central Ethiopia using participatory methodologies.

Study design

Participatory situation analysis (PSA).

Methods

The study was conducted with carthorse‐ and donkey‐owners in 16 sites in central Ethiopia. Multiple participatory methodologies were utilised, including ranking, matrices and focus group discussions. Owners’ perceptions on frequency, importance, morbidity and mortality of volunteered diseases and the clinical signs that owners attributed to each disease were obtained; information regarding the impact of these diseases and health concerns was also sought.

Results

A total of 40 separate disease and health problems were volunteered by carthorse‐ and donkey‐owners. Horse‐owners volunteered a musculoskeletal syndrome (with the local name ‘bird’, clinical signs suggest possible disease pathologies including equine exertional rhabdomyolysis), colic and epizootic lymphangitis most frequently, whereas donkey‐owners volunteered sarcoids, nasal discharge and wounds to occur most frequently. One problem (coughing) was volunteered frequently by both horse‐ and donkey‐owners. Owners demonstrated knowledge of differing manifestations and severity of these problems, which resulted in differing impacts on the working ability of the animal.

Conclusions

Although many of the diseases and clinical signs had been previously reported, this study also identified some previously unreported priorities such as rabies in donkeys, an unidentified musculoskeletal syndrome in horses and respiratory signs in both horses and donkeys. The information gathered during this participatory study with owners may be used to inform future veterinary and educational programme interventions, as well as identify future research priorities.
Factors associated with survival of horses following relaparotomy
Authors: Findley J. A. , Salem S. , Burgess R. , Archer D. C.
Published: August 2016

Reasons for performing study

Relaparotomy may be required to investigate and manage complications that occur following surgical management of colic.

Objectives

To report factors associated with survival following relaparotomy.

Study design

Retrospective cohort study.

Methods

Records of horses that had undergone exploratory laparotomy for treatment of colic over a 10‐year period (2002–2012) and had undergone relaparotomy <8 weeks following the initial surgery were reviewed. Descriptive data were generated and association with survival time was modelled using Cox proportional hazards models.

Results

Relaparotomy was performed in 96 horses at <8 weeks following initial surgery at a median of 4 days. This represented 6.3% of horses that underwent laparotomy during the study period (n = 1531). Relaparotomy was most frequently undertaken based on signs of persistent post‐operative colic (76%; n = 73). Short‐term survival for horses undergoing relaparotomy due to persistent colic was 53%, incisional dehiscence 50%, post‐operative reflux 37%, haemoperitoneum 17% and septic peritonitis 0%. Median survival was 6 days for all horses undergoing relaparotomy and 778 days for those that recovered following anaesthesia. Nonsurvival was associated with increased packed cell volume at 24 h following initial laparotomy (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04–1.10, P = 0.009), peritonitis as a reason for undertaking relaparotomy (HR 4.41, 95% CI 1.43–13.6, P = 0.01) and adhesions found at relaparotomy (HR 1.77, 95% CI 1.03–3.04, P = 0.04). Increased likelihood of survival was associated with colic signs being the reason for performing relaparotomy (HR 0.48, 95% CI 0.26–0.88, P = 0.02) and small intestinal distension found at relaparotomy (HR 0.53, 95% CI 0.29–0.96, P = 0.04).

Conclusions

This study has provided information about survival rates and risk factors for survival in horses undergoing relaparotomy that can assist clinicians and owners when determining whether to perform relaparotomy and in predicting the likely surgical outcome.
Improved radiological diagnosis of palmar osteochondral disease in the Thoroughbred racehorse
Authors: Davis A. M. , Fan X. , Shen L. , Robinson P. , Riggs C. M.
Published: August 2016

Background

Palmar osteochondral disease (POD) is common in the Thoroughbred racehorse yet difficult to diagnose by radiography alone.

Objectives

To improve the sensitivity and specificity for diagnosing POD from radiographs.

Study design

Prospective, longitudinal study.

