bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of leucocytes cell population data in the early detection of sepsis
Authors: Urrechaga Eloísa , Bóveda Oihane , Aguirre Urko
Published: August 2017

Aims

The cell population data (CPD) parameters reported by XN analyser (Sysmex, Kobe, Japan) reflect the size and internal structure of leucocytes. We aimed to assess the clinical utility of these parameters as biomarkers for the early diagnosis of sepsis.

Methods

The study group (G1) included 586 controls (no quantitative or morphological alterations in the complete blood count) and 137 patients diagnosed with sepsis. The reliability of the model was evaluated using a validation group (G2) of 212 controls and 60 patients with sepsis. The optimal cut-off for the diagnosis of sepsis and the OR for CPD were established using a univariate logistic regression. A multivariate logistic regression model was then created. The OR and area under the curve were recorded. A risk stratification scale (neutrophils and monocytes (NEMO)) for diagnosing sepsis was established on the basis of the coefficients of the multivariate model.

Results

MO-X and neutrophils fluorescence intensity (NE-SFL) were found to be the most relevant of the CPD in predicting sepsis applying multivariate analysis to G1.NEMO score was composed using the above-mentioned CPD and subsequently stratified into three risk groups: mild (≤3), moderate (4≤NEMO≤5) and high (≥6). The OR for patients with a score of 4–5 was 10 and 249 for a score of ≥6. When applied to G2, the positive predictive value was 84.8 % and the negative predictive value was 96.0%.

Conclusions

CPD are potentially useful for the early diagnosis of sepsis. Their values were used to compose in NEMO score can help in rapid and reliable decision making.
Comparison of karyotyping,TCL1fluorescence in situ hybridisation and TCL1 immunohistochemistry in T cell prolymphocytic leukaemia
Authors: Sun Yi , Tang Guilin , Hu Zhihong , Thakral Beenu , Miranda Roberto N , Medeiros L Jeffrey , Wang Sa A
Published: August 2017

Aims

T cell prolymphocytic leukaemia (T-PLL) is defined as an aggressive T cell leukaemia composed of small to medium-sized lymphocytes with a mature T cell immunophenotype. Most of these cases are known to be associated with inv(14q11q32)/t(14;14)(q11;q32) or rarely t(X;14)(q28;q11). However, T-PLL can show variations in clinical presentation, morphology or immunophenotype that can make a diagnosis of T-PLL challenging. We aim to explore the value of ancillary testing in the diagnosis of T-PLL.

Methods

With this large cohort of 69 patients with T-PLL, we compared the diagnostic utility of conventional cytogenetics,TCL1rearrangement by fluorescence in situ hybridisation (FISH) and TCL1 expression by immunohistochemistry (IHC).

Results

Conventional karyotyping was performed in all 69 patients and was abnormal in 44 (65%), showing 14q32 abnormalities in 31 (43%) and t(X;14) (MTCP) in 2 (3%).TCL1rearrangement was assessed by FISH in 26 cases and was positive in 23 (85%). All cases with 14q32 abnormalities shown by karyotype were positive forTCL1rearrangement by FISH, whereas 12/15 (80%) cases without 14q32 abnormalities were also positive. TCL1 overexpression by IHC was detected in 51/64 (81%), including 40/42 (95%) cases withTCL1/14q32 rearrangement, and 3 cases without, showing a concordance of 89%. TCL1 IHC was negative in both cases with t(X;14)(q28;q11).

Conclusions

Our study shows that TCL1 by IHC is a convenient test, positive in >80% T-PLL. Conventional cytogenetics is insensitive in the detection of 14q32/TCL1rearrangements but provides more complete information of the chromosomal landscape of T-PLL. FISH forTCL1rearrangement is very valuable in diagnostic challenging cases.
Ethical behaviour of physicians and psychologists: similarities and differences
Authors: Ferencz Kaddari Michall , Koslowsky Meni , Weingarten Michael A
Published: August 2017

Objective

To compare the coping patterns of physicians and clinical psychologists when confronted with clinical ethical dilemmas and to explore consistency across different dilemmas.

Population

88 clinical psychologists and 149 family physicians in Israel.

Method

Six dilemmas representing different ethical domains were selected from the literature. Vignettes were composed for each dilemma, and seven possible behavioural responses for each were proposed, scaled from most to least ethical. The vignettes were presented to both family physicians and clinical psychologists.

Results

Psychologists’ aggregated mean ethical intention score, as compared with the physicians, was found to be significantly higher (F(6, 232)=22.44, p<0.001, η2=0.37). Psychologists showed higher ethical intent for two dilemmas: issues of payment (they would continue treating a non-paying patient while physicians would not) and dual relationships (they would avoid treating the son of a colleague). In the other four vignettes, psychologists and physicians responded in much the same way. The highest ethical intent scores for both psychologists and physicians were for confidentiality and a colleague’s inappropriate practice due to personal problems.

