bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole genome sequencing of 56Mimulusindividuals illustrates population structure and local selection
Authors: Puzey Joshua R. , Willis John H. , Kelly John K.
Published: November 2015

Across western North America,Mimulus guttatusexists as many local populations adapted to site-specific challenges including salt spray, temperature, water availability, and soil chemistry. Gene flow between locally adapted populations will effect genetic diversity in both local demes and across the larger meta-population. A single population of annualM. guttatusfrom Iron Mountain, Oregon (IM) has been extensively studied and we here building off this research by analyzing whole genome sequences from 34 inbred lines from IM in conjunction with sequences from 22Mimulusindividuals from across the geographic range. Three striking features of these data address hypotheses about migration and selection in a locally adapted population. First, we find very high intra-population polymorphism (synonymous π = 0.033). Variation outside genes may be even higher, but is difficult to estimate because excessive divergence affects read mapping. Second, IM exhibits a significantly positive genome-wide average for Tajima’s D. This indicates allele frequencies are typically more intermediate than expected from neutrality, opposite the pattern observed in other species. Third, IM exhibits a distinctive haplotype structure. There is a genome-wide excess of positive associations between minor alleles; consistent with an important effect of gene flow from nearbyMimuluspopulations. The combination of multiple data types, including a novel, tree-based analytic method and estimates for structural polymorphism (inversions) from previous genetic mapping studies, illustrates how the balance of strong local selection, limited dispersal, and meta-population dynamics manifests across the genome.
MAGELLAN: a tool to explore small fitness landscapes
Authors: Brouillet S , Annoni H , Ferretti L , Achaz G
Published: November 2015

1

In a fitness landscape, fitness values are associated to all genotypes corresponding to several, potentially all, combinations of a set of mutations. In the last decade, many small experimental fitness landscapes have been partially or completely resolved, and more will likely follow. MAGELLAN is a web-based graphical software to explore small fitness/energy landscapes through dynamic visualization and quantitative measures. It can be used to explore input custom landscapes, previously published experimental landscapes or randomly generated model landscapes.
Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
Authors: Raj Anil , Wang Sidney H. , Shim Heejung , Harpak Arbel , Li Yang I. , Englemann Brett , Stephens Matthew , Gilad Yoav , Pritchard Jonathan K.
Published: November 2015

Accurate annotation of protein coding regions is essential for understanding how genetic information is translated into biological functions. Here we describe riboHMM, a new method that uses ribosome footprint data along with gene expression and sequence information to accurately infer translated sequences. We applied our method to human lymphoblastoid cell lines and identified 7,273 previously unannotated coding sequences, including 2,442 translated upstream open reading frames. We observed an enrichment of harringtonine-treated ribosome footprints at the inferred initiation sites, validating many of the novel coding sequences. The novel sequences exhibit significant signatures of selective constraint in the reading frames of the inferred proteins, suggesting that many of these are functional. Nearly 40% of bicistronic transcripts showed significant negative correlation in the levels of translation of their two coding sequences, suggesting a key regulatory role for these novel translated sequences. Our work significantly expands the set of known coding regions in humans.
RNA structure replaces the need for U2AF2 in splicing
Authors: Lin Chien-Ling , Taggart Allison J. , Lim Kian Huat , Cygan Kamil J. , Ferraris Luciana , Creton Robbert , Huang Yen-Tsung , Fairbrother William G.
Published: November 2015

RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.
SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes
Authors: Shen Yue , Stracquadanio Giovanni , Wang Yun , Yang Kun , Mitchell Leslie A. , Xue Yaxin , Cai Yizhi , Chen Tai , Dymond Jessica S. , Kang Kang , Gong Jianhui , Zeng Xiaofan , Zhang Yongfen , Li Yingrui , Feng Qiang , Xu Xun , Wang Jun , Wang Jian , Yang Huanming , Boeke Jef D. , Bader Joel S.
Published: November 2015

Synthetic chromosome rearrangement and modification byloxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome armsynIXR(43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64synIXRSCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designedloxPsymsites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.
Bison and cattle grazing management, bare ground coverage, and links to suspended sediment concentrations in grassland streams
Authors: Grudzinski Bartosz P. , Daniels Melinda D. , Anibas Kyle , Spencer David
Published: November 2015

This study quantified the impact of bison and cattle grazing management practices on bare ground coverage at the watershed, riparian, and forested riparian scales within the Flint Hills ecoregion in Kansas. We tested for correlations between bare ground coverage and fluvial suspended sediment concentrations during base‐flow and storm‐flow events. We used remotely sensed imagery combined with field surveys to classify ground cover and quantify the presence of bare ground. Base‐flow water samples were collected bi‐monthly during rain‐free periods and 24 h following precipitation events. Storm‐flow water samples were collected on the rising limb of the hydrograph, using single‐stage automatic samplers. Ungrazed treatments contained the lowest coverage of bare ground at the watershed, riparian, and forested riparian scales. Bison treatments contained the highest coverage of bare ground at the watershed scale, while high‐density cattle treatments contained the highest coverage of bare ground at the riparian and forested riparian scales. In bison and cattle‐grazed treatments, a majority of bare ground was located near fence lines, watershed boundaries, and third‐ and fourth‐order stream segments. Inorganic sediment concentrations at base flow were best predicted by riparian bare ground coverage, while storm‐flow sediment concentrations were best predicted by watershed scale bare ground coverage.
Apportionment of bioavailable phosphorus loads entering Cayuga Lake, New York
Authors: Prestigiacomo Anthony R. , Effler Steven W. , Gelda Rakesh K. , Matthews David A. , Auer Martin T. , Downer Benjamin E. , Kuczynski Anika , Walter M. Todd
Published: November 2015

