bluuebunny/crossref_metadata_2025 huggingface dataset:
Scrambling the skin: Simulated Skin Re-Arrangement Using Apparent Motion
Authors: Seizova-Cajic Tatjana , Ludvigsson Sandra , Sourander Birger , Popov Melinda , Taylor Janet L
Published: December 2019

I.

ABSTRACT

An age-old hypothesis proposes that object motion across the receptor surface organizes sensory maps (Lotze, 19thcentury). Skin patches learn their relative positions from the order in which they are stimulated during motion events. We test this idea by reversing the local motion within a 6-point apparent motion sequence along the forearm. In the ‘Scrambled’ sequence, two middle locations were touched in reversed order (1-2-4-3-5-6, followed by 6-5-3-4-2-1, in a continuous loop). This created a local acceleration, a double U-turn, within an otherwise constant-velocity motion, as if the physical location of skin patches 3 and 4 was surgically swapped. The control condition, ‘Orderly’, proceeded at constant velocity at inter-stimulus onset interval (ISOI) of 120 ms. In the test, our twenty participants reported motion direction between the two middle tactors, presented on their own at 75, 120 or 190-ms ISOI. Results show degraded motion discrimination following exposure to Scrambled pattern: for the 120-ms test stimulus, it was 0.31 d’ weaker than following Orderly conditioning (p = .007). This is the aftereffect we expected; its maximal expression would be a complete reversal in perceived motion direction between locations 3 and 4 for either motion direction. We propose that the somatosensory system was beginning to ‘correct’ reversed local motion to uncurl and remove the U-turns that always occurred on the same part of the receptor surface. Such de-correlation between accelerations and their location on the sensory surface is one possible mechanism for organization of sensory maps.
The Effect of New Nurses’ Clinical Competence on Career Adaptation
Authors: Lee Kyu Ho , Lee Mi Joon
Published: December 2019

Background

New nurses need a certain period of time to adapt to the organization due to a lack of clinical competence, and also immaturity in social skill. The purpose of this study was to evaluate the effects of new nurses’ clinical competence on career adaptation in order to use the results as basic information for developing education programs to improve their adaptability in clinical practice.

Method

This study employed a descriptive survey to investigate the clinical competence and the career adaptability of new nurses working in a general hospital. The study subjects were 61 new nurses with less than one year of work experience and data was collected from June, 2018 to July, 2019. Data was analyzed using frequency analysis, descriptive statistics, t-test, ANOVA, Pearson’s correlation coefficients, and multiple regression analysis.

Results

On average, the study subjects have worked for 11.33±1.51 months. In this study, the average clinical competence of new nurses was 2.21±0.61, and career adaptability was 3.00±0.39. The clinical competence of new nurses was positively correlated with career adaptability (r=.453, p<.001). Among the sub-categories of clinical competence, developing professional and legal implementation were found to affect career adaptability (t=2.24, p=.030).

Conclusion

The clinical competence of the new nurses was shown to positively affect their career adaptability, and it was confirmed that developing professional and legal implementation in the subcategories of clinical competence affected the career adaptability of the new nurses. Thus, it is necessary to establish a program that provides support for new nurses to enable them to build professional identities that they can be proud of.
Cerebellar dopamine D2 receptors regulate preference for social novelty
Authors: Cutando Laura , Puighermanal Emma , Castell Laia , Tarot Pauline , Belle Morgane , Bertaso Federica , Arango-Lievano Margarita , Ango Fabrice , Rubinstein Marcelo , Chédotal Alain , Mameli Manuel , Valjent Emmanuel
Published: December 2019

The cerebellum, a primary center involved in the control of sensorimotor tasks, also contributes to higher cognitive functions including reward, emotion and social interaction. The regulation of these behaviors has been largely ascribed to the monoaminergic system in limbic regions. However, the contribution of cerebellar dopamine signaling in the modulation of these functions remains largely unknown due to the lack of precise characterization of cerebellar dopaminoceptive neurons. By combining cell type-specific transcriptomic and histological analyses, 3D imaging and electrophysiology we demonstrate that cerebellar dopamine D2 receptors (D2R) in mice are preferentially expressed in Purkinje cells (PCs). While activation of D2R regulate synaptic efficacy onto PCs, their deletion or overexpression in PCs bidirectionally controls preference for social novelty without affecting motor functions. Altogether, these findings demonstrate novel D2R’s roles in PC function and causally link cerebellar D2R levels of expression to social behaviors.
Evolutionary conservation and multilevel post-translational control of S-adenosyl-homocysteine-Hydrolase in land plants
Authors: Alegre Sara , Pascual Jesús , Trotta Andrea , Angeleri Martina , Rahikainen Moona , Brosche Mikael , Moffatt Barbara , Kangasjärvi Saijaliisa
Published: December 2019

