bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversational structures of Alto Perené (Arawak) of Peru
Authors: Mihas Elena , Santos Pérez Gregorio
Published: January 2017

Drawing on extensive fieldwork in the research community, the book is a focused exploration of discourse patterns of Alto Perené Arawak, with emphasis on conversational structures. The book’s methodological scaffold is based on proposals and insights from multiple research fields, such as comparative conversation analysis, sociology, interactional linguistics, documentary linguistics, anthropological linguistics, and prosodic typology. The interactional patterns of a small Arawak language of Peru are shown to share the common infrastructure reported in the organization of conversation across other languages and cultures. Yet the analysis demonstrates a variety of unique nuances in the organization of interactional behavior of Alto Perené Arawak participants. The peculiarities observed are attributed to the language-specific semiotic resources and participants’ orientation to the local cultural norms. The book’s structured examination of conversational data of a small indigenous language of South America is anticipated to be of utility to linguistic research on understudied non-Western languages.
ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER
Authors: Costello Joseph L. , Castro Inês G. , Hacker Christian , Schrader Tina A. , Metz Jeremy , Zeuschner Dagmar , Azadi Afsoon S. , Godinho Luis F. , Costina Victor , Findeisen Peter , Manner Andreas , Islinger Markus , Schrader Michael
Published: January 2017

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering.
VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis
Authors: Hua Rong , Cheng Derrick , Coyaud Étienne , Freeman Spencer , Di Pietro Erminia , Wang Yuqing , Vissa Adriano , Yip Christopher M. , Fairn Gregory D. , Braverman Nancy , Brumell John H. , Trimble William S. , Raught Brian , Kim Peter K.
Published: January 2017

Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them. Depletion of either ACBD5 or VAP expression results in increased peroxisome mobility, suggesting that VAP–ACBD5 complex acts as the primary ER–peroxisome tether. We also demonstrate that tethering of peroxisomes to the ER is necessary for peroxisome growth, the synthesis of plasmalogen phospholipids, and the maintenance of cellular cholesterol levels. Collectively, our data highlight the importance of VAP–ACBD5–mediated contact between the ER and peroxisomes for organelle maintenance and lipid homeostasis.
All that is old does not wither: Conservation of outer kinetochore proteins across all eukaryotes?
Authors: Senaratne Aruni P. , Drinnenberg Ines A.
Published: January 2017

The kinetochore drives faithful chromosome segregation in all eukaryotes, yet the underlying machinery is diverse across species. D’Archivio and Wickstead (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608043) apply sensitive homology predictions to identify proteins in kinetoplastids with similarity to canonical outer kinetochore proteins, suggesting some degree of universality in the eukaryotic kinetochore.
Incredibly close—A newly identified peroxisome–ER contact site in humans
Authors: Schuldiner Maya , Zalckvar Einat
Published: January 2017

Peroxisomes are tiny organelles that control important and diverse metabolic processes via their interplay with other organelles, including the endoplasmic reticulum (ER). In this issue, Costello et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607055) and Hua et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608128) identify a peroxisome–ER contact site in human cells held together by a tethering complex of VAPA/B (vesicle-associated membrane protein–associated proteins A/B) and ACBD5 (acyl Co-A binding protein 5).
GWAR: robust analysis and meta-analysis of genome-wide association studies
Authors: Dimou Niki L , Tsirigos Konstantinos D , Elofsson Arne , Bagos Pantelis G
Published: January 2017

Motivation

In the context of genome-wide association studies (GWAS), there is a variety of statistical techniques in order to conduct the analysis, but, in most cases, the underlying genetic model is usually unknown. Under these circumstances, the classical Cochran-Armitage trend test (CATT) is suboptimal. Robust procedures that maximize the power and preserve the nominal type I error rate are preferable. Moreover, performing a meta-analysis using robust procedures is of great interest and has never been addressed in the past. The primary goal of this work is to implement several robust methods for analysis and meta-analysis in the statistical package Stata and subsequently to make the software available to the scientific community.

Results

The CATT under a recessive, additive and dominant model of inheritance as well as robust methods based on the Maximum Efficiency Robust Test statistic, the MAX statistic and the MIN2 were implemented in Stata. Concerning MAX and MIN2, we calculated their asymptotic null distributions relying on numerical integration resulting in a great gain in computational time without losing accuracy. All the aforementioned approaches were employed in a fixed or a random effects meta-analysis setting using summary data with weights equal to the reciprocal of the combined cases and controls. Overall, this is the first complete effort to implement procedures for analysis and meta-analysis in GWAS using Stata.

