bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery of Genome Editing Reagents to Hematopoietic Stem/Progenitor Cells
Authors: Hoban Megan D. , Romero Zulema , Cost Gregory J. , Mendel Matthew , Holmes Michael , Kohn Donald B.
Published: February 2016

This unit describes the protocol for the delivery of reagents for targeted genome editing to CD34+ hematopoietic stem/progenitor cells (HSPCs). Specifically, this unit focuses on the process of thawing and pre‐stimulating CD34+ HSPCs, as well as the details of their electroporation with in vitro‐transcribed mRNA‐encoding site‐specific nucleases [in this case zinc‐finger nucleases (ZFNs)]. In addition, discussed is delivery of a gene editing donor template in the form of an oligonucleotide or integrase‐defective lentiviral vector (IDLV). Finally, an analysis of cell survival following treatment and downstream culture conditions are presented. While optimization steps might be needed for each specific application with respect to nuclease and donor template amount, adherence to this protocol will serve as an excellent starting point for this further work. © 2016 by John Wiley & Sons, Inc.
Silicon‐Modified Rare‐Earth Transitions—A New Route to Near‐ and Mid‐IR Photonics
Authors: Lourenço Manon A. , Hughes Mark A. , Lai Khue T. , Sofi Imran M. , Ludurczak Willy , Wong Lewis , Gwilliam Russell M. , Homewood Kevin P.
Published: February 2016

Silicon underpins microelectronics but lacks the photonic capability needed for next‐generation systems and currently relies on a highly undesirable hybridization of separate discrete devices using direct band gap semiconductors. Rare‐earth (RE) implantation is a promising approach to bestow photonic capability to silicon but is limited to internal RE transition wavelengths. Reported here is the first observation of direct optical transitions from the silicon band edge to internal f‐levels of implanted REs (Ce, Eu, and Yb); this overturns previously held assumptions about the alignment of RE levels to the silicon band gap. The photoluminescence lines are massively redshifted to several technologically useful wavelengths and modeling of their splitting indicates that they must originate from the REs. Eu‐implanted silicon devices display a greatly enhanced electroluminescence efficiency of 8%. Also observed is the first crystal field splitting in Ce luminescence. Mid‐IR silicon photodetectors with specific detectivities comparable to existing state‐of‐the‐art mid‐IR detectors are demonstrated.
Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma
Authors: Huang Shengnan , Duan Shaofeng , Wang Jing , Bao Shijin , Qiu Xiaojing , Li Chunming , Liu Ying , Yan Lijuan , Zhang Zhenzhong , Hu Yurong
Published: February 2016

Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the efficient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA‐181b inhibitor (anti‐miR‐181b) is successfully condensed into polyethyleneimine (PEI)‐modified and folate receptor (FR)‐targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti‐miR‐181b/PTPAuNCs nanocomplexes (PTPAuNC‐NPs), which begin with chemical modification of AuNCs with SH‐PEG5000‐folic acid (SH‐PEG5000‐FA) and SH‐PEG5000 through a gold–sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti‐miR‐181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC‐NPs can efficiently deliver anti‐miR‐181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC‐7721 tumor‐bearing nude mice under near‐infrared radiation. All these results suggest that PTPAuNC‐NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.
High‐Performance Flexible Multilayer MoS2 Transistors on Solution‐Based Polyimide Substrates
Authors: Song Won Geun , Kwon Hyuk‐Jun , Park Jozeph , Yeo Junyeob , Kim Minjeong , Park Suntak , Yun Sungryul , Kyung Ki‐Uk , Grigoropoulos Costas P. , Kim Sunkook , Hong Young Ki
Published: February 2016

Transition metal dichalcogenides (TMDs) layers of molecular thickness, in particular molybdenum disulfide (MoS2), become increasingly important as active elements for mechanically flexible/stretchable electronics owing to their relatively high carrier mobility, wide bandgap, and mechanical flexibility. Although the superior electronic properties of TMD transistors are usually integrated into rigid silicon wafers or glass substrates, the achievement of similar device performance on flexible substrates remains quite a challenge. The present work successfully addresses this challenge by a novel process architecture consisting of a solution‐based polyimide (PI) flexible substrate in which laser‐welded silver nanowires are embedded, a hybrid organic/inorganic gate insulator, and multilayers of MoS2. Transistors fabricated according to this process scheme have decent properties: a field‐effect‐mobility as high as 141 cm2 V−1 s−1 and an Ion/Ioff ratio as high as 5 × 105. Furthermore, no apparent degradation in the device properties is observed under systematic cyclic bending tests with bending radii of 10 and 5 mm. Overall electrical and mechanical results provide potentially important applications in the fabrication of versatile areas of flexible integrated circuitry.
Copper‐Mediated ortho‐Arylation of Benzamides with Arylboronic Acid
Authors: Gui Qingwen , Chen Xiang , Hu Liang , Wang Dadian , Liu Jidan , Tan Ze
Published: February 2016

