bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone H3 lysine 4 methylation signature associated with human undernutrition
Authors: Uchiyama Robin , Kupkova Kristyna , Shetty Savera J. , Linford Alicia S. , Pray-Grant Marilyn G. , Wagar Lisa E. , Davis Mark M. , Haque Rashidul , Gaultier Alban , Mayo Marty W. , Grant Patrick A. , Petri William A. , Bekiranov Stefan , Auble David T.
Published: November 2018

Chronically undernourished children become stunted during their first 2 years and thereafter bear burdens of ill health for the rest of their lives. Contributors to stunting include poor nutrition and exposure to pathogens, and parental history may also play a role. However, the epigenetic impact of a poor environment on young children is largely unknown. Here we show the unfolding pattern of histone H3 lysine 4 trimethylation (H3K4me3) in children and mothers living in an urban slum in Dhaka, Bangladesh. A pattern of chromatin modification in blood cells of stunted children emerges over time and involves a global decrease in methylation at canonical locations near gene start sites and increased methylation at ectopic sites throughout the genome. This redistribution occurs at metabolic and immune genes and was specific for H3K4me3, as it was not observed for histone H3 lysine 27 acetylation in the same samples. Methylation changes in stunting globally resemble changes that occur in vitro in response to altered methylation capacity, suggesting that reduced levels of one-carbon nutrients in the diet play a key role in stunting in this population. A network of differentially expressed genes in stunted children reveals effects on chromatin modification machinery, including turnover of H3K4me3, as well as posttranscriptional gene regulation affecting immune response pathways and lipid metabolism. Consistent with these changes, reduced expression of the endocytic receptor gene LDL receptor 1 (LRP1) is a driver of stunting in a mouse model, suggesting a target for intervention.
Klotho controls the brain–immune system interface in the choroid plexus
Authors: Zhu Lei , Stein Liana R. , Kim Daniel , Ho Kaitlyn , Yu Gui-Qiu , Zhan Lihong , Larsson Tobias E. , Mucke Lennart
Published: November 2018

Significance

Global depletion of klotho accelerates aging, whereas klotho overexpression counteracts aging-related impairments. Why klotho is expressed at much higher levels in the choroid plexus than in other brain regions is unknown. We demonstrate in mice that aging is associated with klotho depletion in the choroid plexus. Reducing klotho selectively within the choroid plexus triggered inflammation within this structure and enhanced activation of innate immune cells within an adjacent brain region following a peripheral immune challenge. In cell culture, we identified a signaling pathway by which klotho suppresses activation of macrophages. Our findings shed light on klotho functions in the choroid plexus and provide a plausible mechanism by which klotho depletion from this structure promotes brain inflammation during the aging process.
Conserved behavioral circuits govern high-speed decision-making in wild fish shoals
Authors: Hein Andrew M. , Gil Michael A. , Twomey Colin R. , Couzin Iain D. , Levin Simon A.
Published: November 2018

Significance

To survive, animals must quickly detect and respond to predators. However, the rules wild animals use to translate sensory cues into evasion decisions remain largely unknown. We developed an automated system to present visual threat stimuli to mixed-species groups of foraging fish in a coral reef. Using hundreds of stimulus presentations to fish from nine families, we show that escape decisions are governed by a conserved set of decision-making rules that transform sensory input into evasive actions. Our methodology allows us to quantitatively analyze these rules, revealing both how they map onto previously studied neural circuits and how they function under dynamic natural conditions.
Golgi-localized LOT regulates
trans
-Golgi network biogenesis and pollen tube growth
Authors: Jia Peng-Fei , Xue Yong , Li Hong-Ju , Yang Wei-Cai
Published: November 2018

Significance

The plant
trans
-Golgi network (TGN) is spatially separated from the Golgi and functions as an independent cargo sorting station. The molecular mechanism and significance of its generation and separation from the Golgi are largely unclear. This study identified a Golgi-localized component that is essential for TGN biogenesis and sheds light on the regulation of post-Golgi trafficking.
Alpine ice evidence of a three-fold increase in atmospheric iodine deposition since 1950 in Europe due to increasing oceanic emissions
Authors: Legrand Michel , McConnell Joseph R. , Preunkert Susanne , Arienzo Monica , Chellman Nathan , Gleason Kelly , Sherwen Tomás , Evans Mat J. , Carpenter Lucy J.
Published: November 2018

Significance

Our measurements show a tripling of iodine in Alpine ice between 1950 and 1990. A 20th century increase in global iodine emissions has been previously found from model simulations, based on laboratory studies, but, up to now, long-term iodine records exist only in polar regions. These polar records are influenced by sea ice processes, which may obscure global iodine trends. Our results suggest that the increased iodine deposition over the Alps is consistent with increased oceanic iodine emissions coupled with a change in the iodine speciation, both driven by increasing anthropogenic NO
x
emissions. In turn, the recent increase of iodine emissions implies that iodine-related ozone loss in the troposphere is more active now than in the preindustrial period.
Quantitative constraints on autoxidation and dimer formation from direct probing of monoterpene-derived peroxy radical chemistry
Authors: Zhao Yue , Thornton Joel A. , Pye Havala O. T.
Published: November 2018