The integration of the phosphorus (P) bioavailability concept into a P loading analysis for Cayuga Lake, New York, is documented. Components of the analyses included the: (1) monitoring of particulate P (PP), soluble unreactive P (SUP), and soluble reactive P (SRP), supported by biweekly and runoff event‐based sampling of the lake's four largest tributaries; (2) development of relationships between tributary P concentrations and flow; (3) algal bioavailability assays of PP, SUP, and SRP from primary tributaries and the three largest point sources; and (4) development of P loading estimates to apportion contributions according to individual nonpoint and point sources, and to represent the effects of interannual variations in tributary flows on P loads. Tributary SRP, SUP, and PP are demonstrated to be completely, mostly, and less bioavailable, respectively. The highest mean bioavailability for PP was observed for the stream with the highest agriculture land use. Point source contributions to the total bioavailable P load (BAPL) are minor (5%), reflecting the benefit of reductions from recent treatment upgrades. The BAPL represented only about 26% of the total P load, because of the large contribution of the low bioavailable PP component. Most of BAPL (>70%) is received during high flow intervals. Large interannual variations in tributary flow and coupled BAPL will tend to mask future responses to changes in individual inputs.
Assessing Satellite and Ground‐Based Potential Evapotranspiration for Hydrologic Applications in the Colorado River Basin
Authors: Barik Muhammad G. , Hogue Terri S. , Franz Kristie J. , Kinoshita Alicia M.
Published: November 2015

This study evaluates a remotely sensed and two ground‐based potential evapotranspiration (PET) products for hydrologic application in the Upper Colorado River Basin (UCRB). The remotely sensed Moderate Resolution Imaging Spectroradiometer product (MODIS‐PET) is a continuous, daily time series with 250 m resolution derived using the Priestley‐Taylor (P‐T) equation. The MODIS‐PET is evaluated against regional flux tower data as well as a synthetic pan product (Epan; 0.125°, daily) derived from the North American Land Data Assimilation System (NLDAS) and a Hargreaves PET derived from DAYMET variables (DAYMET‐PET; 1 km, daily). Compared to point‐scale PET computed using regional flux tower data, the MODIS‐PET had lower errors, with RMSE values ranging from 2.24 to 2.85 mm/day. Epan RMSE values ranged from 3.70 to 3.76 mm/day and DAYMET‐PET RMSE values ranged from 3.55 to 4.58 mm/day. Further investigation showed biases in temperature and radiation data contribute to uncertainty in the MODIS‐PET values, while bias in NLDAS temperature, downward shortwave (SW↓), and downward longwave (LW↓) propagate in the Epan estimates. Larger discrepancies between methods were observed in the warmer, drier regions of the UCRB, however, the MODIS‐PET was more responsive to landcover transitions and better captured basin heterogeneity. Results indicate the satellite‐based MODIS product can serve as a viable option for obtaining spatial PET values across the UCRB.
Improving the Quality of Imaging in the Emergency Department
Authors: Blackmore C. Craig , Castro Alexandra
Published: November 2015

Imaging is critical for the care of emergency department (ED) patients. However, much of the imaging performed for acute care today is overutilization, creating substantial cost without significant benefit. Further, the value of imaging is not easily defined, as imaging only affects outcomes indirectly, through interaction with treatment. Improving the quality, including appropriateness, of emergency imaging requires understanding of how imaging contributes to patient care. The six‐tier efficacy hierarchy of Fryback and Thornbury enables understanding of the value of imaging on multiple levels, ranging from technical efficacy to medical decision‐making and higher‐level patient and societal outcomes. The imaging efficacy hierarchy also allows definition of imaging quality through the Institute of Medicine (IOM)'s quality domains of safety, effectiveness, patient‐centeredness, timeliness, efficiency, and equitability and provides a foundation for quality improvement. In this article, the authors elucidate the Fryback and Thornbury framework to define the value of imaging in the ED and to relate emergency imaging to the IOM quality domains.
Generation of Evidence and Translation Into Practice: Lessons Learned and Future Directions
Authors: McCabe Aileen Mairéad , Kuppermann Nathan
Published: November 2015

The generation, validation, and then translation of definitive evidence to bedside evidence‐based practice is inconsistent and presents many challenges to emergency department (ED) researchers and clinicians. This is particularly true for diagnostic imaging in the ED, where benefits and drawbacks may be difficult to assess in the chaotic ED setting. This article describes, in large part, the experience of the Pediatric Emergency Care Applied Research Network (PECARN) in deriving and validating the traumatic brain injury prediction rules and how PECARN is translating these prediction rules into clinical practice. Furthermore, we discuss the potential for patient/parent shared decision‐making with a focus on patient‐centered outcomes in ED research and the role this shared decision‐making may play in enhancing knowledge translation and implementation of evidence‐based care in the ED.
Variation in Pediatric Cervical Spine Computed Tomography Radiation Dose Index
Authors: Marin Jennifer R. , Sengupta Debapriya , Bhargavan‐Chatfield Mythreyi , Kanal Kalpana M. , Mills Angela M. , Applegate Kimberly E.
Published: November 2015

Objectives

The objective was to evaluate variation in the current estimated radiation dose index for pediatric cervical spine (c‐spine) computed tomography (CT) examinations.

