bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities
Authors: Honce Justin M. , Nagae Lidia , Nyberg Eric
Published: September 2015

Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes.
Biochemical Characterisation of Phage Pseudomurein Endoisopeptidases PeiW and PeiP Using Synthetic Peptides
Authors: Schofield Linley R. , Beattie Amy K. , Tootill Catherine M. , Dey Debjit , Ronimus Ron S.
Published: September 2015

Pseudomurein endoisopeptidases cause lysis of the cell walls of methanogens by cleaving the isopeptide bond Ala-ε-Lys in the peptide chain of pseudomurein. PeiW and PeiP are two thermostable pseudomurein endoisopeptidases encoded by phage ΨM100 ofMethanothermobacter wolfeiand phages ΨM1 and ΨM2 ofMethanothermobacter marburgensis, respectively. A continuous assay using synthetic peptide substrates was developed and used in the biochemical characterisation of recombinant PeiW and PeiP. The advantages of these synthetic peptide substrates over natural substrates are sensitivity, high purity, and characterisation and the fact that they are more easily obtained than natural substrates. In the presence of a reducing agent, purified PeiW and PeiP each showed similar activity under aerobic and anaerobic conditions. Both enzymes required a divalent metal for activity and showed greater thermostability in the presence of Ca2+. PeiW and PeiP involve a cysteine residue in catalysis and have a monomeric native conformation. The kinetic parameters,KMandkcat, were determined, and theε-isopeptide bond between alanine and lysine was confirmed as the bond lysed by these enzymes in pseudomurein. The new assay may have wider applications for the general study of peptidases and the identification of specific methanogens susceptible to lysis by specific pseudomurein endoisopeptidases.
Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer
Authors: Kuhnert Frank , Chen Guoying , Coetzee Sandra , Thambi Nithya , Hickey Carlos , Shan Jing , Kovalenko Pavel , Noguera-Troise Irene , Smith Eric , Fairhurst Jeanette , Andreev Julian , Kirshner Jessica R. , Papadopoulos Nicholas , Thurston Gavin
Published: September 2015

The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monoclonal antibody that binds human Dll4 with sub-nanomolar affinity and inhibits Notch signaling. Administering REGN421 to immunodeficient mice engineered to express human Dll4 inhibited the growth of several human tumor xenografts in association with the formation of nonfunctional tumor blood vessels. In ovarian tumor xenograft models, Dll4 was expressed specifically by the tumor endothelium, and Dll4 blockade by human-specific or mouse-specific Dll4 antibodies exerted potent antitumor activity, which relied entirely on targeting Dll4 expressed by tumor stromal cells but not by the tumor cells themselves. However, Dll4 blockade reduced Notch signaling in both blood vessels and tumor cells surrounding the blood vessels, suggesting that endothelial-expressed Dll4 might induce Notch signaling in adjacent ovarian tumor cells. The antitumor effects of targeting Dll4 were augmented significantly by simultaneous inhibition of VEGF signaling, whereas this combined blockade reversed normal organ vascular changes induced by Dll4 blockade alone. Overall, our findings deepen the rationale for antibody-based strategies to target Dll4 in ovarian cancers, especially in combination with VEGF blockade. Cancer Res; 75(19); 4086–96. ©2015 AACR.
Metformin Use and Risk of Colorectal Adenoma after Polypectomy in Patients with Type 2 Diabetes Mellitus
Authors: Marks Amy R. , Pietrofesa Ralph A. , Jensen Christopher D. , Zebrowski Alexis , Corley Douglas A. , Doubeni Chyke A.
Published: September 2015

Background: Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes.

Methods: Retrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and ≥1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication.

Results: Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ≥1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65–0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72–1.12; Q2: HR, 0.89; 95% CI, 0.70–1.12; Q3: HR, 0.80; 95% CI, 0.63–1.01; Q4: HR, 0.50; 95% CI, 0.42–0.60, Ptrend < 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline.

Conclusion: Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes.

Impact: Metformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use. Cancer Epidemiol Biomarkers Prev; 24(11); 1692–8. ©2015 AACR.
Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities
Authors: Gréen Henrik , Hasmats Johanna , Kupershmidt Ilya , Edsgärd Daniel , de Petris Luigi , Lewensohn Rolf , Blackhall Fiona , Vikingsson Svante , Besse Benjamin , Lindgren Andrea , Brandén Eva , Koyi Hirsh , Peterson Curt , Lundeberg Joakim
Published: September 2015

Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression.

Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy–Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis.

Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients' myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8–18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17–0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia.

Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/carboplatin chemotherapy. Clin Cancer Res; 22(2); 366–73. ©2015 AACR.
Comparison of Quality of Life Perceived by Patients with Bioprosthetic versus Mechanical Valves after Composite Aortic Root Replacement
Authors: Repack Adrienne , Ziganshin Bulat A. , Elefteriades John A. , Mukherjee Sandip K.
Published: September 2015

Objective: To assess whether postoperative quality of life (QOL) for composite aortic root replacement patients differs according to whether it is based on the use of mechanical valves or bioprosthetic valves. Methods: The study included 146 consecutive patients who underwent composite aortic root replacement at our institution from January 2010 to April 2014 with bioprosthetic (34.9%, n = 51) and mechanical (65.1%, n = 95) valves. Patient-perceived QOL was measured by administering the Short Form (SF)-36v2 Health Survey and a series of supplemental questions to further evaluate valve-specific differences. Final survey participation (n = 121) included 82.9% of the qualifying patients, and involved 76.5% (39/51) of those with bioprosthetic valves and 86.3% (82/95) of those with mechanical valves. Reasons for not completing the survey included 5 expired patients (3.4%), 1 lost due to a language barrier (0.7%), 6 who refused to participate (4.1%) and 13 who were lost to follow-up (8.9%). The mean follow-up time was 32 months (range 4-56 months). Results: Patients in the bioprosthetic valve group were older (mean age 67.5 ± 13.6 years) and included more females (25.6% or 10/39) than those in the mechanical valve group (mean age 56.6 ± 12.0 years; 11.0% or 9/82 were female). No significant differences were found between the bioprosthetic and mechanical valve groups for any QOL aspects scored by the SF-36v2 survey. All 8 domains and 2 summary scales comprising the QOL evaluation were above national norms calculated using gender- and age-matched, norm-based scoring for a standard national average of 50. The supplemental questions indicated satisfaction with each valve type despite characteristics that were of concern to patients. In the mechanical valve group, 90.2% (74/82) reported that the audible valve click was not troublesome, 85.4% (70/82) that taking a blood thinner regularly did not affect daily life and 81.7% (67/82) that blood testing for anticoagulation therapy was not troublesome. Conclusions: Receiving a tissue or a mechanical valve does not directly affect postoperative QOL. Answers to supplemental questions suggest that prior concerns with mechanical valves do not affect patients in the commonly anticipated negative manner. The preconception of a heavy QOL burden for mechanical composite grafts is contradicted by this study.
Breast Cancer Survivors' Knowledge of Hereditary Breast and Ovarian Cancer following Genetic Counseling: An Exploration of General and Survivor-Specific Knowledge Items
Authors: Scherr Courtney L. , Christie Juliette , Vadaparampil Susan T.
Published: September 2015

Background: Previous studies found genetic counseling increased participants' knowledge about hereditary breast and ovarian cancer (HBOC). However, most explored knowledge gain in unaffected women and the scale most commonly used does not include items that may be more pertinent to breast cancer (BC) survivors. Aims: To explore whether genetic counseling impacts BC survivors' knowledge about HBOC and BC survivor-specific information. Methods: The National Center for Human Genome Research Knowledge Scale and 5 additional items specific to BC survivors were tested among BC survivors; before genetic counseling (time 1), 2-3 weeks after genetic counseling (time 2), and 6 months following genetic counseling (time 3). Results: A statistically significant change in knowledge over time was found. Post hoc analyses revealed statistically significant increases in knowledge between time 1 (median = 7.00) and time 2 (median = 10.00; p < 0.005), and between time 1 and time 3 (median = 9.00; p < 0.005). Conclusion: Knowledge increased following genetic counseling, but the highest total average score at any time was <70% out of 100%. Additional analyses revealed items with low rates of correct response at all three time points, raising several concerns and the consideration of alternative approaches to measuring knowledge.
Features of Cutaneous Malignant Melanoma Metastatic to the Retina and Vitreous
Authors: Breazzano Mark P. , Barker-Griffith Ann E.
Published: September 2015

Background/Aims: To report a case of cutaneous malignant melanoma with cerebral metastasis found to have vitreoretinal metastasis upon referral for neovascular glaucoma. Methods: The clinical history and ocular examination findings, including histologic, cytologic, genetic, and immunohistochemical features of the vitreoretinal metastatic tumor, were reviewed. Additionally, the histologic and immunohistochemical features of the primary skin tumor and brain metastasis were also assessed. Results: A 62-year-old woman with cutaneous malignant melanoma metastatic to the right frontal lobe (BRAF V600E negative) was evaluated for blurred vision in the right eye. Neovascular glaucoma, iritis, and posterior synechiae with no view of the retina or vitreous were evident on examination. Vitreoretinal biopsy and enucleation specimen both showed widespread neoplastic involvement of the retina and residual vitreous strands after vitrectomy. Choroid, trabeculum, and other intraocular structures were devoid of tumor burden. Diagnosis of cutaneous malignant melanoma metastatic to the retina and vitreous was confirmed, and the patient expired shortly thereafter. Conclusion: Cutaneous malignant melanoma metastatic to the eye has a relatively greater preference for the retina and frequently presents with uveitis and glaucoma. Neovascular glaucoma in these cases may likely be attributable to unusually increased vascular endothelial growth factor production by the intraocular melanoma tumor cells.
Expression of p16 and p53 in Intraepithelial Periocular Sebaceous Carcinoma
Authors: Bell W. Robert , Singh Kamaljeet , Rajan KD Anand , Eberhart Charles G.
Published: September 2015

