bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble Neuregulin1 is strongly up-regulated in the rat model of Charcot-Marie-Tooth 1A disease
Authors: Fornasari Benedetta Elena , Ronchi Giulia , Pascal Davide , Visigalli Davide , Capodivento Giovanna , Nobbio Lucilla , Perroteau Isabelle , Schenone Angelo , Geuna Stefano , Gambarotta Giovanna
Published: January 2018

Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve development through the activation of the transmembrane co-receptors ErbB2–ErbB3. Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and transiently up-regulated after acute peripheral nerve injury, thus suggesting that they play a crucial role also in the response to nerve damage. Here we show that in the rat experimental model of the peripheral demyelinating neuropathy Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms (soluble, type α and β, type a and b) is strongly up-regulated, as well as the expression of NRG1 co-receptors ErbB2–ErbB3, thus showing that CMT1A nerves have a gene expression pattern highly reminiscent of injured nerves. Because it has been shown that high concentrations of soluble NRG1 negatively affect myelination, we suggest that soluble NRG1 over-expression might play a negative role in the pathogenesis of CMT1A disease, and that a therapeutic approach, aimed to interfere with NRG1 activity, might be beneficial for CMT1A patients. Further studies will be necessary to test this hypothesis in animal models and to evaluate NRG1 expression in human patients.

Impact statement

Charcot-Marie-Tooth1A (CMT1A) is one of the most frequent inherited neurological diseases, characterized by chronic demyelination of peripheral nerves, for which effective therapies are not yet available. It has been recently proposed that the treatment with soluble Neuregulin1 (NRG1), a growth factor released by Schwann cells immediately after acute nerve injury, might be effective in CMT1A treatment. However, the expression of the different isoforms of endogenous NRG1 in CMT1A nerves has not been yet investigated. In this preliminary study, we demonstrate that different isoforms of soluble NRG1 are strongly over-expressed in CMT1A nerves, thus suggesting that a therapeutic approach based on NRG1 treatment should be carefully reconsidered. If soluble NRG1 is over-expressed also in human CMT1A nerves, a therapeutic approach aimed to inhibit (instead of stimulate) the signal transduction pathways driven by NRG1 might be fruitfully developed. Further studies will be necessary to test these hypotheses.
Focus on the target: Angiographic features of the fistulous point and prognosis of transvenous embolization of cavernous sinus dural arteriovenous fistula
Authors: Guo Hui , Yin QianKun , Liu Peng , Guan Ning , Huo Xiaochuan , Li Youxiang
Published: January 2018

Background and purpose

Transvenous embolization (TVE) is widely utilized as an effective and safe treatment option for cavernous sinus dural arteriovenous fistula (CS-dAVF); however, detecting the exact location of the fistula is challenging. The present study identified the angiographic features of the fistulous point and evaluated the match with the microcatheter tip and fistulous point.

Materials and methods

An analysis cohort of 45 consecutive patients with CS-dAVF treated by TVE was analyzed retrospectively. The patients were divided into two groups, 22 matches and 23 mismatches, according to whether the fistulous point and the microcatheter tip were in the same compartment of the cavernous sinus (CS). The angiographic findings, the location of the fistulas, the position of the microcatheter tips, the volume of embolic materials, complications, and outcomes were assessed.

Results

Several angiographic features defined the fistulous points, such as the early opacified area, jellyfish-like sign, changes in the density of the contrast medium, the juncture of different arterial supply, enlarged feeders, and hand-injection angiograms. The fistulas were primarily in the posterosuperior portion of the CS (80%) and medial side (73.3%) according to the internal carotid artery. Both groups achieved effective TVE; the matched group required less embolic material than the mismatched group ( p = 0.024). The patients with cranial nerve dysfunction (CND) required more embolic materials than others ( p = 0.032).

Conclusion

The fistulous point in most of the CS-dAVFs could be isolated by careful analysis of the angiography images. The matching of the microcatheter tip and fistulous point in the same compartment of CS can reduce the dosage of embolic materials, and a low volume of embolic materials might cause fewer CND complications.
A novel energy-coupling-based control method for double-pendulum overhead cranes with initial control force constraint
Authors: Zhang Menghua , Ma Xin , Rong Xuewen , Song Rui , Tian Xincheng , Li Yibin
Published: January 2018

A novel energy-coupling-based control method for under-actuated double-pendulum overhead cranes with initial control force constraint is proposed in this article. The significant feature of the designed controller is its superior control performance as well as its strong robustness with respect to parameter variations and external disturbances. By incorporating a smooth hyperbolic tangent function into the control law, the proposed controller guarantees soft start of the trolley. Moreover, to improve the transient performance of the crane system, coupling behavior among the trolley movement, the hook swing, and the payload swing is enhanced by introducing a generalized payload horizontal-displacement signal. Lyapunov techniques and LaSalle’s invariance theorem are utilized to prove the stability of the designed closed-loop system. Simulation results demonstrate that the new energy-coupling control method achieves superior control performance and strong robustness over different payload masses, cable lengths, desired positions, and external disturbances with reduced initial control force.
Temperature control and crack prevention during construction in steep slope dams and stilling basins in high-altitude areas
Authors: Li Bingqi , Wang Zhenhong , Jiang Yunhui , Zhu Zhenyang
Published: January 2018

