bluuebunny/crossref_metadata_2025 huggingface dataset:
On What There Isn’t
Authors: Priest Graham
Published: December 2016

Chapter 5 provides a discussion of Quine and Russell on non-existent objects. Their arguments aim to show that Meinong’s notion of such objects is incoherent. Quine’s well known argument about the fat man in the doorway is discussed and rejected.
Other Issues from the First Edition
Authors: Priest Graham
Published: December 2016

Chapter 13 takes up a number of objections to the material of the first edition not already dealt with. Amongst the topics discussed are: identity, fiction, de re and de dicto attitudes.
How the Particular Quantifier Became Existentially Loaded Behind our Backs
Authors: Priest Graham
Published: December 2016

Chapter 18 traces how the particular quantifier came to be read as `there exists’. The reading is, historically, very recent, and the arguments for reading it this way, less than happy.
Biomartr: genomic data retrieval with R
Authors: Drost Hajk-Georg , Paszkowski Jerzy
Published: December 2016

Motivation

Retrieval and reproducible functional annotation of genomic data are crucial in biology. However, the current poor usability and transparency of retrieval methods hinders reproducibility. Here we present an open source R package, biomartr, which provides a comprehensive easy-to-use framework for automating data retrieval and functional annotation for meta-genomic approaches. The functions of biomartr achieve a high degree of clarity, transparency and reproducibility of analyses.

Results

The biomartr package implements straightforward functions for bulk retrieval of all genomic data or data for selected genomes, proteomes, coding sequences and annotation files present in databases hosted by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EMBL-EBI). In addition, biomartr communicates with the BioMart database for functional annotation of retrieved sequences. Comprehensive documentation of biomartr functions and five tutorial vignettes provide step-by-step instructions on how to use the package in a reproducible manner.

Availability and Implementation

The open source biomartr package is available at https://github.com/HajkD/biomartr and https://cran.r-project.org/web/packages/biomartr/index.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
Measuring and Valuing Health Benefits for Economic Evaluation
Authors: Brazier John , Ratcliffe Julie , Saloman Joshua , Tsuchiya Aki
Published: December 2016

This is the second edition of the first comprehensive textbook about the measurement and valuation of health benefits for economic evaluation. The National Institute for Health and Care Excellence (NICE) and similar agencies around the word require cost-effectiveness evidence in the form of incremental cost per quality-adjusted life year (QALY) in order to make comparisons across competing demands on resources, and this has resulted in an explosion of theoretical and empirical work in the field. This book addresses the theoretical and practical considerations in the measurement and valuation of health benefit with empirical examples and applications to help clarify understanding and make relevant links to the real world. It includes a glossary of key terms and provides guidance on the use of different methods and instruments. This updated edition provides an-up-to date review of the theoretical basis of the QALY; the definition of health; the techniques of valuation (including ordinal); the modelling of health state values (including mapping between measures); a detailed review of generic preference-based measures and other instruments for obtaining health state utility values (with recent developments); cross-cultural issues (including the disability-adjusted life year); the aggregation of QALYs; and the practical issues surrounding the use of utility values in cost-effectiveness models. The book concludes with a discussion on the way forward in light of the substantial methodological differences, the role of normative judgements, and where further research is most likely to take forward this fascinating component of health economics.
The Almost Right Word: The Move From Medical to Health Humanities
Authors: Jones Therese , Blackie Michael , Garden Rebecca , Wear Delese
Published: December 2016

Since the emergence of the field in the 1970s, several trends have begun to challenge the original assumptions, claims, and practices of what became known as the medical humanities. In this article, the authors make the case for the health humanities as a more encompassing label because it captures recent theoretical and pedagogical developments in higher education such as the shift from rigid disciplinary boundaries to multi- and interdisciplinary inquiry, which has transformed humanities curricula in health professions. Calling the area of study health humanities also underscores the crucial distinction between medicine and health. Following a brief history of the field and the rationales that brought humanities disciplines to medical education in the first place—the “why” of the medical humanities—the authors turn to the “why” of the health humanities, using disability studies to illuminate those methodologies and materials that represent the distinction between the two. In addition, the authors make note of how humanities inquiry has now expanded across the landscape of other health professions curricula; how there is both awareness and evidence that medicine is only a minor determinant of health in human populations alongside social and cultural factors; and finally, how the current movement in health professions education is towards interdisciplinary and interprofessional learning experiences for students.
Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain
Authors: Gálvez Rafael , Navez Marie-Louise , Moyle Graeme , Maihöfner Christian , Stoker Malcolm , Ernault Etienne , Nurmikko Turo J. , Attal Nadine
Published: December 2016

Objectives:

To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain.

Methods:

A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using “bedside tests” and Brief Pain Inventory (question 5).

