bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Time PCR Method for Detection of Salmonella spp. in Environmental Samples
Authors: Kasturi Kuppuswamy N. , Drgon Tomas
Published: May 2017

The methods currently used for detecting
Salmonella
in environmental samples require 2 days to produce results and have limited sensitivity. Here, we describe the development and validation of a real-time PCR
Salmonella
screening method that produces results in 18 to 24 h. Primers and probes specific to the gene
invA
, group D, and
Salmonella enterica
serovar Enteritidis organisms were designed and evaluated for inclusivity and exclusivity using a panel of 329
Salmonella
isolates representing 126 serovars and 22 non-
Salmonella
organisms. The
invA
- and group D-specific sets identified all the isolates accurately. The PCR method had 100% inclusivity and detected 1 to 2 copies of
Salmonella
DNA per reaction. Primers specific for
Salmonella
-differentiating fragment 1 (Sdf-1) in conjunction with the group D set had 100% inclusivity for 32
S
. Enteritidis isolates and 100% exclusivity for the 297 non-Enteritidis
Salmonella
isolates. Single-laboratory validation performed on 1,741 environmental samples demonstrated that the PCR method detected 55% more positives than the
V
itek
i
mmuno
d
iagnostic
a
ssay
s
ystem (VIDAS) method. The PCR results correlated well with the culture results, and the method did not report any false-negative results. The receiver operating characteristic (ROC) analysis documented excellent agreement between the results from the culture and PCR methods (area under the curve, 0.90; 95% confidence interval of 0.76 to 1.0) confirming the validity of the PCR method.

IMPORTANCE
This validated PCR method detects 55% more positives for
Salmonella
in half the time required for the reference method, VIDAS. The validated PCR method will help to strengthen public health efforts through rapid screening of
Salmonella
spp. in environmental samples.
Potential for Waterborne and Invertebrate Transmission of West Nile Virus in the Great Salt Lake, Utah
Authors: Lund Melissa , Shearn-Bochsler Valerie , Dusek Robert J. , Shivers Jan , Hofmeister Erik
Published: May 2017

In November and December of 2013, a large mortality event involving 15,000 to 20,000 eared grebes (
Podiceps nigricollis
) occurred at the Great Salt Lake (GSL), UT. The onset of the outbreak in grebes was followed by a mortality event in >86 bald eagles (
Haliaeetus leucocephalus
). During the die-off, West Nile virus (WNV) was detected by reverse transcription-PCR (RT-PCR) or viral culture in the carcasses of grebes and eagles submitted to the National Wildlife Health Center. However, no activity of mosquitoes, the primary vectors of WNV, was detected by the State of Utah's WNV monitoring program. The transmission of WNV has rarely been reported during the winter in North America in the absence of known mosquito activity; however, the size of this die-off, the habitat in which it occurred, and the species involved are unique. We experimentally investigated whether WNV could survive in water with a high salt content, as found at the GSL, and whether brine shrimp, the primary food of migrating eared grebes on the GSL, could have played a role in the transmission of WNV to feeding birds. We found that WNV can survive up to 72 h at 4°C in water containing 30 to 150 ppt NaCl, and brine shrimp incubated with WNV in 30 ppt NaCl may adsorb WNV to their cuticle and, through feeding, infect epithelial cells of their gut. Both mechanisms may have potentiated the WNV die-off in migrating eared grebes on the GSL.

IMPORTANCE
Following a major West Nile virus die-off of eared grebes and bald eagles at the Great Salt Lake (GSL), UT, in November to December 2013, this study assessed the survival of West Nile virus (WNV) in water as saline as that of the GSL and whether brine shrimp, the major food for migrating grebes, could have played a role as a vector for the virus. While mosquitoes are the major vector of WNV, under certain circumstances, transmission may occur through contaminated water and invertebrates as food.
RoxB Is a Novel Type of Rubber Oxygenase That Combines Properties of Rubber Oxygenase RoxA and Latex Clearing Protein (Lcp)
Authors: Birke Jakob , Röther Wolf , Jendrossek Dieter
Published: May 2017

Only two types of rubber oxygenases, rubber oxygenase (RoxA) and latex clearing protein (Lcp), have been described so far. RoxA proteins (RoxAs) are
c
-type cytochromes of ≈70 kDa produced by Gram-negative rubber-degrading bacteria, and they cleave polyisoprene into 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD), a C
15
oligo-isoprenoid, as the major end product. Lcps are common among Gram-positive rubber degraders and do not share amino acid sequence similarities with RoxAs. Furthermore, Lcps have much smaller molecular masses (≈40 kDa), are
b
-type cytochromes, and cleave polyisoprene to a mixture of C
20
, C
25
, C
30
, and higher oligo-isoprenoids as end products. In this article, we purified a new type of rubber oxygenase, RoxB

