bluuebunny/crossref_metadata_2025 huggingface dataset:
KIF21A influences breast cancer metastasis and survival
Authors: Lucanus Anton J. , King Victoria , Yip George W.
Published: December 2016

Breast cancer pathogenesis is known to be propagated by the differential expression of a group of proteins called the Kinesin Superfamily (KIFs), which are instrumental in the intracellular transport of chromosomes along microtubules during mitosis. During mitosis, KIFs are strictly regulated through temporal synthesis so that they are only present when needed. However, their misregulation may contribute to uncontrolled cell growth due to premature sister chromatid separation, highlighting their involvement in tumorigenesis. One particular KIF, KIF21A, was recently found to promote the survival of human breast cancer cellsin vitro. However, how KIF21A influences other cancerous phenotypes is currently unknown. This study therefore aimed to consolidate thein vitrorole of KIF21A in breast cancer metastasis, while also analysing KIF21A expression in human breast cancer tissue to determine its prognostic value. This was achieved by silencing KIF21A in MCF-7 and MDA-MB-231 breast cancer cell lines via siRNA transfection. Migration, invasion, proliferation, and adhesion assays were then performed to measure the effects of KIF21A silencing on oncogenic behaviour. Immunohistochemistry was also conducted in 263 breast cancer tissue samples to compare KIF21A expression levels against various prognostic outcomes and clinicopathological parameters. KIF21A knockdown reduced cell migration (by 42.8% [MCF-7] and 69.7% [MDA-MB-231]) and invasion (by 72.5% [MCF-7] and 42.5% [MDA-MB-231]) in both cell lines, but had no effect on adhesion or proliferation, suggesting that KIF21A plays an important role in the early stages of breast cancer metastasis. Unexpectedly however, KIF21A was shown to negatively correlate with various pro-malignant clinicopathological parameters, including tumour size and histological grade, and high KIF21A expression predicted better breast cancer survival (hazard ratio = 0.45), suggesting that KIF21A is a tumour suppressor. The conflicting outcomes ofin vitroandin vivodata may be due to the possible multi-functionality of KIF21A or study limitations, and means no definitive conclusions can be drawn about the role of KIF21A in breast cancer. This warrants further investigation, which may prove pivotal to the development of novel chemotherapeutic strategies to mediate KIF21A’s function and enhance prognostic outcomes.
The centrosome is a selective phase that nucleates microtubules by concentrating tubulin
Authors: Woodruff Jeffrey B. , Gomes Beatriz Ferreira , Widlund Per O. , Mahamid Julia , Hyman Anthony A.
Published: December 2016

Centrosomes are non-membrane-bound compartments that nucleate microtubule arrays. They consist of nanometer-scale centrioles surrounded by a micron-scale, dynamic assembly of protein called the pericentriolar material (PCM). To study how PCM forms a spherical compartment that nucleates microtubules, we reconstituted PCM-dependent microtubule nucleationin vitrousing recombinantC.elegansproteins. We found that macromolecular crowding drives phase separation of the key PCM scaffold protein SPD-5 into spherical droplets that morphologically and dynamically resemblein vivoPCM. These SPD-5 droplets recruited the microtubule polymerase ZYG-9 (XMAP215 homologue) and the microtubule-stabilizing protein TPXL-1 (TPX2 homologue). Together, these three proteins concentrated tubulin ~4- fold over background, which was sufficient to reconstitute nucleation of microtubule astersin vitro.Our results suggest thatin vivoPCM is a selective phase that organizes microtubule arrays through localized concentration of tubulin by microtubule effector proteins.

One Sentence Summary

Phase separation ofC. eleganscentrosome proteins drive the formation of micron-sized microtubule organizing centers.
Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques
Authors: Prall Trent M. , Graham Michael E. , Karl Julie A. , Wiseman Roger W. , Ericsen Adam J. , Raveendran Muthuswamy , Harris R. Alan , Muzny Donna M. , Gibbs Richard A. , Rogers Jeffrey , O’Connor David H.
Published: December 2016

Killer cell Immunoglobulin-like Receptors (KIRs) modulate disease progression of pathogens including HIV, malaria, and hepatitis C. Cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens and so considerable effort has been put into characterizing their KIR genetics. However, previous studies have relied on cDNA cloning and Sanger sequencing that lacks the throughput of current sequencing platforms. In this study, we present a high throughput, full-length allele discovery method utilizing PacBio circular consensus sequencing (CCS). We also describe a new approach to Macaque Exome Sequencing (MES) and the development of the Rhexome1.0, an adapted target capture reagent that includes macaque-specific capture probesets. By using sequence reads generated by whole genome sequencing (WGS) and MES to inform primer design, we were able to increase the sensitivity of KIR allele discovery. We demonstrate this increased sensitivity by defining nine novel alleles within a cohort of Mauritian cynomolgus macaques (MCM), a geographically isolated population with restricted KIR genetics that was thought to be completely characterized. Finally, we describe an approach to genotyping KIRs directly from sequence reads generated using WGS/MES reads. The findings presented here expand our understanding of KIR genetics in MCM by associating new genes with all eight KIR haplotypes and demonstrating the existence of at least oneKIR3DSgene associated with every haplotype.
Aspace-jumpderivation for non-local models of cell-cell adhesion and non-local chemotaxis
Authors: Buttenschön Andreas , Hillen Thomas , Gerisch Alf , Painter Kevin J.
Published: December 2016

