bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttranslational Modifications and the Immunogenicity of Biotherapeutics
Authors: Jefferis Roy
Published: April 2016

Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs) bothin vivoandin vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA); aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs) are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs), a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.
Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy
Authors: Wang Cheng-Zhi , Kazmierczak Robert A. , Eisenstark Abraham
Published: April 2016

Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such asSalmonella,Listeria,Escherichia, andClostridiumhave proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeuticSalmonellamodels, the most intensively studied bacterial genus in this field. One of theseSalmonellamodels is ourSalmonella entericaserovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypesin vitroandin vivo, and what is currently known about the mechanisms by which they target and destroy tumors.
Broad Spectrum Anti-Quorum Sensing Activity of Tannin-Rich Crude Extracts of Indian Medicinal Plants
Authors: Shukla Varsha , Bhathena Zarine
Published: April 2016

Quorum sensing (QS) mechanisms have been demonstrated to have significance in expression of pathogenicity in infectious bacteria. In Gram negative bacteria the autoinducer molecules that mediate QS are acyl homoserine lactones (AHL) and in Gram positive bacteria they are peptides called autoinducing peptides (AIP). A screening of tannin-rich medicinal plants was attempted to identify extracts that could interrupt the QS mechanisms in both Gram positive and Gram negative bacteria over a wide range of concentrations and therefore potentially be potent agents that could act as broad spectrum QS inhibitors. Six out of the twelve Indian medicinal plant extracts that were analyzed exhibited anti-QS activity inChromobacterium violaceum12472 and inS.aureusstrain withagr:blaZfusion over a broad range of subinhibitory concentrations, indicating that the extracts contain high concentration of molecules that can interfere with the QS mechanisms mediated by AHL as well as AIP.
Form and Function of Sleep Spindles across the Lifespan
Authors: Clawson Brittany C. , Durkin Jaclyn , Aton Sara J.
Published: April 2016

Since the advent of EEG recordings, sleep spindles have been identified as hallmarks of non-REM sleep. Despite a broad general understanding of mechanisms of spindle generation gleaned from animal studies, the mechanisms underlying certain features of spindles in the human brain, such as “global” versus “local” spindles, are largely unknown. Neither the topography nor the morphology of sleep spindles remains constant throughout the lifespan. It is likely that changes in spindle phenomenology during development and aging are the result of dramatic changes in brain structure and function. Across various developmental windows, spindle activity is correlated with general cognitive aptitude, learning, and memory; however, these correlations vary in strength, and even direction, depending on age and metrics used. Understanding these differences across the lifespan should further clarify how these oscillations are generated and their function under a variety of circumstances. We discuss these issues, and their translational implications for human cognitive function. Because sleep spindles are similarly affected in disorders of neurodevelopment (such as schizophrenia) and during aging (such as neurodegenerative conditions), both types of disorders may benefit from therapies based on a better understanding of spindle function.
Prevalence of Diabetic Foot Disease in Patients with Diabetes Mellitus under Renal Replacement Therapy in Lleida, Spain
Authors: Dòria Montserrat , Rosado Verónica , Pacheco Linda Roxana , Hernández Marta , Betriu Àngels , Valls Joan , Franch-Nadal Josep , Fernández Elvira , Mauricio Dídac
Published: April 2016

Aim. To assess the prevalence of diabetic foot and other associated conditions in patients with diabetes mellitus under renal replacement in the region of Lleida, Spain.Methods. This was an observational, cross-sectional study of 92 dialysis-treated diabetic patients. Besides a podiatric examination, we explored the presence of cardiovascular risk factors, late diabetes complications, including peripheral neuropathy, atherosclerotic disease, and peripheral artery disease. We assessed risk factors for foot ulceration and amputation by logistic regression.Results. Prevalent diabetic foot was found in 17.4% of patients, foot deformities were found in 54.3%, previous ulcer was found in 19.6%, and amputations were found in 16.3%; and 87% of them had some risk of suffering diabetic foot in the future. We observed a high prevalence of patients with peripheral neuropathy and peripheral artery disease (89.1% and 64.2%, resp.). Multivariable analysis identified diabetic retinopathy and advanced atherosclerotic disease (stenosing carotid plaques) as independent risk factors for foot ulceration (p=0.004andp=0.023, resp.) and diabetic retinopathy also as an independent risk factor for lower-limb amputations (p=0.013). Moreover, there was a temporal association between the initiation of dialysis and the incidence of amputations.Conclusion. Diabetic patients receiving dialysis therapy are at high risk of foot complications and should receive appropriate and intensive foot care.
Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway
Authors: Crowther Andrew J. , Ocasio Jennifer K. , Fang Fang , Meidinger Jessica , Wu Jaclyn , Deal Allison M. , Chang Sha X. , Yuan Hong , Schmid Ralf , Davis Ian , Gershon Timothy R.
Published: April 2016