Availability and Implementation

A Stata program and a web-server are freely available for academic users at http://www.compgen.org/tools/GWAR

Supplementary information

Supplementary data are available at Bioinformatics online.
NetLand: quantitative modeling and visualization of Waddington’s epigenetic landscape using probabilistic potential
Authors: Guo Jing , Lin Feng , Zhang Xiaomeng , Tanavde Vivek , Zheng Jie
Published: January 2017

Waddington’s epigenetic landscape is a powerful metaphor for cellular dynamics driven by gene regulatory networks (GRNs). Its quantitative modeling and visualization, however, remains a challenge, especially when there are more than two genes in the network. A software tool for Waddington’s landscape has not been available in the literature. We present NetLand, an open-source software tool for modeling and simulating the kinetic dynamics of GRNs, and visualizing the corresponding Waddington’s epigenetic landscape in three dimensions without restriction on the number of genes in a GRN. With an interactive and graphical user interface, NetLand can facilitate the knowledge discovery and experimental design in the study of cell fate regulation (e.g. stem cell differentiation and reprogramming).

Availability and Implementation

NetLand can run under operating systems including Windows, Linux and OS X. The executive files and source code of NetLand as well as a user manual, example models etc. can be downloaded from http://netland-ntu.github.io/NetLand/.

Supplementary information

Supplementary data are available at Bioinformatics online.
chainCleaner improves genome alignment specificity and sensitivity
Authors: Suarez Hernando G , Langer Bjoern E , Ladde Pradnya , Hiller Michael
Published: January 2017

Motivation

Accurate alignments between entire genomes are crucial for comparative genomics. However, computing sensitive and accurate genome alignments is a challenging problem, complicated by genomic rearrangements.

Results

Here we present a fast approach, called chainCleaner, that improves the specificity in genome alignments by accurately detecting and removing local alignments that obscure the evolutionary history of genomic rearrangements. Systematic tests on alignments between the human and other vertebrate genomes show that chainCleaner (i) improves the alignment of numerous orthologous genes, (ii) exposes alignments between exons of orthologous genes that were masked before by alignments to pseudogenes, and (iii) recovers hundreds of kilobases in local alignments that otherwise would fall below a minimum score threshold. Our approach has broad applicability to improve the sensitivity and specificity of genome alignments.

Availability and Implementation

http://bds.mpi-cbg.de/hillerlab/chainCleaner/ or https://github.com/ucscGenomeBrowser/kent

Supplementary information

Supplementary data are available at Bioinformatics online.
Multi-rate Poisson tree processes for single-locus species delimitation under maximum likelihood and Markov chain Monte Carlo
Authors: Kapli P , Lutteropp S , Zhang J , Kobert K , Pavlidis P , Stamatakis A , Flouri T
Published: January 2017

Motivation

In recent years, molecular species delimitation has become a routine approach for quantifying and classifying biodiversity. Barcoding methods are of particular importance in large-scale surveys as they promote fast species discovery and biodiversity estimates. Among those, distance-based methods are the most common choice as they scale well with large datasets; however, they are sensitive to similarity threshold parameters and they ignore evolutionary relationships. The recently introduced “Poisson Tree Processes” (PTP) method is a phylogeny-aware approach that does not rely on such thresholds. Yet, two weaknesses of PTP impact its accuracy and practicality when applied to large datasets; it does not account for divergent intraspecific variation and is slow for a large number of sequences.

Results

We introduce the multi-rate PTP (mPTP), an improved method that alleviates the theoretical and technical shortcomings of PTP. It incorporates different levels of intraspecific genetic diversity deriving from differences in either the evolutionary history or sampling of each species. Results on empirical data suggest that mPTP is superior to PTP and popular distance-based methods as it, consistently yields more accurate delimitations with respect to the taxonomy (i.e., identifies more taxonomic species, infers species numbers closer to the taxonomy). Moreover, mPTP does not require any similarity threshold as input. The novel dynamic programming algorithm attains a speedup of at least five orders of magnitude compared to PTP, allowing it to delimit species in large (meta-) barcoding data. In addition, Markov Chain Monte Carlo sampling provides a comprehensive evaluation of the inferred delimitation in just a few seconds for millions of steps, independently of tree size.

