bluuebunny/crossref_metadata_2025 huggingface dataset:
Detrital zircon U–Pb geochronology of a Cenozoic foreland basin in Northeast India: Implications for zircon provenance during the collision of the Indian and Asian plates
Authors: Baral Upendra , Lin Ding , Goswami Tapos Kumar , Sarma Mondip , Qasim Muhammad , Bezbaruah Devojit
Published: October 2018

Geochronology is useful for understanding provenance, and while it has been applied to the central and western Himalaya, very little data are available in the eastern Himalaya. This study presents detrital zircon U–Pb ages from the late Palaeocene–Eocene Yinkiong Group in NE India. The samples are from the late Palaeocene to early Eocene Lower Yinkiong Formation, and the Upper Yinkiong Formation deposited during the early to mid‐Eocene within the Himalayan foreland basin. The U–Pb ages of the detrital zircon within the Lower Yinkiong Formation are older than late Palaeozoic, with a cratonic and early Himalayan Thrust Belt affinity, whereas the Cenozoic grains in the Upper Yinkiong Formation indicate a Himalayan Thrust Belt source and possibly a granitic body within the Asian plate. The shift of the sources and the changes in the foreland basin system strongly suggest that the India–Asia collision in the Eastern Himalaya began before or immediately after the deposition of the Upper Yinkiong Formation, i.e., within the early Eocene (c. 56 to 50 Ma).
Lysosome: The metabolic signaling hub
Authors: Lamming Dudley W. , Bar‐Peled Liron
Published: October 2018

For the past five decades, the lysosome has been characterized as an unglamorous cellular recycling center. This notion has undergone a radical shift in the last 10 years, with new research revealing that this organelle serves as a major hub for metabolic signaling pathways. The discovery that master growth regulators, including the protein kinase mTOR (mechanistic target of rapamycin), make their home at the lysosomal surface has generated intense interest in the lysosome's key role in nutrient sensing and cellular homeostasis. The transcriptional networks required for lysosomal maintenance and function are just being unraveled and their connection to lysosome‐based signaling pathways revealed. The catabolic and anabolic pathways that converge on the lysosome connect this organelle with multiple facets of cellular function; when these pathways are deregulated they underlie multiple human diseases, and promote cellular and organismal aging. Thus, understanding how lysosome‐based signaling pathways function will not only illuminate the fascinating biology of this organelle but will also be critical in unlocking its therapeutic potentials.
Automated thawing increases recovery of colony‐forming units from banked cord blood unit grafts
Authors: Muñiz Alers Saisha M. , Page Kristin , Simmons Ryan , Waters‐Pick Barbara , Cheatham Lynn , Troy Jesse D. , Kurtzberg Joanne
Published: October 2018

BACKGROUND

The cell dose infused for cord blood transplantation strongly correlates with outcomes following transplantation. Post thaw recoveries can be improved by washing cord blood units (CBUs) in dextran/albumin. Early methods used a labor‐intensive manual process. We have recently developed and validated an automated washing method. We now report our results of a study comparing cellular recoveries achieved after manual and automated wash, as well as the impact on engraftment following allogeneic transplantation.

STUDY DESIGN AND METHODS

CBUs distributed by the Carolinas Cord Blood Bank for clinical use at Duke University after manual or automated wash were included in this report. Precryopreservation total nucleated cell count, total CD34+, colony‐forming units, recoveries, and sterility were analyzed by wash method. Patient age, cell dose/weight, diagnosis, conditioning regimen, immunosuppression, and time to neutrophil engraftment were also analyzed.

RESULTS

Manual and automated washed CBUs yielded similar total nucleated cell count and total CD34+ recoveries. Significantly higher colony‐forming units recoveries were achieved after automated washing. Patients who received CBUs washed via an automated method experienced earlier neutrophil engraftment.

CONCLUSION

While manual and automated washing achieved similar post thaw cellular recoveries, automated washed CBUs demonstrated higher colony‐forming unit recovery, which is an important predictor of potency and engraftment. Furthermore, we demonstrated that automated washing was associated with earlier neutrophil engraftment. Our findings favor the use of an automated wash method over a manual approach.
The Impact of Aligning the Strategies of CREM with Those of a Corporate Business Using Real Options
Authors: Makaringi Singita , Mokoka Khabane , Schmidt Jake
Published: October 2018

The article investigates the benefits of incorporating corporate real estate management (CREM) in the main business units of the company. Prior studies have illustrated that CREM unit in major companies is treated as a separately entity with less focus on its contribution to maximization of shareholders’ wealth. This article uses real option approach, specifically Samuelson-McKean (1965) model to extrapolate the value of CREM of listed South African insurance company. The results show that when CREM is insourced and treated as a significant part of the main insurance, shareholders’ wealth is maximised-value of the company increases, total costs are managed and financial parameters increase investment value-volatility can be as high as 100%. Although, the data is on financial services, the results can be replicated in other industries given that the analysed company has exposure to a number of industries.
Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches
Authors: Bardsley E. N. , Paterson D. J.
Published: October 2018