Methods

This was a retrospective analysis of pediatric (age younger than 19 years) c‐spine CT examinations from the American College of Radiology Dose Index Registry, July 2011 through December 2014. We used the volume CT dose index (CTDIvol) as the radiation dose estimate and used summary statistics to describe patient and hospital characteristics.

Results

There were 12,218 pediatric CT c‐spine examinations performed across 296 participating hospitals. Fifty‐six percent were in male patients, and 79% were in children older than 10 years. Most hospitals (55%) were community hospitals without trauma designations, and the largest proportion of examinations (41%) were performed at these hospitals. The median CTDIvol was 15 mGy (interquartile range = 9 to 23 mGy) representing a more than 2.5‐fold difference between the 25th and 75th percentiles. Pediatric hospitals (both trauma and nontrauma centers) delivered the lowest CTDIvol across all age groups and showed the least amount of variability in dose.

Conclusions

There is significant variation in the radiation dose index for pediatric c‐spine CT examinations. Pediatric hospitals practice at lower CT dose estimates than other hospitals. Individual hospitals should examine their practices in an effort to ensure standardization and optimization of CT parameters to minimize radiation exposures to pediatric patients.
Funding Research in Emergency Diagnostic Imaging: Summary of a Panel Discussion at the 2015 Academic Emergency Medicine Consensus Conference
Authors: Cherney Alan R. , Marin Jennifer R. , Brown Jeremy , Anise Ayodola , Krosnick Steven , Henriksen Kerm , Lewis Roger J. , Mills Angela M.
Published: November 2015

As part of the 2015 Academic Emergency Medicine consensus conference “Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization,” a panel of representatives from the National Institute of Health's Office of Emergency Care Research, the National Institute of Biomedical Imaging and Bioengineering, the Agency for Healthcare Research and Quality, and the Patient‐Centered Outcomes Research Institute was assembled to discuss future opportunities for funding research in this particular area of interest. Representatives from these agencies and organizations discussed their missions and priorities and how they distribute funding. They also addressed questions on mechanisms for new and established researchers to secure future funding.
Clinical Decision Rules for Diagnostic Imaging in the Emergency Department: A Research Agenda
Authors: Finnerty Nathan M. , Rodriguez Robert M. , Carpenter Christopher R. , Sun Benjamin C. , Theyyunni Nik , Ohle Robert , Dodd Kenneth W. , Schoenfeld Elizabeth M. , Elm Kendra D. , Kline Jeffrey A. , Holmes James F. , Kuppermann Nathan
Published: November 2015

Background

Major gaps persist in the development, validation, and implementation of clinical decision rules (CDRs) for diagnostic imaging.

Objectives

The objective of this working group and article was to generate a consensus‐based research agenda for the development and implementation of CDRs for diagnostic imaging in the emergency department (ED).

Methods

The authors followed consensus methodology, as outlined by the journal Academic Emergency Medicine (AEM), combining literature review, electronic surveys, telephonic communications, and a modified nominal group technique. Final discussions occurred in person at the 2015 AEM consensus conference.

Results

A research agenda was developed, prioritizing the following questions: 1) what are the optimal methods to justify the derivation and validation of diagnostic imaging CDRs, 2) what level of evidence is required before disseminating CDRs for widespread implementation, 3) what defines a successful CDR, 4) how should investigators best compare CDRs to clinical judgment, and 5) what disease states are amenable (and highest priority) to development of CDRs for diagnostic imaging in the ED?

Conclusions

The concepts discussed herein demonstrate the need for further research on CDR development and implementation regarding diagnostic imaging in the ED. Addressing this research agenda should have direct applicability to patients, clinicians, and health care systems.
Knowledge Translation and Barriers to Imaging Optimization in the Emergency Department: A Research Agenda
Authors: Probst Marc A. , Dayan Peter S. , Raja Ali S. , Slovis Benjamin H. , Yadav Kabir , Lam Samuel H. , Shapiro Jason S. , Farris Coreen , Babcock Charlene I. , Griffey Richard T. , Robey Thomas E. , Fortin Emily M. , Johnson Jamlik O. , Chong Suzanne T. , Davenport Moira , Grigat Daniel W. , Lang Eddy L.
Published: November 2015