Results:

Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12.

Conclusions:

Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.
Trends in net survival from pancreatic cancer in six European Latin countries: results from the SUDCAN population-based study
Authors: Bouvier Anne-Marie , Bossard Nadine , Colonna Marc , Garcia-Velasco Adelaida , Carulla Maria , Manfredi Sylvain
Published: December 2016

Pancreatic cancer represents a real clinical challenge. The aim of the SUDCAN collaborative study was to compare the net survival from pancreatic cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland) and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000–2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. Results were reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modelling strategy. There were little differences between countries in age-standardized net survivals (2000–2004). The 5-year net survival was poor (range: 6–10%). The changes in net survival from 1992 to 2004 were mostly related to early survival and patients aged 60 years. A slight decrease in the excess mortality rate between 1992 and 2004 was observed, limited to the 18 months after diagnosis. This study confirmed that, despite some improvement, survival from pancreatic cancer is still poor throughout European Latin countries. The major improvements in clinical imaging did not result in improvements in prognosis. Development of truly innovative treatments is highly needed to improve prognosis.
Trends in net survival from stomach cancer in six European Latin countries: results from the SUDCAN population-based study
Authors: Glória Luísa , Bossard Nadine , Bouvier Anne-Marie , Mayer-da-Silva Alexandra , Faivre Jean , Miranda Ana
Published: December 2016

Gastric cancers are a clinical challenge. The aim of the SUDCAN collaborative study was to compare the net survival from gastric cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland) and explore the trends in net survival and in the dynamics of the excess mortality rates (EMRs) up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000–2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. These trend analyses were carried out using a flexible excess rate modelling strategy. There were little differences between countries in age-standardized net survival for stomach cancer (2000–2004). The 5-year net survival ranged between 26 (Spain) and 32% (Italy). There was a small increase in the age-standardized net survival at 1 year between 1992 and 2004. The increase was also observed in the 5-year net survival, except in France, where the increase was less marked. A slight decrease in the EMR between 1992 and 2004 was limited to the 24 months after diagnosis. In addition, the decrease in the EMR was the same whatever the year of diagnosis. There were minor differences in survival from stomach cancer between European Latin countries. A slight improvement in the 5-year net survival was observed in all countries and the major gain was observed during the 24 months after diagnosis. Development of innovative treatments is needed to improve the prognosis.
Repair of Large Abdominal Wall Defects Using Total Anterior Aponeurotic Flap: Anatomical Feasibility Study and Comparison with Ramirez’s Technique
Authors: Staszewicz Wojciech , Assalino Michela , Morel Philippe , Fasel Jean H. D. , Stimec Bojan V. , Tobalem Mickael
Published: December 2016

In this cadaveric study, we explored the feasibility of a maximal mobilization of the superficial abdominal fascia, in a continuous flap, to achieve a tension-free covering of midline defects. The aponeurosis of the external oblique muscle was incised along the anterior axillary line and then detached up to the anterior rectus sheath. The latter was opened between the external and the internal oblique aponeurosis while keeping the continuity with the external oblique fascia. The obtained flap was solid and uninterrupted. The width gain reached 15 ± 3 cm on each sides, providing tissue advancement 60% longer than Ramirez’s technique (n = 8). The described technique allows large covering with respect to the anatomical planes. Further clinical tests should evaluate the validity of such concept in the repair of giant and asymmetrical hernias.
The Use of a Hyaluronic Acid–Carboxymethylcellulose Membrane as an Adhesion Barrier during Nipple Delay before Nipple-preserving Mastectomy
Authors: Lamelas Andreas M. , Jablonka Eric M. , Harmaty Marco A. , Torina Philip J.
Published: December 2016

The desire for nipple-preserving mastectomies has increased over the past decade as studies have proven that the procedure has comparable oncologic risk as a traditional mastectomy in both therapeutic and prophylactic cases. Partial or complete nipple necrosis is a well-known complication of this procedure with rates in the literature ranging between 1% and 9%. In high-risk patients, surgeons are performing a delay procedure before the mastectomy to help improve nipple vascularity and decrease necrosis rates. We present a technique of using a short-lasting bioresorbable hyaluronate–carboxymethylcellulose membrane (Seprafilm; Genzyme, Cambridge, Mass.) during the delay procedure as an interpositional sheet, which prevents adhesion of the anterior breast skin from the underlying gland to both block revascularization to improve nipple perfusion and prevent the need for redissection of the previously created plane during the final mastectomy.
Controversies Regarding Diagnosis and Treatment of Severe Hypertension in Pregnancy
Authors: BARTON JOHN R. , SIBAI BAHA M.
Published: December 2016

