bluuebunny/crossref_metadata_2025 huggingface dataset:
Report of the 14th International Conference on Malignant Lymphoma (ICML) Closed Workshop on Future Design of Clinical Trials in Lymphomas
Authors: Stathis Anastasios , Iasonos Alexia , Seymour John F. , Thieblemont Catherine , Ribrag Vincent , Zucca Emanuele , Younes Anas
Published: March 2018

The 14th ICML held in Lugano in June 2017 was preceded by a closed workshop (organized in collaboration with the American Association for Cancer Research and the European School of Oncology) where experts in preclinical and clinical research in lymphomas met to discuss the current drug development landscape focusing on critical open questions that need to be addressed in the future to permit a more efficient drug development paradigm in lymphoma. Topics discussed included both preclinical models that can be used to test new drugs and drug combinations, as well as the optimal design of clinical trials and the endpoints that should be used to facilitate accelerated progress. This report represents a summary of the workshop. Clin Cancer Res; 24(13); 2993–8. ©2018 AACR.
RIP1–HAT1–SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
Authors: Carafa Vincenzo , Nebbioso Angela , Cuomo Francesca , Rotili Dante , Cobellis Gilda , Bontempo Paola , Baldi Alfonso , Spugnini Enrico P. , Citro Gennaro , Chambery Angela , Russo Rosita , Ruvo Menotti , Ciana Paolo , Maravigna Luca , Shaik Jani , Radaelli Enrico , De Antonellis Pasquale , Tarantino Domenico , Pirolli Adele , Ragno Rino , Zollo Massimo , Stunnenberg Hendrik G. , Mai Antonello , Altucci Lucia
Published: March 2018

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.

Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.

Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo.

Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. Clin Cancer Res; 24(12); 2886–900. ©2018 AACR.
Exosome-Based Detection of EGFR T790M in Plasma from Non–Small Cell Lung Cancer Patients
Authors: Castellanos-Rizaldos Elena , Grimm Dominik G. , Tadigotla Vasisht , Hurley James , Healy John , Neal Patricia L. , Sher Mia , Venkatesan Raajdeep , Karlovich Chris , Raponi Mitch , Krug Anne , Noerholm Mikkel , Tannous Jihane , Tannous Bakhos A. , Raez Luis E. , Skog Johan K.
Published: March 2018

Purpose: About 60% of non–small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third-generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a noninvasive option to detect the mutation; however, sensitivity is low as many patients have too few detectable copies in circulation. Here, we have developed and validated a novel test that overcomes the limited abundance of the mutation by simultaneously capturing and interrogating exosomal RNA/DNA and cfDNA (exoNA) in a single step followed by a sensitive allele-specific qPCR.

Experimental Design: ExoNA was extracted from the plasma of NSCLC patients with biopsy-confirmed T790M-positive (N = 102) and T790M-negative (N = 108) samples. The T790M mutation status was determined using an analytically validated allele-specific qPCR assay in a Clinical Laboratory Improvement Amendment laboratory.

Results: Detection of the T790M mutation on exoNA achieved 92% sensitivity and 89% specificity using tumor biopsy results as gold standard. We also obtained high sensitivity (88%) in patients with intrathoracic disease (M0/M1a), for whom detection by liquid biopsy has been particularly challenging.

Conclusions: The combination of exoRNA/DNA and cfDNA for T790M detection has higher sensitivity and specificity compared with historical cohorts using cfDNA alone. This could further help avoid unnecessary tumor biopsies for T790M mutation testing. Clin Cancer Res; 24(12); 2944–50. ©2018 AACR.
A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Méndez Eduardo , Rodriguez Cristina P. , Kao Michael C. , Raju Sharat , Diab Ahmed , Harbison R. Alex , Konnick Eric Q. , Mugundu Ganesh M. , Santana-Davila Rafael , Martins Renato , Futran Neal D. , Chow Laura Q.M.
Published: March 2018

Purpose: The WEE1 tyrosine kinase regulates G2–M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. Thus, a need arises to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel.

Patients and Methods: We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with stage III/IVB HNSCC with borderline-resectable or -unresectable disease, but who were candidates for definitive chemoradiation. Escalating AZD1775 was administered orally twice a day over 2.5 days on the first week, then in combination with fixed cisplatin (25 mg/m2) and docetaxel (35 mg/m2) for 3 additional weeks. The primary outcome measure was adverse events to establish MTD. Secondary measures included response rates, pharmacokinetics (PK), pharmacodynamics, and genomic data.

Results: The MTD for AZD1775 was established at 150 mg orally twice per day for 2.5 days. RECISTv1.1 responses were seen in 5 of 10 patients; histologic adjustment revealed three additional responders. The only drug-limiting toxicity was grade 3 diarrhea. The PK C8hr target of 240 nmol/L was achieved on day 4 at all three doses tested. Pharmacodynamic analysis revealed a reduction in pY15-Cdk, and increases in γH2AX, CC3, and RPA32/RPA2 were noted in responders versus nonresponders.