Organic peroxy radicals (RO
2
) are key intermediates in the atmospheric degradation of organic matter and fuel combustion, but to date, few direct studies of specific RO
2
in complex reaction systems exist, leading to large gaps in our understanding of their fate. We show, using direct, speciated measurements of a suite of RO
2
and gas-phase dimers from O
3
-initiated oxidation of α-pinene, that ∼150 gaseous dimers (C
16–20
H
24–34
O
4–13
) are primarily formed through RO
2
cross-reactions, with a typical rate constant of 0.75–2 × 10
−12
cm
3
molecule
−1
s
−1
and a lower-limit dimer formation branching ratio of 4%. These findings imply a gaseous dimer yield that varies strongly with nitric oxide (NO) concentrations, of at least 0.2–2.5% by mole (0.5–6.6% by mass) for conditions typical of forested regions with low to moderate anthropogenic influence (i.e., ≤50-parts per trillion NO). Given their very low volatility, the gaseous C
16–20
dimers provide a potentially important organic medium for initial particle formation, and alone can explain 5–60% of α-pinene secondary organic aerosol mass yields measured at atmospherically relevant particle mass loadings. The responses of RO
2
, dimers, and highly oxygenated multifunctional compounds (HOM) to reacted α-pinene concentration and NO imply that an average ∼20% of primary α-pinene RO
2
from OH reaction and 10% from ozonolysis autoxidize at 3–10 s
−1
and ≥1 s
−1
, respectively, confirming both oxidation pathways produce HOM efficiently, even at higher NO concentrations typical of urban areas. Thus, gas-phase dimer formation and RO
2
autoxidation are ubiquitous sources of low-volatility organic compounds capable of driving atmospheric particle formation and growth.
Long-range regulation of p53 DNA binding by its intrinsically disordered N-terminal transactivation domain
Authors: Krois Alexander S. , Dyson H. Jane , Wright Peter E.
Published: November 2018

Atomic resolution characterization of the full-length p53 tetramer has been hampered by its size and the presence of extensive intrinsically disordered regions at both the N and C termini. As a consequence, the structural characteristics and dynamics of the disordered regions are poorly understood within the context of the intact p53 tetramer. Here we apply
trans
-intein splicing to generate segmentally
15
N-labeled full-length p53 constructs in which only the resonances of the N-terminal transactivation domain (NTAD) are visible in NMR spectra, allowing us to observe this region of p53 with unprecedented detail within the tetramer. The N-terminal region is dynamically disordered in the full-length p53 tetramer, fluctuating between states in which it is free and fully exposed to solvent and states in which it makes transient contacts with the DNA-binding domain (DBD). Chemical-shift changes and paramagnetic spin-labeling experiments reveal that the amphipathic AD1 and AD2 motifs of the NTAD interact with the DNA-binding surface of the DBD through primarily electrostatic interactions. Importantly, this interaction inhibits binding of nonspecific DNA to the DBD while having no effect on binding to a specific p53 recognition element. We conclude that the NTAD:DBD interaction functions to enhance selectivity toward target genes by inhibiting binding to nonspecific sites in genomic DNA. This work provides some of the highest-resolution data on the disordered N terminus of the nearly 180-kDa full-length p53 tetramer and demonstrates a regulatory mechanism by which the N terminus of p53 transiently interacts with the DBD to enhance target site discrimination.
PPARγ-K107 SUMOylation regulates insulin sensitivity but not adiposity in mice
Authors: Katafuchi Takeshi , Holland William L. , Kollipara Rahul K. , Kittler Ralf , Mangelsdorf David J. , Kliewer Steven A.
Published: November 2018

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and is the target for the insulin-sensitizing thiazolidinedione (TZD) drugs used to treat type 2 diabetes. In cell-based in vitro studies, the transcriptional activity of PPARγ is inhibited by covalent attachment of small ubiquitin-related modifier (SUMOylation) at K107 in its N terminus. However, whether this posttranslational modification is relevant in vivo remains unclear. Here, using mice homozygous for a mutation (K107R) that prevents SUMOylation at this position, we demonstrate that PPARγ is SUMOylated at K107 in white adipose tissue. We further show that in the context of diet-induced obesity PPARγ-K107R–mutant mice have enhanced insulin sensitivity without the corresponding increase in adiposity that typically accompanies PPARγ activation by TZDs. Accordingly, the PPARγ-K107R mutation was weaker than TZD treatment in stimulating adipocyte differentiation in vitro. Moreover, we found that both the basal and TZD-dependent transcriptomes of inguinal and epididymal white adipose tissue depots were markedly altered in the K107R-mutant mice. We conclude that PPARγ SUMOylation at K107 is physiologically relevant and may serve as a pharmacologic target for uncoupling PPARγ’s beneficial insulin-sensitizing effect from its adverse effect of weight gain.
Observing Eurolects
Authors: Dilāns Gatis
Published: November 2018

The aim of this corpus-driven study is to examine intra-linguistic comparisons between a language variety used in EU Latvian directives and Latvian legal texts. The findings of the study show that there are lexical items (Europeisms) suggesting a conventionalized type of Eurospeak, but no patterned variation at other linguistic levels. These identified lexical forms showed divergent variability from their counterparts in the national measures of transposition. The reasons for such phenomena were due to highly conventionalized standards of EU translation.
Observing Eurolects
Authors: Biel Łucja
Published: November 2018

