bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic emission source characterisation using evolutionary optimisation
Authors: Worden K. , Spencer A. B. , Packo P. , Staszewski W. J. , Uhl T. , Pierce S. G.
Published: April 2018

When a crack initiates and grows in a metal or composite structure, for example, due to high cycle fatigue, the crack propagation gives rise to acoustic emissions (AE)—ultrasonic waves travelling through the structure. Because the presence and rate of growth of any cracks are important pieces of information about the condition or health of the structure, the monitoring of AE activity using sensors mounted on its surface is a potentially useful technique of structural health monitoring. In tests, acoustic emissions are often simulated by breaking a pencil lead against the surface of the structure in a standardised way (a "Hsu‐Nielsen" source), but the forces that this imparts are not well understood at present. The current paper proposes a new evolutionary optimisation‐based approach to source characterisation. The principle is to introduce a parametrised representation of a general source and then identify the parameters that allow the source to best match responses measured elsewhere on the structure. The predicted responses are modelled using a local interaction simulation approach (LISA) algorithm to simulate the propagation of the ultrasonic waves. The approach is validated here using experiments on AE propagation in thin plate‐like structures, where the ultrasound propagates as Lamb waves. Three separate case studies are proposed here. In the first case, an idealised point source is simulated using laser‐generated ultrasound, and the optimisation algorithm uses a two‐dimensional LISA model. A differential evolution optimisation scheme is used to find the optimal profile of forcing to match the simulation with experiment. In the second case, the two‐dimensional LISA approach is used to characterise the forces associated with standard pencil lead breaks. The final study addresses the full three‐dimensional wave propagation. Because of the computational expense of the latter calculation, the LISA algorithm is implemented using a CUDA graphics card computer system.
Phytolith‐associated potassium in fern: characterization, dissolution properties and implications for slash‐and‐burn agriculture
Authors: Tran C. T. , Mai N. T. , Nguyen V. T. , Nguyen H. X. , Meharg A. , Carey M. , Dultz S. , Marone F. , Cichy S. B. , Nguyen M. N.
Published: April 2018

In recent time, phytoliths (silicon deposition between plant cells) have been recognized as an important nutrient source for crops. The work presented here aims at highlighting the potential of phytolith‐occluded K pool in ferns. Dicranopteris linearis (D. linearis) is a common fern in the humid subtropical and tropical regions. Burning of the fern D. linearis is, in slash‐and‐burn regions, a common practice to prepare the soil before planting. We characterised the phytolith‐rich ash derived from the fern D. linearis and phytolith‐associated potassium (K) (phytK), using X‐ray tomographic microscopy in combination with kinetic batch experiments. D. linearis contains up to 3.9 g K/kg d.wt, including K subcompartmented in phytoliths. X‐ray tomographic microscopy visualized an interembedding structure between organic matter and silica, particularly in leaves. Corelease of K and Si observed in the batch experiments confirmed that the dissolution of ash phytoliths is one of major factors controlling K release. Under heat treatment, a part of the K is made available, while the remainder entrapped into phytoliths (ca. 2.0–3.3%) is unavailable until the phytoliths are dissolved. By enhanced removal of organic phases, or forming more stable silica phases, heat treatment changes dissolution properties of the phytoliths, affecting K release for crops and soils. The maximum releases of soluble K and Si were observed for the phytoliths treated at 500–800 °C. For quantitative approaches for the K provision of plants from the soil phytK pool in soils, factors regulating phytolith dissolution rate have to be considered.
Site visits in interfaith and religious studies pedagogy: Reflections on visiting a Hindu temple in central Pennsylvania
Authors: Long Jeffery D.
Published: April 2018

Site visits provide an irreplaceable learning experience to students in both religious studies and the emerging field of interfaith studies. The conceptual core of this thesis is the claim, drawn from feminist epistemology, that an embodied pedagogy – a pedagogy which engages students not only intellectually, but as embodied beings who inhabit a space, engage in physical activities, and undergo various sensory experiences – is ultimately more enriching than a pedagogy centered exclusively in the classroom. Factors that make a site visit a successful instance of embodied pedagogy include the provision of sufficient context to students in advance for them to understand and appreciate the experience, an opportunity afterward to reflect on this experience in an intentional way, ensuring the site and the community whose space it is are treated with proper respect, and ensuring that the religious sensibilities of one's students are also similarly respected.
Perception, Intuition, and Reliability
Authors: Hauser Kai , Öner Tahsİn
Published: April 2018