Availability and Implementation

mPTP is implemented in C and is available for download at http://github.com/Pas-Kapli/mptp under the GNU Affero 3 license. A web-service is available at http://mptp.h-its.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Generative adversarial networks recover features in astrophysical images of galaxies beyond the deconvolution limit
Authors: Schawinski Kevin , Zhang Ce , Zhang Hantian , Fowler Lucas , Santhanam Gokula Krishnan
Published: January 2017

Observations of astrophysical objects such as galaxies are limited by various sources of random and systematic noise from the sky background, the optical system of the telescope and the detector used to record the data. Conventional deconvolution techniques are limited in their ability to recover features in imaging data by the Shannon–Nyquist sampling theorem. Here, we train a generative adversarial network (GAN) on a sample of 4550 images of nearby galaxies at 0.01 < z < 0.02 from the Sloan Digital Sky Survey and conduct 10× cross-validation to evaluate the results. We present a method using a GAN trained on galaxy images that can recover features from artificially degraded images with worse seeing and higher noise than the original with a performance that far exceeds simple deconvolution. The ability to better recover detailed features such as galaxy morphology from low signal to noise and low angular resolution imaging data significantly increases our ability to study existing data sets of astrophysical objects as well as future observations with observatories such as the Large Synoptic Sky Telescope (LSST) and the Hubble and James Webb space telescopes.
Provoked Vestibulodynia
Authors: Dargie Emma , Gilron Ian , Pukall Caroline F.
Published: January 2017

Objectives:

Provoked vestibulodynia (PVD) is an idiopathic vulvar pain condition characterized by burning pain at the vaginal opening in response to contact or pressure. Previous research has established some of the psychosocial difficulties experienced by these patients, but direct comparisons with other pain conditions are needed. The purpose of this study was to compare women with PVD to those with postherpetic neuralgia and pain-free control participants.

Materials and Methods:

Participants were invited to complete an anonymous online survey consisting of sociodemographic questions and a range of validated measures.

Results:

Women with PVD and postherpetic neuralgia (PHN) did not differ in terms of pain catastrophizing or pain anxiety, but women with PHN reported greater pain disability than those with PVD. Participants in both pain groups reported significantly more symptoms of stress, depression, anxiety, and sleep disturbances than pain-free controls; women with PHN reported more symptoms of depression than those with PVD, with no other differences between pain groups. Groups did not differ on relationship adjustment, but participants with PVD reported poorer sexual functioning than the other groups.

Discussion:

These results indicate that women with PVD and PHN experience similar mental health difficulties, but women with PHN experience more severe impact on their day-to-day functioning and mood. These results support the classification of PVD as a chronic pain condition, as both the pain groups differed from pain-free control participants on a range of measures. Finally, the presence of mental health difficulties and poorer sexual functioning highlights the importance of conducting biopsychosocial pain assessments.
A novel functional correction method for habitual patellar dislocation using autologous hamstring tendon: a case report
Authors: Ikuta Yasunari , Adachi Nobuo , Deie Masataka , Ishikawa Masakazu , Nakamae Atsuo , Ochi Mitsuo
Published: January 2017

Habitual patellar dislocation is an uncommon condition. In this case, a patient demonstrated lateral patellar dislocation in the middle or terminal range of flexion. A functional correction of the patella was devised so that the fixation site of the autologous graft on the femur was able to stabilize the patella selectively during the middle or terminal range of flexion. It is not the anatomical medial patellofemoral ligament attachment of the femur that is essential, but that a relevant fixation point on the femur should be sought in each patient to obtain stabilization of the patella to reverse habitual patellar dislocation.
Menstrual and reproductive factors in the risk of thyroid cancer in Japanese women: the Japan Public Health Center-Based Prospective Study
Authors: Shin Sangah , Sawada Norie , Saito Eiko , Yamaji Taiki , Iwasaki Motoki , Shimazu Taichi , Sasazuki Shizuka , Inoue Manami , Tsugane Shoichiro
Published: January 2017

The aim of this study was to evaluate the associations between menstrual and reproductive factors and thyroid cancer risk among Japanese women. A total 54 776 women aged 40–69 years completed a self-administered questionnaire, which included menstrual and reproductive history. During 1990–2012, 187 newly diagnosed cases of thyroid cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for menstrual and reproductive factors and incidence of thyroid cancer were estimated using Cox proportional hazards regression. Postmenopausal women who had natural menopause were at reduced risk of thyroid cancer than premenopausal women in the age–area-adjusted model (HR: 0.62 per 1 year increase, 95% CI: 0.39–0.99), but this association was slightly attenuated and no longer statistically significant in the multivariable-adjusted model. On analysis by menopausal status, an inverse association between age at menarche and risk of thyroid cancer was observed for premenopausal women (HR: 0.83 per 1 year increase, 95% CI: 0.70–0.98,Ptrend=0.03), but not for postmenopausal women. The risk of thyroid cancer increased with surgical menopause compared with natural menopause (HR: 2.34, 95% CI: 1.43–3.84). Although increasing age at menopause and duration of fertility were associated with an increased risk of thyroid cancer, this association was not observed among postmenopausal women. This study confirmed that early age at menarche for premenopausal women and surgical menopause and late age at natural menopause for postmenopausal women were associated with the development of thyroid cancer. Our results support the hypothesis that exposure to estrogens increases the risk of thyroid cancer.
Trends in hepatocyte growth factor, insulin-like growth factor 1, thyroid-stimulating hormone, and leptin expression levels in uveal melanoma patient serum and tumor tissues: correlation to disease progression
Authors: Oba Junna , Esmaeli Bita , Ellerhorst Julie A. , Lyons Genevieve R. , Milton Denái R. , Wang Wei-Lien , Macedo Mariana P. , Lazar Alexander J. , Grimm Elizabeth A. , Chattopadhyay Chandrani
Published: January 2017