Cardiac sympathetic overactivity is a well‐established contributor to the progression of neurogenic hypertension and heart failure, yet the underlying pathophysiology remains unclear. Recent studies have highlighted the importance of acutely regulated cyclic nucleotides and their effectors in the control of intracellular calcium and exocytosis. Emerging evidence now suggests that a significant component of sympathetic overactivity and enhanced transmission may arise from impaired cyclic nucleotide signalling, resulting from compromised phosphodiesterase activity, as well as alterations in receptor‐coupled G‐protein activation. In this review, we address some of the key cellular and molecular pathways that contribute to sympathetic overactivity in hypertension and discuss their potential for therapeutic targeting.
Measurements of two-dimensional spatial coherence of normal-incidence seafloor scattering
Authors: Brown Daniel C. , Brownstead Cale F. , Lyons Anthony P. , Gabrielson Thomas B.
Published: October 2018

Measurements have been made near normal incidence of the two-dimensional spatial coherence of the acoustic field scattered from the lakebed in Seneca Lake, New York. In the test region, the lakebed consists of a series of sediment layers created by a sequence of distinct depositional processes. The spatial coherence length of the scattered field is shown to be dependent on the structure of the underlying sediment sequences. Significant ping-to-ping variability in the spatial coherence surface was also observed for each sediment sequence. This variability is quantified by a two-dimensional spatial coherence metric that measures the coherence lengths and asymmetric coherence surface orientation. The ping-to-ping variation of the surface asymmetry appears to be linked to the spatial isotropy of the sediment scattering strength. The scattering strength of the deepest observed sequence in the sub-bottom is the most spatially isotropic and the ping-to-ping variability of the coherence lengths and surface orientations are random. The scattering strength of the shallower sequences is spatially anisotropic and the coherence lengths and surface orientations show intervals of non-random ping-to-ping behavior.
Utility of Activity Monitors and Thermometry in Assessing Sleep Stages and Sleep Quality
Authors: Swalve Natashia , Harfmann Brianna , Mitrzyk John , Montoye Alexander H. K.
Published: October 2018

Activity monitors provide an inexpensive and convenient way to measure sleep, yet relatively few studies have been conducted to validate the use of these devices in examining measures of sleep quality or sleep stages and if other measures, such as thermometry, could inform their accuracy. The purpose of this study was to compare one research-grade and four consumer-grade activity monitors on measures of sleep quality (sleep efficiency, sleep onset latency, and wake after sleep onset) and sleep stages (awake, sleep, light, deep, REM) against an electroencephalography criterion. The use of a skin temperature device was also explored to ascertain whether skin temperature monitoring may provide additional data to increase the accuracy of sleep determination. Twenty adults stayed overnight in a sleep laboratory during which sleep was assessed using electroencephalography and compared to data concurrently collected by five activity monitors (research-grade: ActiGraph GT9X Link; consumer-grade: Fitbit Charge HR, Fitbit Flex, Jawbone UP4, Misfit Flash) and a skin temperature sensor (iButton). The majority of the consumer-grade devices overestimated total sleep time and sleep efficiency while underestimating sleep onset latency, wake after sleep onset, and number of awakenings during the night, with similar results being seen in the research-grade device. The Jawbone UP4 performed better than both the consumer- and research-grade devices, having high levels of agreement overall and in epoch-by-epoch sleep stage data. Changes in temperature were moderately correlated with sleep stages, suggesting that addition of skin temperature could increase the validity of activity monitors in sleep measurement.
Relationships Between Outdoor Time, Physical Activity, Sedentary Time, and Body Mass Index in Children: A 12-Country Study
Authors: Larouche Richard , Mire Emily F. , Belanger Kevin , Barreira Tiago V. , Chaput Jean-Philippe , Fogelholm Mikael , Hu Gang , Lambert Estelle V. , Maher Carol , Maia José , Olds Tim , Onywera Vincent , Sarmiento Olga L. , Standage Martyn , Tudor-Locke Catrine , Katzmarzyk Peter T. , Tremblay Mark S. , _ _
Published: October 2018

Purpose: This study investigated the relationship between outdoor time and physical activity (PA), sedentary time (SED), and body mass index z scores among children from 12 lower-middle-income, upper-middle-income, and high-income countries. Methods: In total, 6478 children (54.4% girls) aged 9–11 years participated. Outdoor time was self-reported, PA and SED were assessed with ActiGraph GT3X+ accelerometers, and height and weight were measured. Data on parental education, neighborhood collective efficacy, and accessibility to neighborhood recreation facilities were collected from parent questionnaires. Country latitude and climate statistics were collected through national weather data sources. Gender-stratified multilevel models with parental education, climate, and neighborhood variables as covariates were used to examine the relationship between outdoor time, accelerometry measures, and body mass index z scores. Results: Each additional hour per day spent outdoors was associated with higher moderate- to vigorous-intensity PA (boys: +2.8 min/d; girls: +1.4 min/d), higher light-intensity PA (boys: +2.0 min/d; girls: +2.3 min/d), and lower SED (boys: −6.3 min/d; girls: −5.1 min/d). Effect sizes were generally weaker in lower-middle-income countries. Outdoor time was not associated with body mass index z scores. Conclusions: Outdoor time was associated with higher PA and lower SED independent of climate, parental education, and neighborhood variables, but effect sizes were small. However, more research is needed in low- and middle-income countries.
T
reg
cells—the next frontier of cell therapy
Authors: Bluestone Jeffrey A. , Tang Qizhi
Published: October 2018