While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiotherapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine whether the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that Trp53 (p53) was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies, because they retain apoptosis competence. Cancer Res; 76(11); 3211–23. ©2016 AACR.
MYC-Driven Neuroblastomas Are Addicted to a Telomerase-Independent Function of Dyskerin
Authors: O'Brien Rosemary , Tran Sieu L. , Maritz Michelle F. , Liu Bing , Kong Cheng Fei , Purgato Stefania , Yang Chen , Murray Jayne , Russell Amanda J. , Flemming Claudia L. , von Jonquieres Georg , Pickett Hilda A. , London Wendy B. , Haber Michelle , Gunaratne Preethi H. , Norris Murray D. , Perini Giovanni , Fletcher Jamie I. , MacKenzie Karen L.
Published: April 2016

The RNA-binding protein dyskerin, encoded by the DKC1 gene, functions as a core component of the telomerase holoenzyme as well as ribonuclear protein complexes involved in RNA processing and ribosome biogenesis. The diverse roles of dyskerin across many facets of RNA biology implicate its potential contribution to malignancy. In this study, we examined the expression and function of dyskerin in neuroblastoma. We show that DKC1 mRNA levels were elevated relative to normal cells across a panel of 15 neuroblastoma cell lines, where both N-Myc and c-Myc directly targeted the DKC1 promoter. Upregulation of MYCN was shown to dramatically increase DKC1 expression. In two independent neuroblastoma patient cohorts, high DKC1 expression correlated strongly with poor event-free and overall survival (P < 0.0001), independently of established prognostic factors. RNAi-mediated depletion of dyskerin inhibited neuroblastoma cell proliferation, including cells immortalized via the telomerase-independent ALT mechanism. Furthermore, dyskerin attenuation impaired anchorage-independent proliferation and tumor growth. Overexpression of the telomerase RNA component, hTR, demonstrated that this proliferative impairment was not a consequence of telomerase suppression. Instead, ribosomal stress, evidenced by depletion of small nucleolar RNAs and nuclear dispersal of ribosomal proteins, was the likely cause of the proliferative impairment in dyskerin-depleted cells. Accordingly, dyskerin suppression caused p53-dependent G1 cell-cycle arrest in p53 wild-type cells, and a p53-independent pathway impaired proliferation in cells with p53 dysfunction. Together, our findings highlight dyskerin as a new therapeutic target in neuroblastoma with crucial telomerase-independent functions and broader implications for the spectrum of malignancies driven by MYC family oncogenes. Cancer Res; 76(12); 3604–17. ©2016 AACR.
Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma
Authors: Takayama Yusuke , Hattori Noboru , Hamada Hironobu , Masuda Takeshi , Omori Keitaro , Akita Shin , Iwamoto Hiroshi , Fujitaka Kazunori , Kohno Nobuoki
Published: April 2016

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. In this study, we examined the antiangiogenic effects of PAI-1 inhibition in MPM. We administered the PAI-1 inhibitor, SK-216, to orthotopic mouse models in which MPM cells expressing high levels of VEGF (VEGFA) or bFGF (FGF2) were intrapleurally transplanted. SK-216 administration reduced tumor weights and the degree of angiogenesis in intrapleural tumors, irrespective of their angiogenic expression profiles. In addition, a combination of SK-216 and the chemotherapeutic agent cisplatin significantly reduced tumor weights compared with monotherapy, prolonging the survival of animals compared with cisplatin treatment alone. Furthermore, SK-216 inhibited migration and tube formation of cultured human umbilical vein endothelial cells induced by various angiogenic factors known to be secreted by MPM. These findings suggest that PAI-1 inactivation by SK-216 may represent a general strategy for inhibiting angiogenesis, including for the treatment of MPM. Cancer Res; 76(11); 3285–94. ©2016 AACR.
A Phase I, First-in-Human Study of AMG 780, an Angiopoietin-1 and -2 Inhibitor, in Patients with Advanced Solid Tumors
Authors: Dowlati Afshin , Vlahovic Gordana , Natale Ronald B. , Rasmussen Erik , Singh Indrajeet , Hwang Yuying C. , Rossi John , Bass Michael B. , Friberg Gregory , Pickett Cheryl A.
Published: April 2016

Purpose: To assess the toxicity, pharmacokinetics, tumor vascular response, tumor response, and pharmacodynamics of AMG 780, a mAb designed to inhibit the interaction between angiopoietin-1 and -2 and the Tie2 receptor.

Experimental Design: This was a phase I dose-escalation study of patients with advanced solid tumors refractory to standard treatment without previous antiangiogenic treatment. AMG 780 was administered by intravenous infusion every 2 weeks in doses from 0.1 to 30 mg/kg. The primary endpoints were incidences of dose-limiting toxicity (DLT) and adverse events (AE), and pharmacokinetics. Secondary endpoints included tumor response, changes in tumor volume and vascularity, and anti-AMG 780 antibody formation.