The objective of management of severe hypertension in pregnancy is not for the return of normal blood pressure but rather reduction of blood pressure to a level associated with a decreased risk of end-organ damage including cerebral, cardiac, or renal dysfunction. The parenteral agents labetalol and hydralazine are currently the most widely recommended antihypertensive agents for acute reductions of elevated blood pressure related to preeclampsia. Overcorrection of blood pressure with any antihypertensive agent is possible resulting in reduced uteroplacental blood flow, but is more likely to be encountered in patients <32 weeks’ gestation and in those whose fetuses have intrauterine growth retardation.
Transvaginal Ultrasound for the Diagnosis of Abnormal Uterine Bleeding
Authors: WHEELER KAREN C. , GOLDSTEIN STEVEN R.
Published: December 2016

Transvaginal ultrasound is the first-line imaging test for the evaluation of abnormal uterine bleeding in both premenopausal and postmenopausal women. Transvaginal ultrasound can be used to diagnose structural causes of abnormal bleeding such as polyps, adenomyosis, leiomyomas, hyperplasia, and malignancy, and can also be beneficial in making the diagnosis of ovulatory dysfunction. Traditional 2-dimensional imaging is often enhanced by the addition of 3-dimension imaging with coronal reconstruction and saline infusion sonohysterography. In this article we discuss specific ultrasound findings and technical considerations useful in the diagnosis of abnormal uterine bleeding.
Wet-Peeling Technique of Deep Anterior Lamellar Keratoplasty With Hypotonic Water and Blunt Dissection for Healed Hydrops
Authors: Zhao Zelin , Li Jinyang , Zheng Qinxiang , Lin Wei , Jhanji Vishal , Chen Wei
Published: December 2016

Purpose:

To describe the surgical technique and outcomes of “wet-peeling” deep anterior lamellar keratoplasty (DALK) using sterile water and blunt dissection in cases with corneal scarring after healed corneal hydrops.

Methods:

Manual DALK using a “wet-peeling” technique was performed in 20 eyes of 20 consecutive patients with healed corneal hydrops between June 2011 and October 2013.

Results:

Intraoperative microperforations were encountered in 2 (10%) cases. None of the cases required conversion to penetrating keratoplasty. There was significant improvement in mean best-corrected visual acuity at the end of 24 months postoperatively (0.99 ± 0.30 logMAR vs. 0.20 ± 0.11 logMAR; P < 0.001). The postoperative mean residual stromal bed thickness was 48.9 ± 5.9 μm, and mean central corneal thickness was 557.2 ± 50.3 μm. The mean endothelial density was 2021 ± 236 cells/mm2 at the final follow-up.

Conclusions:

Manual DALK using sterile water can be successfully performed in corneas with healed hydrops. Favorable visual outcomes may be attributed to thin residual bed thickness postoperatively.
Associations Between Spatial and Temporal Contrast Sensitivity and Reading
Authors: Brussee Tamara , van den Berg Thomas J. T. P. , van Nispen Ruth M. A. , van Rens Ger H. M. B.
Published: December 2016

Purpose

To gain insight into the association between optical and neural components of contrast sensitivity (CS), operationalized as spatial CS (optical and neural) or temporal CS (solely neural), and reading speed in a clinical sample of healthy adults of various ages. Furthermore, precision and agreement of the two methods were assessed.

Methods

The Mars test and the temporal CS implementation of the C-Quant device were used to measure spatial CS and temporal CS, respectively. Tests were performed with 71 normally sighted adults: mean age 55 (range 18–86) years. Pearson’s correlation analyses were performed between spatial CS or temporal CS, and reading speed and partial correlations controlled for age are presented. Precision of the measurement was defined by the coefficient of repeatability and repeated measures standard deviations. Differences between spatial CS and temporal CS values were determined with 95% limits of agreement.

Results

A correlation was found between reading speed and both spatial CS (r = 0.470; P < .001) and temporal CS (r = 0.258; P = .04); partial correlations controlled for age were r = 0.175 (P = .17) and r = 0.152 (P = .24), respectively. Coefficient of repeatability was 0.13 log units and 0.24 log units for spatial CS and temporal CS test, respectively. A proportional difference of 0.1 log units was found between spatial CS and temporal CS measurements.

Conclusions

A significant correlation was found between both spatial CS and temporal CS and reading speed indicating that, besides optical components, neural aspects may be important in defining reading speed. The stronger correlation between spatial CS and reading speed is suggested to reflect a deterioration of both optical and neural factors with increasing age. The coefficients of repeatability for spatial CS and temporal CS found in the present study are in agreement with previous research, and the difference found between the two methods might be attributed to the psychometric differences between the methods.
Reconstruction of the Irradiated Breast: A National Claims-Based Assessment of Postoperative Morbidity
Authors: Chetta Matthew D. , Aliu Oluseyi , Zhong Lin , Sears Erika D. , Waljee Jennifer F. , Chung Kevin C. , Momoh Adeyiza O.
Published: December 2016

Background:

Implant-based reconstruction rates have risen among irradiation-treated breast cancer patients in the United States. This study aims to assess the morbidity associated with various breast reconstruction techniques in irradiated patients.