Xsp

(RoxB of
Xanthomonas
sp. strain 35Y). RoxB

Xsp

is distantly related to RoxAs and resembles RoxAs with respect to molecular mass (70.3 kDa for mature protein) and cofactor content (2
c
-type hemes). However, RoxB

Xsp

differs from all currently known RoxAs in having a distinctive product spectrum of C
20
, C
25
, C
30
, and higher oligo-isoprenoids that has been observed only for Lcps so far. Purified RoxB

Xsp

revealed the highest specific activity of 4.5 U/mg (at 23°C) of all currently known rubber oxygenases and exerts a synergistic effect on the efficiency of polyisoprene cleavage by RoxA

Xsp

. RoxB homologs were identified in several other Gram-negative rubber-degrading species, pointing to a prominent function of RoxB for the biodegradation of rubber in Gram-negative bacteria.

IMPORTANCE
The enzymatic cleavage of rubber (polyisoprene) is of high environmental importance given that enormous amounts of rubber waste materials are permanently released (e.g., by abrasion of tires). Research from the last decade has discovered rubber oxygenase A, RoxA, and latex clearing protein (Lcp) as being responsible for the primary enzymatic attack on the hydrophobic and water-insoluble biopolymer poly(
cis
-1,4-isoprene) in Gram-negative and Gram-positive rubber-degrading bacteria, respectively. Here, we provide evidence that a third type of rubber oxygenase is present in Gram-negative rubber-degrading species. Due to its characteristics, we suggest the designation RoxB for the new type of rubber oxygenase. Bioinformatic analysis of genome sequences indicates the presence of
roxB
homologs in other Gram-negative rubber degraders.
Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia
Authors: Hosokawa Ami , Umazume Takeshi , Yamada Takahiro , Minakami Hisanori
Published: May 2017

A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW) 28–6/7. Cardiac status was checked regularly. Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32–0/7decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased pulmonary arterial pressure, increased systemic vascular resistance (approximate 3000  dyn s/cm5) and biphasic intrarenal venous flow pattern 3.5 hours prior to childbirth at GW 32–3/7. Epigastralgia, tachycardia (160 bpm) and marked hypertension (201/111 mm Hg) occurring 2 hours after echocardiography necessitated caesarean section, with subsequent development of HELLP syndrome. Acute fluid shift from the splanchnic vasculature to central vasculature may have occurred causing HELLP syndrome as a result from vasospasm associated with sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains unclear.
A confirmed case of sugammadex-induced anaphylaxis in a UK hospital
Authors: O'Donnell Robert , Hammond Jack , Soltanifar Sam
Published: May 2017

We report the first published case of confirmed anaphylaxis to sugammadex in a UK hospital. The patient was given a bolus of sugammadex at the end of surgery. Four minutes later, he developed hypotension and a widespread erythematous rash. Multiple epinephrine boluses were administered and a continuous intravenous infusion of epinephrine commenced. The patient later reported auditory awareness, which occurred while the diagnosis of anaphylaxis was being made and initial treatment initiated. Serial serum tryptase levels were consistent with a type I hypersensitivity reaction. Skin prick and intradermal testing were performed 6 months later confirming allergy to sugammadex. This case restates the potential for hypersensitivity reactions to develop following the administration of sugammadex and makes clinicians aware that such reactions may require prolonged treatment with intravenous infusions of epinephrine. Finally, this case highlights the importance of maintaining or re-establishing anaesthesia while managing the emergent situation in order to avoid unintentional awareness.
Quadriceps strengthening with and without blood flow restriction in the treatment of patellofemoral pain: a double-blind randomised trial
Authors: Giles Lachlan , Webster Kate E , McClelland Jodie , Cook Jill L
Published: May 2017

Background

Quadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow restriction (BFR) training may provide a low-load quadriceps strengthening method to treat PFP.

Methods

Seventy-nine participants were randomly allocated to a standardised quadriceps strengthening (standard) or low-load BFR. Both groups performed 8 weeks of leg press and leg extension, the standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of 1RM. Interventions were compared using repeated-measures analysis of variance for Kujala Patellofemoral Score, Visual Analogue Scale for ‘worst pain’ and ‘pain with daily activity’, isometric knee extensor torque (Newton metre) and quadriceps muscle thickness (cm). Subgroup analyses were performed on those participants with painful resisted knee extension at 60°.

Results

Sixty-nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR group had a 93% greater reduction in pain with activities of daily living (p=0.02) than the standard group. Participants with painful resisted knee extension (n=39) had greater increases in knee extensor torque with BFR than standard (p<0.01). No between-group differences were found for change in Kujala Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07) or quadriceps thickness (p=0.2). No difference was found between interventions at 6 months.