The question of how we can know anything about ideal entities to which we do not have access through our senses has been a major concern in the philosophical tradition since Plato'sPhaedo. This article focuses on the paradigmatic case of mathematical knowledge. Following a suggestion by Gödel, we employ concepts and ideas from Husserlian phenomenology to argue that mathematical objects – and ideal entities in general – are recognized in a process very closely related to ordinary perception. Our analysis combines Husserl's insights into the nature of perception and the phenomena of evidence and justification with case studies of the role of intuition in axiomatic set theory.
Absence of interaction between porcine endogenous retrovirus and porcine cytomegalovirus in pig‐to‐baboon renal xenotransplantation in vivo
Authors: Fishman Jay A. , Sachs David H. , Yamada Kazuhiko , Wilkinson Robert A.
Published: April 2018

Background

Studies of xenotransplantation from swine have identified porcine viruses as potential barriers to clinical trials. The biology of these viruses has not been extensively investigated in the in vivo xeno‐environment. Enhancement of viral gene expression by viral and cellular factors acting intranshas been demonstrated for certain viruses, including bidirectional interactions between human herpesviruses and endogenous (HERV) and exogenous (HIV) retroviruses. Both porcine cytomegalovirus (PCMV) and porcine endogenous retrovirus (PERV) infections have been identified in xenografts from swine.PERVreceptors exist on human cells with productive infection in vitro in permissive human target cell lines.PCMVis largely species‐specific with infection restricted to the xenograft in pig‐to‐baboon transplants. It is unknown whether coinfection byPCMVaffects the replication ofPERVwithin xenograft tissues which might have implications for the risk of retroviral infection in the human host.

Methods

A series of 11 functioning, life‐supporting pig‐to‐baboon kidney xenografts fromPERV‐positive miniature swine were studied with and withoutPCMVco‐infection. Frozen biopsy samples were analyzed using quantitative, real‐timePCRwith internal controls.

Results

PERVreplication was not altered in the presence ofPCMVcoinfection (P = .70). The absence of variation with coinfection was confirmed whenPERVquantitation was expressed relative to simultaneous cellularGAPDHlevels with or withoutPCMVcoinfection (P = .59).

Conclusions

PCMVcoinfection does not alter the replication ofPERVin life‐supporting renal xenotransplantation in vivo in baboons.
Fenómeno y sujeto:  el fundamento de la presencia
Authors: Calderón Jacinto H.
Published: April 2018

La filosofía, en su pretensión de ser un discurso ceñido a lo real, tiene que rendir cuentas a lo que en este artículo llamamos “presencia”, es decir, a la condición fenoménica de todo ente que se presenta al psiquismo. En este sentido, encontramos que Kant, estableciendo su idealismo trascendental, se atiene a la presencia hasta que el sujeto aparece y lo presente parece cambiar de fundamento. En este momento aparece la doctrina de la ciencia de Fichte, planteando la presencia en otros términos que, de ser correctos, nos permiten acceder a una nueva dimensión de la filosofía.

 
Active nematic emulsions
Authors: Guillamat Pau , Kos Žiga , Hardoüin Jérôme , Ignés-Mullol Jordi , Ravnik Miha , Sagués Francesc
Published: April 2018

Droplets of active fluid form a dynamically self-assembled material based on the cross-talk between active and passive defects.
Nonlinear fracture toughness measurement and crack propagation resistance of functionalized graphene multilayers
Authors: Cao Changhong , Mukherjee Sankha , Howe Jane Y. , Perovic Doug D. , Sun Yu , Singh Chandra Veer , Filleter Tobin
Published: April 2018

Functionalized graphene multilayer is tougher than graphene.
Inducing ferromagnetism and Kondo effect in platinum by paramagnetic ionic gating
Authors: Liang Lei , Chen Qihong , Lu Jianming , Talsma Wytse , Shan Juan , Blake Graeme R. , Palstra Thomas T. M. , Ye Jianting
Published: April 2018

Platinum thin film becomes ferromagnetic when under a large electric field and in proximity to local magnetic moments.
Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms
Authors: Garcia-Rubio Rocio , Alcazar-Fuoli Laura , Monteiro Maria Candida , Monzon Sara , Cuesta Isabel , Pelaez Teresa , Mellado Emilia
Published: April 2018

Triazole antifungal compounds are the first treatment choice for invasive aspergillosis. However, in the last decade the rate of azole resistance among
Aspergillus fumigatus
strains has increased notoriously. The main resistance mechanisms are well defined and mostly related to point mutations of the azole target, 14-α sterol demethylase (
cyp51A
), with or without tandem repeat integrations in the
cyp51A
promoter. Furthermore, different combinations of five Cyp51A mutations (F46Y, M172V, N248T, D255E, and E427K) have been reported worldwide in about 10% of all
A. fumigatus
isolates tested. The azole susceptibility profile of these strains shows elevated azole MICs, although on the basis of the azole susceptibility breakpoints, these strains are not considered azole resistant. The purpose of the study was to determine whether these
cyp51A
polymorphisms (single nucleotide polymorphisms [SNPs]) are responsible for the azole susceptibility profile and whether they are reflected in a poorer azole treatment response
in vivo
that could compromise patient treatment and outcome. A mutant with a
cyp51A
deletion was generated and became fully susceptible to all azoles tested. Also, three
cyp51A
gene constructions with different combinations of SNPs were generated and reintroduced into an azole-susceptible wild-type (WT) strain (the Δ
akuB
KU80
strain). The alternative model host
Galleria mellonella
was used to compare the virulence and voriconazole response of
G. mellonella
larvae infected with
A. fumigatus
strains with WT
cyp51A
or
cyp51A
with SNPs. All strains were pathogenic in
G. mellonella
larvae, although they did not respond similarly to voriconazole therapeutic doses. Finally, the full genomes of these strains were sequenced and analyzed in comparison with those of
A. fumigatus
WT strains, revealing that they belong to different strain clusters or lineages.
Increasing the Antimicrobial Activity of Nisin-Based Lantibiotics against Gram-Negative Pathogens
Authors: Li Qian , Montalban-Lopez Manuel , Kuipers Oscar P.
Published: April 2018