Purpose: Identifying intraepithelial sebaceous carcinoma cells in small periocular biopsies can be difficult, particularly in the conjunctiva. The goal of this study was to evaluate p53 and p16 immunohistochemistry as potential markers of intraepithelial sebaceous carcinoma. Procedures: A total of 25 tumors, including 4 recurrent lesions, were stained for p16 and p53, with intensity scored as negative, weak, moderate or strong. Results: Expression of p16 was detected in intraepithelial sebaceous carcinoma cells in 24 of the 25 cases (96%), with only 1 case showing weak immunoreactivity. Intraepithelial p53 immunoreactivity was present in 17 of 25 tumors (68%), but was weak in 3 cases. Expression levels remained relatively stable in primary and recurrent tumors, but varied in a few cases between intraepithelial and subepithelial sites. Conclusions: Intraepithelial sebaceous carcinomas stained for p53 and p16 demonstrated moderate to strong immunoreactivity in 100% of cases for at least one of these proteins, suggesting that together they are useful markers for determining the extent of tumor spread. Of the two, p16 was immunoreactive in more cases than p53.
Photoreceptor Outer Segment on Internal Limiting Membrane after Macular Hole Surgery: Implications for Pathogenesis
Authors: Grinton Michael E. , Sandinha Maria T. , Steel David H.W.
Published: September 2015

Purpose: This report presents a case, which highlights key principles in the pathophysiology of macular holes. It has been hypothesized that anteroposterior (AP) and tangential vitreous traction on the fovea are the primary underlying factors causing macular holes [Nischal and Pearson; in Kanski and Bowling: Clinical Ophthalmology: A Systemic Approach, 2011, pp 629-631]. Spectral domain optical coherence tomography (OCT) has subsequently corroborated this theory in part but shown that AP vitreofoveal traction is the more common scenario [Steel and Lotery: Eye 2013;27:1-21]. Methods: This study was conducted as a single case report. Results: A 63-year old female presented to her optician with blurred and distorted vision in her left eye. OCT showed a macular hole with a minimum linear diameter of 370 µm, with persistent broad vitreofoveal attachment on both sides of the hole edges. The patient underwent combined left phacoemulsification and pars plana vitrectomy, internal limiting membrane (ILM) peel and gas injection. The ILM was examined by electron microscopy and showed the presence of a cone outer segment on the retinal side. Post-operative OCT at 11 weeks showed a closed hole with recovery of the foveal contour and good vision. Conclusion: Our case shows the presence of a photoreceptor outer segment on the retinal side of the ILM and reinforces the importance of tangential traction in the development of some macula holes. The case highlights the theory of transmission of inner retinal forces to the photoreceptors via Müller cells and how a full thickness macular hole defect can occur in the absence of AP vitreomacular traction.
Acute Kidney Injury and Renal Recovery with the Use of Aminoglycosides: A Large Retrospective Study
Authors: Paquette François , Bernier-Jean Amélie , Brunette Véronique , Ammann Hélène , Lavergne Valéry , Pichette Vincent , Troyanov Stéphan , Bouchard Josée
Published: September 2015

Background: Recent acute kidney injury (AKI) guidelines, based on studies performed a decade ago, recommend avoiding aminoglycosides (AGs) in patients at risk of AKI. Whether present patient characteristics and management have changed this risk is uncertain. We determined the current incidence, risk factors and outcomes of AG-AKI. Methods: We retrospectively identified adult patients who received gentamicin or tobramycin for ≥5 days in 2 large university-affiliated centers, excluding critically ill and dialysis patients. We assessed the incidence of Risk, Injury, Failure, Loss and End-stage kidney disease criteria of AKI risk and then matched each AKI to 2 controls of same age and gender to determine factors associated with AG-AKI and its recovery, defined by a creatinine within 150% of baseline by 21 days. Results: Since 2001, the frequency of AG administration and dosing declined, but the incidence of AG-AKI remained constant. Of the 562 patients who received AG for ≥5 days, 65 (12%) developed AG-AKI after 11 (IQR 8-15) days, with 56, 29 and 15% having stages 1, 2 and 3 AKI, respectively. We matched these to 130 controls. In this nested case-control study, independent AKI risk factors were vancomycin coadministration, high AG trough levels and heart failure. AG-AKI compared to AG exposure without AKI was associated with greater mortality. Renal recovery occurred in 51% of the AKI patients and was less likely with heart failure and higher AKI severity. Conclusion: AG administration has recently decreased but the risk of AKI remained unchanged and half of the patients did not recover. Vancomycin coadministration, high AG trough levels and heart failure independently predicted AKI.
A Abolição da Escravidão nos Livros Didáticos: Textos e Imagens na Construção da História na Escola
Authors: Pastore Victor Doutel
Published: September 2015