Conclusion

Compared with standard quadriceps strengthening, low load with BFR produced greater reduction in pain with daily living at 8 weeks in people with PFP. Improvements were similar between groups in worst pain and Kujala score. The subgroup with painful resisted knee extension had larger improvements in quadriceps strength from BFR.

Trial registration number

12614001164684.
Exercise therapy for functional capacity in chronic diseases: an overview of meta-analyses of randomised controlled trials
Authors: Pasanen Tero , Tolvanen Samppa , Heinonen Ari , Kujala Urho M
Published: May 2017

Objective

To summarise all meta-analyses of randomised controlled trials that have evaluated the effects of exercise therapy on functional capacity in patients with chronic diseases.

Design

Umbrella review of meta-analyses of randomised controlled trials.

Data sources

We systematically searched the CENTRAL, CINAHL, DARE, Medline, OTSeeker, PEDro, SPORTDiscus, ProQuest Nursing & Allied Health Database, Web of Science, Scopus, OpenGrey and BMC Proceedings from database inception to 1 September 2016.

Eligibility criteria for selecting studies

We included meta-analyses that compared the effects of exercise therapy with no treatment or usual care in adults with non-communicable chronic diseases and included outcomes related to functional capacity. We excluded meta-analyses with less than 100 patients.

Results

Eighty-five meta-analyses with 22 different chronic diseases were included. The exercise interventions resulted in statistically significant (p<0.05) improvements for 126 of 146 (86%) functional capacity outcomes, compared with the control group. The standardised mean differences were small in 64 (44%), moderate in 54 (37%) and large in 28 (19%) of the 146 functional capacity outcomes. The results were similar for aerobic exercise, resistance training, and aerobic and resistance training combined. There were no significant differences in serious adverse effects between the intervention and control groups in any of the meta-analyses.

Conclusion

Exercise therapy appears to be a safe way to improve functional capacity and reduce disability in individuals with chronic disease.
Proper Electronic Order Linkage of Electrocardiograms at a Large Children's Hospital Improves Reporting and Revenue
Authors: Spar David S , Mays Wayne A , Cooper David S , Sullivan Lucille , Hicks Terra , B Anderson Jeffrey
Published: May 2017

Electrocardiograms (ECGs) are performed to determine an individual's cardiac rhythm. Approximately 25,000 ECGs are performed yearly throughout our hospital system. Historically only 68% of all ECGs were performed with the proper order linked to the electronic ECG reading system (MUSE). Failure to link the orders to the electronic reading system leads to problems in patient safety, reporting and hospital revenue.

Our aim was to increase the percentage of linked ECG orders in MUSE compared to total ECGs performed from 68% to 95%.

We created a detailed process map of ECG order linking to the MUSE electronic system. FMEA and Pareto chart creation were used to determine etiology of process failures. Multiple interventions (LOR1 to LOR3) were implemented utilizing the PDSA technique. Process control charts were used to evaluate change.

FMEA and Pareto chart determined most common failures were related to: 1) ECG order not electronically acquired properly, 2) duplicate ECGs and 3) ECG order was not electronically placed. We performed multiple interventions including: 1) ECG performance education, 2) created reminders on the ECG machines, 3) specialized electronic linking system for physician readers and 4) bar-code scanners for all ECG machines. These changes improved ECG order linking to MUSE from 68% to 95% over 6-months. In direct comparison between fiscal year (FY) FY2014 to FY2015, the number of ECGs performed increased 2% while billing increased by 23%.

Utilization of quality improvement methodology allowed us to identify failures for ECG order linking. We established multiple successful interventions amongst different hospital locations and improved our compliance, billing and reporting of ECGs.
Sound: a non-invasive measure of cough intensity
Authors: Lee Kai K , Matos Sergio , Ward Katie , Rafferty Gerrard F , Moxham John , Evans David H , Birring Surinder S
Published: May 2017

Introduction

Cough intensity is an important determinant of cough severity reported by patients. Cough sound analysis has been widely validated for the measurement of cough frequency but few studies have validated its use in the assessment of cough strength. We investigated the relationship between cough sound and physiological measures of cough strength.

Methods

32 patients with chronic cough and controls underwent contemporaneous measurements of voluntary cough sound, flow and oesophageal pressure. Sound power, peak energy, rise-time, duration, peak-frequency, bandwidth and centroid-frequency were assessed and compared with physiological measures. The relationship between sound and subjective cough strength Visual Analogue Score (VAS), the repeatability of cough sounds and the effect of microphone position were also assessed.

