bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO Inhibitors
Authors: Rahman Muhammad M. , Hazan Allon , Selway Joanne L. , Herath Dimalee S. , Harwood Catherine A. , Pirzado Muhammad S. , Atkar Ravinder , Kelsell David P. , Linton Kenneth J. , Philpott Mike P. , Neill Graham W.
Published: February 2018

Small-molecule inhibitors of the Hedgehog (HH) pathway receptor Smoothened (SMO) have been effective in treating some patients with basal cell carcinoma (BCC), where the HH pathway is often activated, but many patients respond poorly. In this study, we report the results of investigations on PTCH1 signaling in the HH pathway that suggest why most patients with BCC respond poorly to SMO inhibitors. In immortalized human keratinocytes, PTCH1 silencing led to the generation of a compact, holoclone-like morphology with increased expression of SMO and the downstream HH pathway transcription factor GLI1. Notably, although siRNA silencing of SMO in PTCH1-silenced cells was sufficient to suppress GLI1 activity, this effect was not phenocopied by pharmacologic inhibition of SMO, suggesting the presence of a second undefined pathway through which SMO can induce GLI1. Consistent with this possibility, we observed increased nuclear localization of SMO in PTCH1-silenced cells as mediated by a putative SMO nuclear/nucleolar localization signal [N(o)LS]. Mutational inactivation of the N(o)LS ablated this increase and suppressed GLI1 induction. Immunohistologic analysis of human and mouse BCC confirmed evidence of nuclear SMO, although the pattern was heterogeneous between tumors. In PTCH1-silenced cells, >80% of the genes found to be differentially expressed were unaffected by SMO inhibitors, including the putative BCC driver gene CXCL11. Our results demonstrate how PTCH1 loss results in aberrant regulation of SMO-independent mechanisms important for BCC biology and highlights a novel nuclear mechanism of SMO-GLI1 signaling that is unresponsive to SMO inhibitors.

Significance: This study describes novel noncanonical Hedgehog signaling, where SMO enters the nucleus to activate GLI1, a mode that is unaffected by SMO inhibitors, thus prompting re-evaluation of current BCC treatment as well as new potential therapies targeting nuclear SMO. Cancer Res; 78(10); 2577–88. ©2018 AACR.
The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection
Authors: Billatos Ehab , Vick Jessica L. , Lenburg Marc E. , Spira Avrum E.
Published: February 2018

Lung cancer remains the leading cause of cancer-related death due to its advanced stage at diagnosis. Early detection of lung cancer can be improved by better defining who should be screened radiographically and determining which imaging-detected pulmonary nodules are malignant. Gene expression biomarkers measured in normal-appearing airway epithelium provide an opportunity to use lung cancer–associated molecular changes in this tissue for early detection of lung cancer. Molecular changes in the airway may result from an etiologic field of injury and/or field cancerization. The etiologic field of injury reflects the aberrant physiologic response to carcinogen exposure that creates a susceptible microenvironment for cancer initiation. In contrast, field cancerization reflects effects of “first-hit” mutations in a clone of cells from which the tumor ultimately arises or the effects of the tumor on the surrounding tissue. These fields might have value both for assessing lung cancer risk and diagnosis. Cancer-associated gene expression changes in the bronchial airway have recently been used to develop and validate a 23-gene classifier that improves the diagnostic yield of bronchoscopy for lung cancer among intermediate-risk patients. Recent studies have demonstrated that these lung cancer–related gene expression changes extend to nasal epithelial cells that can be sampled noninvasively. While the bronchial gene expression biomarker is being adopted clinically, further work is necessary to explore the potential clinical utility of gene expression profiling in the nasal epithelium for lung cancer diagnosis, lung cancer risk assessment, and precision medicine for lung cancer treatment and chemoprevention. Clin Cancer Res; 24(13); 2984–92. ©2018 AACR.
Disruption of Wnt/β-Catenin Exerts Antileukemia Activity and Synergizes with FLT3 Inhibition in FLT3-Mutant Acute Myeloid Leukemia
Authors: Jiang Xuejie , Mak Po Yee , Mu Hong , Tao Wenjing , Mak Duncan H. , Kornblau Steven , Zhang Qi , Ruvolo Peter , Burks Jared K. , Zhang Weiguo , McQueen Teresa , Pan Rongqing , Zhou Hongsheng , Konopleva Marina , Cortes Jorge , Liu Qifa , Andreeff Michael , Carter Bing Z.
Published: February 2018

Purpose: Wnt/β-catenin signaling is required for leukemic stem cell function. FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous FLT3 signaling increases β-catenin nuclear localization and transcriptional activity. FLT3 tyrosine kinase inhibitors (TKI) are used clinically to treat FLT3-mutated AML patients, but with limited efficacy. We investigated the antileukemia activity of combined Wnt/β-catenin and FLT3 inhibition in FLT3-mutant AML.

Experimental Design: Wnt/β-catenin signaling was inhibited by the β-catenin/CBP antagonist C-82/PRI-724 or siRNAs, and FLT3 signaling by sorafenib or quizartinib. Treatments on apoptosis, cell growth, and cell signaling were assessed in cell lines, patient samples, and in vivo in immunodeficient mice by flow cytometry, Western blot, RT-PCR, and CyTOF.