Cellular adhesion provides one of the fundamental forms of biological interaction between cells and their surroundings, yet the continuum modelling of cellular adhesion has remained mathematically challenging. In 2006, Armstronget al.proposed a mathematical model in the form of an integro-partial differential equation. Although successful in applications, a derivation from an underlying stochastic random walk has remained elusive. In this work we develop a framework by which non-local models can be derived from a space-jump process. We show how the notions of motility and a cell polarization vector can be naturally included. With this derivation we are able to include microscopic biological properties into the model. We show that particular choices yield the original Armstrong model, while others lead to more general models, including a doubly non-local adhesion model and non-local chemotaxis models. Finally, we use random walk simulations to confirm that the corresponding continuum model represents the mean field behaviour of the stochastic random walk.
Large-scale reduction of the Bacillus subtilis genome: consequences for the transcriptional network, resource allocation, and metabolism
Authors: Reuß Daniel R. , Altenbuchner Josef , Mäder Ulrike , Rath Hermann , Ischebeck Till , Sappa Praveen Kumar , Thürmer Andrea , Guérin Cyprien , Nicolas Pierre , Steil Leif , Zhu Bingyao , Feussner Ivo , Klumpp Stefan , Daniel Rolf , Commichau Fabian M. , Völker Uwe , Stülke Jörg
Published: December 2016

Understanding cellular life requires a comprehensive knowledge of the essential cellular functions, the components involved, and their interactions. Minimized genomes are an important tool to gain this knowledge. We have constructed strains of the model bacterium, Bacillus subtilis, whose genomes have been reduced by ∼36%. These strains are fully viable, and their growth rates in complex medium are comparable to those of wild type strains. An in-depth multi-omics analysis of the genome reduced strains revealed how the deletions affect the transcription regulatory network of the cell, translation resource allocation, and metabolism. A comparison of gene counts and resource allocation demonstrates drastic differences in the two parameters, with 50% of the genes using as little as 10% of translation capacity, whereas the 6% essential genes require 57% of the translation resources. Taken together, the results are a valuable resource on gene dispensability in B. subtilis, and they suggest the roads to further genome reduction to approach the final aim of a minimal cell in which all functions are understood.
Central bank capitalism: Visible hands, audible voices
Authors: Holmes Douglas R.
Published: December 2016

Central bankers can create money out of thin air; they can stop the misbehaviour of some of the most powerful institutions in the contemporary world – financial markets – in a matter of hours, if not minutes. In the era of central bank capitalism virtually every aspect of economic life has come under the sway of financial and monetary concerns. The author has focused on a particularly uncanny aspect of this regime: how central bankers endow the future with discernible features that we – the public – can reflect and act upon, animating or curtailing our propensity to produce, consume, borrow, and lend. Central bankers – rather than predicting the future – seek to create elements of a tractable future. They do this with words. They use language to sustain not merely the ideas that animate our economic future, but also the structures of feeling, the sentiments, and expectations that make them real. This article examines a series of communicative experiments that transformed the dynamics of contemporary capitalism, imparting its powerful capabilities to the visible hands and audible voices of a tiny group of government appointees – central bankers.
Islamizing finance: From magical capitalism to a spiritual economy
Authors: Rudnyckyj Daromir
Published: December 2016

Anthropological analyses of the assemblage of religious practice and economic action have often been viewed as evidence of mystification and have focused on the ‘occult’ dimensions of late capitalism. In contrast, this article approaches the magic of capitalism not in terms of occult or millennial practices, but rather as the tricks and sleight of hand techniques deployed by economic experts. The article describes how the initial iteration of Islamic finance in Malaysia relied on what experts refer to as ‘tricks’ (hiyal) – legal stratagems that transformed impermissible contracts into ones capable of being deemed permissible by Islamic scholars. The article describes how today, experts are seeking to reform Islamic finance in Malaysia by creating a spiritual economy that moves away from a regime based on tricks to one based on eliciting the ethical practices conducive to neoliberalism: entrepreneurship, risk calculation, and cost‐benefit analysis. In so doing, the article argues that the spiritual economy of Islamic finance seeks to create a regime of production and capital circulation grounded in the ethical principles and ascetic pieties of neoliberal Islam.
Magical contracts, numinous capitalism
Authors: Westbrook David A.
Published: December 2016