Will regulatory T cells be a frontline therapy for autoimmunity and other diseases?
Building blocks of the human brain
Authors: Nowakowski Tomasz Jan
Published: October 2018

Area-specific excitatory neuron subtypes emerge before sensory experience
Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-Resistant Pseudomonas aeruginosa Infection
Authors: Kang Hee Kyoung , Seo Chang Ho , Luchian Tudor , Park Yoonkyung
Published: October 2018

Pseudin-2, isolated from the frog
Pseudis paradoxa
, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable antimicrobial peptides (AMPs), we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity.
Method-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in
Candida
and
Aspergillus
Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion Methods
Authors: Espinel-Ingroff A. , Turnidge J. , Alastruey-Izquierdo A. , Botterel F. , Canton E. , Castro C. , Chen Y.-C. , Chen Y. , Chryssanthou E. , Dannaoui E. , Garcia-Effron G. , Gonzalez G. M. , Govender N. P. , Guinea J. , Kidd S. , Lackner M. , Lass-Flörl C. , Linares-Sicilia M. J. , López-Soria L. , Magobo R. , Pelaez T. , Quindós G. , Rodriguez-Iglesia M. A. , Ruiz M. A. , Sánchez-Reus F. , Sanguinetti M. , Shields R. , Szweda P. , Tortorano A. , Wengenack N. L. , Bramati S. , Cavanna C. , DeLuca C. , Gelmi M. , Grancini A. , Lombardi G. , Meletiadis J. , Negri C. E. , Passera M. , Peman J. , Prigitano A. , Sala E. , Tejada M.
Published: October 2018

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of
Candida
or
Aspergillus
species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171
Candida albicans
, 215 
C. dubliniensis
, 4,418 
C. glabrata
species complex, 157 
C.
guilliermondii
(
Meyerozyma guilliermondii
), 676 
C. krusei
(
Pichia kudriavzevii
), 298 
C.
lusitaniae
(
Clavispora lusitaniae
), 911 
C.
parapsilosis
sensu stricto
, 3,691 
C.
parapsilosis
species complex, 36 
C.
metapsilosis
, 110 
C.
orthopsilosis
, 1,854 
C.
tropicalis
, 244
Saccharomyces cerevisiae
, 1,409
Aspergillus fumigatus
, 389 
A.
flavus
, 130 
A.
nidulans
, 233 
A.
niger
, and 302 
A.
terreus
complex isolates.
P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1β in a Human Tonsil Explant Model
Authors: Soare Alexandra Y. , Durham Natasha D. , Gopal Ramya , Tweel Benjamin , Hoffman Kevin W. , Brown Julia A. , O’Brien Megan , Bhardwaj Nina , Lim Jean K. , Chen Benjamin K. , Swartz Talia H.
Published: October 2018

Patients who are chronically infected with HIV-1 experience sequelae related to chronic inflammation. The mechanisms of this inflammation have not been elucidated. Here, we describe a class of drugs that target the P2X proinflammatory signaling receptors in a human tonsil explant model. This model highlights differences in HIV-1 stimulation of lymphoid tissue inflammation and peripheral blood. These drugs serve to block both HIV-1 infection and production of IL-10 and IL-1β in lymphoid tissue, suggesting a novel approach to HIV-1 therapeutics in which both HIV-1 replication and inflammatory signaling are simultaneously targeted.
A 1,000-Year-Old RNA Virus
Authors: Peyambari Mahtab , Warner Sylvia , Stoler Nicholas , Rainer Drew , Roossinck Marilyn J.
Published: October 2018

A virus related to plant chrysoviruses was found in numerous ancient samples of maize, with nearly complete genomes in three samples. The age of the ancient samples (i.e., about 1,000 years old) was confirmed by carbon dating. Chrysoviruses are persistent plant viruses. They infect their hosts from generation to generation by transmission through seeds and can remain in their hosts for very long time periods. When modern corn samples were analyzed, a closely related chrysovirus was found with only about 3% divergence from the ancient sequences. This virus represents the oldest known plant virus.
The Interaction between ORF18 and ORF30 Is Required for Late Gene Expression in Kaposi's Sarcoma-Associated Herpesvirus
Authors: Castañeda Angelica F. , Glaunsinger Britt A.
Published: October 2018

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma and other B-cell cancers and remains a leading cause of death in immunocompromised individuals. A key step in the production of infectious virions is the transcription of viral late genes, which generates capsid and structural proteins and requires the coordination of six viral proteins that form a complex. The role of these proteins during transcription complex formation and the importance of protein-protein interactions are not well understood. Here, we focused on a central component of the complex, ORF18, and revealed that disruption of its interaction with even a single component of the complex (ORF30) prevents late gene expression and completion of the viral lifecycle. These findings underscore how individual interactions between the late gene transcription components are critical for both the stability and function of the complex.
Undernutrition, obesity and governance: a unified framework for upholding the right to food
Authors: Bump Jesse B
Published: October 2018

This paper addresses the need for conceptual and analytic clarity on nutrition governance, an essential underpinning of more effective approaches for undernutrition, the ‘single greatest constraint to global development' and obesity, which already accounts for 4% of the world’s disease burden and is growing rapidly.