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial compounds containing lanthionine and methyl-lanthionine residues. Nisin, one of the most extensively studied and used lantibiotics, has been shown to display very potent activity against Gram-positive bacteria, and stable resistance is rarely observed. By binding to lipid II and forming pores in the membrane, nisin can cause the efflux of cellular constituents and inhibit cell wall biosynthesis. However, the activity of nisin against Gram-negative bacteria is much lower than that against Gram-positive bacteria, mainly because lipid II is located at the inner membrane, and the rather impermeable outer membrane in Gram-negative bacteria prevents nisin from reaching lipid II. Thus, if the outer membrane-traversing efficiency of nisin could be increased, the activity against Gram-negative bacteria could, in principle, be enhanced. In this work, several relatively short peptides with activity against Gram-negative bacteria were selected from literature data to be fused as tails to the C terminus of either full or truncated nisin species. Among these, we found that one of three tails (tail 2 [T2; DKYLPRPRPV], T6 [NGVQPKY], and T8 [KIAKVALKAL]) attached to a part of nisin displayed improved activity against Gram-negative microorganisms. Next, we rationally designed and reengineered the most promising fusion peptides. Several mutants whose activity significantly outperformed that of nisin against Gram-negative pathogens were obtained. The activity of the tail 16 mutant 2 (T16m2) construct against several important Gram-negative pathogens (i.e.,
Escherichia coli
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
,
Enterobacter aerogenes
) was increased 4- to 12-fold compared to that of nisin. This study indicates that the rational design of nisin can selectively and significantly improve its outer membrane-permeating capacity as well as its activity against Gram-negative pathogens.

IMPORTANCE
Lantibiotics are antimicrobial peptides that are highly active against Gram-positive bacteria but that have relatively poor activity against most Gram-negative bacteria. Here, we modified the model lantibiotic nisin by fusing parts of it to antimicrobial peptides with known activity against Gram-negative bacteria. The appropriate selection of peptidic moieties that could be attached to (parts of) nisin could lead to a significant increase in its inhibitory activity against Gram-negative bacteria. Using this strategy, hybrids that outperformed nisin by displaying 4- to 12-fold higher levels of activity against relevant Gram-negative bacterial species were produced. This study shows the power of modified peptide engineering to alter target specificity in a desired direction.
Efficacy of Silver Dihydrogen Citrate and Steam Vapor against a Human Norovirus Surrogate, Feline Calicivirus, in Suspension, on Glass, and on Carpet
Authors: Buckley David , Dharmasena Muthu , Fraser Angela , Pettigrew Charles , Anderson Jeffery , Jiang Xiuping
Published: April 2018

Carpets and other soft surfaces have been associated with prolonged and reoccurring human norovirus (HuNoV) outbreaks. Environmental hygiene programs are important to prevent and control HuNoV outbreaks. Despite our knowledge of HuNoV transmission via soft surfaces, no commercially available disinfectants have been evaluated on carpets. Our aim was to adapt a current standardized method for virucidal testing by assessing two disinfection technologies, silver dihydrogen citrate (SDC) and steam vapor, against one HuNoV surrogate, feline calicivirus (FCV), on wool and nylon carpets. First, we evaluated the effect of both technologies on the appearance of carpet. Next, we evaluated the efficacy of SDC in suspension and the efficacy of SDC and steam vapor against FCV on a glass surface, each with and without serum. Lastly, we tested both technologies on two types of carpet, wool and nylon. Both carpets exhibited no obvious color changes; however, SDC treatments left a residue while steam vapor left minor abrasions to fibers. SDC in suspension and on glass reduced FCV by 4.65 log
10
and >4.66 log
10
PFU, respectively, but demonstrated reduced efficacy in the presence of serum. However, SDC was only efficacious against FCV on nylon (3.62-log
10
PFU reduction) and not wool (1.82-log
10
PFU reduction). Steam vapor reduced FCV by >4.93 log
10
PFU on glass in 10 s and >3.68 log
10
PFU on wool and nylon carpet carriers in 90 s. There was a limited reduction of FCV RNA under both treatments compared to that of infectivity assays, but RNA reductions were higher in samples that contained serum.

