bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel grass–endophyte associations reduce the feeding behaviour of invasive European rabbits (Oryctolagus cuniculus)
Authors: Pennell Christopher G. L. , Rolston M. Philip , Latham A. David M. , Mace Wade J. , Vlaming Ben , van Koten Chikako , Latham M. Cecilia , Brown Samantha , Card Stuart D.
Published: March 2017

Context Small mammalian herbivores, such as European rabbits (Oryctolagus cuniculus), can have significant unwanted impacts on agriculture and horticulture and can attract birds of prey and avian scavengers to airports, increasing the risk of bird strike. Sustainable wildlife management tools that have high efficacy and animal welfare are needed to mitigate these impacts. Aim We assessed perennial ryegrass (Lolium perenne) and tall fescue (Festuca arundinacea) cultivars associated with selected Epichloë endophytes, originally developed for bird management at airports, to determine their feeding-deterrent properties towards invasive rabbits. Methods A pellet feed trial using caged domestic rabbits and a pen trial using wild rabbits were conducted to assess rabbit responses to food pellets with novel endophyte-infected or uninfected grass seed and to plots planted with endophyte-infected or uninfected grasses, respectively. Key results Caged rabbits ate significantly less food pellets containing endophyte-infected grass straw than pellets containing endophyte-free grass straw. Wild rabbits consumed significantly less herbage from plots planted with endophyte-infected grasses than those of the equivalent endophyte-free grass cultivars. Temporal patterns of rabbit feeding behaviour support the hypothesis that deterrence in rabbits resulted from post-ingestion feedback associated with grass–endophyte secondary metabolites. Conclusions Although more research is required on the exact mechanism of action in rabbits, our results suggest novel endophyte-infected grass associations may substantially reduce rabbit feeding behaviour and possibly rabbit numbers in areas where these grasses are sown. Implications Novel grass–endophyte associations have great potential for deterring problem wildlife at airports and other amenity areas.
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
Authors: Ehrlich Marc , Mozafari Sabah , Glatza Michael , Starost Laura , Velychko Sergiy , Hallmann Anna-Lena , Cui Qiao-Ling , Schambach Axel , Kim Kee-Pyo , Bachelin Corinne , Marteyn Antoine , Hargus Gunnar , Johnson Radia Marie , Antel Jack , Sterneckert Jared , Zaehres Holm , Schöler Hans R. , Baron-Van Evercooren Anne , Kuhlmann Tanja
Published: March 2017

Significance

Understanding of myelin diseases and development of new treatment options are at least partly hampered by the limited availability of human oligodendrocytes. Induced pluripotent stem cells (iPSC) may be an ideal tool to circumvent this problem; however, rapid and efficient protocols to generate oligodendrocytes from human iPSC are currently lacking. The induction of the transcription factors SOX10, OLIG2, and NKX6.2 in iPSC-derived neural progenitors accelerates oligodendroglial differentiation significantly resulting in up to 70% of O4
+
oligodendrocytes within 28 d. These oligodendrocytes myelinate the CNS during development and after demyelination, and are suitable for pharmacological screens and disease modeling. The strategy presented herein will markedly facilitate the studying of human myelin diseases and the development of screening platforms for drug discovery.
Assessing significance in a Markov chain without mixing
Authors: Chikina Maria , Frieze Alan , Pegden Wesley
Published: March 2017

Significance

Markov chains are simple mathematical objects that can be used to generate random samples from a probability space by taking a random walk on elements of the space. Unfortunately, in applications, it is often unknown how long a chain must be run to generate good samples, and in practice, the time required is often simply too long. This difficulty can preclude the possibility of using Markov chains to make rigorous statistical claims in many cases. We develop a rigorous statistical test for Markov chains which can avoid this problem, and apply it to the problem of detecting bias in Congressional districting.
Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5
Authors: Hu Ming-Ming , Liao Chen-Yang , Yang Qing , Xie Xue-Qin , Shu Hong-Bing
Published: March 2017

Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I–mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells. Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection. At the late phase of viral infection, both MDA5 and RIG-I are desumoylated by SENP2, resulting in their K48-linked polyubiquitination and degradation. These findings suggest that dynamic sumoylation and desumoylation of MDA5 and RIG-I modulate efficient innate immunity to RNA virus and its timely termination.
Systematic inference of functional phosphorylation events in yeast metabolism
Authors: Chen Yu , Wang Yonghong , Nielsen Jens
Published: March 2017

Motivation

Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention.