Researchers have attempted to optimize imaging utilization by describing which clinical variables are more predictive of acute disease and, conversely, what combination of variables can obviate the need for imaging. These results are then used to develop evidence‐based clinical pathways, clinical decision instruments, and clinical practice guidelines. Despite the validation of these results in subsequent studies, with some demonstrating improved outcomes, their actual use is often limited. This article outlines a research agenda to promote the dissemination and implementation (also known as knowledge translation) of evidence‐based interventions for emergency department (ED) imaging, i.e., clinical pathways, clinical decision instruments, and clinical practice guidelines. We convened a multidisciplinary group of stakeholders and held online and telephone discussions over a 6‐month period culminating in an in‐person meeting at the 2015 Academic Emergency Medicine consensus conference. We identified the following four overarching research questions: 1) what determinants (barriers and facilitators) influence emergency physicians’ use of evidence‐based interventions when ordering imaging in the ED; 2) what implementation strategies at the institutional level can improve the use of evidence‐based interventions for ED imaging; 3) what interventions at the health care policy level can facilitate the adoption of evidence‐based interventions for ED imaging; and 4) how can health information technology, including electronic health records, clinical decision support, and health information exchanges, be used to increase awareness, use, and adherence to evidence‐based interventions for ED imaging? Advancing research that addresses these questions will provide valuable information as to how we can use evidence‐based interventions to optimize imaging utilization and ultimately improve patient care.
Relation between age of first drinking and mental health and alcohol and drug disorders in adulthood: evidence from a 35‐year cohort study
Authors: Newton‐Howes G. , Boden J. M.
Published: November 2015

Aims

To estimate associations between age of first drinking (AFD) and alcohol use disorder, nicotine dependence, cannabis dependence, illicit drug dependence, major depression and anxiety disorder in adulthood, net of a series of covariate factors.

Design

Data were obtained from a longitudinal birth cohort.

Setting

Christchurch, New Zealand.

Participants

The Christchurch Health Development Study (CHDS), a longitudinal study of a cohort born in 1977 and studied to age 35 years. Analysis samples ranged in size from 1056 (ages 11–13 years) to 962 (age 35 years); 50.2% of the total sample was male.

Measurements

A measure of AFD (ages 5–13+ years) was generated using latent class analysis. Outcome measures included: major depression, anxiety disorders, alcohol use disorder, nicotine dependence, cannabis dependence and other illicit drug dependence during the period 15–35 years. Covariate factors measured during childhood included family socio‐economic status, family functioning, parental alcohol‐related attitudes/behaviours and individual factors.

Findings

Earlier AFD was associated significantly (P < 0.05) with increased risk of later alcohol use disorders, nicotine dependence and illicit drug dependence, and was associated marginally (P < 0.10) with cannabis dependence, but not depression or anxiety disorder. After controlling for covariate factors, the associations between AFD and outcomes were no longer statistically significant [alcohol use disorder: B = –0.07, 95% confidence interval (CI) = –0.22, 0.08; nicotine dependence: B = –0.15, 95% CI = –0.34, 0.04; illicit drug dependence: B = –0.29, 95% CI = –0.73, 0.15; cannabis dependence: B = –0.05, 95% CI = –0.31, 0.22].

Conclusions

The associations between age of first drinking and later alcohol/drug disorders appear to be accounted for at least to some degree by factors related to characteristics of the individual and family during childhood.
Awareness and use of electronic cigarettes and heat‐not‐burn tobacco products in Japan
Authors: Tabuchi Takahiro , Kiyohara Kosuke , Hoshino Takahiro , Bekki Kanae , Inaba Yohei , Kunugita Naoki
Published: November 2015

Background and Aims

In addition to some electronic cigarettes (e‐cigarettes), new heat‐not‐burn tobacco products Ploom and iQOS have recently begun to be sold by tobacco companies. These products are regulated differently in Japan, depending on whether the contents are liquid or tobacco leaf. Our objective was to estimate percentages of awareness and use of e‐cigarettes and heat‐not‐burn tobacco products among the Japanese population, including minors.

Design and Setting

An internet survey (randomly sampled research agency panellists) with a propensity score adjustment for “being a respondent in an internet survey” using a nationally representative sample in Japan.

Participants

A total of 8240 respondents aged 15–69 years in 2015 (4084 men and 4156 women).

Measurements

Adjusted percentages of awareness and use of e‐cigarettes (nicotine or non‐nicotine e‐cigarettes) and heat‐not‐burn products among total participants; product types and percentages ever used among e‐cigarettes ever users.

Findings

Of respondents in Japan, 48% [95% confidence interval (CI) = 47–49] were aware of e‐cigarettes and heat‐not‐burn tobacco products, 6.6% (95% CI = 6.1–7.1) had ever used, 1.3% (95% CI = 1.0–1.5) had used in the last 30 days and 1.3% (95% CI = 1.1–1.6) had experience of > 50 sessions. Seventy‐two per cent (95% CI = 69–76) of ever users used non‐nicotine e‐cigarettes, while 33% (95% CI = 30–37) of them used nicotine e‐cigarettes, which has the majority share world‐wide; 7.8% (95% CI = 5.5–10.0) and 8.4% (95% CI = 6.1–10.7) of them used the new devices, Ploom and iQOS, respectively, with a relatively higher percentage among the younger population.

