bluuebunny/crossref_metadata_2025 huggingface dataset:
The Fountain of Health: Bringing Seniors’ Mental Health Promotion into Clinical Practice
Authors: Thoo Vanessa , Freer Janya , Cassidy Keri-Leigh
Published: January 2016

BackgroundThe Fountain of Health (FoH) initiative offers valuable evidence-based mental health knowledge and provides clinicians with evaluated tools for translating knowledge into practice, in order to reduce seniors’ risks of mental disorders, including dementia.MethodsA presentation on mental health promotion and educational materials were disseminated to mental health clinicians including physicians and other allied health professionals either in-person or via tele-education through a provincial seniors’ mental health network. Measures included: 1) a tele-education quality evaluation form, 2) a knowledge transfer questionnaire, 3) a knowledge translation-to-practice evaluation tool, and 4) a quality assurance questionnaire.ResultsA total of 74 mental health clinicians received the FoH education session. There was a highly significant (p < .0001) difference in clinicians’ knowledge transfer questionnaire scores pre- and post-educational session. At a two-month follow-up, 19 (25.7%) participants completed a quality assurance questionnaire, with all 19 (100%) of respondents stating they would positively recommend the FoH information to colleagues and patients. Eleven (20.4%) translation-to-practice forms were also collected at this interval, tracking clinician use of the educational materials.ConclusionsThe use of a formalized network for knowledge transfer allows for education and evaluation of health-care practitioners in both acquisition of practical knowledge and subsequent clinical behavior change.
Oral Abstract Presentations at the 8th Canadian Conference on Dementia (CCD), Ottawa, October 2015
Authors: Authors Various
Published: January 2016

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Winter Issue 2015
Authors: Madden Ken , Rapoport Mark , Maxwell Coleen
Published: January 2016

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The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions
Authors: Esserman Denise , Allore Heather G. , Travison Thomas G.
Published: January 2016

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results.
CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level.
In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters.
Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients
Authors: Han Ling , Pisani M. A. , Araujo K.L. B. , Allore Heather G.
Published: January 2016

Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior (Induction) and posterior (Subsequent) to each treatment episode of receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for the Subsequent than the Induction intervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.
The Validity of Disease-Specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions
Authors: Ware Jr. John E. , Gandek Barbara , Allison Jeroan
Published: January 2016

Background: A crucial assumption underlying all disease-specific quality of life (QOL) measures, that patients can validly differentiate a specific disease in the presence of multiple chronic conditions, has not been tested using multiple methods. Our objective was to evaluate the convergent and discriminant validity of QOL attributions to specific diseases among adults with multiple chronic conditions (MCC).
Methods: Adults age 18 and older (N=4,480) sampled from eight pre-identified condition groups (asthma, COPD, angina/MI with angina, congestive heart failure, diabetes, chronic kidney disease, osteoarthritis, rheumatoid arthritis) completed an Internet survey. Comorbid conditions were determined using a 35-condition checklist. Product-moment correlations were analyzed separately by pre-identified condition group using the multitrait-multimethod of construct validation, where traits were defined by 9-26 conditions and each condition was measured by two methods: disease severity rating and Disease-specific Quality of Life Impact Scale (QDIS) global rating. A third method (symptom or clinical marker) was available for the eight pre-identified conditions. Convergent validity was supported when correlations among different methods of measuring the same condition (trait) were substantial (r≥ 0.40). Discriminant validity was supported when correlations between the same and different methods of measuring different conditions were significantly lower than corresponding convergent correlations.
Results: In support of convergent validity, 22 of 24 convergent correlations were substantial (r=0.38-0.84, median=0.53). In support of discriminant validity, 833 of 924 tests (90.2%) yielded significantly higher convergent than discriminant correlations across the eight pre-identified conditions. Exceptions to this pattern of results were most often observed for comorbid conditions within the same clinical area.
Conclusions: Collectively, convergent and discriminant test results support the construct validity of disease-specific QOL impact attributions across MCC within the eight pre-identified conditions. Noteworthy exceptions should be considered when interpreting some specific QOL impact attributions and warrant further study. Pursuit of a summary disease-specific QOL impact score standardized across MCC is recommended.
An Empirical Method of Detecting Time-Dependent Confounding: An Observational Study of Next Day Delirium in a Medical ICU
Authors: Murphy T. E. , Ness P.H. Van , Araujo K.L.B. , Pisani M.A.
Published: January 2016