Conclusions

Responses to the dilemmas by physicians and psychologists can be categorised into two groups: (1) similar behaviours on the part of both professions when confronting dilemmas concerning confidentiality, inappropriate practice due to personal problems, improper professional conduct and academic issues and (2) different behaviours when confronting either payment issues or dual relationships.
Frontline ADAPT therapy to treat patients with symptomatic M2 and M3 occlusions in acute ischemic stroke: initial experience with the Penumbra ACE and 3MAX reperfusion system
Authors: Altenbernd Jens , Kuhnt Oliver , Hennigs Svenja , Hilker Ruediger , Loehr Christian
Published: August 2017

Background

After a series of positive studies for mechanical thrombectomy in large vessel occlusion acute ischemic stroke, the question remains, can symptomatic patients with distal vessel occlusion benefit from mechanical thrombectomy?

Purpose

To assess the safety and efficacy of the 3MAX reperfusion system as frontline therapy for M2 and M3 occlusions.

Methods

This study retrospectively collected data on 58 patients treated for M2 and M3 occlusions between January and September 2016. Of these 58 patients, 31 had an isolated M2 or M3 occlusion. Eligible patients were treated with 3MAX by adirect first pass aspiration (ADAPT) technique within 6 hours following stroke onset. Effectiveness was defined by functional independence (90-day modified Rankin Scale core 0–2) and revascularization to modified Thrombolysis in Cerebral Infarction (mTICI) 2b–3 scores adjudicated by a core laboratory, while complication rates were used to determine safety of the device and the procedure.

Results

Patients with an isolated M2 or M3 occlusion had a mean age of 68.6±13.3 years (range 18–90 years), a median National Institutes of Health Stroke Score of 15 (IQR 9–19), and ASPECTS score of 9 (IQR 8–10). After intervention, 100% (31/31) of patients were revascularized to mTICI 2b–3; 77.4% (24/31) of patients showed revascularization to mTICI 3. Aspiration alone led to revascularization in 83.9% (26/31) of patients. At 90 days, 96.8% (30/31) of patients had achieved functional independence. The incidence of symptomatic intracranial hemorrhage was 0% (0/31).

Conclusions

Results suggest that the 3MAX reperfusion system is safe and effective in achieving successful revascularization and functional independence for patients with acute ischemic stroke secondary to M2 and M3 occlusions using ADAPT, either as frontline monotherapy, or in combination with adjunctive devices.
Current applications and future perspectives of robotics in cerebrovascular and endovascular neurosurgery
Authors: Menaker Simon A , Shah Sumedh S , Snelling Brian M , Sur Samir , Starke Robert M , Peterson Eric C
Published: August 2017

Advances in robotic medicine have been adopted by various surgical subspecialties as the benefits of this technology become more readily apparent: precision in narrow operative windows, tremor controlled movements, and modestly improved outcomes, among others. Vascular neurosurgery, in particular, remains open to newer and more cutting edge treatment options for complex pathologies, and robotics may be on the horizon for such advances. We seek to provide a broad overview of these innovations in vascular neurosurgery for both practitioners well acquainted with robotics and those seeking to become more familiar. Technologies under development for cerebrovascular and endovascular neurosurgery include robot assisted angiography, guided operative microscopes, coil insertion systems, and endoscopic clipping devices. Additionally, robotic systems in the fields of interventional cardiology and radiology have potential applications to endovascular neurosurgery but require proper modifications to navigate complex intracerebral vasculature. Robotic technology is not without drawbacks, as broad implementation may lead to increased cost, training time, and potential delays in emergency situations. Further cultivation of current multidisciplinary technologies and investment into newer systems is necessary before robotics can make a sizable impact in clinical practice.
Angiographic and clinical outcomes of balloon remodeling versus unassisted coil embolization in the ruptured aneurysm cohort of the GEL THE NEC study
Authors: Dabus Guilherme , Brinjikji Waleed , Amar Arun P , Delgado Almandoz Josser E , Diaz Orlando M , Jabbour Pascal , Hanel Ricardo , Hui Ferdinand , Kelly Michael , Layton Kennith F , Miller Jeffrey W , Levy Elad I , Moran Christopher J , Suh Dae Chul , Woo Henry , Sellar Robbin , Hoh Brian , Evans Avery , Kallmes David F
Published: August 2017

Background and purpose

GEL THE NEC (GTN) was a multicenter prospective registry developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We compared the angiographic and clinical outcomes of aneurysms treated with balloon assisted coil embolization (BACE) versus unassisted coil embolization (CE) in the ruptured aneurysm cohort.

