bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual Localisation for Onychomatricoma on the 5th Toenail: A Case Report and Review of the Literature
Authors: Coutellier A. , Théate I. , Vanhooteghem O.
Published: July 2016

Onychomatricoma is a rare and benign tumour of the nail matrix but originates rarely from the ventral portion of the proximal nail fold. This tumour is characterised by fingerlike projections that invade the nail plate. This lesion, of unknown aetiology, is typically asymptomatic with slow progression. Localisation on the finger is the most frequently described. We report the case of a 68-year-old woman who has an onychomatricoma in an unusual location, the fifth toe of the left foot. Due to its clinical appearance, the tumour can be confused with and treated as onychomycosis. However, if it is resistant to an oral antifungal well behaved treatment, one must consider onychomatricoma diagnosis.
Success Rates of Vitrectomy in Treatment of Rhegmatogenous Retinal Detachment
Authors: Mohamed Yasser Helmy , Ono Kozue , Kinoshita Hirofumi , Uematsu Masafumi , Tsuiki Eiko , Fujikawa Azusa , Kitaoka Takashi
Published: July 2016

Aim. To investigate the anatomical success rates of pars plana vitrectomy (PPV) after primary rhegmatogenous retinal detachment (RRD).Methods. This retrospective study was conducted between December 2008 and October 2014 at Nagasaki University Hospital. The preoperative data recorded included the lens status, location of the retinal tear, whether a tear was visualized, presence of multiple tears, macula status, presence of peripheral lattice retinal degeneration, and best-corrected visual acuity (BCVA). The primary outcome measures were anatomical (primary and final) and functional success (visual acuity better than 6/60).Results. This study evaluated 422 eyes of 411 patients with a mean age of57.7±11.2years. The single-operation reattachment rate (primary anatomical success) was 89.8%. The final anatomical success rate was 100% after 2–6 operations (mean =3.14±1.03). Functional success rate after the primary reattachment operation was 96.7%, while it was 97.2% at the end of the follow-up. Multiple logistic regression analysis of the possible risk factors for the primary anatomical failure showed a significant relation with the 25 G instruments (P=0.002) and the presence of multiple tears (P=0.01).Conclusion. The primary anatomical success of PPV for primary uncomplicated RRD was 89.8% and the final anatomical success rate was 100%.
A Study of the Far Infrared Spectrum of N-Acetyl-D-Glucosamine Using THz-TDS, FTIR, and Semiempirical Quantum Chemistry Methods
Authors: Chamorro-Posada Pedro , Silva-Castro Iosody , Vázquez-Cabo José , Martín-Ramos Pablo , López-Santos José María , Martín-Gil Jesús
Published: July 2016

The far infrared spectrum of N-acetyl-D-glucosamine has been studied by combining THz–TDS and FTIR characterization techniques with theoretical studies based on semiempirical quantum chemistry methods. A strong spectral peak at 60 cm−1 has been identified, which constitutes the main signature of the material in the terahertz band. Calculated molecular vibrations are in good qualitative and semiquantitative agreement with both the THz-TDS and FTIR experiments. In comparison to previous DFT-based studies, the semiempirical approach chosen herein, suitable for parallel multi-core and GPU acceleration, allows for a full study using periodic boundary conditions and no further approximations within a constrained computing time.
The Comparison of Distributed P2P Trust Models Based on Quantitative Parameters in the File Downloading Scenarios
Authors: Wang Jingpei , Liu Jie
Published: July 2016

Varied P2P trust models have been proposed recently; it is necessary to develop an effective method to evaluate these trust models to resolve the commonalities (guiding the newly generated trust models in theory) and individuality (assisting a decision maker in choosing an optimal trust model to implement in specific context) issues. A new method for analyzing and comparing P2P trust models based on hierarchical parameters quantization in the file downloading scenarios is proposed in this paper. Several parameters are extracted from the functional attributes and quality feature of trust relationship, as well as requirements from the specific network context and the evaluators. Several distributed P2P trust models are analyzed quantitatively with extracted parameters modeled into a hierarchical model. The fuzzy inferring method is applied to the hierarchical modeling of parameters to fuse the evaluated values of the candidate trust models, and then the relative optimal one is selected based on the sorted overall quantitative values. Finally, analyses and simulation are performed. The results show that the proposed method is reasonable and effective compared with the previous algorithms.
Integrated Resistivity and Ground Penetrating Radar Observations of Underground Seepage of Hot Water at Blawan-Ijen Geothermal Field
Authors: Maryanto Sukir , Suciningtyas Ika Karlina Laila Nur , Dewi Cinantya Nirmala , Rachmansyah Arief
Published: July 2016