Longitudinal research on older persons in the medical intensive care unit (MICU) is often complicated by the time-dependent confounding of concurrently administered interventions such as medications and intubation. Such temporal confounding can bias the respective longitudinal associations between concurrently administered treatments and a longitudinal outcome such as delirium. Although marginal structural models address time-dependent confounding, their application is non-trivial and preferably justified by empirical evidence. Using data from a longitudinal study of older persons in the MICU, we constructed a plausibility score from 0 – 10 where higher values indicate higher plausibility of time-dependent confounding of the association between a time-varying explanatory variable and an outcome. Based on longitudinal plots, measures of correlation, and longitudinal regression, the plausibility scores were compared to the differences in estimates obtained with non-weighted and marginal structural models of next day delirium. The plausibility scores of the three possible pairings of daily doses of fentanyl, haloperidol, and intubation indicated the following: low plausibility for haloperidol and intubation, moderate plausibility for fentanyl and haloperidol, and high plausibility for fentanyl and intubation. Comparing multivariable models of next day delirium with and without adjustment for time-dependent confounding, only intubation’s association changed substantively. In our observational study of older persons in the MICU, the plausibility scores were generally reflective of the observed differences between coefficients estimated from non-weighted and marginal structural models.
Individualized Absolute Risk Calculations for Persons with Multiple Chronic Conditions: Embracing Heterogeneity, Causality, and Competing Events
Authors: Allore Heather , McAvay Gail , Fragoso Carlos A. Vaz , Murphy Terrence E.
Published: January 2016

Approximately 75% of adults over the age of 65 years are affected by two or more chronic medical conditions. We provide a conceptual justification for individualized absolute risk calculators for competing patient-centered outcomes (PCO) (i.e. outcomes deemed important by patients) and patient reported outcomes (PRO) (i.e. outcomes patients report instead of physiologic test results). The absolute risk of an outcome is the probability that a person receiving a given treatment will experience that outcome within a pre-defined interval of time, during which they are simultaneously at risk for other competing outcomes. This allows for determination of the likelihood of a given outcome with and without a treatment. We posit that there are heterogeneity of treatment effects among patients with multiple chronic conditions (MCC) largely depends on those coexisting conditions.
We outline the development of an individualized absolute risk calculator for competing outcomes using propensity score methods that strengthen causal inference for specific treatments. Innovations include the key concept that any given outcome may or may not concur with any other outcome and that these competing outcomes do not necessarily preclude other outcomes. Patient characteristics and MCC will be the primary explanatory factors used in estimating the heterogeneity of treatment effects on PCO and PRO. This innovative method may have wide-spread application for determining individualized absolute risk calculations for competing outcomes. Knowing the probabilities of outcomes in absolute terms may help the burgeoning population of patients with MCC who face complex treatment decisions.
Can a Mendelian Randomization Study Predict the Results of a Clinical Trial? Yes and No
Authors: Abbate Antonio , Dinarello Charles A. , Peruzzi Mariangela , Sciarretta Sebastiano , Frati Giacomo , Zoccai Giuseppe Biondi
Published: January 2016

Randomized controlled trials are considered at the top of the evidence hierarchy. However, in several cases randomized trials cannot be conducted or have not yet been completed. In such settings observational studies may provide important inference, yet traditional statistical adjustment methods fall short of controlling for all potential confounders, as unknown confounders cannot be taken care of by even the most sophisticated statistical tools. The mendelian randomization study is a type of research design which simultaneously exploits random transmission of genes and genetic linkage to obtain inferential estimates from the association between specific genetic variants known to modulate given risk factors and the corresponding outcomes of interests. Despite several developments in this field, there remain several areas of further research, and discrepancies between mendelian randomization studies and the corresponding randomized trials have already been recognized. Nonetheless, it is likely that this novel type of study will be used more commonly in the future, and a working knowledge of its pros, cons, and range of validity is crucial for conscientious interpretation and application. We thus aimed to concisely yet poignantly introduce the scholarly reader to this novel type of research design, notwithstanding that complementarity prevails in most cases over overlap between mendelian randomization studies and randomized trials.
Higher Performance of QuantiFERON TB Compared to Tuberculin Skin Test in Latent Tuberculosis Infection Prospective Diagnosis
Authors: Dhaouadi Tarak , Sfar Imen , Mouelhi Leila , Tekaya Raoudha , Mahmoud Ines , Bargaoui Jalila , Daghbouj Raoudha , Abdelmoula Leila , Najjar Taoufik , Abdallah Taieb Ben , Gorgi Yousr
Published: January 2016