Materials and methods

GTN was performed at 27 centers in five countries. Patients aged 21–90 years with a ruptured aneurysm 3–15 mm in size were eligible for enrollment. We analyzed demographics/comorbidities, aneurysm location, and geometry, including maximum diameter, neck size, and dome to neck ratio, immediate and long term angiographic outcomes (graded by an independent core laboratory using the modified Raymond Scale), and procedure related adverse events. Angiographic and clinical outcomes were studied using χ2and t tests.

Results

Of the 599 patients in the GTN, 194 met the inclusion criteria. 84 were treated with BACE and 110 with CE. There were more prior smokers in the BACE group (p=0.01). The BACE group also had more vertebrobasilar aneurysms (p=0.006) and a larger mean neck size (p=0.02). More aneurysms were immediately completely occluded in the BACE group (p=0.02) Procedure- related major morbidity and mortality were no different between the techniques (p=0.4 and p=1, respectively).

Conclusions

In this prospective ruptured aneurysm cohort from the GTN, BACE resulted in greater occlusion rates compared with unassisted CE with similar morbi-mortality.
Increasing water temperatures exacerbate the potential for density dependence in juvenile steelhead
Authors: Myrvold Knut Marius , Kennedy Brian Patrick
Published: August 2017

We studied the potential effects of predicted climate change on the energetic demands of juvenile steelhead (Oncorhynchus mykiss) and their consequences for local population size and structure in Idaho, USA. Projected increases in water temperature incurred on average a 10% higher energetic cost by 2040 (range 7.0%–12.5% among study reaches in the watershed) and a 16% increase (range 8.5%–21.3%) by 2080 following the A1B scenario. The predicted increase in energetic cost was largest in the coolest stream reaches, where the proportional increases in energetic cost exceed that of temperature. Energetically, and in absence of increases in food supply, local densities were consequently expected to decline. We examined which factors best described the shape of current size distributions to explore future size distributions as temperatures increase. Mass distribution skewness was best explained by local biomass (positive relationship) and water temperature (negative relationship). The results suggest that local steelhead cohorts will approach a platykurtic, slightly negatively skewed distribution with increasing temperatures and demonstrate that temperature can exacerbate demographic density dependence in fish populations.
IMPACT AND ADAPTATION OF SOUTH-EAST ASIAN FARMERS TO CLIMATE CHANGE: CONCLUSIONS AND POLICY RECOMMENDATIONS
Authors: KURUKULASURIYA PRADEEP , MENDELSOHN ROBERT
Published: August 2017

This study finds that South-East Asian farming is sensitive to climate change. Traditional Ricardian studies at the country and regional levels reveal that net revenue is affected by seasonal climate. A structural Ricardian model of growing season choice reveals climate change will reduce net revenues in the near term by 4–8% and in the long term by 10–18%. The implications of this impact on key sustainable development goals such as poverty reduction is likely to be profound. The study finds that farmers who rely on cultivating in three seasons will be especially hard hit by climate change relative to those that rely only on a single season. The results indicate that farmers will switch from 3 seasons to 1 season per year and reduce some of the losses that they would otherwise sustain. An analysis of crop adaptation finds that farmers will also adjust irrigation, crop choice, and the timing of planting in response to climate change. The livestock adaptation study finds that farmers will move towards livestock as climate warms. Farmers will also shift their choice of species away from large animals and move towards small animals. An analysis of perceptions finds that farmers throughout the region are aware that temperature is rising and they generally perceive that precipitation is falling. Half of the farmers interviewed have begun to take measures such as those reported in this study to adapt to climate change. The overall results suggest that acting on their self-interest, the agriculture sector will undertake a great deal of adaptation on its own. However, measures taken by the government such as providing up-to-date weather reports, extension, irrigation and assistance with new varieties can also be effective.
Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung
Authors: Vermeulen Zarha , Hervent Anne-Sophie , Dugaucquier Lindsey , Vandekerckhove Leni , Rombouts Miche , Beyens Matthias , Schrijvers Dorien M. , De Meyer Guido R. Y. , Maudsley Stuart , De Keulenaer Gilles W. , Segers Vincent F. M.
Published: August 2017

The neuregulin-1 (NRG-1)/receptor tyrosine-protein kinase erbB (ErbB) system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies have indicated that NRG-1 has antifibrotic effects in the left ventricle, which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. In this study, we hypothesized that the antifibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages. We also hypothesized that the antifibrotic effect of NRG-1 may be active in other organs, such as the skin and lung. First, in a mouse model of angiotensin II (ANG II)-induced myocardial hypertrophy and fibrosis, NRG-1 treatment (20 µg·kg−1·day−1 ip) significantly attenuated myocardial hypertrophy and fibrosis and improved passive ventricular stiffness (4 wk). Interestingly, 1 wk after exposure to ANG II, NRG-1 already attenuated myocardial macrophage infiltration and cytokine expression. Furthermore, mice with myeloid-specific deletion of the ErbB4 gene ( ErbB4F/FLysM-Cre+/−) showed an intensified myocardial fibrotic response to ANG II. Consistently, NRG-1 activated the ErbB4 receptor in isolated macrophages, inhibited phosphatidylinositide 3-kinase/Akt and STAT3 signaling pathways, and reduced the release of inflammatory cytokines. Further experiments showed that the antifibrotic and anti-inflammatory effects of NRG-1 were reproducible in mouse models of bleomycin-induced dermal and pulmonary fibrosis. Overall, this study demonstrates that the antifibrotic effect of NRG-1 in the heart is linked to anti-inflammatory activity NRG-1/ErbB4 signaling in macrophages. Second, this study shows that NRG-1 has antifibrotic and anti-inflammatory effects in organs other than the heart, such as the skin and lung.