Results: Forty-five patients were enrolled across nine dose cohorts. Three patients had DLTs (0.6, 10, and 30 mg/kg), none of which prevented dose escalation. At 30 mg/kg, no MTD was reached. Pharmacokinetics of AMG 780 were dose proportional; median terminal elimination half-life was 8 to 13 days. No anti-AMG 780 antibodies were detected. At week 5, 6 of 16 evaluable patients had a >20% decrease in volume transfer constant (Ktrans), suggesting reduced capillary blood flow/permeability. The most frequent AEs were hypoalbuminemia (33%), peripheral edema (29%), decreased appetite (27%), and fatigue (27%). Among 35 evaluable patients, none had an objective response; 8 achieved stable disease.

Conclusions: AMG 780 could be administered at doses up to 30 mg/kg every 2 weeks in patients with advanced solid tumors. AMG 780 treatment resulted in tumor vascular effects in some patients. AEs were in line with toxicity associated with antiangiopoietin treatment. Clin Cancer Res; 22(18); 4574–84. ©2016 AACR.
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia
Authors: Teachey David T. , Lacey Simon F. , Shaw Pamela A. , Melenhorst J. Joseph , Maude Shannon L. , Frey Noelle , Pequignot Edward , Gonzalez Vanessa E. , Chen Fang , Finklestein Jeffrey , Barrett David M. , Weiss Scott L. , Fitzgerald Julie C. , Berg Robert A. , Aplenc Richard , Callahan Colleen , Rheingold Susan R. , Zheng Zhaohui , Rose-John Stefan , White Jason C. , Nazimuddin Farzana , Wertheim Gerald , Levine Bruce L. , June Carl H. , Porter David L. , Grupp Stephan A.
Published: April 2016

Chimeric antigen receptor (CAR)–modified T cells with anti-CD19 specificity are a highly effective novel immune therapy for relapsed/refractory acute lymphoblastic leukemia. Cytokine release syndrome (CRS) is the most significant and life-threatening toxicity. To improve understanding of CRS, we measured cytokines and clinical biomarkers in 51 CTL019-treated patients. Peak levels of 24 cytokines, including IFNγ, IL6, sgp130, and sIL6R, in the first month after infusion were highly associated with severe CRS. Using regression modeling, we could accurately predict which patients would develop severe CRS with a signature composed of three cytokines. Results were validated in an independent cohort. Changes in serum biochemical markers, including C-reactive protein and ferritin, were associated with CRS but failed to predict development of severe CRS. These comprehensive profiling data provide novel insights into CRS biology and, importantly, represent the first data that can accurately predict which patients have a high probability of becoming critically ill.

Significance: CRS is the most common severe toxicity seen after CAR T-cell treatment. We developed models that can accurately predict which patients are likely to develop severe CRS before they become critically ill, which improves understanding of CRS biology and may guide future cytokine-directed therapy. Cancer Discov; 6(6); 664–79. ©2016 AACR.

See related commentary by Rouce and Heslop, p. 579.

This article is highlighted in the In This Issue feature, p. 561
Chronic Obstructive Pulmonary Disease and Cardiac Repolarization: Data from a Randomized Controlled Trial
Authors: Sievi Noriane A. , Clarenbach Christian F. , Kohler Malcolm
Published: April 2016

Background: Altered cardiac repolarization is a risk factor for sudden cardiac death and seems to be increased in chronic obstructive pulmonary disease (COPD) patients. Objective: Lung volume reduction surgery (LVRS) has been shown to improve breathing mechanics and lung function in patients with severe COPD and emphysema and possibly also improve altered cardiac repolarization. Methods: Thirty patients scheduled for LVRS were randomized to LVRS or to the control group. We investigated the treatment effect 3 months after LVRS on measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) derived from electrocardiography. Univariable and multivariable analyses were used to identify possible confounders influencing the treatment effect. Results: LVRS was associated with an improvement in lung function (mean ± SD residual volume/total lung capacity of -9 ± 11% and forced expiratory volume in 1 s of +30 ± 29%). LVRS did not significantly reduce QTc (median -5.3 ms, 95% confidence interval, CI -15.5 to 3.7, p = 0.214) and QT dispersion (median -3.0 ms, 95% CI -13.0 to 7.0, p = 0.536) compared to the control group. No significant association between change in QTc and change in QT dispersion, respectively, and change in possible confounders was found. Conclusion: LVRS seems to have no effect on cardiac repolarization in patients with COPD. Thus, lung hyperinflation seems not to be a causal mechanism for altered cardiac repolarization in COPD patients.
Enrichment of Cells with Cancer Stem Cell-Like Markers in Relapses of Chemoresistant Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Grau Juan J. , Mesía Ricard , de la Iglesia-Vicente Maria , Williams Estrelania S. , Taberna Miren , Caballero Miguel , Larque Ana-Belen , de la Oliva Jorge , Cordón-Cardo Carlos , Domingo-Domenech Josep
Published: April 2016