Background: The Tuberculin skin test (TST) has been used for years in the latent tuberculosis infection (LTBI) diagnosis, but it has, well-documented, low sensitivity and specificity. Interferon-γ release assays (IGRA) has been reported to be more sensitive and specific than TST. Therefore, this study aimed to evaluate the performance of a commercial IGRA, QuantiFERON®-TB Gold In-Tube (QFT-GIT), comparatively to TST in LTBI diagnosis.
Patients and Methods: This study included 238 patients who were candidate for an anti-TNF therapy. The screening for LTBI was performed by both TST and QFT-GIT test for all patients. In order to evaluate the strength of associations, the odds ratios (OR) together with 95% confidence intervals (CI) were calculated. The correlation between QFT-GIT and TST was evaluated using κ statistics.
Results: Sixty-three (26.4%) sera were positive for QFT-GIT with a mean level of IFN-γ of about 1.18 IU/ml, while 81 (34%) patients were positive for TST. Agreement between QFT-GIT and TST was poor (37 QFT-GIT+/TST- and 55 QFT-GIT-/TST+), κ=0.09 (SD=0.065). The positivity of QFT-GIT was not influenced by BCG vaccination or by immunosuppression. Nevertheless, it was significantly associated to both history of an earlier tuberculosis disease (HETD) and its radiological sequel (RS), p=6E-7 and p=1E-8, respectively. Inversely, the TST results were not correlated to either HETD or RS, but the TST positivity was less frequent in immunosuppressed patients (45.5% vs. 73.9%), p=1E-5, OR (95% CI) = 0.29 [0.17-0.52]. Moreover, the extent of both the immunosuppression period and the time elapsed from the last BCG injection was significantly correlated to a lesser TST positivity, p=3E-12 and p=5E-7, respectively. Among the QFT-GIT-/TST+ patients (n=55) whom received an anti-TNF agent without any prophylactic treatment of LTBI, no tuberculosis was detected with a median follow-up of 78 weeks [56-109].
Conclusion: Our study suggests that the QFT-GIT has a higher performance comparatively to TST in the LTBI screening that is unaffected by either BCG vaccination or immunosuppression. Therefore, IGRAs has to replace TST especially in patients who are under consideration for an anti-TNF therapy.
The REST remodeling complex protects genomic integrity during embryonic neurogenesis
Authors: Nechiporuk Tamilla , McGann James , Mullendorff Karin , Hsieh Jenny , Wurst Wolfgang , Floss Thomas , Mandel Gail
Published: January 2016

The timely transition from neural progenitor to post-mitotic neuron requires down-regulation and loss of the neuronal transcriptional repressor, REST. Here, we have used mice containing a gene trap in the Rest gene, eliminating transcription from all coding exons, to remove REST prematurely from neural progenitors. We find that catastrophic DNA damage occurs during S-phase of the cell cycle, with long-term consequences including abnormal chromosome separation, apoptosis, and smaller brains. Persistent effects are evident by latent appearance of proneural glioblastoma in adult mice deleted additionally for the tumor suppressor p53 protein (p53). A previous line of mice deleted for REST in progenitors by conventional gene targeting does not exhibit these phenotypes, likely due to a remaining C-terminal peptide that still binds chromatin and recruits co-repressors. Our results suggest that REST-mediated chromatin remodeling is required in neural progenitors for proper S-phase dynamics, as part of its well-established role in repressing neuronal genes until terminal differentiation.
Local mechanical forces promote polarized junctional assembly and axis elongation in Drosophila
Authors: Yu Jessica C , Fernandez-Gonzalez Rodrigo
Published: January 2016