Conclusions: The triplet combination of AZD1775, cisplatin, and docetaxel is safe and tolerable. Preliminary results show promising antitumor efficacy in advanced HNSCC, meriting further investigation at the recommended phase II dose. Clin Cancer Res; 24(12); 2740–8. ©2018 AACR.
Tradução e adaptação cultural do Safety Attitudes Questionnaire – Short Form 2006 para Portugal
Authors: Ricardo Fonseca Saraiva Dora Maria , Antunes de Almeida Anabela
Published: March 2018

Introdução: A segurança do doente é um parâmetro integrante da qualidade dos cuidados e uma prioridade dos sistemas de saúde. O Safety Attitudes Questionnaire (SAQ) – Short Form 2006 é o instrumento mais utilizado e rigorosamente validado para medir o clima de segurança do doente entre os prestadores de cuidados de saúde. Objetivo: O objetivo deste estudo foi traduzir e adaptar culturalmente este instrumento para Portugal originando a versão SAQ – Short Form 2006 PT. Material e métodos: Para o processo de tra­dução e adaptação cultural realizou-se um estudo meto­do­lógico baseado nas recomendações de Beaton e colaboradores [Recommendations for the Cross-Cultural Adaptation of Health Status Measures, 2002] com as etapas: tradução, síntese, retrotradução, avaliação por uma comissão de especialistas, pré-teste e submissão dos relatórios aos autores do instrumento. Resultados: O SAQ – Short Form 2006 foi traduzido linguisticamente e adaptado culturalmente ao novo contexto mantendo a congruência com a versão original. A validade de conteúdo foi garantida através de uma comissão de especialistas, que assegurou a equivalência semântica, idiomática, experimental e conceitual entre o instrumento original e a versão portuguesa. Conclusão: O SAQ – Short Form 2006 foi traduzido e adaptado para Portugal com sucesso, permitindo a sua aplicação em contexto cultural português.
Validation of Reference Charts for Mid-Trimester Fetal Biometry
Authors: van de Kamp K. , Pajkrt E. , Zwinderman A.H. , van der Post J.A. , Snijders R.J.M.
Published: March 2018

Objective: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project. Methods: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18–23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution. Results: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight. Conclusions: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account.
Biology Explaining Tooth Repair and Regeneration: A Mini-Review
Authors: Balic Anamaria
Published: March 2018

The tooth is an intricate composition of precisely patterned, mineralized matrices and soft tissues. Mineralized tissues include enamel (produced by the epithelial cells called ameloblasts), dentin and cementum (produced by mesenchymal cells called odontoblasts and cementoblasts, respectively), and soft tissues, which include the dental pulp and the periodontal ligament along with the invading nerves and blood vessels. It was perceived for a very long time that teeth primarily serve an esthetical function. In recent years, however, the role of healthy teeth, as well as the impact of oral health on general well-being, became more evident. Tooth loss, caused by tooth decay, congenital malformations (tooth agenesis), trauma, periodontal diseases, or age-related changes, is usually replaced by artificial materials which lack many of the important biological characteristics of the natural tooth. Human teeth have very low to almost absent regeneration potential, due to early loss of cell populations with regenerative capacity, namely stem cells. Significant effort has been made in recent decades to identify and characterize tooth stem cells, and to unravel the developmental programs which these cells follow in order to generate a tooth.
Gut Microbiota Dysbiosis in Children with Relapsing Idiopathic Nephrotic Syndrome
Authors: Tsuji Shoji , Suruda Chikushi , Hashiyada Masaki , Kimata Takahisa , Yamanouchi Sohsaku , Kitao Tetsuya , Kino Jiro , Akane Atsushi , Kaneko Kazunari
Published: March 2018

Background: While the etiology of idiopathic nephrotic syndrome (idiopathic nephrotic syndrome [INS]; characterized by repeated relapses and comorbid allergic conditions) remains unknown, recent evidence suggests that dysfunction in regulatory T cells (Tregs) plays an important role in the development of INS as well as allergic diseases. We hypothesized that dysbiosis involving decreased butyric acid-producing gut microbiota leads to defective induction and differentiation of peripherally induced Tregs, resulting in INS relapse. Methods: Study subjects were 12 children with INS, 8 classified as relapsing (R group; median age: 3.0 years) and 4 as non-relapsing (NR group; median age: 4.3 years), and 11 healthy children (HC group; median age: 5.1 years) serving as normal controls. Measurement of microbiota was performed using 16S ribosomal RNA metagenomic analysis, and fecal butyric acid was measured using high performance liquid chromatography. Flow-cytometric analysis of Tregs and CD4-positive (CD4+) cells in peripheral blood was also performed. Results: Metagenomic analysis of gut microbiota using feces showed that the proportion of butyric acid-producing bacteria was significantly lower in R (median 6.36%) than HC (median 18.84%; p = 0.0013), but no different between NR (median 16.71%) and HC (p = 0.29). Fecal organic acid analysis revealed significantly lower butyric acid quantities in R than HC (medians: 0.48 vs. 0.99 mg/g, p = 0.042). Circulating Tregs as a proportion of CD4+ cells were decreased in 75% of R and NR. Conclusion: Pediatric relapsing INS patients show gut microbiota dysbiosis, characterized by a decreased proportion of butyric acid-producing bacteria and lower fecal butyric acid quantities, concomitant with reduced circulatory Tregs.
USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma
Authors: Jia Meng , Guo Yaman , Lu Xiubo
Published: March 2018