This exploratory study was carried out to determine the expression levels of hepatocyte growth factor (HGF), insulin-like growth factor 1, thyroid-stimulating hormone (TSH), and leptin in serum and tumor samples from patients with uveal melanoma and to investigate the potential association of these expression levels with disease progression and patient survival. Seventeen patients, including nine nonmetastatic and eight metastatic, were included in the study. Eighteen healthy individuals served as controls. The levels of these four proteins in serum and tissue samples were determined by enzyme-linked immunosorbent assays and immunohistochemical staining, respectively. Associations between protein levels and survival, disease progression, and other clinicopathological factors were analyzed statistically. Serum levels of HGF were significantly higher and TSH levels were lower in uveal melanoma patients than in healthy individuals, but the level of neither protein differed significantly between metastatic and nonmetastatic groups. Of the four proteins tested, only serum TSH was significantly associated with patient survival. No correlation was observed between the tissue and serum levels of each protein. The levels of HGF in serum may be markers of uveal melanoma development. The prognostic and predictive values of these potential markers need to be determined in a larger cohort.
A Holistic Approach to Antiaging as an Adjunct to Antiaging Procedures: A Review of the Literature
Authors: Saluja Sandeep S. , Fabi Sabrina G.
Published: January 2017

BACKGROUND

Aging is a multifactorial process and depends on both intrinsic and extrinsic factors. Procedural options for diminishing signs of intrinsic aging and cosmetic rejuvenation have expanded dramatically. However, less attention is paid to counseling patients on options for mitigating extrinsic factors related to aging.

OBJECTIVE

The objective of this study was to review changes that occur with intrinsic and extrinsic aging, and provide evidence-based holistic counseling recommendations that can be used synergistically with aesthetic procedures to maximize antiaging interventions.

MATERIALS AND METHODS

A PubMed search was conducted for articles on intrinsic and extrinsic aging as it relates to skin, fat, muscle, and bone. Key clinical trials and studies on the effect of diet, hormones, exercise, sleep, stress, dental hygiene, smoking, pollution, and oxidative stress on the aging process are reviewed, and treatment recommendations are summarized based on available evidence.

RESULTS

Conventional cosmetic procedures and cosmeceuticals work together with nutritious diet, exercise, dental hygiene, hormonal balance, stress reduction, smoking and pollution avoidance, and healthy sleep patterns for a better effect on antiaging.

CONCLUSION

A combination approach of multiple nonsurgical modalities along with healthy lifestyle recommendations to minimize intrinsic and extrinsic aging factors allows cosmetic practitioners to target multiple facets of aging concurrently and maximize the aesthetic interventions cosmetic dermatologists/practitioners provide.
General Guidelines for Quality Assurance of Immunohistochemistry in a Mohs Lab
Authors: Kinas Carrie G. , Carroll Bryan T.
Published: January 2017

BACKGROUND

The adoption of recently created protocols introduces Mohs laboratories to the principles of immunohistochemistry (IHC) performance validation and clinical laboratory regulations that are unique to these evolving technologies.

OBJECTIVE

To review Food and Drug Administration (FDA) IHC reagent classifications, IHC validation protocols, and quality assurance (QA) procedures and documentation needed in conjunction with IHC test guidelines.

METHODS

A focused review of IHC reagent classifications and guidelines in clinical testing laboratories was conducted using PubMed and FDA source documents.

RESULTS

The IHC regulation requirements are determined by the 3 FDA classifications of reagents: in vitro diagnostic reagents, analyte-specific reagents, and research use only reagents. To account for performance variability, IHC reagents benefit from routine validation and QA programs. We present our IHC adoption procedures for QA and documentation of IHC tests in a Mohs laboratory.

CONCLUSION

Incorporating a well-organized IHC validation and QA program into Mohs laboratories can increase regulatory compliance and reagent performance.
Association between anxiety and severe quality-of-life impairment in postmenopausal women: analysis of a multicenter Latin American cross-sectional study
Authors: Núñez-Pizarro Jorge L. , González-Luna Alejandro , Mezones-Holguín Edward , Blümel Juan E. , Barón Germán , Bencosme Ascanio , Benítez Zully , Bravo Luz M. , Calle Andrés , Flores Daniel , Espinoza María T. , Gómez Gustavo , Hernández-Bueno José A. , Martino Mabel , Lima Selva , Monterrosa Alvaro , Mostajo Desiree , Ojeda Eliana , Onatra William , Sánchez Hugo , Tserotas Konstantinos , Vallejo María S. , Witis Silvina , Zúñiga María C. , Chedraui Peter
Published: January 2017

Objective:

To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women.

