bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster formation in the W 40 and Serpens South complex triggered by the expanding H ii region
Authors: Shimoikura Tomomi , Dobashi Kazuhito , Nakamura Fumitaka , Shimajiri Yoshito , Sugitani Koji
Published: October 2018

We present the results of mapping observations covering a large area of 1 square degree around W 40 and Serpens South carried out in the 12CO (J = 1–0), 13CO (J = 1–0), C18O (J = 1–0), CCS (JN = 87–76), and N2H+ (J = 1–0) emission lines with the 45 m Nobeyama Radio Telescope. W 40 is a blistered H ii region, and Serpens South is an infrared dark cloud accompanied by a young cluster. The relation between these two regions, which are separated by ∼20′ on the sky, has not been recognizable so far. We found the C18O emission is distributed smoothly throughout the W 40 and Serpens South regions, and that the two regions seem to be physically connected. We divided the C18O emission into four groups in terms of the spatial distributions around the H ii region which we call 5, 6, 7, and 8 km s−1 components according to their typical LSR velocity, and propose a three-dimensional model of the W 40 and Serpens South complex. We found two elliptical structures in the position–velocity diagrams, which can be explained as part of two expanding shells. One of the shells is small inner shell just around the H ii region, and the other is a large outer shell corresponding to the boundary of the H ii region. Dense gas associated with the young cluster of Serpens South is likely to be located at the surface of the outer shell, indicating that the natal clump of the young cluster is interacting with the outer shell being compressed by the expansion of the shell. We suggest that the expansion of the shell induced the formation of the young cluster.
How Mass Immigration Affects Countries with Weak Economic Institutions: A Natural Experiment in Jordan
Authors: Nowrasteh Alex , Forrester Andrew C , Blondin Cole
Published: October 2018

To what extent does immigration affect the economic institutions in destination countries? While there is much evidence that economic institutions in developed nations are either unaffected or improved after immigration, there is little evidence of how immigration affects the economic institutions of developing countries that typically have weaker institutions. Using the Synthetic Control Method, this study estimates a significant and long-lasting positive effect on Jordanian economic institutions from the surge of refugees from the First Gulf War. The surge of refugees to Jordan in 1990–1991 was massive, equal to 10 percent of Jordan’s population in 1990. Importantly, these refugees were able to have a large and direct impact on Jordanian economic institutions because they could work, live, and vote immediately upon entry due to a quirk in Jordanian law. The refugee surge was the main mechanism by which Jordan’s economic institutions improved in the decades that followed.
Noise Exposure May Diminish the Musician Advantage for Perceiving Speech in Noise
Authors: Skoe Erika , Camera Sarah , Tufts Jennifer
Published: October 2018

Objective:

Although numerous studies have shown that musicians have better speech perception in noise (SPIN) compared to nonmusicians, other studies have not replicated the “musician advantage for SPIN.” One factor that has not been adequately addressed in previous studies is how musicians’ SPIN is affected by routine exposure to high levels of sound. We hypothesized that such exposure diminishes the musician advantage for SPIN.

Design:

Environmental sound levels were measured continuously for 1 week via body-worn noise dosimeters in 56 college students with diverse musical backgrounds and clinically normal pure-tone audiometric averages. SPIN was measured using the Quick Speech in Noise Test (QuickSIN). Multiple linear regression modeling was used to examine how music practice (years of playing a musical instrument) and routine noise exposure predict QuickSIN scores.

Results:

Noise exposure and music practice were both significant predictors of QuickSIN, but they had opposing influences, with more years of music practice predicting better QuickSIN scores and greater routine noise exposure predicting worse QuickSIN scores. Moreover, mediation analysis suggests that noise exposure suppresses the relationship between music practice and QuickSIN scores.

Conclusions:

Our findings suggest a beneficial relationship between music practice and SPIN that is suppressed by noise exposure.
Social Risk and Mortality
Authors: Checa Caterina , Abellana Rosa , Verdú-Rotellar Jose-Maria , Berenguera Anna , Domingo Mar , Calero Esther , Muñoz Pérez Miguel-Angel
Published: October 2018

Background

Heart failure (HF) is a chronic condition that usually leads to death a few years after diagnosis. Although several clinical factors have been found to be related to increased mortality, less is known about the impact of social context, especially at the end stage of the disease. Knowing about social context is important to properly classify risk and provide holistic management for patients with advanced HF.

Objective

The aim of this study was to determine the impact of social context on mortality in patients with advanced HF.

Methods

A retrospective cohort study was conducted using data from clinical records on community-dwelling patients with HF and with New York Heart Association IV functional class living in Catalonia in northeastern Spain. Clinical data, patient dependency for basic activities of daily living, and social assessments were collected between 2010 and 2013. The primary outcome was all-cause mortality.