Trans-methylation reactions are intrinsic to cellular metabolism in all living organisms. In land plants, a range of substrate-specific methyltransferases catalyze the methylation of DNA, RNA, proteins, cell wall components and numerous species-specific metabolites, thereby providing means for growth and acclimation in various terrestrial habitats. Trans-methylation reactions consume vast amounts of S-adenosyl-L-methionine (SAM) as a methyl donor in several cellular compartments. The inhibitory reaction by-product, S-adenosyl-L-homocysteine (SAH), is continuously removed by SAH hydrolase (SAHH) activity, and in doing so essentially maintains trans-methylation reactions in all living cells. Here we report on the evolutionary conservation and multilevel post-translational control of SAHH in land plants. We find that SAHH forms oligomeric protein complexes in phylogenetically divergent land plants, and provide evidence that the predominant enzyme is a tetramer. By analyzing light-stress-induced adjustments occurring on SAHH inArabidopsis thalianaandPhyscomitrella patens, we demonstrate that both angiosperms and bryophytes undergo regulatory adjustments in the levels of protein complex formation and post-translational modification of this metabolically central enzyme. Collectively, these data suggest that plant adaptation to terrestrial environments involved evolution of regulatory mechanisms that adjust the trans-methylation machinery in response to environmental cues.
Study on Spatial-temporal Variation of Atmospheric Pollution in China between 2014 and 2019
Authors: Peng Guo , Batalbievna Umarova Aminat , Yunqi Luan
Published: December 2019

The study in this paper reveals that the atmospheric contaminants in mainland China is of concentricity in spatial distribution, persistence in temporal distribution and correlation between different parameters. This spatial-temporal variation law plays an important role in improving and addressing the problem with atmospheric environment of given cities and regions by employing focused and pointed measures. In this paper, seven kinds of atmospheric pollution parameters including PM2.5, PM10, AQI, CO, NO2, O3 and SO2 in 370 Chinese cities from 2014 to 2019 are analyzed based on their hourly mass concentration. The spatial-temporal variations of each parameter in each separated year are obtained by using interpolation calculation towards the annual atmospheric pollution parameters. The results show that higher mass concentration (including the highest mass concentration) of PM2.5, AQI, PM10, CO, NO2, SO2 mainly concentrated in Beijing-Tianjin-Hebei region in the northeast of mainland China and its neighboring regions and Xinjiang region in the northwest of mainland China. The spatial variation of PM2.5, AQI, PM10, CO, NO2, SO2 experienced similar trend. Higher mass concentration (including the highest mass concentration) of O3 mainly concentrated in Qinghai and Inner Mongolia in the central north of mainland China and Shandong on the right side of Beijing-Tianjin-Hebei region. The spatial variation of O3 experienced different trend from that of other parameters. PM2.5, AQI, PM10 indicated increase and decrease, followed by increase and decrease again with time, which was a S-shaped change. Almost the same temporal variation happened to PM2.5, AQI, PM10 and to CO, NO2, SO2, which was opposite to O3. The analysis from the perspective of the annual highest mass concentration of PM2.5, AQI, PM10, NO2 and O3 indicates the atmospheric environment of mainland China had not been authentically improved by 2019. The analysis from the perspective of the annual highest mass concentration of CO and SO2 indicates the atmospheric environment of mainland China had been authentically improved by 2019. What should we do immediately is to strengthen environmental governance and address the source of contamination in Beijing-Tianjin-Hebei region in the northeast of China, Xinjiang region in the northwest of China, Qinghai and Inner Mongolia regions in the central north of China.
Endosperm and seed transcriptomes reveal possible roles for small RNA pathways in wild tomato hybrid seed failure
Authors: Florez-Rueda Ana Marcela , Fiscalini Flurin , Roth Morgane , Grossniklaus Ueli , Städler Thomas
Published: December 2019

Crosses between the wild tomato speciesSolanum peruvianumandS. chilenseresult in hybrid seed failure (HSF), characterized by endosperm misdevelopment and embryo arrest. We previously showed that genomic imprinting, the parent-of-origin–dependent expression of alleles, is perturbed in hybrid endosperm, with many of the normally paternally expressed genes losing their imprinted status. Here, we report transcriptome-based analyses of gene and small RNA expression levels. We identified 2,295 genes and 468 small RNAs (sRNAs) as differentially expressed (DE) when comparing reciprocal hybrid seed to seeds and endosperms from the two within-species crosses. Our analyses uncovered a pattern of overdominance in endosperm gene expression in both cross directions, in marked contrast to the patterns of sRNA expression in whole seeds. Intriguingly, patterns of increased gene expression resembled the previously reported increased maternal expression proportions in hybrid endosperms. We identified physical clusters of sRNAs; DE sRNAs exhibited reduced levels of expression in hybrid seeds from both cross directions. Moreover, sRNAs mapped to genes coding for key proteins involved in epigenetic regulation of gene expression, suggesting a regulatory feedback mechanism. We describe examples of genes that are targets of sRNA-mediated gene silencing; in these cases, reduced sRNA expression was concomitant with increased gene expression in hybrid seeds. Our analyses also show thatS. peruvianumdominance impacts gene and sRNA expression in hybrid seeds. Overall, our study indicates roles for sRNA-mediated epigenetic regulation in HSF between closely related wild tomato species.
metabolisHMM: Phylogenomic analysis for exploration of microbial phylogenies and metabolic pathways
Authors: McDaniel E.A. , Anantharaman K. , McMahon K.D.
Published: December 2019