Much of US social reality is constructed through contractual rituals, typically thought to be words that create enforceable relations. Such relations are backed by the power of the state and are said to exist on some plane above the empirical. Politically, we speak of a social contract. Economically, contracts lie at the heart of markets, and thus of a commercial society. But just how do individuals use words that construct a suprasensible reality which third parties must respect? Why do some words become ‘binding’, and not others? Such questions have long vexed legal scholars who have been candid, if not comfortable, with the ‘metaphysical’ character of contract law and its complex, and shifting, invocation of a suprasensible social order. It is often said that this social order is founded on the autonomous individual with the power to bind herself (liberalism). Contracts thus not only articulate social relations, they legitimate such relations as something done by and among the parties. As contract law and jurisprudence develop, however, the individual becomes ever more clearly subordinate, i.e. the imaginary of the individual as an autonomous agent who somehow ‘makes’ the contract, who acts upon the social with her words, becomes increasingly difficult to sustain. The magic of contract still works; commercial society still knits itself. But the belief that individuals make the law, rather than the other way around, comes to seem naïve. By extension, the social must still be legitimate (what alternative is there?), but its legitimacy is hardly, if at all, derived from its liberal character. Instead, liberalism emerges as the way law presents itself, and the individual with whom we thought we began emerges as a somewhat disingenuous representation of contemporary law.
The magic of making money: A cultural flow perspective on profit
Authors: Urban Greg
Published: December 2016

Conceptualized in terms of rational calculation and market logic, entrepreneurship appears as a straightforward matter of reckoning risks and rewards, assessing the prospects for profit. When viewed through an ethnographic lens, however, more mysterious – even ‘magical’ – aspects come into focus. This article explores the magical aspects through three case studies, each revealing a distinct process: symbolic efficacy, the conversion of words into things, and the ability to peer into the future. While exposing these otherwise hidden aspects, the article simultaneously explores a view of profit as arising from the capture – in different ways – of freely flowing, non‐commoditized culture. The entrepreneur taps into cultural flows that are propelled by the force of interest, and, by capturing the flows, turns the culture into commodities capable of yielding profit. In these cases we glimpse the truth of Marcel Mauss's claim many years ago: ‘Though we may feel ourselves to be very far removed from magic, we are still very much bound up with it’ (Mauss 1972: 178).
Introducing ‘Young Minds Matter’
Authors: Hafekost Jennifer , Johnson Sarah , Lawrence David , Sawyer Michael , Ainley John , Mihalopoulos Cathrine , Zubrick Stephen R.
Published: December 2016

Young Minds Matter: The second Australian Child and Adolescent Survey of Mental Health and Wellbeing provides updated national prevalence estimates of mental disorders in children and adolescents and measures the burden and impact of these disorders and the use of services and unmet need for services in the health and education sectors. The field work for Young Minds Matter included face‐to‐face interviews with the primary carer of 6,310 children and adolescents aged 4–17 years who were randomly selected from across Australia. This article describes the survey, the response rates achieved and the representativeness of the sample.
Do Pro‐Poor Schools Reach Out to the Poor? Location Choice of BRAC and ROSC Schools in Bangladesh
Authors: Asadullah M. Niaz
Published: December 2016

Location choice of ‘one teacher, one classroom’ non‐formal primary schools pioneered by Bangladesh Rural Advancement Committee (BRAC) is studied vis‐à‐vis its replication under government‐managed Reaching‐Out‐of‐School (ROSC) project using school Census data. Both types of schools have a statistically significant presence in poor sub‐districts within a district. However, BRAC schools avoid pockets that lack public infrastructure and suffer from female illiteracy, while ROSC schools have greater presence in regions that have poor access to cities and roads. Moreover, ROSC schools better target regions that are under‐served by government schools; the opposite is true for BRAC schools and state‐recognised madrasas.
Birds of a Feather Flock Together: Correlation in BMI Categories in Long‐Term Relationships
Authors: Brown Heather
Published: December 2016

This is the first article to explore partner correlations across Body Mass Index (BMI) categories for couples in long‐term, stable relationships using data from the Household, Income and Labour Dynamics in Australia Survey 2006–2011. The moderating effects of three hypotheses on this correlation are tested: (i) selection; (ii) relationship stability; and (iii) social obligation or environment. The results show gender‐asymmetric effects in the correlation in BMI categories. Selection explains the majority of the correlation for men and all of the correlation in BMI categories for women. Some evidence of variables related to stability and social obligation are significantly associated with weight outcomes for men.
Ageing, Death and Life Satisfaction: Evidence from the Household, Income and Labour Dynamics in Australia Survey
Authors: Wooden Mark , Li Ning
Published: December 2016

Does subjective well‐being rise or fall with age or are most people, especially those in old age, sufficiently resilient that levels of subjective well‐being are very stable over the life course? This article uses longitudinal data from the Household, Income and Labour Dynamics in Australia Survey and finds that self‐reported life satisfaction among a large sample of Australians does vary over time. Nevertheless, over much of adulthood—between ages 25 and 65 years—the range in this variation is very small. As people enter old age, however, life satisfaction falls quite sharply. Furthermore, this fall does not appear to be entirely driven by mortality, with the decline beginning many years prior to death.
Australian Superannuation: The Current State of Play
Authors: Chomik Rafal , Piggott John
Published: December 2016

This article focuses on the challenges facing superannuation, the income replacement pillar of Australia's retirement income system, as it matures. We discuss four questions: In an era when households are making critical and complex choices that most have never previously confronted, how should policy‐makers and private providers guide choices? How should superannuation be taxed? How should the drawdown phase be structured? And to what extent will the Superannuation Guarantee be able to meet the objective of providing retirement income to substitute or supplement the age pension? This article attempts to provide perspective on each of the issues and concludes with a statement of research need.
Preliminary report on the archaeobotanical investigations at Tell Abraq with special attention to chaff impressions in mud brick
Authors: Willcox George , Tengberg Margareta
Published: December 2016

