bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy in Sickle Cell Disease Is a Very High-Risk Situation: An Observational Study
Authors: Elenga Narcisse , Adeline Aurélie , Balcaen John , Vaz Tania , Calvez Mélanie , Terraz Anne , Accrombessi Laetitia , Carles Gabriel
Published: June 2016

Sickle cell disease is a serious genetic disorder affecting 1/235 births in French Guiana. This study aimed to describe the follow-up of pregnancies among sickle cell disease patients in Cayenne Hospital, in order to highlight the most reported complications. 62 records of pregnancies were analyzed among 44 females with sickle cell disease, between 2007 and 2013. Our results were compared to those of studies conducted in Brazil and Guadeloupe. There were 61 monofetal pregnancies and 2 twin pregnancies, 27 pregnancies among women with SS phenotype, 30 SC pregnancies, and five S-beta pregnancies. The study showed that the follow-up of patients was variable, but no maternal death was found. We also noted that the main maternofetal complications of pregnancies were anemia (36.5%), infection (31.7%), vasoocclusive crisis (20.6%), preeclampsia (17.5%), premature birth (11.1%), intrauterine growth retardation (15.9%), abnormal fetal heart rate (14.3%), and intrauterine fetal death (4.8%). Pregnancies were more at risk among women with SS phenotype. Pregnancy in sickle cell disease patients requires a supported multidisciplinary team including the primary care physician, the obstetrician, and the Integrated Center for Sickle Cell Disease.
Patterns and Determinants of Treatment Seeking among Previously Untreated Psychotic Patients in Aceh Province, Indonesia: A Qualitative Study
Authors: Marthoenis Marthoenis , Aichberger Marion C. , Schouler-Ocak Meryam
Published: June 2016

Immediate treatment of first-episode psychosis is essential in order to achieve a positive outcome. However, Indonesian psychiatric patients often delay accessing health services, the reason for which is not yet fully understood. The current study aimed to understand patterns of treatment seeking and to reveal determinants of the delay in accessing psychiatric care among first-time user psychotic patients. Qualitative interviews were conducted with sixteen family members who accompanied the patients to a psychiatric hospital. Many families expressed beliefs that mental illness appertains tovillage sicknessand nothospital sickness; therefore, they usually take the patients to traditional or religious healers before taking them to a health professional. They also identified various factors that potentially delay accessing psychiatric treatment: low literacy and beliefs about the cause of the illness, stigmatisation, the role of extended family, financial problems, and long distance to the psychiatric hospital. On the other hand, the family mentioned various factors related to timely help seeking, including being a well-educated family, living closer to health facilities, previous experience of successful psychotic therapy, and having more positive symptoms of psychosis. The findings call for mental health awareness campaigns in the community.
The Multiobjective Trajectory Optimization for Hypersonic Glide Vehicle Based on Normal Boundary Intersection Method
Authors: Li Zhengnan , Yang Tao , Feng Zhiwei
Published: June 2016

To solve the multiobjective optimization problem on hypersonic glider vehicle trajectory design subjected to complex constraints, this paper proposes a multiobjective trajectory optimization method that combines the boundary intersection method and pseudospectral method. The multiobjective trajectory optimization problem (MTOP) is established based on the analysis of the feature of hypersonic glider vehicle trajectory. The MTOP is translated into a set of general optimization subproblems by using the boundary intersection method and pseudospectral method. The subproblems are solved by nonlinear programming algorithm. In this method, the solution that has been solved is employed as the initial guess for the next subproblem so that the time consumption of the entire multiobjective trajectory optimization problem shortens. The maximal range and minimal peak heat problem is solved by the proposed method. The numerical results demonstrate that the proposed method can obtain the Pareto front of the optimal trajectory, which can provide the reference for the trajectory design of hypersonic glider vehicle.
A Review of Surrogate Assisted Multiobjective Evolutionary Algorithms
Authors: Díaz-Manríquez Alan , Toscano Gregorio , Barron-Zambrano Jose Hugo , Tello-Leal Edgar
Published: June 2016

Multiobjective evolutionary algorithms have incorporated surrogate models in order to reduce the number of required evaluations to approximate the Pareto front of computationally expensive multiobjective optimization problems. Currently, few works have reviewed the state of the art in this topic. However, the existing reviews have focused on classifying the evolutionary multiobjective optimization algorithms with respect to the type of underlying surrogate model. In this paper, we center our focus on classifying multiobjective evolutionary algorithms with respect to their integration with surrogate models. This interaction has led us to classify similar approaches and identify advantages and disadvantages of each class.
Signaling-Free Max-Min Airtime Fairness in IEEE 802.11 Ad Hoc Networks
Authors: Lee Youngsoo , Park Eun-Chan , Choi Chong-Ho
Published: June 2016