Results: We found significantly higher β-catenin expression in cytogenetically unfavorable and relapsed AML patient samples and in the bone marrow–resident leukemic cells compared with circulating blasts. Disrupting Wnt/β-catenin signaling suppressed AML cell growth, induced apoptosis, abrogated stromal protection, and synergized with TKIs in FLT3-mutated AML cells and stem/progenitor cells in vitro. The aforementioned combinatorial treatment improved survival of AML-xenografted mice in two in vivo models and impaired leukemia cell engraftment. Mechanistically, the combined inhibition of Wnt/β-catenin and FLT3 cooperatively decreased nuclear β-catenin and the levels of c-Myc and other Wnt/β-catenin and FLT3 signaling proteins. Importantly, β-catenin inhibition abrogated the microenvironmental protection afforded the leukemic stem/progenitor cells.

Conclusions: Disrupting Wnt/β-catenin signaling exerts potent activities against AML stem/progenitor cells and synergizes with FLT3 inhibition in FLT3-mutant AML. These findings provide a rationale for clinical development of this strategy for treating FLT3-mutated AML patients. Clin Cancer Res; 24(10); 2417–29. ©2018 AACR.
Integrated Pharmacokinetic/Pharmacodynamic Model of a Bispecific CD3xCD123 DART Molecule in Nonhuman Primates: Evaluation of Activity and Impact of Immunogenicity
Authors: Campagne Olivia , Delmas Audrey , Fouliard Sylvain , Chenel Marylore , Chichili Gurunadh R. , Li Hua , Alderson Ralph , Scherrmann Jean-Michel , Mager Donald E.
Published: February 2018

Purpose: Flotetuzumab (MGD006 or S80880) is a bispecific molecule that recognizes CD3 and CD123 membrane proteins, redirecting T cells to kill CD123-expressing cells for the treatment of acute myeloid leukemia. In this study, we developed a mathematical model to characterize MGD006 exposure–response relationships and to assess the impact of its immunogenicity in cynomolgus monkeys.

Experimental Design: Thirty-two animals received multiple escalating doses (100-300-600-1,000 ng/kg/day) via intravenous infusion continuously 4 days a week. The model reflects sequential binding of MGD006 to CD3 and CD123 receptors. Formation of the MGD006/CD3 complex was connected to total T cells undergoing trafficking, whereas the formation of the trimolecular complex results in T-cell activation and clonal expansion. Activated T cells were used to drive the peripheral depletion of CD123-positive cells. Anti-drug antibody development was linked to MGD006 disposition as an elimination pathway. Model validation was tested by predicting the activity of MGD006 in eight monkeys receiving continuous 7-day infusions.

Results: MGD006 disposition and total T-cell and CD123-positive cell profiles were well characterized. Anti-drug antibody development led to the suppression of T-cell trafficking but did not systematically abolish CD123-positive cell depletion. Target cell depletion could persist after drug elimination owing to the self-proliferation of activated T cells generated during the first cycles. The model was externally validated with the 7-day infusion dosing schedule.

Conclusions: A translational model was developed for MGD006 that features T-cell activation and expansion as a key driver of pharmacologic activity and provides a mechanistic quantitative platform to inform dosing strategies in ongoing clinical studies. Clin Cancer Res; 24(11); 2631–41. ©2018 AACR.
Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted Photodynamic Therapy of Prostate Cancer Xenografts
Authors: Kim Kwanghee , Watson Philip A. , Lebdai Souhil , Jebiwott Sylvia , Somma Alexander J. , La Rosa Stephen , Mehta Dipti , Murray Katie S. , Lilja Hans , Ulmert David , Monette Sebastien , Scherz Avigdor , Coleman Jonathan A.
Published: February 2018

Purpose: WST11 vascular targeted photodynamic therapy (VTP) is a local ablation approach relying upon rapid, free radical-mediated destruction of tumor vasculature. A phase III trial showed that VTP significantly reduced disease progression when compared with active surveillance in patients with low-risk prostate cancer. The aim of this study was to identify a druggable pathway that could be combined with VTP to improve its efficacy and applicability to higher risk prostate cancer tumors.

Experimental Design: Transcriptome analysis of VTP-treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for combination therapy. The efficacy of the combination therapy was assessed in mice bearing LNCaP-AR or VCaP tumors.

Results: Gene set enrichment analysis identifies the enrichment of androgen-responsive gene sets within hours after VTP treatment, suggesting that the androgen receptor (AR) may be a viable target in combination with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using androgen deprivation therapy (ADT), degarelix, in combination with VTP. Compared with either ADT or VTP alone, a single dose of degarelix in concert with VTP significantly inhibited tumor growth. A sharp decline in serum prostate-specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by VTP and degarelix displayed intense terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining 7 days after treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition.