Examination of impressions from chaff‐tempered mud brick proved rewarding, given the poor preservation of carbonised seed and grain material at Tell Abraq. Individual chaff elements were found to be recognisable from the impressions and it was shown that naked wheat and barley chaff were used as a tempering medium. Charcoal samples indicate that two species of mangrove were present, one of which is no longer found in the area. Tamarisk and Ziziphus were also present. Date charcoal was common. This study remains preliminary, and further sampling and analyses have been planned for the future.
Adolescent drinking—a touch of social class?
Authors: Pape Hilde , Norström Thor , Rossow Ingeborg
Published: December 2016

Aims

To estimate whether parental socio‐economic status (SES) is associated with adolescent drinking, and the degree to which a possible association may be accounted for by various parental factors.

Design and setting

Cross‐sectional Norwegian school survey from 2006 (response rate: 86%).

Participants

Students aged 13–14 years (n = 5797), 15–16 years (n = 6613) and 17–18 years (n = 5351), of whom 51% were girls.

Measurements

Parents' education was our main SES indicator, and we distinguished between low (7%) and middle/high (93%) educational level. The outcomes comprised past‐year drinking and intoxication. We also applied measures on general parenting, parents' alcohol‐related permissiveness and parental intoxication. The main analyses were conducted using Poisson regression.

Findings

Parents' education had no statistically significant impact on alcohol use among the 17–18‐year‐olds, while 13–16‐year‐olds with low educated parents had an elevated relative risk (RR) of both drinking [RR = 1.21, 95% confidence interval (CI) = 1.13–1.29] and intoxication (RR = 1.32, 95% CI = 1.21–1.44). The RRs became statistically insignificant when including all the parental factors as covariates in the regression models. Among adolescents who had consumed alcohol, low parental education was related to more frequent drinking (RR = 1.24, 95% CI = 1.11–1.38) and intoxication episodes (RR = 1.42, 95% CI = 1.22–1.66). Again, the RRs became statistically insignificant when we accounted for all the parental factors. This pattern was replicated when we applied an alternative indicator for low parental SES.

Conclusions

Adolescent drinking in Norway appears to be related inversely to parents' social standing. The elevated risk of low socio‐economic status vanishes when general parenting, alcohol‐related parental permissiveness and parents' drinking are accounted for.
Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists
Authors: Atkinson Victoria , Long Georgina V. , Menzies Alexander M. , McArthur Grant , Carlino Matteo S. , Millward Michael , Roberts‐Thomson Rachel , Brady Benjamin , Kefford Richard , Haydon Andrew , Cebon Jonathan
Published: December 2016

BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug‐related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT). We provide guidance on managing adverse events likely to arise during treatment with combination BRAF and MEK inhibition with CombiDT: pyrexia, skin conditions, fatigue; and discuss management of CombiDT during surgery and radiotherapy. By improving tolerability and in particular preventing unnecessary treatment cessations or reduction in drug exposure, best outcomes can be achieved for patients undergoing CombiDT therapy.
Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation
Authors: Knops Noël , Herman Jean , van Dyck Maria , Ramazani Yasaman , Debbaut Edward , van Damme‐Lombaerts Rita , Levtchenko Elena , van den Heuvel Lambertus P. , Fieuws Steffen , Kuypers Dirk
Published: December 2016

Aims

Despite longstanding recognition of significant age‐dependent differences in drug disposition during childhood, the exact course and the underlying mechanisms are not known. Our aim was to determine the course and determinants of individual relative dose requirements, during long‐term follow‐up in children on tacrolimus.

Methods

This was a cohort study in a tertiary hospital with standardized annual pharmacokinetic (PK) follow‐up (AUC0–12hr) in recipients of a renal allograft (≤19 years), between 1998 and 2015. In addition, the presence of relevant pharmacogenetic variants was determined. The evolution of dose‐corrected exposure was evaluated using mixed models.

Results

A total of 184 PK visits by 43 children were included in the study (median age: 14.6). AUC0–12h corrected for dose per kg demonstrated a biphasic course: annual increase 4.4% (CI: 0.3–8.7%) until ±14 years of age, followed by 13.4% increase (CI 8.7–18.3%). Moreover, exposure corrected for dose per m2 proved stable until 14 years (+0.8% annually; CI: −3.0 to +4.8%), followed by a steep increase ≥14 years (+11%; CI: 7.0–16.0%). Analysis according to bone maturation instead of age demonstrated a similar course with a distinct divergence at TW2: 800 (P = 0.01). Genetic variation in CYP3A4, CYP3A5, and CYP3A7 was associated with altered dose requirements, independent of age.