Conclusions

Approximately half the respondents in a Japanese internet survey were aware of e‐cigarettes and heat‐not‐burn tobacco products, 6.6% had ever used. More than 70% of ever users used non‐nicotine e‐cigarettes, the sale of which is not legally prohibited, even to minors, in Japan, and 33% of them used nicotine e‐cigarettes; 3.5% of never smoking men and 1.3% of never smoking women had ever used e‐cigarettes. Corresponding figures for use in the last 30 days were 0.6% and 0.3%, predominantly non‐nicotine e‐cigarettes.
Detection of volume loss using the Nexfin device in blood donors
Authors: Nicia S. B. , van Veelen T. A. , Stens J. , Koopman M. M. W. , Boer C.
Published: November 2015

We investigated which haemodynamic parameters derived from Nexfin non‐invasive continuous arterial blood pressure measurements are optimal to detect controlled volume loss in spontaneously breathing subjects. Haemodynamic monitoring was performed in 40 whole‐blood donors. Mean arterial pressure, cardiac index, systemic vascular resistance index and pulse pressure variation were recorded during controlled breathing, and a Valsalva manoeuvre was performed before and after blood donation. Blood donation resulted in a reduction in cardiac index (from 3.96 ± 0.84 l.min−1.m2 to 3.30 ± 0.61 l.min−1.m2; p < 0.001), an increase in systemic vascular resistance (from 1811 ± 450 dyn.s.cm−5.m2 to 2137 ± 428 dyn.s.cm−5.m2; p < 0.001) and an increase in pulse pressure variation (from 13.4 ± 5.1 to 15.3 ± 5.4%; p = 0.02). The area under the receiver operating characteristic curve to detect volume loss was highest for cardiac index (0.94, 95% CI 0.88–0.99) and systemic vascular resistance (0.90, 95% CI 0.82–0.99). Nexfin is a non‐invasive haemodynamic monitor that can feasibly detect volaemic changes in spontaneously breathing subjects.
A randomised comparison between ultrasound and nerve stimulation for infraclavicular catheter placement
Authors: Dhir S. , Armstrong K. , Armstrong P. , Bouzari A. , Mall J. , Yu J. , Ganapathy S. , King G.
Published: November 2015

We conducted this study to determine if placement of infraclavicular catheters guided by ultrasound is quicker than placement guided by nerve stimulation. Infraclavicular brachial plexus catheters were inserted in 210 randomly allocated patients who were scheduled for elective hand or elbow surgery. Needle and catheter placement was guided by ultrasound (n = 105) or by nerve stimulation (n = 105). The primary outcome was time to sensory block success. Success rate was similar between the two techniques (83.2% vs 81.4%, p = 0.738). However, placement of ultrasound‐guided catheters took less time (7.2 [2.5] vs 9.6 [3.6] min, p < 0 .001). Pain and satisfaction scores, and incidence of nerve deficit, were also similar with both techniques.
Health‐related quality of life is unimpaired in children and adolescents with Marfan syndrome despite its distinctive phenotype
Authors: Mueller Goetz C. , Steiner Kristoffer , Wild Jeske M. , Stark Veronika , Kozlik‐Feldmann Rainer , Mir Thomas S.
Published: November 2015

Aim

Marfan syndrome (MFS) is a progressive, life‐threatening genetic disorder of the connective tissue, which causes impaired quality of life (QoL) in adults. This study investigated the quality of life in children and adolescents, taking into account their gender, age and how MFS affected their organs.

Methods

This prospective nonrandomised single‐centre study included 46 patients with verified MFS with a mean age of 10.98 years (±3.72). QoL was measured using the self‐reported, multidimensional KINDL‐R questionnaire and compared with an age‐matched control group of 174 children and adolescents.

Results

No significant overall reduction of QoL was found. Total QoL scores for patients diagnosed at four to seven years were the same as the control group (77.65 ± 9.37 versus 77.06 ± 11.72), but they were higher for patients aged eight to 16 years (75.15 ± 9.19 versus 70.46 ± 11.35, p = 0.025). No gender‐specific differences or impairments in QoL during adolescence were observed (p > 0.05). Analysis of the effect of organ manifestation on QoL showed better or equal QoL scores (p > 0.05), despite distinctive phenotypes such as ectopia lentis.

Conclusion

QoL was fairly good in paediatric patients with MFS, and there was no impairment during adolescence. Despite the distinctive phenotype, quality of life was unimpaired in younger patients.
The course of social cognitive and metacognitive ability in depression: Deficit are only partially normalized after full remission of first episode major depression
Authors: Ladegaard Nicolai , Videbech Poul , Lysaker Paul H. , Larsen Erik R.
Published: November 2015

Objectives

Research has suggested that patients suffering from major depressive disorder (MDD) experience deficits in the related domains of social cognition and metacognition. Most research has focused on detecting deficits among persons who are acutely symptomatic. Thus, little is known about whether these deficits persist after symptoms have remitted. As a first, this study investigated social cognitive and metacognitive deficits in patients with MDD in the acute and remitted state.

Design

Longitudinal case–control.