Results

Sound power and energy correlated strongly with cough flow (median Spearman’s r=0.87–0.88) and oesophageal pressure (median Spearman’s r=0.89). Sound power and energy correlated strongly with cough strength VAS (median Spearman’s r=0.84–0.86) and were highly repeatable (intraclass correlation coefficient=0.93–0.94) but both were affected by change in microphone position.

Conclusions

Cough sound power and energy correlate strongly with physiological measures and subjective perception of cough strength. Power and energy are highly repeatable measures but the microphone position should be standardised. Our findings support the use of cough sound as an index of cough strength.
Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial
Authors: Body Richard , Boachie Charles , McConnachie Alex , Carley Simon , Van Den Berg Patricia , Lecky Fiona E
Published: May 2017

Background

Observational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively ‘rule out’ and ‘rule in’ acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible.

Methods

Patients presenting to two EDs with suspected cardiac chest pain were randomised to receive care guided by the MACS decision rule (intervention group) or standard care (controls). The primary efficacy outcome was a successful discharge from the ED, defined as a decision to discharge within 4 hours of arrival providing that the patient did not have a missed acute myocardial infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or coronary revascularisation) within 30 days. Feasibility outcomes included recruitment and attrition rates.

Results

In total, 138 patients were included between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%) had incident MACE within 30 days. All 131 patients completed 30-day follow-up and were included in the final analysis with no missing data for the primary analyses. Compared with standard care, a significantly greater proportion of patients whose care was guided by the MACS rule were successfully discharged within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No patients in either group who were discharged within 4 hours had a diagnosis of AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention group).

Conclusions

In this pilot trial, use of the MACS rule led to a significant increase in safe discharges from the ED but a larger, fully powered trial remains necessary. Our findings seem to support the feasibility of that trial.

Trial registration number

ISRCTN 86818215.

Research Ethics Committee reference

13/NW/0081.

UKCRN registration ID

14334.
Closing the theory to practice gap for newly qualified doctors: evaluation of a peer-delivered practical skills training course for newly qualified doctors in preparation for clinical practice
Authors: Beane A , Padeniya A , De Silva A P , Stephens T , De Alwis S , Mahipala P G , Sigera P C , Munasinghe S , Weeratunga P , Ranasinghe D , Deshani E M , Weerasinghe T , Thilakasiri K , Jayasinghe K A S , Dondorp A M , Haniffa R
Published: May 2017

Purpose

The Good Intern Programme (GIP) in Sri Lanka has been implemented to bridge the ’theory to practice gap’ of doctors preparing for their internship. This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills Training (ACST) course as part of the GIP.

Study design

The ACST course was developed by an interprofessional faculty, including newly graduated doctors awaiting internship (pre-intern), focusing on the recognition and management of common medical and surgical emergencies. Course delivery was entirely by pre-intern doctors to their peers. Knowledge was evaluated by a pre- and post-course multiple choice test. Participants’ confidence (post-course) and 12 acute care skills (pre- and post-course) were assessed using Likert scale-based questions. A subset of participants provided feedback on the peer learning experience.

Results

Seventeen courses were delivered by a faculty consisting of eight peer trainers over 4 months, training 320 participants. The mean (SD) multiple choice questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post-course (p<0.05). Increased overall confidence in managing ward emergencies was reported by 97.2% (n=283) of respondents. Participants rated their post-course skills to be significantly higher (p<0.05) than pre-course in all 12 assessed skills. Extended feedback on the peer learning experience was overwhelmingly positive and 96.5% would recommend the course to a colleague.

Conclusions

A peer-delivered ACST course was extremely well received and can improve newly qualified medical graduates’ knowledge, skills and confidence in managing medical and surgical emergencies. This peer-based model may have utility beyond pre-interns and beyond Sri Lanka.
A brief introduction to the use of X-ray computed tomography (CT) for analysis of natural deformation structures in reservoir rocks
Authors: Wennberg Ole Petter , Rennan Lars
Published: May 2017

X-ray computed tomography (CT) is frequently used for non-destructive imaging and analysis of internal features in rock samples. In this paper we review the method for analysis of subseismic deformation structures in reservoir rocks, and provide some examples of different types of structures. Both medical CT and high-resolution µCT have great potential for identification of small-scale deformation structures in reservoir rocks and samples from outcrop analogues. The CT imaging techniques provide 3D data that are used in combination with 2D information from core or outcrop, thin-section and scanning electron microscopy (SEM). CT and µCT are used for quantitative and qualitative analysis of individual fractures and fracture networks, and for imaging and analysis of internal heterogeneities of fault rocks and deformation bands. The benefit of CT is that 3D properties (e.g. structure size, connectivity and variation in aperture) are actually characterized in 3D, contrary to traditional 2D methods using core surface, thin-section and outcrop. Limitations and uncertainties arise from artefacts during acquisition and processing, scale of observation and resolution, and manual steps involved in the segmentation of the CT volume. Increased availability of medical CT and µCT scanners and improved resolution should in the future lead to improved description and modelling of small-scale reservoir structures.
β-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma
Authors: Savvidou Ioanna , Khong Tiffany , Cuddihy Andrew , McLean Catriona , Horrigan Stephen , Spencer Andrew
Published: May 2017