We propose a novel media access control (MAC) protocol, referred to assignaling-free max-min airtime fair(SMAF) MAC, to improve fairness and channel utilization in ad hoc networks based on IEEE 802.11 wireless local area networks (WLANs). We introducebusy time ratio(BTR) as a measure for max-min airtime fairness. Each node estimates its BTR and adjusts the transmission duration by means of frame aggregation and fragmentation, so that it can implicitly announce the BTR to neighbor nodes. Based on the announced BTR, each of the neighbor nodes controls its contention window. In this way, the SMAF MAC works in a distributed manner without the need to know the max-min fair share of airtime, and it does not require exchanging explicit control messages among nodes to attain fairness. Moreover, we successfully incorporate the hidden node detection and resolution mechanisms into the SMAF MAC to deal with the hidden node problem in ad hoc networks. The simulation results confirm that the SMAF MAC enhances airtime fairness without degrading channel utilization, and it effectively resolves several serious problems in ad hoc networks such as the starvation, performance anomaly, and hidden node problems.
Traumatic Cardiac Injury: Ventricular Perforation Caught on CT
Authors: Golshani Behrad , Dong Paul , Evans Scott
Published: June 2016

Myocardial rupture is a rare imaging diagnosis given its clinical severity and high mortality. Early findings should be promptly communicated to the trauma service to ensure immediate intervention. We present a rare case of blowout perforation of the right ventricle which was prospectively diagnosed on computed tomography (CT) leading to emergent operative repair. The patient subsequently survived and was discharged after a lengthy hospital course.
Similarity Solution for High Weissenberg Number Flow of Upper-Convected Maxwell Fluid on a Linearly Stretching Sheet
Authors: Mohamadali Meysam , Ashrafi Nariman
Published: June 2016

High Weissenberg boundary layer flow of viscoelastic fluids on a stretching surface has been studied. The flow is considered to be steady, low inertial, and two-dimensional. Upon proper scaling and by means of an exact similarity transformation, the nonlinear momentum and constitutive equations of each layer transform into the respective system of highly nonlinear and coupled ordinary differential equations. Numerical solutions to the resulting boundary value problem are obtained using an efficient shooting technique in conjunction with a variable stepping method for different values of pressure gradients. It is observed that, unlike the Newtonian flows, in order to maintain a potential flow, normal stresses must inevitably develop. The velocity field and stresses distributions over plate are presented for difference values of pressure gradient and Weissenberg numbers.
Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression
Authors: Oh Ah-Young , Jung Youn Sang , Kim Jiseon , Lee Jee-Hyun , Cho Jung-Hyun , Chun Ho-Young , Park Soyoung , Park Hyunchul , Lim Sikeun , Ha Nam-Chul , Park Jong Sook , Park Choon-Sik , Song Gyu-Yong , Park Bum-Joon
Published: June 2016

The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung cancer tissues and cells. DX2 prevented oncogene-induced apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo. SLCB050 reduced the viability of human lung cancer cells, especially small cell lung cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras–driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non–small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791–804. ©2016 AACR.
Mathematical Modeling of Cancer Immunotherapy and Its Synergy with Radiotherapy
Authors: Serre Raphael , Benzekry Sebastien , Padovani Laetitia , Meille Christophe , André Nicolas , Ciccolini Joseph , Barlesi Fabrice , Muracciole Xavier , Barbolosi Dominique
Published: June 2016

Combining radiotherapy with immune checkpoint blockade may offer considerable therapeutic impact if the immunosuppressive nature of the tumor microenvironment (TME) can be relieved. In this study, we used mathematical models, which can illustrate the potential synergism between immune checkpoint inhibitors and radiotherapy. A discrete-time pharmacodynamic model of the combination of radiotherapy with inhibitors of the PD1–PDL1 axis and/or the CTLA4 pathway is described. This mathematical framework describes how a growing tumor first elicits and then inhibits an antitumor immune response. This antitumor immune response is described by a primary and a secondary (or memory) response. The primary immune response appears first and is inhibited by the PD1–PDL1 axis, whereas the secondary immune response happens next and is inhibited by the CTLA4 pathway. The effects of irradiation are described by a modified version of the linear-quadratic model. This modeling offers an explanation for the reported biphasic relationship between the size of a tumor and its immunogenicity, as measured by the abscopal effect (an off-target immune response). Furthermore, it explains why discontinuing immunotherapy may result in either tumor recurrence or a durably sustained response. Finally, it describes how synchronizing immunotherapy and radiotherapy can produce synergies. The ability of the model to forecast pharmacodynamic endpoints was validated retrospectively by checking that it could describe data from experimental studies, which investigated the combination of radiotherapy with immune checkpoint inhibitors. In summary, a model such as this could be further used as a simulation tool to facilitate decision making about optimal scheduling of immunotherapy with radiotherapy and perhaps other types of anticancer therapies. Cancer Res; 76(17); 4931–40. ©2016 AACR.
Remodeling of the Epithelial–Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging
Authors: Pal Rahul , Shilagard Tuya , Yang Jinping , Villarreal Paula , Brown Tyra , Qiu Suimin , McCammon Susan , Resto Vicente , Vargas Gracie
Published: June 2016

Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial–connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, “ECTI contour,” is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo. Cancer Res; 76(16); 4637–47. ©2016 AACR.
Acute Sensitivity of Ph-like Acute Lymphoblastic Leukemia to the SMAC-Mimetic Birinapant
Authors: Richmond Jennifer , Robbins Alissa , Evans Kathryn , Beck Dominik , Kurmasheva Raushan T. , Billups Catherine A. , Carol Hernan , Heatley Sue , Sutton Rosemary , Marshall Glenn M. , White Deborah , Pimanda John , Houghton Peter J. , Smith Malcolm A. , Lock Richard B.
Published: June 2016

Ph-like acute lymphoblastic leukemia (ALL) is a genetically defined high-risk ALL subtype with a generally poor prognosis. In this study, we evaluated the efficacy of birinapant, a small-molecule mimetic of the apoptotic regulator SMAC, against a diverse set of ALL subtypes. Birinapant exhibited potent and selective cytotoxicity against B-cell precursor ALL (BCP-ALL) cells that were cultured ex vivo or in vivo as patient-derived tumor xenografts (PDX). Cytotoxicity was consistently most acute in Ph-like BCP-ALL. Unbiased gene expression analysis of BCP-ALL PDX specimens identified a 68-gene signature associated with birinapant sensitivity, including an enrichment for genes involved in inflammatory response, hematopoiesis, and cell death pathways. All Ph-like PDXs analyzed clustered within this 68-gene classifier. Mechanistically, birinapant sensitivity was associated with expression of TNF receptor TNFR1 and was abrogated by interfering with the TNFα/TNFR1 interaction. In combination therapy, birinapant enhanced the in vivo efficacy of an induction-type regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering a preclinical rationale to further evaluate this SMAC mimetic for BCP-ALL treatment. Cancer Res; 76(15); 4579–91. ©2016 AACR.
Retail Pharmacy Policy to End the Sale of Tobacco Products: What Is the Impact on Disparity in Neighborhood Density of Tobacco Outlets?
Authors: Tucker-Seeley Reginald D. , Bezold Carla P. , James Peter , Miller Melecia , Wallington Sherrie F.
Published: June 2016

Background: Population-level research on the implications of retail pharmacy policies to end the sale of tobacco products is scant, and the impact of such policies on racial/ethnic and socioeconomic disparities across neighborhoods in access to tobacco products remains unexplored.

Methods: We investigated the association between neighborhood sociodemographic characteristics and tobacco retail density in Rhode Island (RI; N = 240 census tracts). We also investigated whether the CVS Health (N = 60) policy to end the sale of tobacco products reduces the disparity in the density of tobacco retail across neighborhoods, and we conducted a prospective policy analysis to determine whether a similar policy change in all pharmacies in RI (N = 135) would reduce the disparity in tobacco retail density.

Results: The results revealed statistically significant associations between neighborhood sociodemographic characteristics and tobacco retail outlet density across RI neighborhoods. The results when excluding the CVS Health locations, as well as all pharmacies as tobacco retailers, revealed no change in the pattern for this association.

Conclusions: The results of this study suggest that while a commendable tobacco control policy, the CVS Health policy appears to have no impact on the neighborhood racial/ethnic and socioeconomic disparities in the density of tobacco retailers in RI. Prospective policy analyses showed no impact on this disparity even if all other pharmacies in the state adopted a similar policy.

Impact: Policy efforts aimed at reducing the disparity in access to tobacco products should focus on reducing the density of tobacco outlets in poor and racial/ethnic neighborhoods. Cancer Epidemiol Biomarkers Prev; 25(9); 1305–10. ©2016 AACR.
A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer
Authors: Hoogstins Charlotte E.S. , Tummers Quirijn R.J.G. , Gaarenstroom Katja N. , de Kroon Cor D. , Trimbos J. Baptist M.Z. , Bosse Tjalling , Smit Vincent T.H.B.M. , Vuyk Jaap , van de Velde Cornelis J.H. , Cohen Adam F. , Low Philip S. , Burggraaf Jacobus , Vahrmeijer Alexander L.
Published: June 2016

Purpose: Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is often difficult and can lead to incomplete tumor removal. Near-infrared fluorescence imaging has the potential to improve the detection of malignant tissue during surgery, significantly improving outcome. Here, we report the use of OTL38, a near-infrared (796 nm) fluorescent agent, that binds folate receptor alpha, which is expressed in >90% of epithelial ovarian cancers.