Background/Aims: To investigate the clinical significance and functional mechanisms of deubiquitinase USP33 in papillary thyroid carcinoma (PTC). Methods: Immunohistochemistry staining was conducted to explore the expression of USP33 in PTC tissues and adjacent normal thyroid tissues. Patients’ prognosis was evaluated by disease-free survival. The prognostic role of USP33 was tested by univariate and multivariate analyses. To confirm the effect of USP33 in cell proliferation and invasion, overexpression and knockdown of USP33 were performed in two PTC cell lines. Besides, cell cycle, immunoprecipitation, and apoptosis experiments were conducted to further explore the signaling pathways. Results: By analyzing series of 158 PTC tissues, we found that USP33 was down-regulated in tumor tissue compared with normal thyroid tissues, which was closely associated with lymph node metastasis (P<0.001). In particular, univariate and multivariate analyses indicated that USP33 was an independent prognostic biomarker for PTC, low USP33 expression indicated high recurrence risk. Cellular studies with TPC-1 and BCPAP cells demonstrated that USP33 can attenuate the cell capacities of proliferation, migration and invasion. Fluorescence-activated cell sorting experiment found no significant effect of USP33 on cell cycle, whereas the apoptotic caspase proteins were activated by USP33-overexpression. Moreover, the interaction between USP33 and Robo1 protein was identified, and knockdown of Robo1 enhancing the oncogenic effect upon USP33-knockdown, suggesting that USP33 may inhibit tumor progression through Robo1 signaling. Conclusions: Our data demonstrated that USP33 downregulation in PTC tissues was correlated with poor clinical outcome, which may serve as a novel biomarker and potential therapeutic target.
Sepia Ink Oligopeptide Induces Apoptosis of Lung Cancer Cells via Mitochondrial Pathway
Authors: Wang Xiaohua , Chen Cheng , Zhou Guoren , Ye Jinjun , Yin Rong , Feng Dongjie , Zhang Shuai , Wang Xiaojun , Zhao Xin , Zhang Zhi
Published: March 2018

Background/Aims: Our previous study suggested the anti-tumor activity of sepia ink oligopeptide (SIO). Here we sought to investigate the underlying molecular mechanism. Methods: Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by Annexin V/Propidium Iodide (PI) staining. The mitochondria pathway was characterized by quantification of Bcl-2, Bax, Caspase-9 and Cyto-C. The death receptor pathway was analyzed by determinement of Fas, Caspase-8 and NIK. The endoplasmic reticulum (ER)-dependent pathway was determined by measurement the expression of CHOP, Caspase-12, GRP78 and Calpain. The associated gene expression was quantified by RT-PCR and protein level was determined by immunoblotting. Results: We demonstrated treatment with structurally modified SIO (CSIO, 5 µM) significantly inhibited cell proliferation and induced apoptosis in lung cancer cell line A549. The mitochondrial pathway, death receptor pathway and ER stress induced apoptosis were stimulated upon CSIO treatment. The administration with respective inhibitors including midiv-1 (50 µM for 2 h), PDTC (20 µM PDTC for 30 min) and ALLN (20 mM ALLN for 5 h) readily reversed the apoptosis inducing effect of CSIO. Conclusion: Our data demonstrates that CSIO is capable of induction apoptosis in lung cancer cell line, which is mediated by all three classical apoptotic pathways. Our results warrant further in vivo investigations of the anti-tumor potential of CSIO.
High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium
Authors: Lu Zhongyan , Shen Hong , Shen Zanming
Published: March 2018

Background/Aims: In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. Methods: RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. Results: The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. Conclusions: These results indicated that the alterations of cellular metabolism promote the alterations in cellular immunity, repair, and homeostasis in the rumen epithelium, thereby leading to the switch of concentrate effects from positive to negative with regard to animal production and health.
Maxillary removable partial denture combined with O’ring attachment implant: a case report
Authors: Costa Tiago Rebelo , Yamaguchi Cláudio Akira , Galhardo Alessandra Pucci Mantelli , Stegun Roberto Chaib , Costa Bruno , Mukai Márcio Katsuyoshi
Published: March 2018