Methods:

This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review.

Results:

Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score ≥17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6).

Conclusions:

In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important.
Factors Determining the Uptake of Influenza Vaccination Among Children With Chronic Conditions
Authors: Chau Janita Pak Chun , Lo Suzanne Hoi Shan , Choi Kai Chow , Chau Matthew Hoi Kin , Tong Danny Wah Kun , Kwong Tany Kam Yuk , Thompson David R.
Published: January 2017

Background:

Studies report that the influenza vaccination uptake rate among children with chronic conditions is alarmingly low. In Hong Kong, there has been no study examining parental decision making about influenza vaccination for children with chronic conditions, thereby limiting the knowledge base to inform the development of specific strategies to improve influenza vaccination rates. The aim of this study was to identify factors determining the uptake of influenza vaccination among children with chronic conditions.

Methods:

We conducted a cross-sectional survey of 623 parents with children having a chronic condition recruited from pediatric wards and specialty outpatient departments of 2 acute hospitals. A questionnaire developed by Daley et al based on the Health Belief Model was used to examine parents’ beliefs and attitudes toward influenza and vaccination.

Results:

The parents’ and their children’s mean age were 40.1 ± 8.1 and 8.0 ± 4.5 years, respectively. Among the children, the most prevalent chronic conditions were asthma, chronic respiratory disease and cardiomyopathy. One-third (33%) of the children had influenza vaccination in the past 12 months. More than one-third (39%) of parents intended to vaccinate their children against influenza in the coming influenza season. A multivariable logistic regression analysis revealed that all subscale scores except perceived severity and knowledge about influenza were independently significantly associated with uptake.

Conclusions:

The findings indicate that parents of children with chronic conditions lack awareness of the risks of influenza and have insufficient understanding about the benefits of vaccination. These findings could inform the development of interventions to promote vaccination uptake among children with chronic conditions.
Economic evaluation of an implementation strategy for the management of low back pain in general practice
Authors: Jensen Cathrine Elgaard , Riis Allan , Petersen Karin Dam , Jensen Martin Bach , Pedersen Kjeld Møller
Published: January 2017

In connection with the publication of a clinical practice guideline on the management of low back pain (LBP) in general practice in Denmark, a cluster randomised controlled trial was conducted. In this trial, a multifaceted guideline implementation strategy to improve general practitioners' treatment of patients with LBP was compared with a usual implementation strategy. The aim was to determine whether the multifaceted strategy was cost effective, as compared with the usual implementation strategy. The economic evaluation was conducted as a cost–utility analysis where cost collected from a societal perspective and quality-adjusted life years were used as outcome measures. The analysis was conducted as a within-trial analysis with a 12-month time horizon consistent with the follow-up period of the clinical trial. To adjust for a priori selected covariates, generalised linear models with a gamma family were used to estimate incremental costs and quality-adjusted life years. Furthermore, both deterministic and probabilistic sensitivity analyses were conducted. Results showed that costs associated with primary health care were higher, whereas secondary health care costs were lower for the intervention group when compared with the control group. When adjusting for covariates, the intervention was less costly, and there was no significant difference in effect between the 2 groups. Sensitivity analyses showed that results were sensitive to uncertainty. In conclusion, the multifaceted implementation strategy was cost saving when compared with the usual strategy for implementing LBP clinical practice guidelines in general practice. Furthermore, there was no significant difference in effect, and the estimate was sensitive to uncertainty.
Multimorbidity and the Risk of All-Cause 30-Day Readmission in the Setting of Multidisciplinary Management of Chronic Heart Failure
Authors: Wiley Joshua F. , Chan Yih-Kai , Ahamed Yasmin , Ball Jocasta , Carrington Melinda J. , Riegel Barbara , Stewart Simon
Published: January 2017

Background:

Multimorbidity has an adverse effect on health outcomes in hospitalized individuals with chronic heart failure (CHF), but the modulating effect of multidisciplinary management is unknown.

Objective:

The aim of this study was to test the hypothesis that increasing morbidity would independently predict an increasing risk of 30-day readmission despite multidisciplinary management of CHF.

Methods:

We studied patients hospitalized for any reason with heart failure receiving nurse-led, postdischarge multidisciplinary management. We profiled a matrix of expected comorbidities involving the most common coexisting conditions associated with CHF and examined the relationship between multimorbidity and 30-day all-cause readmission.