Methods:

From the MarketScan Commercial Claims and Encounters database, the authors selected breast cancer patients who had undergone mastectomy, irradiation, and breast reconstruction from 2009 to 2012. Demographic and clinical treatment data, including data on the timing of irradiation relative to breast reconstruction were recorded. Complications and failures after implant and autologous reconstruction were also recorded. A multivariable logistic regression model was developed with postoperative complications as the dependent variable and patient demographic and clinical variables as independent variables.

Results:

Four thousand seven hundred eighty-one irradiated patients who met the inclusion criteria were selected. A majority of the patients [n = 3846 (80 percent)] underwent reconstruction with implants. Overall complication rates were 45.3 percent and 30.8 percent for patients with implant and autologous reconstruction, respectively. Failure of reconstruction occurred in 29.4 percent of patients with implant reconstruction compared with 4.3 percent of patients with autologous reconstruction. In multivariable logistic regression, irradiated patients with implant reconstruction had two times the odds of having any complication and 11 times the odds of failure relative to patients with autologous reconstruction.

Conclusions:

Implant-based breast reconstruction in the irradiated patient, although popular, is associated with significant morbidity. Failures of reconstruction with implants in these patients approach 30 percent in the short term, suggesting a need for careful shared decision-making, with full disclosure of the potential morbidity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Smile Reanimation after Unilateral Facial Palsy by Lengthening Temporalis Myoplasty: Objective and Subjective Evaluation on 25 Cases
Authors: Foirest Claire , Granger Benjamin , Gatignol Peggy , Bernat Isabelle , Nguyen Yann , Lamas Georges , Tankere Frederic
Published: December 2016

Background:

Comparison of functional results of lengthening temporalis myoplasty relies in current practice on subjective scales. The goal of this study was to define a simple, reproducible, objective scale validated through a comparison with a subjective scale for smile symmetrization results after temporal muscle myoplasty.

Methods:

A retrospective study was conducted on 25 patients having a unilateral facial palsy and rehabilitated with lengthening temporalis myoplasty. Evaluation consisted of objective measures: smile horizontal symmetry between left and right sides, vertical symmetry, and smile width on healthy and paretic sides on preoperative and postoperative photographs. Subjective scales were also used (i.e., a numeric scale and the Terzis and Noah scale) by a jury (four professionals and four nonprofessionals) and the patient himself or herself. Each evaluation was performed in three conditions: at rest, at intermediary smile, and at maximum smile.

Results:

Comparison of objective measures on the impaired side showed a postoperative improvement in the three conditions evaluation. Reproducibility of the numeric scale was weak for evaluation at rest and fair for maximum smile evaluation (intraclass correlation coefficient of 0.57). The Terzis and Noah scale was not reproducible from one observer to another. At maximum smile, a correlation between smile symmetry in the vertical plane, smile symmetry in the horizontal plane, and professional evaluation with the numeric scale on the one hand and global patient satisfaction on the other hand was observed.

Conclusion:

Postoperative smile horizontal symmetry between left and right sides, and smile vertical symmetry, are good indicators with which to assess postoperative results of facial palsy rehabilitation.
What Do Participants of the Crohn's and Colitis UK (CCUK) Annual York Walk Think of Their Inflammatory Bowel Disease Care? A Short Report on a Survey
Authors: Mikocka-Walus Antonina , Power Madeleine , Rook Lisa , Robins Gerry
Published: December 2016

There has been a growing interest in a patient-centered model of care in inflammatory bowel disease; however, no relevant study using a mixed methodology has been conducted to date. Thus, our multidisciplinary group aimed to explore the issue of patient involvement in care among the inflammatory bowel disease community. A mixed-methods anonymous survey was conducted during the Crohn's and Colitis UK annual event. Summary statistics were used to describe the sample, and a simple thematic analysis identified key themes in qualitative responses. There were 64 survey respondents, representing 73% of the total family/friend groups participating (N = 87). Overall, 75% of respondents answered that they had the opportunity to discuss their care with their inflammatory bowel disease practitioner and 81% felt their opinions were taken on board and valued. A clear majority (84%) had at some point been treated by a gastroenterologist. In contrast, less than half (44%) had the opportunity for a dietician consultation and only 28% had the opportunity for a psychologist/counselor consultation. Although satisfaction with inflammatory bowel disease care was high, access to specialty services was concerning. Efforts should be made to provide access to mental health practitioners for those with clinically significant anxiety and/or depression.
Halloysite nanotube-based electrospun ceramic nanofibre mat: a novel support for zeolite membranes
Authors: Chen Zhuwen , Zeng Jiaying , Lv Dong , Gao Jinqiang , Zhang Jian , Bai Shan , Li Ruili , Hong Mei , Wu Jingshen
Published: December 2016