IMPORTANCE
Human noroviruses (HuNoV) account for ca. 20% of all diarrheal cases worldwide. Disease symptoms may include diarrhea and vomit, with both known to contribute to transmission. The prevention and control of HuNoV are difficult because they are environmentally resilient and resistant to many disinfectants. Several field studies have linked both hard and soft surfaces to HuNoV outbreaks. However, many disinfectants efficacious against HuNoV surrogates are recommended for hard surfaces, but no commercially available products have demonstrated efficacy against these surrogates on soft surfaces. Our research objectives were to evaluate liquid and steam-based technologies in suspension and on hard surface carriers in addition to adapting and testing a protocol for assessing the virucidal effects of disinfection technologies on carpet carriers. These results will inform both the government and industry regarding a standard method for evaluating the virucidal effects of disinfectants on carpet while demonstrating their efficacy relative to suspension and hard-surface tests.
Endoribonuclease YbeY Is Linked to Proper Cellular Morphology and Virulence in Brucella abortus
Authors: Budnick James A. , Sheehan Lauren M. , Colquhoun Jennifer M. , Dunman Paul M. , Walker Graham C. , Roop R. Martin , Caswell Clayton C.
Published: April 2018

The YbeY endoribonuclease is one of the best-conserved proteins across the kingdoms of life. In the present study, we demonstrated that YbeY in
Brucella abortus
is linked to a variety of important activities, including proper cellular morphology, mRNA transcript levels, and virulence. Deletion of
ybeY
in
B. abortus
led to a small-colony phenotype when the bacteria were grown on agar medium, as well as to significant aberrations in the morphology of the bacterial cell as evidenced by electron microscopy. Additionally, compared to the parental strain, the Δ
ybeY
strain was significantly attenuated in both macrophage and mouse models of infection. The Δ
ybeY
strain also showed increased sensitivities to several
in vitro
-applied stressors, including bile acid, hydrogen peroxide, SDS, and paraquat. Transcriptomic analysis revealed that a multitude of mRNA transcripts are dysregulated in the Δ
ybeY
strain, and many of the identified mRNAs encode proteins involved in metabolism, nutrient transport, transcriptional regulation, and flagellum synthesis. We subsequently constructed gene deletion strains of the most highly dysregulated systems, and several of the YbeY-linked gene deletion strains exhibited defects in the ability of the bacteria to survive and replicate in primary murine macrophages. Taken together, these data establish a clear role for YbeY in the biology and virulence of
Brucella
; moreover, this work further illuminates the highly varied roles of this widely conserved endoribonuclease in bacteria.

IMPORTANCE
Brucella
spp. are highly efficient bacterial pathogens of animals and humans, causing significant morbidity and economic loss worldwide, and relapse of disease often occurs following antibiotic treatment of human brucellosis. As such, novel therapeutic strategies to combat
Brucella
infections are needed. Ribonucleases in the brucellae are understudied, and these enzymes represent elements that may be potential targets for future treatment approaches. The present work demonstrates the importance of the YbeY endoribonuclease for cellular morphology, efficient control of mRNA levels, and virulence in
B. abortus
. Overall, the results of this study advance our understanding of the critical roles of YbeY in the pathogenesis of the intracellular brucellae and expand our understanding of this highly conserved RNase.
Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis
Authors: Schwebke Jane R. , Gaydos Charlotte A. , Nyirjesy Paul , Paradis Sonia , Kodsi Salma , Cooper Charles K.
Published: April 2018

Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the
Candida
gene
its2
, and
Trichomonas vaginalis
culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.
Effect of emotional content on online video sharing among health care professionals and researchers (DIFFUSION): results and lessons learnt from a randomised controlled trial
Authors: Kiriya Junko , Edwards Phil , Roberts Ian
Published: April 2018

Objectives

We assessed the effect of emotional content on the extent to which online videos are shared among health professionals.

Setting

We conducted a two-arm randomised controlled trial. We sent a link to one of two videos by email to participants asking them to watch the video and forward it to their colleagues.

Participants

Health professionals and researchers (obstetrics, gynaecology and midwifery) with an email address apart from those in countries where access to YouTube is banned. We estimated that 7000 participants were required.

Interventions

We compared two online videos providing background information about the WOMAN trial. The videos were the same length and had the same content. However, the intervention video had more emotional impact than the control video.

Outcome measures

The primary outcome was video sharing and the secondary outcome was views generated by participants. We conducted a χ2test for the primary outcome and t-test for the secondary outcome.

