bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of observational pain assessment instruments for use with nonverbal intubated critically ill adult patients in the emergency department: an assessment of their suitability and psychometric properties
Authors: Varndell Wayne , Fry Margaret , Elliott Doug
Published: September 2016

Aim and objective

To examine the psychometric properties and suitability of the available observational pain instruments for potential use with nonverbal critically ill adult patients in the emergency department.

Background

In the emergency department, assessing pain in critically ill patients is challenging, especially those unable to communicate the presence of pain. Critically ill patients are commonly unable to verbally communicate pain due to altered oral communication (e.g. endotracheal intubation) and/or diminished consciousness (e.g. sedation, delirium), placing them at great risk of inadequate pain management. Over half of intensive care critically ill intubated patients experience moderate‐to‐severe pain whilst intubated and mechanically ventilated.

Design

Systematic review.

Data sources

TheCINAHL,EMBASE,MEDLINE, ProQuest databases, and the Cochrane Library and the National Institute of Clinical Excellence were also searched from their date of inception to April 2016, with no language restrictions applied.

Review method

Studies were identified using predetermined inclusion criteria. Data were extracted and summarised and underwent evaluation using published classification of psychometric tests for consistency of interpretation.

Results

Twenty‐six studies evaluating five observational pain assessment instruments that had been used with critically ill intubated patients were identified. All five instruments included behavioural indicators, with two including physiologic indicators. All five instruments have undergone validity and reliability testing involving nonverbal critically ill intubated patients, three were examined for feasibility, and one instrument underwent sensitivity and specificity testing. None have been tested within the emergency department with nonverbal critically ill intubated adult patients.

Conclusion

The use of an appropriate and valid observational pain assessment instrument is fundamental to detecting and optimising pain management in nonverbal critically ill intubated patients in the emergency department. Of the observational pain assessment instruments reviewed, the Critical‐Care Pain Observation Tool was identified as most appropriate for testing in a prospective trial in an emergency department setting.
Taking actions to quit chewing betel nuts and starting a new life: taxi drivers’ successful experiences of quitting betel nut chewing
Authors: Yang Tsui‐Yun , Lin Hung‐Ru
Published: September 2016

Aims and objectives

To understand taxi drivers’ successful experiences of quitting betel nut chewing.

Background

Previous studies verified that betel nut chewing significantly increases the risk of oral cancer. In Taiwan, taxi drivers work for approximately 10–13 hours per day, and 31·7–80% of them choose to chew betel nuts for their invigorating qualities, which enable them to work more hours and receive more income.

Design

A qualitative research design was used.

Methods

This study used the grounded theory method with purposive sampling to perform in‐depth interviews with male taxi drivers who had successfully quit betel nut chewing for more than six months.

Results

The interviewed participants were 25 taxi drivers aged 45–67 who had chewed betel nuts for an average of 30·9 years. A constant comparative analysis of the 25 interviews revealed six categories, namely the first experience of chewing betel nuts, a part of work and life, perceiving the impact of betel nuts, trying to change, acting to quit betel nut chewing and starting a new life.

Conclusions

During the cessation process, taxi drivers tended to be affected by their addiction to chewing betel nuts and the temptation of friends’ invitations to chew betel nuts. However, their recognition of the physical effects of betel nut chewing and their sense of responsibility and commitment to family were the critical factors affecting their determination to quit betel nut chewing. Their willpower to not to chew betel nuts and the source of their motivation to exercise self‐control also contributed to their success.

Relevance to clinical practice

Healthcare personnel should understand the experiences and perceptions of betel nut chewers, strengthen their understanding of the effects of betel nut chewing on physical health during the cessation period and support their self‐efficacy and quitting behaviours with the assistance of significant others.
Caregiver burden and prevalence of depression, anxiety and sleep disturbances in Alzheimer's disease caregivers in China
Authors: Liu Shuai , Li Chonghui , Shi Zhihong , Wang Xiaodan , Zhou Yuying , Liu Shuling , Liu Jing , Yu Tao , Ji Yong
Published: September 2016

Aims and objectives

To evaluate caregiver burden and factors that influence this burden among caregivers and patients with Alzheimer's disease in China.