Methods

Radiographs in nine different projections were made of metacarpophalangeal joints (MCPJ) of 50 Thoroughbreds. Post‐mortem, MCPJs were dissected and gross pathology was scored. Three experienced Thoroughbred clinicians read each radiograph and recorded their findings. Another clinician reviewed each radiograph alongside the related gross specimens in order to correlate radiological findings with joint pathology. This served as a ‘gold standard’. The performance of each clinician at detecting POD was compared with the ‘gold standard’. Radiological features associated with POD were identified and presented to the clinicians in a training manual, prior to them re‐reading the radiographs. The ability of each clinician to diagnose POD was reassessed.

Results

Palmar osteochondral disease was a common finding (88/100 joints). All three clinicians demonstrated low sensitivity and low specificity at detecting POD (mean 0.37 and 0.75, respectively). Conversely, the sensitivity and specificity for POD in the ‘gold standard’ was high (0.95 and 1.0). POD was associated with primary radiological features (e.g. focal radiolucencies in the palmar condyles, disruption of the outline of subchondral bone and focal sclerosis of the palmar condyles) and secondary features (e.g. basilar and apical osteophytes on the proximal sesamoid bones, flattening of the palmar condyles and cavitation of the dorso‐distal aspect of the third metacarpal bone). Secondary radiographic features were often easier to detect. Following training the performance of clinicians at identifying POD was significantly improved.

Main limitations

Only two clinicians completed the study; low proportion of POD negative cases in the study.

Conclusions

Clinicians frequently overlook key radiological features related to POD. Alerting clinicians to relevant radiological features improved the sensitivity and specificity of diagnosis.
Key principles of ecosystem‐based management: the fishermen's perspective
Authors: Long Rachel D , Charles Anthony , Stephenson Robert L
Published: August 2016

Despite the growing popularity of ecosystem‐based management (EBM) in national legislation and in research and institutional literature, there is often an implementation gap ‘on the ground’, impeding widespread adoption in fisheries. This gap reflects in part the differing understandings of EBM held by fishermen and by management institutions. To explore and seek to close this gap, the underlying principles of EBM considered priorities by fishermen were systematically compared with the priorities identified in the published literature. The fishermen's priorities were determined by asking Atlantic Canadian fishermen to identify the EBM principles they consider most important. Four priority principles were identified: Sustainability, Stakeholder Involvement, Develop Long‐Term Objectives and Use of All Forms of Knowledge. The latter two were not frequently noted as priorities in the literature, while some literature priorities were less commonly chosen by fishermen, indicating a significant difference in perspectives on EBM. The rationale for fishermen's choice of priorities was explored by analysing the fishery management issues they raised – many directly connected to the above four priorities. In addition, another principle, Commit to Principles of Equity, often arose as an implicit priority among fishermen. We suggest that success in implementation of EBM may depend on reconciling differing priorities among its underlying principles, and combining knowledge and expertise from fishermen with research and institutional sources. The comparative methodology used here, which could be replicated elsewhere, should lead to better recognition of local challenges in EBM implementation and encourage support for EBM, to further its contribution to sustainable fisheries.
Multidimensional Family Therapy: Evidence Base for Transdiagnostic Treatment Outcomes, Change Mechanisms, and Implementation in Community Settings
Authors: Liddle Howard A.
Published: August 2016

This article summarizes the 30+‐year evidence base of Multidimensional Family Therapy (MDFT), a comprehensive treatment for youth substance abuse and antisocial behaviors. Findings from four types of MDFT studies are discussed: hybrid efficacy/effectiveness randomized controlled trials, therapy process studies, cost analyses, and implementation trials. This research has evaluated various versions of MDFT. These studies have systematically tested adaptations of MDFT for diverse treatment settings in different care sectors (mental health, substance abuse, juvenile justice, and child welfare), as well as adaptations according to treatment delivery features and client impairment level, including adolescents presenting with multiple psychiatric diagnoses. Many published scientific reviews, including meta‐analyses, national and international government publications, and evidence‐based treatment registries, offer consistent conclusions about the clinical effectiveness of MDFT compared with standard services as well as active treatments. The diverse and continuing MDFT research, the favorable, multi‐source independent evaluations, combined with the documented receptivity of youth, parents, community‐based clinicians and administrators, and national and international MDFT training programs (U.S.‐based organization is MDFT International, www.mdft.org; and Europe‐based organization is www.mdft.nl) all support the potential for continued transfer of MDFT to real‐world clinical settings.
Research review on the pharmacological effects of astragalosideIV
Authors: Li Lei , Hou Xiaojiao , Xu Rongfang , Liu Chang , Tu Menbayaer
Published: August 2016