Results

Data from 1148 New York Heart Association class IV patients were analyzed. Mean (SD) age was 82 (9.0) years, and 61.7% were women. The mean (SD) follow-up was 18.2 (11.9) months. Mortality occurred in 592 patients. Social risk was identified in 63.6% of the patients, and 9.3% acknowledged having social problems. In the adjusted multivariate model, being male (hazard ratio (HR), 1.82; 95% confidence interval [CI], 1.16–2.83), having high dependency on others for basic activities of daily living (HR, 2.16; 95% CI, 1.21–3.85), and presenting with a social problem (HR, 2.46; 95% CI, 1.22–4.97) were related to an increased risk of mortality.

Conclusions

An unfavorable social profile is an independent risk factor for mortality in patients with advanced HF.
Association Between Medication Adherence and Admission Blood Pressure Among Patients With Ischemic Stroke
Authors: Chen Min-Jie , Wu Chan-Chan , Wan Li-Hong , Zou Guan-Yang , Neidlinger Susan Holli
Published: October 2018

Background:

Poor medication adherence is one of the most important factors underlying uncontrolled blood pressure, and ensuing hypertension is the leading risk factor for stroke. However, the influence of prestroke medication nonadherence on the admission blood pressure of patients with hypertension who have had an ischemic stroke remains unclear.

Objective:

The aims of this study were to explore the influence of medication nonadherence on the admission blood pressure of patients with hypertension who have had an ischemic stroke and to analyze the reasons for medication nonadherence preceding stroke.

Methods:

A sample population of 301 patients with hypertension who have had an ischemic stroke was recruited. A questionnaire was used to investigate sociodemographic data and reasons for nonadherence. The 4-item Medication Adherence Scale was used to investigate prestroke medication adherence. Blood pressure was measured upon patient admission. Logistic regression analysis was used to identify factors influencing adherence.

Results:

In this cohort, 80.73% of the patients exhibited uncontrolled blood pressure on admission, and 26.58% had undiagnosed hypertension. Of the patients aware of their diagnosis, 75.11% were nonadherent and 10.40% had never used antihypertensive medicines. Uncontrolled admission blood pressure was positively influenced by medication nonadherence. The main causes of nonadherence included forgetfulness (58.08%), lack of belief in the need for long-term antihypertensive treatment (27.27%), and no awareness of the importance of long-term medication (24.75%).

Conclusions:

Stroke education in China should focus on patients' poor understanding of the importance for sustained antihypertensive medication adherence to improve blood pressure control and prevent stroke.
Preoperative Assessment of Cervical Vestibular Evoked Myogenic Potentials (cVEMPs) Help in Predicting Hearing Preservation After Removal of Vestibular Schwannomas Through a Middle Fossa Craniotomy
Authors: Hochet Baptiste , Achard Sophie , Lorenz Mark Brandt , Baroncini Marc , Berama Amine , Gabanou Frederic , Devambez Marion , Lejeune Jean-Paul , Vincent Christophe , Bonne Nicolas-Xavier
Published: October 2018

Objective:

To determine whether cervical vestibular evoked myogenic potentials (cVEMPs) are predictive of hearing preservation in patients undergoing vestibular schwannoma removal through middle fossa craniotomy approach.

Study Design:

Retrospective case study.

Setting:

Tertiary referral center.

Patients:

Eighteen patients who underwent a middle fossa craniotomy for vestibular schwannoma (stage I or II of Koos classification) with attempted hearing preservation from January 2008 to February 2016 were retrospectively reviewed.

Intervention:

Pre-surgical cVEMPs test, videonystagmography (caloric test), and magnetic resonance imaging (MRI) as well as a pre- and post-surgical audiometry test.

Main Outcome Measures:

cVEMPs parameters including amplitude asymmetry ratio (AR), P13, and N23 latencies and peak-to-peak amplitude between P13 and N23 waves were calculated. Hearing data were classified according to the AAO-HNS hearing classes. The nerve of origin of the tumor was specified during surgery and the largest tumor diameter was measure on MRI axial plane on T2-CISS weighed images.

Results:

Preoperative amplitude asymmetry ratio was lower (n = 15, Mann–Whitney U test, p < 0.001) in the group with postoperative hearing preservation (n = 11) compared with the group with postoperative hearing preservation failure (n = 4). The positive predictive value of an AR less than 24% to assess postoperative hearing preservation is 91.6%. Tumor size and localization were not correlated with cVEMPs, nor with caloric testing in this group of small-sized intracanalicular vestibular schwannomas.

Conclusions:

Our data suggest that cVEMPs may help predict hearing preservation outcome in vestibular schwannoma surgery via the middle fossa craniotomy approach.
Collaborative Online International Learning to Prepare Students for Multicultural Work Environments
Authors: de Castro A.B. , Dyba Natalia , Cortez Elizabeth D. , Pe Benito Genecar G.
Published: October 2018

Background

Collaborative Online International Learning (COIL) is a pedagogical approach using digital technology to provide experiential international learning without travel abroad. Through web-based, cross-country intellectual exchange, COIL helps prepare nursing students for increasingly diverse and multicultural health care work environments globally.