O presente artigo explora os discursos e perspectivas sobre a Abolição da Escravidão transmitidos pelos livros didáticos de História do Brasil do início do século XX até a década de 1980. Para tanto, considerou-se as atuais linhas teóricas de pesquisa, baseadas em autores como Alain Choppin e Circe Bittencourt, que pensam os manuais escolares como documentos históricos, objetos da cultura material responsáveis por produzir e disseminar valores de determinada época, com intenções específicas e parciais. Além disso, são objetos cuja função ultrapassa o caráter ideológico, pois representam currículos, pedagogias e métodos escolares e editoriais que também são históricos. A pesquisa busca aliar tanto o campo das representações quanto o campo metodológico-pedagógico para a análise de alguns autores clássicos de diferentes momentos da produção didática brasileira, como Antônio José Borges Hermida e Joel Rufino dos Santos. Partindo da problemática de como é representado o tema da Abolição e qual o lugar concedido aos negros escravos nessas fontes - considerando a articulação entre textos e imagens - pode-se refletir a construção e consolidação de perspectivas sobre a História e o papel da escola nesse processo.
A Não-Apropriação da República das Letras Francesa pela Era Digital: Dialogando com as Ideias de Denis Diderot e Michel Foucault sobre a Postura de Autor
Authors: Paiva Thayenne Roberta Nascimento
Published: September 2015

Tendo como objetivo analisar um possível retrocesso, presente na atualidade, em relação às ideias de disseminação do conhecimento, lema aclamado pela República das Letras francesa, especialmente século XVIII, mobilizamos dois filósofos para pensarmos o caso, em termos de postura do autor frente sua produção discursiva. Para tanto, valemo-nos de algumas ideias do filósofo Michel Foucault desenvolvidas especialmente em seu ensaio "O que é um autor?". Por outro lado, discorreremos sobre as concepções do filósofo Denis Diderot sobre esta mesma função, respeitando as devidas diferenças de tempo e espaço e apresentando outra perspectiva sobre o que foi a sua interpretação acerca da postura do autor, na época da República das Letras francesa. Ademais, iremos discorrer sobre possíveis aniquilamentos e a não-apropriação em torno do verdadeiro ideal da República das Letras, na atualidade, a partir da intensificação e do cerceamento de antigas posturas da função de autor, especialmente, na Era Digital
Nonstatin Low-Density Lipoprotein–Lowering Therapy and Cardiovascular Risk Reduction—Statement From
ATVB
Council
Authors: Hegele Robert A. , Gidding Samuel S. , Ginsberg Henry N. , McPherson Ruth , Raal Frederick J. , Rader Daniel J. , Robinson Jennifer G. , Welty Francine K.
Published: September 2015

Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional nonstatins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points, whereas adding a fibrate or niacin showed no incremental benefit. Among emerging nonstatins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 added to a statin and given for ≤78 weeks showed preliminary evidence of reductions in CVD outcomes. Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.
Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart
Authors: Jagannathan Rajaganapathi , Thapa Dharendra , Nichols Cody E. , Shepherd Danielle L. , Stricker Janelle C. , Croston Tara L. , Baseler Walter A. , Lewis Sara E. , Martinez Ivan , Hollander John M.
Published: September 2015

Background—

Cardiomyocytes are rich in mitochondria which are situated in spatially distinct subcellular regions, including those under the plasma membrane, subsarcolemmal mitochondria, and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabetic insult. The objective of this study was to determine whether mitochondrial genome–encoded proteins are regulated by microRNAs inside the mitochondrion and whether subcellular spatial location or diabetes mellitus influences the dynamics.

Methods and Results—

Using microarray technology coupled with cross-linking immunoprecipitation and next generation sequencing, we identified a pool of mitochondrial microRNAs, termed mitomiRs, that are redistributed in spatially distinct mitochondrial subpopulations in an inverse manner following diabetic insult. Redistributed mitomiRs displayed distinct interactions with the mitochondrial genome requiring specific stoichiometric associations with RNA-induced silencing complex constituents argonaute-2 (Ago2) and fragile X mental retardation–related protein 1 (FXR1) for translational regulation. In the presence of Ago2 and FXR1, redistribution of mitomiR-378 to the interfibrillar mitochondria following diabetic insult led to downregulation of mitochondrially encoded F0 component ATP6. Next generation sequencing analyses identified specific transcriptome and mitomiR sequences associated with ATP6 regulation. Overexpression of mitomiR-378 in HL-1 cells resulted in its accumulation in the mitochondrion and downregulation of functional ATP6 protein, whereas antagomir blockade restored functional ATP6 protein and cardiac pump function.