Results

We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae, among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology.

Availability and Implementation

Matlab codes for flux balance analysis in this study are available in Supplementary material.

Supplementary information

Supplementary data are available at Bioinformatics online.
The landscape of genetic susceptibility correlations among diseases and traits
Authors: Ohn Jung Hun
Published: March 2017

Objective: The aim of the study was to comprehensively explore the genetic susceptibility correlations among diseases and traits from large-scale individual genotype data.

Materials and Methods: Based on a knowledge base of genetic variants significantly (P < 5 × 10−8) linked with human phenotypes, genetic risk scores (GRSs) of diseases or traits were calculated for 2504 individuals with whole-genome sequencing data from the 1000 Genomes Project. Associations between diseases/traits were statistically evaluated by pairwise correlation analysis of GRSs. Overlaps between the genetic susceptibility correlations and disease comorbidity associations from hospital claims data in more than 30 million patients in United States were assessed.

Results: Correlation analysis of GRSs revealed 823 significant correlations among 78 diseases and 89 traits (false discovery rate adjusted P-value or Q-value < 0.01). It is noticeable that GRSs were correlated in 464 associations (56.4%) even if they were combinations of distinct sets of risk variants without chromosomal linkage, suggesting the presence of genetic interactions beyond chromosome position. When 312 significant genetic susceptibility correlations between diseases were compared to nationwide disease comorbidity correlations obtained from data from 32 million Medicare claims in the United States, 108 overlaps (34.6%) were found that had both genetic susceptibility and epidemiologic comorbid correlations.

Conclusion: The study suggests that common genetic background exists between diseases and traits with epidemiologic associations. The GRS correlation approach provides a rich source of candidate associations among diseases and traits from the genetic perspective, warranting further epidemiologic studies.
Liquid Consumption
Authors: Bardhi Fleura , Eckhardt Giana M
Published: March 2017

This article introduces a new dimension of consumption as liquid or solid. Liquid consumption is defined as ephemeral, access based, and dematerialized, while solid consumption is defined as enduring, ownership based, and material. Liquid and solid consumption are conceptualized as existing on a spectrum, with four conditions leading to consumption being liquid, solid, or a combination of the two: relevance to the self, the nature of social relationships, accessibility to mobility networks, and type of precarity experienced. Liquid consumption is needed to explain behavior within digital contexts, in access-based consumption, and in conditions of global mobility. It highlights a consumption orientation around values of flexibility, adaptability, fluidity, lightness, detachment, and speed. Implications of liquid consumption are discussed for the domains of attachment and appropriation; the importance of use value; materialism; brand relationships and communities; identity; prosumption and the prosumer; and big data, quantification of the self, and surveillance. Lastly, managing the challenges of liquid consumption and its effect on consumer welfare are explored.
A possible time-delayed brightening of the Sgr A* accretion flow after the pericenter passage of the G2 cloud
Authors: Kawashima Tomohisa , Matsumoto Yosuke , Matsumoto Ryoji
Published: March 2017

A possibility of time-delayed radio brightenings of Sgr A* triggered by the pericenter passage of the G2 cloud is studied by carrying out global three-dimensional magnetohydrodynamic simulations, taking into account the radiative cooling of the tidal debris of the G2 cloud. Magnetic fields in the accretion flow are strongly perturbed and reorganized after the passage of G2. We have found that the magnetic energy in the accretion flow increased by a factor of 3–4 in 5–10 yr after the passage of G2 through a dynamo mechanism driven by the magneto-rotational instability. Since this B-field amplification enhances the synchrotron emission from the disk and the outflow, the radio and the infrared luminosity of Sgr A* are expected to increase some time, around 2020. The time delay of the radio brightening enables us to determine the rotation axis of the preexisting disk.
Variation Among Pediatric Orthopaedic Surgeons When Diagnosing and Treating Pediatric and Adolescent Distal Radius Fractures
Authors: Dua Karan , Stein Matthew K. , O’Hara Nathan N. , Brighton Brian K. , Hennrikus William L. , Herman Martin J. , Lawrence J. Todd , Mehlman Charles T. , Otsuka Norman Y. , Shrader M. Wade , Smith Brian G. , Sponseller Paul D. , Abzug Joshua M.
Published: March 2017

Background:

Distal radius fractures are the most common injury in the pediatric population. The purpose of this study was to determine the variation among pediatric orthopaedic surgeons when diagnosing and treating distal radius fractures.