Conclusions: Improvement of local tumor control following androgen deprivation combined with VTP provides the rationale and preliminary protocol parameters for clinical trials in patients presented with locally advanced prostate cancer. Clin Cancer Res; 24(10); 2408–16. ©2018 AACR.
Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors
Authors: Oei Vincent Yi Sheng , Siernicka Marta , Graczyk-Jarzynka Agnieszka , Hoel Hanna Julie , Yang Weiwen , Palacios Daniel , Almåsbak Hilde , Bajor Malgorzata , Clement Dennis , Brandt Ludwig , Önfelt Björn , Goodridge Jodie , Winiarska Magdalena , Zagozdzon Radoslaw , Olweus Johanna , Kyte Jon-Amund , Malmberg Karl-Johan
Published: February 2018

Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles. Kinetics experiments revealed that CAR expression was optimal after 3 days of IL15 stimulation prior to transfection, consistently achieving over 80% expression. CAR-engineered NK cells acquired increased degranulation toward CD19+ targets, and maintained their intrinsic degranulation response toward CD19− K562 cells. The response of redirected NK-cell subsets against CD19+ targets was dependent on their intrinsic thresholds for activation determined through both differentiation and education by killer cell immunoglobulin-like receptors (KIR) and/or CD94/NKG2A binding to self HLA class I and HLA-E, respectively. Redirected primary NK cells were insensitive to inhibition through NKG2A/HLA-E interactions but remained sensitive to inhibition through KIR depending on the amount of HLA class I expressed on target cells. Adaptive NK cells, expressing NKG2C, CD57, and self-HLA–specific KIR(s), displayed superior ability to kill CD19+, HLA low, or mismatched tumor cells. These findings support the feasibility of primary allogeneic NK cells for CAR engineering and highlight a need to consider NK-cell diversity when optimizing efficacy of cancer immunotherapies based on CAR-expressing NK cells. Cancer Immunol Res; 6(4); 467–80. ©2018 AACR.
Alopecia Areata and Habit Tic Deformities
Authors: Horne Marina Isabel , Utzig Joyce B. , Rieder Evan A. , Vincenzi Colombina , Tosti Antonella
Published: February 2018

Nail involvement is a very common finding in patients with alopecia areata (AA). Most commonly evidenced by nail pitting, nail abnormalities can affect up to 66% of AA patients. We present two cases of the unusual association between habit tic nail deformities and AA.
Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions
Authors: Bischoff Joachim
Published: February 2018

Antineoplastic agents directly targeting tumor cells have represented the major strategy of systemic anticancer therapy for many years. Nevertheless, overcoming resistance mechanisms remains a great challenge because treatment options are limited in many cases. From this point of view, immunotherapeutic approaches seem promising in a broad spectrum of solid tumors. These include in particular the currently available inhibitors directed against immune checkpoints leading to a significant T-cell activation. To date, the programmed death receptor 1 (PD-1) and its ligand are the most prominent targets in this context. However, the role of checkpoint inhibitors in the treatment of breast cancer is still being debated, and the main focus is on triple-negative breast cancer patients as a target population in many ongoing trials. Moreover, the potential superiority of combinations with other anticancer drugs such as cytotoxics and targeted agents will be discussed.
ПРОГРАМА ІНФОРМАТИЗАЦІЇ УНІВЕРСИТЕТІВ. СТРАТЕГІЯ, СТАБІЛЬНА ТА ЗМІНА СКЛАДОВІ
Authors: Mintser O. P.
Published: February 2018

The issues of program informatisation of higher educational establishments of the medical field, introduction of mixed learning technology, in order to increase the competitiveness of Ukrainian medical universities, the widespread use of e-learning, electronic learning management, information and methodological support for the development of educational content are considered. It is emphasized that there are currently no alternatives to informatisation of educational institutions, and the main goal of informatisation of higher education institutions in the medical field should be to ensure harmonization between market needs in medical and pharmaceutical specialists with specific competencies, with world tendencies and results of functioning of higher educational institutions.
ВИКОРИСТАННЯ МЕТОДУ МОНТЕ-КАРЛО ДЛЯ МАРКОВСЬКИХ ЛАНЦЮГІВ ДЛЯ ПРОГНОЗУВАННЯ ПОШИРЕНОСТІ ІШЕМІЧНОЇ ХВОРОБИ СЕРЦЯ В УКРАЇНІ
Authors: Ivanchuk M. A. , Ivanchuk P. R.
Published: February 2018

In medical forecasting, there are often challenges in which it is necessary to assess the risk that is continuous for a long time, and important events can occur more than once. One of the ways of solving problems of this type is the use of Markov models.Markov models suggest that the patient is always in one of the finite numbers of discrete states of health, called the Markov states. All events are modeled as a transition from one state to another. In order for the Markov chain to end, it must contain at least one absorbing state from which the patient can't pass into other states. In medical models, such a condition is the death of the patient, as this is the only condition from which the patient can't escape. The purpose of this work is to build a Markov chain for predicting the prevalence of coronary heart disease in UkraineTo test the predictive quality, the model was built since 1996. The data obtained for the model for 1996-2012 were compared with known epidemiological data. The average prediction error is 3.2 %. We predict an increase in the incidence of coronary heart disease to 35 041.2 per 100 000 population in 2025.
Ventricular Fibrillation Conversion Testing After Implantation of a Subcutaneous Implantable Cardioverter Defibrillator
Authors: Friedman Daniel J. , Parzynski Craig S. , Heist E. Kevin , Russo Andrea M. , Akar Joseph G. , Freeman James V. , Curtis Jeptha P. , Al-Khatib Sana M.
Published: February 2018

Background:

Compared with transvenous implantable cardioverter defibrillators (ICDs), subcutaneous (S)-ICDs require a higher energy for effective defibrillation. Although ventricular fibrillation conversion testing (CT) is recommended after S-ICD implantation to ensure an adequate margin between the defibrillation threshold and maximum device output (80J), prior work found that adherence to this recommendation is declining.

