bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians
Authors: Vermeulen Eric , van den Anker John N , Della Pasqua Oscar , Hoppu Kalle , van der Lee Johanna H 
Published: September 2016

Abstract

Objectives
In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT.

Methods
Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies.

Key findings
The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose-finding study.

Conclusions
The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.
StreetWise: developing a serious game to support forensic mental health service users' preparation for discharge: a feasibility study
Authors: Reynolds L. M. , Davies J. P. , Mann B. , Tulloch S. , Nidsjo A. , Hodge P. , Maiden N. , Simpson A. 
Published: September 2016

Accessible summaryWhat is known on the subject?

Serious gaming can support learning and development.

The use of serious games for skills development and the rehearsal of the management of events that cannot be replicated in real life is well established. Few serious games have been used in mental health services, and none in forensic mental health care.

What this paper adds to existing knowledge?

How a serious game may be coproduced by forensic mental health service users and game developers

The acceptability of the therapeutic use of serious gaming by forensic mental health service users and providers.

What are the implications for practice?

Computer games may be used by practitioners in their therapeutic work with forensic mental health service users.

Mental health nurses to use serious games to creatively and safely bridge the gap for service users between receiving care in controlled environments and living more independent in the community.

AbstractIntroductionAssessment of users' skills and confidence to safely respond to risky community‐based situations underpins discharge planning. Serious games have been used for skills development, and this study trialled their use in forensic mental health services.AimThe aim was to develop and test the acceptability and usability of an innovative serious game to support forensic mental health service users' preparation for discharge.MethodA prototype serious game was developed by service users and researchers. Acceptability and usability testing was undertaken and service providers interviewed about the acceptability of serious gaming for forensic mental health services.ResultA prototype game was produced and successfully trialled by service users. However, both service users and providers identified that work needed to be done to develop and test a game with greater complexity.DiscussionThe acceptability and usability of using serious games to support service users to develop skills needed for successful discharge was demonstrated.Implications for practiceMental health practitioners may use gaming to support their practice and work innovatively with other professions such as game developers to create new ways of working in forensic mental health services.
Decline of cellular activation in non‐B cells after rituximab treatment in hepatitis C‐associated mixed cryoglobulinemia vasculitis
Authors: Emmanuel B. , Sidique N. , Zhang X. , Poonia B. , Sneller M. C. , Kottilil S. 
Published: September 2016

SummaryMixed cryoglobulinemic vasculitis is associated with the monoclonal expansion of pathognomonic B cells in chronic hepatitis C. Recently, treatment with B‐cell depletion, including rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from the active disease. We investigated whether B‐cell depletion therapy has an impact on activation of non‐B cells in the periphery. Results demonstrated that B‐cell depletion therapy is associated with a statistically significant decline in activated T cells, from pretherapy to follow‐up while on rituximab therapy: CD4+ CD38+ HLA‐DR+ (DR+), CD8+ CD38, CD8+ CD38+ DR+, and CD8+ DR+. Birmingham Vasculitis Activity Score and cryoglobulin had a strong correlation coefficient (R) of 0.72 (P=.0005), while cryoglobulin showed moderate correlation with CD8+ DR+ (R=.61), CD3+ CD38+ DR+ (R=.57), CD3+ DR+ (R=.50), CD4+ CD38+ DR+ (R=.53), CD4+ DR+ (R=.52), and CD8+ CD38+ DR+ (R=.67). These results suggest B‐cell expansion has a direct and indirect effect on the pathogenesis of Hepatitis C‐associated mixed cryoglobulinemic vasculitis.
Generative Metrics: An Overview
Authors: Blumenfeld Lev 
Published: September 2016

AbstractThis overview article covers the field of metrics as a branch of linguistics, focusing on the generative tradition. A brief outline of the basic ideas of foundational papers by Halle & Keyser and Kiparsky is followed by a discussion of three theoretical issues: the nature of representations; gradience and variation; and the interface of metrics with phonology. The last section covers theoretical approaches to typology.
Comparative transcriptomics reveal host‐specific nucleotide variation in entomophthoralean fungi
Authors: De Fine Licht Henrik H. , Jensen Annette B. , Eilenberg Jørgen 
Published: September 2016