The governance of nutrition, which is essential to designing and implementing policies to realise the right to food, is among the most important and most defining duties of society. But research and action on nutrition governance are hampered by the absence of conceptual rigour, even as the continuing very high burden of undernutrition and the rapid rise in obesity highlight the need for such structures. The breadth of nutrition itself suggests that governance is both needed and sure to be complicated.

This analysis explores the reasons attention has come to governance in development policy making, and why it has focused on nutrition governance in particular. It then assesses how the concept of nutrition governance has been used, finding that it has become increasingly prominent in scholarship on poor nutritional outcomes, but remains weakly specified and is invoked by different authors to mean different things. Undernutrition analysts have stressed coordination problems and structural issues related to the general functioning of government. Those studying obesity have emphasised international trade policies, regulatory issues and corporate behaviour.

This paper argues that the lack of a clear, operational definition of governance is a serious obstacle to conceptualising and solving major problems in nutrition. To address this need, it develops a unified definition of nutrition governance consisting of three principles: accountability, participation and responsiveness. These are justified with reference to the social contract that defines modern nations and identifies citizens as the ultimate source of national power and legitimacy. A unified framework is then employed to explore solutions to nutrition governance problems.
Cohort Study of Pulmonary Tuberculosis (COSMOTB) identifying drug-resistant mutations: protocol for a prospective observational study in Korea
Authors: Min Jinsoo , Chung Chaeuk , Lim Jinsook , Park Jong Hyock , Shin Kyeong Seob , Jung Sung-Soo , Lee Ki Man
Published: October 2018

Introduction

Drug-resistant tuberculosis (TB) is a global concern. The proper diagnosis and management of drug-resistant TB are critical for improving treatment outcome. Molecular-based genotypic drug-susceptibility testing (DST) was developed to identify drug-resistant TB; however, discordant results from phenotypic and genotypic DST analyses have alarmed clinicians and raised concerns about the test’s utility. Moreover, the characteristics of disputed mutations are not well studied and only based on retrospective study findings.

Methods and analysis

We describe a 28-month prospective observational cohort study ongoing at two university-affiliated hospitals in South Korea. The cohort study will enrol and evaluate 600 adults with pulmonary TB. Relevant clinical and epidemiological data will be collected prospectively and participants will be evaluated at each hospital during anti-TB treatment to identify factors associated with TB treatment outcomes. Respiratory specimens will be collected at select visits. After generating a well-characterised cohort, patterns of drug resistance on both phenotypic and genotypic DSTs and associated mutations including the disputed mutation will be evaluated. We will also identify various clinical and socioeconomic factors that affect the causes of drug resistance and their clinical outcomes.

Ethics and dissemination

The study protocol is approved by the Institutional Review Boards of Chungbuk National University Hospital and Chungnam National University Hospital. Study results will be disseminated through peer-reviewed journals and conference presentations.

Trial registration number

KCT0002594.
Detection and treatment initiation for depression and alcohol use disorders: facility-based cross-sectional studies in five low-income and middle-income country districts
Authors: Rathod Sujit D , Roberts Tessa , Medhin Girmay , Murhar Vaibhav , Samudre Sandesh , Luitel Nagendra P , Selohilwe One , Ssebunnya Joshua , Jordans Mark J D , Bhana Arvin , Petersen Inge , Kigozi Fred , Nakku Juliet , Lund Crick , Fekadu Abebaw , Shidhaye Rahul
Published: October 2018

Objectives

To estimate the proportion of adult primary care outpatients who are clinically detected and initiate treatment for depression and alcohol use disorder (AUD) in low-income and middle-income country (LMIC) settings.

Design

Five cross-sectional studies.

Setting

Adult outpatient services in 36 primary healthcare facilities in Sodo District, Ethiopia (9 facilities); Sehore District, India (3); Chitwan District, Nepal (8); Dr Kenneth Kaunda District, South Africa (3); and Kamuli District, Uganda (13).

Participants

Between 760 and 1893 adults were screened in each district. Across five districts, between 4.2% and 20.1% screened positive for depression and between 1.2% and 16.4% screened positive for AUD. 96% of screen-positive participants provided details about their clinical consultations that day.

Primary outcomes

Detection of depression, treatment initiation for depression, detection of AUD and treatment initiation for AUD.