Background

Long‐term care can reduce the quality of life for caregivers and result in both mental and physical exhaustion. However, little is known about caregiver burden and associated factors in China.

Design

The study had a quantitative cross‐sectional design.

Methods

A total of 309 caregivers and their patients were included in the study. The patients' cognitive, psychological and functional status and their caregivers' burden, sleep quality and mental state were evaluated. Descriptive analyses, single‐factor regression and stepwise factor regression were used to determine the effects of various factors on caregiver burden.

Results

Older females and spouses still play an important role in providing family care for those with dementia. Most of the caregivers were the sole full‐time caregiver and had little time for themselves. Sleepiness was a common physical problem for caregivers, and some of them had moderate to severe depression and anxiety. A lower functional status of the patient was associated with higher caregiver burden. Poorer physical status compared with before caregiving began, lower life satisfaction, and higher degrees of depression and anxiety were associated with higher caregiver burden.

Conclusion

Depression, anxiety and sleep problems are the main challenges that are faced by family caregivers of patients with Alzheimer's disease. Caregivers' functional status, lower life satisfaction, depression and anxiety influenced caregiver burden. Caregiver burden was related to the severity of the patient's dementia and the personal factors of the caregivers.

Relevance to clinical practice

To provide information about caregivers' current status while caring for patients with Alzheimer's disease and to understand caregiver burden and its related factors. Professionals who work with Alzheimer's disease should pay more attention to caregiver burden, especially those with mental and physical problems.
Health promotion among older adults in Austria: a qualitative study
Authors: Boggatz Thomas , Meinhart Christoph Matthias
Published: September 2016

Aims and objectives

To determine the types of attitudes to health promotion among older Austrians.

Background

Health promotion in old age becomes increasingly important in the current period of demographic transition. Interventions are likely to be successful if they take the attitude of older persons into consideration. There may be several types of attitudes to health promotion among older adults.

Design

Cross‐sectional qualitative study.

Methods

Semi‐structured interviews were conducted in a purposive sample consisting of 36 home‐dwelling older persons from local communities in the federal province of Salzburg, Austria. Data were analysed using qualitative content analysis according to Mayring and subsequent construction of types.

Results

There are three main types of attitudes to health promotion. ‘Health promoters through everyday activities’ considered domestic work and walks to be sufficient in keeping up their health. Fitness‐oriented persons practised sports of some type. Users of complementary methods practised such methods to some degree. These types of attitudes could be further differentiated according to their outcome expectations. In addition to benefits for health, socialising was also an important outcome. Physical decline may reduce a fitness‐oriented attitude, whereas encouragement by others may trigger it.

Conclusion

Older adults have various attitudes to health promotion, but these are not immutable.

Relevance to clinical practice

Health promotion programmes that are not restricted to a narrow focus on health but provide the opportunity to socialise may support older adults in maintaining a healthy lifestyle.
Healthcare‐professional patients’ conceptions of being ill and hospitalised – a phenomenographic study
Authors: Prenkert Malin , Carlsson Eva , Svantesson Mia , Anderzén‐Carlsson Agneta
Published: September 2016

Aims and objectives

To describe the variation of conceptions of being ill and hospitalised, from the perspective of healthcare‐professional patients.

Background

Previous literature focuses on either physicians’ or nurses’ experiences of being a patient, without aiming at determining a variation of ways of understanding that phenomena. Nor have we been able to identify any study reporting other healthcare professionals’ experiences.

Design

This study has an inductive descriptive design.

Methods

Qualitative interviews with healthcare professionals (n = 16), who had been hospitalised for at least two days. Phenomenographic data analysis was conducted.

Results

The feelings of security were based on knowledge, insight and trust, and acceptance of the healthcare system. Being exposed and totally dependent due to illness provoked feelings of vulnerability and insecurity. The patients used their knowledge to achieve participation in the care. The more severe they perceived their illness to be, the less they wanted to participate and the more they expressed a need for being allowed to surrender control. The patients’ ideal picture of care was sometimes disrupted, and based on their experience, they criticised care and made suggestions that could contribute to general care improvements.