AbstractObligate parasites are under strong selection to increase exploitation of their host to survive while evading detection by host immune defences. This has often led to elaborate pathogen adaptations and extreme host specificity. Specialization on one host, however, often incurs a trade‐off influencing the capacity to infect alternate hosts. Here, we investigate host adaptation in two morphologically indistinguishable and closely related obligate specialist insect‐pathogenic fungi from the phylum Entomophthoromycota,Entomophthora muscae sensu strictoandE. muscae sensu lato,pathogens of houseflies (Musca domestica) and cabbage flies (Delia radicum), respectively. We compared single nucleotide polymorphisms within and between these twoE. muscaespecies using 12RNA‐seq transcriptomes from five biological samples. All five isolates contained intra‐isolate polymorphisms that segregate in 50:50 ratios, indicative of genetic duplication events or functional diploidy. Comparative analysis ofdN/dSratios between the multinucleateE. muscae s.str. andE. muscae s.l. revealed molecular signatures of positive selection in transcripts related to utilization of host lipids and the potential secretion of toxins that interfere with the host immune response. Phylogenetic comparison with the nonobligate generalist insect‐pathogenic fungusConidiobolus coronatusrevealed a gene‐family expansion of trehalase enzymes inE. muscae. The main sugar in insect haemolymph is trehalose, and efficient sugar utilization was probably important for the evolutionary transition to obligate insect pathogenicity inE. muscae. These results support the hypothesis that genetically based host specialization in specialist pathogens evolves in response to the challenge of using resources and dealing with the immune system of different hosts.
Investigation on the anaerobic propionate degradation by Escherichia coli K12
Authors: Simonte Francesca M. , Dötsch Andreas , Galego Lisete , Arraiano Cecilia , Gescher Johannes 
Published: September 2016

SummaryPropionate is an abundant carboxylic acid in nature. Microorganisms metabolize propionate aerobically via the 2‐methylcitrate pathway. This pathway depends on a series of three reactions in the citric acid cycle that leads to the conversion of succinate to oxaloacetate. Interestingly, the γ‐proteobacterium Escherichia coli can use propionate as a carbon and electron source under oxic but not under anoxic conditions. RT‐PCR and transcriptomic analysis revealed a posttranscriptional regulation of the prpBCDE‐gene cluster encoding the necessary enzymes for propionate metabolism. The polycistronic mRNA seems to be hydrolyzed in the 3′–5′ direction under anoxic conditions. This regulatory strategy is highly constructive because the last gene of the operon encodes the first enzyme of the propionate metabolism. Further analysis revealed that RNase R is involved in the hydrolysis of the prp transcripts. Consequently, an rnr‐deletion strain could metabolize propionate under anoxic conditions. To the best of our knowledge, this is the first study describing the influence of RNase R on the anaerobic metabolism of E. coli.
Vision in the common bed bug Cimex lectulariusL. (Hemiptera: Cimicidae): eye morphology and spectral sensitivity
Authors: MCNEILL C. A. , ALLAN S. A. , KOEHLER P. G. , PEREIRA R. M. , WEEKS E. N. I. 
Published: September 2016

AbstractBed bugs as pests of public health importance recently experienced a resurgence in populations throughout the U.S. and other countries. Consequently, recent research efforts have focused on improving understanding of bed bug physiology and behaviour to improve management. While few studies have investigated the visual capabilities of bed bugs, the present study focused specifically on eye morphology and spectral sensitivity. A 3‐D imaging technique was used to document bed bug eye morphology from the first instar through adult and revealed morphological characteristics that differentiate the common bed bug from the tropical bed bug as well as sex‐specific differences. Electrophysiological measurements were used to evaluate the spectral sensitivity of adult bed bugs. Male bed bugs were more responsive than females at some wavelengths. Electrophysiological studies provided evidence for at least one photoreceptor with a spectral sensitivity curve peak in the green (λmax 520 nm) region of the spectrum. The broadened long wavelength portion of the spectral sensitivity curve may potentially indicate another photoreceptor in the yellow–green (λmax 550 nm) portion of the spectrum or screening pigments. Understanding more about bed bug visual biology is vital for designing traps, which are an important component of integrated bed bug management.
An assay for entry of secreted fungal effectors into plant cells
Authors: Lo Presti Libera , Zechmann Bernd , Kumlehn Jochen , Liang Liang , Lanver Daniel , Tanaka Shigeyuki , Bock Ralph , Kahmann Regine 
Published: September 2016

Summary

Successful colonization of plants by prokaryotic and eukaryotic pathogens requires active effector‐mediated suppression of defense responses and host tissue reprogramming. Secreted effector proteins can either display their activity in the apoplast or translocate into host cells and function therein. Although characterized in bacteria, the molecular mechanisms of effector delivery by fungal phytopathogens remain elusive.