Oral rehabilitation with free-end removable partial denture (RPD) is one of the major challenges in prosthodontic dentistry. The absence of a distal abutment produces undesirable RPD movement during masticatory function due to the high resilience of the residual ridge, which limits the denture efficiency and may damage the abutment teeth and bone over time. The advent of dental implants made possible to substitute the missing teeth with fixed implant-supported dentures as the first choice treatment to overcome such inconveniences. However, this indication may not be suitable for all patients due to financial, anatomical or systemic health conditions. Nevertheless it is possible to improve free extension RPD by using implants in the posterior edentulous ridge to achieve biological, biomechanical, physiological and social benefits. This article aims to present a case report on oral rehabilitation in which a RPD was made combined with an implant for posterior support in a sizeable edentulous ridge. The patient appreciated the retention improvement and the aesthetic result. The combination of a RPD with a posterior implant is an alternative treatment for cases in which implant-supported fixed prosthesis is not indicated, reducing the displacement and minimizing the limitations of the free-end devices.
Síndrome de Sjögren primária: aspectos relevantes para os dentistas
Authors: Cavalcante Wanessa Siqueira , Lourenço Silvia Vanessa , Florezi Giovanna Piacenza , Bologna Sheyla Batista , Hsieh Ricardo , Vanini Jaqueline Vaz , Antunes Milena Monteiro de Souza , Paula Fernanda de , Pasoto Sandra Gofinet , Silva Luiz Fernando Ferraz da , Nico Marcello Menta Simonsen
Published: March 2018

Objetivo: Esta revisão de literatura tem o propósito de oferecer aos cirurgiões-dentistas entendimento sobre os principais achados clínico-epidemiológicos da síndrome de Sjögren primária (SSp), bem como ressaltar os principais aspectos etiopatogênicos e histopatológicos da doença. Métodos: Buscou-se na base de dados Pubmed/Medline e ScienceDirect os descritores “síndrome de Sjögren”, “glândulas salivares”, “xerostomia”, “diagnóstico”, “glândula salivar menor”, “etiologia”, “biopsia” entre os anos de 1991 a 2017. Discussão: A SSp é uma exocrinopatia autoimune que tem como substrato, em especial, as glândulas lacrimais e salivares, culminando com os sintomas de xeroftalmia e xerostomia. Seu principal achado morfológico é a presença de agregados de leucócitos mononucleares ao redor dos ductos e ácinos. Outras manifestações sistêmicas podem estar presentes, acarretando considerável morbidade nos pacientes acometidos. Atualmente, foi publicado o mais novo conjunto de critérios diagnósticos da doença, sendo um marco histórico no diagnóstico precoce da enfermidade, fundamental para diminuir os altos números de subdiagnósticos e otimizar a conduta clínica. Conclusão: Esta revisão abordou os aspectos clínicos-epidemiológicos, histopatológicos e etiopatogênicos da SSp, objetivando melhor compreensão dessa doença multifatorial e, portanto, a necessidade de uma conduta multidisciplinar e do papel fundamental do cirurgião-dentista no manejo dos pacientes acometidos por essa síndrome.
Biosynthesis of phospholipases and proteinases using clinical and environmental strains of Cryptococcus neoformans
Authors: Cardoso Pedro Henrique Magalhães , Santos Rennan Luiz Oliveira dos , Souza Ana Clara , Baroni Francisco de Assis , Domaneschi Carina , Paula Claudete Rodrigues
Published: March 2018

Objetivo: Comparar a produção de enzimas (proteinases e fosfolipases) entre os isolados de origem clínica e de origem ambiental de Cryptococcus neoformans, uma vez que pesquisas com isolados de origem clínica e ambiental contribuem para a compreensão dos mecanismos envolvidos no controle destas infecções. Metodologia: Nesta pesquisa, 78 isolados de C. neoformans de origem clínica e ambiental foram testados para demonstrar um fenótipo possivelmente associado e sua virulência. Resultados: Observamos que as cepas de origem clínica tiveram uma taxa de produção de fosfolipase maior comparada à de proteinase. As cepas de origem ambiental não apresentaram tal diferenciação. Conclusão: Estes aspectos enfatizam o papel da fosfolipase em casos de infecções de C. neoformans de origem clínica e podem ser um marcador para evidenciar estas espécies.
Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease
Authors: Beckman Joshua A. , Duncan Meredith S. , Alcorn Charles W. , So-Armah Kaku , Butt Adeel A. , Goetz Matthew Bidwell , Tindle Hilary A. , Sico Jason J. , Tracy Russel P. , Justice Amy C. , Freiberg Matthew S.
Published: March 2018

Background:

The effect of human immunodeficiency virus (HIV) on the development of peripheral artery disease (PAD) remains unclear. We investigated whether HIV infection is associated with an increased risk of PAD after adjustment for traditional atherosclerotic risk factors in a large cohort of HIV-infected (HIV+) and demographically similar HIV-uninfected veterans.

Methods:

We studied participants in the Veterans Aging Cohort Study from April 1, 2003 through December 31, 2014. We excluded participants with known prior PAD or prevalent cardiovascular disease (myocardial infarction, stroke, coronary heart disease, and congestive heart failure) and analyzed the effect of HIV status on the risk of incident PAD events after adjusting for demographics, PAD risk factors, substance use, CD4 cell count, HIV-1 ribonucleic acid, and antiretroviral therapy. The primary outcome is incident peripheral artery disease events. Secondary outcomes include mortality and amputation in subjects with incident PAD events by HIV infection status, viral load, and CD4 count.