Experimental Design: We first performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At fixed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the first study, three doses were selected and administered to 12 patients who had epithelial ovarian cancer and were scheduled for cytoreductive surgery. We measured tolerability and blood pharmacokinetics, as well as the ability to detect the tumor using intraoperative fluorescence imaging.

Results: Intravenous infusion of OTL38 in 30 healthy volunteers yielded an optimal dosage range and time window for intraoperative imaging. In 12 patients with ovarian cancer, OTL38 accumulated in folate receptor alpha–positive tumors and metastases, enabling the surgeon to resect an additional 29% of malignant lesions that were not identified previously using inspection and/or palpation.

Conclusions: This study demonstrates that performing real-time intraoperative near-infrared fluorescence imaging using a tumor-specific agent is feasible and potentially clinically beneficial. Clin Cancer Res; 22(12); 2929–38. ©2016 AACR.
Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma
Authors: Böhm Steffen , Montfort Anne , Pearce Oliver M.T. , Topping Joanne , Chakravarty Probir , Everitt Gemma L.A. , Clear Andrew , McDermott Jackie R. , Ennis Darren , Dowe Thomas , Fitzpatrick Amanda , Brockbank Elly C. , Lawrence Alexandra C. , Jeyarajah Arjun , Faruqi Asma Z. , McNeish Iain A. , Singh Naveena , Lockley Michelle , Balkwill Frances R.
Published: June 2016

Purpose: The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSC), and its relationship to treatment response.

Experimental Design: We obtained pre- and posttreatment omental biopsies and blood samples from a total of 54 patients undergoing platinum-based NACT and 6 patients undergoing primary debulking surgery. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC, flow cytometry, electrochemiluminescence assays, and RNA sequencing and related our findings to the histopathologic treatment response.

Results: There was evidence of T-cell activation in omental biopsies after NACT: CD4+ T cells showed enhanced IFNγ production and antitumor Th1 gene signatures were increased. T-cell activation was more pronounced with good response to NACT. The CD8+ T-cell and CD45RO+ memory cell density in the tumor microenvironment was unchanged after NACT but biopsies showing a good therapeutic response had significantly fewer FoxP3+ T regulatory (Treg) cells. This finding was supported by a reduction in a Treg cell gene signature in post- versus pre-NACT samples that was more pronounced in good responders. Plasma levels of proinflammatory cytokines decreased in all patients after NACT. However, a high proportion of T cells in biopsies expressed immune checkpoint molecules PD-1 and CTLA4, and PD-L1 levels were significantly increased after NACT.

Conclusions: NACT may enhance host immune response but this effect is tempered by high/increased levels of PD-1, CTLA4, and PD-L1. Sequential chemoimmunotherapy may improve disease control in advanced HGSC. Clin Cancer Res; 22(12); 3025–36. ©2016 AACR.
Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts
Authors: Sharma Priyanka , López-Tarruella Sara , García-Saenz Jose Angel , Ward Claire , Connor Carol S. , Gómez Henry L. , Prat Aleix , Moreno Fernando , Jerez-Gilarranz Yolanda , Barnadas Augusti , Picornell Antoni C. , del Monte-Millán Maria , Gonzalez-Rivera Milagros , Massarrah Tatiana , Pelaez-Lorenzo Beatriz , Palomero María Isabel , González del Val Ricardo , Cortes Javier , Fuentes Rivera Hugo , Bretel Morales Denisse , Márquez-Rodas Iván , Perou Charles M. , Wagner Jamie L. , Mammen Joshua M.V. , McGinness Marilee K. , Klemp Jennifer R. , Amin Amanda L. , Fabian Carol J. , Heldstab Jaimie , Godwin Andrew K. , Jensen Roy A. , Kimler Bruce F. , Khan Qamar J. , Martin Miguel
Published: June 2016

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC.

Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated.

Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event.

Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.
Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy
Authors: Wang Yunle , Liu Jiabao , Tao Zhiwen , Wu Peng , Cheng Weili , Du Yingqiang , Zhou Ningtian , Ge Yingbin , Yang Zhijian
Published: June 2016

Background: Hepatocyte growth factor (HGF) is widely known as a protective factor in ischemic myocardium, however HGF sensitive cellular mechanism remained ill-defined. Autophagy at early stage of hypoxia has been demonstrated to play a role in protecting myocardium both in vivo and vitro. We performed this study to investigate the association between the protective effect of HGF and autophagy. Methods: Ventricular myocytes were isolated from neonatal rat heart (NRVMs). We evaluated cardiomyocytes apoptosis by Hoechst staining and flow cytometry. Autophagy was assessed by transmission electron microscope and mRFP-GFP-LC3 adenovirus infection. Mitochondrial membrane potential was estimated by JC-1 staining. Western blotting and ELISA assay were used to quantify protein concentrations. Results: We found that autophagy in NRVMs increased at early stage after hypoxia and HGF release was consistent with the change of autophagy. Exogenous HGF enhanced autophagy and decreased apoptosis, while neutralizing HGF yielded opposite effects. Besides, inhibition of autophagy increased apoptosis of myocytes. Furthermore, exogenous HGF induced Parkin, the marker of mitochondrial autophagy, indicating increased clearance of injured mitochondria. Conclusions: Our results revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. Upregulation of Parkin through administration of exogenous HGF may be a potential therapeutic strategy ptotecting myocytes during ischemia.
Postdischarge Bleeding After Percutaneous Coronary Intervention and Subsequent Mortality and Myocardial Infarction
Authors: Valle Javier A. , Shetterly Susan , Maddox Thomas M. , Ho P. Michael , Bradley Steven M. , Sandhu Amneet , Magid David , Tsai Thomas T.
Published: June 2016

Background—

Bleeding after hospital discharge from percutaneous coronary intervention (PCI) is associated with increased risk of subsequent myocardial infarction (MI) and death; however, the timing of adverse events after these bleeding events is poorly understood. Defining this relationship may help clinicians identify critical periods when patients are at highest risk.

Methods and Results—

All patients undergoing PCI from 2004 to 2007 who survived to hospital discharge without a bleeding event were identified from the HMO Research Network-Stent (HMORN-Stent) Registry. Postdischarge rates and timing of bleeding-related hospitalizations, MI, and death were defined. We then assessed the association between postdischarge bleeding–related hospitalizations with death and MI using Cox proportional hazards models. Among 8137 post-PCI patients surviving to hospital discharge without in-hospital bleeding, 391 (4.8%) had bleeding-related hospitalization after discharge, with the highest incidence of bleeding-related hospitalizations occurring within 30 days of discharge (n=79, 20.2%). Postdischarge bleeding–related hospitalization after PCI was associated with subsequent death or MI (hazard ratio, 3.09; 95% confidence interval, 2.41–3.96), with the highest risk for death or MI occurring in the first 60 days after bleeding-related hospitalization (hazard ratio, 7.16; confidence interval, 3.93–13.05).

Conclusions—

Approximately 1 in 20 post-PCI patients are readmitted for bleeding, with the highest incidence occurring within 30 days of discharge. Patients having postdischarge bleeding are at increased risk for subsequent death or MI, with the highest risk occurring within the first 60 days after a bleeding-related hospitalization. These findings suggest a critical period after bleeding events when patients are most vulnerable for further adverse events.
Transcatheter Replacement of Failed Bioprosthetic Valves
Authors: Simonato Matheus , Webb John , Kornowski Ran , Vahanian Alec , Frerker Christian , Nissen Henrik , Bleiziffer Sabine , Duncan Alison , Rodés-Cabau Josep , Attizzani Guilherme F. , Horlick Eric , Latib Azeem , Bekeredjian Raffi , Barbanti Marco , Lefevre Thierry , Cerillo Alfredo , Hernández José María , Bruschi Giuseppe , Spargias Konstantinos , Iadanza Alessandro , Brecker Stephen , Palma José Honório , Finkelstein Ariel , Abdel-Wahab Mohamed , Lemos Pedro , Petronio Anna Sonia , Champagnac Didier , Sinning Jan-Malte , Salizzoni Stefano , Napodano Massimo , Fiorina Claudia , Marzocchi Antonio , Leon Martin , Dvir Danny
Published: June 2016

Background—

Transcatheter valve implantation inside failed bioprosthetic surgical valves (valve-in-valve [ViV]) may offer an advantage over reoperation. Supra-annular transcatheter valve position may be advantageous in achieving better hemodynamics after ViV. Our objective was to define targets for implantation that would improve hemodynamics after ViV.