Conclusions—

We propose mitomiRs can translationally regulate mitochondrially encoded proteins in spatially distinct mitochondrial subpopulations during diabetes mellitus. The results reveal the requirement of RNA-induced silencing complex constituents in the mitochondrion for functional mitomiR translational regulation and provide a connecting link between diabetic insult and ATP synthase function.
Differences in Quality of Life Between Atrial Fibrillation Patients with Low Stroke Risk Treated With and Without Catheter Ablation
Authors: Bai Ying , Bai Rong , Wu Jia‐Hui , Zhang Ting , Liu Nian , Shi Xu‐Bo , Liu Xin‐Yao , Liu Xiao‐Hui , Du Xin , Dong Jian‐Zeng , Ma Chang‐Sheng
Published: September 2015

Background

Impacts of a single radiofrequency ablation (
RFA
) on quality of life (QoL) were not well investigated in atrial fibrillation (
AF
) patients with low stroke risk.

Methods and Results

Nine hundred
AF
patients with low
CHADS
2
score (ie,
CHADS
2
≤1) who completed both a baseline and 6‐month Atrial Fibrillation Effect on QualiTy‐of‐life (
AFEQT
) questionnaire were selected from The Chinese Atrial Fibrillation Registry between 2011 and 2013. A final cohort of 222 patients was constructed after a propensity score matching with 74 in the
RFA
group and 148 in the non‐
RFA
group. Domains of
AFEQT
were balanced at baseline between the 2 groups. No statistically significant differences were noted in QoL (all
P
>0.05) when
AFEQT
at 6 months was compared between groups, except for the symptoms domain (83.07±12.37 units in the
RFA
group vs. 77.68±17.14 units in the non‐
RFA
group;
P
=0.008) and treatment satisfaction domain (76.34±14.92 units in the
RFA
group vs. 70.38±16.81 units in the non‐
RFA
group;
P
=0.01). Within‐group changes in all domains and the global score of the questionnaire were moderate to large, whereas between‐group comparisons in baseline to 6‐month changes and QoL at 6 months were small to moderate according to Cohen effect sizes.

Conclusions

QoL was balanced at baseline and improved at 6 months in both groups from this observational propensity‐matched cohort based on the
AFEQT
questionnaire. However,
RFA
treatment was only associated with small‐to‐moderate superiorities over non‐
RFA
treatment. The role of
RFA
in QoL improvement among
AF
patients with low stroke risk requires further research.
The Sonic Witness: On the Political Potential of Field Recordings in Acoustic Art
Authors: Fiebig Gerald
Published: September 2015

Contemporary sonic artworks often use field recordings from places of historic or social significance to address political issues. This article discusses relevant works for radio and fixed media by Peter Cusack, Jacob Kirkegaard, Eliška Cílková, Anna Friz and Public Studio, Stéphane Garin and Sylvestre Gobart, Ultra-red, and Matthew Herbert and outlines how they use both audio and visual/textual information to create awareness of the issues inscribed in these places, from current environmental concerns to the memory of genocide and displacement.
Changing Music’s Constitution: Network Music and Radical Democratization
Authors: Knotts Shelly
Published: September 2015

A review of radical democratic theories influenced by technological developments and nonhierarchical network structures allows us to analyze factors influencing hierarchical structure in music ensembles. Network music ensembles are uniquely positioned to deploy heterarchical technologies that enable them to address radical democratic concerns relating to communication structures and power distribution. This essay provides examples of current politically tinged explorations in network music and examines the room left for maneuvering in developing systems that consider the implication of data structures on sociopolitical hierarchy.
Physical Glitch Music: A Brutalist Noise Ensemble
Authors: Zareei Mo H. , Carnegie Dale A. , Kapur Ajay
Published: September 2015

This article introduces an ensemble of mechatronic sound-sculptures designed and developed to realize glitch music outside of computers; the sculptures instead create glitches mechanically, physically and visibly. A brief description of the three different instrument types forming the ensemble is followed by a discussion of how the sound-sculptures employ a Brutalist “anti-beauty” approach in terms of both design and ideology.
The Signification of the Copula in Fernando de Enzinas’ Syncategoremata
Authors: Pérez-Ilzarbe Paloma
Published: September 2015