Advances in high-throughput sequencing technologies and bioinformatic pipelines have exponentially increased the amount of data that can be obtained from uncultivated microbial lineages inhabiting diverse ecosystems. Various annotation tools and databases currently exist for predicting the functional potential of sequenced genomes or microbial communities based upon sequence identity. However, intuitive, reproducible, and user-friendly tools for further exploring and visualizing functional guilds of microbial community metagenomic sequencing datasets remains lacking. Here, we present metabolisHMM, a series of workflows for visualizing the distribution of curated and user-provided Hidden Markov Models (HMMs) to understand metabolic characteristics and evolutionary histories of microbial lineages. metabolisHMM performs functional annotations with a set of curated or user-defined HMMs to 1) construct ribosomal protein and single marker gene phylogenies, 2) summarize the presence/absence of metabolic pathway markers, and 3) create heatmap visualizations of presence/absence summaries.

Availability and Implementation

metabolisHMM is freely available on Github athttps://github.com/elizabethmcd/metabolisHMMand on PyPi athttps://pypi.org/project/metabolisHMM/under the GNU General Public License v3.0.
Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration
Authors: McCormick Rachel , Pearce Ian , Kaye Stephen , Haneef Atikah
Published: December 2019

Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruch’s membrane (BM), however, the diseased native BM and related structures still leave the potential for transplanted cells to succumb to disease. In this work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the basal surface was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for two weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This would allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function two-fold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.
The open bar is closed: restructuration of a native parasitoid community following successful control of an invasive pest
Authors: Muru David , Borowiec Nicolas , Thaon Marcel , Ris Nicolas , Viciriuc Madalina I. , Warot Sylvie , Vercken Elodie
Published: December 2019

Abstract

The rise of the Asian chestnut gall waspDryocosmus kuriphilusin France has benefited the native community of parasitoids originally associated with oak gall wasps by becoming an additional trophic subsidy and therefore perturbing population dynamics of local parasitoids. However, the successful biological control of this pest has then led to significant decreases in its population densities. Here we investigate how the invasion of the Asian chestnut gall waspDryocosmus kuriphilusin France and its subsequent control by the exotic parasitoidTorymus sinensishas impacted the local community of native parasitoids.

We explored 5 years of native community dynamics within 26 locations during the rise and fall of the invasive pest. In an attempt to understand how mechanisms such as local extinction or competition come into play, we analyzed how the patterns of co-occurrence between the different native parasitoid species changed through time.

Our results demonstrate that native parasitoid communities experienced increased competition as theD. kuriphiluslevels of infestation decreased. During the last year of the survey, two alternative patterns were observed depending on the sampled location: either native parasitoid communities were represented by an extremely limited number of species occurring at low densities, in some cases no native parasitoid species at all, or they were dominated by one main parasitoid:Mesopolobus sericeus. These two patterns seemed to correlate with the habitat type,M. sericeusbeing more abundant in semi-natural habitats compared to agricultural lands, the former known to be natural reservoirs for native parasitoids. These results highlight how the “boom-and-bust” dynamics of an invasive pest followed by successful biological control can deeply alter the structure of native communities of natural enemies.

This article has been peer-reviewed and recommended byPeer Community in Zoologyhttps://doi.org/10.24072/pci.zool.100004
A single-cell survey ofDrosophilablood
Authors: Tattikota Sudhir Gopal , Hu Yanhui , Liu Yifang , Cho Bumsik , Barrera Victor , Steinbaugh Michael , Yoon Sang-Ho , Comjean Aram , Li Fangge , Dervis Franz , Hung Ruei-Jiun , Nam Jin-Wu , Sui Shannan Ho , Shim Jiwon , Perrimon Norbert
Published: December 2019

Drosophilablood cells, called hemocytes, are classified into plasmatocytes, crystal cells, and lamellocytes based on the expression of a few marker genes and cell morphologies, which are inadequate to classify the complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) to map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes into different states based on the expression of genes involved in cell cycle, antimicrobial response, and metabolism together with the identification of intermediate states. Further, we discovered rare subsets within crystal cells and lamellocytes that express fibroblast growth factor (FGF) ligandbranchlessand receptorbreathless, respectively. We demonstrate that these FGF components are required for mediating effective immune responses against parasitoid wasp eggs, highlighting a novel role for FGF signaling in inter-hemocyte crosstalk. Our scRNA-seq analysis reveals the diversity of hemocytes and provides a rich resource of gene expression profiles for a systems-level understanding of their functions.