Results:

A total of 830 patients (mean age 73 ± 13 years and 65% men) were assessed. Multimorbidity was common, with an average of 6.6 ± 2.4 comorbid conditions with sex-based differences in prevalence of 4 of 10 conditions. Within 30 days of initial hospitalization, 216 of 830 (26%) patients were readmitted for any reason. Greater multimorbidity was associated with increasing readmission (4%–44% for those with 0–1 to 8–9 morbid conditions; adjusted odds ratio, 1.25; 95% confidence interval, 1.13–1.38) for each additional condition. Three distinct classes of patient emerged: class 1—diabetes, metabolic, and mood disorders; class 2—renal impairment; and class 3—low with relatively fewer comorbid conditions. Classes 1 and 2 had higher 30-day readmission than class 3 did (adjusted P < .01 for both comparisons).

Conclusions:

These data affirm that multimorbidity is common in adult CHF inpatients and in potentially distinct patterns linked to outcome. Overall, greater multimorbidity is associated with a higher risk of 30-day all-cause readmission despite high-quality multidisciplinary management. More innovative approaches to target-specific clusters of multimorbidity are required to improve health outcomes in affected individuals.
Is Serial Electroneuronography Indicated Following Temporal Bone Trauma?
Authors: Remenschneider Aaron Kyle , Michalak Suzanne , Kozin Elliott D. , Barber Samuel , De Venecia Ronald K. , Hadlock Tessa A. , Jung David H.
Published: January 2017

Objective:

Contemporary guidelines advise facial nerve (FN) decompression within 2 weeks of temporal bone trauma if a single electroneuronography (ENoG) demonstrates more than 90% degeneration of the FN. We report a case series demonstrating the potential of serial ENoG to guide FN management more than 2 weeks following injury.

Patients:

Adults with traumatic temporal bone fractures and resultant ipsilateral FN paresis.

Intervention:

Serial ENoG followed by observation or decompression of the FN.

Main Outcome Measure:

House–Brackmann (HB) graded FN function.

Results:

Nine cases of blunt temporal bone trauma resulting in ispilateral FN paralysis were identified and reviewed. Two patients were women, and average age at the time of trauma was 30 years (range, 17–52). Immediate paralysis occurred in four cases, while five were delayed. A single ENoG was performed in seven patients and was predictive of final function in six, while one patient had an initially reassuring ENoG but did not obtain full recovery of FN function (HB 4). Two patients underwent serial ENoG on a weekly basis which, while initially reassuring, demonstrated declining FN function on subsequent testing. Decompression was performed in both patients with excellent recovery of FN function (HB1 and HB2).

Conclusions:

The majority of ENoGs performed within 2 weeks of temporal bone trauma provide sufficient prognostic data for treatment decisions; however, in selected cases, a single ENoG may not adequately predict long-term FN outcomes. For patients failing to improve with observation alone, serial ENoG may capture declining FN function, identifying patients that may benefit from late decompression.
Intermittent Aortic Valve Opening and Risk of Thrombosis in Ventricular Assist Device Patients
Authors: Mahr Claudius , Chivukula Venkat Keshav , McGah Patrick , Prisco Anthony R. , Beckman Jennifer A. , Mokadam Nahush A. , Aliseda Alberto
Published: January 2017

The current study evaluates quantitatively the impact that intermittent aortic valve (AV) opening has on the thrombogenicity in the aortic arch region for patients under left ventricular assist device (LVAD) therapy. The influence of flow through the AV, opening once every five cardiac cycles, on the flow patterns in the ascending aortic is measured in a patient-derived computed tomography image-based model, after LVAD implantation. The mechanical environment of flowing platelets is investigated, by statistical treatment of outliers in Lagrangian particle tracking, and thrombogenesis metrics (platelet residence times and activation state characterized by shear stress accumulation) are compared for the cases of closed AV versus intermittent AV opening. All hemodynamics metrics are improved by AV opening, even at a reduced frequency and flow rate. Residence times of platelets or microthrombi are reduced significantly by transvalvular flow, as are the shear stress history experienced and the shear stress magnitude and gradients on the aortic root endothelium. The findings of this device-neutral study support the multiple advantages of management that enables AV opening, providing a rationale for establishing this as a standard in long-term treatment and care for advanced heart failure patients.
The Homburg Lung: Efficacy and Safety of a Minimal-Invasive Pump-Driven Device for Veno-Venous Extracorporeal Carbon Dioxide Removal
Authors: Seiler Frederik , Trudzinski Franziska C. , Hennemann Kai , Niermeyer Tom , Schmoll Christian , Kamp Annegret , Bals Robert , Muellenbach Ralf M. , Haake Hendrik , Lepper Philipp M.
Published: January 2017