Axis elongation is a conserved process in which the head-to-tail or anterior-posterior (AP) axis of an embryo extends. In Drosophila, cellular rearrangements drive axis elongation. Cells exchange neighbours by converging into transient multicellular vertices which resolve through the assembly of new cell interfaces parallel to the AP axis. We found that new interfaces elongate in pulses correlated with periodic contractions of the surrounding cells. Inhibiting actomyosin contractility globally, or specifically in the cells around multicellular vertices, disrupted the rate and directionality of new interface assembly. Laser ablation indicated that new interfaces sustained greater tension than non-elongating ones. We developed a method to apply ectopic tension and found that increasing AP tension locally increased the elongation rate of new edges by more than twofold. Increasing dorsal-ventral tension resulted in vertex resolution perpendicular to the AP direction. We propose that local, periodic contractile forces polarize vertex resolution to drive Drosophila axis elongation.
Give it a REST!
Authors: Pollard Steven M , Angeles Marques-Torrejon Maria
Published: January 2016

The REST protein helps to prevent the premature activation of genes that are only expressed in mature neurons, and is now found to protect the genome of neural progenitor cells.
Observations of energetic turbulence on the Weddell Sea continental slope
Authors: Fer Ilker , Darelius Elin , Daae Kjersti B.
Published: January 2016

Turbulence profile measurements made on the upper continental slope and shelf of the southeastern Weddell Sea reveal striking contrasts in dissipation and mixing rates between the two sites. The mean profiles of dissipation rates from the upper slope are 1–2 orders of magnitude greater than the profiles collected over the shelf in the entire water column. The difference increases toward the bottom where the dissipation rate of turbulent kinetic energy and the vertical eddy diffusivity on the slope exceed 10−7 W kg−1 and 10−2 m2 s−1, respectively. Elevated levels of turbulence on the slope are concentrated within a 100 m thick bottom layer, which is absent on the shelf. The upper slope is characterized by near‐critical slopes and is in close proximity to the critical latitude for semidiurnal internal tides. Our observations suggest that the upper continental slope of the southern Weddell Sea is a generation site of semidiurnal internal tide, which is trapped along the slope along the critical latitude, and dissipates its energy in a
 m thick layer near the bottom and within
 km across the slope.
Large‐Area Multicolor Emissive Patterns of Quantum Dot–Polymer Films via Targeted Recovery of Emission Signature
Authors: Malak Sidney T. , Jung Jaehan , Yoon Young Jun , Smith Marcus J. , Lin Chun Hao , Lin Zhiqun , Tsukruk Vladimir V.
Published: January 2016

A facile one‐step fabrication of large‐area multicolored emissive photopatterns in mixed quantum dot‐polymer films is demonstrated. This is in sharp contrast to the current photopatterning approaches that utilize only a single quantum dot (QD) component for single‐color patterns. Strategies are presented that allow for either selective or collective modification of specific predetermined photoluminescent peaks of green and red QDs during photopattern development. These strategies yield novel patterns and allow for unprecedented control over how the color contrast of the photopattern evolves with continuous light illumination. These results clearly show that the evolution of the emission spectra of a multicolor mixed QD‐polymer film can be readily tailored during pattern development, either by careful selection of the excitation wavelength or through combinations of controllably unstable and stable QDs with different recovery rates. Notably, these strategies are simple, fast, and robust, yielding high‐resolution microscopic patterns over large areas (up to fractions of a cm2). Furthermore, the flexibility and capabilities of these strategies greatly expand the potential applications of multicolor emissive photopatterns, particularly in the areas of sensing, imaging, and lasing systems where it is important to exert delicate control over the intensity of selected colors within specific spatial regions.
Lateral meningocele (Lehman) syndrome: A child with a novel NOTCH3 mutation
Authors: Ejaz Resham , Qin Wen , Huang Lijia , Blaser Susan , Tetreault Martine , Hartley Taila , Boycott Kym M. , Carter Melissa T. ,   Care4Rare Canada Consortium
Published: January 2016

Lateral meningocele syndrome (LMS), or Lehman syndrome, is a rare disorder characterized by multiple lateral spinal meningoceles, distinctive facial features, joint hypermobility and hypotonia, along with skeletal, cardiac, and urogenital anomalies. Heterozygous NOTCH3 mutations affecting the terminal exon 33 were recently reported as causative in six families with LMS. We report a boy with LMS, the fourteenth reported case, with a de novo 80 base pair deletion in exon 33 of NOTCH3. Our patient's prenatal findings, complex cardiac anomalies, and severe feeding difficulties further expand our understanding of this rare condition. © 2016 Wiley Periodicals, Inc.
Scholarly publication and collaboration in Brazil: The role of geography
Authors: Sidone Otávio José Guerci , Haddad Eduardo Amaral , Mena‐Chalco Jesús Pascual
Published: January 2016