Results

We randomly allocated 8353 email addresses, 4178 to the intervention video and 4175 to the control. Of these, 221 (5.3%) watched the intervention video and 215 (5.1%) watched the control. In the intervention group, 44 (1.1%) forwarded the video compared with 37 (0.9%) in the control group (risk ratio 1.2 [95% CI 0.8 to 1.8], p=0.44). Mean number of views generated by participants allocated to the intervention video was 0.04 and the control video was 0.03 (mean difference 0.01 [95% CI −0.02 to 0.04], p=0.53).

Conclusions

We found no evidence that emotional content increased forwarding. The trial had low power due to the low video watching rate and the small number of outcome events. A key challenge for online dissemination is ensuring recipients watch the video.

Trial registration number

NCT02109159; Results.
Using the Oxford Foot Model to determine the association between objective measures of foot function and results of the AOFAS Ankle-Hindfoot Scale and the Foot Function Index: a prospective gait analysis study in Germany
Authors: Kostuj Tanja , Stief Felix , Hartmann Kirsten Anna , Schaper Katharina , Arabmotlagh Mohammad , Baums Mike H , Meurer Andrea , Krummenauer Frank , Lieske Sebastian
Published: April 2018

Objective

After cross-cultural adaption for the German translation of the Ankle-Hindfoot Scale of the American Orthopaedic Foot and Ankle Society (AOFAS-AHS) and agreement analysis with the Foot Function Index (FFI-D), the following gait analysis study using the Oxford Foot Model (OFM) was carried out to show which of the two scores better correlates with objective gait dysfunction.

Design and participants

Results of the AOFAS-AHS and FFI-D, as well as data from three-dimensional gait analysis were collected from 20 patients with mild to severe ankle and hindfoot pathologies.

Kinematic and kinetic gait data were correlated with the results of the total AOFAS scale and FFI-D as well as the results of those items representing hindfoot function in the AOFAS-AHS assessment. With respect to the foot disorders in our patients (osteoarthritis and prearthritic conditions), we correlated the total range of motion (ROM) in the ankle and subtalar joints as identified by the OFM with values identified during clinical examination ‘translated’ into score values. Furthermore, reduced walking speed, reduced step length and reduced maximum ankle power generation during push-off were taken into account and correlated to gait abnormalities described in the scores. An analysis of correlations with CIs between the FFI-D and the AOFAS-AHS items and the gait parameters was performed by means of the Jonckheere-Terpstra test; furthermore, exploratory factor analysis was applied to identify common information structures and thereby redundancy in the FFI-D and the AOFAS-AHS items.

Results

Objective findings for hindfoot disorders, namely a reduced ROM, in the ankle and subtalar joints, respectively, as well as reduced ankle power generation during push-off, showed a better correlation with the AOFAS-AHS total score—as well as AOFAS-AHS items representing ROM in the ankle, subtalar joints and gait function—compared with the FFI-D score.

Factor analysis, however, could not identify FFI-D items consistently related to these three indicator parameters (pain, disability and function) found in the AOFAS-AHS. Furthermore, factor analysis did not support stratification of the FFI-D into two subscales.

Conclusions

The AOFAS-AHS showed a good agreement with objective gait parameters and is therefore better suited to evaluate disability and functional limitations of patients suffering from foot and ankle pathologies compared with the FFI-D.
Access to palliative care by disease trajectory: a population-based cohort of Ontario decedents
Authors: Seow Hsien , O’Leary Erin , Perez Richard , Tanuseputro Peter
Published: April 2018

Objectives

To examine access to palliative care between different disease trajectories and compare to other geographic areas.

Design

A retrospective population-based decedent cohort study using linked administrative data.

Setting

Ontario, Canada.

Participants

Ontario decedents between 1 April 2010 and 31 December 2012. Patients were categorised into disease trajectories: terminal illness (eg, cancer), organ failure (eg, chronic heart failure), frailty (eg, dementia), sudden death or other.

Interventions

Receipt of palliative care services from institutional and community settings, derived from a validated list of palliative care codes from multiple administrate databases.

Outcome measures

Receiving any palliative care services in the last year of life (yes/no), intensity (total days) and time of initiation of palliative care, in hospital and community sectors. Multivariable analysis examined the association between disease trajectory and the receipt of palliative care in the last year of life.

Results

We identified 235 159 decedents in Ontario. In the last year of life, 88% of terminal illness, 44% of organ failure and 32% of frailty decedents accessed at least one palliative care service. Most care was provided during an inpatient hospitalisation. Terminal illness decedents received twice as many palliative care days (mean of 49 days) compared with organ failure and frailty decedents. Patients with terminal illness initiated palliative care median of 107 days before death compared with median of 19 days among those using the US Medicare hospice benefit.