NEW & NOTEWORTHY Our study contributes to the understanding of the antifibrotic effect of neuregulin-1 during myocardial remodeling. Here, we show that the antifibrotic effect of neuregulin-1 is at least partially mediated through anti-inflammatory activity, linked to receptor tyrosine-protein kinase erbB-4 activation in macrophages. Furthermore, we show that this effect is also present outside the heart.

Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nrg-1-inhibits-macrophage-activation-during-tissue-fibrosis/ .
Temporal dynamics of cardiac hypertrophic growth in response to pressure overload
Authors: Wang Yuan , Zhang Yuannyu , Ding Guanqiao , May Herman I. , Xu Jian , Gillette Thomas G. , Wang Hang , Wang Zhao V.
Published: August 2017

Hypertension is one of the most important risk factors of heart failure. In response to high blood pressure, the left ventricle manifests hypertrophic growth to ameliorate wall stress, which may progress into decompensation and trigger pathological cardiac remodeling. Despite the clinical importance, the temporal dynamics of pathological cardiac growth remain elusive. Here, we took advantage of the puromycin labeling approach to measure the relative rates of protein synthesis as a way to delineate the temporal regulation of cardiac hypertrophic growth. We first identified the optimal treatment conditions for puromycin in neonatal rat ventricular myocyte culture. We went on to demonstrate that myocyte growth reached its peak rate after 8–10 h of growth stimulation. At the in vivo level, with the use of an acute surgical model of pressure-overload stress, we observed the maximal growth rate to occur at day 7 after surgery. Moreover, RNA sequencing analysis supports that the most profound transcriptomic changes occur during the early phase of hypertrophic growth. Our results therefore suggest that cardiac myocytes mount an immediate growth response in reply to pressure overload followed by a gradual return to basal levels of protein synthesis, highlighting the temporal dynamics of pathological cardiac hypertrophic growth.

NEW & NOTEWORTHY We determined the optimal conditions of puromycin incorporation in cardiac myocyte culture. We took advantage of this approach to identify the growth dynamics of cardiac myocytes in vitro. We went further to discover the protein synthesis rate in vivo, which provides novel insights about cardiac temporal growth dynamics in response to pressure overload.
Optoacoustic Detection of Early Therapy-Induced Tumor Cell Death Using a Targeted Imaging Agent
Authors: Xie Bangwen , Tomaszewski Michal R. , Neves André A. , Ros Susana , Hu De-En , McGuire Sarah , Mullins Stefanie R. , Tice David , Sainson Richard C.A. , Bohndiek Sarah E. , Wilkinson Robert W. , Brindle Kevin M.
Published: August 2017

Purpose: The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU).

Experimental Design: C2Am was labeled with a NIR fluorophore and injected intravenously into mice bearing human colorectal TRAIL-sensitive Colo205 and TRAIL-resistant HT-29 xenografts that had been treated with a potent agonist of TRAILR2 and in Colo205 tumors treated with 5-FU.

Results: Three-dimensional (3D) MSOT images of probe distribution showed development of tumor contrast within 3 hours of probe administration and a signal-to-background ratio in regions containing dead cells of >10 after 24 hours. A site-directed mutant of C2Am that is inactive in PS binding showed negligible binding. Tumor retention of the active probe was strongly correlated (R2 = 0.97, P value < 0.01) with a marker of apoptotic cell death measured in histologic sections obtained post mortem.

Conclusions: The rapid development of relatively high levels of contrast suggests that NIR fluorophore-labeled C2Am could be a useful optoacoustic imaging probe for detecting early therapy-induced tumor cell death in the clinic. Clin Cancer Res; 23(22); 6893–903. ©2017 AACR.
Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers
Authors: Hai Josephine , Liu Shengwu , Bufe Lauren , Do Khanh , Chen Ting , Wang Xiaoen , Ng Christine , Li Shuai , Tsao Ming-Sound , Shapiro Geoffrey I. , Wong Kwok-Kin
Published: August 2017

Purpose: KRAS-activating mutations are the most common oncogenic driver in non–small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multitargeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations.

Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines. Murine autochthonous and human transplant models were used to test the therapeutic efficacy and pharmacodynamic effects of dual treatment.