Methods

Forty‐four drug‐naïve depressed patients and an equal number of matched healthy controls were assessed in multiple domains of social cognition including theory of mind, social perception, and metacognition. Additionally, a comprehensive neurocognitive (non‐social) test battery was utilized. Following baseline assessment, patients were enrolled in an outpatient treatment programme. Patients reaching remission within 6 months (n = 29) were reassessed 6 months post‐remission. Included for analysis were only patients who followed a course of remission (n = 29) and their paired healthy controls (n = 29).

Results

Analyses of variance revealed that remitted patients performed significantly better at retest than at baseline on nearly all measures. These effects withstood adjusting for test–retest effects. Moreover, remitted patients performed up to level of healthy controls on some but not all social cognitive tasks and metacognition at retest.

Conclusions

Overall, results suggests that social cognitive and metacognitive ability may improve with symptom remission in major depression although it may not reach a level equal to persons who have never experienced depression.

Practitioner points

Many with first‐episode depression experience deficits in social cognition.

When first‐episode depression remits, social cognition may improve.

After remission, first‐episode depressed patients may still experience deficits in social cognition.

We have yet to determine whether social cognitive deficits existed prior to the onset of depression.

Longer‐term longitudinal studies of social cognition in depression are needed.

Treatment was pharmacological and non‐manualized psychotherapy, the effects of which were not controlled for.

Sample sizes were modest, which must caution against generalization of the results.
Who can escape the natural number bias in rational number tasks? A study involving students and experts
Authors: Obersteiner Andreas , Hoof Jo Van , Verschaffel Lieven , Dooren Wim Van
Published: November 2015

Many learners have difficulties with rational number tasks because they persistently rely on their natural number knowledge, which is not always applicable. Studies show that such a natural number bias can mislead not only children but also educated adults. It is still unclear whether and under what conditions mathematical expertise enables people to be completely unaffected by such a bias on tasks in which people with less expertise are clearly biased. We compared the performance of eighth‐grade students and expert mathematicians on the same set of algebraic expression problems that addressed the effect of arithmetic operations (multiplication and division). Using accuracy and response time measures, we found clear evidence for a natural number bias in students but no traces of a bias in experts. The data suggested that whereas students based their answers on their intuitions about natural numbers, expert mathematicians relied on their skilled intuitions about algebraic expressions. We conclude that it is possible for experts to be unaffected by the natural number bias on rational number tasks when they use strategies that do not involve natural numbers.
Modelling non‐normal data: The relationship between the skew‐normal factor model and the quadratic factor model
Authors: Smits Iris A. M. , Timmerman Marieke E. , Stegeman Alwin
Published: November 2015

Maximum likelihood estimation of the linear factor model for continuous items assumes normally distributed item scores. We consider deviations from normality by means of a skew‐normally distributed factor model or a quadratic factor model. We show that the item distributions under a skew‐normal factor are equivalent to those under a quadratic model up to third‐order moments. The reverse only holds if the quadratic loadings are equal to each other and within certain bounds. We illustrate that observed data which follow any skew‐normal factor model can be so well approximated with the quadratic factor model that the models are empirically indistinguishable, and that the reverse does not hold in general. The choice between the two models to account for deviations of normality is illustrated by an empirical example from clinical psychology.
Mast cells in asthma – state of the art
Authors: Bradding P. , Arthur G.
Published: November 2015

Mast cells (MCs) play a central role in tissue homoeostasis, sensing the local environment through numerous innate cell surface receptors. This enables them to respond rapidly to perceived tissue insults with a view to initiating a co‐ordinated programme of inflammation and repair. However, when the tissue insult is chronic, the ongoing release of multiple pro‐inflammatory mediators, proteases, cytokines and chemokines leads to tissue damage and remodelling. In asthma, there is strong evidence of ongoing MC activation, and their mediators and cell–cell signals are capable of regulating many facets of asthma pathophysiology. This article reviews the evidence behind this.
RNA‐Seq data analysis identifies the comprehensive profile of in vivo interferon‐β‐stimulated genes in multiple sclerosis
Authors: Satoh Jun‐ichi , Takitani Mika , Miyoshi Junko , Kino Yoshihiro
Published: November 2015

Objectives

Interferon‐beta (IFNβ) is the most widely used drug for reducing the disease activity of multiple sclerosis (MS), although a considerable population of MS patients are refractory to IFNβ. To establish personalized therapy for MS, the molecular mechanism underlying the therapeutic effects of IFNβ in MS should be thoroughly characterized by aid of next‐generation sequencing technology.

Methods

To elucidate a comprehensive profile of in vivo IFNβ‐stimulated genes (ISGs) in MS patients, we analyzed a RNA sequencing (RNA‐Seq) dataset numbered SRP045500, composed of the genome‐wide transcriptome of whole blood and purified populations of CD4+ T cells, B cells, and monocytes isolated from MS patients at the time‐point before and 24 h after the first treatment with IFNβ1a.