Methods:

We studied first-time recipients of S-ICDs (between September 28, 2012, and April 1, 2016) in the National Cardiovascular Database Registry ICD Registry to determine predictors of use of CT, predictors of an insufficient safety margin (ISM, defined as ventricular fibrillation conversion energy >65J) during testing, and inhospital outcomes associated with use of CT. Multivariable logistic regression analysis was used to predict use of CT and ISM. Inverse probability weighted logistic regression analysis was used to examine the association between use of CT and inhospital adverse events including death.

Results:

CT testing was performed in 70.7% (n=5624) of 7960 patients with S-ICDs. Although deferral of CT was associated with several patient characteristics (including increased body mass index, increased body surface area, severely reduced ejection fraction, dialysis dependence, warfarin use, anemia, and hypertrophic cardiomyopathy), the facility effect was comparatively more important (area under the curve for patient level versus generalized linear mixed model: 0.619 versus 0.877). An ISM occurred in 6.9% (n=336) of 4864 patients without a prior ICD and was more common among white patients and those with ventricular pacing on the preimplant ECG, higher preimplant blood pressure, larger body surface area, higher body mass index, and lower ejection fraction. A risk score was able to identify patients at low (<5%), medium (5% to 10%), and high risk (>10%) for ISM. CT testing was not associated with a composite of inhospital complications including death.

Conclusions:

Use of CT testing after S-ICD implantation was driven by facility preference to a greater extent than patient factors and was not associated with a composite of inhospital complications or death. ISM was relatively uncommon and is associated with several widely available patient characteristics. These data may inform ICD system selection and a targeted approach to CT.
Growth Differentiation Factor 11 Promotes Abnormal Proliferation and Angiogenesis of Pulmonary Artery Endothelial Cells
Authors: Yu Xiufeng , Chen Xinxin , Zheng Xiao Dong , Zhang Junting , Zhao Xijuan , Liu Ying , Zhang Hongyue , Zhang Lixin , Yu Hao , Zhang Min , Ma Cui , Hao Xuewei , Zhu Daling
Published: February 2018

Disordered proliferation and angiogenesis of pulmonary artery endothelial cells is an important stage in the development of pulmonary arterial hypertension. Recent studies revealed that GDF11 (growth differentiation factor 11) induces endothelial cells proliferation and migration; however, whether GDF11 is directly involved in the pathogenesis of pulmonary arterial hypertension remains unknown. Here, we found that GDF11 was significantly upregulated and activated in 2 experimental pulmonary arterial hypertension models and cultured pulmonary artery endothelial cells. Genetic ablation of
gdf11
in endothelial cells rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. Moreover, we found that hypoxia significantly increased cell cycle progression, proliferation, migration, adhesion, and tube formation, which were significantly inhibited by GDF11 small interfering RNA. These events could be reproduced using cultured pulmonary artery endothelial cells and were dependent on Smad signaling. Moreover, hypoxia-induced GDF11 expression was regulated by the transcription factor zinc finger protein 740, which assisted RNA polymerase in recognizing and binding to the GDF11 promoter sequence located at a site (−753/−744; CCCCCCCCAC) upstream of the gene. This study identified a novel growth and differentiation factor signaling pathway involved in the zinc finger protein 740/GDF11/transforming growth factor-β receptor I/Smad signaling axis and involved in pulmonary artery endothelial cells proliferation and angiogenesis. These results provide critical insights for the development of novel therapeutic strategies for pulmonary arterial hypertension involving components of the GDF11 signaling system.
Divine Provision and the “Preternatural Imagination” of Edward Burne-Jones in the Mosaics of “The American Church” in Rome
Authors: Hostetter Smith Rachel
Published: February 2018

This essay examines the multiplicity of ways the building and decoration of the American church of St. Paul’s Within-the-Walls in Rome signaled the dawning of a “new age,” politically and spiritually, as the first Protestant church constructed within the city of Rome, initiated immediately after the city was freed from papal rule in 1870. The mosaics, designed by Pre-Raphaelite artist Edward Burne-Jones and completed with the help of his assistant Thomas Rooke in the decades that follow, present Christ, and the Church in particular, as sources of divine sustenance and verdant life in the barren wilderness of this world. But it is the splendor of their design and the material magnificence of the mosaics themselves that create the first powerful and most lasting impact. Viewed through the lens of what P. T. Forsyth described as the “preternatural imagination” of Burne-Jones, these mosaics are distinctly contemporary works deeply rooted in religious and artistic tradition that address the transitional times for which they were made.
Associating sex-biased and seasonal behaviour with contact patterns and transmission risk in Gopherus agassizii
Authors: Aiello C.M. , Esque T.C. , Nussear K.E. , Emblidge P.G. , Hudson P.J.
Published: February 2018