Methods:

Nine pediatric orthopaedic surgeons reviewed 100 sets of wrist radiographs and were asked to describe the fracture, prescribe the type of treatment and length of immobilization, and determine the next follow-up visit. κ statistics were performed to assess the agreement with the chance agreement removed.

Results:

Only fair agreement was present when diagnosing and classifying the distal radius fractures (κ=0.379). There was poor agreement regarding the type of treatment that would be recommended (κ=0.059). There was no agreement regarding the length of immobilization (κ=−0.004).

Poor agreement was also present regarding when the first follow-up visit should occur (κ=0.088), whether or not new radiographs should be obtained at the first follow-up visit (κ=0.133), and if radiographs were necessary at the final follow-up visit (κ=0.163). Surgeons had fair agreement regarding stability of the fracture (κ=0.320).

A subgroup analysis comparing various traits of the treatment immobilization showed providers only had a slight level of agreement on whether splint or cast immobilization should be used (κ=0.072). There was poor agreement regarding whether long-arm or short-arm immobilization should be prescribed (κ=−0.067).

Twenty-three of the 100 radiographs were diagnosed as a torus/buckle fracture by all 9 surgeons. κ analysis performed on all the treatment and management questions showed that each query had poor agreement.

Conclusions:

The interobserver reliability of diagnosing pediatric distal radius fractures showed only fair agreement. This study demonstrates that there is no standardization regarding how to treat these fractures and the length of immobilization required for proper fracture healing. Better classification systems of distal radius fractures are needed that standardize the treatment of these injuries.

Level of Evidence:

Level II.
Accuracy and Reliability of Computed Tomography and Magnetic Resonance Imaging Compared With True Anatomic Femoral Version
Authors: Beebe Michael J. , Wylie James D. , Bodine Bill G. , Kapron Ashley L. , Maak Travis G. , Mei-Dan Omer , Aoki Stephen K.
Published: March 2017

Background:

Abnormal torsion of the femur is correlated to lower extremity pathologies. Although computed tomography (CT) scan is the gold standard torsional measurement, magnetic resonance imaging (MRI) is proposed as a viable alternative. Our aim was to determine the accuracy and consistency of MRI and CT femur rotational studies based on 4 described protocols.

Methods:

Twelve cadaveric femora were stripped of soft tissue before imaging and physical assessment of torsion. Four advanced imaging series were obtained for each specimen: CT with axial cuts of the femoral neck (CT-axial); CT with oblique cuts of the femoral neck (CT-oblique); MRI with axial cuts of the femoral neck (MR-axial); MRI with oblique cuts of the femoral neck (MR-oblique). Anatomic specimens were placed with the posterior femoral condyles flat on a dissection table for assessment of true torsion with digital images. Three independent reviewers performed all measurements, including true torsion, using imaging software. Bland-Altman analysis was repeated with the data from each reviewer.

Results:

Interobserver repeatability for all groups was high at 0.95, 0.87, 0.90, 0.97, and 0.92 for CT-axial, CT-oblique, MR-axial, MR-oblique, and true torsion, respectively. CT-axial had the lowest mean difference from clinical imaging for all three observers (all <1 degree) and held the tightest 95% limits of agreement for 2/3 observers. As torsion increases from neutral, MR-oblique linearly overestimates the rotation compared with true torsion. CT-oblique and MR-axial showed slightly greater differences from true torsion compared with CT-axial, but did not reach clinical significance.

Conclusions:

CT-axial was both most accurate and reproducible when compared with true torsion of the femur and should be the gold standard imaging modality; however, both MR-axial and CT-oblique were accurate to a level that is likely less than clinical significance. MR-axial images should be used in clinical situations where radiation exposure needs to be limited. MR-oblique images can overestimate true antetorsion and should not be used.

Clinic Significance:

CT-axial followed by MRI-axial is the most accurate and consistent in measuring true torsion of the femur.
Incorporating Inflammation into Mortality Risk in Pediatric Acute Respiratory Distress Syndrome
Authors: Zinter Matt S. , Orwoll Benjamin E. , Spicer Aaron C. , Alkhouli Mustafa F. , Calfee Carolyn S. , Matthay Michael A. , Sapru Anil
Published: March 2017

Objectives:

In pediatric acute respiratory distress syndrome, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk stratification of poor outcomes.