Brazilian scholarly output has rapidly increased, accompanied by the expansion of domestic collaborations. In this paper, we identify spatial patterns of collaboration in Brazil and measure the role of geographic proximity in determining the interaction among researchers. Using a database comprising more than one million researchers and seven million publications, we consolidated information on interregional research collaboration in terms of scientific coauthorship networks among 4,615 municipalities during the period between 1992 and 2009, which allowed us to analyze a range of data unprecedented in the literature. The effects of geographic distance on collaboration were measured for different areas by estimating spatial interaction models. The main results provide strong evidence of geographic deconcentration of collaboration in recent years, with increased participation of authors in scientifically less traditional regions, such as south and northeast Brazil. Distance remains a significant factor in determining the intensity of knowledge flow in collaboration networks in Brazil, as an increase of 100 km between two researchers reduces the probability of collaboration by an average of 16%, and there is no evidence that the effect of distance has diminished over time, although the magnitude of such effects varies among networks of different areas.
Hemispheric differences in language processing in autism spectrum disorders: A meta‐analysis of neuroimaging studies
Authors: Herringshaw Abbey J. , Ammons Carla J. , DeRamus Thomas P. , Kana Rajesh K.
Published: January 2016

Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta‐analytic approach. Activation likelihood estimation (ALE) meta‐analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within‐group analysis showed largely overlapping patterns of language‐related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo‐activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context‐dependency. Autism Res 2016, 9: 1046–1057. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
YedY: A Mononuclear Molybdenum Enzyme with a Redox‐Active Ligand?
Authors: Lee Chi Chung , Sickerman Nathaniel S. , Hu Yilin , Ribbe Markus W.
Published: January 2016

A recent electrochemical investigation suggests that the mononuclear molybdenum enzyme YdeY utilizes redox‐active ligands during catalysis.
Detailed Investigation of the Structural, Thermal, and Electronic Properties of Gold Isocyanide Complexes with Mechano‐Triggered Single‐Crystal‐to‐Single‐Crystal Phase Transitions
Authors: Seki Tomohiro , Sakurada Kenta , Muromoto Mai , Seki Shu , Ito Hajime
Published: January 2016

Mechano‐induced phase transitions in organic crystalline materials, which can alter their properties, have received much attention. However, most mechano‐responsive molecular crystals exhibit crystal‐to‐amorphous phase transitions, and the intermolecular interaction patterns in the daughter phase are difficult to characterize. We have investigated phenyl(phenylisocyanide)gold(I) (1) and phenyl(3,5‐dimethylphenylisocyanide)gold(I) (2) complexes, which exhibit a mechano‐triggered single‐crystal‐to‐single‐crystal phase transition. Previous reports of complexes 1 and 2 have focused on the relationships between the crystalline structures and photoluminescence properties; in this work we have focused on other aspects. The face index measurements of complexes 1 and 2 before and after the mechano‐induced phase transitions have indicated that they undergo non‐epitaxial phase transitions without a rigorous orientational relationship between the mother and daughter phases. Differential scanning calorimetry analyses revealed the phase transition of complex 1 to be enthalpically driven by the formation of new aurophilic interactions. In contrast, the phase transition of complex 2 was found to be entropically driven, with the closure of an empty void in the mother phase. Scanning electron microscopy observation showed that the degree of the charging effect of both complexes 1 and 2 was changed by the phase transitions, which suggests that the formation of the aurophilic interactions affords more effective conductive pathways. Moreover, flash‐photolysis time‐resolved microwave conductivity measurements revealed that complex 1 increased in conductivity after the phase change, whereas the conductivity of complex 2 decreased. These contrasting results were explained by the different patterns in the aurophilic interactions. Finally, an intriguing disappearing polymorphism of complex 2 has been reported, in which a polymorph form could not be obtained again after some period of time, even with repeated trials. The present studies provide us with a variety of hitherto unknown insights into mechano‐responsive molecular crystals, which help us to understand the phase transition behaviors upon mechanical stimulation and establish rational design principles.
Nanostructured Silicon‐Based Fingerprint Dusting Powders for Enhanced Visualization and Detection by Mass Spectrometry
Authors: Guinan Taryn M. , Kobus Hilton , Lu Yiqing , Sweetman Martin , McInnes Steven J. P. , Kirkbride K. Paul , Voelcker Nicolas H.
Published: January 2016