Geothermal resource investigation was accomplished for Blawan-Ijen geothermal system. Blawan geothermal field which located in the northern part of Ijen caldera presents hydrothermal activity related with Pedati fault and local graben. There were about 21 hot springs manifestations in Blawan-Ijen area with calculated temperature about 50°C. We have performed several geophysical studies of underground seepage of hot water characterization. The geoelectric resistivity and GPR methods are used in this research because both of them are very sensitive to detect the presence of hot water. These preliminary studies have established reliable methods for hydrothermal survey that can accurately investigate the underground seepage of hot water with shallow depth resolution. We have successfully identified that the underground seepage of hot water in Blawan geothermal field is following the fault direction and river flow which is evidenced by some hot spring along the Banyu Pahit river with resistivity value less than 40 Ωm and medium conductivity.
Mutation Testing Approach to Negative Testing
Authors: Strug Joanna
Published: July 2016

Negative testing deals with an important problem of assessing a system ability to handle unexpected situations. Such situations, if unhandled, may lead to system failures that in some cases can have catastrophic consequences. This paper presents a mutation testing-based approach for generation of test cases supporting negative testing. Application of this approach can provide, in a systematic and human-unbiased way, test cases effectively testing wide range of unexpected situations. Thus, it can contribute to improvement of a tested system. The paper formally defines mutation operators used to control the generation process, describes a generic framework for the generation and execution of the test cases, and explains how to interpret results.
Using Recycled Glass and Zeolite in Concrete Pavement to Mitigate Heat Island and Reduce Thermal Cracks
Authors: Pancar Erhan Burak
Published: July 2016

Urban heat island (UHI) effect is built environmental issue related to pavements. It is desired to reduce pavement high surface temperature in summer to mitigate UHI effect. High surface temperature also affects slab temperature difference (the top surface temperature minus the bottom surface temperature of the slab). The increased slab temperature difference induces a high possibility of cracking in concrete roads. The prime aim of this study was to reduce the slab surface temperature by using recycled glass as a fine aggregate and zeolite as cement in concrete. Recycled glass was used to replace fine aggregate in proportions of 10%, 20%, and 30% by total weight of aggregate. Zeolite replaced Portland cement in proportions of 10% and 30% for three different proportions of recycled glass concrete mixtures. Optimum proportions were determined by examining mechanical properties of samples and alkali-silica reactions. It was noticed that using recycled glass and zeolite together in concrete reduces pavement surface temperature and temperature gradient in summer.
Revisits within 48 Hours to a Thai Emergency Department
Authors: Sri-on Jiraporn , Nithimathachoke Adisak , Tirrell Gregory Philip , Surawongwattana Sataporn , Liu Shan Woo
Published: July 2016

Objective. Emergency department (ED) revisits are a common ED quality measure. This study was undertaken to ascertain the contributing factors of revisits within 48 hours to a Thai ED and to explore physician-related, illness-related, and patient-related factors behind those revisits.Methods. This study was a chart review from one tertiary care, urban Thai hospital from October 1, 2009, to September 31, 2010. We identified patients who returned to the ED within 48 hours for the same or related complaints after their initial discharge. Three physicians classified revisit as physician-related, illness-related, and patient-related factors.Results. Our study included 172 ED patients’ charts. 86/172 (50%) were male and the mean age was38 ± 5.6(SD) years. The ED revisits contributing factors were physician-related factors [86/172 (50.0%)], illness-related factors [61/172 (35.5%)], and patient-related factor [25/172 (14.5%)], respectively. Among revisits classified as physician-related factors, 40/86 (46.5%) revisits were due to misdiagnosis and 36/86 (41.9%) were due to suboptimal management. Abdominal pain [27/86 (31.4%)] was the majority of physician-related chief complaints, followed by fever [16/86 (18.6%)] and dyspnea [15/86 (17.4%)].Conclusion. Misdiagnosis and suboptimal management contributed to half of the 48-hour repeat ED visits in this Thai hospital.
Thrombin Cleavage of Osteopontin Modulates Its Activities in Human CellsIn Vitroand Mouse Experimental Autoimmune EncephalomyelitisIn Vivo
Authors: Boggio Elena , Dianzani Chiara , Gigliotti Casimiro Luca , Soluri Maria Felicia , Clemente Nausicaa , Cappellano Giuseppe , Toth Erika , Raineri Davide , Ferrara Benedetta , Comi Cristoforo , Dianzani Umberto , Chiocchetti Annalisa
Published: July 2016

Osteopontin is a proinflammatory cytokine and plays a pathogenetic role in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), by recruiting autoreactive T cells into the central nervous system. Osteopontin functions are modulated by thrombin cleavage generating N- and C-terminal fragment, whose individual roles are only partly known. Published data are difficult to compare since they have been obtained with heterogeneous approaches. Interestingly, thrombin cleavage of osteopontin unmasks a cryptic domain of interaction withα4β1integrin that is the main adhesion molecule involved in lymphocyte transmigration to the brain and is the target for natalizumab, the most potent drug preventing relapses. We produced recombinant osteopontin and its N- and C-terminal fragments in an eukaryotic system in order to allow their posttranslational modifications. We investigated,in vitro,their effect on human cells andin vivoin EAE. We found that the osteopontin cleavage plays a key role in the function of this cytokine and that the two fragments exert distinct effects bothin vitroandin vivo. These findings suggest that drugs targeting each fragment may be used to fine-tune the pathological effects of osteopontin in several diseases.
Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2
Authors: Zhang Jia-Xing , Chen Zhen-Hua , Xu Yi , Chen Jie-Wei , Weng Hui-Wen , Yun Miao , Zheng Zou-San , Chen Cui , Wu Bing-Li , Li En-Min , Fu Jian-Hua , Ye Sheng , Xie Dan
Published: July 2016

Purpose:

We previously reported the oncogenic role of paired-like homeodomain 2 (PITX2) in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify the miRNA regulators of PITX2 and the mechanism underlying the pathogenesis of ESCC.

Experimental Design:

Using miRNA profiling and bioinformatics analyses, we identified miR-644a as a negative mediator of PITX2 in ESCC. A series of in vivo and in vitro assays were performed to confirm the effect of miR-644a on PITX2-mediated ESCC malignancy.

Results:

ESCC cells and tissues expressed less miR-644a than normal epithelial controls. In patient samples, lower expression of miR-644a in ESCC tissues was significantly correlated with tumor recurrence and/or metastasis, such that miR-644a, PITX2, and the combination of the two were independent prognostic indicators for ESCC patient's survival (P < 0.05). Gain- and loss-of-function studies demonstrated that miR-644a inhibited ESCC cell growth, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. In addition, miR-644a dramatically suppressed self-renewal and stem cell–like traits in ESCC cells. Furthermore, the effect of upregulation of miR-644a was similar to that of PITX2 knockdown in ESCC cells. Mechanistic studies revealed that miR-644a attenuates ESCC cells' malignancy and stem cell–associated phenotype, at least partially, by inactivation of the Akt/GSK-3β/β-catenin signaling pathway through PITX2. Furthermore, promoter hypermethylation caused downregulation of miR-644a in ESCC.

Conclusions:

Downregulation of miR-644a plays an important role in promoting both aggressiveness and stem-like traits of ESCC cells, suggesting that miR-644a may be useful as a novel prognostic biomarker or therapeutic target for the disease. Clin Cancer Res; 23(1); 298–310. ©2016 AACR.
FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer
Authors: Walker Amanda J. , Wedam Suparna , Amiri-Kordestani Laleh , Bloomquist Erik , Tang Shengui , Sridhara Rajeshwari , Chen Wei , Palmby Todd R. , Fourie Zirkelbach Jeanne , Fu Wentao , Liu Qi , Tilley Amy , Kim Geoffrey , Kluetz Paul G. , McKee Amy E. , Pazdur Richard
Published: July 2016

On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36–0.59; P < 0.0001]. Safety data confirmed the known adverse reaction profile of palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968–72. ©2016 AACR.
Alternative Lengthening of Telomeres and Loss of DAXX/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors
Authors: Singhi Aatur D. , Liu Ta-Chiang , Roncaioli Justin L. , Cao Dengfeng , Zeh Herbert J. , Zureikat Amer H. , Tsung Allan , Marsh J. Wallis , Lee Kenneth K. , Hogg Melissa E. , Bahary Nathan , Brand Randall E. , McGrath Kevin M. , Slivka Adam , Cressman Kristi L. , Fuhrer Kimberly , O'Sullivan Roderick J.
Published: July 2016

Purpose: Pancreatic neuroendocrine tumors (PanNET) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing has identified recurrent mutations in the genes DAXX and ATRX, which correlate with loss of protein expression and alternative lengthening of telomeres (ALT). Both ALT and DAXX/ATRX loss were initially reported to be associated with a favorable prognosis; however, recent studies suggest the contrary. Our aims were to assess the prevalence and prognostic significance of ALT and DAXX/ATRX in both primary and metastatic PanNETs.

Experimental Design: Telomere-specific FISH and DAXX/ATRX IHC was performed on a multi-institutional cohort of 321 patients with resected PanNET and 191 distant metastases from 52 patients. These results were correlated with clinicopathologic features, including disease-free survival (DFS) and disease-specific survival (DSS).

Results: The prevalence of ALT and DAXX/ATRX loss in resected PanNETs was 31% and 26%, respectively, and associated with larger tumor size, higher WHO grade, lymph node metastasis, and distant metastasis (P < 0.001). The 5-year DFS and 10-year DSS of patients with ALT-positive and DAXX/ATRX-negative PanNETs were 40% and 50%, respectively, as compared with 96% and 89%, respectively, for wild-type PanNETs. Among distant metastases, ALT and DAXX/ATRX loss was 67% and 52%, respectively, and only occurred in the setting of an ALT-positive and DAXX/ATRX-negative primary PanNET. By multivariate analysis, both ALT and DAXX/ATRX loss were negative, independent prognostic factors for DFS.

Conclusions: ALT and DAXX/ATRX loss in PanNETs was associated with shorter DFS and DSS and likely plays a significant role in driving metastatic disease. Clin Cancer Res; 23(2); 600–9. ©2016 AACR.
MOR209/ES414, a Novel Bispecific Antibody Targeting PSMA for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Hernandez-Hoyos Gabriela , Sewell Toddy , Bader Robert , Bannink Jeannette , Chenault Ruth A. , Daugherty Mollie , Dasovich Maria , Fang Hang , Gottschalk Rebecca , Kumer John , Miller Robert E. , Ravikumar Padma , Wiens Jennifer , Algate Paul A. , Bienvenue David , McMahan Catherine J. , Natarajan Sateesh K. , Gross Jane A. , Blankenship John W.
Published: July 2016

Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains a highly unmet medical need and current therapies ultimately result in disease progression. Immunotherapy is a rapidly growing approach for treatment of cancer but has shown limited success to date in the treatment of mCRPC. We have developed a novel humanized bispecific antibody, MOR209/ES414, built on the ADAPTIR (modular protein technology) platform, to redirect T-cell cytotoxicity toward prostate cancer cells by specifically targeting T cells through CD3ϵ to prostate cancer cells expressing PSMA (prostate-specific membrane antigen). In vitro cross-linking of T cells with PSMA-expressing tumor cells by MOR209/ES414 triggered potent target-dependent tumor lysis and induction of target-dependent T-cell activation and proliferation. This activity occurred at low picomolar concentrations of MOR209/ES414 and was effective at low T-effector to tumor target cell ratios. In addition, cytotoxic activity was equivalent over a wide range of PSMA expression on target cells, suggesting that as few as 3,700 PSMA receptors per cell are sufficient for tumor lysis. In addition to high sensitivity and in vitro activity, MOR209/ES414 induced limited production of cytokines compared with other bispecific antibody formats. Pharmacokinetic analysis of MOR209/ES414 demonstrated a serum elimination half-life in NOD/SCID γ (NSG) mice of 4 days. Administration of MOR209/ES414 in murine xenograft models of human prostate cancer significantly inhibited tumor growth, prolonged survival, and decreased serum prostate-specific antigen levels only in the presence of adoptively transferred human T cells. On the basis of these preclinical findings, MOR209/ES414 warrants further investigation as a potential therapeutic for the treatment of CRPC. Mol Cancer Ther; 15(9); 2155–65. ©2016 AACR.
Concepts to Target MYC in Pancreatic Cancer
Authors: Wirth Matthias , Mahboobi Siavosh , Krämer Oliver H. , Schneider Günter
Published: July 2016

Current data suggest that MYC is an important signaling hub and driver in pancreatic ductal adenocarcinoma (PDAC), a tumor entity with a strikingly poor prognosis. No targeted therapies with a meaningful clinical impact were successfully developed against PDAC so far. This points to the need to establish novel concepts targeting the relevant drivers of PDAC, like KRAS or MYC. Here, we discuss recent developments of direct or indirect MYC inhibitors and their potential mode of action in PDAC. Mol Cancer Ther; 15(8); 1792–8. ©2016 AACR.
Mitochondrial β-Carotene 9′,10′ Oxygenase Modulates Prostate Cancer Growth via NF-κB Inhibition: A Lycopene-Independent Function
Authors: Gong Xiaoming , Marisiddaiah Raju , Zaripheh Susan , Wiener Doris , Rubin Lewis P.
Published: July 2016

Despite numerous inquiries into protective roles of lycopene in prostate cancer prevention or therapy, little is known about mechanisms by which lycopene or its metabolites inhibit prostate cancer. The enzyme β-carotene 9′,10′-oxygenase (BCO2), which catalyzes asymmetric cleavage of several carotenoids, is the principal regulator of lycopene metabolism, but the range of BCO2 biological functions is incompletely understood. This study investigated expression and functional roles of BCO2 in human prostate cancer. Expression of the bco2 gene is dramatically decreased in prostate cancer tissue and in a range of prostate cancer cell lines as compared with nonneoplastic prostate tissue and normal prostatic epithelial cells, respectively. Inhibition of DNA methyltransferase activity restored bco2 expression in prostate cancer cell lines tested. Treatment with lycopene or its metabolite, apo-10-lycopenal, also increased bco2 expression and reduced cell proliferation in androgen-sensitive cell lines, but lycopene neither altered bco2 expression nor cell growth in androgen-resistant cells. Notably, restoring bco2 expression in prostate cancer cells inhibited cell proliferation and colony formation, irrespective of lycopene exposure. Exogenous expression of either wild-type BCO2 or a mutant (enzymatically inactive) BCO2 in prostate cancer cells reduced NF-κB activity and decreased NF-κB nuclear translocation and DNA binding. Together, these results indicate epigenetic loss of BCO2 expression is associated with prostate cancer progression. Moreover, these findings describe previously unanticipated functions of BCO2 that are independent of its enzymatic role in lycopene metabolism.

Implications: This study identifies BCO2 as a tumor suppressor in prostate cancer. BCO2-mediated inhibition of NF-κB signaling implies BCO2 status is important in prostate cancer progression. Mol Cancer Res; 14(10); 966–75. ©2016 AACR.
Effectiveness of Left Atrial Appendage Exclusion Procedures to Reduce the Risk of Stroke: A Systematic Review of the Evidence
Authors: Noelck North , Papak Joel , Freeman Michele , Paynter Robin , Low Allison , Motu’apuaka Makalapua , Kondo Karli , Kansagara Devan
Published: July 2016

Background—

Atrial fibrillation is an important cause of cardioembolic stroke. Oral anticoagulants (OAC) reduce stroke risk but increase the risk of serious bleeding. Left atrial appendage (LAA) procedures have been developed to isolate the LAA from circulating blood flow, as an alternative to OAC. We conducted a systematic review of the benefits and harms of surgical and percutaneous LAA exclusion procedures.

Methods and Results—

We searched multiple data sources, including Ovid MEDLINE, Cochrane, and Embase, through January 7, 2015. Of 2567 citations, 20 primary studies met prespecified inclusion criteria. We abstracted data on patient characteristics, stroke, mortality, and adverse effects. We assessed study quality and graded the strength of evidence using published criteria. Trials found low-strength evidence that percutaneous LAA exclusion confers similar risks of stroke and mortality as continued OAC, but this evidence was limited to the Watchman device in patients eligible for long-term OAC. Observational studies found moderate-strength evidence of serious harms with a variety of percutaneous LAA procedures. There is low-strength evidence that surgical LAA exclusion does not add significant harm during heart surgery for another indication, but evidence on stroke reduction is insufficient.

Conclusions—

There is limited evidence that the Watchman device may be noninferior to long-term OAC in selected patients. Data on effectiveness of LAA exclusion devices is lacking in patients ineligible for long-term OAC. Percutaneous LAA devices are associated with high rates of procedure-related harms. Although surgical LAA exclusion during heart surgery does not seem to add incremental harm, there is insufficient evidence of benefit.
Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs
Authors: Kent Seamus , Haynes Richard , Hopewell Jemma C. , Parish Sarah , Gray Alastair , Landray Martin J. , Collins Rory , Armitage Jane , Mihaylova Borislava
Published: July 2016

Background—

Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown.

Methods and Results—

25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol–lowering treatment. The net effects of niacin–laropiprant on quality–adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin–laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs.

Conclusions—

In HPS2-THRIVE, the addition of extended-release niacin–laropiprant to statin-based therapy reduced quality of life–adjusted survival and increased hospital costs.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00461630.
Diabetes-Induced Jagged1 Overexpression in Endothelial Cells Causes Retinal Capillary Regression in a Murine Model of Diabetes Mellitus
Authors: Yoon Chang-Hwan , Choi Young-Eun , Cha Young Ryun , Koh Seok-Jin , Choi Jae-il , Kim Tae-Won , Woo Se Joon , Park Young-Bae , Chae In-Ho , Kim Hyo-Soo
Published: July 2016

Background:

Several mechanisms have been proposed to account for diabetes-induced microvasculopathy (DMV). Although Notch signaling was reported to be affected by glucose metabolism in endothelial cells during developmental angiogenesis, it has not been investigated in vascular remodeling of adult capillaries in relation to diabetes mellitus.

Methods:

We induced diabetes mellitus in 8-week-old adult mice by intravenously administering streptozotocin. After 6 weeks, we harvested organs, including retina, heart, and skeletal muscle, and evaluated the capillaries with immunofluorescence and confocal microscopy. We modulated endothelial Notch signaling using chemical inhibitors in wild-type mice or transgenic mice, inducing conditional knockout of Jagged1 or Mib1.

Results:

DMV was characterized by capillary remodeling, regression, and decreased density. Notch ligand Jagged1, but not δ-like ligand 4, was markedly increased in endothelial cells of diabetic mice. Using endothelium-specific Jagged1 knockdown mice, we found that blocking Jagged1 prevented DMV even under diabetic conditions. Furthermore, in the inducible endothelium-specific Jagged1 knockdown mice, blocking Jagged1 even at 4 weeks after the establishment of DMV could reverse it, leading to normalization of retinal vasculature. A search for downstream signals revealed that diabetes mellitus decreased the nuclear localization of Notch1 intracellular domain and reduced the expression of VE-cadherin and N-cadherin in endothelial cells. Chemical Notch inhibition phenocopied DMV in normal mice.

Conclusions:

Our findings indicate that diabetes mellitus induces Jagged1 overexpression and suppresses Notch signaling in endothelial cells, leading to DMV in adult mice. We conclude that dysregulated intercellular Notch signaling may be a novel mechanism of DMV.
Underutilization of Ambulatory ECG Monitoring After Stroke and Transient Ischemic Attack
Authors: Edwards Jodi D. , Kapral Moira K. , Fang Jiming , Saposnik Gustavo , Gladstone David J.
Published: July 2016

Background and Purpose—

Detection and treatment of atrial fibrillation is a major goal in secondary stroke prevention. Guidelines recommend at least 24 hours of ECG monitoring after stroke. However, it is unclear how often this is done in routine practice.

Methods—

In this longitudinal cohort study using data from the Ontario Stroke Registry, we analyzed consecutive patients presenting to designated stroke centers in Ontario, Canada (2003–2013) with a first acute ischemic stroke or transient ischemic attack (TIA) in sinus rhythm and without known atrial fibrillation. The primary outcome was the proportion of patients who received at least 24-hour Holter monitoring within 30 days after stroke/TIA. Secondary analyses assessed total duration of ECG monitoring completed within 90 days after stroke/TIA, temporal trends in monitoring use, and use of Holter monitoring relative to echocardiography.

Results—

Among 17 398 consecutive eligible patients (mean age 68.8±14.3 years), 30.6% had at least 24 hours of Holter monitoring within 30 days after stroke/TIA. Less than 1% of patients received prolonged monitoring beyond 48 hours. The median time to start monitoring was 9 days poststroke (interquartile range 3–25). Stroke/TIA patients were nearly twice as likely to receive an echocardiogram than a Holter monitor within 90 days (odds ratio 1.8, 95% confidence interval 1.67–2.01).

Conclusions—

Less than one third of patients in our cohort received guideline-recommended 24-hour Holter monitoring, and <1% received prolonged ambulatory ECG monitoring. These findings highlight a modifiable evidence-practice gap that likely contributes to an overdiagnosis of strokes as cryptogenic, an underdiagnosis of atrial fibrillation, and missed anticoagulant treatment opportunities for secondary stroke prevention.
Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke
Authors: Lees Kennedy R. , Khatri Pooja , Alexandrov Andrei V. , Bivard Andrew , Boltze Johannes , Broderick Joseph P. , Campbell Bruce C.V. , Creighton Francis M. , Fiorella David , Furlan Anthony J. , Gorelick Philip B. , Hess David C. , Kim Won-Ki , Latour Lawrence L. , Liebeskind David S. , Luby Marie , Lyden Patrick , Lynch John Kylan , Marshall Randolph S. , Menon Bijoy K. , Muir Keith W. , Palesch Yuko , Peng Helen , Pryor Kent E. , Mocco J , Rasmussen Peter , Sacco Ralph L. , Schwamm Lee H. , Smith Eric E. , Solberg Yoram , Vagal Achala , Warach Steven , Wechsler Lawrence R. , Wintermark Max , Yoo Albert J. , Zander Kay M.
Published: July 2016

Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines ≥2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care.
Remote Intracerebral Hemorrhage After Intravenous Thrombolysis
Authors: Prats-Sánchez Luis , Camps-Renom Pol , Sotoca-Fernández Javier , Delgado-Mederos Raquel , Martínez-Domeño Alejandro , Marín Rebeca , Almendrote Miriam , Dorado Laura , Gomis Meritxell , Codas Javier , Llull Laura , Gómez González Alejandra , Roquer Jaume , Purroy Francisco , Gómez-Choco Manuel , Cánovas David , Cocho Dolores , Garces Moises , Abilleira Sonia , Martí-Fàbregas Joan
Published: July 2016

Background and Purpose—

Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator.

Methods—

This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses.

Results—

We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3–27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6–14.1) increased the risk of rPH.

Conclusions—

The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.
Agonistic, Convivial, and Conceptual Aesthetics in New Social Design
Authors: Koskinen Ilpo
Published: July 2016

This paper explores aesthetics in what it calls new social design. It asks, “How can designers work with aesthetics when the main design object is social, and traditional object-bound aesthetic concepts lose their validity.” It describes three approaches to aesthetics: agonistic, which sees aesthetics as a way to lure people to interact with controversial content; convivial, which finds aesthetics in community interactions; and conceptual, which does away with aesthetics. All these have precedents in art.
Systems Intertwined: A Systemic View on the Design Situation
Authors: Lurås Sigrun
Published: July 2016

Designers are often facing complex design situations which may be challenging to grasp. In this paper I aim at making visible what designers need to make sense of through a systemic model of the design situation presenting the design situation as a system of three interconnected systems: the systems we design; the systems we design for; and the systems we design within. Using the theories of Dewey, Schön and Vickers, I discuss sensemaking and judgment-making in the context of design, and through the model I highlight how we may change the design situation we continuously strive to make sense of through our designs. The model was developed within the design research project Ulstein Bridge Concept, which addressed the design of a ship's bridge. However, it is of a generic nature and is applicable to any design project taking place in a complex context.
Decentering the Human in the Design of Collaborative Cities
Authors: Forlano Laura
Published: July 2016

Cities are currently being redesigned with sensors and data at their core. Environmental monitoring, crime tracking and traffic mapping are just a few examples of the socio-technical systems that are remaking cities. These systems are emergent sites of politics, values, and ethics where human and nonhuman actors collaborate, negotiate and debate the futures of their cities. One the one hand, they can be used for prediction, measurement and decision-making, but, on the other hand, they can also be harnessed to imagine alternative possible urban futures. Designers have an important role to play in mediating, making sense of, and intervening in these projects, which are at the intersection of the work of a variety of stakeholders including governments, business and citizens. This article draws on science and technology studies (STS) to think through ways designers can evolve existing human-centered design (HCD) methodologies to contend with socio-technical complexity at a time of great economic and environmental crisis. In particular, this article argues that it is necessary to create and explore methodologies that decenter the human and take the nonhuman seriously in order to meaningfully engage in the design of cities with more responsible, accountable, and ethical ways of engaging with emerging technologies.
Baudrillard and the Bauhaus: The Political Economy of Design
Authors: Holt Matthew
Published: July 2016

Though better known in the Anglophone world as the guru of postmodern “hyperreality”, the French philosopher and radical sociologist Jean Baudrillard devoted a great deal of attention to theorizing design. This paper singles out the moment—inspired by a conference he attended in 1972 in New York at MoMA—where he advances the argument that contemporary design, understood as articulating and incorporating the entirety of the artificial environment, is a direct manifestation of the most significant development in political economy since the industrial revolution—what Baudrillard calls the “political economy of the sign.” According to Baudrillard the origin of this expanded sense of design is the Bauhaus. That school sought to extend the role and mission of design to all fabricated phenomena, in the process collapsing any distinction between objects (and environments), turning them all into a fusion of art and technology, aesthetics and functionality. In explicating Baudrillard's argument, this paper also traces the missing presence of design in traditional political economy, arguing that Baudrillard was one of the first authors, albeit critically, to identify the now essential role of design in postindustrial capitalism.
Two new Platessa (Bacillariophyceae) from Amazonia: Platessa guianensis spec. nov., and P. itoupensis spec. nov.
Authors: TUDESQUE LOÏC , COHU RENÉ LE , WETZEL CARLOS E.
Published: July 2016

Recent investigations in the deep rainforest of Amazonia in French Guiana and in the north of Brazil revealed the presence of two new Platessa species. Detailed light (LM) and scanning electron microscope (SEM) observations were used to describe the morphology and the ultrastructure of these new monoraphid diatoms, Platessa guianensis and P. itoupensis. They display the taxonomic features characteristic of the genus Platessa, namely almost flat valves, straight raphe fissures and uni- to multiseriate striae with specific features such as the ornementation of the striae and the morphology of the groove surrounding the raphe endings. These two Platessa are the first ones described from Amazonia. They are compared with the two types of two similar species described originally from Indonesia (i.e. Platessa brevicostata and Platessa cataractarum) whose original materials are also here re-illustrated in LM and SEM. The taxonomical diagnosis is completed with comments on ecology issues. In addition, we proposed the recombination of three Achnanthes into Platessa based on published literature.
Systematics of Ichnanthus hoffmannseggii and allies (Poaceae, Paspaleae) based on molecular and morphological evidence
Authors: SILVA CHRISTIAN , DAVIDSE GERRIT , SCHNADELBACH ALESSANDRA SELBACH , DE OLIVEIRA REYJANE PATRÍCIA
Published: July 2016

Ichnanthus hoffmannseggii is an annual panicoid grass that occurs in sandy and open areas of Brazil and currently includes I. piresii in its synonymy. However, herbarium and field work led us to question this circumscription. In a previous phylogenetic study, a specimen with morphological affinities to I. hoffmannseggii was recovered as more related to Echinolaena oplismenoides (currently I. oplismenoides). This study aimed to clarify the relationship between I. hoffmannseggii, I. oplismenoides, and I. piresii using molecular and macro- and micromorphological data. We recognize these three taxa as distinct species and provide characters for distinguishing them and related species, including descriptions, comments, illustrations, distribution maps, SEM images of the upper anthecium, and phylogenetic relationships.
Lectotypifications and taxonomic changes in Brazilian Crotalaria L. (Leguminosae)
Authors: FLORES ANDRÉIA SILVA , ROCKINGER ALEXANDER , RODRIGUES RODRIGO SCHÜTZ , TOZZI ANA MARIA GOULART DE AZEVEDO
Published: July 2016

As part of a revision of the species of Crotalaria L. (Papilionoideae, Crotalarieae) occurring in Brazil, eleven lectotypifications are proposed for: Crotalaria acutiflora Benth., Crotalaria depauperata Mart. ex Benth., Crotalaria holosericea Nees & Mart., Crotalaria holosericea var. grisea Benth., Crotalaria laeta Mart. ex Benth., Crotalaria leptophylla Benth., Crotalaria rufipila Benth., Crotalaria unifoliolata Benth., Crotalaria vitellina Ker-Gawl., Crotalaria vitellina var. glabrata Benth., and Crotalaria vitellina var. minor Benth. Four new synonyms are also proposed.
Sponges of the family Axinellidae (Porifera: Demospongiae) in Indonesia
Authors: ALVAREZ BELINDA , VOOGD NICOLE J. DE , SOEST ROB W.M VAN
Published: July 2016

Nine species in five genera of the family Axinellidae, including three new species, Axinella badungensis sp. nov., A. balinensis sp. nov. and Phycopsis pesgalli sp. nov. are recorded from Indonesian waters within the limits of the Western Coral Triangle province. Descriptions and discussion of those species are presented here. Four new combinations, Phakettia arbora (Sim, Kim & Byeon, 1990) comb.nov., P. trachys (De Laubenfels, 1954) comb.nov., Echinoclathria retepora (Lendenfeld, 1887) comb.nov. and Amphimedon hispidula (Ridley, 1884) comb.nov. are also established here. The distributions of species previously described are here extended to the study area with the exception of Phakellia atypica which seems so far restricted to Indonesia.
Two new species of quill mites (Acari: Syringophilidae) associated with the Chestnut-fronted Helmetshrike Prionops scopifrons (Peters) (Passeriformes: Vangidae) in Kenya
Authors: KLIMOVIČOVÁ MIROSLAVA , SKORACKI MACIEJ , HROMADA MARTIN
Published: July 2016

Two new species of syringophilid mites collected from Prionops scopifrons (Peters) (Passeriformes: Vangidae) in Kenya are described: Neoaulonastus prionops sp. nov. and Picobia meru sp. nov. They are the first syringophilid records from birds of the family Vangidae.
Generic redescription, two new species, and a key to the species of the cicada genus Ariasa Distant, 1905 with the description of a new genus (Hemiptera: Cicadidae: Cicadinae: Fidicinini)
Authors: SANBORN Allen F.
Published: July 2016

The cicada genus Ariasa Distant, 1905 is redescribed.  Ariasa albimaculosa n. sp. is described from Colombia and A. bartletti n. sp. is described from Peru.  The current 14 species of Ariasa are listed along with their synonymies, known distribution of each species, and a key to the species is provided.  The first records of Ariasa bilaqueata (Uhler, 1903) for Peru and French Guiana are provided. Cracenpsaltria brasiliorum (Kirkaldy, 1909) rev. stat., n. comb. is determined to be the correct name for the taxon Cicada marginata Olivier, 1790 and the new genus Cracenpsaltria n. gen. is erected for the taxon.  The distribution of C. brasiliorum rev. stat., n. comb. is expanded to include Bolivia and Peru.
Stapecolis, new genus of Ochlerini (Hemiptera: Pentatomidae: Discocephalinae)
Authors: GARBELOTTO THEREZA DE A. , CAMPOS LUIZ A. , GRAZIA JOCELIA
Published: July 2016

A cladistic analysis of the Herrichela clade (Ochlerini) was conducted to solve problems concerning the systematics of the genus Alitocoris Sailer; this recovered monophyletic groups which are considered to be new genera. Stapecolis gen. nov. is here proposed for two species (S. latus sp. nov. and S. bimaculatus sp. nov.) representing one of those monophyletic groups. The new genus is supported by ten synapomorphies, five of them pertaining to the morphology of the pygophore have not been found together in any other genera of Ochlerini. The female genitalia also has characteristics different from closely related genera.
Two new species of Microcosmodes Strand (Coleoptera: Carabidae: Panagaenini) from Oman and Iran
Authors: HÄCKEL MARTIN , AZADBAKHSH SAEED
Published: July 2016

Two new species of the genus Microcosmodes Strand, M. arabicus from Oman and M. persicus from Iran, are described, compared with related taxa, and their affinities are discussed. The species are very similar and belong to the same species group.
Review of the genus Tricheops Newman (Coleoptera: Cerambycidae: Cerambycinae) with description of two new species from Western Australia
Authors: Evans Brenda , Ślipiński Adam
Published: July 2016

Two new species of Tricheops Newman, T. remus sp. nov. and T. guillemeti sp. nov. from Western Australia are described and illustrated. The genus Tricheops is redescribed and a key to species is provided. The structures associated with the unusual three-lobed eyes of Tricheops and Bardistus Newman are discussed.