Highlights

scRNA-seq ofDrosophilablood recovers plasmatocytes, crystal cells, and lamellocytes

scRNA-seq identifies different plasmatocyte states based on the expression of genes involved in cell cycle regulation, antimicrobial response, and metabolism

Pseudotemporal ordering of single cells identifies crystal cell and lamellocyte intermediate states

scRNA-seq uncovers a novel role for FGF signaling in inter-hemocyte crosstalk
A modified two-color flow cytometry assay to quantify in-vitro reinvasion and determine invasion phenotypes at lowPlasmodium falciparumparasitemia
Authors: Atuh Ngoh Ines , Nota Anong Damian , Cho Fru Jerome , Bojang Fatoumata , Mbye Haddijatou , Amambua-Ngwa Alfred
Published: December 2019

Two-color flow cytometry(2cFCM) is the most accessible method for phenotyping parasite invasion. However, current protocols require samples of field isolates at ∼1% parasitemia for assay set-up, which are becoming more uncommon in low transmission settings. Current protocols, therefore, have to be adapted for low parasitemia if the method must have continued applicability in this era of elimination. Optimizing the protocol requires addressing; interference from young uninfected RBCs background fluorescence and biased phenotypes due to limited labeled RBCs availability and/or parasite density per assay. Here, we used SYBR Green I and CTFR Proliferation fluorescent dyes to set-up invasion assays withPlasmodium falciparum3D7, Dd2 and field isolates cultures (diluted at 0.05% to 2.0% parasitemia) against varying unlabeled to labeled RBC ratios (1:1 to 1:4). We showed that a shorter SYBR Green I staining time of 20 minutes, down from 1hour, minimized background fluorescence from uninfected RBCs (mean= 0.03% events) and allowed 2cFCM to accurately quantify reinvasion for an assay at 0.02% parasitemia. An increase in labeled target RBCs to 1:3 per assays significantly increased heterologous reinvasion (p<0.001). This resulted in a 10% greater invasion inhibition by enzyme treatments (p<0.05). Strain-specific invasion phenotype could be accurately determined for samples with as low as 0.3% parasitemia. Samples above 0.8% parasitemia were less accurate. These findings show that invasion pathway phenotypes can be obtained for field samples with low parasitemia at greater sensitivity and reproducibility by increasing the proportion of labeled RBCs per assay by at least 2-fold what is in current methods.
Human follicular helper T cell promoter connectomes reveal novel genes and regulatory elements at SLE GWAS loci
Authors: Su Chun , Johnson Matthew E. , Torres Annabel , Thomas Rajan M. , Manduchi Elisabetta , Sharma Prabhat , Le Coz Carole , Leonard Michelle E. , Lu Sumei , Hodge Kenyaita M. , Chesi Alessandra , Pippin James , Romberg Neil , Grant Struan F. A. , Wells Andrew D.
Published: December 2019

Systemic lupus erythematosus (SLE) is a complex inflammatory disease mediated by autoreactive antibodies that damages multiple tissues in children and adults. Genome-wide association studies (GWAS) have statistically implicated hundreds of loci in the susceptibility to human disease, including SLE, but the majority have failed to identify the causal variants or the effector genes. As a physicochemical approach to detecting functional variants and connecting them to target genes, we generated comprehensive, high-resolution maps of SLE variant accessibility and gene connectivity in the context of the three-dimensional chromosomal architecture of human tonsillar follicular helper T cells (TFH), a cell type required for the production of anti-nuclear antibodies characteristic of SLE. These spatial epigenomic maps identified a shortlist of over 400 potentially functional variants across 48 GWAS-implicated SLE loci. Twenty percent of these variants were located in open promoters of highly-expressed TFH genes, while 80% reside in non-promoter genomic regions that are connected in 3D to genes that likewise tend to be highly expressed in TFH. Importantly, we find that 90% of SLE-associated variants exhibit spatial proximity to genes that are not nearby in the 1D sequence of the genome, and over 60% of variants ‘skip’ the nearest gene to physically interact only with the promoters of distant genes. Gene ontology confirmed that genes in spatial proximity to SLE variants reside in highly SLE-relevant networks, including accessible variants that loop 200-1000 kb to interact with the promoters of the canonical TFH genesBCL6andCXCR5. CRISPR-Cas9 genome editing confirmed that these variants reside in novel, distal regulatory elements required for normalBCL6andCXCR5expression by T cells. Furthermore, SLE-associated SNP-promoter interactomes implicated a set of novel genes with no known role in TFH or SLE disease biology, including the homeobox-interacting protein kinase HIPK1 and the Ste kinase homolog MINK1. Targeting these kinases in primary human TFH cells inhibited production of IL-21, a requisite cytokine for production of class-switched antibodies by B cells. This 3D-variant-to-gene mapping approach gives mechanistic insight into the SLE-associated regulatory architecture of the human genome.
PiVR: an affordable and versatile closed-loop platform to study unrestrained sensorimotor behavior
Authors: Tadres David , Louis Matthieu
Published: December 2019