The copper‐mediated direct ortho CH bond arylation of benzamide derivatives with arylboronic acids was achieved by employing an 8‐aminoquinoline moiety as the bidentate directing group. Various biaryls were synthesized in good yields with excellent regioselectivity. The reaction shows good functional group compatibility and proceeds in a highly selective manner at the ortho‐position of the benzamides. Deuterium‐labelling experiments indicated that the ortho CH bond cleavage of benzamide was involved in the rate‐determining step of the arylation.

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A Ruthenium Catalyst for Olefin Metathesis Featuring an Anti‐Bredt N‐Heterocyclic Carbene Ligand
Authors: Martin David , Marx Vanessa M. , Grubbs Robert H. , Bertrand Guy
Published: February 2016

A ruthenium complex bearing an “anti‐Bredt” N‐heterocyclic carbene was synthesized, characterized and evaluated as a catalyst for olefin metathesis. Good conversions were observed at room temperature for the formation of di‐ and tri‐substituted olefins by ring‐closing metathesis. It also allowed for the ring‐opening metathesis polymerization of cyclooctadiene, as well as for the cross‐metathesis of cis‐1,4‐diacetoxy‐2‐butene with allylbenzene, with enhanced Z/E kinetic selectivity over classical NHC‐based catalysts.

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Chemical conversion and liquid–liquid extraction of 5‐hydroxymethylfurfural from fructose by slug flow microreactor
Authors: Shimanouchi Toshinori , Kataoka Yoshitaka , Tanifuji Tatsuya , Kimura Yukitaka , Fujioka Satoko , Terasaka Koichi
Published: February 2016

A dehydration of fructose in the water/methyl isobuthyl ketone (MIBK) biphasic system can yield 5‐hydroxymethylfurfural (HMF) to be successfully extracted into the organic MIBK phase. The HMF production and yield in MIBK phase was discussed by using a simplified model taking into consideration of the slug flow. The extraction resistance of HMF across the interface between water and MIBK depended on the line velocity and the flow rate ratio. It was likely that the velocity field generated in the slug flow contributed to an increase in the mass transfer of HMF. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2135–2143, 2016
Improved survival with combined modality therapy in the modern era for primary mediastinal B‐cell lymphoma
Authors: Jackson Matthew W. , Rusthoven Chad G. , Jones Bernard L. , Kamdar Manali , Rabinovitch Rachel
Published: February 2016

Primary mediastinal B‐cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan–Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow‐up of 36 months. Median age was 36 years; 43% received RT. 5‐year OS for the entire cohort was 87%, and for the no‐RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. Am. J. Hematol. 91:476–480, 2016. © 2016 Wiley Periodicals, Inc.
Amphiphilic acrylate copolymer fatliquor for ecological leather: Influence of molecular weight on performances
Authors: Du Jinxia , Shi Lu , Peng Biyu
Published: February 2016

With increasing demand for ecological leather, ecological fatliquors with good comprehensive properties are getting more and more attention. The amphiphilic acrylate copolymer containing both hydrophilic (carboxyl) and hydrophobic (long alkyl) groups is one of the main alternatives to conventional fatliquors. In this paper, a series of poly(acrylic acid‐co‐stearyl acrylate) with different relative molecular weights were prepared, and the influence of the molecular weight on their application performances were evaluated. The results show that lower relative molecular weight of copolymers is conducive to the penetration and absorption, and it improves the softness and fiber separation of leather. When the number average molecular weight (Mn) of copolymer is higher than 25,000, its penetration and absorption become worse and the resulting leather feels hard. In addition, the amphiphilic acrylate copolymers can impart excellent oxidation resistance and transference resistance to leather, which is a considerable improvement over the conventionally retanned and fatliquored leather. The copolymer has great penetration and absorption ability when Mn is within the range of 9,000–15,000, and it gives leather excellent integrated properties, such as filling, softness, mechanical strength, extraction resistance, and oxidation resistance, which can meet requirements of ecological leather. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43440.
A highly selective electrochemical sensor for nifedipine based on layer‐by‐layer assembly films from polyaniline and multiwalled carbon nanotube
Authors: Wang Qiguan , Zhao Rongna , Wang Sumin , Guo Hao , Li Jinhua , Zhou Hongwei , Wang Xinhai , Wu Xinming , Wang Yan , Chen Weixing , Zhang Wenzhi
Published: February 2016