Results: We demonstrate that combined inhibition of mTOR and WEE1 induced potent synergistic cytotoxic effects selectively in KRAS-mutant NSCLC cell lines, delayed human tumor xenograft growth and caused tumor regression in a murine lung adenocarcinoma model. Mechanistically, we show that inhibition of mTOR potentiates WEE1 inhibition by abrogating compensatory activation of DNA repair, exacerbating DNA damage in KRAS-mutant NSCLC, and that this effect is due in part to reduction in cyclin D1.

Conclusions: These findings demonstrate that compromised DNA repair underlies the observed potent synergy of WEE1 and mTOR inhibition and support clinical evaluation of this dual therapy for patients with KRAS-mutant lung cancers. Clin Cancer Res; 23(22); 6993–7005. ©2017 AACR.
Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma
Authors: Hynds Robert E. , Janes Sam M.
Published: August 2017

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo. The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491–3. ©2017 AACR.

See related article by Pagano et al., p. 514
CD28 and 41BB Costimulation Enhances the Effector Function of CD19-Specific Engager T Cells
Authors: Velasquez Mireya Paulina , Szoor Arpad , Vaidya Abishek , Thakkar Aarohi , Nguyen Phuong , Wu Meng-Fen , Liu Hao , Gottschalk Stephen
Published: August 2017

T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs [engager (ENG) T cells]. As BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells. CD19-ENG T cells expressing CD80 and 41BBL on their cell surface (CD19-ENG.41BBL/CD80 T cells) were generated by retroviral transduction. CD19-ENG.41BBL/CD80 T cells retained their antigen specificity and had superior effector function compared with both unmodified T cells and CD19-ENG T cells expressing either CD80, 41BBL, or no costimulatory molecule, as judged by cytokine (IFNγ and IL2) production, T-cell proliferation, and their ability to sequentially kill target cells. In vivo, CD19-ENG.41BBL/CD80 T cells had superior antileukemia activity in the BV173 xenograft model, resulting in a survival advantage in comparison to CD19-ENG T cells. Thus, provision of costimulation is critical for the effector function of ENG T cells. Cancer Immunol Res; 5(10); 860–70. ©2017 AACR.
Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now
Authors: Dugas Camille , Perron Julie , Kearney Michèle , Mercier Roxanne , Tchernof André , Marc Isabelle , Weisnagel S. John , Robitaille Julie
Published: August 2017

Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing many health problems such as obesity. There is an urgent need to find new strategies to prevent obesity development among high-risk populations such as those children. Accordingly, the aim of this review was to summarize current knowledge on the postnatal prevention of childhood obesity in offspring born from mothers with GDM. Specifically, this review addresses the impact of breastfeeding, complementary feeding practices as well as dietary intake and physical activity during childhood on obesity risk of children exposed to GDM in utero. Furthermore, breast milk composition of diabetic mothers and its potential impact on growth is discussed. According to the available literature, breastfeeding may reduce obesity risk in children exposed to GDM in utero but a longer duration seems necessary to achieve its protective effect against obesity. Detailed analysis of breast milk composition of mothers with GDM will be necessary to fully understand the relationship between breastfeeding and obesity in this specific population. This review highlights the need for more studies addressing the impact of complementary feeding practices and lifestyle habits during childhood on obesity risk of children exposed to GDM in utero.
Targeting miR-423-5p Reverses Exercise Training–Induced HCN4 Channel Remodeling and Sinus Bradycardia
Authors: D’Souza Alicia , Pearman Charles M. , Wang Yanwen , Nakao Shu , Logantha Sunil Jit R.J. , Cox Charlotte , Bennett Hayley , Zhang Yu , Johnsen Anne Berit , Linscheid Nora , Poulsen Pi Camilla , Elliott Jonathan , Coulson Jessica , McPhee Jamie , Robertson Abigail , da Costa Martins Paula A. , Kitmitto Ashraf , Wisløff Ulrik , Cartwright Elizabeth J. , Monfredi Oliver , Lundby Alicia , Dobrzynski Halina , Oceandy Delvac , Morris Gwilym M. , Boyett Mark R.
Published: August 2017

Rationale:

Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current,
I
f
, underlies exercise training–induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes.

Objective:

To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4.

Methods and Results:

As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3′-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and
I
f
. Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5.