Tools enabling closed-loop experiments are crucial to delineate causal relationships between the activity of genetically-labeled neurons and specific behaviors. We developed the RaspberryPiVirtualReality system (PiVR) to conduct closed-loop optogenetic stimulation of neural functions in unrestrained animals. PiVR is an experimental platform that operates at high-temporal resolution (>50 Hz) with low latencies (~10 ms), while being affordable (<$500) and easy to build (<6 hours). This tool was designed to be accessible to a wide public, from highschool students to professional researchers studying systems neuroscience. We illustrate the functionality of PiVR by focusing on sensory navigation in response to gradients of chemicals (chemotaxis) and light (phototaxis). We show howDrosophilaflies perform negative chemotaxis by modulating their locomotor speed to avoid locations associated with optogenetically-evoked bitter taste. InDrosophilalarvae, we use innate positive chemotaxis to compare orientation behavior elicited by real- and virtual-odor gradients with static shapes as well as by turbulent virtual-odor plumes. Finally, we examine how positive phototaxis emerges in zebrafish larvae from the modulation of turning maneuvers during the ascent of virtual white-light gradients. Besides its application to study chemotaxis and phototaxis, PiVR is a versatile tool designed to bolster efforts to map and to functionally characterize neural circuits.
High-throughput cryo-EM enabled by user-free preprocessing routines
Authors: Li Yilai , Cash Jennifer N. , Tesmer John. J.G. , Cianfrocco Michael A.
Published: December 2019

The growth of single-particle cryo-EM into a mainstream structural biology tool has allowed for many important biological discoveries. Continued developments in data collection strategies alongside new sample preparation devices heralds a future where users will collect multiple datasets per microscope session. To make cryo-EM data processing more automatic and user-friendly, we have developed an automatic pipeline for cryo-EM data preprocessing and assessment using a combination of deep learning and image analysis tools. We have verified the performance of this pipeline on a number of datasets and extended its scope to include sample screening by the user-free assessment of the qualities of a series of datasets under different conditions. We propose that our workflow provides a decision-free solution for cryo-EM, making data preprocessing more generalized and robust in the high-throughput era as well as more convenient for users from a range of backgrounds.
Measuring the spatial heterogeneity on the reduction of vaginal fistula burden in Ethiopia between 2005 and 2016
Authors: Deribe Kebede , Fronterre Claudio , Dejene Tariku , Biadgilign Sibhatu , Deribew Amare , Abdullah Muna , Cano Jorge
Published: December 2019

Vaginal fistula is a shattering maternal complication characterized by an anomalous opening between the bladder and/or rectum and vagina resulting in continuous leakage of urine or stool. Although prevalent in Ethiopia, its magnitude and distribution is not well studied. We used statistical mapping models using 2005 and 2016 Ethiopia Demographic Health Surveys data combined with a suite of potential risk factors to estimate the burden of vaginal fistula among women of childbearing age. The estimated number of women of childbearing age with lifetime and untreated vaginal fistula in 2016 were 72,533 (95% CI 38,235–124,103) and 31,961 (95% CI 11,596–70,309) respectively. These figures show reduction from the 2005 estimates: 98,098 (95% CI 49,819–170,737) lifetime and 59,114 (95% CI 26,580–118,158) untreated cases of vaginal fistula. The number of districts having more than 200 untreated cases declined drastically from 54 in 2005 to 6 in 2016. Our results show a significant subnational variation in the burden of vaginal fistula. Overall, between 2005 and 2016 there was substantial reduction in the prevalence of vaginal fistula in Ethiopia. Our results help guide local level tracking, planning, spatial targeting of resources and implementation of interventions against vaginal fistula.
The Australian Real‐Time Fiscal Database: An Overview with Illustrations of Its Use in Analysing Fiscal Policy
Authors: Lee Kevin , Morley James , Shields Kalvinder , Tan Madeleine Sui‐Lay
Published: December 2019

This paper describes a fiscal database for Australia including measures of government spending, revenue, deficits, debt and various sub‐aggregates as initially published and subsequently revised. The data vintages are collated from various sources and provide a comprehensive description of the Australian fiscal environment as experienced in real time. Methods are described which exploit the richness of the real‐time data sets, and they are illustrated through an analysis of the extent to which stated fiscal plans are realised in practice and through the estimation of fiscal multipliers which draw a distinction between policy responses and policy initiatives. We find predictable differences between plans and actual fiscal policy and a larger multiplier for policy initiatives than for implementation errors.
Patterns of alcohol consumption in 16 cohorts of Australian young adults aged 15–24 between 2001 and 2016
Authors: Callinan Sarah , Pennay Amy , Livingston Michael , Kuntsche Emmanuel
Published: December 2019

Background and aims

Repeated cross‐sectional surveys have identified substantial declines in adolescent drinking in Australia and some other countries in recent years. There is debate about whether these declines will be maintained as the cohort ages. This study modelled alcohol consumption over time to check for cohort effects reflecting a decrease in youth consumption, and then used this model to predict how decreases in youth drinking will be sustained through to adulthood.

Design

Longitudinal study using data from the Household Income and Labour Dynamics in Australia (HILDA) survey from 2001 to 2016. Piecewise latent growth models were estimated to assess consumption trajectories for each birth cohort from ages 15–18 and 18–24 years.