Results

Among depression screen-positive participants, clinical detection of depression ranged from 0% in India to 11.7% in Nepal. Small proportions of screen-positive participants received treatment (0% in Ethiopia, India and South Africa to 4.2% in Uganda). Among AUD screen-positive participants, clinical detection of AUD ranged from 0% in Ethiopia and India to 7.8% in Nepal. Treatment was 0% in all countries aside Nepal, where it was 2.2%.

Conclusions

The findings of this study suggest large detection and treatment gaps for adult primary care patients, which are likely contributors to the population-level mental health treatment gap in LMIC. Primary care facilities remain unfulfilled intervention points for reducing the population-level burden of disease in LMIC.
Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (The GerMoT study)
Authors: Ekdahl Anne Wissendorff , Axmon Anna , Sandberg Magnus , Steen Carlsson Katarina
Published: October 2018

Introduction

Comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary diagnostic process used to determine the medical, psychological and functional capabilities of frail older people. The primary aim of our current study is to confirm whether CGA-based outpatient care is superior than usual care in terms of health-related outcomes, resource use and costs.

Methods and analysis

The Geriatric Mobile Team trial is designed as a single-centre randomised, controlled, assessor-blinded (at baseline) trial. All participants will be identified via local healthcare registries with the following inclusion criteria: age ≥75 years, ≥3 different diagnoses and ≥3 visits to the emergency care unit (with or without admittance to hospital) during the past 18 months. Nursing home residency will be an exclusion criterion. Baseline assessments will be done before the 1:1 randomisation. Participants in the intervention group will, after an initial CGA, have access to care given by a geriatric team in addition to usual care. The control group receives usual care only. The primary outcome is the total number of inpatient days during the follow-up period. Assessments of the outcomes: mortality, quality of life, health care use, physical functional level, frailty, dependence and cognition will be performed 12 and 24 months after inclusion. Both descriptive and analytical statistics will be used, in order to compare groups and for analyses of outcomes over time including changes therein. The primary outcome will be analysed using analysis of variance, including in-transformed values if needed to achieve normal distribution of the residuals.

Ethics and dissemination

Ethical approval has been obtained and the results will be disseminated in national and international journals and to health care leaders and stakeholders. Protocol amendments will be published in ClinicalTrials.gov as amendments to the initial registrationNCT02923843. In case of success, the study will promote the implementation of CGA in outpatient care settings and thereby contribute to an improved care of older people with multimorbidity through dissemination of the results through scientific articles, information to politicians and to the public.

Trial registration number

NCT02923843; Pre-results.
Initial treatment of steroid-sensitive idiopathic nephrotic syndrome in children with mycophenolate mofetilversusprednisone: protocol for a randomised, controlled, multicentre trial (INTENT study)
Authors: Ehren Rasmus , Benz Marcus R , Doetsch Jorg , Fichtner Alexander , Gellermann Jutta , Haffner Dieter , Höcker Britta , Hoyer Peter F , Kästner Bärbel , Kemper Markus J , Konrad Martin , Luntz Steffen , Querfeld Uwe , Sander Anja , Toenshoff Burkhard , Weber Lutz T
Published: October 2018

Introduction

Idiopathic nephrotic syndrome is the most common glomerular disease in childhood with an incidence of 1.8 cases per 100 000 children in Germany. The treatment of the first episode implies two aspects: induction of remission and sustainment of remission. The recent Kidney Disease Improving Global Outcomes, American Academy of Pediatrics and German guidelines for the initial treatment of the first episode of a nephrotic syndrome recommend a 12-week course of prednisone. Despite being effective, this treatment is associated with pronounced glucocorticoid-associated toxicity due to high-dose prednisone administration over a prolonged period of time. The aim of the INTENT study (Initial treatment of steroid-sensitive idiopathic nephrotic syndrom in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial) is to show that an alternative treatment regimen with mycophenolic acid is not inferior regarding sustainment of remission, but with lower toxicity compared with treatment with glucocorticoids only.

Methods and design

The study is designed as an open, randomised, controlled, multicentre trial. 340 children with a first episode of steroid-sensitive nephrotic syndrome and who achieved remission by a standard prednisone regimen will be enrolled in the trial and randomised to one of two treatment arms. The standard care group will be treated with prednisone for a total of 12 weeks; in the experimental group the treatment is switched to mycophenolate mofetil, also for a total of 12 weeks in treatment duration. The primary endpoint is the occurrence of a treated relapse within 24 months after completion of initial treatment.

Ethics and dissemination

Ethics approval for this trial was granted by the ethics committee of the Medical Faculty of the University of Heidelberg (AFmu-554/2014). The study results will be published in accordance with the Consolidated Standards of Reporting Trials statement and the Standard Protocol Items: Recommendations for Interventional Trials guidelines. Our findings will be submitted to major international paediatric nephrology and general paediatric conferences and submitted for publication in a peer-reviewed, open-access journal.

Trial registration number

DRKS0006547; EudraCT2014-001991-76; Pre-result.