Results

We identified a set of 914 in vivo ISGs, containing a number of non‐coding RNAs and pseudogenes, along with differential spliced genes in the whole blood of MS patients. The set of 914 ISGs were relevant to the molecular pathways defined as “interferon signaling” and “proteasome,” and were closely associated with gene ontology terms of antiviral and immune responses. We also identified 640, 653 and 1018 ISGs from CD4+ T cells, B cells, and monocytes of MS patients receiving IFNβ treatment, respectively, and extracted 95 genes shared among the three cell types as the core set of ISGs. They included 78 genes that might serve as the most consistent blood biomarkers for assessment of the immediate early in vivo response to IFNβ treatment in MS.

Conclusions

RNA‐Seq data analysis promotes us to characterize the comprehensive profile of in vivo ISGs in MS patients receiving IFNβ treatment.
The alveolar process following single‐tooth extraction: a study of maxillary incisor and premolar sites in man
Authors: Misawa Mônica , Lindhe Jan , Araújo Mauricio G.
Published: November 2015

Objective

The present investigation was performed to determine some dimensional alterations that occur in the alveolar process of the incisor and premolar sites of the maxilla following tooth removal.

Material and methods

Computer‐assisted cone‐beam computed tomography (CBCT) scans were obtained from the maxilla using an iCAT unit, and involved edentulous and contralateral tooth sites. For each site included in the study, parasagittal and axial reconstructions, 1 mm apart, were made and measurements of different variables (cross‐sectional area, height, and width) performed.

Results

The study involved 69 subjects and disclosed that the cross‐sectional area and the height and width of the alveolar process of the lateral incisor site were the smallest and those of the second premolar the largest. All parameters had been significantly reduced after the completion of the ≥1 year of healing. Thus, the overall (i) cross‐sectional area was reduced from 99.1 to 65.0 mm2, (ii) the height from 11.5 to 9.5 mm, and (iii) the width from 8.5 to 3.2 mm (marginal 1/3rd), 8.9 to 4.8 mm (middle portion), and 9.0 to 5.7 mm (apical portion).

Conclusion

The removal of single tooth caused marked hard tissue diminution. The loss of hard tissue was most pronounced in the buccal and marginal portions of the edentulous ridge that in most sites had acquired a triangular shape.
Maxillary 3‐implant removable prostheses without palatal coverage on Locator abutments – a case series
Authors: Mo Arild , Hjortsjö Carl , Olsen‐Bergem Heming , Jokstad Asbjørn
Published: November 2015

Objectives

The aim of this study was to present the clinical outcomes of patients with an edentulous maxilla treated with a removable prosthesis without palatal coverage retained by Locator abutments on three titanium implants.

Material and methods

All the patients in a private dental clinic consecutively treated up to 6 years earlier were invited for a follow‐up examination (n = 23). Two implants were placed bilaterally and one implant anteriorly in a tripod pattern. All patients underwent a clinical and radiological examination and completed questionnaires related to their experiences and satisfaction with the reconstructions. The prosthesis and implants were examined for adverse biological or technical aspects. Patient satisfaction and quality of life outcomes were collected using a self‐reported Denture Satisfaction Scale and OHIP‐20. Statistical analyses were limited to descriptive statistics.

Results

Twenty‐one of 23 invited participants consented to participate. We report in this study the outcomes of the study participants who had received their implants more than 2 years ago (n = 12). None of their 36 implants gave any indications of mobility or tenderness upon percussion. Suppuration was observed on one implant. Probing around the implants caused no (53%) or minor bleeding (47%). The incidence of adverse biological and technical events was near non‐existent. The rates of replacement of male attachments varied, as did any changes of male attachment retention force. All participants described the task of insertion and removal of the prosthesis as unproblematic. The marginal bone loss ranged between 0 and 5.3 mm. The OHIP‐20 and the Denture Satisfaction Questionnaire scores were high.

Conclusions

The results in this clinical study are positive and promising. Admittedly, the study design is purely retrospective and observational with a small participant cohort, so the technical solution of placing three implants in the edentulous maxilla to retain a removable prosthesis should be appraised further in more controlled studies.
A meta‐analysis of math performance in Turner syndrome
Authors: Baker Joseph M , Reiss Allan L
Published: November 2015

Aim

Studies investigating the relationship between Turner syndrome and math learning disability have used a wide variation of tasks designed to test various aspects of mathematical competencies. Although these studies have revealed much about the math deficits common to Turner syndrome, their diversity makes comparisons between individual studies difficult. As a result, the consistency of outcomes among these diverse measures remains unknown. The overarching aim of this review is to provide a systematic meta‐analysis of the differences in math and number performance between females with Turner syndrome and age‐matched neurotypical peers.

Method

We provide a meta‐analysis of behavioral performance in Turner syndrome relative to age‐matched neurotypical populations on assessments of math and number aptitude. In total, 112 comparisons collected across 17 studies were included.

Results

Although 54% of all statistical comparisons in our analyses failed to reject the null hypothesis, our results indicate that meaningful group differences exist on all comparisons except those that do not require explicit calculation.