The chapter explores the Polish Eurolect, the largest Slavonic language in the EU. In respect of EU-rooted phenomena, the Polish Eurolect shows a high frequency of semantic Europeisms and a low overlap of lexical bundles. As regards contact-induced features, the Eurolect is subject to strong interference from EU English in the form of borrowings and calques, including punctuation, capitalisation, morphology, lexis and structure. Another type of contact-induced features are differences in the distribution of linguistic features that are triggered or suppressed as a result of contact. Intra-linguistic variation is also strongly demonstrated as register mixing. Hybrid phenomena are significantly more intense in the early phase and are reduced later due to the institutionalisation of translation process.
Observing Eurolects
Authors: Blini Lorenzo
Published: November 2018

This chapter aims to establish whether or not the legislative Spanish used in the European Union can be considered a different linguistic variety compared to the legislative variety used in national transposition measures. The study was carried out by performing a comparative analysis of a corpus of EU directives and the corresponding Spanish implementing measures. A quantitative approach was used along with qualitative observations in order to highlight characteristic features at several linguistic levels (lexical, morphological, morphosyntactic, syntactic, and textual). The results enable us to identify a Spanish Eurolect as a distinct linguistic variety, which tends to make use of a less marked register and more standardised patterns and contains fewer typical features of legal discourse.
The rhomboid protease GlpG has weak interaction energies in its active site hydrogen bond network
Authors: Gaffney Kristen A. , Hong Heedeok
Published: November 2018

Intramembrane rhomboid proteases are of particular interest because of their function to hydrolyze a peptide bond of a substrate buried in the membrane. Crystal structures of the bacterial rhomboid protease GlpG have revealed a catalytic dyad (Ser201-His254) and oxyanion hole (His150/Asn154/the backbone amide of Ser201) surrounded by the protein matrix and contacting a narrow water channel. Although multiple crystal structures have been solved, the catalytic mechanism of GlpG is not completely understood. Because it is a serine protease, hydrogen bonding interactions between the active site residues are thought to play a critical role in the catalytic cycle. Here, we dissect the interaction energies among the active site residues His254, Ser201, and Asn154 ofEscherichia coliGlpG, which form a hydrogen bonding network. We combine double mutant cycle analysis with stability measurements using steric trapping. In mild detergent, the active site residues are weakly coupled with interaction energies (ΔΔGInter) of ‒1.4 kcal/mol between His254 and Ser201 and ‒0.2 kcal/mol between Ser201 and Asn154. Further, by analyzing the propagation of single mutations of the active site residues, we find that these residues are important not only for function but also for the folding cooperativity of GlpG. The weak interaction between Ser and His in the catalytic dyad may partly explain the unusually slow proteolysis by GlpG compared with other canonical serine proteases. Our result suggests that the weak hydrogen bonds in the active site are sufficient to carry out the proteolytic function of rhomboid proteases.
Predicting Mortality in Nursing Home Residents With Dementia and Pneumonia Treated With Antibiotics: Validation of a Prediction Model in a More Recent Population
Authors: Rauh Simone P , Heymans Martijn W , van der Maaden Tessa , Mehr David R , Kruse Robin L , de Vet Henrica C W , van der Steen Jenny T
Published: November 2018

Background

We aimed to find the best predictive model for 14-day mortality in antibiotic-treated nursing home residents with dementia and pneumonia by first applying an existing model to the recent PneuMonitor study. Second, we evaluated whether model performance improved by revising variables or adding variables related to recent changes in the care for older people.

Methods

The original prognostic model included gender, respiratory rate, respiratory difficulty, pulse rate, decreased alertness, fluid intake, eating dependency, and pressure sores. This model was applied to 380 recent pneumonia episodes in nursing home residents with dementia, updated by considering revising and/or adding variables, internally validated using bootstrapping, and transformed into a simplified risk score that can be used in clinical practice. Model performance was evaluated by Hosmer-Lemeshow statistics and calibration graphs to assess calibration; and area under the receiver operating characteristic curve (AUC) to assess discrimination.

Results

The newer cohort had lower 14-day mortality and was less often dehydrated or malnourished. Median AUC of the original model over the imputed datasets was 0.76 (interquartile range: 0.76–0.77), compared to 0.80 in the old cohort. Extending the model with dehydration, bowel incontinence, increase in eating dependency and cardiovascular history, while removing pressure sores, improved AUC: 0.80 (interquartile range: 0.80–0.81) after internal validation. Calibration remained adequate (Hosmer-Lemeshow statistic: p = .67).