An uniformly distributed film consisting of polyaniline (PANI) nanoparticles and carboxylic acid functionalized multiwalled carbon nanotubes (MWNTs‐COOH) was successfully assembled on ITO plates from a layer‐by‐layer (LBL) method by using electrostatic interactions as the main driving force. The good conjugation between PANI nanoparticles and MWNTs‐COOH resulted in significant electrochemical performance variation of the obtained films. In addition, the assembled MWNT‐COOH/PANI/ITO showed synergistic effect to the electrochemical oxidation of nifedipine (NIF) when used as a sensor. Compared with bare ITO, the oxidation potential of NIF can be decreased about 170 mV on MWNT‐COOH/PANI/ITO, and the lower detection limit of NIF was as low as 1.0 × 10−6 mol/L. In addition, the assembled electrode gave no responses to interferences such as glucose, urea, ascorbic acid, and trisodium citrate, which showed high selectivity for recognition and quantification of NIF. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43452.
Low k epoxy resin containing cycloaliphatic hydrocarbon with high crosslinking density
Authors: Kong Lingqiang , Cheng Yuanrong , Jin Yunxia , Qi Tianke , Xiao Fei
Published: February 2016

High performance epoxy resins have attracted much research interest in the last decades. Herein, two novel epoxy monomers containing cycloaliphatic hydrocarbon, 1,4‐bis(4‐(N,N‐diglycidylamino)phenoxy)cyclohexane (CyhEP) and 1,3‐bis(4‐(N,N‐diglycidylamino)phenoxy)adamantane (AdaEP) were synthesized and characterized. They were cured with 4‐methylhexahydrophthalic anhydride (MHHPA) to prepare the highly crosslinked thermosets. Both epoxy resins show good thermal stability (Td5 > 300 °C), high glass transition temperature (> 200 °C), and high storage modulus (> 3.2 GPa) due to their highly crosslinked structure. The AdaEP/MHHPA resin shows a low dielectric constant (3.4 at 1 MHz) because of the introduction of bulky rigid adamantane into the polymer. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43456.
Multiple Framing: Verbal, Facial, and Vocal Cues in Risky Choice
Authors: Garelik Steven , Wang X.T. (Xiao‐Tian)
Published: February 2016

Verbal framing effects have been widely studied, but little is known about how people react to multiple framing cues in risk communication, where verbal messages are often accompanied by facial and vocal cues. We examined joint and differential effects of verbal, facial, and vocal framing on risk preference in hypothetical monetary and life–death situations. In the multiple framing condition with the factorial design (2 verbal frames × 2 vocal tones × 4 basic facial expressions × 2 task domains), each scenario was presented auditorily with a written message on a photo of the messenger's face. Compared with verbal framing effects resulting in preference reversal, multiple frames made risky choice more consistent and shifted risk preference without reversal. Moreover, a positive tone of voice increased risk‐seeking preference in women. When the valence of facial and vocal cues was incongruent with verbal frame, verbal framing effects were significant. In contrast, when the affect cues were congruent with verbal frame, framing effects disappeared. These results suggest that verbal framing is given higher priority when other affect cues are incongruent. Further analysis revealed that participants were more risk‐averse when positive affect cues (positive tone or facial expressions) were congruently paired with a positive verbal frame whereas participants were more risk‐seeking when positive affect cues were incongruent with the verbal frame. In contrast, for negative affect cues, congruency promoted risk‐seeking tendency whereas incongruency increased risk‐aversion. Overall, the results show that facial and vocal cues interact with verbal framing and significantly affect risk communication. Copyright © 2016 John Wiley & Sons, Ltd.
President's page
Authors: Caidi Nadia
Published: February 2016

EDITOR'S SUMMARY

Starting her leadership year, incoming ASIS&T president Nadia Caidi noted the great success of the 2015 Annual Meeting, focusing on information science with impact. Over the next year Caidi is committed to celebrating the Association's members, connecting with other organizations focused on information issues and analyzing the Association's structure and policies to ensure its future strength. An emphasis on membership and engagement runs through each of these goals, to enhance appreciation of the Association as a collective home for those in the field of information science and technology. Members are invited to share ideas through numerous committees and task forces, listed with their chairpersons and heads, as these groups reach out to the membership over the coming year to encourage all to feel involved with ASIS&T. Looking forward to the 2016 Annual Meeting in Copenhagen, Caidi sets her sights on the Association gaining broader recognition and strength and becoming more international, diverse and inclusive.
Indispensable Institutions: Making a Case for Public Libraries as Local E‐Government Service Administrators
Authors: Million A. J.
Published: February 2016