Conclusions

Healthcare‐professional patients have various conceptions of being ill and hospitalised. Based on the general nature of the many needs expressed, we believe that the insights provided in this study can be transferred so as to also be valid for lay patients. Possibly, an overhaul of routines for discharge planning and follow‐up, and adopting a person‐centred approach to care, can resolve some of the identified shortcomings.

Relevance to clinical practice

The results can be used for the purpose of developing knowledge for healthcare professions and for educational purposes.
Genome divergence and diversification within a geographic mosaic of coevolution
Authors: Parchman Thomas L. , Buerkle C. Alex , Soria‐Carrasco Víctor , Benkman Craig W.
Published: September 2016

Despite substantial interest in coevolution's role in diversification, examples of coevolution contributing to speciation have been elusive. Here, we build upon past studies that have shown both coevolution between South Hills crossbills and lodgepole pine (Pinus contorta), and high levels of reproductive isolation between South Hills crossbills and other ecotypes in the North American red crossbill (Loxia curvirostra) complex. We used genotyping by sequencing to generate population genomic data and applied phylogenetic and population genetic analyses to characterize the genetic structure within and among nine of the ecotypes. Although genome‐wide divergence was slight between ecotypes (FST = 0.011–0.035), we found evidence of relative genetic differentiation (as measured byFST) between and genetic cohesiveness within many of them. As expected for nomadic and opportunistic breeders, we detected no evidence of isolation by distance. The one sedentary ecotype, the South Hills crossbill, was genetically most distinct because of elevated divergence at a small number of loci rather than pronounced overall genome‐wide divergence. These findings suggest that mechanisms related to recent local coevolution between South Hills crossbills and lodgepole pine (e.g. strong resource‐based density dependence limiting gene flow) have been associated with genome divergence in the face of gene flow. Our results further characterize a striking example of coevolution driving speciation within perhaps as little as 6000 years.
Identification of pneumococcal proteins that are functionally linked to penicillin‐binding protein 2b (PBP2b)
Authors: Straume Daniel , Stamsås Gro Anita , Berg Kari Helene , Salehian Zhian , Håvarstein Leiv Sigve
Published: September 2016

The oval shape of pneumococci results from a combination of septal and lateral peptidoglycan synthesis. The septal cross‐wall is synthesized by the divisome, while the elongasome drives cell elongation by inserting new peptidoglycan into the lateral cell wall. Each of these molecular machines contains penicillin‐binding proteins (PBPs), which catalyze the final stages of peptidoglycan synthesis, plus a number of accessory proteins. Much effort has been made to identify these accessory proteins and determine their function. In the present paper we have used a novel approach to identify members of the pneumococcal elongasome that are functionally closely linked to PBP2b. We discovered that cells depleted in PBP2b, a key component of the elongasome, display several distinct phenotypic traits. We searched for proteins that, when depleted or deleted, display the same phenotypic changes. Four proteins, RodA, MreD, DivIVA and Spr0777, were identified by this approach. Together with PBP2b these proteins are essential for the normal function of the elongasome. Furthermore, our findings suggest that DivIVA, which was previously assigned as a divisomal protein, is required to correctly localize the elongasome at the negatively curved membrane region between the septal and lateral cell wall.
Candida infections in paediatrics: Results from a prospective single‐centre study in a tertiary care children's hospital
Authors: Mesini Alessio , Bandettini Roberto , Caviglia Ilaria , Fioredda Francesca , Amoroso Loredana , Faraci Maura , Mattioli Girolamo , Piaggio Giorgio , Risso Francesco M. , Moscatelli Andrea , Loy Anna , Castagnola Elio
Published: September 2016

To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single‐centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005‐2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non‐albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90‐day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions.
Sleep disturbances in irritable bowel syndrome: a systematic review
Authors: Tu Q. , Heitkemper M. M. , Jarrett M. E. , Buchanan D. T.
Published: September 2016

Background

Sleep disturbances are well‐documented among persons with irritable bowel syndrome (IBS). Difficulty in falling asleep, shorter sleep time, frequent arousal and awakenings, or non‐restorative sleep are the most common manifestations. Sleep disturbances are also related to a higher risk of having IBS. Some researchers have provided evidence of a positive association between poorer subjective sleep quality and increased severity and frequency in gastrointestinal (GI) symptoms in those with IBS. However, findings from studies using objective sleep and activity measures, such as polysomnography and actigraphy, are inconclusive.