Results:

Among 91 953 participants, over a median follow up of 9.0 years, there were 7708 incident PAD events. Rates of incident PAD events per 1000 person-years were higher among HIV+ (11.9; 95% confidence interval [CI], 11.5–12.4) than uninfected veterans (9.9; 95% CI, 9.6–10.1). After adjustment for demographics, PAD risk factors, and other covariates, HIV+ veterans had an increased risk of incident PAD events compared with uninfected veterans (hazard ratio [HR], 1.19; 95% CI, 1.13–1.25). This risk was highest among those with time-updated HIV viral load >500 copies/mL (HR, 1.51; 95% CI, 1.38–1.65) and CD4 cell counts <200 cells/mm
3
(HR, 1.91; 95% CI, 1.71–2.13). In contrast, HIV+ veterans with time updated CD4 cell count ≥500 cells/mm
3
had no increased risk of PAD (HR, 1.03; 95% CI, 0.96–1.11). Mortality rates after incident PAD events are high regardless of HIV status. HIV infection did not affect rates of amputation after incident PAD events.

Conclusions:

Infection with HIV is associated with a 19% increased risk of PAD beyond that explained by traditional atherosclerotic risk factors. However, for those with sustained CD4 cell counts <200 cells/mm
3
, the risk of incident PAD events is nearly 2-fold higher whereas for those with sustained CD4 cell counts ≥500 cells/mm
3
there is no excess risk of incident PAD events compared with uninfected people.
Shared and Distinct Rupture Discriminants of Small and Large Intracranial Aneurysms
Authors: Varble Nicole , Tutino Vincent M. , Yu Jihnhee , Sonig Ashish , Siddiqui Adnan H. , Davies Jason M. , Meng Hui
Published: March 2018

Background and Purpose—

Many ruptured intracranial aneurysms (IAs) are small. Clinical presentations suggest that small and large IAs could have different phenotypes. It is unknown if small and large IAs have different characteristics that discriminate rupture.

Methods—

We analyzed morphological, hemodynamic, and clinical parameters of 413 retrospectively collected IAs (training cohort; 102 ruptured IAs). Hierarchal cluster analysis was performed to determine a size cutoff to dichotomize the IA population into small and large IAs. We applied multivariate logistic regression to build rupture discrimination models for small IAs, large IAs, and an aggregation of all IAs. We validated the ability of these 3 models to predict rupture status in a second, independently collected cohort of 129 IAs (testing cohort; 14 ruptured IAs).

Results—

Hierarchal cluster analysis in the training cohort confirmed that small and large IAs are best separated at 5 mm based on morphological and hemodynamic features (area under the curve=0.81). For small IAs (<5 mm), the resulting rupture discrimination model included undulation index, oscillatory shear index, previous subarachnoid hemorrhage, and absence of multiple IAs (area under the curve=0.84; 95% confidence interval, 0.78–0.88), whereas for large IAs (≥5 mm), the model included undulation index, low wall shear stress, previous subarachnoid hemorrhage, and IA location (area under the curve=0.87; 95% confidence interval, 0.82–0.93). The model for the aggregated training cohort retained all the parameters in the size-dichotomized models. Results in the testing cohort showed that the size-dichotomized rupture discrimination model had higher sensitivity (64% versus 29%) and accuracy (77% versus 74%), marginally higher area under the curve (0.75; 95% confidence interval, 0.61–0.88 versus 0.67; 95% confidence interval, 0.52–0.82), and similar specificity (78% versus 80%) compared with the aggregate-based model.

Conclusions—

Small (<5 mm) and large (≥5 mm) IAs have different hemodynamic and clinical, but not morphological, rupture discriminants. Size-dichotomized rupture discrimination models performed better than the aggregate model.
Distribution and Temporal Trends From 1993 to 2015 of Ischemic Stroke Subtypes
Authors: Ornello Raffaele , Degan Diana , Tiseo Cindy , Di Carmine Caterina , Perciballi Laura , Pistoia Francesca , Carolei Antonio , Sacco Simona
Published: March 2018

Background and Purpose—

Preventive strategies, together with demographic and socioeconomic changes, might have modified the worldwide distribution of ischemic stroke (IS) subtypes. We investigated those changes by means of a systematic review and meta-analysis.

Methods—

We evaluated all population- and hospital-based studies reporting the distribution of IS etiologic subtypes according to the TOAST criteria (Trial of ORG 10172 in Acute Stroke Treatment). Studies were identified by searching articles indexed on PubMed and Scopus from January 1, 1993, to June 30, 2017. Two independent investigators extracted data and checked them for accuracy. Proportions of each etiologic subtype were pooled according to a random effect meta-analytic model weighted by study size; temporal trends were assessed using a mixed-effect meta-regression model.