Interactions between wildlife hosts act as transmission routes for directly transmitted pathogens and vary in ways that affect transmission efficiency. Identifying drivers of contact variation can allow both contact inference and estimation of transmission dynamics despite limited data. In desert tortoises, mating strategy, burrow use and seasonal change influence numerous behaviours and likely shape contact patterns. In this study, we ask to what extent tortoise contact behaviour varies between sexes and seasons, and whether space or burrow-use data can be used to infer contact characteristics consistent with those recorded by proximity loggers. We identified sex and season-biased contact behaviour in both wild and captive populations indicative of female-female avoidance and seasonal male mate-seeking behaviour. Space and burrow-use patterns were informative, but did not always predict the extent of sex or seasonal biases on contact. We discuss the implications these findings have for transmission patterns and disease mitigation in tortoise populations.
Behavioural dominance of the invasive red-billed leiothrix (Leiothrix lutea) over European native passerine-birds in a feeding context
Authors: Pereira Pedro Filipe , Lourenço Rui , Mota Paulo Gama
Published: February 2018

Behavioural dominance and aggressiveness may be crucial traits facilitating the establishment of invasive species. Few studies considered agonistic interactions between exotic and native bird species in feeding contexts, particularly when the exotic has social habits. We aimed to know if individuals of a social invasive species, the red-billed leiothrixLeiothrix lutea, are: more aggressive; the initiators of the first interaction; and dominant (i.e., won most interactions) over native opponents in a feeding context. We performed an experiment in a closed environment forcing dyadic interactions between an individual of a native species facing a leiothrix individual. We found that the leiothrix was the initiator in most experiments, being apparently dominant over natives. However, the invader was not more aggressive than natives. This can increase the risk of injury for natives because the leiothrix has a relatively larger body size. We discuss possible negative impacts of the leiothrix on native species.
Comments on taxonomic status and host association of some Laimaphelenchus spp. (Rhabditida: Aphelenchoidea)
Authors: Pedram Majid , Pourhashemi Mehdi , Hosseinzadeh Jaafar , Koolivand Davoud
Published: February 2018

A reverse taxonomic approach for characterisation of several populations of an aphelenchid nematode recovered from declined oak trees in the Zagros forests, Ilam, western Iran, revealed that their 28S rDNA D2-D3 sequences matched two available sequences of the same genomic fragment belonging to two species,Laimaphelenchus belgradiensisandL. hyrcanus. Further morphological studies yielded new morphological traits that had been overlooked in their original descriptions, and a new hypothesis helping to disentangle these taxa, which have the same 28S sequences and the same phylogenetic placement, is proposed. In a similar fashion, the taxonomic status of some other species of the genus having a similar morphology or similar genomic sequences are reviewed. The possibility of proposing new synonyms was evaluated and tentative reasons for the new habitat of the recovered populations ofLaimaphelenchusfrom the Zagros forests discussed.
Vertebrate endemism in south-eastern Africa numerically redefines a biodiversity hotspot
Authors: PERERA SANDUN J. , PROCHEŞ ŞERBAN , RATNAYAKE-PERERA DAYANI , RAMDHANI SYD
Published: February 2018

We use numerical methods to explore patterns of vertebrate endemism in south-eastern Africa, refining the boundaries of the intuitively-defined Maputaland-Pondoland-Albany biodiversity hotspot, also proposing a zoogeographic regionalisation. An incidence matrix of 300 vertebrate species endemic to south-eastern Africa sensu lato in 37 operational geographic units were used in (a) phenetic cluster analysis (PCA) using the algorithm of unweighted pair-group method with arithmetic averages (phenetic approach), and (b) parsimony analysis of endemicity (PAE; parsimony approach), in order to numerically evaluate the bioregional delimitations. The analyses provide a valid biogeographical entity 37% larger than the Maputaland-Pondoland-Albany hotspot, but substantially (131%) higher in vertebrate endemicity viz. the Greater Maputaland-Pondoland-Albany (GMPA) region of vertebrate endemism. South-east Africa is recognised as a dominion in the global zoogeographical area hierarchy, with subordinate units including the GMPA province. Various spatially-based measures of endemism were mapped for vertebrate species restricted to the dominion, i.e. endemic to south-eastern Africa sensu stricto. Areas and centres of endemism detected respectively from PAE and PCA, within the south-east Africa dominion also support the refined boundary of the GMPA region of endemism, which provides a better spatial conservation priority compared to the Maputaland-Pondoland-Albany hotspot. Reptiles and amphibians are found to be the main drivers of the overall pattern of endemism, while the pattern in freshwater fish is the most distinctive. Our analyses also indicate a good congruence of the centres of endemism across different terrestrial vertebrate taxa.
Illustrated accounts of coccinellid predators of Maconellicoccus hirsutus (Green) (Hemiptera: Sternorrhyncha: Pseudococcidae) on mulberry in India, with description of a new species of Scymnus Kugelann (Coleoptera: Coccinellidae) from West Bengal
Authors: POORANI J. , LALITHA N.
Published: February 2018