Conclusions

Terminal illness decedents are more likely to receive any palliative care, with increased intensity and earlier before death than organ failure or frailty decedents. These data serve as a useful comparison for other countries with similar and different healthcare systems and eligibility criteria.
Collection and sharing of medical information and medical intelligence (M2I) in NATO: a transversal survey
Authors: Bedubourg Gabriel , Wiik H , Queyriaux B , Lausund P , Meynard J-B
Published: April 2018

Introduction

There is a requirement for adequate medical expertise to be available throughout the range of potential future operations involving members of the North Atlantic Treaty Organization (NATO). The aim of this study was to assess the collection and sharing of medical intelligence and medical information (M2I) by NATO Nations, Partner Nations and NATO Command Structure and NATO Force Structure Headquarters (NCS/NFS HQs).

Materials and methods

A transversal survey was conducted between December 2014 and March 2015 using a survey form on M2I sent to NATO Nations and Partnership for Peace (PfP) Nations as well as NCS/NFS HQs.

Results

Correctly completed responses were received from 15/40 (37.5%) of the possible NATO and PfP Nations (37.5%) and 7/8 (87.5%) of the NCS/NFS HQs (100.0%). Deficiencies in the collection of M2I data were found due to lack of specific doctrines, networks, tools, structures and organisation.

Conclusions

The survey provided an indication even though the participation rate was low for Nations. Part of the problem is thought to be that medical information and medical intelligence often lie in different chains of command. Future directions for this research could include studying the possibilities of a new specific information technology (IT) system to collect and to share M2I. Collection and sharing of M2I within the NATO/PfP community requires facilitation in order to strengthen the basis for decision-making and force health protection. The development of a dedicated NATO IT system may be a precondition for the implementation of an efficient M2I network.
Risk factors for lower limb injuries during initial naval training: a prospective study
Authors: Bonanno Daniel R , Munteanu S E , Murley G S , Landorf K B , Menz H B
Published: April 2018

Introduction

This study aimed to identify risk factors associated with the development of common lower limb injuries during initial defence training in naval recruits who were enrolled in a randomised trial.

Methods

Three-hundred and six naval recruits were randomly allocated flat insoles (n=153) or foot orthoses (n=153) while undertaking 11 weeks of initial training. Participant characteristics (including anthropometrics, general health, physical activity, fitness and foot characteristics) were collected at the baseline assessment and injuries were documented prospectively. Injury was defined as the combined incidence of participants with medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain throughout the 11 weeks of training. A discriminant function analysis was used to explore the ability of baseline measures to predict injury.

Results

Overall, 67 (21.9%) participants developed an injury. Discriminant function analysis revealed that participants who sustained an injury were slightly younger (mean 21.4±SD 4.1 vs 22.5±5.0 years) and were less likely to be allocated to the foot orthosis group (40% vs 53%) compared with those who remained uninjured. The accuracy of these baseline variables to predict injury was moderate (78.1%).

Conclusions

Lower limb injury was not accurately predicted from health questionnaires, fitness results and clinical assessments in naval recruits undertaking initial defence training. However, although not reaching statistical significance, the use of foot orthoses may be protective against common lower limb injuries.

Trial registration number

ACTRN12615000024549; Post-results.
Modified cosmology through Renyi and logarithmic entropies
Authors: Jawad Abdul , Iqbal Ayesha
Published: April 2018

We consider two different entropic corrections to Bekenstein entropy, namely Renyi entropy and logarithmic-corrected entropy, and develop the entropic force, heat flow across the horizon and pressure. We also derive the expressions for Newton’s law of gravitation and verify with Bekenstein entropy by taking [Formula: see text] in the case of Renyi entropy and [Formula: see text] for logarithmic entropy. The modified Friedmann equations are also being developed by using Newton’s first law of thermodynamics in both cases. In the presence of these equations, we also analyze the validity of generalized second law of thermodynamics for both entropy corrections on the apparent horizon. It is found that this law remains valid throughout the region under certain assumptions for nonflat FRW universe.
Covariance estimation using random permutations
Authors: Padmakumari Lakshmi , Maheswaran S.
Published: April 2018

This paper explores a novel technique to compute the level of covariance between any two genuinely correlated assets by adopting the idea of random permutations by proposing an unbiased covariance estimator “[Formula: see text]” based on daily high-low prices. The main goal is to boost the relative efficiency of the estimator by increasing the number of random permutations. We validate this claim with the help of simulations later. Further, we prove theoretically and through simulations that the proposed estimator is unbiased for a pair of random walks. Upon empirically implementing the estimator in a dataset of three sets of stock indices: Nifty, FTSE100 and S&P500 after accounting for exchange effects (USDINR and GBPINR) over a sample period of 252 months (Jan 1996–Dec 2016), we do not find evidence of any bias in the estimator. Also, there is a visible asymmetry in the correlation between US-Indian markets from the two investor’s point of view.
Klf4 has an unexpected protective role in perivascular cells within the microvasculature
Authors: Haskins Ryan M. , Nguyen Anh T. , Alencar Gabriel F. , Billaud Marie , Kelly-Goss Molly R. , Good Miranda E. , Bottermann Katharina , Klibanov Alexander L. , French Brent A. , Harris Thurl E. , Peirce Shayn M. , Isakson Brant E. , Owens Gary K.
Published: April 2018