Astragalus membranaceus Bungehas been used to treat numerous diseases for thousands of years. As the main active substance ofAstragalus membranaceus Bunge, astragalosideIV(AS‐IV) also demonstrates the potent protective effect on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver fibrosis, and diabetic nephropathy. Based on studies published during the past several decades, the current state ofAS‐IVresearch and the pharmacological effects are detailed, elucidated, and summarized. This review systematically summarizes the pharmacological effects, metabolism mechanism, and the toxicity ofAS‐IV.AS‐IVhas multiple pharmacologic effects, including anti‐inflammatory, antifibrotic, antioxidative stress, anti‐asthma, antidiabetes, immunoregulation, and cardioprotective effect via numerous signaling pathways. According to the existing studies and clinical practices,AS‐IVpossesses potential for broad application in many diseases.
Do Tighter Loan Covenants Signal Improved Future Corporate Results? The Case of Performance Pricing Covenants
Authors: Beyhaghi Mehdi , Panyagometh Kamphol , Gottesman Aron A. , Roberts Gordon S.
Published: August 2016

Covenants in corporate bonds and loan agreements mitigate agency conflicts between borrowers and lenders and may provide a signal of borrower quality to help resolve information asymmetry. Performance pricing covenants in bank loans specify automatic adjustments to loan spreads based on borrowers’ subsequent performance. Our covenant signaling framework views interest‐decreasing performance pricing as a tight covenant associated with borrowers’ private information on improved future performance accompanied by reduced credit risk. This positive signal is associated with larger positive loan announcement returns and greater improvements in future borrower performance. Further, in addition to signaling value, we find that the spread impact of this class of covenant also depends on its option value and reduction in transaction costs.
Influence of highly permeable faults within a low‐porosity and low‐permeability reservoir on migration and storage of injected CO2
Authors: Bu F. , Xu T. , Wang F. , Yang Z. , Tian H.
Published: August 2016

Faults in CO2 storage reservoirs affect the migration and spatial distribution of injected CO2 in reservoir formations. Based on geological data from the Ordos CO2 geological storage demonstration project site, A 2D numerical model of the CO2 storage reservoir was constructed to study the influence of high‐porosity and high‐permeability faults within a low‐porosity and low‐permeability reservoir. The results show that the faults had a significant effect on CO2 migration and storage. If the permeability of the fault zone increased by 2–3 orders of magnitude (a common range of variation in fault zone) and porosity increased correspondingly compared to the base case (no fault in strata), the CO2 migration distance in the reservoir after 100 years was approximately 1.18 times larger than that of the base case without faults, and the total CO2 storage amount in the entire reservoir increased by 1.40–1.61 times. The faults weakened the sealing ability of the local interlayer caprocks (mudstone), which resulted in CO2 migrating through mudstone and entering in the neighboring interlayer storage stratum. When highly permeable faults existed, the CO2 migration distance and storage amount in the neighboring interlayer storage stratum were approximately two times and 19.41 times (maximum value) higher, respectively, compared with the case without a fault. Therefore, the faults distributed in strata should be given sufficient attention when selecting a CO2 sequestration site.
Efficacy of DSP30‐IL2/TPA for detection of cytogenetic abnormalities in chronic lymphocytic leukaemia/small lymphocytic lymphoma
Authors: Holmes P. J. , Peiper S. C. , Uppal G. K. , Gong J. Z. , Wang Z.‐X. , Bajaj R.
Published: August 2016

Introduction

Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG‐oligonucleotide DSP30/Interleukin‐2 (IL‐2) and DSP30/IL‐2 in combination with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA).