Extracorporeal carbon dioxide removal (ECCO2R) is increasingly considered a viable therapeutic approach in the management of hypercapnic lung failure to avoid intubation or to allow lung-protective ventilator settings. This study aimed to analyze efficacy and safety of a minimal-invasive ECCO2R device, the Homburg lung. The Homburg lung is a pump-driven system for veno-venous ECCO2R with ¼″ tubing and a 0.8 m2 surface oxygenator. Vascular access is usually established via a 19F/21 cm bilumen cannula in the right internal jugular vein. For this work, we screened patient registries from two German centers for patients who underwent ECCO2R with the Homburg lung because of hypercapnic lung failure since 2013. Patients who underwent extracorporeal membrane oxygenation before ECCO2R were excluded. Patients who underwent ECCO2R more than one time were only included once. In total, 24 patients (aged 53.86 ± 12.49 years; 62.5% male) were included in the retrospective data analysis. Ventilatory failure occurred because of chronic obstructive pulmonary disease (50%), cystic fibrosis (16.7%), acute respiratory distress syndrome (12.5%), and other origins (20.8%). The system generated a blood flow of 1.18 ± 0.23 liters per minute (lpm). Sweep gas flow was 3.87 ± 2.97 lpm. Within 4 hours, paCO2 could be reduced significantly from 82.05 ± 15.57 mm Hg to 59.68 ± 12.27 mm Hg, thereby, increasing pH from 7.23 ± 0.10 to 7.36 ± 0.09. Cannulation-associated complications were transient arrhythmia (1/24 patients) and air embolism (1/24). Fatal complications did not occur. In conclusion, the Homburg lung provides effective carbon dioxide removal in hypercapnic lung failure. The cannulation is a safe procedure, with complication rates comparable to those in central venous catheter implantation.
Therapeutic Interventions and Risk Factors of Bleeding During Extracorporeal Membrane Oxygenation
Authors: Lotz Christopher , Streiber Nils , Roewer Norbert , Lepper Philipp M. , Muellenbach Ralf M. , Kredel Markus
Published: January 2017

Bleeding is the most common complication during extracorporeal membrane oxygenation (ECMO). It is associated with an increased mortality and represents the most frequent cause of preliminary ECMO termination. We performed a retrospective analysis in a single ECMO referral center delineating the risk factors and therapeutic interventions of bleeding during adult ECMO in a total of 59 patients. The median length of ECMO support was 158 hours, with an all-cause mortality of 41%. Bleeding occurred on 40% of the days. On multivariate analysis, fungal pneumonia was the only significant factor associated with the occurrence of a bleeding event. The most common bleeding locations were the ECMO cannulation sites. Termination of ECMO support was the most successful therapeutic intervention, followed by the administration of tranexamic acid, replacement of the membrane oxygenator or the ECMO system, administration of factor VIIa, and repositioning of at least one ECMO cannula. Moreover, the transfusion of platelets was a successful mean, as well as the utilization of desmopressin to enhance platelet function. As such, further delineation of the coagulation disorders during ECMO support to provide a sophisticated pharmacotherapy may stop this serious adverse event.
Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions
Authors: Arashiki Nobuto , Takakuwa Yuichi
Published: January 2017

Purpose of review

The article summarizes new insights into the molecular mechanisms for the maintenance and regulation of the asymmetric distribution of phospholipids in human erythrocyte membranes. We focus on phosphatidylserine, which is primarily found in the inner leaflet of the membrane lipid bilayer under low Ca2+ conditions (<1 μmol/l) and is exposed to the outer leaflet under elevated Ca2+ concentrations (>1 μmol/l), when cells become senescent. Clarification of the molecular basis of phosphatidylserine flipping and scrambling is important for addressing long-standing questions regarding phosphatidylserine functions.

Recent findings

ATP11C, a P-IV ATPase, has been identified as a major flippase in analyses of patient erythrocytes with a 90% reduction in flippase activity. Phospholipid scramblase 1 (PLSCR1) has been defined as a Ca2+-activated scramblase that is completely suppressed by membrane cholesterol under low Ca2+ concentrations.

For survival, phosphatidylserine surface exposure is prevented by cholesterol-mediated suppression of PLSCR1 under low Ca2+ concentrations, irrespective of flipping by ATP11C. In senescent erythrocytes, PLSCR1 is activated by elevated Ca2+, resulting in phosphatidylserine exposure, allowing macrophage phagocytosis. These recent molecular findings establish the importance of the maintenance and regulation of phosphatidylserine distribution for both the survival and death of human erythrocytes.
RNA splicing during terminal erythropoiesis
Authors: Conboy John G.
Published: January 2017

Purpose of review

Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation.