Conclusions:

HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes.
A new species of the genus Chrysacris Zheng, 1983 from China (Orthoptera: Acridoidea, Acrididae)
Authors: CAO CHENG-QUAN , SHI JIAN-PING , YIN ZHAN
Published: August 2017

The Chrysacris Zheng, 1983 is a median genus in Acrididae, which contains 18 species [Tu & Cheng, 1964; Zheng, 1983; Lian & Zheng, 1987; Li & Chen, 1988; Zheng, 1988; Liu, 1990; Ren et al, 1991; Liang & Jia, 1992; Zheng et al, 1992; Ren et al, 1993; Zhang & Zheng, 1993; Zheng, 1993; Zheng & Shi, 1993; Niu, 1994; Ren et al, 1994; Zheng et al, 1995; Yin et al, 1996; Ren 2001; Ren et al, 2002; Yin et al, 2003; Zheng et al, 2011; Dong et al, 2015; Eades, et al, 2017; Zhang et al, 2017], mainly distributed in Heilongjiang, Jilin, Liaoning, Inner Mongolia, Shanxi, Shaanxi, Henan and Guizhou provinces of China. A new species of the genus Chrysacris is described from Inner Mongolia, China in this paper. Type specimens are deposited in the Natural Museum of Hebei University, Baoding, Hebei, China.
Storybridging: Four steps for constructing effective health narratives
Authors: Boeijinga Anniek , Hoeken Hans , Sanders José
Published: August 2017

Objective:

To develop a practical step-by-step approach to constructing narrative health interventions in response to the mixed results and wide diversity of narratives used in health-related narrative persuasion research.

Method:

Development work was guided by essential narrative characteristics as well as principles enshrined in the Health Action Process Approach.

Results:

The ‘storybridging’ method for constructing health narratives is described as consisting of four concrete steps: (a) identifying the stage of change, (b) identifying the key elements, (c) building the story, and (d) pre-testing the story. These steps are illustrated by means of a case study in which an effective narrative health intervention was developed for Dutch truck drivers: a high-risk, underprivileged occupational group.

Conclusion:

Although time and labour intensive, the Storybridging approach suggests integrating the target audience as an important stakeholder throughout the development process. Implications and recommendations are provided for health promotion targeting truck drivers specifically and for constructing narrative health interventions in general.
Within Your Control? When Problem Solving May Be Most Helpful
Authors: Sarfan Laurel D. , Gooch Peter , Clerkin Elise M.
Published: August 2017

Emotion regulation strategies have been conceptualized as adaptive or maladaptive, but recent evidence suggests emotion regulation outcomes may be context-dependent. The present study tested whether the adaptiveness of a putatively adaptive emotion regulation strategy—problem solving—varied across contexts of high and low controllability. The present study also tested rumination, suggested to be one of the most putatively maladaptive strategies, which was expected to be associated with negative outcomes regardless of context. Participants completed an in vivo speech task, in which they were randomly assigned to a controllable ( n = 65) or an uncontrollable ( n = 63) condition. Using moderation analyses, we tested whether controllability interacted with emotion regulation use to predict negative affect, avoidance, and perception of performance. Partially consistent with hypotheses, problem solving was associated with certain positive outcomes (i.e., reduced behavioral avoidance) in the controllable (vs. uncontrollable) condition. Consistent with predictions, rumination was associated with negative outcomes (i.e., desired avoidance, negative affect, negative perception of performance) in both conditions. Overall, findings partially support contextual models of emotion regulation, insofar as the data suggest that the effects of problem solving may be more adaptive in controllable contexts for certain outcomes, whereas rumination may be maladaptive regardless of context.
Dancing in chains: Creative practices in/of organizations
Authors: Ortmann Günther , Sydow Jörg
Published: August 2017

According to Friedrich Nietzsche, artists impose restrictions on themselves to encourage creativity and even have a way of “making things difficult” – imposing new constraints on themselves within which they have to dance. At least in the arts, it is difficulty rather than ease which promotes creativity in accordance with this view. This goes beyond the well-known idea of rules and other structures not only restricting but also enabling creativity; it also goes beyond insight into the creativity-enhancing effects of constraints, as recently emphasized in organization studies. Nietzsche adds three dimensions to this dialectic: time and the process of dancing inspired and encouraged by constraints; the opposition of old and new constraints; and the quality of intended, stimulating self-binding. We see this as an opportunity to explore the inspiring potential of Nietzsche’s piece about arts, “Dancing in chains”, when it comes to the different realm of creative practices and creativity in and of organizations. Such an exploration can obviously not aim to offer recipes of how to bring about valuable novelty, but simply intends to identify pertinent themes, issues and questions for organization studies – topics and aspects brought into a new or sharper light when looked at from Nietzsche’s perspective and that of some other philosophers, including Jon Elster’s analyses of constraints in general and of the complications of self-binding in order to promote creativity in particular. Also, we consider Míchel de Certeau’s “silent production” and Martha Feldman’s improvisational routines as being cases of “dancing in chains”.
Market Failures and Market Framings: Can a market be transformed from the inside?
Authors: Geiger Susi , Gross Nicole
Published: August 2017