Purpose

This systematic review of the literature between 1990 and 2015 evaluates the evidence of sleep disturbances in adults with IBS and their relationship with GI symptoms.
Industry Wages Across Countries and Over Time: A New Database of Micro Survey Data
Authors: Le Van Ha , De Haan Jakob , Dietzenbacher Erik
Published: September 2016

This paper presents a newly collected database on industry wages. The underlying data are micro datasets collected through nationally representative household surveys which are mostly conducted by national statistical agencies. In comparison with wage measures based on macroeconomic data sources, we find that industry wages based on micro survey data are more reliable. Furthermore, data from nationally representative micro surveys are becoming increasingly available, thus allowing for better coverage, especially of low‐income countries. The database provides a reliable source of data for research on inter‐industry wage structures and gender wage differentials, across countries and over time. It may also serve as a basis for further research on the determinants and implications of inter‐industry and gender wage variations.
Analysis of Networks with Missing Data with Application to the National Longitudinal Study of Adolescent Health
Authors: Gile Krista J. , Handcock Mark S.
Published: September 2016

It is common in the analysis of social network data to assume a census of the networked population of interest. Often the observations are subject to partial observation due to a known sampling or unknown missing data mechanism. However, most social network analysis ignores the problem of missing data by including only actors with complete observations. We address the modelling of networks with missing data, developing previous ideas in missing data, network modelling and network sampling. We use several methods including the mean value parameterization to show the quantitative and substantive differences between naive and principled modelling approaches. We also develop goodness-of-fit techniques to understand model fit better. The ideas are motivated by an analysis of a friendship network from the National Longitudinal Study of Adolescent Health.
Arthroscopy of the Dorsal and Plantar Pouches of the Tarsocrural Joint for the Treatment of Osteochondritis Dissecans in the Horse: Clinical Features and Follow‐Up
Authors: James Oliver , Payne Richard , Bathe Andrew , Greet Tim , Wylie Claire
Published: September 2016

Objective

To describe the clinical details and pathology within the dorsal and plantar pouches of the tarsocrural joint of a population of horses that underwent arthroscopic surgery for tarsocrural osteochondritis dissecans (OCD).

Study Design

Retrospective cohort study.

Animals

Horses referred for arthroscopic treatment of tarsocrural OCD between 2005 and 2013 (102 horses; 144 joints).

Methods

Case records of all horses that had tarsocrural arthroscopy for OCD at Rossdales Equine Hospital, Newmarket, United Kingdom were included. Cases from 3 ECVS Diplomates were included, 1 of whom routinely examined 70 plantar pouches concurrently with routine dorsal pouch investigation. A structured questionnaire was used to obtain follow‐up data alongside examination of racing records where appropriate. Descriptive data and 95% CI were calculated.

Results

Of the 70 joints that had both dorsal and plantar pouches examined, there was cartilage erosion/degeneration in 22 dorsal pouches (31.4%), cartilage wear lines in 32 plantar pouches (45.7%), and fragments were removed at the time of surgery from 7 plantar pouches (10.0%). Of the plantar pouches with wear lines, 18 (25.7%) had no evidence of cartilage abnormalities (separate from the OCD lesion) within the dorsal pouch. From the 102 horses with available follow‐up, 34 horses (66.7%) achieved their intended use postsurgery.

Conclusion

Routine plantar pouch investigation is warranted in cases of tarsocrural OCD to provide further information on the health of the joint and allows for removal of fragments from the plantar pouch that may not have been identified by routine diagnostic radiography.
Frequency of Undetected Glove Perforation and Associated Risk Factors in Equine Surgery
Authors: Elce Yvonne A. , Laverty Sheila , Almeida da Silveira Eduardo , Piat Perrine , Trencart Pierre , Ruzickova Pavlina , Reardon Richard J. M.
Published: September 2016

Objective

To estimate the frequency of undetected perforations in surgical gloves during equine surgery and to identify risk factors associated with occurrence.