Porous silicon microparticles (pSi MPs) functionalized with fluorescent dyes (lissamine and carboxy‐5‐fluorescein) and intrinsically luminescent pSi MPs were explored as novel fingerprint dusting powders. The versatility of luminescent pSi MPs is demonstrated through time‐gated imaging of their long‐lived (lifetime>28 μs) near‐IR emission, and mass spectrometry analysis of fingerprints dusted with luminescent pSi MPs to provide further information on exogenous small molecules present in latent fingerprints.
Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma
Authors: Takahashi Yoko , Lee Junegoo , Pickering Curtis , Bell Diana , Jiffar Tilahun W. , Myers Jeffrey N. , Hanna Ehab Y. , Kupferman Michael E.
Published: January 2016

Background

Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC.

Methods

Using the human‐derived SNUC MDA8788‐6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo.

Results

The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788‐6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788‐6 cells both in vitro and in vivo.

Conclusion

Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926–E1934, 2016
Visualising apoptosis in live zebrafish using fluorescence lifetime imaging with optical projection tomography to map FRET biosensor activity in space and time
Authors: Andrews Natalie , Ramel Marie‐Christine , Kumar Sunil , Alexandrov Yuriy , Kelly Douglas J. , Warren Sean C. , Kerry Louise , Lockwood Nicola , Frolov Antonina , Frankel Paul , Bugeon Laurence , McGinty James , Dallman Margaret J. , French Paul M. W.
Published: January 2016

Fluorescence lifetime imaging (FLIM) combined with optical projection tomography (OPT) has the potential to map Förster resonant energy transfer (FRET) readouts in space and time in intact transparent or near transparent live organisms such as zebrafish larvae, thereby providing a means to visualise cell signalling processes in their physiological context. Here the first application of FLIM OPT to read out biological function in live transgenic zebrafish larvae using a genetically expressed FRET biosensor is reported. Apoptosis, or programmed cell death, is mapped in 3‐D by imaging the activity of a FRET biosensor that is cleaved by Caspase 3, which is a key effector of apoptosis. Although apoptosis is a naturally occurring process during development, it can also be triggered in a variety of ways, including through gamma irradiation. FLIM OPT is shown here to enable apoptosis to be monitored over time, in live zebrafish larvae via changes in Caspase 3 activation following gamma irradiation at 24 hours post fertilisation. Significant apoptosis was observed at 3.5 hours post irradiation, predominantly in the head region.

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Electrochemical comportment of Ni–Ti alloys immersed in two types of artificial saliva
Authors: Othman Houda , Etteyeb Naceur
Published: January 2016

The main objective of this work was to study the electrochemical behavior of Ni–Ti alloy immersed in two types of artificial saliva: neutral saliva (Ringer's solution, pH = 7.4) and acidic saliva (Fusayama solution pH ∼ 2.3). This study was conducted by the application of various electrochemical methods [monitoring of the corrosion potential over time; E = f(t), polarization curves; j = f(E), and electrochemical impedance spectroscopy EIS]. The overall results showed that the acidification of the saliva and/or the increase of its temperature causes the ignition of the corrosion phenomena of the Ni–Ti alloy. Indeed, the corrosion rate increases significantly with increasing temperature and the decreasing of the pH medium. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 778–784, 2017.
Transcriptomic Changes in Osteoblasts Following Endothelial Cell‐Cocultivation Suggest a Role of Extracellular Matrix in Cellular Interaction
Authors: Lampert Florian M. , Simunovic Filip , Finkenzeller Günter , Pfeifer Dietmar , Stark G. Björn , Winninger Oscar , Steiner Dominik
Published: January 2016

Vascularization is important for bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1,004 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. The microarray data could be confirmed by performing quantitative real time RT‐PCR on selected genes. Furthermore, we could show that the ECM produced by HUVECs increased the expression of the osteogenic differentiation marker alkaline phosphatase (ALP) in hOBs. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction. J. Cell. Biochem. 117: 1869–1879, 2016. © 2016 Wiley Periodicals, Inc.
Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects
Authors: Kitami Megumi , Kaku Masaru , Rocabado Juan Marcelo Rosales , Ida Takako , Akiba Nami , Uoshima Katsumi
Published: January 2016