This article deals with a brief difficultas in the Tractatus de compositione propositionis mentalis by Fernando de Enzinas: qualiter copule significent tempus et an copule de presenti et preterito sint synonime. A progressive determination of the signification of the copula is analysed: first, Enzinas defines his position about the principal syncategorematic signification of the copula; then, he analyses the sense of the consignification of time traditionally attributed to the copula. The originality of Enzinas’ position is highlighted, given the fact that he gives preference to the question as to how the copulae signify time rather than the question as to which time the copulae signify.
The genus Chorisodontium (Dicranaceae, Musci) in the Neotropics
Authors: Frahm Jan-Peter
Published: September 2015

All the species of Chorisodontium recorded from the neotropical mountains (Bolivia Costa Rica) have been critically revised. Three species, C. nigricans Herz., C. mittenii (C. Müll.) Broth. and C. wallisii (C. Müll.) Broth. are accepted. Chorisodontium speciosum (Hook. f. & Wils.) Broth. is placed as a variety to C. wallisii.
Bryophyte floras of tropical Pacific islands
Authors: Miller H. A. , Whittier H. O.
Published: September 2015

A review of the status of bryological research in each of the nations, states or governmental units of southern Melanesia, Micronesia and tropical Polynesia shows the imperfect state of knowledge about the Pacific tropical islands. Best known overall are Hawaii and Micronesia with Wallis and Futuna, the Marquesas and the high mountains of Fiji seeming to be the least known potentially species rich areas. Involvement of residents from Pacific islands in botanical study and preservation of ecosystems should be encouraged by tropical bryologists.
News and Notes
Authors: Thiers Barbara M.
Published: September 2015

News and Notes
Diversity and distribution of Asian Lejeuneaceae subfamily Ptychanthoideae

Authors: Gradstein S. Rob
Published: September 2015

A synopsis is provided of 88 species in 17 genera currently recognized in Lejeuneaceae subfamily Ptychanthoideae sensu lato (including Nipponolejeunea) of Asia. Taxonomic novelties include Thysananthus flavescens (Hatt.) comb. nov. (for Mastigolejeunea flavescens (Hatt.) Mizut.), Spruceanthus macrostipulus (Steph.) comb. nov. (for Archilejeunea macrostipula (Steph.) Verd.) and the reduction of Platylejeunea Mizut. to synonymy under Lopholejeunea.
The Bryoflora of Fernando de Noronha, Brasil
Authors: Vital Daniel , Giancotti Christina , Pursell Ronald A.
Published: September 2015

Twenty-two species of bryophytes are reported from Fernando de Noronha. One of these, Fissidens veracruzensis Pursell, has not been reported previously from Brasil
Las Hepaticas comunicadas para Costa Rica
Authors: Z. María Isabel Morales
Published: September 2015

A survey of the literature and a few unpublished identifications of recent collections indicate that 426 taxa have been reported from Costa Rica, including Cocos Island. The distribution of each taxon is indicated by province and parameters are given for most localities within each province.
Three new species of the genus Xiphidiopsis Redtenbacher, 1891 (Orthoptera: Tettigoniidae: Meconematinae) in China
Authors: HAN LI , DI JUAN-XIA , CHANG YAN-LIN , SHI FU-MING
Published: September 2015

The article reported three new species of the genus Xiphidiopsis Redtenbacher, 1891 in China: Xiphidiopsis (Xiphidiopsis) minorincisus Han, Chang & Shi sp. nov., Xiphidiopsis (Xiphidiopsis) protensus Han, Chang & Shi sp. nov. and Xiphidiopsis (Xiphidiopsis) anisolobulus Han, Di & Shi sp. nov. The type material is deposited in the Museum of Hebei University, Baoding, P. R. China.
Candeocoris bistillatus, new genus and new species of Ochlerini from Ecuador (Hemiptera: Heteroptera: Pentatomidae)
Authors: ROELL TALITA , CAMPOS LUIZ ALEXANDRE
Published: September 2015

Recent examination of specimens from Ecuador revealed a series of males and females of an undescribed species clearly belonging to the Discocephalinae. The new species presents characteristics similar to genera of both Discocephalini and Ochlerini, preventing an undoubtful placement of the new species within any genus and tribe. We conducted a cladistic analysis to investigate the possible relationships of the new species within Discocephalinae. The new species was recovered as sister-group to the remaining Ochlerini, supporting the proposition of a new genus, so Candeocoris bistillatus Roell & Campos, gen. n. et sp. n. are described within Ochlerini. The new genus is recognized for its dark glossy aspect, tumid vertex of head, long and sinuous labrum, base of labium placed close to anterior limit of eyes, thick bristles on meso- and metatibiae, pygophore globose, and laterotergites 9 touching each other. The new species is recognized by a large yellow spot on each corium, yellow spots on each segment of the connexivum, bucculae with anterior tooth, laminar projections on superior layer of ventral rim of pygophore, vesica with a single median projection, and broad gonocoxites 8.
Revealing the diversity of Cloeodes Traver, 1938 (Ephemeroptera: Baetidae) in the Neotropics: description of eleven new species from Brazilian mountain ranges
Authors: SALLES F.F. , MASSARIOL F.C. , ANGELI K.B. , LIMA M.M. , GATTOLLIAT J-L. , SARTORI M.
Published: September 2015