Some key parameters of supports such as porosity, pore shape and size are of great importance for fabrication and performance of zeolite membranes. In this study, we fabricated millimetre-thick, self-standing electrospun ceramic nanofibre mats and employed them as a novel support for zeolite membranes. The nanofibre mats were prepared by electrospinning a halloysite nanotubes/polyvinyl pyrrolidone composite followed by a programmed sintering process. The interwoven nanofibre mats possess up to 80% porosity, narrow pore size distribution, low pore tortuosity and highly interconnected pore structure. Compared with the commercial α-Al
2
O
3
supports prepared by powder compaction and sintering, the halloysite nanotube-based mats (HNMs) show higher flux, better adsorption of zeolite seeds, adhesion of zeolite membranes and lower Al leaching. Four types of zeolite membranes supported on HNMs have been successfully synthesized with either
in situ
crystallization or a secondary growth method, demonstrating good universality of HNMs for supporting zeolite membranes.
A new self-propelled magnetic bearing with helical windings
Authors: Shayak B.
Published: December 2016

In this work, a design is proposed for an active, permanent magnet based, self-propelled magnetic bearing, i.e. levitating motor having the following features: (i) simple winding structure, (ii) high load supporting capacity, (iii) no eccentricity sensors, (iv) stable confinement in all translational dimensions, (v) stable confinement in all rotational dimensions, and (vi) high efficiency. This design uses an architecture consisting of a helically wound three-phase stator, and a rotor with the magnets also arranged in a helical manner. Active control is used to excite the rotor at a torque angle lying in the second quadrant. This torque angle is independent of the rotor's position inside the stator cavity; hence the control algorithm is similar to that of a conventional permanent magnet synchronous motor. It is motivated through a physical argument that the bearing rotor develops a lift force proportional to the output torque and that it remains stably confined in space. These assertions are then proved rigorously through a calculation of the magnetic fields, forces and torques. The stiffness matrix of the system is presented and a discussion of stable and unstable operating regions is given.
Closed-form rocking overturning conditions for a family of pulse ground motions
Authors: Dimitrakopoulos Elias G. , Fung Edwin Dat Win
Published: December 2016

This paper characterizes the stability of a rigid rocking block subjected to a family of multi-lobe pulse ground motions. It unveils a counter to intuition plurality of overturning (OT) modes despite the short duration and bounded energy of the examined ground motions. Accordingly, it describes with original closed-form expressions the critical conditions of all OT modes involving a finite number of impacts. It also proposes pertinent semi-analytical, exact analytical and approximate analytical solutions with respect to the determination of the (unknown) times of impact, as appropriate. The analysis reveals that thefirst, orlower bound, critical OT mode is in most cases toppling during free rocking after one impact specifically before the end of the pulse. For this case, it elucidates the physical mechanism behind the timing of impact that producesminimumamplitude andmaximumamplitudecriticalOT, respectively, and proposes pertinent closed-form approximations. Finally, the study derives, in ‘universal’ terms, global ‘safety walls’ against rocking OT considering a large number of different pulse shapes.
Modification of the Streptococcus mutans transcriptome by LrgAB and environmental stressors
Authors: Rice Kelly C. , Turner Matthew E. , Carney O’neshia V. , Gu Tongjun , Ahn Sang-Joon
Published: December 2016

The Streptococcus mutans Cid/Lrg system is central to the physiology of this cariogenic organism, affecting oxidative stress resistance, biofilm formation and competence. Previous transcriptome analyses of lytS (responsible for the regulation of lrgAB expression) and cidB mutants have revealed pleiotropic effects on carbohydrate metabolism and stress resistance genes. In this study, it was found that an lrgAB mutant, previously shown to have diminished aerobic and oxidative stress growth, was also much more growth impaired in the presence of heat and vancomycin stresses, relative to wild-type, lrgA and lrgB mutants. To obtain a more holistic picture of LrgAB and its involvement in stress resistance, RNA sequencing and bioinformatics analyses were used to assess the transcriptional response of wild-type and isogenic lrgAB mutants under anaerobic (control) and stress-inducing culture conditions (aerobic, heat and vancomycin). Hierarchical clustering and principal components analyses of all differentially expressed genes revealed that the most distinct gene expression profiles between S. mutans UA159 and lrgAB mutant occurred during aerobic and high-temperature growth. Similar to previous studies of a cidB mutant, lrgAB stress transcriptomes were characterized by a variety of gene expression changes related to genomic islands, CRISPR-C as systems, ABC transporters, competence, bacteriocins, glucosyltransferases, protein translation, tricarboxylic acid cycle, carbohydrate metabolism/storage and transport. Notably, expression of lrgAB was upregulated in the wild-type strain under all three stress conditions. Collectively, these results demonstrate that mutation of lrgAB alters the transcriptional response to stress, and further support the idea that the Cid/Lrg system acts to promote cell homeostasis in the face of environmental stress.
Biased phylodynamic inferences from analysing clusters of viral sequences
Authors: Dearlove Bethany L. , Xiang Fei , Frost Simon D. W.
Published: December 2016