Study Design

Observational cohort study.

Sample Population

Surgical gloves—292 pairs.

Methods

Water leak tests were performed on gloves after equine surgery to detect perforations. Fifty pairs of unused gloves were also tested. Potential risk factors were recorded. Logistic regression was used to explore associations between putative risk factors and perforation.

Results

No perforations were detected in the unused gloves. Of 292 pairs of used gloves tested, 80 (27%) had at least one glove perforation per pair. The frequency of perforations was not different between surgery diplomates and residents (P=.69). The length and type of surgery were significantly associated with the likelihood of undetected glove perforation with surgeries longer than 60 minutes approximately 2.5 times more likely to result in glove perforation (P=.005). Surgery classified as soft tissue, orthopedic or exploratory celiotomy was 3 times more likely to result in glove perforation than minimally invasive surgery. The perforations occurred significantly more frequently in the nondominant hand (19%) than the dominant hand (11%) (P=.009).

Conclusion

There is a high occurrence of undetected glove perforation in equine surgery. Precautions can be suggested based on this study although further investigation is required to assess whether glove perforations are associated with surgical site infections.
A Zero-Dimensional Model and Protocol for Simulating Patient-Specific Pulmonary Hemodynamics From Limited Clinical Data
Authors: Kheyfets Vitaly O. , Dunning Jamie , Truong Uyen , Ivy Dunbar , Hunter Kendall , Shandas Robin
Published: September 2016

In pulmonary hypertension (PH) diagnosis and management, many useful functional markers have been proposed that are unfeasible for clinical implementation. For example, assessing right ventricular (RV) contractile response to a gradual increase in pulmonary arterial (PA) impedance requires simultaneously recording RV pressure and volume, and under different afterload/preload conditions. In addition to clinical applications, many research projects are hampered by limited retrospective clinical data and could greatly benefit from simulations that extrapolate unavailable hemodynamics. The objective of this study was to develop and validate a 0D computational model, along with a numerical implementation protocol, of the RV–PA axis. Model results are qualitatively compared with published clinical data and quantitatively validated against right heart catheterization (RHC) for 115 pediatric PH patients. The RV–PA circuit is represented using a general elastance function for the RV and a three-element Windkessel initial value problem for the PA. The circuit mathematically sits between two reservoirs of constant pressure, which represent the right and left atriums. We compared Pmax, Pmin, mPAP, cardiac output (CO), and stroke volume (SV) between the model and RHC. The model predicted between 96% and 98% of the variability in pressure and 98–99% in volumetric characteristics (CO and SV). However, Bland Altman plots showed the model to have a consistent bias for most pressure and volumetric parameters, and differences between model and RHC to have considerable error. Future studies will address this issue and compare specific waveforms, but these initial results are extremely promising as preliminary proof of concept of the modeling approach.
A Computational Efficient Method to Assess the Sensitivity of Finite-Element Models: An Illustration With the Hemipelvis
Authors: O'Rourke Dermot , Martelli Saulo , Bottema Murk , Taylor Mark
Published: September 2016

Assessing the sensitivity of a finite-element (FE) model to uncertainties in geometric parameters and material properties is a fundamental step in understanding the reliability of model predictions. However, the computational cost of individual simulations and the large number of required models limits comprehensive quantification of model sensitivity. To quickly assess the sensitivity of an FE model, we built linear and Kriging surrogate models of an FE model of the intact hemipelvis. The percentage of the total sum of squares (%TSS) was used to determine the most influential input parameters and their possible interactions on the median, 95th percentile and maximum equivalent strains. We assessed the surrogate models by comparing their predictions to those of a full factorial design of FE simulations. The Kriging surrogate model accurately predicted all output metrics based on a training set of 30 analyses (R2 = 0.99). There was good agreement between the Kriging surrogate model and the full factorial design in determining the most influential input parameters and interactions. For the median, 95th percentile and maximum equivalent strain, the bone geometry (60%, 52%, and 76%, respectively) was the most influential input parameter. The interactions between bone geometry and cancellous bone modulus (13%) and bone geometry and cortical bone thickness (7%) were also influential terms on the output metrics. This study demonstrates a method with a low time and computational cost to quantify the sensitivity of an FE model. It can be applied to FE models in computational orthopaedic biomechanics in order to understand the reliability of predictions.
A Robust and Subject-Specific Hemodynamic Model of the Lower Limb Based on Noninvasive Arterial Measurements
Authors: Dumas Laurent , El Bouti Tamara , Lucor Didier
Published: September 2016