EDITOR'S SUMMARY

While electronic access to government information is an expressed goal, implementation varies widely by locality, purpose and focus. Public libraries are uniquely situated to serve e‐government administration by assembling and managing online collections of local electronic government records. Materials to be collected should reflect local and patron needs, be permitted by law and be accessible online. Libraries already provide internet access and reference support, and they are increasingly serving as intermediaries as agencies cut staffing as they move materials online. Libraries promote transparency, in strong demand by the public and necessary for citizen participation in the democratic process. Libraries are trusted institutions, and, supported by librarians’ competencies, they enable access, digital preservation and support for online collections. Numerous public and private libraries serve as depositories of state and federal government records, providing access points for citizens to obtain information. With the foundation of skills, capabilities and precedents, it would not be difficult for public libraries to expand on their tradition of managing and supporting access to information to administer online collections of local government information.
Research Ethics in an Age of Big Data
Authors: Sula Chris Alen
Published: February 2016

EDITOR'S SUMMARY

The era of big data introduces new considerations into the traditional context of research ethics. Ethical questions may be considered in terms of accuracy, humane treatment, informed participants and the necessity and applicability of the work, but big data complicates these issues. Since social media participants reflect certain demographic features, data drawn from those sources should not be taken to represent the general population. Big data collection may be more invasive than necessary due to easy access, and consent may be nonexistent. Data that was once anonymous may become identifiable, last indefinitely and conflict with goals for publication. Ways to respect ethics in big data research include involving participants throughout the process, avoiding collecting information that should remain private, notifying participants of their inclusion and providing them options to correct or delete personal information, and using public channels to disseminate research.
Training Your Eye to See Structure
Authors: Creekmore Laura
Published: February 2016

EDITOR'S SUMMARY

Unlike organizing external views of information, content modeling pertains to internal information architecture. Building a content model from scratch is relatively easy, while improving an existing system is more common and usually more challenging. Information architects intuitively recognize content elements for data fields and how these fields might be semantically linked, providing valuable opportunities that enhance a user's experience. Recognizing important data elements and how they might be sorted and associated requires a certain style of thinking, recognition of patterns and a knack for classifying. As categories are identified they lend themselves to defined content structures and interconnections. As an information architect gains practice and experience, the internal structure of content becomes clearer.
Consider developing a college athletics review board to enhance transparency
Authors: Neal Timothy , O'Brien Timothy
Published: February 2016

The recent release of the movie Concussion has generated significant interest in and sensitivity about the medical treatment of athletes at all levels.
Inflammatory response in serrated precursor lesions of the colon classified according to WHO entities, clinical parameters and phenotype–genotype correlation
Authors: Rau Tilman T , Atreya Raja , Aust Daniela , Baretton Gustavo , Eck Matthias , Erlenbach‐Wünsch Katharina , Hartmann Arndt , Lugli Alessandro , Stöhr Robert , Vieth Michael , Wirsing Anna M , Zlobec Inti , Katzenberger Tiemo
Published: February 2016

Studies on traditional serrated adenoma (TSA) and sessile serrated adenoma with dysplasia (SSA‐D) are rare due to the low frequency of these lesions, which are well defined by the latest WHO classification. However, introducing new morphological criteria such as intra‐epithelial lymphocytes (IELs) might facilitate colorectal polyp diagnoses. Additionally, the phenotype–genotype correlation needs to be updated as the terminology has repeatedly changed. This study analysed 516 polyps, consisting of 118 classical adenomas (CAD), 116 hyperplastic polyps (HPP), 179 SSAs, 41 SSA‐Ds, and 62 TSAs. The lesions were analysed in relation to the patients’ clinical parameters including gender, age, localisation, and size. The inflammatory background of the polyps was quantified and BRAF and KRAS mutations as well as MLH1 and CDKN2A promoter methylation were assessed. In multivariate analyses, an increase in IELs was an independent and robust new criterion for the diagnosis of SSA‐D (p < 0.001). Superficial erosions and acute neutrophil granulocytes led to reactive changes potentially resembling dysplasia. KRAS and BRAF mutations were associated with CAD/TSA and HPP/SSA, respectively. However, almost half of TSAs had a BRAF mutation and were KRAS wild type. CDKN2A seems to precede MLH1 hyper‐methylation within the serrated carcinogenesis model. The genotyping of WHO‐based entities – and especially SSA – has sharpened in comparison to previously published data. TSAs can be sub‐grouped according to their mutation status. Of note, the higher number of IELs in SSA‐D reflects their close relationship to colorectal cancers with micro‐satellite instability. Therefore, IELs might represent a new diagnostic tool for SSA‐D.
Ototoxicity and cancer therapy
Authors: Landier Wendy
Published: February 2016