Currently available treatment options are unlikely to be curative for the majority of multiple myeloma patients, emphasizing a continuing role for the introduction of investigational agents that can overcome drug resistance. The canonical Wnt/β-catenin signaling pathway, essential for self-renewal, growth, and survival, has been found to be dysregulated in multiple myeloma, particularly in advanced stages of disease. This provides the rationale for evaluating the novel β-catenin inhibitor BC2059 as monotherapy and in combination with proteasome inhibitors in vitro and in vivo. Here, we show nuclear localization of β-catenin in human myeloma cell lines (HMCL), consistent with activation of the canonical Wnt pathway. BC2059 attenuates β-catenin levels, in both the cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF complex and the expression of its target gene axin 2. Treatment of HMCL with BC2059 inhibits proliferation and induces apoptosis in a dose-dependent manner. This is also observed in HMCL–stromal cell cocultures, mitigating the protective effect afforded by the stroma. Similarly, BC2059 induces apoptosis in primary multiple myeloma samples in vitro, causing minimal apoptosis on healthy peripheral blood mononuclear cells. Furthermore, it synergizes with the proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor growth and prolongs survival with minor on-target side effects. Collectively, these results demonstrate the efficacy of targeting the Wnt/β-catenin pathway with BC2059 both in vitro and in vivo, at clinically achievable doses. These findings support further clinical evaluation of BC2059 for the treatment of multiple myeloma. Mol Cancer Ther; 16(9); 1765–78. ©2017 AACR.
Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non–Small Cell Lung Cancer Cells
Authors: Ross Kayleigh C. , Andrews Andrew J. , Marion Christopher D. , Yen Timothy J. , Bhattacharjee Vikram
Published: May 2017

Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFi). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization. Using the DNA-damaging drug gemcitabine, we show that gemcitabine pretreatment sensitized resistant melanoma cells to BRAFis vemurafenib and dabrafenib. We extended our findings to BRAF WT tumor cell lines that are intrinsically resistant to vemurafenib and dabrafenib. Pretreatment of pancreatic cancer and non–small cell lung cancer cell lines with sublethal doses of 50 and 5 nmol/L of gemcitabine, respectively, enhanced killing by both vemurafenib and dabrafenib. The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. Mol Cancer Ther; 16(8); 1596–609. ©2017 AACR.
NKG2D Ligand–Targeted Bispecific T-Cell Engagers Lead to Robust Antitumor Activity against Diverse Human Tumors
Authors: Godbersen Claire , Coupet Tiffany A. , Huehls Amelia M. , Zhang Tong , Battles Michael B. , Fisher Jan L. , Ernstoff Marc S. , Sentman Charles L.
Published: May 2017

Two new bispecific T-cell engaging (BiTE) molecules with specificity for NKG2D ligands were developed and functionally characterized. One, huNKG2D-OKT3, was derived from the extracellular portion of the human NKG2D receptor fused to a CD3ϵ binding single-chain variable fragment (scFv), known as OKT3. NKG2D has multiple ligands, including MICA, which are expressed by a variety of malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE format that targets MICA on tumor cells and CD3ϵ on human T cells. Both BiTEs specifically activated T cells to kill human tumor cell lines. Cytotoxicity by B2-OKT3, but not huNKG2D-OKT3, is blocked by soluble rMICA. The huNKG2D-OKT3 induced greater T-cell cytokine production in comparison with B2-OKT3. No T-cell pretreatment was required for IFNγ production upon coculture of B2-OKT3 or huNKG2D-OKT3 with T cells and target cells. The effector memory T-cell compartment was the primary source of IFNγ, and culture of T cells and these BiTEs with plate-bound rMICA showed ligand density–dependent production of IFNγ from both CD4+ and CD8+ T cells. There was 2-fold more IFNγ produced per CD8+ T cell and 5-fold greater percentage of CD8+ T cells producing IFNγ compared with CD4+ T cells. In addition, both BiTEs elicited significant antitumor responses against human metastatic melanoma tumor samples using autologous or healthy donor T cells. These data demonstrate the robust antitumor activity of these NKG2D ligand–binding bispecific proteins and support their further development for clinical use. Mol Cancer Ther; 16(7); 1335–46. ©2017 AACR.
Dual Antiplatelet Therapy Continuation Beyond 1 Year After Drug-Eluting Stents
Authors: Ferrante Giuseppe , Condorelli Gianluigi , Pagnotta Paolo , Reimers Bernhard
Published: May 2017

Background—

The benefits and harms of dual antiplatelet therapy (DAPT) continuation beyond 1 year after drug-eluting stent implantation as compared with 1-year DAPT remain controversial.