Cardiovascular diseases are currently the leading cause of mortality in the population of developed countries, due to the constant increase in cardiovascular risk factors, such as high blood pressure, cholesterol, overweight, tobacco use, lack of physical activity, etc. Numerous prospective and retrospective studies have shown that arterial stiffening is a relevant predictor of these diseases. Unfortunately, the arterial stiffness distribution across the human body is difficult to measure experimentally. We propose a numerical approach to determine the arterial stiffness distribution of an arterial network using a subject-specific one-dimensional model. The proposed approach calibrates the optimal parameters of the reduced-order model, including the arterial stiffness, by solving an inverse problem associated with the noninvasive in vivo measurements. An uncertainty quantification analysis has also been carried out to measure the contribution of the model input parameters variability, alone or by interaction with other inputs, to the variation of clinically relevant hemodynamic indices, here the arterial pulse pressure. The results obtained for a lower limb model, demonstrate that the numerical approach presented here can provide a robust and subject-specific tool to the practitioner, allowing an early and reliable diagnosis of cardiovascular diseases based on a noninvasive clinical examination.
Probabilistic Factor Graph Based Approach for Automatic Material Assignments to Three-Dimensional Objects
Authors: Zhang Binbin , Rai Rahul
Published: September 2016

There are strong correlations between material assignment, shape, and functionality of a part in an overall product/assembly. However, these strong correlations are rarely exploited for automated material assignment. We present a probabilistic graphical model to assign materials to the parts (components) of a 3D object (assembly) by identifying the relations between shape, functionality, and material of the parts. By learning the context-dependent correlation with supervision from a set of objects and their segmented parts, the learned model can be used to assign engineering materials to the parts of a query object. Our primary contributions are (a) the engineering materials definition and assignment and (b) assigning engineering materials based on the behavior and form of the parts in the object. The performance of the proposed computational approach is demonstrated by the results of material assignment on various query objects with prespecified engineering performance requirements.
Deep Space Network glitches worry scientists
Authors: Voosen Paul
Published: September 2016

NASA's aging radio antennas have faced years of budget cuts, threatening far-off spacecraft.
A lifeline for Greek science—or living on borrowed time?
Authors: Stokstad Erik
Published: September 2016

New foundation will fund peer-reviewed grants, but scientists fear that it won't bail them out of crisis.
Fossil fishes challenge ‘urban legend’ of evolution
Authors: Pennisi Elizabeth
Published: September 2016

Genome duplications, thought to power evolutionary radiations, can't explain explosion of fishes.
Ballistic miniband conduction in a graphene superlattice
Authors: Lee Menyoung , Wallbank John R. , Gallagher Patrick , Watanabe Kenji , Taniguchi Takashi , Fal’ko Vladimir I. , Goldhaber-Gordon David
Published: September 2016

Rational design of long-period artificial lattices yields effects unavailable in simple solids. The moiré pattern in highly aligned graphene/hexagonal boron nitride (h-BN) heterostructures is a lateral superlattice with high electron mobility and an unusual electronic dispersion whose miniband edges and saddle points can be reached by electrostatic gating. We investigated the dynamics of electrons in moiré minibands by measuring ballistic transport between adjacent local contacts in a magnetic field, known as the transverse electron focusing effect. At low temperatures, we observed caustics of skipping orbits extending over hundreds of superlattice periods, reversals of the cyclotron revolution for successive minibands, and breakdown of cyclotron motion near van Hove singularities. At high temperatures, electron-electron collisions suppress focusing. Probing such miniband conduction properties is a necessity for engineering novel transport behaviors in superlattice devices.
High-resolution interrogation of functional elements in the noncoding genome
Authors: Sanjana Neville E. , Wright Jason , Zheng Kaijie , Shalem Ophir , Fontanillas Pierre , Joung Julia , Cheng Christine , Regev Aviv , Zhang Feng
Published: September 2016