Phylogenetic methods are being increasingly used to help understand the transmission dynamics of measurably evolving viruses, including HIV. Clusters of highly similar sequences are often observed, which appear to follow a ‘power law’ behaviour, with a small number of very large clusters. These clusters may help to identify subpopulations in an epidemic, and inform where intervention strategies should be implemented. However, clustering of samples does not necessarily imply the presence of a subpopulation with high transmission rates, as groups of closely related viruses can also occur due to non-epidemiological effects such as over-sampling. It is important to ensure that observed phylogenetic clustering reflects true heterogeneity in the transmitting population, and is not being driven by non-epidemiological effects.

We quantify the effect of using a falsely identified ‘transmission cluster’ of sequences to estimate phylodynamic parameters including the effective population size and exponential growth rate. Our simulation studies show that taking the maximum size cluster to re-estimate parameters from trees simulated under a randomly mixing, constant population size coalescent process systematically underestimates the overall effective population size. In addition, the transmission cluster wrongly resembles an exponential or logistic growth model 95% of the time. We also illustrate the consequences of false clusters in exponentially growing coalescent and birth-death trees, where again, the growth rate is skewed upwards. This has clear implications for identifying clusters in large viral databases, where a false cluster could result in wasted intervention resources.
Mechanism of Nuclear Movements in a Multinucleated Cell
Authors: Gibeaux Romain , Politi Antonio Z. , Philippsen Peter , Nédélec François
Published: December 2016

Multinucleated cells are important in many organisms but the mechanisms governing the movements of nuclei sharing a common cytoplasm are not understood. In the hyphae of the plant pathogenic fungusAshbya gossypii,nuclei move back and forth, occasionally bypassing each other, and, preventing the formation of nuclear clusters, this is essential for genetic stability. These movements depend on cytoplasmic microtubules emanating from the nuclei, that are pulled by dynein motors anchored at the cortex. Using 3D stochastic simulations with parameters constrained by the literature, we predict the cortical anchors density from the characteristics of nuclear movements. Altogether, the model accounts for the complex nuclear movements seenin vivo,using a minimal set of experimentally determined ingredients. Interestingly, these ingredients power the oscillations of the anaphase spindle in budding yeast, but inA. gossypiithis system is not restricted to a specific nuclear cycle stage, possibly as a result of adaptation to hyphal growth and multinuclearity.
Targeted degradation of CTCF decouples local insulation of chromosome domains from higher-order genomic compartmentalization
Authors: Nora Elphege P , Goloborodko Anton , Valton Anne-Laure , Gibcus Johan Harmen , Uebersohn Alec , Abdennur Nezar , Dekker Job , Mirny Leonid , Bruneau Benoit
Published: December 2016

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and segmental organization into topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding, and CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data supports that CTCF mediates transcriptional insulator function through enhancer-blocking but not direct chromatin barrier activity. These results define the functions of CTCF in chromosome folding, and provide new fundamental insights into the rules governing mammalian genome organization.
The coefficient of determinationR2and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded
Authors: Nakagawa Shinichi , Johnson Paul C. D. , Schielzeth Holger
Published: December 2016

The coefficient of determinationR2quantifies the proportion of variance explained by a statistical model and is an important summary statistic of biological interest. However, estimatingR2for generalized linear mixed models (GLMMs) remains challenging. We have previously introduced a version ofR2that we calledR2GLMMfor Poisson and binomial GLMMs, but not for other distributional families. Similarly, we earlier discussed how to estimate intra-class correlation coefficients ICC using Poisson and binomial GLMMs. In this article, we expand our methods to all other non-Gaussian distributions, in particular to negative binomial and gamma distributions that are commonly used for modelling biological data. While expanding our approach, we highlight two useful concepts for biologists, Jensen’s inequality and the delta method, both of which help us in understanding the properties of GLMMs. Jensen’s inequality has important implications for biologically meaningful interpretation of GLMMs, while the delta method allows a general derivation of variance associated with non-Gaussian distributions. We also discuss some special considerations for binomial GLMMs with binary or proportion data. We illustrate the implementation of our extension by worked examples from the field of ecology and evolution in the R environment. However, our method can be used across disciplines and regardless of statistical environments.
Neutron diffraction of Cu–Zn–Sn ternary alloys: non-invasive assessment of the compositions of historical bronze/brass copper ternary alloys
Authors: Gliozzo Elisabetta , Kockelmann Winfried A. , Artioli Gilberto
Published: December 2016