Date of registration

30 October 2014; 24 February 2017.
Economic burden of hospitalisation for congestive heart failure among adults in the Philippines
Authors: Tumanan-Mendoza Bernadette A , Mendoza Victor L , Bermudez-Delos Santos April Ann A , Punzalan Felix Eduardo R , Pestano Noemi S , Natividad Rudy Boy , Shiu Louie Alfred , Macabeo Renelene , Lam Hilton Y
Published: October 2018

Objectives

Hospitalisation for congestive heart failure (CHF) was reported to be 1648 cases for every 100 000 patient claims in 2014 in the Philippines; however, there are no data regarding its economic impact. This study determined CHF hospitalisation cost and its total economic burden. It compared the healthcare-related hospitalisation cost from the societal perspective with the payer’s perspective, the Philippine Health Insurance Corporation (PhilHealth).

Methods

This is a cost analysis study. Data were obtained from representative government/private hospitals and a drugstore in all regions of the country. Healthcare costs included cost of diagnostics/treatment, professional fees and other CHF-related hospital charges, while non-healthcare costs included production losses, transportation and food expenses.

Results

The overall mean healthcare-related cost for CHF hospitalisation (class III) in government hospitals in the Philippines in 2014 was PHP19 340–PHP28 220 (US$436–US$636). In private hospitals, it was PHP28 370–PHP41 800 (US$639–US$941). In comparison, PhilHealth’s coverage/CHF case rate payment is PHP15 700 (US$354). The mean non-healthcare cost was PHP10 700–PHP14 600 (US$241–US$329). Using PhilHealth’s case rate payment and the prevalence of CHF hospitalisation in 2014, the total economic burden was PHP691 522 200 (US$15 574 824). Using the study results on healthcare-related cost meant that the total economic burden for CHF hospitalisation would instead be PHP851 850 000–PHP1 841 563 000 (US$19 185 811–US$41 476 644).

Conclusions

The calculated healthcare-related hospitalisation cost for CHF in the Philippines in 2014 demonstrates the disparity between the actual cost and PhilHealth’s coverage. This implies a need for policymakers to review its coverage to make healthcare delivery affordable.
Physicians as leaders: are we trying to fit square pegs into round holes?
Authors: Montgomery Anthony
Published: October 2018

The purpose of medical education has changed over the last 70 years. The modern doctor is expected to be a leader who will be skilled in people management, team working and patient engagement. Moreover, the burgeoning literature on the development of medical leadership competency frameworks as a way to inform curriculum development is evidence of a desire to empower physicians to be healthcare leaders. The movement towards developing medical students as leaders has to be contrasted against the fact that high school exam performance and academic achievement continues to be the primary basis for selection to medical school. Not surprisingly, the smart kids are studying medicine. Unfortunately, there is a person–job mismatch between the initial skills that allows an individual entry to medical school and what the job will actually entail. For example, higher levels of intelligence are associated with less effective leadership styles. Thus, we seem to have a conundrum concerning input and output. In the following paper, I will examine the degree to which we are attempting to remould ‘square’ physicians to fit them into a ‘round’ medical landscape. The purpose of the paper is twofold. First, to assess the degree to which we can realistically expect the ‘average’ medical student to be moulded into a leader, and second, to identify what practical steps we can take to enable medical students to take a leadership role.
Physical activity for brain health in older adults
Authors: Liu-Ambrose Teresa , Barha Cindy K. , Best John R.
Published: October 2018

Physical activity is a promising strategy for dementia prevention and disease modification. Here, we provide a narrative review of the current evidence from epidemiological and intervention studies on the role of physical activity and exercise in promoting cognitive health in older adults both without and with cognitive impairment. We highlight some of the potential underlying mechanisms and discuss biological sex as a potential moderating factor. We conclude with limitations and future directions for this rapidly expanding line of research.
State of practice for use of the soil-water characteristic curve (SWCC) in geotechnical engineering
Authors: Fredlund Delwyn G.
Published: October 2018

Routine geotechnical engineering practice has witnessed a significant increase in the usage of unsaturated soil mechanics principles. Laboratory measurement of the soil-water characteristic curve (SWCC) for a soil has been labelled as a primary reason for the improved understanding of unsaturated soil behaviour. Laboratory measurement of the “shrinkage curve” has yielded further insight into the estimation of unsaturated soil property functions (USPFs). The USPFs provide the necessary information for the simultaneous numerical modeling of the saturated and unsaturated portions of the soil profile. This paper presents a state-of-practice summary of the engineering protocols that have emerged amidst the numerous research studies reported over the past couple of decades. It also introduces issues related to hysteresis associated with the SWCC and suggests a pathway forward.
Preparation of yolk–shell structured Ag@Cu particles and their application in high performance electrochemical sensing of p-aminobenzoic acid
Authors: Gan Tian , Wang Zhikai , Chen Mengru , Fu Wanqiu , Wang Haibo , Sun Junyong
Published: October 2018