Setting

Australia.

Participants

This study focused on 5320 (51.9% female) respondents aged between 15 and 22 in wave 1 (2001) to those aged between 17 and 24 in wave 16 (2016).

Measurement

Annual volume of alcohol consumption was calculated as the product of the quantity per occasion and the frequency of drinking expanded to represent drinking occasions per year.

Findings

The model with best fit suggested that consumption increased rapidly [b = 0.667, standard error (SE) = 0.046, P < 0.001] until the legal drinking age of 18 and then plateaued (b = −0.027, SE = 0.016, P = 0.088). More recent cohorts start with significantly lower levels of consumption (b = −0.145, SE = 0.010; P < 0.001) but increase at a faster rate (b = 0.022, SE = 0.003, P < 0.001) between 15 and 18; however, not enough to catch up to earlier cohorts.

Conclusion

Recent decreases in adolescent drinking in Australia may, at least in part, be attributed to lower consumption in recent cohorts of younger drinkers. Results indicate that this group may continue to drink less than previous cohorts as they age into their twenties.
Acceptability and efficacy of naltrexone for criminal justice‐involved individuals with opioid use disorder: a systematic review and meta‐analysis
Authors: Bahji Anees , Carlone David , Altomare Josephine
Published: December 2019

Background and aims

Criminal justice‐involved individuals carry a disproportionately higher burden of opioid use disorder (OUD) than those not involved with the criminal justice system, and are often unable to access opioid agonist therapies such as methadone and buprenorphine. The opioid receptor antagonist naltrexone (NTX) is effective for the prevention of relapse to OUD and may be more acceptable in criminal justice settings. The objectives of this review were to: (1) provide an overall summary effect across studies for the efficacy and acceptability of oral and injectable NTX for the treatment of OUD among criminal justice‐involved individuals and (2) examine systematic variations in study results to explain heterogeneity among study‐specific effects.

Methods

Systematic review and meta‐analysis of 1045 patients across 11 studies (10 randomized controlled trials, one quasi‐experimental study). All available outcomes were pooled using random‐effects meta‐analysis. Subgroup analyses were conducted for oral and injectable naltrexone; meta‐regression analyses were conducted for socio‐demographic and study‐level characteristics.

Results

NTX improved retention in treatment [risk ratio (RR) = 1.31; 95% confidence interval (CI) = 1.05, 1.63], reduced rates of re‐incarceration (RR = 0.70, 95% CI = 0.54–0.92), reduced opioid relapse (RR = 0.63, 95% CI = 0.53–0.76) and improved opioid abstinence (RR = 1.38, 95% CI = 1.16–1.65). While NTX was associated with a greater burden of adverse events overall (RR = 1.49, 95% CI = 1.13–1.95), the findings were inconclusive as to whether or not a difference was present for the number of serious adverse events or overdoses.

Conclusions

Naltrexone appears to be efficacious and acceptable for the treatment of opioid use disorder among criminal justice‐involved individuals; however, the risk for adverse events must be weighed against the potential benefits.
Insecticide resistance status of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) in Australian cotton production valleys
Authors: Hopkinson Jamie , Pumpa Stephanie , van Brunschot Sharon , Fang Cao , Frese Michael , Tay Wee Tek , Walsh Tom
Published: December 2019

The whitefly Bemisia tabaci Middle East‐Asia Minor 1 (MEAM1), previously known as B biotype, is a major agricultural pest with a reputation for developing resistance to insecticides. DNA‐based identification revealed that B. tabaci MEAM1 is the dominant species within Australian cotton cropping. Discriminating doses of 10 mg/L for pyriproxyfen and 300 mg/L for both diafenthiuron and bifenthrin were determined from bioassay data collected in 2010–2015. Resistance to these insecticides was tested in whitefly populations collected in 2017 from cotton crops in Queensland and New South Wales. This study reports on the presence of pyriproxyfen resistance in B. tabaci MEAM1 at seven locations in Queensland and New South Wales. One population from Goondiwindi was resistant to bifenthrin, whereas no populations tested had resistance to diafenthiuron. To determine the presence of resistance alleles to organophosphates and pyrethroids, reference populations of susceptible and resistant whiteflies (pyriproxyfen, bifenthrin and neonicotinoid) were tested. The resistance mutation L925I was found in a pyrethroid‐resistant population and in some individuals from the pyriproxyfen‐resistant population. The mutation F331W that confers organophosphate and carbamate resistance was found in all individuals tested including the susceptible reference population, indicative of a widespread distribution in Australian B. tabaci MEAM1. The cotton industry has revised the insecticide resistance management strategy for B. tabaci, to restrict the usage of pyriproxyfen to a single application within a 30‐day window. Our results argue against the use of organophosphate and carbamate insecticides in Australian cotton, because B. tabaci MEAM1 populations show significant resistance levels. Furthermore, both pesticide groups are highly disruptive to a diverse range of natural enemy populations, and as such, widespread use likely contributes to pest outbreaks.
Kernel naive Bayes discrimination for high‐dimensional pattern recognition
Authors: Koch Inge , Naito Kanta , Tanaka Hiroaki
Published: December 2019