Methods

We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set‐up: unstimulated, DSP30/IL‐2‐stimulated and TPA‐stimulated. In 2012–2013, two cultures were set‐up: unstimulated and stimulated with TPA/DSP30/IL‐2.

Results

In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012–2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL‐2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012–2013. The TPA/DSP30/IL‐2 cultures in 2012–2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL‐2 alone (n = 3).

Conclusions

TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL‐2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities.
Neutrophil CD64 expression as a longitudinal biomarker for severe disease and acute infection in critically ill patients
Authors: de Jong E. , de Lange D. W. , Beishuizen A. , van de Ven P. M. , Girbes A. R. J. , Huisman A.
Published: August 2016

Introduction

Neutrophilic granulocytes express cluster of differentiation 64 (CD64) antigen upon activation. CD64 can be used as a marker of bacterial infection and sepsis. The goal of this study was to determine whether CD64 is a useful biomarker for critically ill patients and analyze longitudinal measurements with regard to outcome and sepsis severity.

Methods

In this prospective observational study, CD64 analysis was performed daily until discharge from ICU or death. Demographics, clinical, laboratory data, and outcome defined as 28‐day survival were recorded. Patients were included when admitted to the ICU with sepsis, severe sepsis, or septic shock and within 24 h from start of antibiotic treatment.

Results

Hundred and fifty‐five consecutive patients were enrolled. At baseline, a difference in CD64 of 2.26 (1.33–4.47) vs. 1.49 (0.89–2.24) (P = 0.004) was seen between patients with a positive culture and negative culture. CD64 at day 1 was higher with patients with septic shock when compared with sepsis (P = 0.012). No difference of CD64 between survivors and nonsurvivors was seen.

Conclusion

This study demonstrated that CD64 discriminates between critically ill patients with culture positive and negative sepsis and correlates with severity of disease. However, CD64 index is not a good predictor for 28‐day mortality in the critically ill patient.
Evaluation of the performance of a point‐of‐care method for total and differential white blood cell count in clozapine users
Authors: Bui H. N. , Bogers J. P. A. M. , Cohen D. , Njo T. , Herruer M. H.
Published: August 2016

Introduction

We evaluated the performance of the HemoCue WBC DIFF, a point‐of‐care device for total and differential white cell count, primarily to test its suitability for the mandatory white blood cell monitoring in clozapine use.

Method

Leukocyte count and 5‐part differentiation was performed by the point‐of‐care device and by routine laboratory method in venous EDTA–blood samples from 20 clozapine users, 20 neutropenic patients, and 20 healthy volunteers. From the volunteers, also a capillary sample was drawn. Intra‐assay reproducibility and drop‐to‐drop variation were tested.

Results

The correlation between both methods in venous samples was r > 0.95 for leukocyte, neutrophil, and lymphocyte counts. The correlation between point‐of‐care (capillary sample) and routine (venous sample) methods for these cells was 0.772; 0.817 and 0.798, respectively. Only for leukocyte and neutrophil counts, the intra‐assay reproducibility was sufficient.

Conclusion

The point‐of‐care device can be used to screen for leukocyte and neutrophil counts. Because of the relatively high measurement uncertainty and poor correlation with venous samples, we recommend to repeat the measurement with a venous sample if cell counts are in the lower reference range. In case of clozapine therapy, neutropenia can probably be excluded if high neutrophil counts are found and patients can continue their therapy.
Recommendation for standardization of haematology reporting units used in the extended blood count
Authors: Brereton M. , McCafferty R. , Marsden K. , Kawai Y. , Etzell J. , Ermens A. ,   the international council for standardization in haematology
Published: August 2016

Introduction

It is desirable in the interest of patient safety that the reporting of laboratory results should be standardized where no valid reason for diversity exists. This study considers the reporting units used for the extended blood cell count and makes a new ICSH recommendation to encourage standardization worldwide.