In the present work, based on material from distinct mountain ranges in Brazil, 11 new species of Cloeodes with hind wings or hind wing pads are described, illustrated and discussed. Among the new species, in C. aiuruoca, C. amantykyra, C. atlanticus, C. boldrinii and C. ioachimi, the apex of the fore femora in the nymphs is extremely projected (a characteristic previously found only in two species of the genus). Cloeodes guara and C. tracheatus share the presence of unusual large and dark gills. Cloeodes melanotarsus is readily distinguished by conspicuous blackish tarsi, C. lucifer by the bright yellow coloration of tergum I, and C. xyrognathos by blade-like incisors. Cloeodes magnus, besides being the largest species of the genus, with a body size reaching 12 mm, possess short maxillary palp. Comments on the presence of C. irvingi and C. opacus in Brazil are also provided. An interactive online key is provided for the nymphs of all the species of Cloeodes in which hind wing pads are present.
Taxonomic review of the major larval pests of bolete fungi (Boletaceae) in Europe: The Pegomya fulgens, furva and tabida species groups (Diptera: Anthomyiidae)
Authors: MICHELSEN VERNER
Published: September 2015

A taxonomic review of the European species of the Pegomya fulgens, furva and tabida species groups is given with emphasis on characters of importance for the identification of males and females. These Pegomya species groups are represented in Europe by two, two and nine species, respectively. Their mycophagous larvae may all feed exclusively on bolete sporocarps of Leccinum and Boletus aff. edulis. Their relationships and biology are summarized. Each species is given a selective list of references and synonymy, richly illustrated descriptions of males and females, a list or summary of the examined material, and a synopsis of the known distribution and biology. Pegomya ringdahli sp. nov., previously confused with P. scapularis (Zetterstedt, 1846), is described from Fennoscandia. Lectotypes are designated for Anthomyia fulgens Meigen, 1826 and Pegomyia (Pegomyia) furva Ringdahl, 1938. An identification key is given to all 17 species (males and females) of Pegomya that supposedly feed as larvae on sporocarps of Boletaceae and Suillaceae in Europe.
A checklist of the ants (Hymenoptera: Formicidae) of Peru
Authors: BEZDĚČKOVÁ KLÁRA , BEZDĚČKA PAVEL , MACHAR IVO
Published: September 2015

The article presents a comprehensive list of the ants (Hymenoptera: Formicidae) of Peru. Distribution data for 592 valid names of species-group taxa in 76 genera and 12 subfamilies were collected through a bibliographical review. The most diverse subfamilies in terms of species richness are Myrmicinae (273 species/subspecies), Formicinae (86 species/subspecies) and Ponerinae (71 species/subspecies). The most diverse genera are Pheidole (86 species/subspecies), Camponotus (73 species/subspecies), and Pseudomyrmex (47 species/subspecies). With respect to geographic divisions, richness is highest in Madre de Dios (245 species/subspecies), followed by Huanuco (109 species/subspecies) and Cusco (104 species/subspecies). Regions in greatest need of additional survey work are Aycucho, Huancavelica, Moquegua and Tacna, from which virtually no information on the ant fauna is available.
Exploring Winter Mortality Variability in Five Regions of England Using Back Trajectory Analysis
Authors: Dimitriou K. , McGregor G. R. , Kassomenos P. A. , Paschalidou A. K.
Published: September 2015

This paper aims to define atmospheric pathways related with the occurrence of daily winter low temperature episodes (LTE) in England, for the 26-yr period 1974–99, and to reveal possible associations with increased mortality rates. For this purpose, backward airmass trajectories, corresponding to LTE in five regions of England, were deployed. A statistically significant increase in mortality levels, at the 0.05 level, was found for LTE, compared to non-LTE days across all five regions. Seven categories of atmospheric trajectory patterns associated with LTE were identified: east, local, west, North Atlantic, Arctic, southwest, and Scandinavian. Consideration of the link between airmass trajectory patterns and mortality levels by region revealed a possible west-to-east split in the nature of air masses connected with elevated mortality. Specifically, for the West Midlands and northwest regions, relatively warm winter weather conditions from the west, most likely associated with the eastward progression of low pressure systems, are allied with the highest daily average mortality counts, whereas, for the northeast, Humberside/York, and southeast regions, cold continental air advection from northern or eastern Europe, which lasts for several days and is linked with either a blocking pattern over the western margins of Europe or an intense high pressure anomaly over eastern or northern Europe, appears important in mortality terms. This finding confirms that winter weather health associations are complex, such that climate setting and airmass climatology need to be taken into account when considering climate and health relationships.
A Modeling Study of a Low-Level Jet along the Yun-Gui Plateau in South China
Authors: He Ming-Yang , Liu Hong-Bo , Wang Bin , Zhang Da-Lin
Published: September 2015