Kernel discriminant analysis translates the original classification problem into feature space and solves the problem with dimension and sample size interchanged. In high‐dimension low sample size (HDLSS) settings, this reduces the ‘dimension’ to that of the sample size. For HDLSS two‐class problems we modify Mika's kernel Fisher discriminant function which – in general – remains ill‐posed even in a kernel setting; see Mika et al. (1999). We propose a kernel naive Bayes discriminant function and its smoothed version, using first‐ and second‐degree polynomial kernels. For fixed sample size and increasing dimension, we present asymptotic expressions for the kernel discriminant functions, discriminant directions and for the error probability of our kernel discriminant functions. The theoretical calculations are complemented by simulations which show the convergence of the estimators to the population quantities as the dimension grows. We illustrate the performance of the new discriminant rules, which are easy to implement, on real HDLSS data. For such data, our results clearly demonstrate the superior performance of the new discriminant rules, and especially their smoothed versions, over Mika's kernel Fisher version, and typically also over the commonly used naive Bayes discriminant rule.
Rachel Fewster: Recipient of NZSA Campbell Award 2018
Authors: Millar Russell
Published: December 2019

A lucky chance encounter for statistical science in NZ.
Book Review
Authors: Maindonald John
Published: December 2019

There is extensive historical commentary, severe testing is a strong theme, and null hypothesis significance testing gets a remake. The statistics wars continue on!
Ziv‐aflibercept: A cost‐effective, off‐label, highly potent antagonist of vascular endothelial growth factor
Authors: Mansour Ahmad M. , Stewart Michael W. , Farah Michel E. , Mansour Hana A. , Chhablani Jay
Published: December 2019

Ziv‐aflibercept (Zaltrap®), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea®), thus making it an attractive option for the off‐label treatment of chorioretinal vascular conditions. Ziv‐aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv‐aflibercept an attractive anti‐VEGF treatment option, especially in low‐ and middle‐income countries where its popularity is increasing.
Shealing: Post‐disaster slow healing and later recovery
Authors: Mika Kasia , Kelman Ilan
Published: December 2019

This paper explores approaches to “later recovery” or “slow recovery” in post‐disaster contexts, viewing it as a positive force by terming it “slow healing” contracted to “shealing.” Slow healing hopes to develop a multi‐scalar, processual, open‐ended, and future‐oriented approach to asynchronous and differentiated processes and practices of individual and collective recovery. “Shealing,” as used here, then denotes ongoing, individual, and collective efforts through remaking and building one's life post‐disaster. This process of shealing, of re‐making and making lives liveable, is a process of assembling, or trying to assemble, life and livelihoods, without necessarily immediately eradicating all traces of destruction which might be vestiges of a life before the disastrous manifestation of compound vulnerabilities. Shealing provides an alternative to assumptive, linear approaches in order to enfold healing and vulnerability reduction within day‐to‐day, continual, accepted, non‐spectacular actions. From a noun or an attribute, “shealing” functions as a verb by being a continuous and open‐ended process in the present, not just a defined stage, whether a hoped‐for endpoint or a recovery of some pre‐disaster state. Shealing allows theorising the many ways of living in and through disaster experiences alongside the range of everyday post‐disaster approaches to re‐making one's life that an individual or community might embrace. Shealing forms a joint scholarly‐practical approach that better addresses what needs to be done and accepted after experiencing a disaster. This paper focuses on disasters, but wider implications and connections emerge, such as for grief, trauma, and social work.
A bivariate joint frailty model with mixture framework for survival analysis of recurrent events with dependent censoring and cure fraction
Authors: Tawiah Richard , McLachlan Geoffrey J. , Ng Shu Kay
Published: December 2019

In the study of multiple failure time data with recurrent clinical endpoints, the classical independent censoring assumption in survival analysis can be violated when the evolution of the recurrent events is correlated with a censoring mechanism such as death. Moreover, in some situations, a cure fraction appears in the data because a tangible proportion of the study population benefits from treatment and becomes recurrence free and insusceptible to death related to the disease. A bivariate joint frailty mixture cure model is proposed to allow for dependent censoring and cure fraction in recurrent event data. The latency part of the model consists of two intensity functions for the hazard rates of recurrent events and death, wherein a bivariate frailty is introduced by means of the generalized linear mixed model methodology to adjust for dependent censoring. The model allows covariates and frailties in both the incidence and the latency parts, and it further accounts for the possibility of cure after each recurrence. It includes the joint frailty model and other related models as special cases. An expectation‐maximization (EM)‐type algorithm is developed to provide residual maximum likelihood estimation of model parameters. Through simulation studies, the performance of the model is investigated under different magnitudes of dependent censoring and cure rate. The model is applied to data sets from two colorectal cancer studies to illustrate its practical value.
A fast score test for generalized mixture models
Authors: Duan Rui , Ning Yang , Wang Shuang , Lindsay Bruce G. , Carroll Raymond J. , Chen Yong
Published: December 2019