Background: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. Methods: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR). Differences in expression between the first and second specimens were assessed. Results: Expression between the first and second specimens varied as follows: CD44 increased by 14.67% (95% confidence interval, CI: 6.94 to 22.40; p < 0.01); HLA-I decreased by 16.72% (95% CI: -23.87 to -9.47; p < 0.01); pancytokeratin decreased by 24.91% (95% CI: -32.8 to -17.7; p < 0.01), and p-EFGR expression decreased by 12.30% (95% CI: -20.61 to -3.98; p < 0.005). Conclusions: Among patients with HNSCC, there is an enrichment of cells with stem-like markers in relapsed tumors when compared with the primary tumor. This finding should be considered when developing treatment strategies.
Elastography Complements Ultrasound as Principle Modality in Breast Lesion Assessment
Authors: Redling Katharina , Schwab Fabienne , Siebert Matthias , Schötzau Andy , Zanetti-Dällenbach Rosanna
Published: April 2016

Background: The study aimed to improve breast cancer diagnosis with new ultrasound (US) modalities. We examined whether real-time elastography (RTE) complements the diagnostic performance of US. Methods: The Ethical Committee approved the study. Patients provided written informed consent and received a whole breast workup. Breast lesions were evaluated by US and RTE. Lesions were assessed by BI-RADS, Tsukuba score (TS) and strain ratio (SR). Results: The study included 164 breast lesions of which 101 were benign and 63 malignant. Women with benign lesions were predominantly premenopausal with sonographic dense breast tissue. Women with breast cancer were mostly postmenopausal, with a low sonographic density. Benign lesions had a mean TS of 2.05, which was significantly lower than the mean TS of 3.25 for malignant lesions. The SR for benign lesions (SR 1.83) was significantly smaller than for breast cancer (SR 4.83). Sensitivity and specificity was 95 and 81% for BI-RADS, 39 and 94% for TS, and 57 and 83% for SR, with a cutoff at 2.5. The combination of BI-RADS, TS and SR yielded a sensitivity of 95% and a specificity of 85%. Conclusion: Besides morphologic features revealed by US, elastic properties of breast lesions obtained by RTE can be exploited for diagnostic breast imaging.
Protein S testing in patients with protein S deficiency, factor V Leiden, and rivaroxaban by North American Specialized Coagulation Laboratories
Authors: Smock Kristi , Plumhoff Elizabeth , Meijer Piet , Hsu Peihong , Zantek Nicole , Heikal Nahla , Van Cott Elizabeth
Published: April 2016

In 2010–2012, the North American Specialized Coagulation Laboratory Association (NASCOLA) distributed 12 proficiency testing challenges to evaluate laboratory testing for protein S (PS). Results were analysed to assess the performance of PS activity, PS free antigen, and PS total antigen testing. Statistical analysis was performed on the numeric results and qualitative classification submitted for each method. There were 2,106 total results: 716 results from PS activity assays, 833 results from PS free antigen assays, and 557 results from PS total antigen assays. The three assay types performed well in the classification of five normal samples and nine abnormal samples, although certain PS activity methods were more likely to classify normal samples as abnormal and one PS total antigen assay was more likely to classify abnormal samples as normal. PS activity methods were affected by interfering substances such as heterozygous or homozygous factor V Leiden mutation (underestimation) and the anticoagulant drug rivaroxaban (overestimation). In conclusion, NASCOLA laboratories using a variety of PS assays performed well in the classification of clearly normal and abnormal samples. Laboratories performing PS activity assays should be aware of potential interferences in samples positive for FV Leiden or containing certain anticoagulant medications.
Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies
Authors: Martin-Rendon Enca
Published: April 2016

Controversies from basic science, discrepancies from clinical trials, and divergent results from meta-analyses have recently arisen in the field of cell therapies for cardiovascular repair and regeneration. Noticeably, there are almost as many systematic reviews and meta-analyses published as there are well-conducted clinical studies. But how do we disentangle the confusion they have raised? This article addresses why results obtained from systematic reviews and meta-analyses of human cell-based cardiac regeneration therapies are still valid to inform the design of future clinical trials. It also addresses how meta-analyses are not free from limitations and how important it is to assess the quality of the evidence and the quality of the systematic reviews and finally how stronger conclusions can be drawn when several pieces of evidence converge.
Role of the ACE2/Angiotensin 1–7 Axis of the Renin–Angiotensin System in Heart Failure
Authors: Patel Vaibhav B. , Zhong Jiu-Chang , Grant Maria B. , Oudit Gavin Y.
Published: April 2016