Ototoxicity is a well‐established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health‐related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration‐approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. Cancer 2016;122:1647‐58. © 2016 American Cancer Society.
Twenty‐one–gene recurrence score assay in BRCA‐associated versus sporadic breast cancers: Differences based on germline mutation status
Authors: Shah Payal D. , Patil Sujata , Dickler Maura N. , Offit Kenneth , Hudis Clifford A. , Robson Mark E.
Published: February 2016

BACKGROUND

Biological differences between BRCA‐associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21‐gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor–positive breast cancer. No reports describe assay results for BRCA‐associated breast cancer.

METHODS

A review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor–positive, node‐negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two‐sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status.

RESULTS

Fifty mutation‐associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P = .9) and tumor size (P = .6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P = .6) and risk category stratification (P = .3). The median RS was higher for cases versus controls (24 vs 16; P < .0001). Risk stratification also differed by mutational status (P = .0002). Cases had more high‐risk disease (28% vs 7%) and intermediate‐risk disease (56% vs 36%) and less low‐risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P = .002).

CONCLUSIONS

Germline BRCA‐associated hormone receptor–positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes. Cancer 2016;122:1178–84. © 2016 American Cancer Society.
Depressive Symptom Inventory Suicidality Subscale: Optimal Cut Points for Clinical and Non‐Clinical Samples
Authors: von Glischinski M. , Teismann T. , Prinz S. , Gebauer J. E. , Hirschfeld G.
Published: February 2016

Suicide is a major cause of death in adulthood and specifically in patients suffering from mental illnesses. The Depressive Symptom Inventory Suicidality Subscale (DSI‐SS) is widely used to detect and prevent suicidal ideation. The aim of the present study was to determine optimal cut points for the DSI‐SS in different populations.

We analysed the data of one population‐based sample (n = 532), one outpatient sample (n = 180) and one inpatient sample (n = 244). Internal consistency, convergent validity and optimal cut points according to receiver operating characteristics were calculated.

In all samples, we found excellent item‐total correlations and internal consistencies for the DSI‐SS. Zero‐order correlations between the DSI‐SS and theoretically related constructs showed positive correlation coefficients, ranging from 0.50 to 0.67. The DSI‐SS differentiated well between patients with and without suicide attempts in the population‐based sample, but less so in the inpatient sample and only marginally in the outpatient sample. A bootstrapping analysis showed some variability in the cut points that emerged as optimal, but there was no overlap between the different samples.

The specific cut points that we identified may be used to improve the diagnostic utility of the DSI‐SS and the chance to detect suicidal ideation. Copyright © 2016 John Wiley & Sons, Ltd.

Key Practitioner Message

We developed cut points for the Depressive Symptom Inventory Suicidality Subscale, to improve the early and valid detection of suicidal ideation by this measure.

The cut points that were identified as optimal varied between the samples.

The cut points differentiated well in a non‐clinical sample, but less well in outpatient and inpatient samples.
Distributions of autofluorescence after compensation: Be panglossian, fret not
Authors: Roederer Mario
Published: February 2016

In this technical note, I describe an in silico model of multiparameter fluorescence measurements that takes into account intrinsic cellular autofluorescence and stained dye fluorescence distributions, fluorescence spectrum spillovers, and photon counting statistics. Using this model, it is easy to manipulate spectral variables as well as error terms to understand the impact of each on the distributions of estimated cell‐associated dyes (e.g., conjugated monoclonal antibodies in immunophenotyping). An application of this model was to understand the genesis of “unusual” autofluorescence distributions that occasionally happen in multi‐color immunophenotyping. These unusual distributions show striking correlated patterns (diagonals) for graphs of certain pairs of parameters. Here I show that these arise from combinations of spillover‐spreading from unviewed parameters. While disconcerting to researchers taught to look for diagonals in distributions as heralding improper compensation, these distributions are in fact appropriate. In general, one can ignore the characteristics of cell distributions within the same limits as background (e.g., as proscribed by a fluorescence‐minus‐one, or FMO, control), as there is essentially no information content in that region. Published 2016 International Society for Advancement of Cytometry. This article is a US Government work, and as such, is in the public domain in the USA.
What products are considered psychoactive under New Zealand's legal market for new psychoactive substances (NPS, ‘legal highs’)? Implications for law enforcement and penalties
Authors: Rychert Marta , Wilkins Chris
Published: February 2016