Results—

Sixty-five studies including patients from 1993 to 2015 were finally included. Overall, ISs were attributed to cardioembolism (22%; 95% confidence interval [CI], 20–23); large artery atherosclerosis (23%; 95% CI, 21–25); small artery occlusion (22%; 95% CI, 21–24); other determined cause (3%; 95% CI, 3–3); and undetermined cause (26%; 95% CI, 24–28). Cardioembolism was the leading IS etiologic subtype in whites (28%; 95% CI, 26–29) and large artery atherosclerosis in Asians (33%; 95% CI, 31–36). Meta-regression showed an increasing temporal trend for cardioembolism in whites (2.4% annually,
P
=0.008) and large artery atherosclerosis in Asians (5.7% annually,
P
<0.001), and a decrease for small artery occlusion in whites (−4.7% annually,
P
=0.001); there was considerable heterogeneity across all the analyses.

Conclusions—

According to our systematic review and meta-analysis, cardioembolism in whites and large artery atherosclerosis in Asians are the leading causes of IS. The heterogeneous distribution of etiologic subtypes of IS may depend on the demographic and socioeconomic characteristics of the different populations. More extensive protocols should be adopted to reduce the persistently relevant proportion of undetermined cause IS.
The Cultural Impact of Islamic Mass Immigration on the Italian Legal System
Authors: Falletti E.
Published: March 2018

Although Italy is a country with a strong tradition of emigration, only in the last twenty- five years have Italians had to face new and pressing social, juridical and cultural problems related to a surge in immigration. The majority of immigrants during this period have been from areas steeped in with a Muslim majority such as Northern and Central Africa and the Middle East. The cultural encounter between the Italian Catholic tradition and the newcomers’ faith and customs has been very pronounced, and often problematic.

The aim of this paper is to investigate the most relevant issues that arise from the interface between the cultural and legal aspects of Islamic culture pertaining to immigrants living in Italy with the Italian legal system. The areas considered are related to self-determination, personal integrity and family law, and were selected for their relevance to analyzing the impact of cultural differences on public policies and social behavior. The methodology used draws from both a comparative and a multidisciplinary approach.
Rediscovery of Cremanthodium principis (Asteraceae, Senecioneae) in northwestern Yunnan, China
Authors: WANG LONG , REN CHEN , YANG QIN-ER
Published: March 2018

The rediscovery of Cremanthodium principis (Asteraceae, Senecioneae) in northwestern Yunnan, China is reported. Based on this finding, the type locality of this species is precisely localized, its habitat preference is specified, and some morphological characters are added for it. Moreover, the finding allows us to gain a better understanding of the taxonomic affinities of C. principis with other species in the genus. We also evaluate the conservation status of C. principis.
Prodromus of a fern flora for Bolivia. XI. Gleicheniaceae
Authors: KESSLER MICHAEL , SMITH ALAN R.
Published: March 2018

We provide a synopsis to the fern family Gleicheniaceae in Bolivia, including four genera and 24 species, with 20 species in the taxonomically difficult genus Sticherus, two Dicranopteris, one Diplopterygium, and one Gleichenella. Gleicheniaceae is one of the most conspicuous fern families in Bolivia, often forming large roadside colonies, but much remains to be learned about the taxonomy and ecology of the family.
Miltochrista wangmini, a new species from China (Lepidoptera, Erebidae, Arctiinae)
Authors: VOLYNKIN ANTON V. , DUBATOLOV VLADIMIR V. , KISHIDA YASUNORI
Published: March 2018

Miltochrista Hübner, [1819] is one of largest genera of lichen-moths (family Erebidae, subfamily Arctiinae, tribe Lithosiini) including more than 160 valid species, widely distributed in Oriental and Palearctic Regions. For a long time, the genus was treated in a wide sense. Holloway (2001) treated Miltochrista as a small group of species close to the type species of the genus Noctua rubicunda [Denis & Schiffermüller], 1775 (a junior synonym of Miltochrista miniata (J.R. Forster, 1771)), whereas the majority of other Palaearctic and Oriental Miltochrista-like species was assigned to the genera Lyclene Moore in Horsfield & Moore, [1860] and Barsine Walker, 1854. Kirti & Singh (2016) synonymized Lyclene with Miltochrista and at present the genus is treated in wide sense. Nevertheless, Miltochrista in its modern treatment is a heterogeneous group, the status of Lyclene and some other species-groups with significantly different male and female genital structures is unclear, and the generic/subgeneric structure of Miltochrista sensu lato is under revision by Volynkin & Dubatolov (in prep.).
Re-examining the rare and the lost: a review of fossil Tortricidae (Lepidoptera)
Authors: HEIKKILÄ MARIA , BROWN JOHN W. , BAIXERAS JOAQUIN , MEY WOLFRAM , KOZLOV MIKHAIL V.
Published: March 2018