In this work, the Ag@Cu particles with yolk–shell nanostructure was prepared by facile solvothermal method, which was modified on glassy carbon electrode (GCE) to fabricate electrochemical sensor for the convenient and fast determination of p-aminobenzoic acid (PABA). The surface morphology and electrochemical properties of the as-prepared Ag@Cu nanocomposite modified electrode were characterized by scanning electron microscopy, transmission electron microscopy, chronocoulometry, and electrochemical impedance spectroscopy. Further, the electrochemical sensing of PABA was performed on the Ag@Cu/GCE using cyclic voltammetry and differential pulse voltammetry techniques, showing high catalytic activity. Under the optimal conditions, the sensor exhibited a wide linear range, high sensitivity, and low detection limit of 0.315 μmol/L for PABA. The developed sensor was also successfully applied for PABA detection in anesthetic and cosmetics with satisfactory results.
Testing merging of dark exotic stars from gravitational waves in the multi-messenger approach
Authors: Addazi Andrea , Marciano Antonino
Published: October 2018

We discuss possible implications of the recent detection by the LIGO and VIRGO collaboration of the gravitational-wave event GW170817, the signal of which is consistent with predictions in general relativity on the merging of neutron stars. A near-simultaneous and spatially correlated observation of a gamma-ray burst, the GRB 170817A signal, was achieved independently by the Fermi Gamma-ray Burst Monitor, and by the Anti-coincidence Shield for the Spectrometer of the International Gamma-Ray Astrophysics Laboratory. Motivated by this near temporal and spatial concomitance of events, which can occur by chance only with the probability [Formula: see text], we speculate on the possibility that new dark stars signals could be detected from the LIGO/VIRGO detectors. This proposal, which aims at providing a test for some models of dark matter, relies on the recent achievement of detecting, for visible ordinary matter, the merging of neutron stars both in the gravitational and the electromagnetic channel. A lack of correlation between the two expected signals would suggest a deviation from the properties of ordinary matter. Specifically, we focus on models of invisible dark matter, and in particular we study the case of mirror dark matter, within the framework of which a large amount of mirror neutron stars are naturally envisaged to occupy our dark matter halo. The observation of an electromagnetically hidden event inside the dark matter halo of our galaxy should provide a hint of new physics. There would be indeed no satisfactorily complete explanation accounting for the lack of electromagnetic signal, if only standard neutron star merging were considered to describe events that happen so close to us.
Structural, electronic and magnetic properties of small FemVn (m + n ≤ 6) clusters: First-principles calculation
Authors: Shan R. , Lv Jin , Wu H. S.
Published: October 2018

In this paper, the structural, electronic and magnetic properties of small Fe[Formula: see text]V[Formula: see text] (m+n [Formula: see text] 6) clusters have been investigated systematically within the framework of the generalized gradient approximation density-functional theory. The results indicate that the low lying isomers of Fe[Formula: see text]V[Formula: see text] alloy clusters all present the classical closely packed geometries with different chemical order when m + n [Formula: see text] 4; the ground state structures prefer to form the Fe–V as much as possible in small proportion V doping. The binding energy of Fe[Formula: see text]V[Formula: see text] clusters always increases with the successive V substitution. The V atom mono-doped and bi-doped make the magnetism of Fe[Formula: see text] clusters decrease 7 [Formula: see text], respectively. With V atom doping increasing, the magnetism presents an overall decreased tendency. The magnetic order bewteen Fe and V atoms undergoes a transition from antiferromagnetic coupling in Fe-rich clusters to the coexistence of antiferromagnetic and ferromagnetic couplings in V-rich clusters, and the atom net charge usually transfer from V to Fe atom in Fe[Formula: see text]V[Formula: see text] alloy clusters.
Getting There
Authors: Dillahunt Tawanna R. , Veinot Tiffany C.
Published: October 2018

Advances in Information and Communication Technologies (ICTs) offer new opportunities for addressing transportation needs; however, past research suggests that opportunities are not equally shared by millions of low-income Americans. We draw from four empirical studies and two case studies to contribute descriptions of the 11 everyday transportation models currently used by residents of low-income and underserved communities to enhance their access to health-enhancing resources. These models fell into personal, private, public, and interpersonal categories. We contribute insights regarding the following barriers and facilitators associated with these models: (1) affordability; (2) individual capabilities; (3) interpersonal trust, care and/or reciprocity; (4) trust in technology; (5) service availability/eligibility; (6) spatial and temporal matches; (7) match between transportation mode and physical needs; (8) service reliability and quality; and (9) infrastructure access. To address these barriers and build on these facilitators, we contribute six supportive policy and design principles. Operationalizing these principles, we propose four new ICT-enhanced models: (1) smart jitneys; (2) generalized, favor-based models; (3) expanded resource pooling; and (4) transportation clubs. The focus of these models on socio-technical integration with current capabilities and resources holds promise for enhancing access to jobs, food, and health care for residents of low-income communities.
IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-γ/IRF-1 pathway
Authors: Klune John R. , Bartels Christian , Luo Jing , Yokota Shinichiro , Du Qiang , Geller David A.
Published: October 2018