The problem of defining what psychoactive products and substances should be covered by legislation aimed at controlling new psychoactive substances (NPS; ‘legal highs’) is central to the current debate on designing new legislative responses to NPS. In New Zealand, implementation of the Psychoactive Substances Act 2013 (PSA) revealed uncertainties about which psychoactive products are covered by the new regime, with important implications for legal penalties. We reviewed five pieces of legislation which can cover substances with psychoactive properties: PSA, Misuse of Drugs Act (MODA), Food Act, Dietary Supplements Regulations and Medicines Act. Our analysis revealed that a number of psychoactive substances which are not MODA‐scheduled may potentially fall under more than one regulatory regime, including kava, Salvia divinorum, nitrous oxide, 25I‐NBOMe, and 1,3‐dimethylbutylamine (DMBA). For example, kava may be classified as a food, a dietary supplement, a herbal remedy, or a psychoactive substance, depending on how it is presented (including advertising and labelling). There are considerable differences in penalties and regulatory requirements between the different legislative regimes and these may result in unnecessary prosecutions or ‘gaming’ of the system. We discuss a number of ways to more clearly categorize products, including a public schedule of psychoactive substances and products, demarcation criteria based on the quantity of the active ingredient, and demarcation based on ‘discernible intoxication’. Routine use of forensic testing is essential to ensure appropriate prosecutions and penalties. Robust safety standards are also required in legislative regimes exempted from psychoactive substances regime to prevent ‘creative compliance’. Copyright © 2016 John Wiley & Sons, Ltd.
Colour quantitation for chemical spot tests for a controlled substances presumptive test database
Authors: Elkins Kelly M. , Weghorst Alex C. , Quinn Alicia A. , Acharya Subrata
Published: February 2016

Crime scene investigators (CSIs) often encounter unknown powders, capsules, tablets, and liquids at crime scenes, many of which are controlled substances. Because most drugs are white powders, however, visual determination of the chemical identity is difficult. Colourimetric tests are a well‐established method of presumptive drug identification. Positive tests are often reported differently, however, because two analysts may perceive colour or record colourimetric results in different ways. In addition to perceiving colour differently, it is very common for there to be poor visibility conditions (e.g. rain, darkness) while performing these tests, further obscuring the results. In order to address these concerns and to create uniformity in the reporting of on‐site colourimetric test results, this study has evaluated two of the state‐of‐the‐art apps (ColorAssist® and Colorimeter®) for reporting the colour test results quantitatively in red‐green‐blue (RGB) format. The compiled library database of presumptive test results contains over 3300 data points including over 800 unique drug/test combinations. Variations observed between test replicates, from performing a test on different days, recording with a different device type (e.g. iPod Touch, iPhone models 4, 5c, 5s, or 6), and using different quantities of drug are discussed. Overall, the least variation in Euclidian norm was observed using ColorAssist® with the camera light (25.1±22.1) while the variation between replicates and data recorded using different devices was similar. The resulting library is uploaded to a smartphone application aimed to aid in identifying and interpreting suspected controlled substance evidence. Copyright © 2016 John Wiley & Sons, Ltd.
Efficacy of alpha‐calcitonin gene‐related peptide in dilating cerebral arteries: protocol for a systematic review and meta‐analysis of in vivo animal studies
Authors: Flynn L.M.C. , Macleod M.R. , Begg C.J. , Andrews P.J.
Published: February 2016

Aneurysmal subarachnoid haemorrhage (SAH) is a type of stroke causing up to 70% of patients to either die or be dependent on others at six months. Delayed cerebral ischaemia (DCI) is the most important cause of poor outcome after the initial injury. Oral nimodipine is the only pharmaceutical treatment with proven benefits and alternative therapies are needed. There are strong associations between DCI and cerebral vessel narrowing but interventions to treat DCI by improving vessel narrowing have been largely ineffective. Alpha‐calcitonin gene‐related peptide (αCGRP) is a potent microvascular vasodilator which may be effective in treating DCI by preventing cerebral vessel narrowing after SAH. This protocol outlines the methodology for a systematic review and meta‐analysis investigating the effect of αCGRP on cerebral vessel narrowing and neurological outcomes after SAH from in vivo animal studies.
In utero exposure to second‐hand smoke activates pro‐asthmatic and oncogenic miRNAs in adult asthmatic mice
Authors: Xiao Rui , Noël Alexandra , Perveen Zakia , Penn Arthur L.
Published: February 2016

Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)‐challenged adult mice that had been exposed in utero to second‐hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6–19 of pregnancy) to SHS (10 mg/m3) or HEPA‐filtered air. All offspring were sensitized and challenged with OVA (19–23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA‐seq). RNA‐seq identified nine miRNAs that were most significantly up‐regulated by in utero SHS exposure. Among these nine, miR‐155‐5p, miR‐21‐3p, and miR‐18a‐5p were also highly correlated with pro‐asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up‐regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro‐asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross‐referenced miRNA‐mRNA expression profiles and identified 16 tumor suppressor genes that were down‐regulated in the in utero‐exposed offspring and that are predicted targets of the up‐regulated oncomirs. In conclusion, in utero SHS exposure activates pro‐asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA‐challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA‐mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA‐regulated tumor suppressor genes. Environ. Mol. Mutagen. 57:190–199, 2016. © 2016 Wiley Periodicals, Inc.
Differential Neural Correlates of Set‐Shifting in the Bingeing–Purging and Restrictive Subtypes of Anorexia Nervosa: An fMRI Study
Authors: Van Autreve Sara , De. Baene Wouter , Baeken Chris , van Heeringen Kees , Vancayseele Nikita , Vervaet Myriam
Published: February 2016

In this study, possible differences in the neural correlates of set‐shifting abilities between the restrictive (AN‐R) and bingeing/purging (AN‐BP) subtypes of anorexia nervosa have been explored. Three groups of participants performed a set‐shifting task during functional magnetic resonance imaging: patients with AN‐R (N = 16), AN‐BP (N = 13) and healthy control participants (N = 15). As in a typical set‐shifting experiment, participants had to switch between two easy tasks (i.e. ‘Is the presented number odd/even’ or ‘Is the presented number smaller/larger than 5’). The trials in which the task was repeated (repeat trials) were compared with trials in which the task was switched (switch trials). With regards to the level of task performance, no significant group differences could be established. However, when comparing switch specific brain activity across study groups, a stronger activation was found in the insula and the precuneus in AN‐R when compared to AN‐BP and HC. These results suggest that the both subtypes of AN might have different neurobiological correlates, and thus, might benefit from different treatment approaches. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.
Quality of network economics optimisation using service level agreement modelling
Authors: Santos‐Boada Germán , de Almeida Amazonas José Roberto , Solé‐Pareta Josep
Published: February 2016

This paper analyses the relationships between different service level agreement (SLA) components, that is, the different types of quality metrics employed by infrastructure and service providers. We propose that the quality of network economics (QoNE) be used to evaluate the quality of a network path for a given SLA model. Our evaluation indicates the usefulness of the QoNE metric, and it provides a new mechanism for the networking community to address network design problems when incorporating new challenges, such as the Internet of Things. We show how the proposed model can be implemented in software‐defined network architecture applicable to networking technologies that include the interconnection of autonomous systems. Copyright © 2016 John Wiley & Sons, Ltd.
A spectral boundary integral method for inviscid water waves in a finite domain
Authors: Im Jeong‐Sook , Billingham John
Published: February 2016

In this paper, we show how the spectral formulation of Baker, Meiron and Orszag can be used to solve for waves on water of infinite depth confined between two flat, vertical walls, and also how it can be modified to take into account water of finite depth with a spatially varying bottom. In each case, we use Chebyshev polynomials as the basis of our representation of the solution and filtering to remove spurious high‐frequency modes. We show that spectral accuracy can be achieved until wave breaking, plunging or wall impingment occurs in two model problems. Copyright © 2016 John Wiley & Sons, Ltd.
Continuous real‐time slope monitoring of the Ingelsberg in Bad Hofgastein, Austria
Authors: Kieffer D. Scott , Valentin Gerald , Unterberger Klaus
Published: February 2016

The Ingelsberg in Bad Hofgastein, Austria, is a highly hazardous mountain slope in the State of Salzburg. The Ingelsberg exhibits periodic episodes of instability, prompting major efforts to construct rock fall retention basins and safety nets to mitigate risks associated with future slope failures. As the results of traditional slope monitoring have proved rather ambiguous, continuous real‐time monitoring of the Ingelsberg was performed from March 2013 through July 2014. The monitoring was undertaken with a Ground Based Interferometric Synthetic Aperture Radar (GB‐InSAR). The data set of approximately 130, 000 radar scans represent the first long‐term GB‐InSAR measurements made in Austria, and indicate an episodic pseudo‐sheeting failure process, somewhat analogous to the calving of a glacier front. Furthermore, reasonable time of failure predictions for rock fall events having volumes of only several tens of cubic meters could be made from the data set. The GB‐InSAR monitoring provides significant insight regarding the overall slope behavior, failure tendencies, and associated geotechnical hazards of the Ingelsberg.
3D images for digital geological mapping
Authors: Gaich Andreas , Pischinger Gerald
Published: February 2016