Problem

Opportunities to engage in multicultural learning experiences have traditionally relied on intensive study abroad trips, which can be prohibitive for students with limited fiscal resources or who are place-bound.

Approach

A COIL experience for undergraduate nursing students at universities in the United States and the Philippines was designed to fulfill academic degree program goals related to professional communication, collaborative practice, and respect for diversity.

Conclusion

After completing the COIL experience, students expressed valuing shared learning with peers in another country and reported gains in intercultural competence. Our efforts indicated that COIL-style endeavors provide meaningful, rewarding opportunities to engage with others across borders, while enhancing students’ skills to relate positively to an increasingly diverse world.
Can Applications Designed to Evaluate Visual Function Be Used in Different iPads?
Authors: de Fez Dolores , Luque María José , García-Domene Mari Carmen , Caballero Maria Teresa , Camps Vicente J.
Published: October 2018

SIGNIFICANCE

Apple devices could be suitable for vision tests, provided that the test has been correctly adapted to the device, after considering the spatial and colorimetric characterization of the screen.

PURPOSE

The majority of vision applications has not been developed by vision or colorimetry experts and suffers from conceptual and design errors that may lead average users to an erroneous assessment of their visual capabilities. The reliability of vision tests depends on the accurate generation of the necessary visual stimuli in a particular device. Our aim was to ascertain whether a given color test, designed for a colorimetrically characterized device, might be used in another similar device.

METHODS

We evaluated color reproduction errors in three iPad tablets of different models with Retina screens, using their individual color characterization models and the model derived for another device.

RESULTS

Our results showed, even with this small sample, the high degree of error caused when disregarding the fact that the colorimetric design valid for a given device may not be correct when displayed in another.

CONCLUSIONS

The distortion of the chromatic content may lead to subjects with vision defects to pass as normal or vice versa, compromising diagnosis reliability.
Bilateral Hyperplasia of the Coronoid Process in Pediatric Patients: What is the Gold Standard for Treatment?
Authors: Farronato Marco , Lucchina Alberta Greco , Mortellaro Carmen , Fama Andrea , Galbiati Guido , Farronato Giampietro , Maspero Cinzia
Published: October 2018

Objectives:

The aim of this systematic review of the literature is to describe treatment options for bilateral coronoid process hyperplasia in pediatric patients, to describe etiologic and diagnostic correlations with the treatment, and to evaluate long-term follow-up treatment outcomes.

Methods:

A systematic revision of the literature was performed in the Medline, PubMed, Cochrane library, and Embase database up to December 5, 2017. Predetermined Medical Subject Heading keywords were used: “bilateral” or “monolateral” and “coronoid” or “coronoid process” and “hyperplasia” and “temporomandibular joint” or “tmj” and “ankylosis” or “trismus” and “treatment.” Results were recorded following PRISMA guidelines.

Results:

The systematic research produced 1459 results excluding duplicates. Two additional studies from “Grey literature” were also considered. After application of inclusion and exclusion criteria, 38 articles were selected for a qualitative synthesis. Data regarding sex and age of presentation were collected and summarized in a study flow diagram.

Conclusion:

It is possible to conclude that early diagnosis is fundamental to restore stomatognathic multifunction. There is lack of longitudinal studies presenting long-term follow-up to determine treatment stability. Coronoidectomy might be considered gold standard treatment for this pathologic condition.
Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor
Authors: Brooker Jack E. , Camison Liliana B. , Bykowski Michael R. , Hurley Ethan T. , Yerneni Saigopalakrishna S. , Campbell Phil G. , Weiss Lee E. , Mooney Mark P. , Cray James , Gilbert James R. , Cooper Gregory M. , Losee Joseph E.
Published: October 2018

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.
Bucket-Handle Bipedicled Scalp Flaps for Coverage of Cranial Constructs in Cranioplasty
Authors: Devulapalli Chris , Mercaitis Orion Paul , Orbe Maria , Salgado Christopher J.
Published: October 2018

Composite frontal scalp defects involving the frontal bone and full thickness scalp can pose a reconstructive challenge. Often, they necessitate the use of microsurgical free tissue transfer, which can be physiologically demanding in high-risk patients with multiple comorbidities, with exposure to prolonged general anesthesia time and increased surgical morbidity. The experience of a single surgeon was reviewed with reconstruction of composite frontal scalp wounds in 4 patients with structural framework and a bipedicled scalp advancement (ie, “bucket handle”) flap, thus obviating the need for free tissue transfer. All 4 patients demonstrated complete wound healing by final follow-up, without need for further reoperations or ulcer recurrence. In face of composite frontal scalp defects in less than ideal candidates for lengthy microsurgical flap procedures, the bucket-handle flap can provide a simple and reliable reconstructive option.
Unilateral Cleft Lip Repair: Assessment of Outcome of Olokun-Olaitan Vermillion Flap Approach
Authors: Aluko-Olokun Bayo , Olaitan Ademola Abayomi , Olubi Olawale , Adediran Olanrewaju Moses
Published: October 2018