The pink hibiscus mealybug, Maconellicoccus hirsutus (Green), is a major pest of mulberry (Morus alba L.), the sole host of the mulberry silkworm, Bombyx mori (L.), which is a source of livelihood to millions of sericulture farmers in India. Several predators, mainly Coccinellidae (Coleoptera), have been reported to feed on M. hirsutus on mulberry. Coccinellid predators of M. hirsutus collected on mulberry from different parts of India are illustrated here with brief diagnostic notes to facilitate their identification. An account of mycophagous species of coccinellids commonly found on mulberry and misreported as predators of mulberry pests is also given with illustrations. Scymnus (Pullus) latifolius sp. nov., a promising predator of M. hirsutus, hitherto misidentified and reported as Scymnus pallidicollis Mulsant, is described and illustrated from West Bengal, India, with detailed biological notes. Keiscymnus taiwanensis Yang & Wu, 1972 is reduced to a new junior synonym of Scymnus pallidicollis Mulsant, 1853 (syn. nov.). Illeis bielawskii Ghorpade, 1976 is found to be a valid species and removed from synonymy with I. bistigmosa Mulsant, 1850 (stat. rev.).
A new genus and species of the family Archipsyllidae (Insecta: Paraneoptera: Permopsocida) from the Late Triassic of Queensland
Authors: LAMBKIN KEVIN J.
Published: February 2018

The dedicated collecting of Robert Knezour of Ipswich continues to uncover remarkable finds in the Late Triassic (Norian) Dinmore fossil insect locality of south-east Queensland. The latest discovery is a forewing of the extinct family Archipsyllidae, described herein as Dinmopsylla semota gen. et sp. nov., the first record of the family from the Triassic and from the southern hemisphere.
Strengthening School–Family Collaboration: An Evaluation of the Family Referral Service in Four Australian Schools
Authors: Hall Martin T , Wurf Gerald
Published: February 2018

This study evaluates the capacity of a school-based family referral service to support school personnel in connecting at-risk students with appropriate community agencies. Through a partnership between New South Wales government departments and a not-for-profit counselling organisation, the family referral service was piloted at four regional, government schools. In phase 1 of the mixed methods evaluation, 135 students completed an online version of the Student Engagement Instrument. In phase 2, 32 primary and secondary teachers participated in four focus groups. Four principals and 19 key stakeholders participated in individual, semi-structured interviews. Findings showed the service increased the schools’ capacity to manage students who were at risk of underachievement and poorer educational outcomes and reduced the workload of principals and teachers. While high Student Engagement Instrument subscale scores were obtained for extrinsic motivation and relationships with teachers, family support for learning received the lowest scores. Recommendations for the wider promotion of school–family partnerships focussing on locating flexible, family referral services within schools are discussed.
Revisiting Who, When, and Why Stakeholders Matter: Trust and Stakeholder Connectedness
Authors: Crane Bret
Published: February 2018

With limited resources and attention, managers have sought ways to categorize and prioritize stakeholders. The underlying assumption is that some stakeholders matter more than others. However, in the information age, stakeholders are increasingly interconnected, where a firm’s actions toward one stakeholder are visible to others and can affect members of the stakeholder ecosystem. Actions by a firm toward any of its stakeholders can signal its trustworthiness and determine to what degree other stakeholders will assume vulnerability and engage in future exchange relationships. In this conceptual article, I present a model of stakeholder connectedness and describe the conditions in which a firm’s actions toward one stakeholder can build or erode trust across stakeholders. This work contributes to current tensions in stakeholder theory by elucidating how the treatment of a single stakeholder, or a narrow group of stakeholders, can have cascading effects on a broader group of stakeholders.
Effect of Hearing Loss on Peer Victimization in School-Age Children
Authors: Warner-Czyz Andrea D. , Loy Betty , Pourchot Hannah , White Trissan , Cokely Elika
Published: February 2018

Nearly one third of school-age children report being bullied, primarily enduring teasing or rumors. Children with hearing loss (HL) are at increased risk of victimization due to being “different” from the general population. This project assesses effects of auditory status on bullying by comparing incidence and type of bullying in 87 youth and adolescents with HL (7–18 years) to published national data from peers in the general population. All participants wore auditory technology (i.e., hearing aids or cochlear implants), communicated orally, and participated in mainstream education. Each participant completed the 2009 National Crime Victimization Survey’s School Crime Supplement. Adolescents with HL endured significantly higher incidence of bullying versus the general population (50.0% vs. 28.0%), particularly for exclusion (26.3% vs. 4.7%) and coercion (17.5% vs. 3.6%). Children younger than 12 years with HL report lower rates of bullying (38.7%) than adolescents with HL, but rates did not differ significantly. Future research should explore risk and protective factors for peer victimization in youth and adolescents with HL to reduce long-term consequences on quality of life.
A 16-Year Review of Participant Diversity in Intervention Research Across a Selection of 12 Special Education Journals
Authors: Sinclair James , Hansen Sarah G. , Machalicek Wendy , Knowles Christen , Hirano Kara A. , Dolata Jill K. , Blakely Allison W. , Seeley John , Murray Christopher
Published: February 2018