How do actors innovate markets in cases of perceived market failures? This paper’s aim is to examine what happens when a market is innovated or, as we call it, ‘redevised’ in situations where public and commercial interests significantly diverge. Market devices can serve an important function in such attempts to innovate markets: they are material and/or social arrangements that are put into place to shape the market in question in certain ways. But can such devices really transform a market from within? To examine this question we trace the history of the Geneva Medicines Patent Pool, a civil society initiative introduced to change pharmaceutical firms’ licensing and collaboration practices in the market for HIV/AIDS medicines. Our empirical results indicate that redevising a market in response to market failures can shift the market’s frames and contribute to altering its practices, but that this is a pragmatic and often lengthy process that is never fully predictable in advance. By attending to the intended and unintended consequences - or misfires - of redevising a market, our study raises important questions around acting in and on the market, market innovation’s’ ontological impact, zooming in and zooming out when studying redevising, and attending to the temporality of market innovation.
Is Commitment to Performance-based Management Compatible with Commitment to University “Publicness”? Academics’ Values in French Universities
Authors: Chatelain-Ponroy Stéphanie , Mignot-Gérard Stéphanie , Musselin Christine , Sponem Samuel
Published: August 2017

Individuals’ values in the context of NPM-based reforms are a central theme in studies of public professional organizations. While organization studies mainly focus on “professional” values, research on public administration primarily addresses the issue of “public” values. This article brings these two research streams together in order to investigate the relationship between two sets of individual values—commitment to performance-based management and normative publicness—in the context of French public universities. It draws on a quantitative survey of academics involved in university governance. The study demonstrates that a positive attitude towards performance-based management is negatively correlated with commitment to university publicness; furthermore, it delineates different groups within the academic profession—according to professional status, managerial position within the organization, and the department’s reputation and ability to generate revenues—which have differing attitudes regarding performance-based management and university publicness.
On Silence, Creativity and Ethics in Organization Studies
Authors: Bigo Vinca
Published: August 2017

Silence is at once a notoriously difficult and most elusive subject. Management and organization studies depict silence as exclusionary, oppressive, needing to be overcome, and as a strategy to resist oppression. The idea that silence might be cultivated for and not against, stressing positive and enabling (and yet non instrumental) aspects of silence, is meanwhile much less considered. Yet if silence excludes, it can exclude all sorts of things, including undesirable things. Silences forge an emptiness, and so a space for the possible emergence of something new, beyond existing beliefs, norms and practices. Certain silences facilitate creativity, including creativity of an ethical sort. The endeavour of this article is to in part interrogate and deconstruct the current status of silence in management and organization studies, and further to anchor the topic more firmly in organizational scholarship and practice, particularly in relation to ethics and creativity.
Practice meta-environment of the cardiovascular perfusionist
Authors: Belway Dean , Rubens Fraser D. , Tran Diem T. T.
Published: August 2017

Though historically the development of cardiovascular perfusion grew out of the need for cardiopulmonary bypass, the application of technologies of extracorporeal support has more recently expanded beyond the traditional domain of the cardiac surgical operative and peri-operative environment. As a result, perfusionists are sometimes required to work in novel clinical settings. As part of our recent national survey to evaluate the effects of changes in entry-to-practice criteria introduced in Canada in 2006, we asked perfusionists if their current position as a perfusionist involves work outside the OR. We found that, in addition to regularly working in the Intensive Care Unit and Cardiac Catheterization Lab, 55.3% of respondents reported working “occasionally” in the Emergency Room and 74.7% reported working “occasionally” or “often” in other clinical areas. However, while 96% of respondents believed their training adequately prepared them for their job as a perfusionist, only 68% felt their training adequately prepared them for their duties outside the operating room. We also noted a trend that admission under experience-based entry-to-practice criteria was associated with a higher likelihood of perceived adequacy of training in preparation for duties outside the OR than education-based admission criteria (72% vs 59.4%, p=0.065). These findings raise important questions pertaining to the sufficiency of perfusion education in Canada and the influence of soft skills in preparing perfusionists for their duties, and indicate that a systematic study of the practice environment of cardiovascular perfusionists is timely.
Rescue intervention after three days of renal ischemia caused by acute complicated type B aortic dissection
Authors: Lai Chih-Hung , Chang Keng-Hao , Chang Szu-Ling , Lai Hui-Chih , Lee Wen-Lieng , Liu Tsun-Jui
Published: August 2017

Complicated type B dissection is associated with a high mortality rate due to malperfusion syndrome or progression of the dissection for which aggressive therapy with an endovascular or surgical intervention is recommended. Herein, we present a patient who received a successful percutaneous rescue intervention after three days of renal ischemia caused by a complicated type B dissection. This type of rescue of percutaneous intervention with branch vessel stenting appears to be useful in treating malperfusion syndrome caused by aortic dissection, even after a period of organ ischemia.
Spontaneous coronary artery dissection causing acute myocardial infarction and cardiac arrest in a 25-year-old male
Authors: Chang Fu-Lan , Chang Wei-Chun , Cheng Yu-Tsung , Liu Tsun-Jui , Lee Wen-Lieng , Lai Chih-Hung
Published: August 2017