This study aimed to assess the outcome of our novel free-hand approach. Numerous cleft lip repair techniques exist, all of which involve incisions on skin and excision of tissue. Unilateral cleft lip is the result of failure of migration of orofacial tissues in-utero. Cleft lip repair should ideally involve an approach that simulates nature by avoiding skin incision and tissue excision, as these are not known to occur in the normal natural sequence of events.

Without incising skin or excising any tissue, vermillion flaps were raised exposing the muscular layer and edges of skin and mucosa. Similar tissue types were advanced and sutured across the cleft, replicating what should have occurred normally.

All 28 patients (100%) treated using our technique had competent lips. Acceptable symmetry of the vermillion was achieved in 24 (85.7%) of the patients. Lip symmetry was judged to be acceptable in 22 (78.6%). Symmetry of the nose was acceptable in 18 (64.3%) of patients.

The Olokun-Olaitan vermillion flap approach proved effective in the repair of unilateral cleft lip, as it compared very favorably with results obtained using Millard's technique.
Tongue Lip Adhesion in the Treatment of Robin Sequence: Respiratory, Feeding, and Surgical Outcomes
Authors: Mermans Joline F. , Lissenberg-Witte Birgit I. , Van Gogh Christine D.L. , Broers Chantal J.M. , Van Hagen Johanna M. , Strijers Rob L.M. , Don Griot Johan P.W.
Published: October 2018

Objective:

Objective evaluation of the efficacy of tongue lip adhesion (TLA) in the management of Robin sequence (RS).

Study Design:

Retrospective cohort study.

Setting:

Tertiary referral hospital.

Patients, Participants:

The craniofacial database of Amsterdam UMC, Vrije Universiteit Amsterdam was searched to identify infants with RS who underwent tong lip adhesion (TLA). Forty-one RS infants who underwent TLA from 1993 to 2016 were identified.

Interventions:

TLA.

Main Outcome Measure:

The outcome measures were pre- and postoperative polysomnography results, nutritional status, weight gain, age at operation, hospital stay length, extubation time after TLA, and complications.

Results:

Forty-one RS patients were included who had TLA at an average age of 26.6 days. In 16 cases a pre- and postoperative polysomnography was performed. In 13 of these cases (81.3%) improvement was observed, in 2 (12.5%) the results were inconclusive, and in 1 (6.3%) no improvement was seen. Patients were extubated after a mean of 2.2 days.

The mean hospital stay was 40.2 days. Reintervention was needed in 7 patients because of a wound dehiscence. The mean age of TLA release was 9.7 months. At discharge, 9 (22%) children still needed total nutritional support for persistent feeding difficulties. The average growth from birth to adhesion release was 4.6 kg.

Conclusion:

This cohort demonstrates that TLA is a successful procedure in children with RS in terms of respiratory, feeding, and growth outcome. Only minor complications were seen in our cohort.
Assessment of Coagulation Homeostasis in Blunt, Penetrating, and Thermal Trauma: Guidance for a Multicenter Systems Biology Approach
Authors: Shupp Jeffrey W. , Brummel-Ziedins Kathleen E. , Cohen Mitchell J. , Freeman Kalev , Hammamieh Rasha , Mudunuri Uma S. , Orfeo Thomas , Moffatt Lauren T. , Brownstein Bernard H. , Mann Kenneth G. , Jett Marti , Pusateri Anthony E.
Published: October 2018

Introduction:

Provisioning care for traumatically injured patients makes conducting research very proximal to injury difficult. These studies also inherently have regulatory barriers to overcome. Here we outline a protocol for acute-phase enrollment of traumatically injured patients into a prospective observational clinical trial with precise and comprehensive sample acquisition in support of a systems biology approach to a research study.

Methods:

Experts in trauma, burn, blood coagulation, computational biology, and integrative systems biology developed a prospective study that would capture the natural history of coagulation pathology after traumatic injury. Blood was sampled at admission and serial time points throughout hospitalization. Concurrently, demographic and outcomes data were recorded and on-site point-of-care testing was implemented. Protocols were harmonized across sites and sampling protocols validated through demonstration of feasibility and sample quality assurance testing. A novel data integration platform was developed to store, visualize, and enable large-scale analysis of empirical and clinical data. Regulatory considerations were also addressed in protocol development.