Design:

Multicenter prospective observational study.

Setting:

We enrolled patients from five academic PICUs between 2008 and 2015.

Patients:

Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of acute respiratory distress syndrome.

Interventions:

Eight proinflammatory and anti-inflammatory cytokines were measured on acute respiratory distress syndrome day 1 and correlated with mortality, ICU morbidity as measured by survivor Pediatric Logistic Organ Dysfunction score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin.

Measurements and Main Results:

We measured biomarker levels in 194 patients, including 38 acute respiratory distress syndrome nonsurvivors. Interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating oxygenation index, interleukin-8, and tumor necrosis factor-R2 was superior to a model of oxygenation index alone in predicting the composite outcome of mortality or severe morbidity (area under the receiver operating characteristic, 0.77 [0.70–0.83] vs 0.70 [0.62–0.77]; p = 0.042).

Conclusions:

In pediatric acute respiratory distress syndrome, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the oxygenation index to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.
RANIBIZUMAB FOR RETINAL VEIN OCCLUSION
Authors: Chatziralli Irini , Theodossiadis George , Chatzirallis Alexandros , Parikakis Efstratios , Mitropoulos Panagiotis , Theodossiadis Panagiotis
Published: March 2017

Purpose:

The purpose of the study was to evaluate the long-term anatomical and functional outcomes in patients with retinal vein occlusion (RVO), either central retinal vein occlusion or branch retinal vein occlusion, treated with intravitreal ranibizumab and to determine the predictive factors of the final visual outcome.

Methods:

This retrospective study included 54 treatment-naive patients with macular edema due to RVO (25 with central retinal vein occlusion and 29 with branch retinal vein occlusion), who were treated with intravitreal ranibizumab (3 monthly injections and pro re nata). Predictive factors for visual outcome were assessed. In addition, the best-corrected visual acuity change and the percentage of patients with edema resolution were evaluated.

Results:

The mean follow-up time was 47.4 ± 11.1 months. At the end of the follow-up, patients with central retinal vein occlusion gained +6.9 letters (∼1 Snellen line), whereas patients with branch retinal vein occlusion gained +15.1 letters (3 Snellen lines). Forty-eight percent of patients in central retinal vein occlusion group and 69.0% in branch retinal vein occlusion group presented resolution of macular edema. Negative predictive factors for the final visual outcome were found to be increasing age, increasing macular thickness, the presence of intraretinal fluid, the duration of RVO >3 months, the ischemic type of RVO, the cystoid type of edema, and the external limiting membrane and ellipsoid zone disruption.

Conclusion:

The various predictive factors that determine the visual outcome and possibly define the patients' prognosis after ranibizumab treatment in RVO have been studied. The long follow-up period showed that ranibizumab seems to be safe and effective in the treatment of the disease.
A Multisite Study Evaluating the Benefits of Early Intervention via Telepractice
Authors: Behl Diane D. , Blaiser Kristina , Cook Gina , Barrett Tyson , Callow-Heusser Catherine , Brooks Betsy Moog , Dawson Pamela , Quigley Suzanne , White Karl R.
Published: March 2017

This study sought to determine the effectiveness of telepractice as a method of delivering early intervention services to families of infants and toddlers who are deaf or hard of hearing. A comparison group design was applied to ascertain the child, family, and provider outcomes via telepractice compared with traditional in-person home visits. A total of 48 children and their families, along with 15 providers from 5 early intervention programs, across the country participated. Children in the telepractice group received more intervention, although the number of prescribed sessions was equal across groups. Analyses of covariance demonstrated that children in the telepractice group scored statistically significantly higher than children in the in-person group on the PLS-5 Receptive Language subscale and PLS-5 Total Language standard scores, and the groups scored similarly on other language measures. There were no statistically significant differences between groups in regard to family outcomes of support, knowledge, and community involvement. Analysis of video recordings of telepractice versus in-person home visits resulted in higher scores for provider responsiveness and parent engagement. This study supports the effectiveness of telepractice in delivering early intervention services to families of children who are deaf or hard of hearing. Further research involving randomized trials with larger, more diverse populations is warranted.
A Context-oriented Communication Algorithm for Advance Care Planning
Authors: Kim JinShil , Kim Shinmi , Shin Mi-Seung , Jin Jae Ok , Kim Yunmi , Lee Mee-Ok
Published: March 2017

Background:

Access to consultation or referral for decisions about advance care planning (ACP) is limited, particularly for nonmalignant models pertinent to palliative care in heart failure (HF).