Recent findings

RNA-seq analysis of highly purified erythroblast populations has revealed an extensive program of alternative splicing of both exons and introns. During normal erythropoiesis, stage-specific splicing transitions alter the structure and abundance of protein isoforms required for optimized red cell production. Mutation or deficiency of splicing regulators underlies hematopoietic disease in myelopdysplasia syndrome patients via disrupting the splicing program.

Erythroid progenitors execute an elaborate alternative splicing program that modulates gene expression posttranscriptionally, ultimately regulating the structure and function of the proteome in a differentiation stage-specific manner during terminal erythropoiesis. This program helps drive differentiation and ensure synthesis of the proper protein isoforms required to produce mechanically stable red cells. Mutation or deficiency of key splicing regulatory proteins disrupts the splicing program to cause disease.
Can Human Papillomavirus DNA Self-sampling be an Acceptable and Reliable Option for Cervical Cancer Screening in Female Sex Workers?
Authors: Wong Eliza L.Y. , Cheung Annie W.L. , Huang Fenwei , Chor Josette S.Y.
Published: January 2017

Background:

The causal relation between human papillomavirus (HPV) and cervical cancer has enabled HPV self-sampling to be envisaged as a possible screening method.

Objectives:

The aim of this study is to explore the acceptability and reliability of HPV DNA self-sampling as an alternative option for cervical screening among female sex workers.

Methods:

Sixty-eight participants carried out self-sampling for HPV testing, gave a clinician-obtained sample for HPV testing, and a Papanicolaou test. After the samplings, the participants were questioned on the acceptability of the tests.

Results:

Most participants (65.6%) preferred to adopt HPV DNA self-sampling in the future; in particular, those without previous experience of Papanicolaou tests marginally significantly preferred self-sampling (86.7%, P = .055). The overall crude agreement in HPV detection rates between clinician and HPV DNA self-sampling was 85.3% (58/68), with a κ of 0.69 (95% confidence interval, 0.51–0.87). The sensitivity and specificity of self-collected samples were 66.7% and 66.1%, respectively, and the positive and negative predicted values were 24.0% and 92.5%, respectively. The prevalence of HPV was slightly higher in self-collected samples (39.7%, 27/68) than in clinician-collected samples (36.8%, 25/68). The participants expressed positive attitudes toward self-sampling but were less confident in their skills of self-sampling compared with clinicians (70.6% versus 91.2%).

Conclusions:

The findings showed that self-sampling could be incorporated into current cervical cancer screening approaches.

Implications for Practice:

Self-sampling could potentially increase compliance to cervical cancer screening and thus reduce the morbidity and mortality from cervical cancer. Further research and education on self-sampling will be required for women of diverse backgrounds.
Faculty Clinical Site Visits in Nurse Practitioner Education
Authors: Pericak Arlene , Graziano Marjorie , McNelis Angela M.
Published: January 2017

Assessing student learning during a site visit in an advanced practice nursing course is important for academic success; however, a gap in the literature exists on students’ perspectives of faculty site visits in nurse practitioner education. This article presents the results of a study on students’ perceptions of the most useful aspects of the site visit, suggestions for improving site visits, and changes made in the practicum after the site visit.
The Age of Value
Authors: Glanzman Renée M.
Published: January 2017

The healthcare industry has historically rewarded providers on the basis of the volume of services rendered, rather than the value of those services. Through the commitment of the Department of Health and Human Services, new programs and legislation have been created to tie provider payment based on the achievement of the Triple Aim: improve the patient experience, reduce cost, and improve overall health. As a result, new programs and legislation have emerged, resulting in the need for cultural shifts, new skills, and new technology for health systems, providers, and patients. This article describes this transition and explores the various operational considerations that will need to be had in order to attain success in this new age of healthcare.
Care Bundles
Authors: Salmond Susan W. , Echevarria Mercedes , Allread Virgina
Published: January 2017

Care bundling is a strategy for reliably delivering quality, evidence-based care for patients undergoing treatments known to be accompanied by potential risks. This article reviews the purpose, types, and components of care bundles, as well as the process for development and implementation.
Case Report
Authors: Blumenthal Ryan , Saayman Gert
Published: January 2017

We present the case of a 41-year-old woman who was fatally injured during a witnessed lightning strike event and in whom autopsy revealed the unusual keraunopathological finding of overt pneumomediastinum. The possible pathophysiological mechanism(s) of causation of this phenomenon are discussed, with specific reference also to the “Macklin” effect and the role of blast overpressures associated with lightning strike. It is suggested that the latter may lead to sudden alveolar rupture, with subsequent rapid tracking of air along bronchovascular sheaths in a centripetal manner toward the hilum of the lung and thus into the mediastinum. A review of the blast literature suggests that this victim would have been exposed to a blast pressure wave of approximately 29-psi (200 kPa) to 72-psi (500 kPa) magnitude.