Here we report the establishment of an assay that is based on biotinylation of effectors in the host cytoplasm as hallmark of uptake. The assay exploits the ability of the bacterial biotin ligase BirA to biotinylate any protein that carries a short peptide (Avitag). It is based on the stable expression of BirA in the cytoplasm of maize plants and on engineering of Ustilago maydis strains to secrete Avitagged effectors.

We demonstrate translocation of a number of effectors in the U. maydis–maize system and show data that suggest that the uptake mechanism could be rather nonspecific

The assay promises to be a powerful tool for the classification of effectors as well as for the functional study of effector uptake mechanism not only in the chosen system but more generally for systems where biotrophic interactions are established.
Fungal diversity and seasonal succession in ash leaves infected by the invasive ascomycete Hymenoscyphus fraxineus
Authors: Cross Hugh , Sønstebø Jørn Henrik , Nagy Nina E. , Timmermann Volkmar , Solheim Halvor , Børja Isabella , Kauserud Håvard , Carlsen Tor , Rzepka Barbara , Wasak Katarzyna , Vivian‐Smith Adam , Hietala Ari M. 
Published: September 2016

Summary

High biodiversity is regarded as a barrier against biological invasions. We hypothesized that the invasion success of the pathogenic ascomycete Hymenoscyphus fraxineus threatening common ash in Europe relates to differences in dispersal and colonization success between the invader and the diverse native competitors.

Ash leaf mycobiome was monitored by high‐throughput sequencing of the fungal internal transcribed spacer region (ITS) and quantitative PCR profiling of H. fraxineus DNA.

Initiation of ascospore production by H. fraxineus after overwintering was followed by pathogen accumulation in asymptomatic leaves. The induction of necrotic leaf lesions coincided with escalation of H. fraxineus DNA levels and changes in proportion of biotrophs, followed by an increase of ubiquitous endophytes with pathogenic potential.

H. fraxineus uses high propagule pressure to establish in leaves as quiescent thalli that switch to pathogenic mode once these thalli reach a certain threshold – the massive feedback from the saprophytic phase enables this fungus to challenge host defenses and the resident competitors in mid‐season when their density in host tissues is still low. Despite the general correspondence between the ITS‐1 and ITS‐2 datasets, marker biases were observed, which suggests that multiple barcodes provide better overall representation of mycobiomes.
Dose and Duration of Opioid Use in Patients with Cancer and Noncancer Pain at an Outpatient Hospital Setting in Malaysia
Authors: Zin Che S. , Rahman Norny A. , Ismail Che R. , Choy Leong W. 
Published: September 2016

AbstractBackgroundThere are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain.MethodsThis retrospective, cross‐sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups.ResultsA total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group.ConclusionsThe finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest.
Eye movement as a biomarker of schizophrenia: Using an integrated eye movement score
Authors: Morita Kentaro , Miura Kenichiro , Fujimoto Michiko , Yamamori Hidenaga , Yasuda Yuka , Iwase Masao , Kasai Kiyoto , Hashimoto Ryota 
Published: September 2016

AimStudies have shown that eye movement abnormalities are possible neurophysiological biomarkers for schizophrenia. The aim of this study was to investigate the utility of eye movement abnormalities in identifying patients with schizophrenia from healthy controls.MethodsEighty‐five patients with schizophrenia and 252 healthy controls participated in this study. Eye movement measures were collected from free viewing, fixation stability, and smooth pursuit tests. In an objective and stepwise method, eye movement measures were extracted to create an integrated eye movement score.ResultsThe discriminant analysis resulted in three eye movement measures; the scanpath length during the free viewing test, the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test, and the duration of fixations during the far distractor paradigm of the fixation stability test. An integrated score using these variables can distinguish patients with schizophrenia from healthy controls with 82% accuracy. The integrated score was correlated with Wechsler Adult Intelligence Scale‐Third Edition full scale IQ, Positive and Negative Syndrome Scale scores, and chlorpromazine equivalents, with different correlation patterns in the three eye movement measures used. The discriminant analysis in subgroups matched for age, sex, years of education, and premorbid IQ revealed a sustained classification rate.ConclusionWe established an integrated eye movement score with high classification accuracy between patients with schizophrenia and healthy controls, although there was a significant effect of medication. This study provides further evidence of the utility of eye movement abnormalities in schizophrenia pathology and treatment.
Triggers for Preeclampsia Onset: a Case‐Crossover Study
Authors: Ford Jane B. , Schemann Kathrin , Patterson Jillian A. , Morris Jonathan , Herbert Robert D. , Roberts Christine L. 
Published: September 2016