Temperature cracks commonly occur during mass concrete construction. Research shows that changes in temperature and peripheral constraints mainly cause crack formation in concrete. Engineers who lack experience often build structures prone to concrete cracks. Dams built in the high-altitude areas of Tibet are examples of such structure. Climatic conditions, such as large temperature variation and strong solar radiation, disrupt temperature control and crack prevention in concrete. In this study, we explored the measures for temperature control and crack prevention that are suitable for concrete structures, especially those built in high-altitude areas with large temperature variation and strong constraint zones. The study was performed in a steep slope dam section and stilling basin in Tibet. The finite element method was used to guide the engineering construction in the area. These methods could be applied to the construction of similar projects in other high-altitude areas.
Navigation control of mobile robot using interval type-2 neural fuzzy controller optimized by dynamic group differential evolution
Authors: Lin Tzu-Chao , Chen Chao-Chun , Lin Cheng-Jian
Published: January 2018

This study developed and effectively implemented an efficient navigation control of a mobile robot in unknown environments. The proposed navigation control method consists of mode manager, wall-following mode, and towards-goal mode. The interval type-2 neural fuzzy controller optimized by the dynamic group differential evolution is exploited for reinforcement learning to develop an adaptive wall-following controller. The wall-following performance of the robot is evaluated by a proposed fitness function. The mode manager switches to the proper mode according to the relation between the mobile robot and the environment, and an escape mechanism is added to prevent the robot falling into the dead cycle. The experimental results of wall-following show that dynamic group differential evolution is superior to other methods. In addition, the navigation control results further show that the moving track of proposed model is better than other methods and it successfully completes the navigation control in unknown environments.
Diagnostic Value of Plasma Vascular Endothelial Growth Factor as a Tumor Marker in Patients with Non-Small Cell Lung Cancer
Authors: Tamura M. , Ohta Y. , Nakamura H. , Oda M. , Watanabe G.
Published: January 2018

We assessed the diagnostic value of circulating VEGF as a tumor marker in patients with lung cancer and compared its clinical utility with that of other markers such as carcinoembryonic antigen (CEA) and cytokeratin 19 (CYFRA). One hundred and sixty non-small cell lung cancer patients and 70 healthy volunteers were included in the study. Circulating VEGF was assessed by enzyme-linked immunosorbent assay (ELISA). The serum concentrations of both CEA and CYFRA were measured by means of immunoradiometric assays. The diagnostic value of plasma VEGF (VEGFp) was better than that of CYFRA and similar to that of CEA. When the diagnostic value of VEGFp and CEA for the diagnosis of adenocarcinoma was compared, the two markers proved to have nearly equal discriminatory power. In diagnosing squamous cell carcinoma, VEGFp showed less discrimination than CYFRA. When the diagnostic value of VEGFp was analyzed for stage I adenocarcinoma patients, VEGFp was slightly more discriminatory than CEA. The combination assay of VEGFp and CEA had a sensitivity of 75% and a specificity of 60% at a cutoff of 104.4 pg/mL for VEGFp and 5.2 ng/mL for CEA. The combination of VEGF and CEA was superior to CEA alone in the early diagnosis of adenocarcinoma of the lung.
Detection of Breast Cancer by Surface-enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry Tissue and Serum Protein Profiling
Authors: Gast Marie-Christine W. , van Dulken Eric J. , van Loenen Thea K.G. , Kingma-Vegter Florine , Westerga Johan , Flohil Claudie C. , Knol Jaco C. , Jimenez Connie R. , van Gils Carla H. , Wessels Lodewijk F.A. , Schellens Jan H.M. , Beijnen Jos H.
Published: January 2018

Aim

Novel diagnostic breast cancer markers have been extensively searched for in the proteome, using, among others, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Thus far, the majority of SELDI-TOF MS studies have investigated samples originating from biorepositories, which hampers biomarker discovery as they likely suffer from variable adherence to collection protocols.

Material and methods

We investigated breast cancer (n=75) and control (n=26) serum and tissue samples, collected prospectively by rigorous adherence to a strictly defined protocol. Sera were collected preoperatively and postoperatively, and serum and tissue samples were analyzed by SELDI-TOF MS using the IMAC30 Ni and Q10 pH 8 array.

Results

Three serum peaks were significantly associated with breast cancer, while in tissue, 27 discriminative peaks were detected. Several peak clusters gradually increased or decreased in intensity from healthy to benign to cancer, or with increasing cancer stage. The constructed classification trees had a tenfold cross-validated performance of 67% to 87%. Two tissue peaks were identified as N-terminal albumin fragments. These are likely to have been generated by (breast) cancer-specific proteolytic activity in the tumor microenvironment.

Conclusions

These albumin fragments can potentially provide insights into the pathophysiological mechanisms associated with, or underlying, breast cancer, and aid in improving breast cancer diagnosis.
Leg placement algorithm for foot impact force minimization
Authors: Luneckas Mindaugas , Luneckas Tomas , Udris Dainius
Published: January 2018

Walking is considered to be a rather complicated task for autonomous robots. Sustaining dynamic stability, adopting different gaits, and calculating correct foot placement are a necessity to overcome irregular terrain, various environments and completing a range of assignments. Besides that, certain assignments require that robots have to walk on fragile surfaces without damaging it. Furthermore, under some other circumstances, if walking is careless, robots could suffer damage caused by the impact of the terrain. Foot placement, leg motion speed must be controlled to avoid braking surface or even sensors on robot’s feet. In this article, a simple leg placement algorithm is proposed that controls hexapod robot’s leg speed. Thus, force dependence on leg motion speed and step height has been measured by using a piezoelectric sensor. Then, by using leg placement algorithm, we show that the reduction of the impact force between robot’s foot and surface is possible. Using this algorithm, robot feet’s impact force with the surface can be minimized to almost 0 N.
Handrail detection and pose estimation for a free-flying robot
Authors: Lee Dong-Hyun , Coltin Brian , Morse Theodore , Park In-Won , Flückiger Lorenzo , Smith Trey
Published: January 2018

We present a handrail detection and pose estimation algorithm for the free-flying Astrobee robots that will operate inside the International Space Station. The Astrobee will be equipped with a single time-of-flight depth sensor and a compliant perching arm to grab the International Space Station handrails. Autonomous perching enables a free-flying robot to minimize power consumption by holding its position without using propulsion. Astrobee is a small robot with many competing demands on its computing, power, and volume resources. Therefore, for perching, we were limited to using a single compact sensor and a lightweight detection algorithm. Moreover, the handrails on the International Space Station are surrounded by various instruments and cables, and the lighting conditions change significantly depending on the light sources, time, and robot location. The proposed algorithm uses a time-of-flight depth sensor for handrail perception under varying lighting conditions and utilizes the geometric characteristics of the handrails for robust detection and pose estimation. We demonstrate the robustness and accuracy of the algorithm in various environment scenarios.
Emerging schooling landscapes in England: How primary system leaders are responding to new school groupings
Authors: Simkins Tim , Coldron John , Crawford Megan , Maxwell Bronwen
Published: January 2018

In England the balance of responsibilities between national and local government for the governance of education is changing. Relationships between schools are shifting and new structures, groups and alliances are being created in response to national policy. The article is part of a project to understand how the new local education landscapes are emerging. Primary schools are relatively reluctant to embrace key aspects of national policy. We analysed interviews with primary system leaders in three contrasting local authorities to find out how they were responding, and why, and the nature of the groups they wanted to join, create or cooperate with. We identify concerns, interests and motivations that conflict with key aspects of national policy. In the process, we supplement earlier contributions as to how school groupings might usefully be categorised.
Creating and testing regulatory focus messages to enhance medication adherence
Authors: O’Connor Ashley , Ladebue Amy , Peterson Jamie , Davis Ryan , Jung Grant Susan , McCreight Marina , Lambert-Kerzner Anne
Published: January 2018

Objectives

Strategies were explored to improve patient adherence to cardioprotective medications by borrowing from a motivational framework used in psychology, regulatory focus theory. The current study is part of a larger randomized control trial and was aimed at understanding what written educational messages, based on patients’ regulatory focus tendency, resonated with each individual as a potential reminder to take medications. This study was also aimed at understanding why messages resonated with the patients.

Methods

Twenty veterans were tested for regulatory fitand presented with messages dependent on focus tendency. In-person semi-structured interviews were conducted to collect feedback of messages. An iterative analysis drawing primarily on matrix and reflexive team analyses was conducted.

Result

Six promotion and six prevention messages emerged, such as “team up with your provider to create a combination of medications to prevent illness” and “Live your best life – Take your medications”. Five themes related to types of health messages that spoke to patients’ regulatory fit were discovered: relatability; empowerment and control; philosophy on life; relationship with provider and medications; and vocabulary effect on the impact of messages.

Discussion

Motivational messages based on regulatory fit may be useful in improving patient medication adherence, leading to improved cardiovascular outcomes.
Identifying COPD patients at risk for worse symptoms, HRQoL, and self-efficacy: A cluster analysis
Authors: Lopes Aline C , Xavier Rafaella F , AC Pereira Ana Carolina , Stelmach Rafael , Fernandes Frederico LA , Harrison Samantha L , Carvalho Celso RF
Published: January 2018

Objectives

To identify clusters of chronic obstructive pulmonary disease (COPD) patients with distinct beliefs about their illness in terms of symptoms, health-related quality of life (HRQoL), self-efficacy, and daily life physical activity (DLPA).