Given the continued changes in demographic diversity of students in the United States, it is important to ensure that participants included in special education research reflect the diversity of the classroom. We examined 16 years of intervention research across 12 special education journals to evaluate the extent to which diverse student populations (e.g., race, ethnicity, disability, sexual orientation, English language learner status) were included in published intervention research. We analyzed 495 intervention articles (9.6%) out of 5,180 total articles. Results revealed that progress has been made in the inclusion of diverse participants in special education intervention research compared with previously conducted reviews, yet some racial and ethnic populations are still underrepresented. We discuss strategies for recruitment and retention of underrepresented diverse populations.
Cardiac surgery patients’ e-health literacy and their use of a digital portal
Authors: Khan Delvin , Fjerbæk Annette , Andreasen Jan J , Thorup Charlotte B , Dinesen Birthe
Published: February 2018

Objective:

To determine how cardiac patients use the Activeheart.dk digital toolbox

Methods:

Mixed-methods study. A total of n = 33 cardiac surgical patients were enrolled in a study, which encouraged use of the Activeheart portal for 4 weeks after discharge. Patients were surveyed with respect to their demographic characteristics, e-health literacy skills, use of the Internet and use of the portal. In addition to the questionnaire survey, qualitative interviews were conducted with six randomly selected patients in order to study users’ experiences with and use of the portal.

Results:

Quantitative results showed no relation between cardiac patients’ prior e-health literacy skills and their use of the portal. Approximately 25 out of 31 patients stated that they had the skills to seek, locate and use health information on the Internet. Among the 17 patients who completed the first and second questionnaires, nine rarely used Activeheart.dk, four used it several times per month, and four several times per week. In 10 out of 16 replies, Activeheart.dk was rated as relevant or very relevant. Themes from the qualitative interviews revealed that the effects of medication and emotional, physical and cognitive changes had a higher impact on the use of the portal than prior e-health literacy skills.

Conclusion:

While participants’ e-health literacy skills ratings were high, and while participants stated that the content of the portal was relevant, their actual use of the portal remained limited. No relationship was found between participants’ e-health literacy skills and their use of the portal. Factors such as patient motivation, resources and timing of the intervention’s introduction seemed to be of greater importance.
Improving mental health knowledge of the Charedi Orthodox Jewish Community in North London: A partnership project
Authors: Perry Aradhana , Gardener Chelsea , Dove Jonathan , Eiger Yocheved , Loewenthal Kate
Published: February 2018

Introduction:

This article describes a successful community-based partnership project between statutory and third-sector services targeting the strictly Orthodox Jewish community (OJC).

Methods:

The City and Hackney Black and Minority Ethnic (BME) Access Service (East London NHS Foundation Trust (ELFT)) collaborated with Bikur Cholim, a local third-sector organisation based in the heart of a north London Charedi OJC, to develop a brief culturally tailored psychoeducational group intervention focusing on mental health promotion and prevention. In total, 34 carers in the Charedi OJC were provided with general information on mental health, the availability of support services and self-care.

Results:

Overall improvements in well-being, increased intentions to access services, particularly talking therapies, and qualitative feedback indicated that the group was very well received.

Conclusion:

The project endorses the value of culturally relevant psychoeducation, enabling suggestions for culturally appropriate service development.
Failure mechanism of fiber-reinforced polymer-confined concrete column with initial defects
Authors: Xu Ying , Liu Chengyin , Chai Lei , Lu Miaomiao , Luo Congcong
Published: February 2018

The effect of initial defect size on the mechanical behavior and failure mode of carbon fiber-reinforced polymer- confined concrete column was investigated through theoretical analysis, finite element software simulation and experiment validation. Qualitative theoretical analysis was firstly explored to study the effect of initial defect size on the mechanical behavior of confined concrete column from macro to micro perspective. Numerical simulations and experimental investigation were then carried out and compared to investigate the mechanical behavior of carbon fiber-reinforced polymer-confined concrete column with initial defects under axial compression and eccentric compression. The variation of defect criticality was investigated by varying the layer number of carbon fiber-reinforced polymer and cross-section size of concrete columns. The effect of initial defect size on the failure mode of carbon fiber-reinforced polymer-confined concrete column was finally demonstrated.
Uneven accountability in the wake of political violence
Authors: Hassan Mai , O’Mealia Thomas
Published: February 2018

The government faces a principal–agent problem with lower-level state officers. Officers are often expected to use the state coercive capacity endowed to them to politically benefit the government. But officers can shirk from the government’s demands. An officer’s actions during bouts of large-scale and highly visible electoral violence reveal the officer’s type, thereby providing the government with the information necessary to solve its principal–agent problem for the future. The government holds officers who used their authority to perpetuate incumbent-instigated violence accountable through positive rewards, while holding officers who used their authority to perpetuate opposition-instigated violence accountable through negative sanctions. We find evidence in support of the theory using micro-level archival data on 2,500 local officer appointments and fine-grained satellite data on the locations of violence in the aftermath of Kenya’s 2007 election. The Kenyan government was more likely to fire officials whose jurisdictions saw opposition-instigated violence that targeted government supporters. But we find the opposite result where violence was instigated by incumbent supporters: there, officers were less likely to be fired if violence occurred in their jurisdiction. Our results indicate that leaders can manipulate accountability processes after political violence to further politicize the state.
Role of Coping Responses in the Relationship Between Perceived Stress and Psychological Well-Being in a Sample of Spanish Educational Teacher Students
Authors: Gustems-Carnicer Josep , Calderon Caterina , Batalla-Flores Alberto , Esteban-Bara Francisco
Published: February 2018