A 25-year-old previously healthy male presented to our emergency room with acute chest pain and ventricular arrhythmia-related cardiac arrest. ST elevation myocardial infarction was diagnosed and coronary angiography revealed diffuse critical narrowing from the proximal to the distal left anterior descending artery. Diffuse intramural hematoma was demonstrated on intravascular ultrasound. Two stents were placed to cover the whole dissection length and flow was successfully restored. Spontaneous coronary artery dissection can be a fatal event and could be mistaken for atherosclerotic plaque or coronary spasm rather than luminal compression on coronary angiography and intravascular imaging is helpful in this condition.
Social and Emotional Learning in Adolescence: Testing the CASEL Model in a Normative Sample
Authors: Ross Katherine M. , Tolan Patrick
Published: August 2017

As Social and Emotional Learning (SEL) expands to focus on adolescent populations, the broadly accepted theoretical framework put forth by the Collaborative for Academic, Social, and Emotional Learning (CASEL) should be empirically tested for measurement utility. Using longitudinal data from the 4-H Study of Positive Youth Development, we first tested and validated the five (self-awareness, self-management, social awareness, relationship skills, responsible decision-making) SEL factor model using confirmatory factor analysis (CFA) in a normative sample of 1,717 U.S. fifth grade youth. The model was then subjected to longitudinal measurement invariance testing using CFA models that included the sixth- and seventh-grade samples to confirm SEL as a robust model across these grades. Validity was further evidenced through relation of the SEL model to important youth outcomes (e.g., academic achievement). Relations were significant and in the expected direction. Implications for application of the model to adolescent development are discussed.
Using Cluster Analysis to Group Countries for Cost-effectiveness Analysis: An Application to Sub-Saharan Africa
Authors: Russell Louise B. , Bhanot Gyan , Kim Sun-Young , Sinha Anushua
Published: August 2017

Objective. To explore the use of cluster analysis to define groups of similar countries for the purpose of evaluating the cost-effectiveness of a public health intervention—maternal immunization—within the constraints of a project budget originally meant for an overall regional analysis. Methods. We used the most common cluster analysis algorithm, K-means, and the most common measure of distance, Euclidean distance, to group 37 low-income, sub-Saharan African countries on the basis of 24 measures of economic development, general health resources, and past success in public health programs. The groups were tested for robustness and reviewed by regional disease experts. Results. We explored 2-, 3- and 4-group clustering. Public health performance was consistently important in determining the groups. For the 2-group clustering, for example, infant mortality in Group 1 was 81 per 1,000 live births compared with 51 per 1,000 in Group 2, and 67% of children in Group 1 received DPT immunization compared with 87% in Group 2. The experts preferred four groups to fewer, on the ground that national decision makers would more readily recognize their country among four groups. Conclusions. Clusters defined by K-means clustering made sense to subject experts and allowed a more detailed evaluation of the cost-effectiveness of maternal immunization within the constraint of the project budget. The method may be useful for other evaluations that, without having the resources to conduct separate analyses for each unit, seek to inform decision makers in numerous countries or subdivisions within countries, such as states or counties.
Methods for Population-Adjusted Indirect Comparisons in Health Technology Appraisal
Authors: Phillippo David M. , Ades Anthony E. , Dias Sofia , Palmer Stephen , Abrams Keith R. , Welton Nicky J.
Published: August 2017

Standard methods for indirect comparisons and network meta-analysis are based on aggregate data, with the key assumption that there is no difference between the trials in the distribution of effect-modifying variables. Methods which relax this assumption are becoming increasingly common for submissions to reimbursement agencies, such as the National Institute for Health and Care Excellence (NICE). These methods use individual patient data from a subset of trials to form population-adjusted indirect comparisons between treatments, in a specific target population. Recently proposed population adjustment methods include the Matching-Adjusted Indirect Comparison (MAIC) and the Simulated Treatment Comparison (STC). Despite increasing popularity, MAIC and STC remain largely untested. Furthermore, there is a lack of clarity about exactly how and when they should be applied in practice, and even whether the results are relevant to the decision problem. There is therefore a real and present risk that the assumptions being made in one submission to a reimbursement agency are fundamentally different to—or even incompatible with—the assumptions being made in another for the same indication. We describe the assumptions required for population-adjusted indirect comparisons, and demonstrate how these may be used to generate comparisons in any given target population. We distinguish between anchored and unanchored comparisons according to whether a common comparator arm is used or not. Unanchored comparisons make much stronger assumptions, which are widely regarded as infeasible. We provide recommendations on how and when population adjustment methods should be used, and the supporting analyses that are required to provide statistically valid, clinically meaningful, transparent and consistent results for the purposes of health technology appraisal. Simulation studies are needed to examine the properties of population adjustment methods and their robustness to breakdown of assumptions.