Objectives:

The aim of this study was to solicit professional opinions about the feasibility of using an exemplary context-oriented communication algorithm for ACP discussions.

Methods:

Using a panel of expert physicians and nurses in cardiovascular care, a 3-round Delphi study was conducted to evaluate the proposed model.

Results:

A consensus was determined based on a content validity ratio (CVR) of 0.318 or greater, a critical value for selection of an item scored as important (≥4 on a 5-point Likert scale). A total of 50, 44, and 38 experts in Korea completed each round, respectively. Item evaluation did not differ across rounds (Friedman χ2>P= .05), except for timing of the ACP discussion. A lack of consensus was observed on the issue of after HF diagnosis for right timing of the ACP discussion across rounds (CVRs from −0.80 to −0.83); consensus was reached on the expectation of a terminal state (CVRs from 0.60 to 0.78). Content validity ratios were moderately high for Korean advance directive, ranging from 0.59 to 0.91. Experts also reached consensus about each of 5 steps of a communication model—patients’ determination of decisional capacity (CVR, 0.72–1.0), awareness (CVR, 0.95–1.0), willingness for advance care planning (CVR, 0.76–0.84), family dynamics (CVR, 0.92–1.0) and patient readiness for advance care planning (CVR, 0.76–0.95).

Conclusions:

A context-oriented communication model could be used to facilitate the decision-making process for palliative care and continuity of care in HF.
Radiofrequency ablation treatment for aldosterone-producing adenomas
Authors: Sacks Barry A. , Sacks Ari C. , Faintuch Salomao
Published: March 2017

Purpose of review

To review the current status of radiofrequency ablation as a primary treatment for hyperfunctioning adrenal nodules, predominantly aldosterone-producing adenomas (APAs).

Recent findings

Radiofrequency ablation is an established treatment for focal benign and malignant lesions, including metastatic disease to the adrenal gland. Hyperaldosteronism is the leading cause of secondary hypertension with up to 80% due to APA, statistically the most common functioning adrenal nodule. Although surgery remains the recommended treatment of choice for confirmed unilateral functioning adrenal nodules, radiofrequency ablation offers a less-invasive approach, with results comparable with surgery.

Radiofrequency ablation of functioning adrenal nodules is a newer application of a technology in use for almost 2 decades. Although limited, reports to date suggest that results are comparable with those of laparoscopic adrenalectomy, but with advantages including being a less-invasive outpatient procedure with lower morbidity, faster recovery, and lower cost. However, the current data are all retrospective, the number of patients treated is small, and reported long-term results are limited.
Efficacy of Reducing Alteplase Dose to Restore Patency in Nonhemodialysis Central Vascular Access Devices
Authors: Plohal Ann , Schiller Krishna
Published: March 2017

Central line-associated bloodstream infections (CLABSIs) are preventable through vigilant and thorough care.1 When CLABSIs occurred at a facility in Southwest Arizona, the root cause analysis discovered that declotting agents, such as alteplase, were not given routinely when nonhemodialysis (non-HD) central vascular access devices (CVADs) lacked blood return. A PICO question was developed that guided the review of literature and central line care standards of practice: In the adult patients with non-HD central lines, what medications are currently recommended to restore patency? As a result of this project, our facility instituted a new protocol using a reduced dose of alteplase to restore patency to non-HD CVADs.
A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma
Authors: Kadota Kyuichi , Miyai Yumi , Katsuki Naomi , Kushida Yoshio , Matsunaga Toru , Okuda Masaya , Yokomise Hiroyasu , Kanaji Nobuhiro , Bandoh Shuji , Haba Reiji
Published: March 2017

For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.
Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2
Authors: Upperman Jeffrey S. , Bucuvalas John C. , Williams Felicia N. , Cairns Bruce A. , Cox Charles S. , Doctor Allan , Tamburro Robert F.
Published: March 2017

Objective:

To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Multiple Organ Dysfunction Workshop (March 26–27, 2015). In addition, the relationship between burn injuries and multiple organ dysfunction syndrome is also included although it was not discussed at the workshop.

Data Sources:

Literature review, research data, and expert opinion.

Study Selection:

Not applicable.

Data Extraction:

Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions and therapies were presented, discussed, and debated with a focus on identifying knowledge gaps and the research priorities.