3D images combine visual and geometric information making them an obvious source for capturing and characterising rock surfaces especially when there are constrained time and access conditions. By taking photographs with an off‐the‐shelf camera and using modern algorithms from photogrammetry, 3D imaging has become state of the art on many conventional tunnel construction sites. Data is acquired on a daily basis, processed, geologically assessed, and finally stored in a suitable data base. The contribution provides a brief introduction of the technology and its measurement capabilities, as well as a description of the practical application during the construction of the 8 km long Gleinalmtunnel in Austria.
Tunnel monitoring in urban environments
Authors: Rabensteiner Klaus , Chmelina Klaus
Published: February 2016

Urban tunnel projects such as new metro lines face particular challenges. Shallow overburden, difficult (hydro)geological conditions and sensitive buildings in close proximity are risks that often cannot be avoided, demanding large and complex geotechnical monitoring programmes. This paper considers the current situation of tunnel monitoring in urban environments and describes two specific monitoring solutions, one for shafts and one for structures, and emphasises the importance of efficient data management with the assistance of a tunnel information system. Finally, the paper gives an overview of recent research activity and emerging sensing technologies.
InSAR monitoring of tunnel induced ground movements
Authors: Barla Giovanni , Tamburini Andrea , Del Conte Sara , Giannico Chiara
Published: February 2016

This paper introduces InSAR (Interferometric Synthetic Aperture Radar) as an advanced tool for measuring and monitoring surface ground movements over time, with interest in all phases of a tunnel project, both in urban and non‐urban areas. Following a preliminary overview of the technology used to compile radar images of the earth's surface, the multi‐image techniques (Persistent Scatterers Interferometry, PSI) and the InSAR algorithm (SqueeSAR) are briefly outlined. Two examples of InSAR data applied to tunnelling projects are presented. In the first case, the integration of InSAR surface measurements into monitoring by conventional methods is discussed as a tool for providing useful information to study the relationship between tunnelling and surface settlements. In the second case, the temporal evolution of ground displacements provided by SqueeSAR is applied in order to understand the link between tunnel excavation and surface movements, along a slope under passed by two large tunnels.
Trade‐off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns
Authors: Martínez Martin , Valencia Miguel , Vidorreta Marta , Luis Elkin O. , Castellanos Gabriel , Villagra Federico , Fernández‐Seara Maria A. , Pastor Maria A.
Published: February 2016

The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade‐off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom‐built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti‐phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722–1737, 2016. © 2016 Wiley Periodicals, Inc.
Individual differences in in vitro and in vivo metabolic clearances of the antipsychotic drug olanzapine from non‐smoking and smoking Japanese subjects genotyped for cytochrome P4502D6 and flavincontaining monooxygenase 3
Authors: Okubo Maho , Narita Momoko , Murayama Norie , Akimoto Youichi , Goto Akiko , Yamazaki Hiroshi
Published: February 2016

Objective

The antipsychotic olanzapine is reportedly metabolized by inducible human cytochrome P450 (CYP) 1A2 and variable copy‐number CYP2D6 and polymorphic flavin‐containing monooxygenase 3 (FMO3) in different pathways. We investigated individual differences in the metabolite formation and clearance of olanzapine in vitro and in vivo.

Methods

Human liver microsomal olanzapine oxidation activities were evaluated, and plasma concentrations of olanzapine were determined in 21 Japanese patients (mean age: 50 years, range: 32–69 years, 14 male and 7 female, including 6 smokers) genotyped for CYP2D6 (*1, *5, and *10) and FMO3 (E158K, C197fsX, R205C, V257M, E308G, and R500X).

Results

Furafylline (a CYP1A2 inhibitor), quinidine (a CYP2D6 inhibitor), and heat treatment (inactivates FMO3) suppressed liver microsomal metabolic clearance of olanzapine by approximately 30%. Olanzapine N‐demethylation and N‐oxygenation were found to be catalyzed by CYP1A2 and CYP2D6 and by CYP2D6 and FMO3, respectively, in experiments using liver microsomes and recombinant enzymes. Plasma concentrations and clearance of olanzapine were not affected by CYP2D6 or FMO3 genotypes or smoking behavior.

Conclusions

Olanzapine clearance was not affected by CYP2D6 or FMO3 genotypes or smoking behavior as a single factor under the present conditions because olanzapine clearance is mediated by multiple enzymes involved in two major and one minor pathways. Copyright © 2016 John Wiley & Sons, Ltd.