Methods

This work is based on a literature review that included the original ICSH recommendations and on data gathered from an international survey of current practice completed by 18 countries worldwide.

Results

The survey results show that significant diversity in the use of reporting units for the blood count exists worldwide. The use of either non‐SI or other units not recommended by the ICSH in the early 1980s has persisted despite the guidance from that time.

Conclusion

The diversity in use of reporting units occurs in three areas: the persistence in use of non‐SI units for RBC, WBC and platelet counts, the use of three different units for haemoglobin concentration and the manual reporting of WBC differential, reticulocytes and nucleated RBCs when the latter are available from automated analysis or can be expressed as absolute numbers by calculation. A new recommendation with a rationale for each parameter is made for standardization of the reporting units used for the extended blood count.
Increased mean corpuscular haemoglobin concentration: artefact or pathological condition?
Authors: Berda‐Haddad Y. , Faure C. , Boubaya M. , Arpin M. , Cointe S. , Frankel D. , Lacroix R. , Dignat‐George F.
Published: August 2016

Introduction

In daily practice in haematology laboratories, spurious increased MCHC induces an analytical alarm and needs prompt corrective action to ensure delivery of the right results to the clinicians. The aim of this study was to establish a ‘decision tree’ using the new parameters red blood cells (RBC‐O) and haemoglobin (HGB‐O) from the Sysmex XN‐10 RET obtained by flow cytometry to deliver appropriate results.

Methods

From 128 unknown patients with MCHC > 365 g/L, all erythrocyte parameters including reticulocyte parameters were measured and analysed in parallel with blood smears, chemistry index and osmolarity. Differences between optical parameters (RBC‐O, HGB‐O) and usual parameters (RBC, HGB) obtained by impedance and photometry were reported also.

Results

Four groups were defined from observations: ‐RBC agglutination (n = 22); ‐optical interference (n = 17); ‐RBC disease (n = 18); and ‐others (n = 71). The use of RBC‐O and HGB‐O permitted efficient correction of the abnormalities when RBC agglutination and/or optical interference were present in 36 of 39 patients. Reticulocyte parameters permitted to elaborate an RBC score that allowed a highly sensitive detection of RBC disease patients (17/18).

Conclusion

Based on new parameters, we propose a ‘decision tree’ that delivers time savings and supports biological interpretation in case of elevated MCHC.
Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques – implications for highly complex MHC‐dependent regulation of natural killer cells
Authors: Walter Lutz , Petersen Beatrix
Published: August 2016

The killer immunoglobulin‐like receptors (KIR) as well as their MHC class I ligands display enormous genetic diversity and polymorphism in macaque species. Signals resulting from interaction between KIR or CD94/NKG2 receptors and their cognate MHC class I proteins essentially regulate the activity of natural killer (NK) cells. Macaque and human KIR share many features, such as clonal expression patterns, gene copy number variations, specificity for particular MHC class I allotypes, or epistasis between KIR and MHC class I genes that influence susceptibility and resistance to immunodeficiency virus infection. In this review article we also annotated publicly available rhesus macaque BAC clone sequences and provide the first description of the CD94–NKG2 genomic region. Besides the presence of genes that are orthologous to human NKG2A and NKG2F, this region contains three NKG2C paralogues. Hence, the genome of rhesus macaques contains moderately expanded and diversified NKG2 genes in addition to highly diversified KIR genes. The presence of two diversified NK cell receptor families in one species has not been described before and is expected to require a complex MHC‐dependent regulation of NK cells.
Ventricular Arrhythmia Burden in Patients With Heart Failure and Cardiac Resynchronization Devices: The Importance of Renal Function
Authors: GANESHA BABU GIRISH , WEBBER MATTHEW , PROVIDENCIA RUI , KUMAR SANJEEV , GOPALAMURUGAN AERAKONDAL , ROGERS DOMINIC P. , DAW HOLLY LOUISE , AHSAN SYED , KHAN FAKHAR , CHOW ANTHONY , LOWE MARTIN , ROWLAND EDWARD , LAMBIASE PIER , SEGAL OLIVER R.
Published: August 2016

VA Burden in Patients With HF

Background

Chronic kidney disease (CKD) is a risk factor for arrhythmias in patients with heart failure (HF). However, the effects of CKD on ventricular arrhythmia (VA) burden in patients with cardiac resynchronization therapy and defibrillator (CRT‐D) devices in a primary prevention setting are unknown.