Results:

A comprehensive Manual of Operations (MOO) was developed and implemented at 3 clinical sites. After regulatory approval, the MOO was followed to collect 5,348 longitudinal samples from 1,547 patients. All samples were collected, processed, and stored per the MOO. Assay results and clinical data were entered into the novel data management platform for analyses.

Conclusion:

We used an iterative, interdisciplinary process to develop a systematic and robust protocol for comprehensive assessment of coagulation in traumatically injured patients. This MOO can be a template for future studies in the acute setting.
DC-SIGN Expression in Intestinal Epithelial Cells Regulates Sepsis-Associated Acute Intestinal Injury Via Activating ERK1/2-NF-κB/P65 Signaling
Authors: Chen Weiwei , Ma Li , Li Ranran , Huang Shunwei , Xie Rongli , Chen Ying , Zhao Bing , Fei Jian , Qu Hongping , Chen Hao , Mao Enqiang , Chen Er-zhen
Published: October 2018

Objective:

The aim of the study was to investigate the role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in intestinal epithelial cells (IECs) in regulating sepsis-induced acute intestinal injury and systemic inflammatory response.

Methods:

To induce sepsis condition, Male C57BL/6 mice were exposed to cecal ligation and puncture (CLP) in vivo, whereas a normal human IECs line (FHs74Int) was stimulated with lipopolysaccharide (LPS) in vitro. DC-SIGN siRNA pretreatment was used to knock down DC-SIGN expression both in vivo and in vitro. The expression of DC-SIGN was detected by western blot and immunohistochemistry. The expression of total and phosphorylation of ERK1/2 and NF-κB/p65 was examined by western blot. The levels of cytokines in serum and culture supernatant were measured by ELISA. The survival rate and organ injures of septic mice were also assessed.

Results:

In vivo, DC-SIGN expression in mouse IECs was time-dependently upregulated by CLP. CLP-induced phosphorylation of ERK1/2 and NF-κB/p65 was effectively inhibited by DC-SIGN siRNA pretreatment, leading to the decrease of systemic inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and IFN-γ), which alleviated multiple organ injuries and increased the survival rate of septic mice. In vitro, DC-SIGN expression in FHs74Int was significantly upregulated by LPS stimulation in a time- and dose-dependent manner. DC-SIGN knockdown abolished LPS-induced ERK1/2 and NF-κB/p65 phosphorylation, resulting in the decrease of cytokines release by FHs74Int.

Conclusions:

Sepsis-induced DC-SIGN expression in IECs plays a significant role in regulating acute intestinal injury and systemic inflammatory response. The inhibition of DC-SIGN exhibited protective effects on sepsis-associated organ injury and systemic inflammation.
Complex Feed-Forward and Feedback Mechanisms Underlie the Relationship Between Traumatic Brain Injury and the Gut–Microbiota–Brain Axis
Authors: Patterson T. Tyler , Nicholson Susannah , Wallace David , Hawryluk Gregory W.J. , Grandhi Ramesh
Published: October 2018

Traumatic brain injury (TBI) contributes to nearly 1 in 3 injury-related deaths in the United States and accounts for a substantial public health burden and cost. The current literature reports that physiologic responses in the gastrointestinal system after TBI include, but are not limited to, epithelial barrier dysfunction, microbiota changes, and immunologic transformations. Recent evidence suggests gut alterations after TBI modify the homeostasis of the bidirectional gut–microbiota–brain axis, resulting in altered immune responses in the periphery and the brain. This cascade possibly contributes to impaired central nervous system (CNS) healing. Although attention to the gut–brain–microbiota axis has been increasing in the literature, the precise mechanisms underlying the changes observed after TBI remain unclear. The purpose of this review are to describe our current understanding regarding alterations to the gut–microbiota–brain axis after TBI, highlight the pathophysiologic changes involved, and evaluate how these variations modify healing in the CNS or even contribute to secondary injury. We also discuss current investigations into potential medical therapies directed at the gut–microbiota–brain axis, which might offer improved outcomes after TBI.
A Comparison of Sacrospinous Hysteropexy Augmented With Polypropylene Mesh Versus Human Dermis at 12-Month Follow-up: An Ambidirectional Study
Authors: Seitz Miriam , Jirschele Kelly , Tran Alexis , Iyer Shilpa , Gafni-Kane Adam , Tomezsko Janet , Botros Sylvia M. , Sand Peter K.
Published: October 2018

Background

Suture-based hysteropexy is performed for pelvic organ prolapse with varying results. Graft augmentation may improve outcomes.

Objective

The aim of this study was to determine whether vaginal hysteropexy with mesh reduces recurrence at 1-year postoperative examination compared with hysteropexy with allograft.