Conclusions

In the newer cohort with less severe illness, model performance of the existing model was adequate, but a new extended model distinguished better between residents at low and high mortality risk.
THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS-2016): INTERNAL DOSIMETRY RESULTS AND COMPARISON WITH MWDS-2013
Authors: Vostrotin Vadim V , Napier Bruce A , Zhdanov Alexei V , Miller Scott C , Sokolova Alexandra B , Bull Richard K , Suslova Klara G , Efimov Alexander V , Smith Michael A , Vvedensky Vladimir E
Published: November 2018

Differences in results from the new Mayak Worker Dosimetry System (MWDS-2016) vs the previous MWDS-2013 are described. Statistical characteristics are shown for the distribution of accumulated absorbed doses to organs for 8340 workers with bioassay data. Differences in mean values of accumulated doses and their relative standard uncertainties calculated by MWDS-2016 and MWDS-2013 were analysed separately for various types of industrial compounds of plutonium, specifically nitrates, mixtures and oxides. Within the range of accumulated doses >1 mGy, lung doses for nitrates and mixtures decreased by 41 and 15%, respectively, and remained at the same level for oxides. Accumulated liver doses within the range >1 mGy increased for nitrates and mixtures by 13 and 8%, respectively, and decreased for oxides by 7%.
Speech-in-Noise and Quality-of-Life Measures in School-Aged Children With Normal Hearing and With Unilateral Hearing Loss
Authors: Griffin Amanda M. , Poissant Sarah F. , Freyman Richard L.
Published: November 2018

Objectives:

(1) Measure sentence recognition in co-located and spatially separated target and masker configurations in school-aged children with unilateral hearing loss (UHL) and with normal hearing (NH). (2) Compare self-reported hearing-related quality-of-life (QoL) scores in school-aged children with UHL and NH.

Design:

Listeners were school-aged children (6 to 12 yrs) with permanent UHL (n = 41) or NH (n = 35) and adults with NH (n = 23). Sentence reception thresholds (SRTs) were measured using Hearing In Noise Test–Children sentences in quiet and in the presence of 2-talker child babble or a speech-shaped noise masker in target/masker spatial configurations: 0/0, 0/−60, 0/+60, or 0/±60 degrees azimuth. Maskers were presented at a fixed level of 55 dBA, while the level of the target sentences varied adaptively to estimate the SRT. Hearing-related QoL was measured using the Hearing Environments and Reflection on Quality of Life (HEAR-QL-26) questionnaire for child subjects.

Results:

As a group, subjects with unaided UHL had higher (poorer) SRTs than age-matched peers with NH in all listening conditions. Effects of age, masker type, and spatial configuration of target and masker signals were found. Spatial release from masking was significantly reduced in conditions where the masker was directed toward UHL subjects’ normal-hearing ear. Hearing-related QoL scores were significantly poorer in subjects with UHL compared to those with NH. Degree of UHL, as measured by four-frequency pure-tone average, was significantly correlated with SRTs only in the two conditions where the masker was directed towards subjects’ normal-hearing ear, although the unaided Speech Intelligibility Index at 65 dB SPL was significantly correlated with SRTs in four conditions, some of which directed the masker to the impaired ear or both ears. Neither pure-tone average nor unaided Speech Intelligibility Index was correlated with QoL scores.

Conclusions:

As a group, school-aged children with UHL showed substantial reductions in masked speech perception and hearing-related QoL, irrespective of sex, laterality of hearing loss, and degree of hearing loss. While some children demonstrated normal or near-normal performance in certain listening conditions, a disproportionate number of thresholds fell in the poorest decile of the NH data. These findings add to the growing literature challenging the past assumption that one ear is “good enough.”
Compensatory and Serial Processing Models for Relating Electrophysiology, Speech Understanding, and Cognition
Authors: Billings Curtis J. , McMillan Garnett P. , Dille Marilyn F. , Konrad-Martin Dawn
Published: November 2018

Objectives:

The objective of this study was to develop a framework for investigating the roles of neural coding and cognition in speech perception.

Design:

N1 and P3 auditory evoked potentials, QuickSIN speech understanding scores, and the Digit Symbol Coding cognitive test results were used to test the accuracy of either a compensatory processing model or serial processing model.

Results:

The current dataset demonstrated that neither the compensatory nor the serial processing model were well supported. An additive processing model may best represent the relationships in these data.

Conclusions:

With the outcome measures used in this study, it is apparent that an additive processing model, where exogenous neural coding and higher order cognition contribute independently, best describes the effects of neural coding and cognition on speech perception. Further testing with additional outcome measures and a larger number of subjects is needed to confirm and further clarify the relationships between these processing domains.
Acute correction of adolescent tibia vara with biplanar medial opening wedge osteotomy without a graft
Authors: Khaled Mohamed , Said Galal , Abubeih Hossam , El-Sherif Essam
Published: November 2018

Background:

This study evaluated the use of biplanar medial opening wedge high tibial osteotomy for correction of adolescent tibia vara. This technique is used successfully in correction of genu varum deformity associated with degenerative knee osteoarthritis.

Methods:

Twenty-two patients with adolescent tibia vara underwent medial opening wedge high tibial osteotomy without bone grafting. Eight patients had bilateral tibia vara. Twelve were boys and 10 were girls. Radiographs were obtained preoperatively and the mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured before and after correction.

Results:

All osteotomies healed within 10 wk. The mTFA was corrected from an average of 13.6 degrees (9-23 degrees) to within 2.6 degrees from normal mechanical tibiofemoral alignment. The mMPTA was corrected from an average of 76.7 degrees (68-81 degrees) to an average of 88 degrees (86-91 degrees) postoperatively. No neurovascular complications or wound infection occurred. There was only one recurrence that required an additional osteotomy leading to a satisfactory result.