Considering the increased interest in cell‐based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti‐apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3‐E1 osteoblastic cells from H2O2‐induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27‐overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4‐week of transplantation, both control cell‐ and Hsp27 overexpressed cell‐transplanted groups showed significantly higher new bone formation in comparison with cell‐free gel‐transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4‐week but did not differentiate into bone‐forming osteoblasts. In conclusion, cell‐containing collagen gel accelerated calvarial bone defect healing in comparison with cell‐free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation‐based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974–1982, 2016. © 2016 Wiley Periodicals, Inc.
Immunohistochemical and ultrastructural evidence of functional organization along the Corydoras paleatus intestine
Authors: Plaul Silvia E. , Pastor Raquel , Díaz Alcira O. , Barbeito Claudio G.
Published: January 2016

The Neotropical catfish, Corydoras paleatus (Callichthyidae) is a facultative air‐breathing teleost that makes use of the caudal portion of the intestine as an accessory air‐breathing organ. This portion is highly modified, being well vascularized with capillaries between epithelial cells, which makes it well suited for gas exchange. Instead, the cranial portion is a digestion and absorption site, as it has a typical intestinal epithelium with columnar cells arranged in a single row, villi and less vascularized tunica mucosa. Therefore, the intestine was studied by light and electron microscopy to assess differences between the cranial, middle and caudal portions. To characterize the potential for cell proliferation of this organ, we used anti‐proliferating cell nuclear antigen antibody and anti‐Na+K+‐ATPase monoclonal antibody to detect the presence of Na+/K+ pump. In C. paleatus it was observed that cell dynamics showed a decreasing gradient of proliferation in cranio‐caudal direction. Also, the intestine of this catfish is an important organ in ionoregulation: the basolateral Na+/K+ pump may have an active role, transporting Na+ out of the cell while helping to maintain the repose potential and to regulate cellular volume. Microsc. Res. Tech. 79:140–148, 2016. © 2016 Wiley Periodicals, Inc.
Modulation of cadmium bioaccumulation and enhancing cadmium tolerance in Pichia kudriavzevii by sodium chloride preincubation
Authors: Ma Ning , Li Chunsheng , Zhang Dandan , Yu Jinzhi , Xu Ying
Published: January 2016

Application of growing microorganisms for cadmium removal is limited by the sensitivity of living cells to cadmium. The effects of sodium chloride (NaCl) preincubation on the cadmium bioaccumulation and tolerance of Pichia kudriavzevii and Saccharomyces cerevisiae were investigated in this study. NaCl preincubation significantly reduced the intracellular and cell‐surface cadmium bioaccumulation of P. kudriavzevii at both 6 and 20 mg L−1 cadmium, while no obvious effect was observed in S. cerevisiae except that the intracellular cadmium bioaccumulation at 20 mg L−1 cadmium was reduced obviously by 20–60 g L−1 NaCl. For both yeasts, the improved contents of protein and proline after NaCl preincubation contributed to the cadmium tolerance. The thiol contents in P. kudriavzevii under cadmium stress were alleviated by NaCl preincubation, which might be due to the decrease of intracellular cadmium bioaccumulation. NaCl preincubation enhanced the contents of glycerol and trehalose in P. kudriavzevii under cadmium stress, while no acceleration was observed in S. cerevisiae. The results suggested that NaCl preincubation could be applied in cadmium removal by growing P. kudriavzevii to increase the cadmium tolerance of the yeast.
Is peer review still the content industry's upper house?
Authors: Baverstock Alison
Published: January 2016

Key points

Although ‘peer review’ has quasi‐sacred status, times are changing, and peer review is not necessarily a single and uniformly reliable gold standard.

For publishers, peer review is a process not an outcome.

Academics understand peer review, but are often ignorant about the quality checking mechanisms within wider publishing.

Self‐publishing has led to the much wider availability of publishing services – these now being used by all stakeholders in publishing.

How should universities evaluate comment and ideas that were first disseminated within a non‐academic market?