The noncoding genome affects gene regulation and disease, yet we lack tools for rapid identification and manipulation of noncoding elements. We developed a CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes
NF1
,
NF2
, and
CUL3
, which are involved in BRAF inhibitor resistance in melanoma. We find that noncoding locations that modulate drug resistance also harbor predictive hallmarks of noncoding function. With a subset of regions at the
CUL3
locus, we demonstrate that engineered mutations alter transcription factor occupancy and long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. Through our expansion of the potential of pooled CRISPR screens, we provide tools for genomic discovery and for elucidating biologically relevant mechanisms of gene regulation.
Spiral density waves in a young protoplanetary disk
Authors: Pérez Laura M. , Carpenter John M. , Andrews Sean M. , Ricci Luca , Isella Andrea , Linz Hendrik , Sargent Anneila I. , Wilner David J. , Henning Thomas , Deller Adam T. , Chandler Claire J. , Dullemond Cornelis P. , Lazio Joseph , Menten Karl M. , Corder Stuartt A. , Storm Shaye , Testi Leonardo , Tazzari Marco , Kwon Woojin , Calvet Nuria , Greaves Jane S. , Harris Robert J. , Mundy Lee G.
Published: September 2016

Gravitational forces are expected to excite spiral density waves in protoplanetary disks, disks of gas and dust orbiting young stars. However, previous observations that showed spiral structure were not able to probe disk midplanes, where most of the mass is concentrated and where planet formation takes place. Using the Atacama Large Millimeter/submillimeter Array, we detected a pair of trailing symmetric spiral arms in the protoplanetary disk surrounding the young star Elias 2-27. The arms extend to the disk outer regions and can be traced down to the midplane. These millimeter-wave observations also reveal an emission gap closer to the star than the spiral arms. We argue that the observed spirals trace shocks of spiral density waves in the midplane of this young disk.
Rethinking the arrow of time
Now The Physics of Time
Richard A. Muller
Norton, 2016. 364 pp.
Authors: Jardine-Wright Lisa
Published: September 2016

Citing shortcomings in Eddington's theory, a physicist proposes a new explanation for the existence of “now”
Constraining lithospheric flow
Authors: Kaus Boris J. P.
Published: September 2016

Geophysical data help to determine the viscosity of Earth's crust and upper mantle
Bee happy
Authors: Mendl Michael T. , Paul Elizabeth S.
Published: September 2016

Bumblebees show decision-making that reflects emotion-like states
Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis
Authors: Pérez-Lago Laura , Martínez-Lirola Miguel , García Sergio , Herranz Marta , Mokrousov Igor , Comas Iñaki , Martínez-Priego Llúcia , Bouza Emilio , García-de-Viedma Darío
Published: September 2016

Current migratory movements require new strategies for rapidly tracking the transmission of high-risk importedMycobacterium tuberculosisstrains. Whole-genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR BeijingM. tuberculosisstrains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain-positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis.
Rhinovirus 16 2A Protease Affects Nuclear Localization of 3CD during Infection
Authors: Walker Erin , Jensen Lora , Croft Sarah , Wei Kejun , Fulcher Alex J. , Jans David A. , Ghildyal Reena
Published: September 2016

The human rhinovirus (HRV) 3C and 2A proteases (3Cproand 2Apro, respectively) are critical in HRV infection, as they are required for viral polyprotein processing as well as proteolysing key host factors to facilitate virus replication. Early in infection, 3Cprois present as its precursor 3CD, which, although the mechanism of subcellular targeting is unknown, is found in the nucleus as well as the cytoplasm. In this study, we use transfected and infected cell systems to show that 2Aproactivity is required for 3CD nuclear localization. Using green fluorescent protein (GFP)-tagged forms of 3Cpro, 3D, and mutant derivatives thereof, we show that 3Cprois located in the cytoplasm and the nucleus, whereas 3CD and 3D are localized predominantly in the cytoplasm, implying that 3D lacks nuclear targeting ability and that 3Cproactivity within 3CD is not sufficient to allow the larger protein into the nucleus. Importantly, by coexpressing mCherry-2Aprofusion proteins, we demonstrate formally that 2Aproactivity is required to allow HRV 3CD access to the nucleus. In contrast, mCherry-3Cprois insufficient to allow 3CD access to the nucleus. Finally, we confirm the relevance of these results to HRV infection by demonstrating that nuclear localization of 3CD correlates with 2Aproactivity and not 3Cproactivity, which is observed only later in infection. The results thus define the temporal activities of 2Aproand 3CD/3Cproactivities in HRV serotype16 infection.