Conclusions:

Medial opening wedge high tibial osteotomy without a bone graft is a simple, reproducible method for correction of mild to moderate adolescent tibia vara.
Maximizing research opportunities as a trainee in orthopaedics
Authors: Roth Travis S. , Osbahr Daryl C.
Published: November 2018

Maximizing research opportunities as a trainee requires genuine scientific curiosity and a strong organizational plan of research execution. Residents or fellows must start early, seek mentorship, and work together to follow through and publish their studies. The purpose of this article is to provide a framework for successful orthopedic research productivity during training, while accounting for the already demanding lifestyle of orthopaedic residents.
Functional and Oncological Outcome After Treatment of Chondroblastoma With Intralesional Curettage
Authors: Ebeid Walid A. , Hasan Bahaa Z. , Badr Ismail T. , Mesregah Mohamed K.
Published: November 2018

Background:

Chondroblastoma is a rare cartilaginous benign bone tumor that commonly arises in long bones of young people. Surgical management is the primary treatment of choice for chondroblastoma and it entails adequate intralesional curettage alone or in combination with adjuvants. This study was performed to describe the epidemiological characteristics and clinical and radiologic results of intralesional curettage of chondroblastoma.

Methods:

This was a retrospective study which included an analysis of 91 patients with chondroblastoma who were treated with intralesional curettage and were followed up between 1994 and 2014 for at least 3 years. Epidemiological data, clinical symptoms, radiologic and histologic investigations, surgery, functional outcomes, complications, and local recurrence rate were analyzed.

Results:

There were 60 males (65.9%) and 31 females (34.1%) with a mean age of 16.4 years. The most commonly involved bone was the proximal tibia in 24 patients (26.4%), followed by distal femur in 20 patients (22%), proximal humerus in 17 patients (18.7%) and proximal femur in 15 patients (16.6%). All patients underwent intralesional curettage. High-speed burr was used in 66 patients (72.5%). The resultant cavity was filled with autogenous bone graft, bone substitute, bone cement or a combination of bone graft and cement. Four patients (4.4%) had complications. Three patients (3.3%) developed local recurrence. Age, site, history of previous intervention or pathologic fracture had no impact on the rate of recurrence. The mean Musculoskeletal Tumor Society (MSTS) score was 28.88 (range, 24 to 30) points.

Conclusions:

Thorough curettage using high-speed burr and bone-grafting or bone cement in the treatment of chondroblastoma has good local control, low recurrence rate and excellent functional long-term outcome.

Level of Evidence:

Level IV, retrospective case series.
The Pediatric Orthopaedic Society of North America (POSNA) Adopts a Member Health and Wellness Charter
Authors: Goldberg Michael J. , Shea Kevin G. , Weiss Jennifer M. , Carter Cordelia W. , Talwalkar Vishwas R. , Schwend Richard M.
Published: November 2018

The Pediatric Orthopaedic Society of North America took actions to address the well-being of its members. The epidemic of physician burnout interferes with the delivery of high-quality care that our patients and families need and deserve, and at the same time places the care-providers at an increased risk of depression and suicide. The actions taken by Pediatric Orthopaedic Society of North America serve as a model for other professional medical societies to emulate.
Disagreement Between Clinicians and Score in Decision-Making Capacity of Critically Ill Patients*
Authors: Bertrand Pierre-Marie , Pereira Bruno , Adda Mireille , Timsit Jean-François , Wolff Michel , Hilbert Gilles , Gruson Didier , Garrouste-Orgeas Maïté , Argaud Laurent , Constantin Jean-Michel , Chabanne Russel , Quenot Jean-Pierre , Bohe Julien , Guerin Claude , Papazian Laurent , Jonquet Olivier , Klouche Kada , Delahaye Arnaud , Riu Beatrice , Zieleskiewicz Laurent , Darmon Michaël , Azoulay Elie , Souweine Bertrand , Lautrette Alexandre
Published: November 2018

Objectives:

To compare the assessment of decision-making capacity of ICU patients by attending clinicians (physicians, nurses, and residents) with a capacity score measured by the Mini-Mental Status Examination, completed by Aid to Capacity Evaluation if necessary. The primary outcome was agreement between physicians’ assessments and the score. Secondary outcomes were agreement between nurses’ or residents’ assessments and the score and identification of factors associated with disagreement.

Design:

A 1-day prevalence study.

Setting:

Nineteen ICUs in France.

Subjects:

All patients hospitalized in the ICU on the study day and the attending clinicians.

Interventions:

The decision-making capacity of patients was assessed by the attending clinicians and independently by an observer using the score.

Measurements and Main Results:

A total of 206 patients were assessed by 213 attending clinicians (57 physicians, 97 nurses, and 59 residents). Physicians designated more patients as having decision-making capacity (n = 92/206 [45%]) than score (n = 34/206 [17%]; absolute difference 28% [95% CI, 20–37%]; p = 0.001). There was a high disagreement between assessments of all clinicians and score (Kappa coefficient 0.39 [95% CI, 0.29–0.50] for physicians; 0.39 [95% CI, 0.27–0.52] for nurses; and 0.46 [95% CI, 0.35–0.58] for residents). The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15 (odds ratio, 2.92 [1.18–7.19], p = 0.02 for physicians; 4.97 [1.50–16.45], p = 0.01 for nurses; and 3.39 [1.12–10.29], p = 0.03 for residents) without differentiating between the Glasgow Coma Scale scores from 10 to 15.