Recent smooth muscle cell (SMC) lineage-tracing studies have revealed that SMCs undergo remarkable changes in phenotype during development of atherosclerosis. Of major interest, we demonstrated that Kruppel-like factor 4 (KLF4) in SMCs is detrimental for overall lesion pathogenesis, in that SMC-specific conditional knockout of the KLF4 gene ( Klf4) resulted in smaller, more-stable lesions that exhibited marked reductions in the numbers of SMC-derived macrophage- and mesenchymal stem cell-like cells. However, since the clinical consequences of atherosclerosis typically occur well after our reproductive years, we sought to identify beneficial KLF4-dependent SMC functions that were likely to be evolutionarily conserved. We tested the hypothesis that KLF4-dependent SMC transitions play an important role in the tissue injury-repair process. Using SMC-specific lineage-tracing mice positive and negative for simultaneous SMC-specific conditional knockout of Klf4, we demonstrate that SMCs in the remodeling heart after ischemia-reperfusion injury (IRI) express KLF4 and transition to a KLF4-dependent macrophage-like state and a KLF4-independent myofibroblast-like state. Moreover, heart failure after IRI was exacerbated in SMC Klf4 knockout mice. Surprisingly, we observed a significant cardiac dilation in SMC Klf4 knockout mice before IRI as well as a reduction in peripheral resistance. KLF4 chromatin immunoprecipitation-sequencing analysis on mesenteric vascular beds identified potential baseline SMC KLF4 target genes in numerous pathways, including PDGF and FGF. Moreover, microvascular tissue beds in SMC Klf4 knockout mice had gaps in lineage-traced SMC coverage along the resistance arteries and exhibited increased permeability. Together, these results provide novel evidence that Klf4 has a critical maintenance role within microvascular SMCs: it is required for normal SMC function and coverage of resistance arteries.

NEW & NOTEWORTHY We report novel evidence that the Kruppel-like factor 4 gene ( Klf4) has a critical maintenance role within microvascular smooth muscle cells (SMCs). SMC-specific Klf4 knockout at baseline resulted in a loss of lineage-traced SMC coverage of resistance arteries, dilation of resistance arteries, increased blood flow, and cardiac dilation.
Vagal stimulation mimics preconditioning and postconditioning of ischemic myocardium in mice by activating different protection mechanisms
Authors: Buchholz Bruno , Kelly Jazmín , Muñoz Marina , Bernatené Eduardo A. , Méndez Diodati Nahuel , González Maglio Daniel H. , Dominici Fernando P. , Gelpi Ricardo J.
Published: April 2018

Vagal stimulation (VS) during myocardial ischemia and reperfusion has beneficial effects. However, it is not known whether short-term VS applied before ischemia or at the onset of reperfusion protects the ischemic myocardium. This study was designed to determine whether short-term VS applied before ischemia or at the onset of reperfusion reduces myocardial infarct size (IS), mimicking classic preconditioning and postconditioning. A second objective was to study the participation of muscarinic and nicotinic receptors in the protection of both preischemic and reperfusion stimulation. FVB mice were subjected to 30 min of regional myocardial ischemia followed by 2 h of reperfusion without VS, with 10-min preischemic VS (pVS), or with VS during the first 10 min of reperfusion (rVS). pVS reduced IS, and this effect was abolished by atropine and wortmannin. rVS also reduced IS in a similar manner, and this effect was abolished by the α7-nicotinic acetylcholine receptor blocker methyllycaconitine. pVS increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation. No changes in Akt and GSK-3β phosphorylation were observed in rVS. Stimulation-mediated IS protection was abolished with the JAK2 blocker AG490. rVS did not modify IL-6 and IL-10 levels in the plasma or myocardium. Splenic denervation and splenectomy did not abolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS by different mechanisms: pVS activated the Akt/GSK-3β muscarinic pathway, whereas rVS activated α7-nicotinic acetylcholine receptors and JAK2, independently of the cholinergic anti-inflammatory pathway.