Methods and Results—

Cases from the Valve-in-Valve International Data (VIVID) registry were analyzed using centralized core laboratory assessment blinded to clinical events. Multivariate analysis was performed to identify independent predictors of elevated postprocedural gradients (mean ≥20 mm Hg). Optimal implantation depths were defined by receiver operating characteristic curve. A total of 292 consecutive patients (age, 78.9±8.7 years; 60.3% male; 157 CoreValve Evolut and 135 Sapien XT) were evaluated. High implantation was associated with significantly lower rates of elevated gradients in comparison with low implantation (CoreValve Evolut, 15% versus 34.2%;
P
=0.03 and Sapien XT, 18.5% versus 43.5%;
P
=0.03, respectively). Optimal implantation depths were defined: CoreValve Evolut, 0 to 5 mm; Sapien XT, 0 to 2 mm (0–10% frame height); sensitivities, 91.3% and 88.5%, respectively. The strongest independent correlate for elevated gradients after ViV was device position (high: odds ratio, 0.22; confidence interval, 0.1–0.52;
P
=0.001), in addition to type of device used (CoreValve Evolut: odds ratio, 0.5; confidence interval, 0.28–0.88;
P
=0.02) and surgical valve mechanism of failure (stenosis/mixed baseline failure: odds ratio, 3.12; confidence interval, 1.51–6.45;
P
=0.002).

Conclusions—

High implantation inside failed bioprosthetic valves is a strong independent correlate of lower postprocedural gradients in both self- and balloon-expandable transcatheter valves. These clinical evaluations support specific implantation targets to optimize hemodynamics after ViV.
Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats
Authors: Lee Jin Hwan , Wei Ling , Gu Xiaohuan , Won Soonmi , Wei Zheng Zachory , Dix Thomas A. , Yu Shan Ping
Published: June 2016

Background and Purpose—

Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke.

Methods—

Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke.

Results—

PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia.

Conclusions—

The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke.
Interaction of Recanalization, Intracerebral Hemorrhage, and Cerebral Edema After Intravenous Thrombolysis
Authors: Cheripelli Bharath Kumar , Huang Xuya , MacIsaac Rachael , Muir Keith W.
Published: June 2016

Background and Purpose—

Both intracerebral hemorrhage (ICH) and brain edema have been attributed to reperfusion after intravenous thrombolysis. We explored the interaction of recanalization and core size for imaging outcomes (ICH and vasogenic brain edema).

Methods—

In patients with anterior circulation occlusion given intravenous thrombolysis <4.5 hours and imaged with computed tomographic (CT) perfusion and CT angiography, we defined volumes of core (relative delay time >2 s and relative cerebral blood flow <40%) and penumbra (relative delay time >2 s). CT and CT angiography at 24 hours were reviewed for ICH (European Cooperative Acute Stroke Study [ECASS]-2 definition), early vasogenic edema (third International Stroke Trial [IST-3] criteria), and recanalization (thrombolysis in myocardial infarction 2–3). Independent effects of recanalization, core volume and potential interactions on edema, ICH and day 90 outcomes were estimated by logistic regression.

Results—

In 123 patients, there was a trend for recanalization to be associated with H1/2 ICH (odds ratio [OR], 2.3 [0.97–5.5];
P
=0.06) but not with PH1/2 ICH (OR, 1.7 [0.33–8.8];
P
=0.5), any edema, or significant brain edema (OR, 1.45 [0.4–4.9];
P
=0.55). Ischemic core (>50 mL) was associated with any ICH (OR, 4.0 [1.6–9.5];
P
=0.003), edema (OR, 5.4 [2–14];
P
<0.01), and significant brain edema (OR, 17.4 [5.3–57];
P
<0.01) but not with PH1/2 ICH (OR, 1.2 [0.23–6.5];
P
=0.8), after controlling for recanalization. There was no significant interaction of recanalization and large core for any adverse outcomes.

Conclusions—

Large ischemic core was associated with poorer outcomes and both early vasogenic brain edema and ICH, but recanalization on 24-hour CT angiography was associated with clinically favorable outcome. There was no significant interaction of recanalization and large core volume for any outcomes. The association of hemorrhage or brain edema with post-thrombolysis reperfusion is unclear.
Majority of 30-Day Readmissions After Intracerebral Hemorrhage Are Related to Infections
Authors: Lord Aaron S. , Lewis Ariane , Czeisler Barry , Ishida Koto , Torres Jose , Kamel Hooman , Woo Daniel , Elkind Mitchell S.V. , Boden-Albala Bernadette
Published: June 2016

Background and Purpose—

Infections are common after intracerebral hemorrhage, but little is known about the risk of serious infection requiring readmission after hospital discharge.

Methods—

To determine if infections are prevalent in patients readmitted within 30 days of discharge, we performed a retrospective cohort study of patients discharged from nonfederal acute care hospitals in California with a primary diagnosis of intracerebral hemorrhage between 2006 and 2010. We excluded patients who died during the index admission, were discharged against medical advice, or were not California residents. Our main outcome was 30-day unplanned readmission with primary infection–related
International Classification of Diseases
, Ninth Revision, Clinical Modification code.