IMPORTANCEThe human rhinovirus genome encodes two proteases, 2A and 3C, as well as a precursor protease, 3CD. These proteases are essential for efficient virus replication. The 3CD protein is found in the nucleus early during infection, though the mechanism of subcellular localization is unknown. Here we show that 2A protease is required for this localization, the 3C protease activity of 3CD is not sufficient to allow 3CD entry into the nucleus, and 3D lacks nuclear targeting ability. This study demonstrates that both 2A and 3C proteases are required for the correct localization of proteins during infection and defines the temporal regulation of 2A and 3CD/3C protease activities during HRV16 infection.
Attenuated Infectious Hematopoietic Necrosis Virus with Rearranged Gene Order as Potential Vaccine
Authors: Rouxel Ronan N. , Tafalla Carolina , Mérour Emilie , Leal Esther , Biacchesi Stéphane , Brémont Michel
Published: September 2016

The genome of infectious hematopoietic necrosis virus (IHNV), a salmonid novirhabdovirus, has been engineered to modify the gene order and to evaluate the impact on a possible attenuation of the virus
in vitro
and
in vivo
. By reverse genetics, eight recombinant IHNVs (rIHNVs), termed NxGy according to the respective positions of the nucleoprotein (N) and glycoprotein (G) genes along the genome, have been recovered. All rIHNVs have been fully characterized
in vitro
for their cytopathic effects, kinetics of replication, and profiles of viral gene transcription. These rIHNVs are stable through up to 10 passages in cell culture. Following bath immersion administration of the various rIHNVs to juvenile trout, some of the rIHNVs were clearly attenuated (N2G3, N2G4, N3G4, and N4G1). The position of the N gene seems to be one of the most critical features correlated to the level of viral attenuation. The induced immune response potential in fish was evaluated by enzyme-linked immunosorbent spot assay (ELISPOT) and seroneutralization assays. The recombinant virus N2G3 induced a strong antibody response in immunized fish and conferred 86% of protection against wild-type IHNV challenge in trout, thus representing a promising starting point for the development of a live attenuated vaccine candidate.

IMPORTANCE
In Europe, no vaccines are available against infectious hematopoietic necrosis virus (IHNV), one of the major economic threats in fish aquaculture. Live attenuated vaccines are conditioned by a sensible balance between attenuation and pathogenicity. Moreover, nonsegmented negative-strain RNA viruses (NNSV) are subject to a transcription gradient dictated by the order of the genes in their genomes. With the perspective of developing a vaccine against IHNV, we engineered various recombinant IHNVs with reordered genomes in order to artificially attenuate the virus. Our results validate the gene rearrangement approach as a potent and stable attenuation strategy for fish novirhabdovirus and open a new perspective for design of vaccines against other NNSV.
Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice
Authors: Jaumain Emilie , Quadrio Isabelle , Herzog Laetitia , Reine Fabienne , Rezaei Human , Andréoletti Olivier , Laude Hubert , Perret-Liaudet Armand , Haïk Stéphane , Béringue Vincent
Published: September 2016

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrPC) and the infecting pathological PrP assemblies (PrPSc) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrPCand in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrPScsignatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD.

IMPORTANCESince the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population.
Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates
Authors: Chen Chia-Yen , Shingai Masashi , Welbourn Sarah , Martin Malcolm A. , Borrego Pedro , Taveira Nuno , Strebel Klaus
Published: September 2016

Although HIV-2 does not encode a
vpu
gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit.

IMPORTANCE
Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a
vpu
gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence.