bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible diodes for radio frequency (RF) electronics: a materials perspective
Authors: Semple James , Georgiadou Dimitra G , Wyatt-Moon Gwenhivir , Gelinck Gerwin , Anthopoulos Thomas D
Published: October 2017

Over the last decade, there has been increasing interest in transferring the research advances in radiofrequency (RF) rectifiers, the quintessential element of the chip in the RF identification (RFID) tags, obtained on rigid substrates onto plastic (flexible) substrates. The growing demand for flexible RFID tags, wireless communications applications and wireless energy harvesting systems that can be produced at a low-cost is a key driver for this technology push. In this topical review, we summarise recent progress and status of flexible RF diodes and rectifying circuits, with specific focus on materials and device processing aspects. To this end, different families of materials (e.g. flexible silicon, metal oxides, organic and carbon nanomaterials), manufacturing processes (e.g. vacuum and solution processing) and device architectures (diodes and transistors) are compared. Although emphasis is placed on performance, functionality, mechanical flexibility and operating stability, the various bottlenecks associated with each technology are also addressed. Finally, we present our outlook on the commercialisation potential and on the positioning of each material class in the RF electronics landscape based on the findings summarised herein. It is beyond doubt that the field of flexible high and ultra-high frequency rectifiers and electronics as a whole will continue to be an active area of research over the coming years.
Effect of triggering angles on the crushing mechanisms of hybrid woven kenaf/aluminum hollow cylinders
Authors: Ismail Al Emran , Noor Fazimah Mat , Mohamad Zaleha , Madlan Mohd Amran , Zulafif Rahim M. , Rasidi Ibrahim M. , Ahmad Sufizar , Rahman Mohd Nasrull Abdol , Salleh Salihatun Md , Sadikin Azmahani , Mahzan Shahruddin , Nor Nik Hisyamudin Muhd
Published: October 2017

This paper presents the effect of triggering angles constructed on the top of hybrid woven kenaf/aluminium hollow cylinders on the energy absorption performances. The crushing performances of aluminium tubes can be found widely in open literature. However, lack number of work on the hybridizing the aluminium tubes with woven kenaf fibre is found. Woven kenaf mats are produced and bathed with polymeric resin before they are wrapped around the aluminium tubes twice. Different fibre orientations, ±θ° are used where θ = 0, 15, 30 and 45. Once the hybrid composite hardened, one of their end are chamfered using different angles of 0°, 30°, 45° and 60°. The tubes are quasi-statically compressed in order to obtain their force-displacement responses and crashworthiness parameters are extracted and discussed with the relation of fibre orientations and chamfering angles. It is found that the chamfering angles are only affected the force-displacement curves during the first stage of elastic deformation whereas there is no obvious effect in the second stage. However, varying the fibre orientations are slightly increased the force-displacement curves especially when the fibre is orientated with 30°. Based on the fracture mechanism observations, most of composite experienced large fragmentation indicating that the composites absorbed the crushing energy ineffectively.
From the microscope to the macroscopic: changing from the bench to portfolio management
Authors: Sachs Michael
Published: October 2017

A role in portfolio management is ideal for individuals who enjoy tackling challenges that have both technical and business components. Portfolio management provides objective insights and analytics to support research and development decision making and planning. Successful practitioners usually have strong analytical abilities developed from a background in either science or business. Portfolio managers often advise key decision makers at both the team and senior management level and thus require robust oral, written, and interpersonal communication skills. Day-to-day tasks are rarely the same, and comfort with change and the unknown is essential. Here I will discuss my experience as a portfolio manager in a larger biopharmaceutical company and the skills from academic research I leveraged to make the transition.
Five years post-DORA: promoting best practices for research assessment
Authors: Schmid Sandra L.
Published: October 2017

The San Francisco Declaration on Research Assessment (DORA) was penned 5 years ago to articulate best practices for how we communicate and judge our scientific contributions. In particular, it adamantly declared that Journal Impact Factor (JIF) should never be used as a surrogate measure of the quality of individual research contributions, or for hiring, promotion, or funding decisions. Since then, a heightened awareness of the damaging practice of using JIFs as a proxy for the quality of individual papers, and to assess an individual’s or institution’s accomplishments has led to changes in policy and the design and application of best practices to more accurately assess the quality and impact of our research. Herein I summarize the considerable progress made and remaining challenges that must be met to ensure a fair and meritocratic approach to research assessment and the advancement of research.
pedigreejs: a web-based graphical pedigree editor
Authors: Carver Tim , Cunningham Alex P , Babb de Villiers Chantal , Lee Andrew , Hartley Simon , Tischkowitz Marc , Walter Fiona M , Easton Douglas F , Antoniou Antonis C
Published: October 2017

Motivation

The collection, management and visualization of clinical pedigree (family history) data is a core activity in clinical genetics centres. However, clinical pedigree datasets can be difficult to manage, as they are time consuming to capture, and can be difficult to build, manipulate and visualize graphically. Several standalone graphical pedigree editors and drawing applications exist but there are no freely available lightweight graphical pedigree editors that can be easily configured and incorporated into web applications.

Results

We developed ‘pedigreejs’, an interactive graphical pedigree editor written in JavaScript, which uses standard pedigree nomenclature. Pedigreejs provides an easily configurable, extensible and lightweight pedigree editor. It makes use of an open-source Javascript library to define a hierarchical layout and to produce images in scalable vector graphics (SVG) format that can be viewed and edited in web browsers.

Availability and implementation

The software is freely available under GPL licence (https://ccge-boadicea.github.io/pedigreejs/).

Supplementary information

Supplementary data are available at Bioinformatics online.
A 3-way hybrid approach to generate a new high-quality chimpanzee reference genome (Pan_tro_3.0)
Authors: Kuderna Lukas F K , Tomlinson Chad , Hillier LaDeana W , Tran Annabel , Fiddes Ian T , Armstrong Joel , Laayouni Hafid , Gordon David , Huddleston John , Garcia Perez Raquel , Povolotskaya Inna , Serres Armero Aitor , Gómez Garrido Jèssica , Ho Daniel , Ribeca Paolo , Alioto Tyler , Green Richard E , Paten Benedict , Navarro Arcadi , Betranpetit Jaume , Herrero Javier , Eichler Evan E , Sharp Andrew J , Feuk Lars , Warren Wesley C , Marques-Bonet Tomas
Published: October 2017

The chimpanzee is arguably the most important species for the study of human origins. A key resource for these studies is a high-quality reference genome assembly; however, as with most mammalian genomes, the current iteration of the chimpanzee reference genome assembly is highly fragmented. In the current iteration of the chimpanzee reference genome assembly (Pan_tro_2.1.4), the sequence is scattered across more then 183 000 contigs, incorporating more than 159 000 gaps, with a genome-wide contig N50 of 51 Kbp. In this work, we produce an extensive and diverse array of sequencing datasets to rapidly assemble a new chimpanzee reference that surpasses previous iterations in bases represented and organized in large scaffolds. To this end, we show substantial improvements over the current release of the chimpanzee genome (Pan_tro_2.1.4) by several metrics, such as increased contiguity by >750% and 300% on contigs and scaffolds, respectively, and closure of 77% of gaps in the Pan_tro_2.1.4 assembly gaps spanning >850 Kbp of the novel coding sequence based on RNASeq data. We further report more than 2700 genes that had putatively erroneous frame-shift predictions to human in Pan_tro_2.1.4 and show a substantial increase in the annotation of repetitive elements. We apply a simple 3-way hybrid approach to considerably improve the reference genome assembly for the chimpanzee, providing a valuable resource for the study of human origins. Furthermore, we produce extensive sequencing datasets that are all derived from the same cell line, generating a broad non-human benchmark dataset.
How to do (or not to do)… Measuring health worker motivation in surveys in low- and middle-income countries
Authors: Borghi J , Lohmann J , Dale E , Meheus F , Goudge J , Oboirien K , Kuwawenaruwa A
Published: October 2017

A health system’s ability to deliver quality health care depends on the availability of motivated health workers, which are insufficient in many low income settings. Increasing policy and researcher attention is directed towards understanding what drives health worker motivation and how different policy interventions affect motivation, as motivation is key to performance and quality of care outcomes. As a result, there is growing interest among researchers in measuring motivation within health worker surveys. However, there is currently limited guidance on how to conceptualize and approach measurement and how to validate or analyse motivation data collected from health worker surveys, resulting in inconsistent and sometimes poor quality measures. This paper begins by discussing how motivation can be conceptualized, then sets out the steps in developing questions to measure motivation within health worker surveys and in ensuring data quality through validity and reliability tests. The paper also discusses analysis of the resulting motivation measure/s. This paper aims to promote high quality research that will generate policy relevant and useful evidence.
Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma
Authors: Shepherd Leah , Ryom Lene , Law Matthew , Hatleberg Camilla Ingrid , de Wit Stephane , Monforte Antonella d'Arminio , Battegay Manuel , Phillips Andrew , Bonnet Fabrice , Reiss Peter , Pradier Christian , Grulich Andrew , Sabin Caroline , Lundgren Jens , Mocroft Amanda
Published: October 2017

Background

Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk.

Methods

Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided.

Results

Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate = 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] = 1.06 to 1.30) and 149 developed HL (incidence rate = 0.44/1000 PYFU, 95% CI = 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 = 8.08, 95% CI = 5.63 to 11.61; HL = 4.58, 95% CI = 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL = 1.97, 95% CI = 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile = 2.91, 95% CI = 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL.

Conclusions

CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.
Impact of Timing and Method of Virus Inoculation on the Severity of Wheat Streak Mosaic Disease
Authors: Wosula E. N. , McMechan A. J. , Knoell E. , Tatineni S. , Wegulo S. N. , Hein G. L.
Published: October 2017

Wheat streak mosaic virus (WSMV), transmitted by the wheat curl mite Aceria tosichella, frequently causes significant yield loss in winter wheat throughout the Great Plains of the United States. A field study was conducted in the 2013–14 and 2014–15 growing seasons to compare the impact of timing of WSMV inoculation (early fall, late fall, or early spring) and method of inoculation (mite or mechanical) on susceptibility of winter wheat cultivars Mace (resistant) and Overland (susceptible). Relative chlorophyll content, WSMV incidence, and yield components were determined. The greatest WSMV infection occurred for Overland, with the early fall inoculations resulting in the highest WSMV infection rate (up to 97%) and the greatest yield reductions relative to the control (up to 94%). In contrast, inoculation of Mace resulted in low WSMV incidence (1 to 28.3%). The findings from this study indicate that both method of inoculation and wheat cultivar influenced severity of wheat streak mosaic; however, timing of inoculation also had a dramatic influence on disease. In addition, mite inoculation provided much more consistent infection rates and is considered a more realistic method of inoculation to measure disease impact on wheat cultivars.
Effects of Changes in Arterial Carbon Dioxide and Oxygen Partial Pressures on Cerebral Oximeter Performance
Authors: Schober Andrew , Feiner John R. , Bickler Philip E. , Rollins Mark D.
Published: October 2017

Background

Cerebral oximetry (cerebral oxygen saturation; ScO2) is used to noninvasively monitor cerebral oxygenation. ScO2 readings are based on the fraction of reduced and oxidized hemoglobin as an indirect estimate of brain tissue oxygenation and assume a static ratio of arterial to venous intracranial blood. Conditions that alter cerebral blood flow, such as acute changes in Paco
2, may decrease accuracy. We assessed the performance of two commercial cerebral oximeters across a range of oxygen concentrations during normocapnia and hypocapnia.

Methods

Casmed FORE-SIGHT Elite (CAS Medical Systems, Inc., USA) and Covidien INVOS 5100C (Covidien, USA) oximeter sensors were placed on 12 healthy volunteers. The fractional inspired oxygen tension was varied to achieve seven steady-state levels including hypoxic and hyperoxic Pao
2 values. ScO2 and simultaneous arterial and jugular venous blood gas measurements were obtained with both normocapnia and hypocapnia. Oximeter bias was calculated as the difference between the ScO2 and reference saturation using manufacturer-specified weighting ratios from the arterial and venous samples.

Results

FORE-SIGHT Elite bias was greater during hypocapnia as compared with normocapnia (4 ± 9% vs. 0 ± 6%; P < 0.001). The INVOS 5100C bias was also lower during normocapnia (5 ± 15% vs. 3 ± 12%; P = 0.01). Hypocapnia resulted in a significant decrease in mixed venous oxygen saturation and mixed venous oxygen tension, as well as increased oxygen extraction across fractional inspired oxygen tension levels (P < 0.0001). Bias increased significantly with increasing oxygen extraction (P < 0.0001).

Conclusions

Changes in Paco
2 affect cerebral oximeter accuracy, and increased bias occurs with hypocapnia. Decreased accuracy may represent an incorrect assumption of a static arterial–venous blood fraction. Understanding cerebral oximetry limitations is especially important in patients at risk for hypoxia-induced brain injury, where Paco
2 may be purposefully altered.
Ten-Year Incidence of High-Energy Geriatric Trauma at a Level 1 Trauma Center
Authors: Lowe Jason A. , Pearson Jeffrey , Leslie Michael , Griffin Russell
Published: October 2017

Objectives:

To examine the characteristics of high-energy geriatric trauma over time.

Design:

Retrospective chart review.

Setting:

Level 1 trauma center.

Patients:

Demographic, injury, and clinical characteristics were compared between 34,017 patients with geriatric and nongeriatric high-energy trauma from 2005 to 2014 using t test, χ2 analysis, and negative binomial regression for annual trend in injuries.

Results:

Geriatric high-energy trauma composed 11.2% of all trauma activations. Patients with geriatric high-energy trauma nearly doubled from the study period of 2005–2014 to previous 10 years (P = 0.0004). Compared with patients with nongeriatric trauma, geriatric high-energy traumas were twice as likely to be due to a fall from height (P < 0.0001), had higher Injury Severity Scores (P < 0.0001), fewer abdominal injuries (P = 0.0011), and have head trauma (P < 0.0001). Fracture patterns were similar between groups. Mortality was higher for all geriatric patients (odds ratio [OR], 4.76; 95% confidence interval [CI], 4.00–5.67), and high-energy mechanisms (OR, 4.71; 95% CI, 3.90–5.68) compared with low-energy mechanisms (OR, 3.00; 95% CI, 2.48–3.62).

Conclusion:

The number of geriatric high-energy traumas has doubled over 10 years. Patients with geriatric trauma are sicker on presentation, based on the Injury Severity Score, and high-energy geriatrics have a 4-fold increase in mortality.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Students’ Perception of Technology Use in Nursing Education
Authors: Williamson Kathleen M. , Muckle Janelle
Published: October 2017

Technology is an integral part of a nurse’s practice; therefore, it is necessary for technology to be integrated into the nursing curriculum for students. Nursing schools are shifting paradigms by integrating technology into the teaching environment to foster active and meaningful learning experiences. Factors related to external influences on individual beliefs, attitudes, and intention to use need to be studied so nurse educators can support the integration of technology into pedagogy. The Technology Acceptance Model was used to evaluate student perceptions of usefulness and ease of use of technology, while matriculated in a baccalaureate level nursing program. Quantitative and qualitative data were collected to uncover how nursing students (N = 375) perceived the usefulness and ease of use of technology while in nursing school. Almost every student (99.7%) owned a smartphone, and 95% were reasonably comfortable using various technologies. Selecting and incorporating technological tools to successfully support learning is essential to overcome challenges and support the innovative delivery of content and use of technology by students.
School Dropout and Associated Factors Among Omani Children with Attention-Deficit Hyperactivity Disorder: A Cross-Sectional Study
Authors: Mirza Hassan , Roberts Emmert , AL-Belushi Mohammed , AL-Salti Humaid , AL-Hosni Amira , Jeyaseelan Lakshmanan , AL-Adawi Samir
Published: October 2017

Objective:

Despite the rising incidence of attention-deficit hyperactivity disorder (ADHD), there is a dearth of studies examining the rate of school dropout and its correlates in non-Western populations.

Methods:

Medical records were scrutinized to identify Omani children diagnosed with ADHD from 2006 to 2014 in a tertiary care hospital in Oman. The persistence of ADHD symptoms, school performance and dropout, as well as sociodemographic characteristics were examined.

Results:

Three hundred sixty-seven children fulfilled the diagnosis of ADHD based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) criteria and 16.6% of them had dropped out of school. School dropout was associated with poor school performance, comorbid conduct disorder, and parental divorce.

Conclusion:

This study from Oman concurs with existing literature that school dropout is common among children with ADHD. Concerted efforts are needed to mitigate this trend. Management strategies should incorporate the treatment of comorbid conduct disorder.
Intracochlear Measurements of Interaural Time and Level Differences Conveyed by Bilateral Bone Conduction Systems
Authors: Farrell Nyssa F. , Banakis Hartl Renee M. , Benichoux Victor , Brown Andrew D. , Cass Stephen P. , Tollin Daniel J.
Published: October 2017

Hypothesis:

Intracochlear pressures (PIC) and stapes velocity (Vstap) elicited by bilaterally placed bone-anchored hearing devices (BAHD) will be systematically modulated by imposed interaural time (ITD) and level differences (ILD), demonstrating the potential for users of bilateral BAHD to access these binaural cues.

Background:

BAHD are traditionally implanted unilaterally under the assumption that transcranial cross-talk limits interaural differences. Recent studies have demonstrated improvements in binaural and spatial performance with bilateral BAHD; however, objective measures of binaural cues from bilateral BAHDs are lacking.

Methods:

Bone-conduction transducers were coupled to both mastoids of cadaveric specimens via implanted titanium abutments. PIC and Vstap were measured using intracochlear pressure probes and laser Doppler vibrometry, respectively, during stimulation with pure-tone stimuli of varied frequency (250–4000 Hz) under ipsilateral, contralateral, and bilateral ITD (−1 to 1 ms) and ILD (−20 to 20 dB) conditions.

Results:

Bilateral stimulation produced constructive and destructive interference patterns that varied dramatically with ITD and stimulus frequency. Variation of ITD led to large variation of PIC and Vstap, with opposing effects in ipsilateral and contralateral ears expected to lead to “ITD to ILD conversion.” Variation of ILD produced more straightforward (monotonic) variations of PIC and Vstap, with ipsilateral-favoring ILD producing higher PIC and Vstap than contralateral-favoring.

Conclusion:

Variation of ITDs and ILDs conveyed by BAHDs systematically modulated cochlear inputs. While transcranial cross-talk leads to complex interactions that depend on cue type and stimulus frequency, binaural disparities potentiate binaural benefit, providing a basis for improved sound localization and speech-in-noise perception.
Value of T1-weighted Magnetic Resonance Imaging in Cholesteatoma Detection
Authors: Fukuda Atsushi , Morita Shinya , Harada Taisuke , Fujiwara Keishi , Hoshino Kimiko , Nakamaru Yuji , Homma Akihiro
Published: October 2017

Objective:

To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma.

Study Design:

A retrospective case review.

Setting:

Tertiary referral center.

Patients:

Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6–82 yr of age).

Intervention:

Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging.

Main Outcome Measures:

Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal.

Results:

The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different (p < 0.001).

Conclusion:

Our results suggest that T1W imaging may aid in the exclusion of false-positive cases on diagnostic non-EP DW MR imaging for cholesteatomas. A combination of non-EP DW and T1W imaging may improve the specificity and accuracy compared with non-EP DW imaging alone.
Patients’ Perspectives on Transplantation While Undergoing Left Ventricular Assist Device Support
Authors: Wilhelms Lidija A. , Blumenthal-Barby Jennifer S. , Kostick Kristin M. , Estep Jerry D. , Bruce Courtenay R.
Published: October 2017

Left-ventricular assist device (LVAD) therapy is a growing mechanical circulatory support therapy used to treat patients with advanced heart failure. There is a general assumption among clinicians that patients would prefer to accept a heart to any other treatment were they eligible. However, little research has been done to clarify the nuances of patient treatment preferences for LVAD therapy versus transplantation. The objective of this study was to investigate this treatment preference assumption from patients’ perspectives. In a single-site study, 15 LVAD patients, 15 LVAD candidates, 15 LVAD decliners, and 15 LVAD caregivers (n = 60) participated in structured, in-depth interviews to assess decisional processes and treatment preferences for advanced heart failure. The interview guides were consistent with the Ottawa framework on decision-making processes. All participants were identified by the LVAD coordination team and recruited consecutively between February and November 2014. The patient and candidate groups included both LVAD designations: destination therapy (n = 22), bridge-to-transplant (n = 4), as well as four participants who deferred designation pending worsening clinical status. The interviews were analyzed using qualitative description with constant comparisons, aided by ATLAS.ti. Although LVAD eligible patients generally show a preference for heart transplantation as the ideal treatment for heart failure, some patients begin to show ambivalence as they experience LVAD therapy and begin to prefer LVAD as a long-term, destination treatment. Some themes that emerged from the interviews concerning transplantation centered on the consequences of multiple major surgeries (i.e., LVAD placement followed by heart transplantation, n = 18), fears surrounding lifestyle changes of accepting a heart transplant (n = 14) and life satisfaction with an LVAD as a “new normal” (n = 18). Findings suggest that experience with an LVAD can sometimes cause ambivalence about transplant with some patients preferring LVAD as destination even when transplant is an option. We provide clinical and programmatic implications of this, concluding with practical recommendations for how to fully address patients’ goals of treatment as their health and situation changes over time.
A Randomized Control Trial of Cardiopulmonary Feedback Devices and Their Impact on Infant Chest Compression Quality
Authors: Austin Andrea L. , Spalding Carmen N. , Landa Katrina N. , Myer Brian R. , Cure Donald , Smith Jason E. , Platt Gerald , King Heather C.
Published: October 2017

Objectives

In effort to improve chest compression quality among health care providers, numerous feedback devices have been developed. Few studies, however, have focused on the use of cardiopulmonary resuscitation feedback devices for infants and children. This study evaluated the quality of chest compressions with standard team-leader coaching, a metronome (MetroTimer by ONYX Apps), and visual feedback (SkillGuide Cardiopulmonary Feedback Device) during simulated infant cardiopulmonary resuscitation.

Methods

Seventy voluntary health care providers who had recently completed Pediatric Advanced Life Support or Basic Life Support courses were randomized to perform simulated infant cardiopulmonary resuscitation into 1 of 3 groups: team-leader coaching alone (control), coaching plus metronome, or coaching plus SkillGuide for 2 minutes continuously. Rate, depth, and frequency of complete recoil during cardiopulmonary resuscitation were recorded by the Laerdal SimPad device for each participant. American Heart Association–approved compression techniques were randomized to either 2-finger or encircling thumbs.

Results

The metronome was associated with more ideal compression rate than visual feedback or coaching alone (104/min vs 112/min and 113/min; P = 0.003, 0.019). Visual feedback was associated with more ideal depth than auditory (41 mm vs 38.9; P = 0.03). There were no significant differences in complete recoil between groups. Secondary outcomes of compression technique revealed a difference of 1 mm. Subgroup analysis of male versus female showed no difference in mean number of compressions (221.76 vs 219.79; P = 0.72), mean compression depth (40.47 vs 39.25; P = 0.09), or rate of complete release (70.27% vs 64.96%; P = 0.54).

Conclusions

In the adult literature, feedback devices often show an increase in quality of chest compressions. Although more studies are needed, this study did not demonstrate a clinically significant improvement in chest compressions with the addition of a metronome or visual feedback device, no clinically significant difference in Pediatric Advanced Life Support–approved compression technique, and no difference between compression quality between genders.
Evolving Models and Ongoing Challenges for HIV Preexposure Prophylaxis Implementation in the United States
Authors: Mayer Kenneth H. , Chan Philip A. , R. Patel Rupa , Flash Charlene A. , Krakower Douglas S.
Published: October 2017

Background:

The use of preexposure prophylaxis (PrEP) for HIV prevention was approved by the Food and Drug Administration in 2012, but delivery to at-risk persons has lagged. This critical review analyzes the current state of PrEP implementation in the United States, by reviewing barriers and innovative solutions to enhance PrEP access and uptake.

Setting:

Clinical care settings, public health programs, and community-based organizations (CBOs).

Methods:

Critical review of recent peer-reviewed literature.

Results:

More than 100 papers were reviewed. PrEP is currently provided in diverse settings. Care models include sexually transmitted disease clinics, community health centers, CBOs, pharmacies, and private primary care providers (PCPs). Sexually transmitted disease clinics have staff trained in sexual health counseling and are linked to public health programs (eg, partner notification services), whereas PCPs and community health centers may be less comfortable counseling and feel time-constrained in managing PrEP. However, PCPs may be ideal PrEP providers, given their long-term relationships with patients, integrating PrEP into routine care. Collaborations with CBOs can expand PrEP care through adherence support and insurance navigation. Pharmacies can deliver PrEP, given their experience with medication dispensing and counseling, and may be more accessible for some patients, but to address other health concerns, liaisons with PCPs may be needed.

Conclusions:

PrEP implementation in the United States is moving forward with the development of diverse models of delivery. Optimal scale-up will require learning about the best features of each model and providing choices to consumers that enhance engagement and uptake.
Brief Report: Declining Baseline Viremia and Escalating Discordant HIV-1 Confirmatory Results Within South Africa's Early Infant Diagnosis Program, 2010–2016
Authors: Mazanderani Ahmad Haeri , Moyo Faith , Kufa Tendesayi , Sherman Gayle G.
Published: October 2017

Objective:

To describe baseline HIV-1 RNA viral load (VL) trends within South Africa's Early Infant Diagnosis program 2010–2016, with reference to prevention of mother-to-child transmission guidelines.

Methods:

HIV-1 total nucleic acid polymerase chain reaction (TNA PCR) and RNA VL data from 2010 to 2016 were extracted from the South African National Health Laboratory Service's central data repository. Infants with a positive TNA PCR and subsequent baseline RNA VL taken at age <7 months were included. Descriptive statistics were performed for quantified and lower-than-quantification limit (LQL) results per annum and age in months. Trend analyses were performed using log likelihood ratio tests. Multivariable linear regression was used to model the relationship between RNA VL and predictor variables, whereas logistic regression was used to identify predictors associated with LQL RNA VL results.

Results:

Among 13,606 infants with a positive HIV-1 TNA PCR linked to a baseline RNA VL, median age of first PCR was 57 days and VL was 98 days. Thirteen thousand one hundred ninety-five (97.0%) infants had a quantified VL and 411 (3.0%) had an LQL result. A significant decline in median VL was observed between 2010 and 2016, from 6.3 log10 (interquartile range: 5.6–6.8) to 5.6 log10 (interquartile range: 4.2–6.5) RNA copies per milliliter, after controlling for age (P < 0.001), with younger age associated with lower VL (P < 0.001). The proportion of infants with a baseline VL <4 Log10 RNA copies per milliliter increased from 5.4% to 21.8%. Subsequent to prevention of mother-to-child transmission Option B implementation in 2013, the proportion of infants with an LQL baseline VL increased from 1.5% to 6.1% (P < 0.001).

Conclusions:

Between 2010 and 2016, a significant decline in baseline viremia within South Africa's Early Infant Diagnosis program was observed, with loss of detectability among some HIV-infected infants.
Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins
Authors: Stephens Andrew D. , Liu Patrick Z. , Banigan Edward J. , Almassalha Luay M. , Backman Vadim , Adam Stephen A. , Goldman Robert D. , Marko John F.
Published: October 2017

Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed “blebs” are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs. Treatment of mammalian cells with histone deacetylase inhibitors to increase euchromatin or histone methyltransferase inhibitors to decrease heterochromatin results in a softer nucleus and nuclear blebbing, without perturbing lamins. Oppositely, treatment with histone demethylase inhibitors increases heterochromatin and chromatin nuclear rigidity, which results in reduced nuclear blebbing in lamin B1 null nuclei. Notably, increased heterochromatin also rescues nuclear morphology in a model cell line for the accelerated aging disease Hutchinson-Gilford progeria syndrome caused by mutant lamin A, as well as cells from patients with the disease. Thus, chromatin histone modification state is a major determinant of nuclear blebbing and morphology via its contribution to nuclear rigidity.
Identification and prioritisation of causal variants in human genetic disorders from exome or whole genome sequencing data
Authors: Paramasivam Nagarajan , Granzow Martin , Evers Christina , Hinderhofer Katrin , Wiemann Stefan , Bartram Claus R. , Eils Roland , Schlesner Matthias
Published: October 2017

With genome sequencing entering the clinics as diagnostic tool to study genetic disorders, there is an increasing need for bioinformatics solutions that enable precise causal variant identification in a timely manner.

Background

Workflows for the identification of candidate disease-causing variants perform usually the following tasks: i) identification of variants; ii) filtering of variants to remove polymorphisms and technical artifacts; and iii) prioritization of the remaining variants to provide a small set of candidates for further analysis.

Methods

Here, we present a pipeline designed to identify variants and prioritize the variants and genes from trio sequencing or pedigree-based sequencing data into different tiers.

Results

We show how this pipeline was applied in a study of patients with neurodevelopmental disorders of unknown cause, where it helped to identify the causal variants in more than 35% of the cases.

Conclusions

Classification and prioritization of variants into different tiers helps to select a small set of variants for downstream analysis.
Analysis of allelic series with transcriptomic phenotypes
Authors: Angeles-Albores David , Sternberg Paul W.
Published: October 2017

Although transcriptomes have recently been used to perform epistasis analyses, they are not yet used to study intragenic function/structure relationships. We developed a theoretical framework to study allelic series using transcriptomic phenotypes. As a proof-of-concept, we apply our methods to an allelic series ofdpy-22, a highly pleiotropicCaenorhabditis elegansgene orthologous to the human geneMED12, which is a subunit of the Mediator complex. Our methods identify functional regions withindpy-22that modulate Mediator activity upon various genetic modules.
Targeted deletion of Nmnat1 in mouse retina leads to early severe retinal dystrophy
Authors: Wang Xiaolin , Fang Yu , Liao Rongsheng , Wang Tao
Published: October 2017

Mutations in NMNAT1 can lead to a very severe type of retinal dystrophy, Leber congenital amaurosis, in human patients, characterized by infantile-onset or congenital retinal dystrophy and childhood blindness. The loss-of-function mouse models of Nmnat1 have not been well-established, since the complete knock-out (KO) of Nmnat1 in mice results in embryonic lethality. Here, we generated retina-specific KO by using the Crxpromotor-driving Cre combined with the flox allele. By a panel of histological and functional analyses, we found that Nmnat1 conditional KO (cKO) mice have early severe retinal dystrophy. Specifically, the photoreceptors of Nmnat1 cKO mice are almost diminished and the retinal functions also become completely abolished. Our results established a loss-of-function model for Nmnat1 in mice, which will be useful for studying the detailed functions of NMNAT1 in the retina.
A 20S proteasome receptor for degradation of intrinsically disordered proteins
Authors: Biran Assaf , Myers Nadav , Adler Julia , Broennimann Karin , Reuven Nina , Shaul Yosef
Published: October 2017

Degradation of intrinsically disordered proteins (IDPs) by the 20S proteasome, unlike ubiquitin-dependent 26S proteasomal degradation, does not require proteasomal targeting by polyubiquitin. However, how these proteins are recognized by the proteasome was unknown. We report here on a mechanism of 20S proteasome targeting. Analysis of protein interactome datasets revealed that the proteasome subunit PSMA3 interacts with many IDPs. By employing in vivo and cell-free experiments we demonstrated that the PSMA3 C-terminus binds p21, c-Fos and p53, all IDPs and 20S proteasome substrates. A 69 amino-acids long fragment is autonomously functional in interacting with IDP substrates. Remarkably, this fragment in isolation blocks the degradation of a large number of IDPs in vitro and increases the half-life of proteins in vivo. We propose a model whereby the PSMA3 C-terminal region plays a role of substrate receptor in the process of proteasomal degradation of many IDPs.
Listeria monocytogenesvirulence factors are secreted in biologically active Extracellular Vesicles
Authors: Coelho Carolina , Brown Lisa , Maryam Maria , Burnet Meagan C. , Kyle Jennifer E. , Heyman Heino M. , Vij Raghav , Ramirez Jasmine , Prados-Rosales Rafael , Lauvau Gregoire , Nakayasu Ernesto S. , Brady Nathan Ryan , Hamacher-Brady Anne , Coppens Isabelle , Casadevall Arturo
Published: October 2017

Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secreted extracellular vesicles (EVs) was not pursued due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteriaare implicated in virulence, toxin release and transference to host cells, eliciting immune responses, and spread of antibiotic resistance.Listeria monocytogenesis a Gram-positive bacterium that is the etiological agent of listeriosis. Here we report thatL. monocytogenesproduces EVs with diameter ranging from 20-200 nm, containing the pore-forming toxin listeriolysin O(LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Using simultaneousmetabolite,protein, andlipidextraction (MPLEx) multi-omics we characterized protein, lipid and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Cell-free EV preparations were toxic to the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion ofplcAincreased EV toxicity, suggesting PI-PLC can restrain LLO activity. Using immunogold electron microscopy we detect LLO localization at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released fromL. monocytogenesthat colocalize with LLO during infection. Our findings demonstrate thatL. monocytogenesutilize EVs for toxin release and implicate these structures in mammalian cytotoxicity.
Contextual Regression: An Accurate and Conveniently Interpretable Nonlinear Model for Mining Discovery from Scientific Data
Authors: Liu Chengyu , Wang Wei
Published: October 2017

Machine learning algorithms such as linear regression, SVM and neural network have played an increasingly important role in the process of scientific discovery. However, none of them is both interpretable and accurate on nonlinear datasets. Here we present contextual regression, a method that joins these two desirable properties together using a hybrid architecture of neural network embedding and dot product layer. We demonstrate its high prediction accuracy and sensitivity through the task of predictive feature selection on a simulated dataset and the application of predicting open chromatin sites in the human genome. On the simulated data, our method achieved high fidelity recovery of feature contributions under random noise levels up to ±200%. On the open chromatin dataset, the application of our method not only outperformed the state of the art method in terms of accuracy, but also unveiled two previously unfound open chromatin related histone marks. Our method fills in the gap of accurate and interpretable nonlinear modeling in scientific data mining tasks.
Active deep learning reduces annotation burden in automatic cell segmentation
Authors: Chowdhury Aritra , Biswas Sujoy K. , Bianco Simone
Published: October 2017

The relationship between cellular architecture and cellular state and function is apparent, but not yet completely understood. Precise characterization of cellular state is important in many fields, from pathology to synthetic biology. High-content high-throughput microscopy is now more than ever accessible to researchers. This allows for collection of large amount of cellular images. Naturally, the analysis of this data cannot be left to manual investigation and needs to resort to the use of efficient computing algorithms for cellular detection, segmentation, and tracking. Annotation is required for building high quality algorithms. Medical professionals and researchers spend a lot of effort and time in annotating cells. This task has proved to be very repetitive and time consuming. The experts’ time is valuable and should be used effectively. Our hypothesis is that active deep learning will help to share some of the burden that researchers face in their everyday work. In this paper, we focus specifically on the problem of cellular segmentation.

We approach the segmentation task using a classification framework. Each pixel in the image is classified based on whether the patch around it resides on the interior, boundary or exterior of the cell. Deep convolutional neural networks (CNN) are used to perform the classification task. Active learning is the method used to reduce the annotation burden. Uncertainty sampling, a popular active learning framework is used in conjunction with CNN to segment the cells in the image. Three datasets of mammalian nuclei and cytoplasm are used for this work. We show that active deep learning significantly reduces the number of training samples required and also improves the quality of segmentation.
Determinants of TRevPAR: hotel, management and tourist destination
Authors: Lado-Sestayo Rubén , Vivel-Búa Milagros , Otero-González Luis
Published: October 2017

Purpose

This paper aims to study the determinants of hotel performance, especially the role of location, in the Spanish hotel market.

Design/methodology/approach

The sample is composed of 1,034 hotels located in 97 tourist destinations in Spain during the period 2005-2011. The estimations were made by generalised least squares using panel data.

Findings

Overall, the results show that hotel attributes are the main determinant of performance. In particular, there is a minimum efficient scale in the hotel business. Location is the second most important determinant. This paper confirms that geographical location models, agglomeration models and competition models are relevant in the study of the effect of location on hotel performance. Regarding management practices, the performance is positively affected by good asset management.

Practical implications

Hotel managers can improve the total net revenue per available room by individually making decisions regarding its characteristics and management practices, especially size and asset efficiency. Moreover, they can collaborate with others (managers and policymakers) to manage tourist destination factors, particularly, demand level, accessibility, negative externalities and market concentration.

Originality/value

This research includes hotel characteristics, management practices and location as determinants of performance, by providing a broader framework of analysis than in previous studies. Regarding location, the empirical analysis considers simultaneously geographical location models, agglomeration models and competition models. The paper studies the Spanish hotel market, which is very important worldwide and which has heterogeneous tourist destinations, thereby making it a good context to analyse the relationship between location and performance.