Conclusions:

The decision-making capacity of ICU patients was largely overestimated by all attending clinicians as compared with a score. The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15, suggesting that clinicians confused consciousness with decision-making capacity.
Implementation of the HEART Pathway: Using the Consolidated Framework for Implementation Research
Authors: Gesell Sabina B. , Golden Shannon L. , Limkakeng Alexander T. , Carr Christine M. , Matuskowitz Andrew , Smith Lane M. , Mahler Simon A.
Published: November 2018

Objective:

The HEART Pathway is an evidence-based decision tool for identifying emergency department (ED) patients with acute chest pain who are candidates for early discharge, to reduce unhelpful and potentially harmful hospitalizations. Guided by the Consolidated Framework for Implementation Research, we sought to identify important barriers and facilitators to implementation of the HEART Pathway.

Study Setting:

Data were collected at 4 academic medical centers.

Study Design:

We conducted semi-structured interviews with 25 key stakeholders (e.g., health system leaders, ED physicians). We conducted interviews before implementation of the HEART Pathway tool to identify potential barriers and facilitators to successful adoption at other regional academic medical centers. We also conducted postimplementation interviews at 1 medical center, to understand factors that contributed to successful adoption.

Data Collection:

Interviews were recorded and transcribed verbatim. We used a Consolidated Framework for Implementation Research framework-driven deductive approach for coding and analysis.

Principal Findings:

Potential barriers to implementation include time and resource burden, challenges specific to the electronic health record, sustained communication with and engagement of stakeholders, and patient concerns. Facilitators to implementation include strength of evidence for reduced length of stay and unnecessary testing and iatrogenic complications, ease of use, and supportive provider climate for evidence-based decision tools.

Conclusions:

Successful dissemination of the HEART Pathway will require addressing institution-specific barriers, which includes engaging clinical and financial stakeholders. New SMART-FHIR technologies, compatible with many electronic health record systems, can overcome barriers to health systems with limited information technology resources.
A Prospective, Open-label Study to Assess the Safety, Tolerability and Efficacy of Anidulafungin in the Treatment of Invasive Candidiasis in Children 2 to <18 Years of Age
Authors: Roilides Emmanuel , Carlesse Fabianne , Leister-Tebbe Heidi , Conte Umberto , Yan Jean L. , Liu Ping , Tawadrous Margaret , Aram Jalal A. , Queiroz-Telles Flavio
Published: November 2018

Background:

Treatment with an echinocandin is recommended as first-line therapy for patients with invasive candidiasis (ICC) including candidemia. Little is known about the efficacy and safety of anidulafungin in children with ICC.

Methods:

Eligible patients with ICC 2 to <18 years old were enrolled into this prospective, open-label, noncomparative, international study (NCT00761267) and received anidulafungin for 10–35 days (3 mg/kg on day 1, 1.5 mg/kg daily thereafter). Safety was assessed through week 6 follow-up. Efficacy, measured by global response (based on clinical and microbiologic responses), was assessed at end of intravenous treatment (EOIVT), end of treatment, weeks 2 and 6 follow-up.

Results:

Forty-nine patients (n = 19, 2 to <5 years; n = 30, 5 to <18 years) received ≥1 dose of anidulafungin (median 11 days; range 1–35 days) and were assessed for safety. Among 48 patients with a Candida species isolated, C. albicans (37.5%), C. parapsilosis (25.0%), C. tropicalis (14.6%) and C. lusitaniae (10.4%) were the most frequent Candida spp. All patients reported ≥1 treatment-emergent adverse event, with diarrhea (22.4%), vomiting (24.5%) and pyrexia (18.4%) being most frequent. Five patients discontinued treatment because of adverse events, of which 4 discontinuations were considered related to anidulafungin. All-cause mortality was 8.2% (4/49) by EOIVT and 14.3% (7/49) by week 6 follow-up. None of 7 deaths during the study period were considered treatment related. Global response success rate was 70.8% at EOIVT.

Conclusions:

These data support the use of anidulafungin as a treatment option for ICC in children 2 to <18 years old at the studied dose.
Specimen Pooling as a Diagnostic Strategy for Microbiologic Confirmation in Children with Intrathoracic Tuberculosis
Authors: Walters Elisabetta , van der Zalm Marieke M. , Demers Anne-Marie , Whitelaw Andrew , Palmer Megan , Bosch Corné , Draper Heather R. , Schaaf H. Simon , Goussard Pierre , Lombard Carl J. , Gie Robert P. , Hesseling Anneke C.
Published: November 2018

Three-hundred four young children with suspected pulmonary tuberculosis had a gastric aspirate, induced sputum and nasopharyngeal aspirate collected on each of 2 consecutive weekdays. Specimens collected on the second day were pooled in the laboratory for each child individually. The diagnostic yield by Xpert and culture from pooled specimens was not significantly different to a single gastric aspirate.
Early-Onset Neonatal Pneumococcal Infection
Authors: Alsubaie Sarah S.
Published: November 2018

Streptococcus pneumoniae (SP) is a major cause of morbidity in childhood but has accounted for only a few reported cases of early-onset neonatal sepsis. Over the past decade, there have been increasing reports of early-onset neonatal sepsis due to SP associated with fulminant systemic disease and high mortality rates. Simultaneous maternal and neonatal sepsis with SP is relatively unusual. The literature reports rare cases of vaginal carriage and/or endometritis with this organism resulting in neonatal sepsis. We present a case of neonatal pneumococcal serotype 1 sepsis and cellulitis occurring concurrently with puerperal pneumococcal bacteremia. A male neonate was born at 38 weeks' gestation after a normal pregnancy. Although he was administered the appropriate antibiotics, the baby developed nape cellulitis and sepsis on the second day of life with SP that progressed to abscess formation requiring surgical drainage. The mother simultaneously developed pneumococcal bacteremia and endometritis 2 hours after delivery. Blood culture isolates from the mother and child were both serogroup 1. Transmission to the neonate may have been ascending or hematogenous.