We re-evaluate eleven fossils that have previously been assigned to the family Tortricidae, describe one additional fossil, and assess whether observable morphological features warrant confident assignment of these specimens to this family. We provide an overview of the age and origin of the fossils and comment on their contribution towards understanding the phylogeny of the Lepidoptera. Our results show that only one specimen, Antiquatortia histuroides Brown & Baixeras gen. and sp. nov., shows a character considered synapomorphic for the family. Six other fossils (Electresia zalesskii Kusnezov, 1941; Tortricidrosis inclusa Skalski, 1973; Tortricites skalskii Kozlov, 1988; Tortricibaltia diakonoffi Skalski, 1992; Polyvena horatis Poinar and Brown, 1993 and a trace fossil purported to be larval feeding damage of Retinia resinella (Linnaeus, 1758)) exhibit a combination of homoplastic characters typical of tortricid moths or characteristic feeding damage. An unnamed species doubtfully assigned to Olethreutinae by Skalski (1992), Spatalistiforma submerga Skalski, 1992, Tortricites florissantanus (Cockerell, 1907), Tortricites destructus (Cockerell, 1916) and Tortricites sadilenkoi Kozlov, 1988 do not show enough character evidence to be convincingly placed in Tortricidae. Therefore, we transfer the three latter species from the collective group Tortricites Kozlov, 1988, defined as an assemblage of fossil leafrollers that cannot be placed with certainty in known genera, to Paleolepidopterites Kozlov, new collective group, defined as a group of fossil lepidopterans whose assignment to a certain family is currently impossible.
Colleagues and Competitors: How Internal Social Comparisons Shape Organizational Search and Adaptation
Authors: Baumann Oliver , Eggers J. P. , Stieglitz Nils
Published: March 2018

Intra-organizational comparisons—managers and units benchmarking their performance against each other—can turn colleagues into competitors. To better understand when organizations should allow or even encourage internal social comparisons, we study their implications for organizational adaptation and performance. We conceptualize internal social comparisons as an upstream competitive process that shapes performance aspirations and creates interdependencies in search behavior. We distinguish this from downstream, product market competition or complementarities where performance is interdependent across units. Integrating both aspects into a computational model, we show how internal social comparisons affect adaptation and performance through two mechanisms: a balancing effect whereby the organization is guaranteed to contain both exploring and exploiting units, and a stabilizing effect whereby internal social comparisons protect against abandoning existing technologies too early. The benefits of upstream comparisons are accentuated when units are downstream complements, helping synchronize search. When units are downstream competitors, these benefits disappear, suggesting substitutive effects. We highlight empirical implications and discuss theoretical links to work on intra-organizational competition, social comparisons and aspiration-driven search, diversification and performance, and the adaptation of multi-business firms.
Introducing a Circular Economy: New Thinking with New Managerial and Policy Implications
Authors: Esposito Mark , Tse Terence , Soufani Khaled
Published: March 2018

Since the industrial revolution, we have been living in a linear economy. Our consumer and “single use” lifestyles have made the planet a “take, make, dispose” world. This refers to a unidirectional model of production: natural resources provide our factory inputs, which are then used to create mass-produced goods to be purchased and, typically, disposed after a single use. This linear economy model of mass production and mass consumption is testing the physical limits of the globe. It is, therefore, unsustainable and a shift toward a circular economy is becoming inevitable.
Testing a Framework of Math Progress Indicators for ESSA: How Opportunity to Learn and Instructional Leadership Matter
Authors: Urick Angela , Wilson Alison S. P. , Ford Timothy G. , Frick William C. , Wronowski Meredith L.
Published: March 2018

Purpose: To advance a framework of indicators that promotes implementation of math standards under the Every Student Succeeds Act (ESSA), we tested a conceptual model of the resources and processes within schools that influence the opportunity to learn mathematics (OTL) in the classroom using a recent administration of the 2011 Trends in International Math and Science Study (TIMSS 2011). There is potential benefit to state departments and system-level practitioners from more information about how schools might influence student access to college and career-ready curriculum. Such information has the potential to shape the kinds of indicators stakeholders put in place to target problems and formulate solutions for math learning. Research Design: To test the fit of our hypothesized model of math content and instruction OTL, we applied structural equation modeling techniques to school and classroom data from 425 fourth-grade U.S. math teachers in TIMSS 2011. Findings: We found a direct influence of instructional leadership on OTL math instruction in the classroom and teacher participation in math professional development. Content-specific resources indirectly influenced both OTL math instruction and content through teacher preparedness. Conclusions: The results of this study demonstrate a potential framework through which school leaders can support the preparedness of teachers in providing students with equitable access to coherent, focused, and rigorous math content.
Active Fault Tolerant Control System for the Measurement Circuit in a Drum Boiler Feed-Water Control System
Authors: Pawlak Mariusz
Published: March 2018