In this study, the three-dimensional structures and diurnal evolution of a typical low-level jet (LLJ) with a maximum speed of 24 m s−1 occurring in the 850–800-hPa layer are examined using both large-scale analysis and a high-resolution model simulation. The LLJ occurred on the eastern foothills of the Yun-Gui Plateau in south China from 1400 LST 29 June to 1400 LST 30 June 2003. The effects of surface radiative heating, topography, and latent heat release on the development of the LLJ case are also studied. Results show that a western Pacific Ocean subtropical high and a low pressure system on the respective southeast and northwest sides of the LLJ provide a favorable large-scale mean pressure pattern for the LLJ development. The LLJ reaches its peak intensity at 850 hPa near 0200 LST with wind directions veering from southerly before sunset to southwesterly at midnight. A hodograph at the LLJ core shows a complete diurnal cycle of the horizontal wind with a radius of 5.5 m s−1. It is found that in an LLJ coordinates system the along-LLJ geostrophic component regulates the distribution and 65% of the intensity of LLJ, whereas the ageostrophic component contributes to the clockwise rotation, thus leading to the formation and weakening of the LLJ during night- and daytime, respectively. Numerical sensitivity experiments confirm the surface radiative heating as the key factor in determining the formation of the nocturnal LLJ. The existence of the Yun-Gui Plateau, and the downstream condensational heating along the mei-yu front play secondary roles in the LLJ formation.
The Dynamics of Australian Monsoon Bursts
Authors: Berry Gareth J. , Reeder Michael J.
Published: September 2015

The wet season of the Australian monsoon is characterized by subseasonal periods of excessively wet or dry conditions, commonly known as monsoon bursts and breaks. This study is concerned with the synoptic evolution prior to monsoon bursts, which are defined here by abrupt transitions of the area-averaged rainfall over the tropical parts of the Australian continent.

There is large variability in the number of monsoon bursts from year to year and in the time interval between consecutive monsoon bursts. Reanalysis data are used to construct a lag composite of the sequence of events prior to a monsoon burst. It is determined that a burst in the Australian monsoon is preceded by the development of a well-defined extratropical wave packet in the Indian Ocean, which propagates toward the Australian continent in the few days leading up to the onset of heavy rainfall in the tropics. As in previous studies on the monsoon onset, the extratropical disturbances propagate equatorward over the Australian continent. These extratropical systems are accompanied by lower-tropospheric airmass boundaries, which also propagate into low latitudes. Ahead of these boundaries, relatively warm moist air is advected from the surrounding oceans, locally increasing the convective available potential energy.

Commonly employed climate indices show that monsoon bursts are more likely to occur when the active phase of the Madden–Julian oscillation is in the vicinity of Australia. Neither El Niño–Southern Oscillation nor the southern annular mode has a significant impact on the occurrence of monsoon bursts.
The Benguela Upwelling System: Quantifying the Sensitivity to Resolution and Coastal Wind Representation in a Global Climate Model*
Authors: Small R. Justin , Curchitser Enrique , Hedstrom Katherine , Kauffman Brian , Large William G.
Published: September 2015

Of all the major coastal upwelling systems in the world’s oceans, the Benguela, located off southwest Africa, is the one that climate models find hardest to simulate well. This paper investigates the sensitivity of upwelling processes, and of sea surface temperature (SST), in this region to resolution of the climate model and to the offshore wind structure. The Community Climate System Model (version 4) is used here, together with the Regional Ocean Modeling System. The main result is that a realistic wind stress curl at the eastern boundary, and a high-resolution ocean model, are required to well simulate the Benguela upwelling system. When the wind stress curl is too broad (as with a 1° atmosphere model or coarser), a Sverdrup balance prevails at the eastern boundary, implying southward ocean transport extending as far as 30°S and warm advection. Higher atmosphere resolution, up to 0.5°, does bring the atmospheric jet closer to the coast, but there can be too strong a wind stress curl. The most realistic representation of the upwelling system is found by adjusting the 0.5° atmosphere model wind structure near the coast toward observations, while using an eddy-resolving ocean model. A similar adjustment applied to a 1° ocean model did not show such improvement. Finally, the remote equatorial Atlantic response to restoring SST in a broad region offshore of Benguela is substantial; however, there is not a large response to correcting SST in the narrow coastal upwelling zone alone.