Heart failure (HF) remains the most common cause of death and disability, and a major economic burden, in industrialized nations. Physiological, pharmacological, and clinical studies have demonstrated that activation of the renin–angiotensin system is a key mediator of HF progression. Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a monocarboxypeptidase that converts angiotensin II into angiotensin 1–7 (Ang 1–7) which, by virtue of its actions on the Mas receptor, opposes the molecular and cellular effects of angiotensin II. ACE2 is widely expressed in cardiomyocytes, cardiofibroblasts, and coronary endothelial cells. Recent preclinical translational studies confirmed a critical counter-regulatory role of ACE2/Ang 1–7 axis on the activated renin–angiotensin system that results in HF with preserved ejection fraction. Although loss of ACE2 enhances susceptibility to HF, increasing ACE2 level prevents and reverses the HF phenotype. ACE2 and Ang 1–7 have emerged as a key protective pathway against HF with reduced and preserved ejection fraction. Recombinant human ACE2 has been tested in phase I and II clinical trials without adverse effects while lowering and increasing plasma angiotensin II and Ang 1–7 levels, respectively. This review discusses the transcriptional and post-transcriptional regulation of ACE2 and the role of the ACE2/Ang 1–7 axis in cardiac physiology and in the pathophysiology of HF. The pharmacological and therapeutic potential of enhancing ACE2/Ang 1–7 action as a novel therapy for HF is highlighted.
Ischemic Stroke or Systemic Embolism After Transseptal Ablation of Arrhythmias in Patients With Cardiac Implantable Electronic Devices
Authors: Madhavan Malini , Yao Xiaoxi , Sangaralingham Lindsey R. , Asirvatham Samuel J. , Friedman Paul A. , McLeod Christopher J. , Sugrue Alan M. , DeSimone Christopher V. , Noseworthy Peter A.
Published: April 2016

Background

Incidental mobile thrombi are commonly found on endovascular leads of cardiac implantable electronic devices (
CIED
s). Transseptal puncture for catheter ablation of arrhythmia poses a risk for paradoxical embolism. We examined risk of ischemic stroke, transient ischemic attack (
TIA
), or systemic embolism after transseptal ablation in patients with and without
CIED
s.

Methods and Results

Using a national administrative claims database, 31 720 patients who underwent a transseptal catheter ablation between January 2004 and September 2014 were identified. Two propensity‐matched cohorts were created by matching demographic variables, administrative variables, Charlson Comorbidity Index,
CHA
2
DS
2
‐Vasc score, and year and indication for ablation (5533 and 11 300 patients with and without
CIED
s). Incidence rates and Cox proportional hazards models were used to estimate risk of ischemic stroke,
TIA
, or systemic embolism for patients with and without
CIED
s. Impact of oral anticoagulation (
OAC
) use on the endpoint was examined. Over a mean follow‐up of 2.1 years, the incidence of the combined endpoint was 1.9 per 100 person‐years in patients with
CIED
s and 1.5 per 100 person‐years in patients without
CIED
s (
P
=0.03). Among patients not on
OAC
, presence of a cardiac device was associated with an increased risk (hazard ratio [
HR
], 1.71 [1.24–2.35];
P
<0.01), whereas there was no association noted among patients treated with
OAC
(
HR
, 0.98 [0.75–1.28]).

Conclusion

CIED
s are associated with an increased risk of stroke,
TIA
, or systemic embolism after transseptal ablation, but this risk is attenuated with postablation
OAC
use. Role of anticoagulation post‐transseptal ablation in patients with
CIED
warrants further investigation.
Tending-toward-Blackness
Authors: Copeland Huey
Published: April 2016

In response to “A Question on Materialisms” (October 155), this text asks anew for a consideration of how blackness—as site, sign, sensibility, and subject position—productively recalibrates both recent and longstanding approaches to the unfolding of the sensible world.
Taxonomic remarks on the genus Ctenodrilus (Annelida: Cirratulidae) including description of a new species from the Pacific Ocean
Authors: MAGALHÃES WAGNER F. , WEIDHASE MICHAEL , SCHULZE ANJA , BAILEY-BROCK JULIE H.
Published: April 2016

A new species of Ctenodrilus is described based on morphology, anatomy and molecular (COI and 16S) data. Phylogenetic analyses revealed that the newly described Hawaiian species is the sister taxon of the widely distributed C. serratus. Comparisons of K2P distances show distances of at least 10.9 % for 16S and 18.7 % for CO1. Morphology of C. serratus differs from C. pacificus sp. nov. in the shape, number and distribution of multidentate hooks along the body, extent in segments of anterior ventral cilia, and presence of stomach cilia. Ctenodrilus pacificus sp. nov. resembles C. parvulus in terms of the internal anatomy but differs in respect to the shape of multidentate hooks. Asexual reproduction in the new species is described including associated changes in the external morphology and internal anatomy. A revision of the taxonomic characters of Ctenodrilus is also presented in order to provide background information for a better assessment of the widely distributed taxon Ctenodrilus serratus.
Eremobiotus ginevrae sp. nov. and Paramacrobiotus pius sp. nov., two new species of Eutardigrada
Authors: LISI OSCAR , BINDA MARIA GRAZIA , PILATO GIOVANNI
Published: April 2016

Two new eutardigrade species are described: Eremobiotus ginevrae sp. nov. and Paramacrobiotus pius sp. nov. The first is similar to Eremobiotus alicatai (Binda, 1969) but differs in the claw shape and dimensions. It has been found in Sicily, Israel and Russia. The second species, belonging to the richtersi group, is currently found exclusively in Sicily. It has a smooth cuticle, three macroplacoids and a microplacoid, eggs with reticulated trunco-conical processes with small terminal thorns; the egg-shell is areolated and the areolae are clearly sculptured.
Comparison of the GPCP 1DD Precipitation Product and NEXRAD Q2 Precipitation Estimates over the Continental United States
Authors: Cui Wenjun , Dong Xiquan , Xi Baike , Stenz Ronald
Published: April 2016

This study compares the Global Precipitation Climatology Project (GPCP) 1 Degree Daily (1DD) precipitation estimates over the continental United States (CONUS) with National Mosaic and Multi-Sensor Quantitative Precipitation Estimation (NMQ) Next Generation (Q2) estimates. Spatial averages of monthly and yearly accumulated precipitation were computed based on daily estimates from six selected regions during the period 2010–12. Both Q2 and GPCP daily precipitation estimates show that precipitation amounts over southern regions (<40°N) are generally larger than northern regions (≥40°N). Correlation coefficients for daily estimates over selected regions range from 0.355 to 0.516 with mean differences (GPCP − Q2) varying from −0.86 to 0.99 mm. Better agreements are found in monthly estimates with the correlations varying from 0.635 to 0.787. For spatially averaged precipitation values averaged from grid boxes within selected regions, GPCP and Q2 estimates are well correlated, especially for monthly accumulated precipitation, with strong correlations ranging from 0.903 to 0.954. The comparisons between two datasets are also conducted for warm (April–September) and cold (October–March) seasons. During the warm season, GPCP estimates are 9.7% less than Q2 estimates, while during the cold season GPCP estimates exceed Q2 estimates by 6.9%. For precipitation over the CONUS, although annual means are close (978.54 for Q2 vs 941.79 mm for GPCP), Q2 estimates are much larger than GPCP over the central and southern United States and less than GPCP estimates in the northeastern United States. These results suggest that Q2 may have difficulties accurately estimating heavy rain and snow events, while GPCP may have an inability to capture some intense precipitation events, which warrants further investigation.
Time-Resolved Detection of Fingermarks on Non-Porous and Semi-Porous Substrates Using Sr2MgSi2O7:Eu2+, Dy3+ Phosphors
Authors: Xiong Xiaobo , Yuan Ximing , Song Jiangqi , Yin Guoxiang
Published: April 2016

Eu2+, Dy3+ co-doped strontium-magnesium silicate phosphors, Sr2MgSi2O7:Eu2+, Dy3+ (SMSEDs), have shown great potential in optoelectronic device due to their unique luminescent property. However, their potential applications in forensic science, latent fingermark detection in particular, are still being investigated. In this contribution, SMSEDs were successfully employed to latent fingermarks on a variety of non-porous and semi-porous surfaces, including aluminum foil, porcelain, glass, painted wood, colored paper, and leather. All the results illustrated that this luminescent powder, as a long-lasting phosphorescence material (LLP), was an ideal time-resolved detection reagent of fingermark for elimination of background interferences from various difficult substrates, and offered a good contrast to allow their identification without the need to enhance the results compared to nanosized organic fluorescent powder.
Detection of Melanoma Cancer Biomarker Dimethyl Disulfide Using Cavity Ringdown Spectroscopy at 266 nm
Authors: Wang Zhennan , Sun Meixiu , Wang Chuji
Published: April 2016

Skin cells emit volatile organic compounds (VOCs), and some of them can be used as biomarkers for screening specific diseases. Dimethyl disulfide (DMDS) has been recently reported as a biomarker of melanoma skin cancer (Kwak et al. “Volatile Biomarkers from Human Melanoma Cells”. J. Chromatogr. B. 2013. 931: 90–96.). With the motivation of diagnosing melanoma using DMDS as its biomarker, we explore the potential of measuring DMDS using an advanced laser spectroscopic technique as an alternative method. We report on the first DMDS measurements using an experimental system based on cavity ringdown spectroscopy (CRDS). The test samples were mixtures of DMDS vapor and nitrogen in different concentrations. Two sampling methods were investigated to dilute the DMDS sample to low concentrations for ringdown measurements. The results showed that the ringdown system responded to various DMDS concentrations linearly and a theoretical detection limit of sub-ppb (parts per billion) could be achieved at the absorption wavelength of 266 nm. This ringdown system exhibited a high dynamic range for DMDS measurements, from ppm (parts per million) to ppt (parts per trillion) levels, given different laser wavelengths used. The feasibility of developing a portable melanoma screening sensor using the CRDS technique was also demonstrated in this study.
Psychometric Consequences of Subpopulation Item Parameter Drift
Authors: Huggins-Manley Anne Corinne
Published: April 2016

This study defines subpopulation item parameter drift (SIPD) as a change in item parameters over time that is dependent on subpopulations of examinees, and hypothesizes that the presence of SIPD in anchor items is associated with bias and/or lack of invariance in three psychometric outcomes. Results show that SIPD in anchor items is associated with a lack of invariance in dimensionality structure of an anchor test, a lack of invariance in scaling coefficients across subpopulations, and a lack of invariance in ability estimates. It is demonstrated that these effects go beyond what can be understood from item parameter drift or differential item functioning.
Perception of family emotional climate by family members of persons with schizophrenia
Authors: Gandhi Sailaxmi , Pavalur Rajitha , Thirthalli Jagadisha , Phillip Mariamma
Published: April 2016

Background:

There is a dearth of instruments to assess schizophrenia persons’ Family Emotional Climate (FEC).

Aim:

This study aims to explore the relation between family members’ personality traits and FEC.

Methods:

We invited a convenience sample of 50 both gender family members who were accompanying the person with schizophrenia for out-patient department (OPD) consultation to provide data on a socio-demographic proforma and the researcher prepared ‘ Emotional climate assessment questionnaire – caregivers’ version’ (ECAQ-C) as well as the Eysenck personality questionnaire.

Results:

Caregivers’ extroversion traits ( r = .427, p = .002) were positively correlated and neuroticism traits were negatively correlated ( r = −.330, p = .019) with their positive perception of FEC. There was a higher perception of positive FEC (mean scores = 65.5 ± 10.5) while caregivers seemed to perceive less negative FEC (mean scores = 36.5 ± 10.2). Caregivers with education above 11th std perceived less (χ2 = 8.6, p = .013) of negative FEC.

Conclusion:

The findings highlight that caregivers’ personality traits seem to influence the FEC. While caregivers’ perception of FEC is positive in this study, those in the higher education group seem to have a better perception of FEC indicating that education also may influence FEC.
Craniosynostosis and Resynostosis
Authors: Hermann C.D. , Hyzy S.L. , Olivares-Navarrete R. , Walker M. , Williams J.K. , Boyan B.D. , Schwartz Z.
Published: April 2016

Craniosynostosis occurs in approximately 1 in 2,000 children and results from the premature fusion of ≥1 cranial sutures. If left untreated, craniosynostosis can cause numerous complications as related to an increase in intracranial pressure or as a direct result from cranial deformities, or both. More than 100 known mutations may cause syndromic craniosynostosis, but the majority of cases are nonsyndromic, occurring as isolated defects. Most cases of craniosynostosis require complex cranial vault reconstruction that is associated with a high risk of morbidity. While the first operation typically has few complications, bone rapidly regrows in up to 40% of children who undergo it. This resynostosis typically requires additional surgical intervention, which can be associated with a high incidence of life-threatening complications. This article reviews work related to the dental and maxillofacial implications of craniosynostosis and discusses clinically relevant animal models related to craniosynostosis and resynostosis. In addition, information is provided on the imaging modalities used to study cranial defects in animals and humans.
Eco-friendly salt-free reactive dyeing of cotton (muslin) fabric after cationization with amino acid from soya
Authors: Samanta Ashis Kumar , Kar Tapas Ranjan , Mukhopadhyay Asis , Shome Debashis , Konar Adwaita
Published: April 2016

Bleached cotton fabric was chemically modified (cationized)with natural amino acids extract obtained by acid hydrolysis (6N HCL) from soya bean seed waste, adding MgCl2 as an acid donor in the pad-dry-calendaring process to investigate the changes in textile properties and its dyeability with reactive dye in both a conventional alkaline dye bath and salt-free acidic dye bath. This modified cotton incorporates new functional groups producing [Formula: see text] in acid bath to obtain cationized cotton, rendering it to eco-friendly salt-free reactive dyeing at acceptable shade depth without much sacrifice of other textile-related properties. Bi-functional high exhaustion-type reactive dye shows better dye uptake than mono-functional cold brand as well as hot brand reactive dye. Moreover, the application of a specific dye fixing agent further improves surface color depth ( K/ S) of the soya-modified cotton fabric. The study of surface morphology of said chemically modified cotton substrate indicates a higher degree of surface deposition, that is, more anchorage of soya extracted amino acids on cotton fabric. Chemical anchorage as per the reaction scheme postulated for such modifications is verified with Fourier transform infrared spectroscopy. Finally, it is revealed that cotton treated with soya extract provides a new route of eco-friendly salt-free reactive dyeing with high exhaustion-type reactive dyes showing much higher dye uptake than the control cotton fabric.
Ecofriendly dyeing of silk with extract of yerba mate (Ilex paraguariensis)
Authors: Giacomini Fernando , Menegazzo Maira Amanda Benedet , dos Santos José Celso Oliveira , Arroyo Pedro Augusto , de Barros Maria Angélica Simões Dornellas
Published: April 2016