Stress in teacher education students is a key issue, due to its physical and social impact and its relevance to students’ future as professionals. This study uses the Perceived Stress Scale, the Coping Responses Inventory—Adult Form, and the Psychological Well-Being Scale to analyze how coping strategies mediate the relationship between stress and well-being in a sample of Spanish teacher education students (n = 334). The results show that the students had a good general level of psychological well-being, although with little personal growth and autonomy. Their level of stress meant that they could offer active, engaged responses, although the coping strategies that were used tended to be avoidance type, which could lead to certain adaptive difficulties. Our results also indicate that coping has a partial mediating role. Finally, organizational actions are proposed for universities that could help to enhance students’ personal resources for dealing with stress.
Is Graphology Useful in Assessing Major Depression?
Authors: Giannini Marco , Pellegrini Pietro , Gori Alessio , Loscalzo Yura
Published: February 2018

This study aimed to develop a handwriting analysis protocol for assessing severe major depressive disorder, in order to evaluate whether graphological analysis could be considered an objective tool and hence if it could be useful for clinicians in their early diagnosis. We modified and improved the methodology described by Lorusso et al. by proposing different graphic indexes based both on the literature and on the observation of a preliminary sample of 13 handwritings of patients affected by major depressive disorder. Then, we recruited 80 participants, divided into two groups: clinical sample ( n = 44) and control group ( n = 36). We used Cohen's Kappa to evaluate the reliability of agreement among four professional graphologists and the consensus between the psychiatric assessment and the ratings given by the judges. We found satisfactory results. Using our protocol, we obtained higher values for Cohen’s Kappa as compared with Lorusso et al. The agreement among graphologists is K = .62, while the K values for the agreement between psychiatric assessment and graphologists range between .47 and .60. The substantial improvements obtained in comparison with Lorusso et al. are encouraging and support further attempts.
The Construction of Social Meaning: A Matched-Guise Investigation of the California Vowel Shift
Authors: Villarreal Dan
Published: February 2018

Past production research on the California Vowel Shift (CVS) has suggested that the CVS carries social meanings of carefreeness, Whiteness, femininity, and privilege (e.g., Eckert 2008b), but it is unclear whether these social meanings reflect listener perceptions. In the present study, Californian listeners heard speech samples, guessed where speakers were from, and rated speakers on language attitudes scales; stimuli in this task were matched guises differing by speakers’ use of two CVS features. The results indicated that listeners associate these features with Californianness, sounding like a Valley girl, and (for male speakers) confidence, complicating the social meanings suggested by production studies. I discuss these results in terms of how interaction context guides the perception of social meaning by activating subsets of the indexical field. This research also introduces two innovative methods for investigating sociolinguistic perception: stimuli created using resynthesized vowels within spontaneous speech produced by multiple speakers, and statistical inference via Bayesian hierarchical modeling.
Reforging the Steel City: Symbolism and Space in Postindustrial Pittsburgh
Authors: Neumann Tracy
Published: February 2018

With an eye to urban branding campaigns in global cities such as New York, in the 1970s and 1980s, Pittsburgh, Pennsylvania’s public officials worked with local corporations and media outlets to market “dynamic” Pittsburgh to a national audience. This article examines the relationship between the “imagined space” of boosters’ urban branding campaigns and their decades-long efforts to physically and economically reorganize the region’s “material space” around service and finance industries, and medical and educational institutions. Through urban branding, local elites’ efforts created new mental maps of the region that excluded its mill towns and manufacturing workers and emphasized, instead, the relationship between the city and its well-heeled suburbs.
Noise-to-state stability analysis for a class of random time-delay nonlinear systems
Authors: Jiao Ticao , Zong Guangdeng , Zhang Cunshan , Du Qinjun , Zhao Yanlei
Published: February 2018

Time-delay systems disturbed by white noise have been comprehensively modelled as stochastic functional differential equations in the existing literature. However, in some specific situations, they cannot always precisely describe the dynamic character of time-delay systems subject to non-white noise disturbances. In this paper, colour noises with finite two-order moments are introduced to time-delay systems (such systems are referred to as random ones). First, we present some general conditions to guarantee the existence and uniqueness of solutions to random time-delay systems. Next, in light of these results and the Lyapunov function approach, the noise-to-state stability and eλ t-weighted integral noise-to-state stability are analysed, respectively. One example is given to illustrate the effectiveness of the obtained results.
Match 2017: Blindsided or Fumbled?
Authors: Chang C. W. David
Published: February 2018

The field of otolaryngology has historically enjoyed extreme interest among residency applicants. However, in the past few years, the number of applicants has precipitously dropped, so that there is no longer a significant excess of applications. It remains important for academic programs to promote student interest in otolaryngology, to break down barriers that may dissuade excellent candidates, and to widen the welcome.