Objective

To determine whether baseline CKD is associated with increased risk of VA in patients implanted with primary prevention CRT‐D devices.

Methods and Results

In this retrospective study, 199 consecutive primary prevention CRT‐D recipients (2005–2010) were stratified by estimated glomerular filtration rate (eGFR) levels prior to device implantation with 106 (53.2%) ≥CKD III (eGFR < 60 mL/min/1.73 m2) (CKD group). CKD group patients were significantly older (70.0 ± 10 years vs. 61.3 ± 12 years, P < 0.05) with higher prevalence of ischemic cardiomyopathy (56.2% vs. 40.2%, P < 0.05). Detected ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes resulting in device therapy occurred significantly more frequently in the CKD group [40/106(37.8%)] than controls [24/93(25.8%)], (odd ratio [OR] = 1.74, 95% confidence interval [CI] = 1.01–3.2, P = 0.05). At 5‐year follow‐up, interval censored data analysis showed 41% VT/VF incidence in the CKD group compared to 24% incidence in controls (P < 0.05). Cox proportional hazards model identified CKD > III as the only predictor of sustained VA in this group (adjusted hazard ratio [HR] 2.92, CI = 1.39–6.1, P = 0.004).

Conclusion

Baseline CKD is a strong independent risk factor for VA in primary prevention CRT‐D recipients. Further understanding of the underlying arrhythmogenic mechanisms relating to CKD may be of interest to allow appropriate correction and prevention. Device programming in this cohort may need to reflect this increased risk.
Performance of an Implantable Cardiac Monitor to Detect Atrial Fibrillation: Results of the DETECT AF Study
Authors: NÖLKER GEORG , MAYER JULIA , BOLDT LEIF‐HENDRIK , SEIDL KARLHEINZ , VAN DRIEL VINCENT , MASSA THOMAS , KOLLUM MARC , BRACHMANN JOHANNES , DENEKE THOMAS , HINDRICKS GERHARD , JUNG WERNER , BRUNNER KYLE J. , KRAUS STACIA , HÜMMER ALEXANDER , LEWALTER THORSTEN
Published: August 2016

DETECT AF Study Results

Introduction

Reliable detection and monitoring of atrial fibrillation (AF) is essential for accurate clinical decision making, which can now be done continuously with the introduction of implantable cardiac monitors (ICM) The DETECT AF study evaluated the performance of the Confirm DM2102 ICM (St. Jude Medical, St. Paul, MN, USA) to accurately detect and monitor AF.

Methods

Ninety patients previously implanted with the ICM and with either suspected or known paroxysmal AF were enrolled at 12 centers in Germany and The Netherlands. At least 2 weeks after ICM implant, patients wore a Holter monitor for 4 days, while the ICM monitored for AF episodes lasting at least 2 minutes. Holter monitor data was analyzed by a blinded, independent core laboratory and compared to the ICM AF detections. Patient and episode sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive (NPV) were calculated using standard analysis and a generalized estimation equation method where appropriate.

Results

A total of 79/90 subjects (61% male, 65.7 ± 9.6 years old) were included in the analysis, totaling 6,894 hours of Holter monitoring. Using a per patient analysis SE was 100%, PPV was 64.0%, SP was 85.7%, and NPV was 100%. Using a per episode analysis, SE was 94.0% and PPV was 64.0%. With an AF duration analysis, the SE was 83.9%, PPV was 97.3%, SP was 99.4% with an NPV of 98.5%.

Conclusion

The SJM Confirm DM2102 can accurately and repeatedly detect paroxysmal AF episodes of at least 2 minutes in length.