Data Synthesis:

Summary of presentations and discussion supported and supplemented by relevant literature.

Conclusions:

Sepsis and trauma are the two conditions most commonly associated with multiple organ dysfunction syndrome both in children and adults. However, many other pathophysiologic processes may result in multiple organ dysfunction syndrome. In this article, we discuss conditions such as liver failure and pancreatitis, pathophysiologic processes such as ischemia and hypoxia, and injuries such as trauma and burns. Additionally, therapeutic interventions such as medications, blood transfusions, transplantation may also precipitate and contribute to multiple organ dysfunction syndrome. The purpose of this article is to describe the association of multiple organ dysfunction syndrome with a variety of conditions and therapies in an attempt to identify similarities, differences, and opportunities for therapeutic intervention.
Precision Medicine With Point-of-Care Ultrasound
Authors: Kessler David , Ng Lorraine , Tessaro Mark , Fischer Jason
Published: March 2017

The Precision Medicine Initiative spearheaded by the National Institute of Health has pioneered a new model of health care focused on health care delivery that is tailored to an individual. Medical advances have already provided clinicians with the tools to better predict treatment outcomes based on the individual needs of each patient's disease process. Three-dimensional printing allows medical devices and implants to be custom made-to-order. Technological advances in preoperative imaging have augmented the ability for surgeons to plan a specific surgical approach for each patient. In a similar vein, point-of-care ultrasound offers the emergency care provider an opportunity to move beyond protocols and provide precise medical care tailored to the acute needs of each ill or injured emergent patient. In this article, we explore several cutting-edge applications of point-of-care ultrasound that can help providers develop a personalized approach to resuscitation and emergent procedures in pediatrics.
Family-Based Crisis Intervention With Suicidal Adolescents
Authors: Wharff Elizabeth A. , Ginnis Katherine B. , Ross Abigail M. , White Erina M. , White Matthew T. , Forbes Peter W.
Published: March 2017

Objective

In current practice, treatment as usual (TAU) for suicidal adolescents includes evaluation, with little or no intervention provided in the emergency department (ED), and disposition, usually to an inpatient psychiatry unit. The family-based crisis intervention (FBCI) is an emergency psychiatry intervention designed to sufficiently stabilize suicidal adolescents within a single ED visit so that they may return home safely with their families. The objective of this article is to report efficacy outcomes related to FBCI for suicidal adolescents and their families.

Methods

A total of 142 suicidal adolescents (age, 13–18 years) and their families presenting for psychiatric evaluation to a large pediatric ED were randomized to receive FBCI or TAU. Patients and caregivers completed self-report measures of suicidality, family empowerment, and satisfaction with care provided at pretest, posttest, and 3 follow-up time points over a 1-month period.

Results

Patients randomized to FBCI were significantly more likely to be discharged home with outpatient follow-up care compared with their TAU counterparts (P < 0.001). Families randomized to the FBCI condition reported significantly higher levels of family empowerment and client satisfaction with care at posttest compared with their TAU counterparts. Gains were maintained over the follow-up period. No completed suicides were reported during the study period in either condition.

Conclusions

Family-based crisis intervention is a model of care for suicidal adolescents that may be a viable alternative to traditional ED care that involves inpatient psychiatric hospitalization.
A Rare Case of Candida Epiglottitis in an Immunocompetent Child
Authors: Beil Elizabeth P. , Sole David P.
Published: March 2017

We present a case of acute Candida epiglottitis in an otherwise healthy and Haemophilus influenzae type B–immunized 4-year-old child. A query of the literature reveals this disease to be commonly found in patients who are immunocompromised by problems including human immunodeficiency virus disease and lymphoma and leukemia. However, there are no published reports of acute Candida epiglottitis in immunocompetent and vaccinated patients. Our case should emphasize to the emergency physician the need to remain vigilant for subtle and atypical presentations of airway-destabilizing diseases.
The Effectiveness of Structured Group Education on Ankylosing Spondylitis Patients
Authors: Kasapoglu Aksoy Meliha , Birtane Murat , Taştekin Nurettin , Ekuklu Galip
Published: March 2017

Background

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton which can lead to structural and functional impairments. It has a negative impact on the person's daily life activities. Early diagnosis, exercise and patient education are factors playing a major role on prognosis.

Objective

The purpose of the study was to compare the structured theoretical and exercise educational program with routine clinic educational efforts on the parameters of the disorder over a 3 month follow up.