In addition, we summarize the neonate and maternal characteristics, clinical courses, and outcomes of published case reports of early-onset neonatal pneumococcal sepsis in the peer-reviewed literature.

Our case highlights the need to consider SP as a cause of neonatal sepsis that can mimic early-onset group B streptococcal infection. Recognition of resistant strains in cases of bacteremia and meningitis is critical, and should be considered in choice of antibiotic therapy.

Enhanced surveillance for the maternal carriage of SP and invasive pneumococcal disease during the neonatal period would help to define the epidemiology.
Longitudinal pattern of pain medication utilization in peripheral neuropathy patients
Authors: Callaghan Brian C. , Reynolds Evan , Banerjee Mousumi , Kerber Kevin A. , Skolarus Lesli E. , Burke James F.
Published: November 2018

We aimed to investigate the pattern and utilization of neuropathic pain medications in peripheral neuropathy patients. Using a privately insured, health care claims database from 2001 to 2014, we identified a retrospective cohort of incident peripheral neuropathy patients (validated ICD-9 definition) after excluding other chronic pain conditions. Outcome measures included opioid prescriptions, chronic opioid therapy (greater than or equal to 90 days of continuous supply), guideline-recommended medications for painful peripheral neuropathy (serotonin reuptake inhibitors, tricyclic antidepressants, and gabapentinoids), and pain specialists (neurologists, physiatrists, and anesthesiologists). Multivariable logistic regression was used to evaluate associations of patient-level factors with these outcomes. The peripheral neuropathy population included 14,426 individuals with a mean (SD) age of 43.1 years (2.8) and 52.4% men followed for 3.1 (1.7) years before and 4.5 (1.4) years after the diagnosis. In this population, 65.9% received ≥1 opioid prescription, and 8.8% received chronic opioid therapy. Of those receiving chronic opioid therapy, only 26.4% received a guideline-recommended medication before chronic opioid status. For guideline-recommended medications, 35.7% received ≥1, 12.4% ≥2, and 3.8% ≥3 different medications. No patient-level factors were associated with both high opioid utilization (initiation and chronic use) and low guideline-recommended medication utilization. Pain specialists were associated with high opioid utilization and high guideline-recommended medication utilization. In conclusion, opioid initiation and transition to chronic opioid therapy are frequent in a peripheral neuropathy population despite few patients receiving more than one guideline-recommended medication. Efforts to decrease opioid utilization and increase guideline-recommended medication use are needed to improve current neuropathic pain treatment.
Effectiveness of Field-Based Resistance Training Protocols on Hip Muscle Strength Among Young Elite Football Players
Authors: Kohavi Bar , Beato Marco , Laver Lior , Freitas Tomas T. , Chung Linda H. , Dello Iacono Antonio
Published: November 2018

Objective:

The objective of this study was to examine the effects of an 8-week progressive resistance training program on hip joint muscles' strength measures, using the Copenhagen adduction (CA) and the sliding hip (SH) exercises.

Design:

Prospective randomized controlled trial.

Setting:

Sport training and medical centers.

Participants:

Forty-two young male football athletes (age 17.5 ± 1.1 years; height 178.3 ± 3.2 cm; body mass 66.1 ± 8.6 kg) allocated to a CA, SH, and matched control (C) group.

Interventions:

Two weekly sessions of CA and SH.

Main Outcome Measures:

Maximal eccentric strength test for the hip adductor (EHAD) and maximal eccentric strength test for the hip abductor (EHAB) muscles, and the relative EHAD/EHAB ratio assessed through a break test in the side-lying position.

Results:

No significant differences between groups were found at baseline for any of the assessed variables (all P > 0.053). The CA group had a significant strength increase in the right and left leg (d = 2.11, d = 1.9, respectively). The SH group also had a significant strength increase in the right and left leg (d = 1.68 and d = 1.67, respectively). The CA group presented EHAD/EHAB improvements in the right and left leg (d = 0.84 and d = 1.14, respectively). The SH group also presented EHAD/EHAB improvements in the right and left leg (d = 1.34 and d = 1.44, respectively).

Conclusions:

Both exercises' protocols were effective in inducing significant increases on EHAD, EHAB, and EHAD/EHAB ratio when compared with the control group. Practitioners should be aware of the training effectiveness of both protocols.
Correlation of Cardiovascular Risk Factors and Biomarkers With Platelet Reactivity in Coronary Artery Disease
Authors: Bobescu Elena , Covaciu Alexandru , Rus Horatiu , Radoi Mariana , Badea Mihaela , Moga Silvia N. , Benza Valentina , Marceanu Luigi G.
Published: November 2018

Background:

Low response to aspirin, aspirin resistance, and high platelet reactivity on aspirin treatment are similar names for lack of response to block arachidonic acid–induced aggregation with aspirin therapy and have an important role in the evolution of coronary artery disease (CAD) with thromboembolic events.