Interleukin-23 (IL-23) is a proinflammatory cytokine initially studied in autoimmune disease that has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in a hepatocyte and nonparenchymal cell (NPC) coculture system, as well as during ischemia-reperfusion (I/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I/R injury. We observed that IL-23 signaling induces not only the IL-17/chemokine (C-X-C motif) ligand 2 (CXCL2) pathway but also the IFN-γ/IRF-1 pathway. Quantification of cytokine genes revealed increased liver expression of IL-17a, CXCL2, and IRF-1 messenger RNA during liver transplantation. Recombinant IL-23 treated hepatocytes, and NPC coculture led to IL-17, CXCL2, IFN-γ, and IRF-1 expression. With anti-IL-17 and anti-Ly6G antibody neutralization, neutrophil recruitment and IFN-γ production were decreased during warm I/R injury. Overexpression of IL-23 in vivo through use of an adenovirus vector also led to expression of IL-17, CXCL2, IFN-γ, and IRF-1. The increased expression of IL-23 also led to increased apoptosis in the liver. By neutralization of IL-23 through use of an anti-IL-23p19 antibody, we were able to attenuate liver damage in a wild-type but not a natural killer T (NKT) cell-deficient mouse. This suggests that IL-23 signaling shares a common pathway with NKT cells. In conclusion, IL-23 is induced early by I/R in the liver. Its signaling leads to activation of the IL-17/CXCL2 and IFN-γ/IRF-1 pathways, resulting in increased apoptosis and necrosis.

NEW & NOTEWORTHY IL-23 is expressed early during cold ischemia-reperfusion (I/R), and this expression is associated with expression of IL-17 and chemokine (C-X-C motif) ligand 2. Neutralization of IL-23 during cold I/R can significantly reduce liver damage as well as decrease cytokine production and neutrophil infiltration in the liver. IL-23 appears to activate IFN-γ production in natural killer T cells within the liver which, in turn, activates interferon regulatory factor-1, a known inflammatory transcription factor during I/R injury.
Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study
Authors: Fontolliet Timothée , Pichot Vincent , Bringard Aurélien , Fagoni Nazzareno , Adami Alessandra , Tam Enrico , Furlan Raffaello , Barthélémy Jean-Claude , Ferretti Guido
Published: October 2018

We performed the first analysis of heart rate variability (HRV) at rest and during exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that between rest and exercise there would be 1) no differences in total power (PTOT) under parasympathetic blockade, 2) a PTOT fall under β1-sympathetic blockade, and 3) no differences in PTOT under blockade of both autonomic nervous system branches. Seven men [24 (3) yr, mean (SD)] performed 5-min cycling (80 W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol, and atropine + metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity was determined by the sequence method. At rest, PTOT and the powers of low- and high-frequency components of HRV (LF and HF, respectively) were dramatically decreased with atropine and double blockade compared with control and metoprolol, with no effects on LF-to-HF ratio and on the normalized LF (LFnu) and HF (HFnu). During exercise, patterns were the same as at rest. Comparing exercise with rest, PTOT varied as hypothesized. For systolic and diastolic blood pressure, resting PTOT was the same in all conditions. During exercise, in all conditions, PTOT was lower than in control. Baroreflex sensitivity decreased under atropine and double blockade at rest and under control and metoprolol during exercise. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise.

NEW & NOTEWORTHY This study provides the first demonstration, by systematic analysis of heart rate variability at rest and during exercise under full autonomic blockade on the same subjects, that suppression of vagal activity is responsible for the disappearance of spontaneous heart rate variability during exercise. This finding supports previous hypotheses on the role of vagal withdrawal in the control of the rapid cardiovascular response at exercise onset.
Palliative Care in Congenital Syndrome of the Zika Virus Associated with Hospitalization and Emergency Consultation: Palliative Care and Congenital Syndrome of Zika
Authors: Rocha Aline Maria de Oliveira , Mello Maria Julia Gonçalves de , Torres Juliane Roberta Dias , Valença Natalia de Oliveira , Maia Alessandra Costa de Azevedo , Cavalcanti Nara Vasconcelos
Published: October 2018

Background. Congenital syndrome of Zika virus (CSZV) is associated with neuromotor and cognitive developmental disorders, limiting the independence and autonomy of affected children and high susceptibility to complications, so palliative care needs to be discussed and applied. Aim. To identify factors associated with emergency visits and hospitalizations of patients with CSZV and clinical interventions performed from the perspective of palliative care. Design. This is a cross-sectional study with bidirectional longitudinal component. Data were collected between May and October 2017 through the review of medical records and interviews with relatives of patients hospitalized. Setting/Participants. The study was developed in a tertiary care hospital involving patients with confirmed CSZV born as of August 2015 and followed up until October 2017. Patients under investigation were excluded. Results. 145 patients were followed up at the specialized outpatient clinic, 92 (63.5%) were consulted at least once in the emergency room, and 49% had already been hospitalized, with the main reason being neurological causes, while 24.1% had never required any emergency visit or hospitalization. No risk factors were associated with the occurrence of consultations or hospitalizations. Such events happened at an early age and were accompanied by a high number of invasive procedures and interventions. An approach in palliative care was only identified in two hospitalized patients. Conclusions. For the patient with known severe malformations caused by congenital infection by the Zika virus with indication of palliative care, this approach could be used in order to allow life without suffering and disproportionate invasive method.