Conclusions

Children exhibit a biphasic course in tacrolimus disposition characterized by a high and stable drug clearance until a specific phase in pubertal development (TW2: 800 at age: ±14 years), followed by an important decline in relative dose requirements thereafter. Pharmacogenetic variation demonstrated an age/puberty independent effect. We suggest a critical reappraisal of current paediatric dosing algorithms for tacrolimus and drugs with a similar disposition.
Disaster resilience: what it is and how it can engender a meaningful change in development policy
Authors: Keating Adriana , Campbell Karen , Mechler Reinhard , Magnuszewski Piotr , Mochizuki Junko , Liu Wei , Szoenyi Michael , McQuistan Colin
Published: December 2016

Disasters pose a growing threat to sustainable development. Disaster risk management efforts have largely failed to arrest the underlying drivers of increased global risk: uncontrolled urbanization and proliferation of assets in hazardous areas. Resilience provides an opportunity to confront the social‐ecological foundations of risk and development; yet it has been vaguely conceptualized, without offering a concrete approach to operationalization. We propose a conceptualization of disaster resilience centred on well‐being: ‘The ability of a system, community or society to pursue its social, ecological and economic development objectives, while managing its disaster risk over time in a mutually reinforcing way.’We present a conceptual framework for understanding the interconnections between disasters and development, and outline how it is being operationalized in practice.
IL‐22‐induced miR‐122‐5p promotes keratinocyte proliferation by targeting Sprouty2
Authors: Jiang Meng , Ma Weiyuan , Gao Yumei , Jia Kun , Zhang Yan , Liu Haidong , Sun Qing
Published: December 2016

Psoriasis is a common inflammatory skin disease, but the exact pathogenesis is largely unknown. Interleukin‐22 (IL‐22) has demonstrated its vital role in T‐cell‐mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. Here, we showed the differentially expressed miRNAs and their potential targets in HaCaT cells stimulated by IL‐22 using miRNA and mRNA microarrays. We revealed a total of 20 significantly changed (more than twofold) miRNAs in HaCaT cells and validated the results with quantitative reverse transcriptase PCR (qRT‐PCR). We demonstrated that miR‐122‐5p was up‐regulated both in HaCaT cells stimulated by IL‐22 and in psoriatic lesions. Then, we aimed to investigate the biological roles and potential mechanism of miR‐122‐5p in keratinocytes. As a result, CCK‐8 assay indicated that overexpression of miR‐122‐5p in keratinocytes promoted proliferation and conversely inhibition of endogenous miR‐122‐5p suppressed proliferation. According to the microarray analysis, we assumed that Sprouty2 (Spry2), a negative regulator of extracellular signal regulated kinase/mitogen‐activated protein kinase signalling pathway, was a direct target gene of miR‐122‐5p. We found that the staining of Spry2 in cytoplasm was mainly localized in both basal and suprabasal layers of epidermis and showed a markedly decreased expression in psoriasis than in normal control by immunohistochemistry. Luciferase reporter and Western blot assays in HaCaT cells demonstrated that Spry2 was a direct target gene of miR‐122‐5p. In conclusion, IL‐22‐induced miR‐122‐5p promotes keratinocyte proliferation possibly by downregulating the expression of Spry2 thus playing important roles in the pathogenesis of psoriasis.
Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans
Authors: Fuentes‐Duculan Judilyn , Bonifacio Kathleen M. , Suárez‐Fariñas Mayte , Kunjravia Norma , Garcet Sandra , Cruz Tristan , Wang Claire Q. F. , Xu Hui , Gilleadeau Patricia , Sullivan‐Whalen Mary , Tirgan Michael H. , Krueger James G.
Published: December 2016

Keloids are benign fibroproliferative tumors more frequently found among African Americans. Until now, keloid etiopathogenesis is not fully understood. To characterize keloids in African Americans, we performed transcriptional profiling of biopsies from large chronic keloids, adjacent non‐lesional (NL) skin (n=3) and a newly formed keloid lesion using Affymetrix HGU133 2.0 plus arrays. Quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry (IHC) staining were performed to confirm increased expression of relevant genes. We identified 1202 upregulated and 961 downregulated differentially expressed genes (DEGs) between keloid and NL skin; 1819 up‐ and 1867 downregulated DEGs between newly formed keloid and NL skin; and 492 up‐ and 775 downregulated DEGs between chronic and newly formed keloid (fold change >2, false discovery rate <0.05). Many of the top upregulated DEGs between chronic keloid and NL skin and between newly formed keloid and NL skin are involved in bone/cartilage formation including Fibrillin 2 (FBN2), Collagen type X alpha 1, Asporin (ASPN), Cadherin 11 (CDH11), Bone morphogenic protein 1 (BMP1), Secreted phosphoprotein 1 and Runt‐related transcription factor 2 (RUNX2). qRT‐PCR confirmed significant (P<.05) upregulation of BMP1, RUNX2, CDH11 and FBN2 in chronic keloid compared to NL skin. IHC staining showed increased protein expression of ASPN, CDH11, BMP1 and RUNX2 on chronic and newly formed keloid compared to NL skin. Our study shows that large keloids in African Americans represent a dysplasia of cutaneous connective tissue towards immature cartilage or bone differentiation. The phenotype is potentially regulated by overexpression of RUNX2. This knowledge may give insights to guide the development of better treatment for the disease in the future.
Phylogenetic profiling and gene expression studies implicate a primary role of PSORS1C2 in terminal differentiation of keratinocytes
Authors: Abbas Zadeh Salman , Mlitz Veronika , Lachner Julia , Golabi Bahar , Mildner Michael , Pammer Johannes , Tschachler Erwin , Eckhart Leopold
Published: December 2016