In biomedical studies, testing for homogeneity between two groups, where one group is modeled by mixture models, is often of great interest. This paper considers the semiparametric exponential family mixture model proposed by Honget al. (2017) and studies the score test for homogeneity under this model. The score test is nonregular in the sense that nuisance parameters disappear under the null hypothesis. To address this difficulty, we propose a modification of the score test, so that the resulting test enjoys the Wilks phenomenon. In finite samples, we show that with fixed nuisance parameters the score test is locally most powerful. In large samples, we establish the asymptotic power functions under two types of local alternative hypotheses. Our simulation studies illustrate that the proposed score test is powerful and computationally fast. We apply the proposed score test to an UK ovarian cancer DNA methylation data for identification of differentially methylated CpG sites.
Weight calibration to improve the efficiency of pure risk estimates from case‐control samples nested in a cohort
Authors: Shin Yei Eun , Pfeiffer Ruth M. , Graubard Barry I. , Gail Mitchell H.
Published: December 2019

Cohort studies provide information on relative hazards and pure risks of disease. For rare outcomes, large cohorts are needed to have sufficient numbers of events, making it costly to obtain covariate information on all cohort members. We focus on nested case‐control designs that are used to estimate relative hazard in the Cox regression model. In 1997, Langholz and Borgan showed that pure risk can also be estimated from nested case‐control data. However, these approaches do not take advantage of some covariates that may be available on all cohort members. Researchers have used weight calibration to increase the efficiency of relative hazard estimates from case‐cohort studies and nested cased‐control studies. Our objective is to extend weight calibration approaches to nested case‐control designs to improve precision of estimates of relative hazards and pure risks. We show that calibrating sample weights additionally against follow‐up times multiplied by relative hazards during the risk projection period improves estimates of pure risk. Efficiency improvements for relative hazards for variables that are available on the entire cohort also contribute to improved efficiency for pure risks. We develop explicit variance formulas for the weight‐calibrated estimates. Simulations show how much precision is improved by calibration and confirm the validity of inference based on asymptotic normality. Examples are provided using data from the American Association of Retired Persons Diet and Health Cohort Study.
Resource utilization and cost effectiveness of treating acute promyelocytic leukaemia using generic arsenic trioxide
Authors: Bankar Aniket , Korula Anu , Kulkarni Uday P. , Devasia Anup J. , NA Fouzia , Lionel Sharon , Abraham Aby , Balasubramanian Poonkuzhali , Janet Nancy Beryl , Nair Sukesh C. , S Sezlian , Jeyaseelan Visali , N Jeyaseelan , Prasad Jasmine , George Biju , Mathews Vikram
Published: December 2019

Arsenic trioxide (ATO)‐based regimens are the standard of care for treating acute promyelocytic leukaemia (APL) and have replaced chemotherapy‐based approaches. However, the cost of “patented” ATO is prohibitive because of patent rights. “Generic” ATO has been used in a few countries, but its implications for health resource utilization (HRU) and cost of treatment are unknown. We hypothesized that treating APL patients using generic ATO (APL‐ATO) will be cost effective compared to the chemotherapy‐based regimen (APL‐CT). In a single‐centre retrospective study, we used a bottom‐up costing method to compare the direct medical cost of treatment and HRU between APL‐ATO and APL‐CT. These costs and the survival and relapse probabilities were imputed in a three‐state Markov decision model to estimate the cost effectiveness of APL‐ATO compared to APL‐CT. The mean cost of treatment for APL‐ATO (n = 30, $8500 ± 2078) was significantly less than for APL‐CT (n = 30, $22 600 ± 5528) (P < 0·001). APL‐ATO reduced hospitalization, antibiotic and antifungal usage (P < 0·001). In the Markov model, five‐year treatment costs were significantly lower for APL‐ATO ($11 131) than for APL‐CT ($17 926) (P < 0·001). Treatment cost and health resource utilization were significantly lower for generic ATO‐treated APL patients compared to the chemotherapy‐based regimen.
Leavers and Remainers after the Brexit referendum: More united than divided after all?
Authors: Hanel Paul H. P. , Wolf Lukas J.
Published: December 2019

Since the British ‘Brexit referendum’ in 2016, tensions between ‘leave’ and ‘remain’ voters have been growing. Using a novel analytical approach based on the full distribution of responses rather than their arithmetic means, Study 1 (N = 1,506) showed on average 90% of overlap among Leavers and Remainers across a range of important variables. Even on the variables that are commonly used to illustrate how Leavers and Remainers differ (e.g., prejudice against immigrants), the amount of overlap was larger than 50%. In Study 2 (N = 206), we demonstrate the importance of focusing on similarities between groups: Presenting the full distribution of responses from Leavers and Remainers rather than their mean differences caused more accurate perceptions of the actual differences and similarities between both groups and higher perceived intergroup harmony. We conclude that similarities between Leavers and Remainers are substantial and that our proposed approach may help to de‐escalate tensions between these and other groups.