Materials and Methods

This randomized, educational intervention study was performed on 41 AS patients. A 5 day structured education and exercise program was applied to the first group of patients (Group 1) in subgroups consisting 4–5 patients each. Patients had group exercises throughout the education program. The second group followed routine clinical care. The effectiveness of the treatment was assessed by Bath ankylosing spondylitis functional (BASFI), Bath ankylosing spondylitis disease activity (BASDAI), Bath ankylosing spondylitis global (BAS-G), Bath ankylosing spondylitis metrology indices (BASMI), chest expansion, short form-36 (SF-36), ankylosing spondylitis quality of life scale (ASQoL) and laboratory parameters in all patients. Patients were evaluated on initiation and after 3 months.

Results

Significant improvements in BASFI, BASDAI and BAS-G, chest expansion, SF-36 and ASQoL indices were observed in Group 1 No difference could be found in BASMI and chest expansion.

Conclusion

A structured educational and exercise intervention had a positive effect on the functional status,disease activity, and general well-being and quality of life. It also, shows that education programs should be within the routine treatment program for AS.
Mixed Connective Tissue Disease and Epitope Spreading
Authors: Escolà-Vergé Laura , Pinal-Fernandez Iago , Fernandez-Codina Andreu , Callejas-Moraga Eduardo L. , Espinosa Juan , Marin Ana , Labrador-Horrillo Moises , Selva-O’Callaghan Albert
Published: March 2017

Objectives

Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading.

Methods

All anti-U1-RNP-positive patients (2010–2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred.

Results

Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred.

Conclusion

Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.
Evolution of mutation rates in hypermutable populations ofEscherichia colipropagated at very small effective population size
Authors: Singh Tanya , Hyun Meredith , Sniegowski Paul
Published: March 2017

Mutation is the ultimate source of the genetic variation—including variation for mutation rate itself—that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower mutation rates in replicate hypermutableEscherichia colipopulations experimentally propagated at very small effective size—a circumstance under which selection is greatly reduced. Several populations went extinct during this experiment, and these populations tended to evolve elevated mutation rates. In contrast, populations that survived to the end of the experiment tended to evolve decreased mutation rates. We discuss the relevance of our results to current ideas about the evolution, maintenance and consequences of high mutation rates.
Dipteran larvae and microbes facilitate nutrient sequestration in theNepenthes gracilispitcher plant host
Authors: Lam Weng Ngai , Chong Kwek Yan , Anand Ganesh S. , Tan Hugh Tiang Wah
Published: March 2017

The fluid-containing traps ofNepenthescarnivorous pitcher plants (Nepenthaceae) are often inhabited by organisms known as inquilines. Dipteran larvae are key components of such communities and are thought to facilitate pitcher nitrogen sequestration by converting prey protein into inorganic nitrogen, although this has never been demonstrated inNepenthes. Pitcher fluids are also inhabited by microbes, although the relationship(s) between these and the plant is still unclear. In this study, we examined the hypothesis of digestive mutualism betweenN. gracilispitchers and both dipteran larvae and fluid microbes. Using dipteran larvae, prey and fluid volumes mimickingin situpitcher conditions, we conductedin vitroexperiments and measured changes in available fluid nitrogen in response to dipteran larvae and microbe presence. We showed that the presence of dipteran larvae resulted in significantly higher and faster releases of ammonium and soluble protein into fluids in artificial pitchers, and that the presence of fluid microbes did likewise for ammonium. We showed also that niche segregation occurs between phorid and culicid larvae, with the former fragmenting prey carcasses and the latter suppressing fluid microbe levels. These results clarify the relationships between several key pitcher-dwelling organisms, and show that pitcher communities facilitate nutrient sequestration in their host.
Global patterns of synchronization in human communications
Authors: Morales Alfredo J. , Vavilala Vaibhav , Benito Rosa M. , Bar-Yam Yaneer
Published: March 2017

Social media are transforming global communication and coordination and provide unprecedented opportunities for studying socio-technical domains. Here we study global dynamical patterns of communication on Twitter across many scales. Underlying the observed patterns is both the diurnal rotation of the Earth, day and night, and the synchrony required for contingency of actions between individuals. We find that urban areas show a cyclic contraction and expansion that resembles heartbeats linked to social rather than natural cycles. Different urban areas have characteristic signatures of daily collective activities. We show that the differences detected are consistent with a new emergent global synchrony that couples behaviour in distant regions across the world. Although local synchrony is the major force that shapes the collective behaviour in cities, a larger-scale synchronization is beginning to occur.
High quality frozen extracts ofXenopus laeviseggs reveal size-dependent control of metaphase spindle micromechanics
Authors: Takagi Jun , Shimamoto Yuta
Published: March 2017