PSORS1C2 is a gene located between coiled‐coil alpha‐helical rod protein 1 (CCHCR1) and corneodesmosin (CDSN) within the psoriasis susceptibility locus 1 (PSORS1). Here, we performed a comparative genomics analysis of the as‐yet incompletely characterized PSORS1C2 gene and determined its expression pattern in human tissues. In contrast to CCHCR1, which is common to all vertebrates investigated, PSORS1C2 and CDSN are present exclusively in mammals, indicating that the latter genes have originated after the evolutionary divergence of mammals and reptiles. CDSN is conserved in aquatic mammals, whereas PSORS1C2 orthologs contain gene‐inactivating frame shift mutations in whales and dolphins, in which the epidermal differentiation programme has degenerated. Reverse‐transcription PCR screening demonstrated that, in human tissues, PSORS1C2 is expressed principally in the epidermis and weakly in the thymus. PSORS1C2 mRNA was strongly upregulated during terminal differentiation of human keratinocytes in vitro. Immunohistochemistry revealed exclusive expression of PSORS1C2 in the granular layer of the epidermis and in cornifying epithelial cells of Hassall's corpuscles of the thymus. In summary, our results identify PSORS1C2 as a keratinocyte cornification‐associated protein that has originated in evolutionarily basal mammals and has undergone gene inactivation in association with the loss of the skin barrier function in aquatic mammals.
Superparamagnetic iron oxide‐enhanced magnetic resonance imaging is useful in predicting malignant potential of vascular transformation of hypointense hypovascular nodules on gadoxetic acid‐enhanced magnetic resonance imaging
Authors: Tanaka Yoshiaki , Nakazawa Takahide , Inoue Tomoyoshi , Yamane Keiko , Kubota Kousuke , Uojima Haruki , Takada Juichi , Okuwaki Yusuke , Hidaka Hisashi , Shibuya Akitaka , Kokubu Shigehiro , Matsunaga Keiji , Koizumi Wasaburo
Published: December 2016

Aim

To examine whether superparamagnetic iron oxide (SPIO)‐enhanced magnetic resonance imaging (MRI) can be used to assess the malignant potential of hepatic hypovascular nodules showing hypointensity during the hepatobiliary phase (HBP) on gadoxetic acid (Gd–EOB–DTPA)‐enhanced MRI.

Methods

The study included 42 patients with chronic liver disease who had small hypovascular nodules (5–15 mm) showing hypointensity during the HBP on Gd–EOB–DTPA‐enhanced MRI. The SPIO‐enhanced T2‐weighted MRI analyzed whether the signal intensity of each nodule was high. Nodules were prospectively followed up until hypervascularization by periodic Gd–EOB–DTPA‐enhanced MRI. Initial MRI findings and clinical variables were used to analyze predictive factors for hypervascularization.

Results

We analyzed 77 nodules, of which 19 (25%) showed hypervascularization during the observation period. The cumulative rates for hypervascularization were 11% and 22% at 1 and 2 years, respectively. Hyperintensity was observed in 12 nodules (16%) on SPIO‐enhanced T2‐weighted MRI; among these, 7 (58%) showed hypervascularization, whereas 12 (18%) of the remaining 65 nodules without hyperintensity showed hypervascularization (P = 0.007). A Cox model revealed that independent predictors of hypervascularization included hyperintense nodules on SPIO‐enhanced MRI (P < 0.001). The cumulative rates for hypervascularization in hyperintense nodules on SPIO‐enhanced MRI were 52% at 1 year, whereas these rates were 3% for non‐hyperintense nodules.

Conclusion

Superparamagnetic iron oxide‐enhanced MRI is useful for predicting the malignant potential of vascular transformation of hypovascular nodules with hypointensity observed in the HBP on Gd–EOB–DTPA‐enhanced MRI.
Drug‐induced nephropathies
Authors: Paueksakon Paisit , Fogo Agnes B
Published: December 2016

Drugs are associated frequently with the development of various types of acute and chronic kidney diseases. Nephrotoxicity is associated most commonly with injury in the tubulointerstitial compartment manifested as either acute tubular injury or acute interstitial nephritis. A growing number of reports has also highlighted the potential for drug‐induced glomerular disease, including direct cellular injury and immune‐mediated injury. Recognition of drug‐induced nephropathies and rapid discontinuation of the offending agents are critical to maximizing the likelihood of renal function recovery. This review will focus on the pathology and pathogenesis of drug‐induced acute interstitial nephritis and drug‐induced glomerular diseases.
Using field photography to study avian moult
Authors: Vieira Bianca P. , Furness Robert W. , Nager Ruedi G.
Published: December 2016