Rather than an upper house, is peer review today more of a galley kitchen?
Mimicking of Chondrocyte Microenvironment Using In Situ Forming Dendritic Polyglycerol Sulfate‐Based Synthetic Polyanionic Hydrogels
Authors: Dey Pradip , Schneider Tobias , Chiappisi Leonardo , Gradzielski Michael , Schulze‐Tanzil Gundula , Haag Rainer
Published: January 2016

A stable polymeric network that mimics the highly polyanionic extracellular cartilage matrix still remains a great challenge. The main aim of this study is to present the synthesis of dendritic polyglycerol sulfate (dPGS)‐based in situ forming hydrogels using strain promoted azide‐alkyne cycloaddition reactions. A real time rheological study has been used to characterize the hydrogel properties. The viability of encapsulated human chondrocytes in the different hydrogels are monitored using live‐dead staining. Furthermore, type I and II collagen gene have been analyzed. Hydrogels with elastic moduli ranging from 1 to 5 kPa have been prepared by varying the dPGS amount. The chondrocyte viability in dPGS hydrogels is found to be higher than in pure PEG and alginate‐based hydrogels after 21 d. The higher cell viability in the dPGS engineered hydrogels can be explained by the fact that dPGS can interact with different proteins responsible for cell growth and proliferation.

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Evaluation of the gap filler radar as an implementation of the 1.5 km CAPPI data in Korea
Authors: Yoo Chulsang , Yoon Jungsoo , Kim Jungho , Ro Yonghun
Published: January 2016

This study evaluated the gap filler radar as an implementation of the 1.5 km CAPPI (constant altitude plan position indicator) data in Korea. The use of the 1.5 km CAPPI data was an inevitable choice, given the topography of the Korean Peninsula and the location of the radar. However, there still exists a significant portion of beam blockage, and thus there has been debate about the need to introduce the gap filler radar (or, the gap‐filler). This study evaluated the possible benefits of introducing gap‐fillers over the Korean Peninsula. As a first step, the radar data error was quantified by G/R ratio and root mean square error (RMSE), and the radar data over the Korean Peninsula were evaluated. The gap‐fillers were then located where the error was high, and their effect was then evaluated by the decrease in the G/R ratio and RMSE. The mean values of the G/R ratio and RMSE of the 1.5 km CAPPI data over the Korean Peninsula were estimated to be about 2.5 and 4.5 mm h–1, respectively. Even after the mean‐field bias correction, the RMSE of the 1.5 km CAPPI data was not decreased and mostly remained very high, around 4.4 mm h–1. Unfortunately, the effect of the gap‐filler on the 1.5 km CAPPI data was also found to be very small, just 1–2%. However, the gap‐filler could be beneficial, if the lowest elevation angle data were used instead of the 1.5 km CAPPI data. The effect of five gap‐fillers could be up to 7% decrease in RMSE.
Linear statistics of matrix ensembles in classical background
Authors: Min Chao , Chen Yang
Published: January 2016

Given a joint probability density function of N real random variables,
, obtained from the eigenvector–eigenvalue decomposition of N × N random matrices, one constructs a random variable, the linear statistics, defined by the sum of smooth functions evaluated at the eigenvalues or singular values of the random matrix, namely,
. For the joint PDFs obtained from the Gaussian and Laguerre ensembles, we compute, in this paper, the moment‐generating function
, where
denotes expectation value over the orthogonal (β = 1) and symplectic (β = 4) ensembles, in the form one plus a Schwartz function, none vanishing over
for the Gaussian ensembles and
for the Laguerre ensembles. These are ultimately expressed in the form of the determinants of identity plus a scalar operator, from which we obtained the large N asymptotic of the linear statistics from suitably scaled F(·). Copyright © 2016 John Wiley & Sons, Ltd.
A quadratic convex combination approach on robust dissipativity and passivity analysis for Takagi–Sugeno fuzzy Cohen–Grossberg neural networks with time‐varying delays
Authors: Nagamani G. , Radhika T.
Published: January 2016

In this paper, the robust dissipativity and passivity criteria for Takagi–Sugeno fuzzy Cohen–Grossberg neural networks with time‐varying delays have been investigated. The delay is of the time‐varying nature, and the activation functions are assumed to be neither differentiable nor strictly monotonic. Furthermore, the description of the activation functions is more general than the commonly used Lipschitz conditions. By using a Lyapunov–Krasovskii functional and employing the quadratic convex combination approach, a set of sufficient conditions are established to ensure the dissipativity of the proposed model. The obtained conditions are presented in terms of linear matrix inequalities, so that its feasibility can be checked easily via standard numerical toolboxes. The quadratic convex combination approach used in our paper gives a reduced conservatism without using Jensen's inequality. In addition to that, numerical examples with simulation results are given to show the effectiveness of the obtained linear matrix inequality conditions. Copyright © 2016 John Wiley & Sons, Ltd.