AbstractBackgroundRisk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset.MethodsWe used a case‐crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1–7 days preceding diagnosis of preeclampsia) and control windows (8–14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported.ResultsAmong 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8–14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset.ConclusionRecent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia.
Huia caspica gen. & comb. nov., a dinoflagellate species that recently crossed the marine‐freshwater boundary
Authors: Gu Haifeng , Mertens Kenneth N. , Liu Tingting 
Published: September 2016

SUMMARYThe dinoflagellate subfamily Diplopsalidoideae encompasses 11 genera whose plate patterns show a large diversity. In a recently published molecular phylogeny (Liu et al.
2015) some of these genera (e.g. Diplopsalis, Diplopelta) are polyphyletic, suggesting that further subdivision of these genera is needed. Here we established the cyst‐theca relationship of Diplopsalis caspica by incubating cysts collected from the East China Sea. Cells of D. caspica display a plate formula of Po, X, 3′, 1a, 6″, 3c+t, ?4s, 5″′, 1″″, characterized by a small, parallelogrammic anterior intercalary plate (1a) located in the middle of the dorsal part of the epitheca. The cysts are spherical and smooth‐walled with a theropylic archeopyle. In addition, we obtained four large subunit ribosomal DNA (LSU rDNA) sequences from the germinated motile cells by single‐cell polymerase chain reaction. Strains of D. caspica from the marine environment of the East China Sea differ at 0–2 positions of LSU rDNA sequences from that of lacustrine strains from NE China. In the molecular phylogeny, D. caspica was close to Lebouraia pusilla but distant from D. lenticula, the type species of Diplopsalis. Our results support the systematic importance of plate 1a, and therefore D. caspica was transferred to a new genus, Huia. The conservative LSU rDNA sequences in H. caspica suggest that the marine‐freshwater transition occurred recently.
Orthographic and phonological processing in developing readers revealed by ERPs
Authors: Eddy Marianna D. , Grainger Jonathan , Holcomb Phillip J. , Gabrieli John D. E. 
Published: September 2016

AbstractThe development of neurocognitive mechanisms in single word reading was studied in children ages 8–10 years using ERPs combined with priming manipulations aimed at dissociating orthographic and phonological processes. Transposed‐letter (TL) priming (barin–BRAIN vs. bosin–BRAIN) was used to assess orthographic processing, and pseudohomophone (PH) priming (brane–BRAIN vs. brant–BRAIN) was used to assess phonological processing. Children showed TL and PH priming effects on both the N250 and N400 ERP components, and the magnitude of TL priming correlated positively with reading ability, with better readers showing larger TL priming effects. Phonological priming, on the other hand, did not correlate with reading ability. The positive correlations between TL priming and reading ability in children points to a key role for flexible sublexical orthographic representations in reading development, in line with their hypothesized role in the efficient mapping of orthographic information onto semantic information in skilled readers.
Pupillary reactivity to negative stimuli prospectively predicts recurrence of major depressive disorder in women
Authors: Kudinova Anastacia Y. , Burkhouse Katie L. , Siegle Greg , Owens Max , Woody Mary L. , Gibb Brandon E. 
Published: September 2016

AbstractThere is a large body of research supporting the association between disrupted physiological reactivity to negative stimuli and depression. The present study aimed to examine whether physiological reactivity to emotional stimuli, assessed via pupil dilation, served as a biological marker of risk for depression recurrence among individuals who are known to be at a higher risk due to having previous history of depression. Participants were 57 women with a history of major depressive disorder (MDD). Pupil dilation to angry, happy, sad, and neutral faces was recorded. Participants' diagnoses and symptoms were assessed 24 months after the initial assessment. We found that women's pupillary reactivity to negative (sad or angry faces) but not positive stimuli prospectively predicted MDD recurrence. Additionally, we found that both hyper‐ and hypopupillary reactivity to angry faces predicted risk for MDD recurrence. These findings suggest that disrupted physiological response to negative stimuli indexed via pupillary dilation could serve as a physiological marker of MDD risk, thus presenting clinicians with a convenient and inexpensive method to predict which of the at‐risk women are more likely to experience depression recurrence.