Methods and Results—

We searched for randomized trials that compared longer than 1-year DAPT versus 1-year DAPT after drug-eluting stenting. A meta-analysis was performed by using standard frequentist and random-effects Bayesian approaches. Four trials comprising 17 650 participants were included. Compared with 1-year DAPT, extended DAPT did not affect all-cause mortality (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.79–1.5;
P
=0.53) or cardiovascular mortality (OR, 1.03; 95% CI, 0.72–1.46;
P
=0.88). Extended DAPT was associated with a reduction in the risk of myocardial infarction (OR, 0.56; 95% CI, 0.43–0.73;
P
<0.001), nonsignificant reductions of stent thrombosis (OR, 0.46; 95% CI, 0.16–1.27;
P
=0.13), similar risk of stroke (OR, 0.91; 95% CI, 0.65–1.26;
P
=0.56), and an increased risk of major bleeding (OR, 1.49; 95% CI, 1.06–2.11;
P
=0.02). By using Bayesian meta-analysis, we found moderate evidence of a reduction of myocardial infarction (OR, 0.62; 95% credible intervals, 0.39–1.05) and weak evidence of an increase in major bleeding (OR, 1.66; 95% credible intervals, 0.89–3.09) associated with extended DAPT.

Conclusions—

In this meta-analysis, extended DAPT beyond 1 year prevented myocardial infarctions and increased major bleedings, but the strength of evidence for these effects was not strong. DAPT continuation beyond 1 year showed no effects on mortality.
High- Versus Low-Gradient Severe Aortic Stenosis
Authors: Taniguchi Tomohiko , Morimoto Takeshi , Shiomi Hiroki , Ando Kenji , Kanamori Norio , Murata Koichiro , Kitai Takeshi , Kawase Yuichi , Izumi Chisato , Miyake Makoto , Mitsuoka Hirokazu , Kato Masashi , Hirano Yutaka , Matsuda Shintaro , Inada Tsukasa , Nagao Kazuya , Murakami Tomoyuki , Takeuchi Yasuyo , Yamane Keiichiro , Toyofuku Mamoru , Ishii Mitsuru , Minamino-Muta Eri , Kato Takao , Inoko Moriaki , Ikeda Tomoyuki , Komasa Akihiro , Ishii Katsuhisa , Hotta Kozo , Higashitani Nobuya , Kato Yoshihiro , Inuzuka Yasutaka , Maeda Chiyo , Jinnai Toshikazu , Morikami Yuko , Saito Naritatsu , Minatoya Kenji , Kimura Takeshi
Published: May 2017

Background—

There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm
2
with peak aortic jet velocity ≤4.0 m/s, and mean aortic pressure gradient ≤40 mm Hg.

Methods and Results—

In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score–matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve–related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25–0.37;
P
<0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32–0.67;
P
<0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23–0.59;
P
<0.001).

Conclusions—

The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp/ctr/index.htm
. Unique identifier: UMIN000012140.
Thirty-Year Mortality After Coronary Artery Bypass Graft Surgery
Authors: Adelborg Kasper , Horváth-Puhó Erzsébet , Schmidt Morten , Munch Troels , Pedersen Lars , Nielsen Per Hostrup , Bøtker Hans Erik , Toft Sørensen Henrik
Published: May 2017

Background—

Data are sparse on long-term mortality after coronary artery bypass graft (CABG) surgery. We examined short-term and long-term mortality of patients undergoing CABG surgery and a general population comparison cohort.

Methods and Results—

Linking data from Danish registries, we conducted a nationwide, population-based cohort study on 51 307 CABG patients and 513 070 individuals from the general population matched on age, sex, and calendar year (1980–2009). The mortality risk was higher in patients having isolated CABG surgery than in the general population, particularly during 0 to 30 days (3.2% versus 0.2%), 11 to 20 years (51.1% versus 35.6%), and 21 to 30 years (62.4% versus 44.8%), but not substantially higher during 31 to 364 days (2.9% versus 2.4%) or 1 to 10 years (30.7% versus 25.8%). The 30-day adjusted mortality rate ratio for isolated CABG surgery was 13.51 (95% confidence interval [CI], 12.59–14.49). Between 31 to 364 days and 1 to 10 years, the isolated CABG surgery cohort had a slightly higher mortality rate than the general population comparison cohort, adjusted mortality rate ratios of 1.15 (95% CI, 1.09–1.21) and 1.09 (95% CI, 1.08–1.11), respectively. Between 11 to 20 years and 21 to 30 years, the adjusted mortality rate ratios were 1.62 (95% CI, 1.58–1.66) and 1.76 (95% CI, 1.62–1.91). Within 30 days, CABG patients had a 25-fold, a 26-fold, and a 18-fold higher risk of dying from myocardial infarction, heart failure, or stroke, respectively, than members of the general population comparison cohort. We found substantial heterogeneity in absolute mortality rates according to baseline risk groups.