Methods

Data were collected for patients who underwent vaginal hysteropexy with either mesh “Uphold” (referred to as “mesh”) or a cadaveric allograft “Axis or Repliform” (referred to as “dermal”). The primary outcome was anatomic success defined as no prolapse Pelvic Organ Prolapse Quantification System stage II or less at 12 months postoperative. The secondary outcomes were recurrence to the hymen and a composite score (any positive response to the 20-item Pelvic Floor Distress Inventory question 3 and cervix ≥ −1/2 total vaginal length at rest or as reference point 3 cm proximal to or above the hymenal ring anteriorly [Ba] ≥0) measured at 12 months.

Results

Two hundred seventy-four patients returned for their 1-year postoperative examination: 93.5% of the mesh group (231/247 subjects) and 95.5% of the dermal group (43/45 subjects). The mesh group had fewer recurrences to or beyond Pelvic Organ Prolapse Quantification System stage II (mesh 18% vs dermal 29%, P = 0.03), to the hymen (2.6% vs 9.3%, P = 0.007), or based on composite score (19 vs 33%, P = 0.007). Questionnaire data improved more in the mesh group (P < 0.0001). The exposure rate was 5.75% (13/247) in the mesh group. Reoperation rate was greater in the dermal group (mesh 4.3%vs dermal 7.3%, P = 02).

Conclusions

Hysteropexy augmented with mesh reduced the recurrence at 1 year compared with hysteropexy with allograft. Fewer patients in the mesh group felt a bulge at 1 year (4.5% vs 20.9%, P < 0.0001). These findings need to be weighed against the mesh exposure rate of 5.75%.
International Liver Transplantation Society Asian Consensus on the Management of Hepatitis C Virus Infection in Resource Limited Setting—From Noncirrhotic to Decompensated Disease and After Liver Transplantation
Authors: Charlton Michael R. , Gane Edward J. , Shukla Aakash , Dashtseren Bekhbold , Duger Davaadorj , Muljono David H. , Payawal Diana A. , Jargalsaikhan Ganbolor , Purnomo Hery D. , Cua Ian H. , Hasan Irsan , Sollano Jose , Win Khin Maung , Lesmana Laurentius A. , Salih Mohammad , Thi Thu Thuy Pham , Shankar Ravi , Saraswat Vivek A.
Published: October 2018

Background.

The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia.

Methods.

To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions.

Results.

An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article.

Conclusions.

With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.
Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation
Authors: Younossi Zobair M. , Marchesini Giulio , Pinto-Cortez Helena , Petta Salvatore
Published: October 2018

Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. Nonalcoholic fatty liver disease is closely associated with a constellation of metabolic comorbidities which include: obesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma and an indication for liver transplantation (LT) in the United States. Therefore, the following recommendations are made based on our current knowledge of NAFLD and its consequences: (1) the evaluation of the risk of liver disease progression can be affected by patient's ethnic origin and sex; (2) fibrosis in NAFLD is the most important predictor of mortality; (3) we recommend that individuals who present with features of metabolic syndrome in the presence of elevated liver enzymes should be screened for NAFLD and, more importantly, nonalcoholic steatohepatitis (NASH); (4) we recommend that NAFLD patients, especially those with multiple risk factors, should be screened for cardiovascular diseases and managed accordingly; (5) comorbidities in NAFLD/NASH patients who are considered for LT need to be assessed in the pretransplant and posttransplant settings because these factors can affect waitlist mortality, resource utilization, as well as posttransplant complications, morbidity, and perhaps, mortality; (6) any attempt to decrease the incidence of NAFLD should ideally address the development of obesity in childhood and early adulthood, favoring the adoption of healthy lifestyles through comprehensive health policy programs.
Clinical Significance of Microvascular Inflammation in the Absence of Anti-HLA DSA in Kidney Transplantation
Authors: Parajuli Sandesh , Redfield Robert R. , Garg Neetika , Aziz Fahad , Mohamed Maha , Astor Brad C. , Zhong Weixong , Djamali Arjang , Mandelbrot Didier A.
Published: October 2018

Background.

Limited information exists about outcomes of HLA donor-specific antibody (DSA) negative (DSA−) microvascular inflammation (MVI).

Methods.

We report our experience with 25 DSA− patients with MVI compared to 155 DSA+ patients who met Banff 2013 criteria for antibody-mediated rejection (AMR). We also compared outcomes to 228 DSA+ patients whose biopsies were negative for rejection and served as a negative control.

Results.

There were no significant differences in the baseline characteristics between the DSA− MVI and DSA+ AMR groups. At the time of diagnosis, both groups had similar graft function. The DSA− group had higher MVI scores but lower C4d scores. At last follow-up, renal function was similar between the groups. There were 12 (48%) graft failures in the DSA− group and 59 (38%) graft failures in the DSA+ group, which was not statistically different. Similar results were found after matching for the MVI scores, C4d, and treatment between 2 groups. We also found similar outcomes between DSA− and DSA+ patients when only including those who would have met Banff 2017 criteria for AMR. In univariate Cox regression analyses, estimated glomerular filtration rate at time of biopsy, glomerulitis, rituximab, diabetes, v score, allograft glomerulopathy, fibrous intimal thickening, tubular atrophy, and interstitial fibrosis scores were associated with graft failure. In multivariate analysis, only estimated glomerular filtration rate was protective. Both groups had significantly worse outcomes than the DSA+-negative controls without AMR.