Neutron diffraction can be used as a tool for the characterization of metal materials in a totally non-invasive mode. In binary alloys with two elements in solid solution, crystallographic structure analysis provides information on the overall element compositions of the metal, based on the linear relationship between elemental fractions and lattice parameters known as Vegard's rule. However, for ternary solid-solution alloys the derivation of the overall metal composition is not straightforward because the problem is mathematically underdetermined. A number of artificially produced samples in the ternary system Cu–Zn–Sn, widely used in antiquity for gunmetal, were investigated by time-of-flight neutron diffraction, inductively coupled plasma mass spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy and electron microprobe analysis. The multi-analysis approach allows definition of the limits and capabilities of neutron diffraction for obtaining the overall composition of a small sample set of ternary alloys, and thus moves the methodical approach a step forward even though it is applicable to the present sample set only. A relation showing an increasing Cu and Sn fraction counterbalanced by decreasing Zn content is presented, which allows the determination of the δ-phase composition from a lattice parameter measurement. Furthermore, the observed Zn loss up to 1.8 wt% for each melting step is of significance for the reconstruction of ancient technologies.
Conformational variation of proteins at room temperature is not dominated by radiation damage
Authors: Russi Silvia , González Ana , Kenner Lillian R. , Keedy Daniel A. , Fraser James S. , van den Bedem Henry
Published: December 2016

Protein crystallography data collection at synchrotrons is routinely carried out at cryogenic temperatures to mitigate radiation damage. Although damage still takes place at 100 K and below, the immobilization of free radicals increases the lifetime of the crystals by approximately 100-fold. Recent studies have shown that flash-cooling decreases the heterogeneity of the conformational ensemble and can hide important functional mechanisms from observation. These discoveries have motivated increasing numbers of experiments to be carried out at room temperature. However, the trade-offs between increased risk of radiation damage and increased observation of alternative conformations at room temperature relative to cryogenic temperature have not been examined. A considerable amount of effort has previously been spent studying radiation damage at cryo-temperatures, but the relevance of these studies to room temperature diffraction is not well understood. Here, the effects of radiation damage on the conformational landscapes of three different proteins (T. daniellithaumatin, hen egg-white lysozyme and human cyclophilin A) at room (278 K) and cryogenic (100 K) temperatures are investigated. Increasingly damaged datasets were collected at each temperature, up to a maximum dose of the order of 107 Gy at 100 K and 105 Gy at 278 K. Although it was not possible to discern a clear trend between damage and multiple conformations at either temperature, it was observed that disorder, monitored byB-factor-dependent crystallographic order parameters, increased with higher absorbed dose for the three proteins at 100 K. At 278 K, however, the total increase in this disorder was only statistically significant for thaumatin. A correlation between specific radiation damage affecting side chains and the amount of disorder was not observed. This analysis suggests that elevated conformational heterogeneity in crystal structures at room temperature is observed despite radiation damage, and not as a result thereof.
Computer simulations of X-ray six-beam diffraction in a perfect silicon crystal. II
Authors: Kohn V. G.
Published: December 2016

This paper reports computer simulations of X-ray six-beam (000, 220, 242, 044, −224, −202) diffraction in a perfect silicon crystal of large thickness where the super-transmission effect prevails,i.e.about 2 cm or more for an X-ray photon energy of 8 keV. Both the plane-wave angular dependence and the six-beam section topographs, which are obtained in experiments with a two-dimensional slit, are calculated. The angular dependence is computed by means of an eigenvalue problem in accordance with Ewald's theory. The section topographs are calculated by means of a fast Fourier transformation procedure from the angular to real space. It is shown that under the effect of X-ray super-transmission the quadrupole part of the photoelectric absorption as well as the Compton scattering give apparent contributions to the minimum absorption coefficient. Comparison of experimental and theoretical results by means of measuring the effective absorption coefficient is proposed. The section topographs for a thick crystal are asymmetric and polarization sensitive. These properties are explained through the angular dependence and the stationary phase method.
The structure of a calcium-dependent phosphoinositide-specific phospholipase C fromPseudomonassp. 62186, the first from a Gram-negative bacterium
Authors: Moroz Olga V. , Blagova Elena , Lebedev Andrey A. , Nørgaard Allan , Segura Dorotea R. , Blicher Thomas H. , Brask Jesper , Wilson Keith S.
Published: December 2016