Methods to obtain moult data from wild birds have not changed much over the last century and most studies still depend on checking museum specimens or capturing birds. Here we assess the applicability of systematic field photography for detecting and scoring moult in adult Black Skimmers Rynchops niger from southern Brazil. Moult data extracted from photographs have a high within‐ (RGLMM = 0.98) and between‐observer repeatability (RGLMM = 0.97) and show very good fit to current Underhill–Zucchini moult models (R2 = 0.75). Photography offers the advantages of being less invasive, requiring less equipment and human effort, being feasible in areas where captures may not be possible, and causing less disturbance, so enhancing the number of sampled individuals.
Levels of extra‐pair paternity are associated with parental care in penduline tits (Remizidae)
Authors: Ball Alex D. , van Dijk René E. , Lloyd Penn , Pogány Ákos , Dawson Deborah A. , Dorus Steve , Bowie Rauri C. K. , Burke Terry , Székely Tamás
Published: December 2016

In most passerine birds, individuals attempt to maximize their fitness by providing parental care while also mating outside their pair bond. A sex‐specific trade‐off between these two behaviours is predicted to occur, as the fitness benefits of extra‐pair mating differ between the sexes. We use nest observations and parentage analysis to reveal a negative association between male care and the incidence of extra‐pair paternity across three species of penduline tit (Remizidae). This provides evidence of a trade‐off between these two behaviours, possibly due to the devaluing of paternal care by extra‐pair offspring.
Diagnostic Profiles: A Standard Setting Method for Use With a Cognitive Diagnostic Model
Authors: Skaggs Gary , Hein Serge F. , Wilkins Jesse L. M.
Published: December 2016

This article introduces the Diagnostic Profiles (DP) standard setting method for setting a performance standard on a test developed from a cognitive diagnostic model (CDM), the outcome of which is a profile of mastered and not‐mastered skills or attributes rather than a single test score. In the DP method, the key judgment task for panelists is a decision on whether or not individual cognitive skill profiles meet the performance standard. A randomized experiment was carried out in which secondary mathematics teachers were randomly assigned to either the DP method or the modified Angoff method. The standard setting methods were applied to a test of student readiness to enter high school algebra (Algebra I). While the DP profile judgments were perceived to be more difficult than the Angoff item judgments, there was a high degree of agreement among the panelists for most of the profiles. In order to compare the methods, cut scores were generated from the DP method. The results of the DP group were comparable to the Angoff group, with less cut score variability in the DP group. The DP method shows promise for testing situations in which diagnostic information is needed about examinees and where that information needs to be linked to a performance standard.
Asymptotic Standard Errors of Observed‐Score Equating With Polytomous IRT Models
Authors: Andersson Björn
Published: December 2016

In observed‐score equipercentile equating, the goal is to make scores on two scales or tests measuring the same construct comparable by matching the percentiles of the respective score distributions. If the tests consist of different items with multiple categories for each item, a suitable model for the responses is a polytomous item response theory (IRT) model. The parameters from such a model can be utilized to derive the score probabilities for the tests and these score probabilities may then be used in observed‐score equating. In this study, the asymptotic standard errors of observed‐score equating using score probability vectors from polytomous IRT models are derived using the delta method. The results are applied to the equivalent groups design and the nonequivalent groups design with either chain equating or poststratification equating within the framework of kernel equating. The derivations are presented in a general form and specific formulas for the graded response model and the generalized partial credit model are provided. The asymptotic standard errors are accurate under several simulation conditions relating to sample size, distributional misspecification and, for the nonequivalent groups design, anchor test length.
Further Study of the Choice of Anchor Tests in Equating
Authors: Trierweiler Tammy J. , Lewis Charles , Smith Robert L.
Published: December 2016

In this study, we describe what factors influence the observed score correlation between an (external) anchor test and a total test. We show that the anchor to full‐test observed score correlation is based on two components: the true score correlation between the anchor and total test, and the reliability of the anchor test. Findings using an analytical approach suggest that making an anchor test a miditest does not generally maximize the anchor to total test correlation. Results are discussed in the context of what conditions maximize the correlations between the anchor and total test.
Juvenile Competency and Pretrial Due Process: A Call for Greater Protections in Massachusetts for Juveniles Residing in Procedural Purgatory
Authors: Rapisarda Mark , Kaplan Wendy J.
Published: December 2016

While juvenile courts continue to balance and reevaluate the dual goals of community safety and rehabilitation of youth, juveniles who are not competent to stand trial have been left without sufficient procedural protections. This paper examines Massachusetts’ approach to juvenile competency, due process, and pretrial procedure, within a national context. The inadequacies of the Massachusetts juvenile competency laws are not unique. Currently there are nineteen states that either entirely lack juvenile‐specific competency legislation or merely incorporate inapposite adult criminal statutes and standards into the juvenile context—making it difficult or impossible for those juvenile courts to dismiss or divert a delinquency petition following an incompetency finding. Massachusetts and states similarly situated should adopt explicit statutory language to delineate the basis for a juvenile incompetency finding and the grounds for dismissing delinquency complaints pretrial after an incompetency finding has been made. This paper proposes that Massachusetts adopt a timeline for effecting such dismissals based in part on the amount of time a juvenile could face if committed to the juvenile correctional authority following an adjudication of delinquency. The paper also recommends best practices of states that are pioneering juvenile legislative reforms like dismissal timelines and incompetency presumptions. Finally, we suggest a more stringent regulatory framework be put in place governing the pretrial detention of youths who have been found not competent to stand trial—a framework that recognizes and preserves the juvenile's substantive rights to education, mental health and rehabilitative services. Without legislation, juveniles found not competent to stand trial remain subject to the prospect of indefinite locked detention, often without access to the necessary services that contribute to future success as well as attainment of competency. This lack of due process runs counter to the foundational goals of the juvenile justice system.
Threats to Perceptions of Fairness in the Termination of Parental Rights
Authors: Wayne Raymie H. , Smith Brenda D.
Published: December 2016