Conclusions—

The isolated CABG cohort had a higher mortality rate than the general population comparison cohort, especially within 30 days of and 10 years after surgery.
Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus
Authors: Dale Caroline E. , Fatemifar Ghazaleh , Palmer Tom M. , White Jon , Prieto-Merino David , Zabaneh Delilah , Engmann Jorgen E.L. , Shah Tina , Wong Andrew , Warren Helen R. , McLachlan Stela , Trompet Stella , Moldovan Max , Morris Richard W. , Sofat Reecha , Kumari Meena , Hyppönen Elina , Jefferis Barbara J. , Gaunt Tom R. , Ben-Shlomo Yoav , Zhou Ang , Gentry-Maharaj Aleksandra , Ryan Andy , Mutsert Renée de , Noordam Raymond , Caulfield Mark J. , Jukema J. Wouter , Worrall Bradford B. , Munroe Patricia B. , Menon Usha , Power Chris , Kuh Diana , Lawlor Debbie A. , Humphries Steve E. , Mook-Kanamori Dennis O. , Sattar Naveed , Kivimaki Mika , Price Jacqueline F. , Davey Smith George , Dudbridge Frank , Hingorani Aroon D. , Holmes Michael V. , Casas Juan P.
Published: May 2017

Background:

The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease.

Methods:

Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.

Results:

Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28–1.71), similar to findings for BMI (1 SD≈4.6 kg/m
2
; OR for CHD, 1.36; 95% CI, 1.22–1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03–1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38–2.42) and OR, 1.98 (95% CI, 1.41–2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%–77% per 1 SD).

Conclusions:

Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
Self-extubation Laryngeal Injuries at an Academic Tertiary Care Center: A Retrospective Pilot Study
Authors: Cohn Jason E. , Touati Andrew , Lentner Mark , Weitzel Mark , Fisher Casey , Sataloff Robert T.
Published: May 2017

Objectives:

The purpose of this study is to identify laryngeal symptoms and injuries in self-extubated patients.

Methods:

A retrospective chart review was conducted to identify symptoms and clinical findings associated with self-extubation. A novel scoring system was developed and used to quantify these findings. Symptom score included all symptoms that patients reported after self-extubation. Clinical score consisted of laryngeal findings visualized on nasopharyngeal laryngoscopy. Finally, a total self-extubation score was calculated as the sum of the symptom and clinical scores. Additionally, duration of intubation and endotracheal tube size were correlated with these scores.

Results:

Sixty (n = 60) patients who self-extubated in our institution’s intensive care unit were identified. Average calculated symptom, clinical, and total self-extubation scores were 0.92, 1.43, and 2.35, respectively. The most common symptom observed was hoarseness (62%), while the most common clinical finding was posterior laryngeal edema (58%). A significant positive correlation was found between duration of intubation and both symptom score and total self-extubation score (r = 0.314, P = .008 and r = 0.223, P = .05, respectively). Symptom score predicted clinical score with a significant positive correlation present (r = 0.278, P = .02).

Conclusions:

This study demonstrates that the majority of self-extubated patients have laryngeal symptoms and clinical findings. A comprehensive, multidisciplinary evaluation is warranted for self-extubations.
Near net shape manufacturing of metal: A review of approaches and their evolutions
Authors: Marini Daniele , Cunningham David , Corney Jonathan R
Published: May 2017

In the last 30 years, the concept of manufacturability has been applied to many different processes in numerous industries. This has resulted in the emergence of several different “Design for Manufacturing” methodologies which have in common the aim of reducing productions costs through the application of general manufacturing rules. Near net shape technologies have expanded these concepts, targeting mainly primary shaping process, such as casting and forging. The desired outcomes of manufacturability analysis for near net shape processes are cost and lead/time reduction through minimization of process steps (in particular cutting and finishing operations) and raw material saving. Product quality improvement, variability reduction and component design functionality enhancement are also achievable through near net shape optimization. Process parameters, product design and material selection are the changing variables in a manufacturing chain that interact in complex, non-linear ways. Consequently, modeling and simulation play important roles in the investigation of alternative approaches. However, defining the manufacturing capability of different processes is also a “moving target” because the various near net shape technologies are constantly improving and evolving so there is challenge in accurately reflecting their requirements and capabilities. In the last decade, for example, computer-aided design, computer numerical control technologies and innovation in materials have impacted enormously on the development of near net shape technologies. This article reviews the different methods reported for near net shape manufacturability assessment and examines how they can make an impact on cost, quality and process variability in the context of a specific production volume. The discussion identifies a lack of structured approaches, poor connection with process optimization methodologies and a lack of empirical models as gaps in the reported approaches.
Evaluation of multiaxial fatigue life prediction criteria for Ni-based superalloy GH4169
Authors: Wu ZR , Li X , Fang L , Song YD
Published: May 2017