Results—

There were 24 540 index intracerebral hemorrhage visits from 2006 to 2010. Unplanned readmissions occurred in 14.5% (n=3550) of index patients. Of 3550 readmissions, 777 (22%) had an infection-related primary diagnosis code. When evaluating primary and all secondary diagnosis codes, infection was associated with 1826 (51%) of readmissions. Other common diagnoses associated with readmission included stroke-related codes (n=840, 23.7%) and aspiration pneumonitis (n=154, 4.3%). The most common infection-related primary diagnosis codes were septicemia (n=420, 11.8%), pneumonia (n=124, 3.5%), urinary tract infection (n=141, 4.0%), and gastrointestinal infection (n=42, 1.2%). Patients with a primary infection–related
International Classification of Diseases
, Ninth Revision, Clinical Modification code on readmission had higher in-hospital mortality compared with other types of readmission (15.6% versus 8.0%,
P
<0.001). After controlling for other predictors of mortality, primary infection–related readmissions remained associated with in-hospital mortality (relative risk, 1.7; 95% confidence interval, 1.3–2.2).

Conclusions—

Infections are associated with a majority of 30-day readmissions after intracerebral hemorrhage and increased mortality. Efforts should be made to reduce infection-related complications after hospital discharge.
PPM1A
Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients
Authors: Gallego-Fabrega Cristina , Carrera Caty , Reny Jean-Luc , Fontana Pierre , Slowik Agnieszka , Pera Joanna , Pezzini Alessandro , Serrano-Heras Gemma , Segura Tomás , Bin Dukhyil Abdul-Aziz A. , Martí-Fàbregas Joan , Muiño Elena , Cullell Natalia , Montaner Joan , Krupinski Jerzy , Fernandez-Cadenas Israel
Published: June 2016

Background and Purpose—

Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients.

Methods—

We performed an epigenetic joint analysis study in 327 patients treated with aspirin. In the discovery stage, we performed a nested case–control study in 38 matched ischemic stroke patients in whom 450 000 methylation sites were analyzed. Nineteen patients presented vascular recurrence after stroke, and 19 matched patients did not present vascular recurrence during the first year of follow-up. In a second stage, 289 new patients were analyzed by EpiTYPER.

Results—

The following 3 differentially methylated candidate CpG sites, were identified in the discovery stage and analyzed in the second stage: cg26039762 (
P
=9.69×10
−06
,
RAF1
), cg04985020 (
P
=3.47×10
−03
,
PPM1A
), and cg08419850 (
P
=3.47×10
−03
,
KCNQ1
). Joint analysis identified an epigenome-wide association for cg04985020 (
PPM1A
;
P
=1.78×10
−07
), with vascular recurrence in patients treated with aspirin.

Conclusions—

The pattern of differential methylation in
PPM1A
is associated with vascular recurrence in aspirin-treated stroke patients.
Early Supported Discharge by Caregiver-Mediated Exercises and e-Health Support After Stroke
Authors: van den Berg Maayken , Crotty Maria , Liu Enwu , Killington Maggie , Kwakkel Gert , van Wegen Erwin
Published: June 2016

Background and Purpose—

This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden.

Methods—

Sixty-three hospitalized stroke patients (mean age 68.7, 64% female) were randomly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care. Primary outcome was the Stroke Impact Scale mobility domain. Secondary outcomes included length of stay, other Stroke Impact Scale domains, readmissions, motor impairment, strength, walking ability, balance, mobility, (extended) activities of daily living, psychosocial functioning, self-efficacy, quality of life, and fatigue. Additionally, caregiver’s self-reported fatigue, symptoms of anxiety, self-efficacy, and strain were assessed. Assessments were completed at baseline and at 8 and 12 weeks.

Results—

Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility (
P
=0.6); however, carers reported less fatigue (4.6, confidence interval [CI] 95% 0.3–8.8;
P
=0.04) and higher self-efficacy (−3.3, CI 95% −5.7 to −0.9;
P
=0.01) at week 12. Per-protocol analysis, examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility (−9.8, CI 95% −20.1 to 0.4;
P
=0.06), significantly improved extended activities of daily living scores at week 8 (−3.6, CI 95% −6.3 to −0.8;
P
=0.01) and week 12 (3.0, CI 95% −5.8 to −0.3;
P
=0.03), a 9-day shorter length of stay (
P
=0.046), and fewer readmissions over 12 months (
P
<0.05).