Bacterial phosphoinositide-specific phospholipases C (PI-PLCs) are the smallest members of the PI-PLC family, which includes much larger mammalian enzymes responsible for signal transduction as well as enzymes from protozoan parasites, yeast and plants. Eukaryotic PI-PLCs have calcium in the active site, but this is absent in the known structures of Gram-positive bacteria, where its role is instead played by arginine. In addition to their use in a number of industrial applications, the bacterial enzymes attract special interest because they can serve as convenient models of the catalytic domains of eukaryotic enzymes forin vitroactivity studies. Here, the structure of a PI-PLC fromPseudomonassp. 62186 is reported, the first from a Gram-negative bacterium and the first of a native bacterial PI-PLC with calcium present in the active site. Solution of the structure posed particular problems owing to the low sequence identity of available homologous structures. Its dependence on calcium for catalysis makes this enzyme a better model for studies of the mammalian PI-PLCs than the previously used calcium-independent bacterial PI-PLCs.
Re-conceiving time in reference and information services work: a qualitative secondary analysis
Authors: Bossaller Jenny , Burns Christopher Sean , VanScoy Amy
Published: December 2016

Purpose

The purpose of this paper is to use the sociology of time to understand how time is perceived by academic librarians who provide reference and information service (RIS).

Design/methodology/approach

This study is a qualitative secondary analysis (QSA) of two phenomenological studies about the experience of RIS in academic libraries. The authors used QSA to re-analyze the interview transcripts to develop themes related to the perception of time.

Findings

Three themes about the experience of time in RIS work were identified. Participants experience time as discrete, bounded moments but sometimes experience threads through these moments that provide continuity, time is framed as a commodity that weighs on the value of the profession, and time plays an integral part of participants’ narratives and professional identities.

Research limitations/implications

Given that the initial consent processes vary across organizations and types of studies, the researchers felt ethically compelled to share only excerpts from each study’s data, rather than the entire data set, with others on the research team. Future qualitative studies should consider the potential for secondary analysis and build data management and sharing plans into the initial study design.

Practical implications

Most discussions of time in the literature are presented as a metric – time to answer a query, time to conduct a task – The authors offer a more holistic understanding of time and its relationship to professional work.

Social implications

The methodology taken in this paper makes sense of the experiences of work in RIS for librarians. It identifies commonalities between the experience of time and work for RIS professionals and those of other professionals, such as physicians and software engineers. It suggests revising models for RIS, as well as some professional values.

Originality/value

This paper contributes a better understanding of time, understudied as a phenomenon that is experienced or perceived, among RISs providers in academic libraries. The use of secondary qualitative analysis is an important methodological contribution to library and information science studies.
Sex‐dependent carry‐over effects on timing of reproduction and fecundity of a migratory bird
Authors: Saino Nicola , Ambrosini Roberto , Caprioli Manuela , Romano Andrea , Romano Maria , Rubolini Diego , Scandolara Chiara , Liechti Felix
Published: December 2016

Life of many organisms flows as a sequence of annual cycles. Timing of cyclical events is shaped by natural selection also via the domino effects that any life history stage has on the stages that follow. Such ‘carry‐over effects’ have major consequences for evolutionary, ecological and demographic processes, but the causes that generate their individual‐level variation, including the effect of sex, are poorly understood.

We used light‐level geolocators to study carry‐over effects on the year‐round life cycle of the long‐distance migratory barn swallow (Hirundo rustica) and sex‐dependent variation in their strength.

Correlation analyses showed that timing of breeding influenced departure time for autumn migration in females but not in males. In addition, strong, time‐mediated carry‐over effects of timing of departure from the wintering areas in sub‐Saharan Africa for spring migration on timing of arrival to the breeding grounds in Italy and Switzerland operated in both sexes. However, carry‐over effects of spring migration phenology on breeding date and seasonal fecundity were observed among females but not among males.

We used partial least squares path modelling to unveil the complex carry‐over effects of phenology during the non‐breeding season in combination with the ecological conditions experienced by individual swallows in the wintering area, as gauged by Normalized Difference Vegetation Index values (NDVI), on breeding performance. Phenology during the non‐breeding season combined withNDVIduring wintering accounted for as much as 65–70% of variation in subsequent seasonal fecundity in females, while such carry‐over effects on breeding success of males were weaker.

Intense, sex‐specific carry‐over effects can have impacted on evolutionary processes, including sexual selection, and affected phenological response to climate change, causing the large population decline observed in this species.