Cell-free extracts from unfertilizedXenopus laeviseggs offer the opportunity for a variety of biochemical assays for analyzing essential cell cycle events, such as metaphase spindle assembly. However, extracts’ utility is often hampered by their short storage-stability duration and high quality variation. Here, we report a simple two-step method for preparing frozen egg extracts that retain spindle assembly activity levels that are close to those of freshly prepared extracts. Extract degradation associated with the freeze-thaw process can be substantially reduced by using centrifugal filter-based dehydration and slow sample cooling. Large amounts of frozen extract stocks from single batch preparations allowed us to collect a large number of data in micromanipulation experiments that are intrinsically low-throughput and, hence, clarify correlations between metaphase spindle size and stiffness. We anticipate that our method provides an assay platform with minimized biological heterogeneity and makes egg extracts more accessible to researchers as distributable material.

The authors describe a method for preparing frozen extracts ofXenopus laeviseggs that retain spindle assembly activity levels that are close to those of freshly prepared extracts. This allowed for clarifying the correlation between spindle size and stiffness.
Pan-cancer scale landscape of simple somatic mutations
Authors: Zhou Nan , Gallego Blanca , Bao Jinku , Tsafnat Guy
Published: March 2017

Genome is the carrier of somatic mutations during the development of cancer. The catalogue of simple somatic mutations (SSM) is a subgroup of somatic mutations. It includes single base substitutions, small deletions and insertions of <= 200 bp, and multiple base substitutions of <= 200 bp. The comprehensive landscape of SSM has not been studied. After analysed 46,692,922 SSM of 10,878 samples, we proposed a pan-cancer scale landscape of SSM for 60 cancer projects in ICGC. In addition, the whole genome sequencing (WGS) and whole exome sequencing (WXS) techniques were compared according to the landscape of SSM. The result indicates numbers of SSM vary dramatically in different cancers. WGS can detect 10 times more single base substitutions and insertions than WXS. In terms of WXS, it called 10 times more deletions than insertions. Multiple base substitutions have not been well studied so they were just observed in a few cancer projects. Cancers generally show high prevalence of C > T substitutions at NpCpG trinucleotide contexts. Skin cancer showed distinct mutational spectra. Breast cancer, bladder cancer, and cervical cancer were found to have similar mutational spectra. Acute myeloid leukemia and lung cancer from South Korea, and colorectal cancer from China show high density of single base substitutions per mega base in chromosome Y. To sum up, our study and findings will be thought provoking in studying SSM in cancer.
Allopatric divergence, local adaptation, and multiple Quaternary refugia in a long-lived tree (Quercus spinosa) from subtropical China
Authors: Feng Li , Zhang Yan-Ping , Chen Xiao-Dan , Yang Jia , Zhou Tao , Bai Guo-Qing , Yang Jiao , Li Zhong-Hu , Peng Ching-I , Zhao Gui-Fang
Published: March 2017

The complex geography and climatic changes occurring in subtropical China during the Tertiary and Quaternary might have provided substantial opportunities for allopatric speciation. To gain further insight into these processes, we reconstruct the evolutionary history ofQuercus spinosa,a common evergreen tree species mainly distributed in this area.

Forty-six populations were genotyped using four chloroplast DNA regions and 12 nuclear microsatellite loci to assess genetic structure and diversity, which was supplemented by divergence time and diversification rate analyses, environmental factor analysis, and ecological niche modeling of the species distributions in the past and at present.

The genetic data consistently identified two lineages: the western Eastern Himalaya-Hengduan Mountains lineage and the eastern Central-Eastern China lineage, mostly maintained by populations’ environmental adaptation. These lineages diverged through climate/orogeny-induced vicariance during the Neogene and remained separated thereafter. Genetic data strongly supported the multiple refugia (per se, interglacial refugia) or refugia within refugia hypotheses to explainQ. spinosaphylogeography in subtropical China.

Q. spinosapopulation structure highlighted the importance of complex geography and climatic changes occurring in subtropical China during the Neogene in providing substantial opportunities for allopatric divergence.