Study Question:

Was to evaluate the correlation between cardiovascular risk factors, biomarkers, and low response to aspirin in patients (pts) with CAD.

Study Design:

Four hundred pts with CAD were divided into 8 groups of study, consistent with the type of CAD and low response to aspirin. Cardiovascular risk factors and biomarkers—including some of high platelet reactivity, endothelial dysfunction, hypercoagulability, and oxidative stress—were evaluated in correlation with low response to aspirin, defined as on treatment aspirin test (ASPItest) >30U by multiple electrode platelet aggregometry.

Results:

In patients with CAD, low response to aspirin was significantly correlated with age older than 65 years, smoking, presence of diabetes mellitus, body mass index >25, hypertension, previous aspirin treatment, low response to clopidogrel, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilation, and total antioxidant status (P < 0.01). In unstable angina patients, low response to aspirin was significantly correlated with male sex (P < 0.03). Incidence of other hypercoagulability biomarkers—S Protein, C Protein, Antithrombin III, and V Factor Leiden resistance to activated protein C—was low and not correlated with low response to aspirin.

Conclusions:

In CAD, low response to aspirin was significantly correlated with age older than 65 years, smoking, presence of diabetes mellitus, body mass index I >25, hypertension, previous aspirin treatment, and only in unstable angina with male sex. Low response to aspirin was also statistically associated with low response to clopidogrel, high mean platelets volume, high von Willebrand factor activity, low flow-mediated vasodilation, and low total antioxidant status values.
Lesions of the Parotid Gland and Buccal Artery After Buccal Fat Pad Reduction
Authors: Vieira Giovanni Modesto , Jorge Fabrício David , Franco Eduardo Jacomino , Dias Leandro da Cunha , Guimarães Maria do Carmo Machado , Oliveira Laudimar Alves de
Published: November 2018

The significant increase in esthetic surgery, especially buccal fat pad reduction, has led to a corresponding increase in lesions and postoperatory after-effects from this surgical procedure. The aim of this study is to discuss the immediate and mediate risks of removing the Bichat ball, as well as describing a clinical study in which this surgical procedure resulted in lesions of the parotid gland and buccal artery, which was confirmed via nuclear magnetic resonance. The facial lesions were remedied via exploratory surgery by opening a new orifice of the glandular duct in the buccal cavity followed by drainage and compressive surgical bandages.
Dissipative structures induced by photoisomerization in a dye-doped nematic liquid crystal layer
Authors: Andrade-Silva I. , Bortolozzo U. , Castillo-Pinto C. , Clerc M. G. , González-Cortés G. , Residori S. , Wilson M.
Published: November 2018

Order–disorder phase transitions driven by temperature or light in soft matter materials exhibit complex dissipative structures. Here, we investigate the spatio-temporal phenomena induced by light in a dye-doped nematic liquid crystal layer. Experimentally, for planar anchoring of the nematic layer and high enough input power, photoisomerization processes induce a nematic–isotropic phase transition mediated by interface propagation between the two phases. In the case of a twisted nematic layer and for intermediate input power, the light induces a spatially modulated phase, which exhibits stripe patterns. The pattern originates as an instability mediated by interface propagation between the modulated and the homogeneous nematic states. Theoretically, the phase transition, emergence of stripe patterns and front dynamics are described on the basis of a proposed model for the dopant concentration coupled with the nematic order parameter. Numerical simulations show quite a fair agreement with the experimental observations.

This article is part of the theme issue ‘Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)’.
Fluctuations out of equilibrium
Authors: Belyi V. V.
Published: November 2018

A generalized fluctuation–dissipation theorem involving slowly varying parameters is presented. Application of the Langevin method, the method of moments and of a multiscale technique reveal that not only dissipation but also dispersive contributions determine the spectral functions of fluctuations in arbitrary statistical systems. The non-Joule dispersive contribution is characterized by a novel non-local effect due to the additional phase shift between the force and the response of the system. This phase shift occurs as a result of parametric control to the system. The general formalism is illustrated by concrete examples and applications.

This article is part of the theme issue ‘Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)’.
Stationary localized structures and the effect of the delayed feedback in the Brusselator model
Authors: Kostet B. , Tlidi M. , Tabbert F. , Frohoff-Hülsmann T. , Gurevich S. V. , Averlant E. , Rojas R. , Sonnino G. , Panajotov K.
Published: November 2018

The Brusselator reaction–diffusion model is a paradigm for the understanding of dissipative structures in systems out of equilibrium. In the first part of this paper, we investigate the formation of stationary localized structures in the Brusselator model. By using numerical continuation methods in two spatial dimensions, we establish a bifurcation diagram showing the emergence of localized spots. We characterize the transition from a single spot to an extended pattern in the form of squares. In the second part, we incorporate delayed feedback control and show that delayed feedback can induce a spontaneous motion of both localized and periodic dissipative structures. We characterize this motion by estimating the threshold and the velocity of the moving dissipative structures.

This article is part of the theme issue ‘Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)’.