Silk fabric was dyed with extract of roasted yerba mate ( Ilex paraguariensis). Dyeing experiments were carried out at varying dyestuff concentration, temperature and pH. The influence of mordants, such as potassium alum and tannin, was investigated. The best results in dyeing were produced with 20 g L–1 of dyestuff concentration, pH 3 and temperature of 90℃. Mordants showed negligible influence. The kinetic study showed that the pseudo-second-order equation better represented experimental data, which is related to the chemisorption process as the rate-controlling step. The equilibrium data were easily adjusted by the Langmuir–Freundlich model, indicating the significant contribution of the chemisorption process in a monolayer followed by a multilayer physisorption. The thermodynamic study indicated that dye adsorption was spontaneous and endothermic.
Physiological and psychological responses while wearing firefighters’ protective clothing under various ambient conditions
Authors: He Jiazhen , Park Eunjin , Li Jun , Kim Eunae
Published: April 2016

Firefighters are required to carry out their responsibilities under a wide range of environmental conditions. For this reason, the physiological and psychological responses of firefighters while wearing their protective clothing should be analyzed to minimize their thermal or cold stress. Four environmental conditions were selected: hot and humid (HH, 34℃, 75% relative humidity (RH)), hot and dry (HD, 34℃, 30% RH), warm and dry (WD, 27℃, 30% RH), and slightly cold (SC, –3℃). Six professional firefighters served as subjects. The exercise was performed on a treadmill at the maximum speed of 8 km/h. The microclimate temperature and RH, skin temperature, heart rate, oxygen uptake, sweat loss, sweat evaporation, moisture accumulation within the outer shell, moisture barrier and thermal liner, and subjective sensations were measured. The microclimate wet-bulb globe temperatures (micro-WBGTs) were calculated. High microclimate measures, skin temperature, and heart rate, as well as low scored subjective sensations, were observed under the HH condition. A 45% difference in RH between HH and HD resulted in clearer differential responses compared with the 7℃ difference in air temperature between HD and WD. Under the SC condition, subjects had a cool to cold feeling. A quite different distribution of moisture accumulation in clothing layers was observed under the SC condition compared with other conditions. This moisture accumulation affected the comfort sensation. A linear relationship was found between the comfort sensation and the micro-WBGT. The micro-WBGT was a good indicator of the physiological status of the wearers. The microclimate, moisture accumulation and its distribution within firefighters’ protective clothing should be extensively studied in the future.
Assessing the First Two Years’ Effectiveness of Statway®
Authors: Yamada Hiroyuki , Bryk Anthony S.
Published: April 2016

Objective: Statway is a community college pathways initiative developed by the Carnegie Foundation for the Advancement of Teaching designed to accelerate students’ progress through their developmental math sequence to acquiring college math credit in statistics. Statway is a multifaceted change initiative designed to address the complex problems that impede student success. Specifically, it is a one-year pathway program through which students acquire college math credit. Instructors use research-based learning principles to improve the content and pedagogy for student learning and incorporate social-psychological interventions to sustain student engagement and persistence. In addition, language supports for students’ accessibility to mathematics learning are integrated into the curriculum. Professional development resources assist faculty as they teach new content utilizing unfamiliar pedagogies. Statway is organized as a networked improvement community intending to accelerate educators’ efforts to continuously improve. This study was aimed to assess the effectiveness of Statway during its first two years of implementation. Method: We applied a multilevel model with propensity score matching to control for possible selection bias and increase the validity of causal inference. Results: We found large effects of Statway on students attaining college math credit with persisting effects into the following year as Statway students also accumulated more college-level credits. These improved outcomes emerged for each gender and race/ethnicity groups and for students with different math placement levels. Conclusion: This study provided robust evidence that Statway increases student success in acquiring college math credit and enhances equity in student outcomes. Directions for future work are suggested.
An empirical investigation of the influence of municipal fiscal policy on firm growth
Authors: Van Cauwenberge Philippe , Beyne Peter , Vander Bauwhede Heidi
Published: April 2016

Over the last decades, many countries experienced a trend towards fiscal decentralisation, with the result that municipal governments have a largely increased degree of autonomy with respect to their fiscal policy. This shift has not been matched however with a change in the focus of the academic research on the economic effects of public finance, which is still predominantly conducted at the national and regional level. In this paper, we study the impact of municipal government taxation and spending on the growth rate of firms. We explore a panel dataset which combines detailed information from the financial accounts of Flemish municipalities with the financial reports of the firms located in those municipalities. Our analysis of data from close to 70,000 firms in 308 municipalities for the period 2004–2013 indicates that municipal fiscal policy has a statistically significant effect on firm added value growth and employment growth. No statistically significant effect was found on asset growth. Overall, the economic significance of municipal fiscal policy turns out to be small and is, for instance, not able to outweigh the effects of the recent financial crisis.