Methods

This cross-sectional study included 150 COPD outpatients. The patients’ illness perceptions, clinical control, HRQoL, self-efficacy, and DLPA (accelerometry) were evaluated. A cluster analysis was conducted using data from the Illness Perceptions Questionnaire - Revised to establish groups of patients with distinct illness perceptions. Differences between clusters were tested using a T-test or a Mann–Whitney U test.

Results

The cluster analysis revealed two groups: distressed ( n = 95) and coping ( n = 55). Despite the fact that both clusters presented similar pulmonary function, between-cluster differences were observed in their self-efficacy, dyspnea, HRQoL, clinical control ( p < 0.001), and educational level ( p = 0.002). The levels of DLPA did not differ between the clusters.

Discussion

We observed that clinically stable COPD patients who displayed higher emotional representations and less coherence had heightened symptoms, poorer HRQoL, worse self-efficacy, and lower educational levels. These results emphasize the need to routinely evaluate illness perceptions in COPD patients to target and tailor the proper treatment to improve these important health outcomes.
The repeated name penalty effect in children’s natural reading: Evidence from eye tracking
Authors: Eilers Sarah , Tiffin-Richards Simon P , Schroeder Sascha
Published: January 2018

We report data from an eye tracking experiment on the repeated name penalty effect in 9-year-old children and young adults. The repeated name penalty effect is informative for the study of children’s reading because it allows conclusions about children’s ability to direct attention to discourse-level processing cues during reading. We presented children and adults simple three-sentence stories with a single referent, which was referred to by an anaphor—either a pronoun or a repeated name—downstream in the text. The anaphor was either near or far from the antecedent. We found a repeated name penalty effect in early processing for children as well as adults, suggesting that beginning readers are already susceptible to discourse-level expectations of anaphora during reading. Furthermore, children’s reading was more influenced by the distance of anaphor and antecedent than adults’, which we attribute to differences in reading fluency and the resulting cognitive load during reading.
Persistent modification of cognitive control through attention training
Authors: Aben Bart , Iseni Blerina , Van den Bussche Eva , Verguts Tom
Published: January 2018

An important aspect of cognitive control is to direct attention towards relevant information and away from distracting information. This attentional modulation is at the core of several influential frameworks, but its trainability and generalisability remain unclear. To address this issue, two groups of subjects were invited to the lab on three consecutive days. On Day 2, they performed an arrow priming task which trained them to adopt an attentional bias towards (prime-attended group) or away from (prime-diverted group) a potentially conflicting prime. Direct generalisation of the attention training was measured by assessing task performance on the same task without the attentional manipulation directly after training (Day 2) and the next day (Day 3), and comparing it to baseline (Day 1). Performance on this direct transfer task showed a difference in attentional modulation between groups directly after training that persisted the next day. No cross-task generalisation was found to two other tasks that were closely or more remotely related to the trained task. Together, these results are in accordance with cognitive control frameworks that limit attentional modulation to the specific features of the trained task.
The use of human dental pulp stem cells for in vivo bone tissue engineering: A systematic review
Authors: Leyendecker Junior Alessander , Gomes Pinheiro Carla Cristina , Lazzaretti Fernandes Tiago , Franco Bueno Daniela
Published: January 2018

Dental pulp represents a promising and easily accessible source of mesenchymal stem cells for clinical applications. Many studies have investigated the use of human dental pulp stem cells and stem cells isolated from the dental pulp of human exfoliated deciduous teeth for bone tissue engineering in vivo. However, the type of scaffold used to support the proliferation and differentiation of dental stem cells, the animal model, the type of bone defect created, and the methods for evaluation of results were extremely heterogeneous among these studies conducted. With this issue in mind, the main objective of this study is to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of human dental pulp stem cells and stem cells from human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The article search was conducted in PubMed/MEDLINE and Web of Science databases. Original research articles assessing potential of human dental pulp stem cells and SHED for in vivo bone tissue engineering, published from 1984 to November 2017, were selected and evaluated in this review according to the following eligibility criteria: published in English, assessing dental stem cells of human origin and evaluating in vivo bone tissue formation in animal models or in humans. From the initial 1576 potentially relevant articles identified, 128 were excluded due to the fact that they were duplicates and 1392 were considered ineligible as they did not meet the inclusion criteria. As a result, 56 articles remained and were fully analyzed in this systematic review. The results obtained in this systematic review open new avenues to perform bone tissue engineering for patients with bone defects and emphasize the importance of using human dental pulp stem cells and SHED to repair actual bone defects in an appropriate animal model.
Screening-detected desmoid tumor of the breast: findings at conventional imaging and digital breast tomosynthesis
Authors: Samardzic Tatjana , Lømo Jon , Skaane Per
Published: January 2018

Desmoid tumor of the breast is a rare benign entity that usually is mistaken for carcinoma clinically and radiologically. We report two cases of desmoid tumor of the breast detected by mammography screening using digital breast tomosynthesis (DBT). The larger tumor was detected at both full-field digital mammography (FFDM) and DBT. The smaller desmoid tumor, however, was identified only at tomosynthesis. Mammographic and ultrasonographic findings at diagnostic work-up were consistent with carcinoma of the breast. Preoperative needle biopsies could not conclusively diagnose the lesions. Both patients underwent excisional biopsy and histopathology revealed fibromatosis of the desmoid type.
Child, Caregiver, and Health Care Provider Perspectives and Experiences Regarding Disclosure of HIV Status to Perinatally Infected Children in Lima, Peru
Authors: Baker Amira Noori , Bayer Angela Marie , Kolevic Lenka , Najarro Lizzete , Viani Rolando Mario , Deville Jaime Gerardo
Published: January 2018

Background:

Despite recommendations for disclosure of HIV status to children living with HIV (CLHIV), fewer than half of CLHIV at the Instituto Nacional de Salud del Niño (INSN) in Lima, Peru, have had disclosure. How and when the disclosure process for CLHIV should take place in Peru has not been studied.

Methods:

We conducted a qualitative study at INSN to explore perceptions and experiences of 6 health care providers (HCPs), 14 disclosed and nondisclosed CLHIV (8-17 years), and their 14 caregivers regarding knowledge of illness, disclosure of HIV status, and appropriate disclosure approaches.

Results:

Disclosed children wanted to be told their diagnosis earlier. Nondisclosed children expressed frustration taking medications. Caregivers and HCPs discussed motivations to disclose, including educating, honesty, improving medication adherence, and preventing secondary transmission.

Conclusion:

Culturally appropriate guidelines and training for HCPs and caregivers are needed to support disclosure of children’s HIV status and ongoing support for CLHIV.
Chinese Ethnicity Is Associated With Concomitant Cartilage Injuries in Anterior Cruciate Ligament Tears
Authors: Chan Chloe Xiaoyun , Wong Keng Lin , Toh Shi Jie , Krishna Lingaraj
Published: January 2018

Background:

Chinese ethnicity is associated with the presence of knee osteoarthritis. This raises the possibility that it may similarly be associated with concomitant meniscus and cartilage injuries in patients with anterior cruciate ligament (ACL) tears. There are currently no published data on the effect of Chinese ethnicity in this regard.

Purpose:

The primary aim was to determine whether Chinese ethnicity is associated with concomitant intra-articular injuries in patients with ACL tears and to verify the correlation of age, sex, body mass index, mechanism of injury, cause of injury, and presence of bone contusions on magnetic resonance imaging with such injuries. A secondary purpose was to determine the optimal time frame for surgical reconstruction in patients with identified risk factors for concomitant injuries.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

The medical records of 696 patients from a multiethnic population who underwent ACL reconstruction from January 2013 to August 2016 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify patient factors that were associated with medial meniscus tears, lateral meniscus tears, and cartilage injuries. Further univariate analysis was conducted to determine the earliest time point for surgery, after which the rate of concomitant injuries was significantly higher.

Results:

Over half (69.1%, n = 481) of our study population sustained at least 1 other concomitant knee injury. Meniscus tears were most frequently associated with ACL tears (24.1% medial, 25.6% lateral, and 15.5% medial and lateral meniscus tears). Cartilage injuries were present in 18.4% of our cohort. Chinese ethnicity was associated with concomitant cartilage injuries. Increased age (≥30 years) was significantly associated with cartilage injuries and male sex with medial and lateral meniscus tears. Among patients with these factors, significantly fewer medial meniscus tears and cartilage injuries were noted when surgery was carried out within 12 months of the index trauma.

Conclusion:

This is one of the first studies to have identified an association between Chinese ethnicity and concomitant cartilage injuries in ACL tears. This study also found an association between increased age and an increased prevalence of cartilage injuries. Male sex was associated with both medial and lateral meniscus tears. Definitive surgery should be performed within 12 months of the index injury to minimize further intra-articular injuries.
Creating Naptime
Authors: Knauert Melissa P , Redeker Nancy S , Yaggi Henry K , Bennick Michael , Pisani Margaret A
Published: January 2018

Introduction:

Patients in the intensive care unit (ICU) have significantly disrupted sleep. Sleep disruption is believed to contribute to ICU delirium, and ICU delirium is associated with increased mortality. Experts recommend sleep promotion as a means of preventing or shortening the duration of delirium. ICU Sleep promotion protocols are highly complex and difficult to implement. Our objective is to describe the development, pilot implementation, and revision of a medical ICU sleep promotion protocol.

Methods:

Naptime is a clustered-care intervention that provides a rest period between 00:00 and 04:00. We used literature review, medical chart review, and stakeholder interviews to identify sources of overnight patient disturbance. With stakeholder input, we developed an initial protocol that we piloted on a small scale. Then, using protocol monitoring and stakeholder feedback, we revised Naptime and adapted it for unitwide implementation.

Results:

We identified sound, patient care, and patient anxiety as important sources of overnight disturbance. The pilot protocol altered the timing of routine care with a focus on medications and laboratory draws. During the pilot, there were frequent protocol violations for laboratory draws and for urgent care. Stakeholder feedback supported revision of the protocol with a focus on providing 60- to 120-minute rest periods interrupted by brief clusters of care between 00:00 and 04:00.

Discussion:

Four-hour blocks of rest may not be possible for all medical ICU patients, but interruptions can be minimized to a significant degree. Involvement of all stakeholders and frequent protocol reevaluation are needed for successful adoption of an overnight rest period.
Willingness to Pay for Teledermoscopy Services at a University Health Center
Authors: Raghu T S , Yiannias James , Sharma Nita , Markus Allan L
Published: January 2018

Background:

The study objective was to investigate the willingness to pay (WTP) for teledermoscopy services among students at a university health center. The hypothesis was that WTP for teledermoscopy among students would exceed the costs for traditional consultation.

Methods:

Between November 2013 and May 2014, students at a university health center were surveyed for their perceptions of teledermoscopy. One set of responses was collected from students visiting the health center for any reason (anonymous sample). An additional set of responses was collected from students visiting for dermatologic lesions (in-person sample). A contingent valuation method with a maximum likelihood estimation procedure was used to estimate the WTP distribution.

Results:

A total of 214 surveys were collected for the anonymous sample and 41 responses for the in-person sample. The mean (standard deviation [SD]) WTP for the anonymous sample was $55.27 ($39.11; 95% confidence interval [CI]: $49.99-$60.55). The mean (SD) WTP for the in-person sample was $52.37 ($26.56; 95% CI: $43.99-$60.75). Median WTP for the 2 samples was similar: $48.84 and $48.01.

Conclusions:

We conclude that students would be willing to pay for teledermoscopy services that would provide the potential for significant system cost savings. This may be especially true in college health or similar settings where dermatology services may not be available.
No taxation, no representation: An investigation of the relationship between natural resources and fiscal decentralization
Authors: Arzaghi Mohammad , Balthrop Andrew
Published: January 2018

Rents from natural resources can alter the relationship between central and local governments by providing a new source of government financing. We develop a model to explore the relationship between fiscal decentralization and resource abundance. Our model indicates that natural resource rents can detach central government expenditures from the tax base so that the central government can spend more to persuade a fractious periphery to remain under central government control. Thus, other things being equal, higher natural resource rents can result in less decentralized government expenditures. We empirically explore the relationship between fiscal decentralization and natural resource rents using a panel of 60 countries over the past 40 years. Empirical results support our economic model: A 1% increase in natural resource rents as a fraction of gross domestic product results in government expenditures that are 0.53% less decentralized.
Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum
Authors: Zhang Meng-Yao , Zhang Yang , Wu Xiao-Dong , Zhang Kun , Lin Peng , Bian Hui-Jie , Qin Min-Min , Huang Wan , Wei Ding , Zhang Zhao , Wu Jiao , Chen Ruo , Feng Fei , Wang Bin , Nan Gang , Zhu Ping , Chen Zhi-Nan
Published: January 2018

Key Points

The CD147-RAP2 interaction is essential for erythrocyte invasion by P falciparum and is independent from the known interactions involved. HP6H8, which specifically interrupts the CD147-RAP2 pair, is capable of complete elimination and prevention of P falciparum infection in humanized mice.
Persistently elevated exhaled nitric oxide fraction is associated with increased risk of exacerbation in COPD
Authors: Alcázar-Navarrete Bernardino , Ruiz Rodríguez Oliverio , Conde Baena Pablo , Romero Palacios Pedro José , Agusti Alvar
Published: January 2018

Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently increased levels of exhaled nitric oxide (FeNO) during follow-up can identify a group of COPD patients at higher risk of AECOPD.

To test this hypothesis, we measuredFeNOlevels (HypAirFeNO®, Medisoft; Sorinnes, Belgium) prospectively in 226 clinically stable COPD outpatients at recruitment and during follow-up (at 6 and 12 months). Patients were stratified according to the number of visits withFeNO≥20 ppb.

FeNOwas <20 ppb in all three visits in 44.2% of patients, 29.6% in visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively, p<0.001). After adjusting for potential confounding variables (log-rank test), the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049–2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter in these patients. Finally, there was no relationship betweenFeNOlevels and circulating eosinophils.

PersistentFeNOlevels ≥20 ppb in clinically stable COPD outpatients are associated with a significantly higher risk of AECOPD.
Intensity of exposure to pulmonary tuberculosis determines risk of tuberculosis infection and disease
Authors: Acuña-Villaorduña Carlos , Jones-López Edward C. , Fregona Geisa , Marques-Rodrigues Patricia , Gaeddert Mary , Geadas Carolina , Hadad David Jamil , White Laura F. , Pereira Dutra Molina Lucilia , Vinhas Solange , Ribeiro-Rodrigues Rodrigo , Salgame Padmini , Palaci Moises , Alland David , Ellner Jerrold J. , Dietze Reynaldo
Published: January 2018

Household contacts of pulmonary tuberculosis (TB) patients are at increased risk of TB infection and disease. However, their risk in relation to the intensity of exposure remains unknown.

We studied smear-positive TB cases and their household contacts in Vitória, Brazil. We collected clinical, demographic and radiographic information from TB cases, and obtained tuberculin skin test (TST) and QuantiFERON-TB Gold (QFT) results from household contacts. We measured intensity of exposure using a proximity score and sleep location in relation to the TB index case and defined infection by TST ≥10 mm or QFT ≥0.35 UI·mL−1. We ascertained secondary TB cases by reviewing local and nationwide case registries.

We included 160 TB index cases and 894 household contacts. 464 (65%) had TB infection and 23 (2.6%) developed TB disease. Risk of TB infection and disease increased with more intense exposures. In an adjusted analysis, the proximity score was associated with TB disease (OR 1.61, 95% CI 1.25–2.08; p<0.000); however, its diagnostic performance was only moderate.

Intensity of exposure increased risk of TB infection and disease among household contacts; however, its diagnostic performance was still suboptimal. A biomarker to target preventive therapy is urgently needed in this at-risk population.
Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease
Authors: Schaeffer Michele R. , Ryerson Christopher J. , Ramsook Andrew H. , Molgat-Seon Yannick , Wilkie Sabrina S. , Dhillon Satvir S. , Mitchell Reid A. , Sheel A. William , Khalil Nasreen , Camp Pat G. , Guenette Jordan A.
Published: January 2018

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.

Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).

On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.

Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.
Efficacy of intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B for post-neurosurgical intracranial infections due to MDR/XDR Acinectobacter baumannii: a retrospective cohort study
Authors: Pan Sijun , Huang Xiaofang , Wang Yesong , Li Li , Zhao Changyun , Yao Zhongxiang , Cui Wei , Zhang Gensheng
Published: January 2018

Background

Post-neurosurgical intracranial infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality. In this study, we analyzed the therapeutic efficacy of intravenous combined with intrathecal/intracerebral ventricle injection of polymyxin B for this type of intracranial infection.

Methods

This retrospective study was conducted from January 2013 to September 2017 at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou,China) and included 61 cases for which cerebrospinal fluid (CSF) cultures were positive for multidrug-resistant or extensively drug-resistant A. baumannii after a neurosurgical operation. Patients treated with intravenous and intrathecal/intracerebral ventricle injection of polymyxin B were assigned to the intrathecal/intracerebral group, and patients treated with other antibiotics without intrathecal/intracerebral injection were assigned to the intravenous group. Data for general information, treatment history, and the results of routine tests and biochemistry indicators in CSF, clinical efficiency, microbiological clearance rate, and the 28-day mortality were collected and analyzed.

Results

The rate of multidrug-resistant or extensively drug-resistant A. baumannii infection among patients who experienced an intracranial infection after a neurosurgical operation was 33.64% in our hospital. The isolated A. baumannii were resistant to various antibiotics, and most seriously to carbapenems (100.00% resistance rate to imipenem and meropenem), cephalosporins (resistance rates of 98.38% to cefazolin, 100.00% to ceftazidime, 100.00% to cefatriaxone, and 98.39% to cefepime). However, the isolated A. baumannii were completely sensitive to polymyxin B (sensitivity rate of 100.00%), followed by tigecycline (60.66%) and amikacin (49.18%). No significant differences in basic clinical data were observed between the two groups. Compared with the intravenous group, the intrathecal/intracerebral group had a significantly lower 28-day mortality (55.26% vs. 8.70%, P = 0.01) and higher rates of clinical efficacy and microbiological clearance (95.65% vs. 23.68%, P < 0.001; 91.30% vs. 18.42%, P < 0.001, respectively).

Conclusions

Intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B is an effective regimen for treating intracranial infections caused by multidrug-resistant or extensively drug-resistant A. baumannii.
Retrospective Survival Analysis of Patients With Advanced Pancreatic Ductal Adenocarcinoma and Germline BRCA or PALB2 Mutations
Authors: Reiss Kim A. , Yu Shun , Judy Renae , Symecko Heather , Nathanson Katherine L. , Domchek Susan M.
Published: January 2018

Purpose

Germline mutations in the homologous recombination (HR) genes BRCA1, BRCA2, and PALB2 confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in HR genes are sensitive to DNA-damaging agents, such as platinum chemotherapies. We hypothesized that patients with PDAC with germline BRCA1, BRCA2, or PALB2 mutations may benefit preferentially from platinum-based chemotherapy.

Materials and Methods

Twenty-nine individuals with deleterious germline mutations in BRCA1, BRCA2, or PALB2 and a diagnosis of advanced PDAC (mut-positive) were matched 2:1 to patients who were noncarrier or untested (control) by age at diagnosis, year of diagnosis, stage, and sex. Patients were identified via one of two available databases at the University of Pennsylvania: the Basser Center for BRCA Registry or the University of Pennsylvania Electronic Medical Patient Record. Treatment history, including exposure to platinum-based chemotherapy, was ascertained. Primary objective was overall survival (OS).

Results

Patients who were mut-positive had an OS of 21.8 months; control patients had an OS of 8.1 months (hazard ratio [HR], 0.35; 95% CI, 0.2 to 0.62; P < .001). With platinum exposure, patients who were mut-positive had an undefined OS (median follow-up, 20.1 months), versus an OS of 15.5 months in the control patients (HR, 0.25; 95% CI, 0.1 to 0.61; P = .002). In patients not treated with platinum, there was no significant difference in OS between groups (HR, 0.54; 95% CI, 0.25 to 1.17; P = .12). When treated with platinum therapy, patients who were mut-positive had a 1-year OS of 94%, compared with a 1-year OS of 60% in control patients.

Conclusion

Platinum-based therapy may confer a survival benefit in patients with advanced PDAC who carry a deleterious germline BRCA1, BRCA2, or PALB2 mutation.
TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency
Authors: Sierra Robert A. , Hoverter Nathan P. , Ramirez Ricardo N. , Vuong Linh M. , Mortazavi Ali , Merrill Bradley J. , Waterman Marian L. , Donovan Peter J.
Published: January 2018

Human embryonic stem cells (hESCs) are exquisitely sensitive to WNT ligands, which rapidly cause differentiation. Therefore, hESC self-renewal requires robust mechanisms to keep the cells in a WNT inactive but responsive state. How they achieve this is largely unknown. We explored the role of transcriptional regulators of WNT signaling, the TCF/LEFs. As in mouse ESCs, TCF7L1 is the predominant family member expressed in hESCs. Genome-wide, it binds a gene cohort involved in primitive streak formation at gastrulation, including NODAL, BMP4 and WNT3. Comparing TCF7L1-bound sites with those bound by the WNT signaling effector β-catenin indicates that TCF7L1 acts largely on the WNT signaling pathway. TCF7L1 overlaps less with the pluripotency regulators OCT4 and NANOG than in mouse ESCs. Gain- and loss-of-function studies indicate that TCF7L1 suppresses gene cohorts expressed in the primitive streak. Interestingly, we find that BMP4, another driver of hESC differentiation, downregulates TCF7L1, providing a mechanism of BMP and WNT pathway intersection. Together, our studies indicate that TCF7L1 plays a major role in maintaining hESC pluripotency, which has implications for human development during gastrulation.
Cold temperature represses daily rhythms in the liver transcriptome of a stenothermal teleost under decreasing day length
Authors: Prokkola Jenni M. , Nikinmaa Mikko , Lewis Mario , Anttila Katja , Kanerva Mirella , Ikkala Kaisa , Seppänen Eila , Kolari Irma , Leder Erica H.
Published: January 2018

The climate change -driven increase in temperature is occurring rapidly and decreasing the predictability of seasonal rhythms at high latitudes. It is therefore urgent to understand how a change in the relationship between the photoperiod and temperature can affect ectotherms in these environments. We tested whether temperature affects daily rhythms of transcription in a cold-adapted salmonid using high-throughput RNA-sequencing. Arctic char (Salvelinus alpinus) from a subarctic population were reared at a high and a low temperature (15°C and 8°C) for one month under natural, decreasing day length during late summer. Liver transcriptomes were compared between samples collected in the middle and towards the end of the light period and in the middle of the dark period. Daily variation in transcription was lower in fish from the low temperature compared to strong daily variation in warm-acclimated fish, suggesting cold temperatures dampen the cycling of transcriptional rhythms under a simultaneously decreasing day length. Different circadian clock genes had divergent expression patterns, responding either by decreased expression or by increased rhythmicity at 15°C compared to 8°C. The results point out mechanisms that can affect the ability of fish to adapt to increasing temperatures caused by climate change.
Lizards assess complex social signals by lateralizing colour but not motion detection
Authors: Batabyal Anuradha , Thaker Maria
Published: January 2018

Vertebrates lateralize many behaviours including social interactions. Social displays typically comprise multiple components, yet our understanding of how these are processed come from studies that typically examine responses to the dominant component or the complex signal as a whole. Here, we examine laterality in lizard responses to determine whether receivers separate the processing of motion and colour signal components in different brain hemispheres. In Psammophilus dorsalis, males display colours that dynamically change during courtship and aggressive interactions. We tested the visual grasp reflex of both sexes using robotic stimuli that mimicked two signal components: (1) multiple speeds of head-bobbing behaviour and (2) multiple colours. We find no laterality in response to different motion stimuli, indicating that motion similarly attracts attention from both visual fields across sexes. Notably, receivers showed left visual field dominance to colours, especially when males were exposed to “aggression-specific” colours and females to “courtship-specific” colours.