Interpretation

Taken together, these results help elucidate our current understanding of math and number weaknesses in Turner syndrome, while highlighting specific topics that require further investigation.
Reflections on the contribution of the Assisting Hand Assessment
Authors: Wallen Margaret
Published: November 2015

This commentary is on the original article by Holmefur and Krumlinde‐Sundholm on pages 618–624 of this issue.
Understanding fatigue in paediatric multiple sclerosis: a systematic review of clinical and psychosocial factors
Authors: Carroll Susan , Chalder Trudie , Hemingway Cheryl , Heyman Isobel , Moss‐Morris Rona
Published: November 2015

Aim

Fatigue in children and adolescents with multiple sclerosis (caMS) is currently poorly understood. This review aimed to provide greater insight into this area and direction for future research by evaluating evidence of associations between fatigue and clinical, psychological, and social factors in caMS.

Method

Studies were identified by searching online databases, hand‐searching reference lists, and requesting unpublished literature from key authors. Studies that examined fatigue in relation to at least one clinical, psychological, or social factor in caMS were included. Data on design, sample characteristics, measures of fatigue, clinical, psychological, and social variables, and key findings were extracted. Twelve studies were narratively synthesized.

Results

Clinical factors appeared largely unrelated to fatigue, whereas associations between fatigue and tests of neurocognitive functioning, and fatigue and diagnosable psychiatric disorders, were mixed. However, fatigue and depressed mood consistently correlated. A small number of studies indicated associations between fatigue and reduced quality of life and school performance.

Interpretation

A sufficient explanatory model of fatigue in caMS is lacking as studies in this area are few and diverse. Future research should endeavour to identify potentially modifiable clinical and psychosocial factors that are associated with fatigue in caMS so that interventions targeting such factors may be developed.
Speech, language, communication, and cerebral palsy
Authors: Pennington Lindsay
Published: November 2015

This commentary is on the original article by Hustad et al. on pages 597–604 of this issue.
Aberrant Notch signalling contributes to hypertrophic scar formation by modulating the phenotype of keratinocytes
Authors: Li Bing , Gao Chao , Diao Jian‐Sheng , Wang Da‐Lei , Chu Fei‐Fei , Li Yang , Wang Gang , Guo Shu‐Zhong , Xia Wei
Published: November 2015

Hypertrophic scar (HS) is characterized by fibroblast hyperproliferation and excessive matrix deposition. Aberrant keratinocyte differentiation and their abnormal cytokine secretion are said to contribute to HS by activating fibroblasts. However, the signalling pathway causing the aberrant keratinocytes in HS has remained unidentified thus far. Given that Notch signalling is crucial in initiating keratinocyte differentiation, we hypothesized that Notch signalling contributes to HS by modulating the phenotype of keratinocytes. We found that Notch1, Notch intracellular domain, Jagged1 and Hes‐1 were overexpressed in the epidermis of patients with HS. Supernatants from recombinant‐Jagged1–treated keratinocyte cultures could accelerate dermal fibroblast proliferation and collagen production. Furthermore, Jagged1 induced keratinocyte differentiation and upregulated the expression of fibrotic factors, including transforming growth factors β1 and β2, insulin‐like growth factor‐1, connective tissue growth factor, vascular endothelial growth factor and epidermal growth factor, while DAPT (a Notch inhibitor) significantly suppressed these processes. In a rabbit ear model of HS, local application of DAPT downregulated the production of fibrotic factors in keratinocytes, together with ameliorated scar hyperplasia. Our findings suggest that Notch signalling contributes to HS by modulating keratinocyte phenotype. These results provide new insights into the pathogenesis of HS and indicate a potential therapeutic target.
Long non‐coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization
Authors: Wang Zhongzhi , Jinnin Masatoshi , Nakamura Kayo , Harada Miho , Kudo Hideo , Nakayama Wakana , Inoue Kuniko , Nakashima Taiji , Honda Noritoshi , Fukushima Satoshi , Ihn Hironobu
Published: November 2015

Long non‐coding RNAs (lncRNAs) are thought to have various functions other than RNA silencing. We tried to evaluate the expression of lncRNAs in patients with systemic sclerosis (SSc) and determined whether lncRNAs controls collagen expression in dermal fibroblasts. lncRNA expression was determined by real‐time PCR and in situ hybridization. Protein and mRNA levels of collagen were analysed using immunoblotting and real‐time PCR. We found TSIX, one of the lncRNAs, was overexpressed in SSc dermal fibroblasts both in vivo and in vitro, which was inhibited by the transfection of transforming growth factor (TGF)‐β1 siRNA. TSIX siRNA reduced the mRNA expression of type I collagen in normal and SSc dermal fibroblasts, but not the levels of major disease‐related cytokines. In addition, TSIX siRNA significantly reduced type I collagen mRNA stability, but not protein half‐lives. Furthermore, we first investigated serum lncRNA levels in patients with SSc, and serum TSIX levels were significantly increased in SSc patients. TSIX is a new regulator of collagen expression which stabilizes the collagen mRNA. The upregulation of TSIX seen in SSc fibroblasts may result from activated endogenous TGF‐β signalling and may play a role in the constitutive upregulation of collagen in these cells. Further studies on the regulatory mechanism of tissue fibrosis by lncRNAs in SSc skin lead to a better understanding of the pathogenesis, new diagnostic methods by their serum levels and new therapeutic approaches using siRNAs.