This paper presents a water-level control system in a drum boiler. The system was equipped with a fault tolerant control–type diagnostic system. The paper presents the results of tests conducted on the fault tolerant control system implemented in the water-level control system in a boiler drum. The diagnostics of the measurement circuits was carried out online. To that end, the appropriate partial models were developed and tested. This allowed for the application of analytical redundancy for the measurement circuits. The paper also identifies the influence of diagnostics and fault tolerance on the values of reliability indices and operating safety of a power unit. Fault tolerant control systems increase the safety of a power unit operation, and the studies described in the paper directly contribute to them. These kinds of systems have not been used so far in power unit automation. Site tests confirmed the validity of the acquired concept for the diagnostic system. Fault tolerant control systems have not been commonly applied in power engineering yet. Studies of the water-level control system in a steam drum using the fault tolerant control system for the measurement circuits as presented in the paper are original ideas, providing a new solution. All control systems made for the study fulfil their role in a satisfactory way, which results in a minor deviation in the water-level adjustment in the boiler drum. The tests confirmed the efficiency of the fault detection algorithm. The created models of the water level and flows proved to be successful. Under a no-fault condition of the facility, there were no errors in the diagnoses and the values of all residua were below the detection thresholds. This was achieved despite a high value of measurement noises. The residua helped detect minor faults.
‘That is how the real mad people behave’: Beliefs about and treatment of mental disorders by traditional medicine-men in Accra, Ghana
Authors: Kpobi Lily , Swartz Leslie
Published: March 2018

Background:

Traditional healing methods are considered central to mental health care in low-income countries such as Ghana, because they are perceived to be more easily accessible, more affordable and generally ascribe similar causal beliefs to those of the patients. However, not much is known about the work of traditional healers largely because their methods are shrouded in mysticism and secrecy. There is a need to understand the ideology and beliefs of traditional healers surrounding mental disorders, including knowledge about their practices in mental health care.

Aims:

In this article, we discuss the causal beliefs and treatment methods of traditional medicine-men from Accra, Ghana. We also describe their diagnostic and treatment methods for mental disorders.

Methods:

Eight medicine-men, indigenous to the Greater Accra Region, were interviewed through individual semi-structured interviews. The data were analysed through thematic analysis.

Results:

The medicine-men’s beliefs about mental illness were dominated by supernatural ideas. Mental illness was also seen as a form of punishment or resulting from envy, and there was a strong reliance on spiritual direction from the gods for diagnosis and treatment.

Conclusion:

These themes are discussed with emphasis on their potential implications for patients, as well as for collaborative efforts.
The Emergence of Shared Leadership in Newly Formed Teams With an Initial Structure of Vertical Leadership: A Longitudinal Analysis
Authors: Fransen Katrien , Delvaux Ellen , Mesquita Batja , Van Puyenbroeck Stef
Published: March 2018

The importance of high-quality leadership for team effectiveness is widely recognized, with recent viewpoints arguing shared leadership to be a more powerful predictor than vertical leadership. To identify changes in leadership structures over time, we longitudinally tracked the leadership structure of 27 newly formed teams ( N = 195), all having an initial structure of vertical leadership. Our findings demonstrated that the average team leadership strengthened over the course of the 24-week project and leadership tended to become more distributed among team members. Regarding the antecedents of these changes, we found evidence that the more team members are perceived as warm or competent, the higher their perceived influence. Finally, examining the consequences of these changes, the leadership structure was found to be related with team performance in that teams with higher average leadership perceptions performed better. These findings underpin the importance of shared leadership, thereby suggesting leaders to empower their team members.
Electrical, thermal and thermo-mechanical properties of epoxy/multi-wall carbon nanotubes/mineral fillers nanocomposites
Authors: Backes Eduardo H , Passador Fabio R , Leopold Christian , Fiedler Bodo , Pessan Luiz A
Published: March 2018

Epoxy/multi-wall carbon nanotubes and epoxy/multi-wall carbon nanotubes/mineral fillers nanocomposites were produced via in situ polymerization assisted by three-roll-milling. Epoxy/multi-wall carbon nanotubes nanocomposites presented very low electrical percolation threshold, near to 0.05 wt %. In this study, we used different mineral fillers, with different aspect ratios: calcium carbonate, montmorillonite, and sepiolite. We evaluated the effect of the addition of these fillers on electrical, thermal, and thermo-mechanical properties of epoxy/multi-wall carbon nanotubes nanocomposites. The addition of calcium carbonate in epoxy/multi-wall carbon nanotubes nanocomposites increased the electrical conductivity of this nanocomposite, due to volume exclusion effect. The addition of sepiolite decreased the loss factor and improved electrical constant, however, reduced the electrical conductivity in these nanocomposites, when compared to epoxy/multi-wall carbon nanotubes. Regarding thermal properties, no significant change in glass transition was observed. Thermo-mechanical analysis for nanocomposites showed slight changes in tan (δ) and storage modulus, which is related to the interaction between epoxy, multi-wall carbon nanotubes and mineral fillers.
Conditional Consent and Purposeful Deception
Authors: Clough Amanda
Published: March 2018

The media has recently given much attention to the ‘stealthing’ trend, undisclosed condom removal during sex and how this may affect consent to sexual activity. This paper seeks to discuss where situations like this sit within the Sexual Offenses Act 2003, and how it may compare to other instances of consent gained in deceitful circumstances.