Conclusions—

Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice, resulting in improved patient-extended activities of daily living, reduced length of stay with fewer readmissions post stroke, and reduced levels of caregiver fatigue with increased feelings of self-efficacy. The current findings justify a larger definite phase III randomized controlled trial.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au
. Unique identifier: ACTRN12613000779774.
Diet analysis indicates seasonal fluctuation in trophic overlap and separation between a native and an introduced shrimp species (Decapoda, Palaemonidae) in the tidal river Thames (U.K.)
Authors: Ashelby Christopher W. , De Grave Sammy , Johnson Magnus L.
Published: June 2016

The diets of Palaemon longirostris and the non-native P. macrodactylus were investigated to explore their competitive interactions. Both species are largely carnivorous with amphipods being the dominant prey. Chironomid larvae were consumed in large numbers by both species in summer. Vacuity coefficients were higher for both species in winter than summer. A high degree of dietary overlap occurs in winter, with less overlap in summer suggesting that the two species compete for food on a seasonal basis, which may be partly attributed to the absence of chironomid larvae, and generally reduced prey availability, in the winter. If summer prey also become limited then competition for food may increase and P. macrodactylus may then have an adverse effect on P. longirostris. An introduction of P. macrodactylus in the summer, when there is less competition for food, may be more likely to lead to a successful colonisation than one in the winter.
Sabk-e Hendi and the Crisis of Authority in Eighteenth-Century Indo-Persian Poetics
Authors: Dudney Arthur
Published: June 2016

Modern debates over the merits of the so-called Indian Style (Sabk-e Hendi) in Persian literature, which was dominant from the late sixteenth to early nineteenth centuries, have been based on problematic assumptions about how literary style is tied to place. Scholars have often therefore interpreted the Persian literary criticism of the first half of the eighteenth century as a contest between Indians who praised Persian texts written in India and Iranians who asserted their privilege as native speakers to denigrate them. A more nuanced reading suggests that the debates mainly addressed stylistic temporality, namely the value of the writing styles of the “Ancients” (motaqaddemin) versus the innovative style of the “Moderns” (motaʾakhkherin). In the thought of the Indian critic Serāj al-Din ʿAli Khān Ārzu (d. 1756), there is clear evidence of a perceived rupture in literary culture that we can call a “crisis of authority.” Ārzu was concerned because Persian poetry had been judged according to “sanad” or precedent, but poets—both Indian and Iranian—were composing in a relatively new style (tāza-guʾi, literally “fresh speech”) that routinely went beyond the available precedents. All poets who know Persian well, he argued, including Indians, are allowed to innovate. While there was obvious rivalry between Persian-knowing Indians and the many Central Asians and Iranians settled in India, the contemporary terms of the debate have little in common with the later nationalism-tinged framing familiar to us.
Re-establishment of Chamaecrista cultrifolia (Leguminosae, Caesalpinioideae) based on morphological and molecular analyses
Authors: BARBOSA ARIANE RAQUEL , MACHADO MARLON CÂMARA , LEWIS GWILYM PETER , FOREST FÉLIX , QUEIROZ LUCIANO PAGANUCCI DE
Published: June 2016

The wide morphological variation observed in Chamaecrista diphylla was analyzed using morphological and molecular data. Three distinct morphotypes were identified, namely: a morphotype corresponding to the original description of Chamaecrista diphylla, a second morphotype corresponding to the original description of the synonym Chamaecrista cultrifolia, and a third morphotype with shared characteristics of the other two, which in the molecular analyses grouped with the C. cultrifolia morphotype. Chamaecrista cultrifolia is re-established as a distinct species, but its circumscription is emended to include the third morphotype identified in the morphological and molecular analyses of this study.
Cloud Radiative Effects and Precipitation in Extratropical Cyclones
Authors: Polly James B. , Rossow William B.
Published: June 2016

Clouds associated with extratropical cyclones complicate the well-developed theory of dry baroclinic waves through feedback on their dynamics by precipitation and cloud-altered radiative heating. The relationships between cyclone characteristics and the diabatic heating associated with cloud radiative effects (CREs) and latent heat release remain unclear. A cyclone tracking algorithm [NASA’s Modeling, Analysis, and Prediction (MAP) Climatology of Midlatitude Storminess (MCMS)] is used to identify over 106 cyclones in 33 years of the ERA-Interim and collect the properties of each disturbance. Considering storm intensity as related to wind speeds, which depend on the pressure gradient, the distribution of cyclone properties is investigated using groups defined by their depth (local pressure anomaly) and the radius of the region within closed pressure contours to investigate variations with longitude (especially ocean and land), hemisphere, and season. Using global data products of cloud radiative effects on in-atmosphere net radiation [the ISCCP radiative flux profile dataset (ISCCP-FD)] and precipitation (GPCP), composites are assembled for each cyclone group and for “nonstormy” locations. On average, the precipitation rate and the CRE are approximately the same among all cyclone groups and do not strongly differ from nonstormy conditions. The variance of both precipitation and CRE increases with cyclone size and depth. In larger, deeper storms, maximum precipitation and CRE increase, but so do the amounts of nonprecipitating and clear-sky conditions.