Termination of parental rights (TPR) proceedings are among the most important family court activities. This study contributes to knowledge of the TPR process by illustrating practices employed in TPR proceedings and considering ways that certain practices can hinder perceptions of fairness. TPR court records from one state were analyzed using inductive coding procedures. The analysis identified nine categories of threats to perceptions of fairness in the TPR process. Findings have implications for procedural justice and the legitimacy of child welfare practice.
Empathy through Animals: Generating Evidence‐based Outcomes for Empathy Development
Authors: Dawson Jamie
Published: December 2016

Low empathy is a prominent trait associated with juvenile offenders. Many juvenile justice service providers strive to reduce risk factors associated with juvenile delinquency, while producing evidence‐based outcomes for targeted programming. The Youth Services Agency (YSA) Nature Center provides empathy development through animal therapy to adjudicated youth. This project generates evidence‐based outcomes and quantifies the impact of animal therapy on empathy development of adjudicated youth at the YSA Nature Center by utilizing self‐assessment tools. Results indicated trends that animal therapy increases the emotional empathy of YSA clients. Qualitative evidence implied that animal therapy had notable therapeutic value to YSA clients.
Evaluating the Effectiveness of a Juvenile Drug Court: Comparisons to Traditional Probation
Authors: Gummelt Ginger , Sullivan Michael
Published: December 2016

Juvenile Drug Courts have been in operation in the United States for over 20 years, yet their effectiveness and design have been challenged throughout the literature. Using data collected from a Juvenile Drug Court (JDC) in Southeast Texas, this project sought to determine if the JDC intervention reduced recidivism compared to a comparison sample of juvenile offenders. Results indicate that the recidivism rates of participants in the JDC were lower than the comparison group, suggesting that the Drug Court intervention was successful. The program completion rates for JDC youths were also higher for those with fewer infractions. Although the JDC youths had statistically lower infractions, the intervention overall appears to need strengthening. A close inspection of program components could document which programmatic skills are tied to efficacy, leading to the achievement of better outcomes.
How the Framework of Implementation Science Guided an Evidence‐Based Dependency Parenting Program Initiative in Florida
Authors: Katz Lynne , Gonzalez Sindy , Ullery Mary Anne , Lang Jovasha K.
Published: December 2016

In Florida, like most states, many of the parenting programs that are being utilized with families in the dependency system are non‐evidence based, and fail to provide quantifiable data on parent progress during and after completion of the programs. Providing pertinent information in court on parents’ progress in a parenting program, as opposed to simply monitoring attendance, is a growing need voiced by dependency judges and child welfare case management professionals. Clear, reliable information related to parenting skills acquisition and insight can help to ensure that families involved in the child welfare system have access to quality services that improve outcomes for their children. The purpose of this paper is to detail how a statewide initiative to increase the number of Florida circuits providing evidence‐based parenting programs to their clients utilized implementation science to guide their process, and the degree to which the participating circuits achieved full implementation of evidence‐based parenting programs.
Not Enough Time in the Day: A Qualitative Assessment of In‐School Physical Activity Policy as Viewed by Administrators, Teachers, and Students
Authors: Gamble Abigail , Chatfield Sheryl L. , Cormack Michael L. , Hallam Jeffrey S.
Published: December 2016

ABSTRACT

BACKGROUND

In recent decades, the alignment of health and education has been at the forefront of school reform. Whereas the establishment of national in‐school physical activity (ISPA) recommendations and state‐level mandates demonstrates success, there has been less achievement in areas that address health disparities. The purpose of this investigation was to explore barriers and facilitators to implementing state‐mandated ISPA policies in the Mississippi Delta.

METHODS

Focus groups or interviews were conducted with district administrators, school principals, teachers, and students. A total of 2 semistructured moderator guides were developed to focus on (1) student ISPA practices and preferences and (2) facilitators and barriers to implementing ISPA policies and practices.

RESULTS

A total of 6 themes were developed. In that, 2 themes addressed participant‐described barriers (primary challenges and interferences and excuses). Three themes highlighted participant‐described facilitators (compromises, things that work, and being active at school). Finally, 1 theme encompassed the participant‐described need to address educating the whole child.

CONCLUSIONS

There is a critical need for meaningful and relevant solutions to circumvent challenges to implementing ISPA policies and practices in the Mississippi Delta. The Whole School, Whole Community, Whole Child model offers a broad means of visualizing rural, low‐income, racially concentrated schools to circumvent challenges and foster ISPA policies and practices.