Conclusions.

Our findings suggest that outcomes and response to treatment with HLA DSA− MVI patients are similarly poor to those with DSA+ MVI patients, supporting a critical role for MVI in the diagnosis of AMR.
Quadriceps Muscle Strength and Body Mass Index Are Associated With Estimates of Physical Activity Postheart Transplantation
Authors: Kelly Rebecca L. , Walsh James R. , Paratz Jennifer D. , Yerkovich Stephanie T. , McKenzie Scott C. , Morris Norman R.
Published: October 2018

Background.

Although exercise capacity improves postheart transplantation (HTx), it remains unclear if the level of physical activity (PA) shows similar improvement. The purpose of this study was to (1) describe PA levels and (2) identify factors which may be associated with levels of PA post-HTx.

Methods.

A prospective observational cross-sectional study was conducted at a single center HTx outpatient clinic. Medically stable adult recipients 6 months or longer post-HTx were recruited. Physical activity level (PAL) and average daily time spent at least moderately active (≥3 metabolic equivalents) were estimated using a multisensor device. Factors investigated were demographic (age, sex, body mass index [BMI], time post-HTx, and reason for HTx), corticosteroid use, exercise capacity (6-min walk distance), and quadriceps muscle strength corrected for body weight (QS%).

Results.

The mean post-HTx time of the 75 participants was 9.2 ± 7.0 years (0.5–26 y). Twenty-seven (36%) participants were classified as extremely inactive (PAL, <1.40), 26 (34.6%) sedentary (1.40 ≤ PAL ≤ 1.69), and 22 (29.3%) active (PAL, ≥1.70). Multivariable analysis showed greater QS% (β = 0.004 (0.002–0.006) P = 0.001) to be independently associated with increased PAL. For increased time, 3 or more metabolic equivalents both greater QS% (β = 0.0164 [0.003–0.029]; P = 0.014) and lower BMI (β = −0.0626 [−0.115 to −0.0099]; P = 0.021) were independently associated.

Conclusions.

The degree of observed sedentary behavior post-HTx is surprising, with the majority of participants not reaching levels of PA recommended for health benefits. QS% and BMI were the only factors found to be independently associated with estimates of PA. Further quality trials are required to demonstrate the long-term benefits of regular PA and investigate ways of increasing adherence to PA post-HTx.
NAFLD and Liver Transplantation in Children—Working Group Report From the ILTS Single Topic Conference on NAFLD
Authors: Cananzi Mara , Vajro Pietro , Rela Mohamed , Dhawan Anil
Published: October 2018

Background

Nonalcoholic fatty liver disease (NAFLD) has now become a common cause of chronic liver disease in children; however, unlike adults liver transplantation is rarely required as treatment. It is important that in children presenting with NAFLD, secondary causes of fatty liver particularly inherited metabolic defects should be excluded.

Methods

A pediatric working group comprised of 3 hepatologists and a liver transplant surgeon was tasked with a set of questions to address the current state of evidence and knowledge about NAFLD in children with particular focus on liver transplantation. A systematic review of the English literature regarding pediatric NAFLD (from birth to 18 years of age) published in the last 2 decades (2000-2018) was carried out. The evidence was evaluated by the subgroup members and further discussed with the wider workshop faculty leading to the recommendations for best practice.

Results

Given the paucity of literature on the subject good quality of evidence was only available on risk factors for NAFLD and medical treatment where the group could make recommendation with high/moderate strength. The evidence on natural history and indications for liver transplantation was poor hence group could not make any recommendations.

Conclusions

Based on the existing literature and subgroups, collective experience NAFLD unlike in adults is a very rare indication for liver transplantation in children. No definitive recommendations could be made about the natural history, indications, and outcome of liver transplantation for NAFLD in children.
Outcomes of Living-donor Liver Transplantation Using Grafts Heterozygous for α-1 Antitrypsin Gene Mutations
Authors: Doshi Sahil D. , Wood Linda , Abt Peter L. , Olthoff Kim M. , Shaked Abraham , Goldberg David S. , Bittermann Therese
Published: October 2018

Background.

Patients heterozygous for an abnormal α-1 antitrypsin (A1AT) mutation may have an increased risk of liver disease in the setting of a secondary contributing factor.

Methods.

This single-center retrospective cohort study compared donor and recipient outcomes of A1AT heterozygous versus normal phenotype adult living-donor liver transplants (LDLTs).

Results.

Between 2010 and 2016, 11 A1AT heterozygous donors and 10 recipients were compared to 57 normal donors and 41 recipients. There were no significant differences in sex, age, or race/ethnicity by A1AT phenotype. Heterozygous donors had significantly lower serum A1AT (median 100 mg/dL versus 131 mg/dL; P < 0.001). Median liver volume at 3 months post-LDLT was not different among donors or their recipients (1164 mm3 in heterozygous versus 1257 mm3 in normal [P = 0.449] for donors; 1563 mm3 versus 1606 mm3 [P = 0.387], respectively, for recipients). Recipient serum alkaline phosphatase at 1 month and 1 year post-LDLT was significantly higher in recipients of A1AT heterozygous grafts (160 U/L versus 99.5 U/L; P = 0.025 at 1 mo) but did not persist at 2 years. In addition, there was no association between A1AT level and liver volume at 3 months posttransplant in donors or recipients.

Conclusions.

Patients with a heterozygous A1AT mutation should be considered for living-liver donation.
Something has to give: scaling combinatorial computing by biological agents exploring physical networks encoding NP-complete problems
Authors: van Delft Falco C. M. J. M. , Ipolitti Giulia , Nicolau Dan V. , Sudalaiyadum Perumal Ayyappasamy , Kašpar Ondřej , Kheireddine Sara , Wachsmann-Hogiu Sebastian , Nicolau Dan V.
Published: October 2018

On-chip network-based computation, using biological agents, is a new hardware-embedded approach which attempts to find solutions to combinatorial problems, in principle, in a shorter time than the fast, but sequential electronic computers. This analytical review starts by describing the underlying mathematical principles, presents several types of combinatorial (including NP-complete) problems and shows current implementations of proof of principle developments. Taking the subset sum problem as example for in-depth analysis, the review presents various options of computing agents, and compares several possible operation ‘run modes’ of network-based computer systems. Given the brute force approach of network-based systems for solving a problem of input size C, 2Csolutions must be visited. As this exponentially increasing workload needs to be distributed in space, time, and per computing agent, this review identifies the scaling-related key technological challenges in terms of chip fabrication, readout reliability and energy efficiency. The estimated computing time of massively parallel or combinatorially operating biological agents is then compared to that of electronic computers. Among future developments which could considerably improve network-based computing, labelling agents ‘on the fly’ and the readout of their travel history at network exits could offer promising avenues for finding hardware-embedded solutions to combinatorial problems.
Deep Convolutional modeling of human face selective columns reveals their role in pictorial face representation
Authors: Grossman Shany , Gaziv Guy , Yeagle Erin M , Harel Michal , Mégevand Pierre , Groppe David M , Khuvis Simon , Herrero Jose L , Irani Michal , Mehta Ashesh D , Malach Rafael
Published: October 2018

Despite the massive accumulation of systems neuroscience findings, their functional meaning remains tentative, largely due to the absence of realistically performing models. The discovery that deep convolutional networks achieve human performance in realistic tasks offers fresh opportunities for such modeling. Here we show that the face-space topography of face-selective columns recorded intra-cranially in 32 patients significantly matches that of a DCNN having human-level face recognition capabilities. Three modeling aspects converge in pointing to a role of human face areas in pictorial rather than person identification: First, the match was confined to intermediate layers of the DCNN. Second, identity preserving image manipulations abolished the brain to DCNN correlation. Third, DCNN neurons matching face-column tuning displayed view-point selective receptive fields. Our results point to a “convergent evolution” of pattern similarities in biological and artificial face perception. They demonstrate DCNNs as a powerful modeling approach for deciphering the function of human cortical networks.
LuxRep: a technical replicate-aware method for bisulfite sequencing data analysis
Authors: Malonzo Maia , Halla-aho Viivi , Konki Mikko , Lund Riikka J. , Lähdesmäki Harri
Published: October 2018

DNA methylation is measured using bisulfite sequencing (BS-seq). Bisulfite conversion can have low efficiency and a DNA sample is then processed multiple times generating DNA libraries with different bisulfite conversion rates. Libraries with low conversion rates are excluded from analysis resulting in reduced coverage and increased costs. We present a method and software, LuxRep, that accounts for technical replicates from different bisulfite-converted DNA libraries. We show that including replicates with low bisulfite conversion rates generates more accurate estimates of methylation levels and differentially methylated sites.

Availability

An implementation of the method is available at https://github.com/tare/LuxGLM/tree/master/LuxRep

Contact

maia.malonzo@aalto.fi
Loss of Kat2A Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells
Authors: Domingues Ana Filipa , Kulkarni Rashmi , Giotopoulos George , Gupta Shikha , Tan Shengjiang , Foerner Elena , Adao Rita Romano , Zeka Keti , Huntly Brian J. , Prabakaran Sudhakaran , Pina Cristina
Published: October 2018

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.