Fatigue tests under multiaxial loading were conducted on Ni-based superalloy GH4169 tubular specimens. The microstructures of fracture surfaces under different loading paths were compared. Several multiaxial fatigue criteria were reviewed and evaluated with multiaxial fatigue test data. The criteria of equivalent strain, maximum shear strain and Kandil–Brown–Miller provided unsatisfactory results for GH4169. Fatemi–Socie and Wu–Hu–Song parameters showed better life prediction abilities for this material. Minor modification has been introduced in Wu–Hu–Song parameter. The material constants of modified Wu–Hu–Song criterion are only dependent on torsional fatigue tests. The satisfactory prediction results based on modified Wu–Hu–Song model were obtained for GH4169.
A simple analytical bending stress model of parabolic leaf spring
Authors: Atig Akram , Ben Sghaier Rabii , Seddik Raoudha , Fathallah Raouf
Published: May 2017

The evaluation of stress distribution, produced by vertical loading along a parabolic leaf spring, presents an essential aspect during the design stage. Commonly, designers utilize the finite element analysis to simulate the stress behaviour of a parabolic leaf spring. Nevertheless, the use of such method is a time-consuming process during the deterministic and the reliability-based fatigue design optimisation. In this study, we propose three analytical models describing the bending stress distribution of a simply supported single asymmetric parabolic leaf spring: (i) an initially curved single asymmetric parabolic leaf spring, subjected to a concentrated load; (ii) a straight single asymmetric parabolic leaf spring, subjected to a uniform load and (iii) an initially curved single asymmetric parabolic leaf spring, subjected to a uniform load. Bending stress distribution results of classical, finite element and proposed models are compared for several case studies. It is observed that the third model is the most precise model compared to the finite element analysis of single asymmetric parabolic leaf spring. Therefore, the suggested model can be used to generate fatigue life diagram that predicts the required mean and alternating load values for a desired fatigue life with an acceptable accuracy and a reduced computational time.
Facilitating Team Reflexivity About Communication
Authors: Hedman-Phillips Eerika , Barge J. Kevin
Published: May 2017

This article explores how team facilitation can promote team reflexivity about communication. We present a case study that was conducted within a participatory action research framework with a Top Management Team for an international manufacturing company. We identify and analyze five key interventions that promoted team reflexivity. These interventions included activities such as (a) framing the facilitation, (b) inquiring into the key issues, (c) role modeling feedback, (d) positive storytelling, and (e) reflecting on concrete communication actions. The findings suggest that reflexivity can be enhanced through positive storytelling and emotion, framing and contextual sensitivity, and addressing interactional challenges within the team. The study complements previous reflexivity research by articulating how self-awareness about a team’s communication shapes the meaning making patterns and action potential of teams as well as how reflexivity is performed in action.
The Call of a Different Drummer: A Conversation With Lyndal Bullock
Authors: Zabel Robert , Kaff Marilyn , Teagarden Jim
Published: May 2017

Lyndal Bullock’s career has focused on children and youth with significant behavior and emotional challenges. His career has spanned experiences as a teacher, counselor, and university professor. Dr. Bullock has twice served as president of the Council of Exceptional Children (CEC). His leadership and mentorship have been recognized by many professional groups and individuals. Dr. Bullock shares his thoughts and reflections on a career marked by the call of a different drummer.
Motivation gains on divisible conjunctive group tasks
Authors: Larson James R. , Bihary Joseph G. , Egan Amanda C.
Published: May 2017

Two studies examined the effort that participants expended on a challenging physical persistence activity when that activity was a critical part of a divisible conjunctive task performed by two people working as a team compared to when it was structured as an individual task performed by one person working alone. It was found that participants put greater effort into that activity when they worked as part of a team task compared to when they worked alone—a motivation gain when working in groups. This gain occurred despite the absence of any apparent task-related ability differences among participants, and is most parsimoniously explained by the greater indispensability associated with working on a critical element of a divisible conjunctive group task. The implications of these results for the occurrence of motivation gains on other types of tasks and in real-world work settings are discussed.