NEW & NOTEWORTHY Our data suggest, for the first time, that vagal stimulation applied briefly either before ischemia or at the beginning of reperfusion mimics classic preconditioning and postconditioning and reduces myocardial infarction, activating different mechanisms. We also infer an important role of α7-nicotinic receptors for myocardial protection independent of the cholinergic anti-inflammatory pathway.
Spheroids of cardiomyocytes derived from human-induced pluripotent stem cells improve recovery from myocardial injury in mice
Authors: Mattapally Saidulu , Zhu Wuqiang , Fast Vladimir G. , Gao Ling , Worley Chelsea , Kannappan Ramaswamy , Borovjagin Anton V. , Zhang Jianyi
Published: April 2018

The microenvironment of native heart tissue may be better replicated when cardiomyocytes are cultured in three-dimensional clusters (i.e., spheroids) than in monolayers or as individual cells. Thus, we differentiated human cardiac lineage-induced pluripotent stem cells in cardiomyocytes (hiPSC-CMs) and allowed them to form spheroids and spheroid fusions that were characterized in vitro and evaluated in mice after experimentally induced myocardial infarction (MI). Synchronized contractions were observed within 24 h of spheroid formation, and optical mapping experiments confirmed the presence of both Ca2+ transients and propagating action potentials. In spheroid fusions, the intraspheroid conduction velocity was 7.0 ± 3.8 cm/s on days 1– 2 after formation, whereas the conduction velocity between spheroids increased significantly ( P = 0.003) from 0.8 ± 1.1 cm/s on days 1– 2 to 3.3 ± 1.4 cm/s on day 7. For the murine MI model, five-spheroid fusions (200,000 hiPSC-CMs/spheroid) were embedded in a fibrin patch and the patch was transplanted over the site of infarction. Later (4 wk), echocardiographic measurements of left ventricular ejection fraction and fractional shortening were significantly greater in patch-treated animals than in animals that recovered without the patch, and the engraftment rate was 25.6% or 30% when evaluated histologically or via bioluminescence imaging, respectively. The exosomes released from the spheroid patch seemed to increase cardiac function. In conclusion, our results established the feasibility of using hiPSC-CM spheroids and spheroid fusions for cardiac tissue engineering, and, when fibrin patches containing hiPSC-CM spheroid fusions were evaluated in a murine MI model, the engraftment rate was much higher than the rates we have achieved via the direct intramyocardial injection.

NEW & NOTEWORTHY Spheroids fuse in culture to produce structures with uniformly distributed cells. Furthermore, human cardiac lineage-induced pluripotent stem cells in cardiomyocytes in adjacent fused spheroids became electromechanically coupled as the fusions matured in vitro, and when the spheroids were combined with a biological matrix and administered as a patch over the infarcted region of mouse hearts, the engraftment rate exceeded 25%, and the treatment was associated with significant improvements in cardiac function via a paracrine mechanism, where exosomes released from the spheroid patch.
Beta-hydroxybutyrate infusion identifies acutely differentially expressed genes related to metabolism and reproduction in the hypothalamus and pituitary of castrated male sheep
Authors: Cope Emily R. , Voy Brynn H. , Whitlock Brian K. , Staton Meg , Lane Thomas , Davitt Jack , Mulliniks J. Travis
Published: April 2018

To identify molecular pathways that couple metabolic imbalances and reproduction, we randomly assigned 10 castrated male sheep to be centrally injected into the lateral ventricle through intracerebroventricular cannulas with 1 ml of β-hydroxybutyric acid sodium salt solution (BHB; 12,800 µmol/l) or saline solution (CON; 0.9% NaCl). Approximately 2 h postinjection, sheep were humanely euthanized, and hypothalamus and pituitary tissues were harvested for transcriptome characterization by RNA sequencing. RNA was extracted from the hypothalamus and pituitary and sequenced at a high depth (hypothalamus: 468,912,732 reads; pituitary: 515,106,092 reads) with the Illumina Hi-Seq 2500 platform and aligned to Bos taurus and Ovis aries genomes. Of the total raw reads, 87% (hypothalamus) and 90.5% (pituitary) mapped to the reference O. aries genome. Within these read sets, ~56% in hypothalamus and 69% in pituitary mapped to either known or putative protein coding genes. Fragments per kilobase of transcripts per million normalized counts were averaged and ranked to identify the transcript expression level. Gene Ontology analysis (DAVID Bioinformatics Resources) was utilized to identify biological process functions related to genes shared between tissues, as well as functional categories with tissue-specific enrichment. Between CON- and BHB-treated sheep, 11 and 44 genes were differentially expressed (adj. P < 0.05) within the pituitary and hypothalamus, respectively. Functional enrichment analyses revealed BHB altered expression of genes in pathways related to stimulus perception, inflammation, and cell cycle control. The set of genes altered by BHB creates a foundation from which to identify the signaling pathways that impact reproduction during metabolic imbalances.
BCI and FES Based Therapy for Stroke Rehabilitation Using VR Facilities
Authors: Lupu Robert Gabriel , Irimia Danut Constantin , Ungureanu Florina , Poboroniuc Marian Silviu , Moldoveanu Alin
Published: April 2018

In recent years, the assistive technologies and stroke rehabilitation methods have been empowered by the use of virtual reality environments and the facilities offered by brain computer interface systems and functional electrical stimulators. In this paper, a therapy system for stroke rehabilitation based on these revolutionary techniques is presented. Using a virtual reality Oculus Rift device, the proposed system ushers the patient in a virtual scenario where a virtual therapist coordinates the exercises aimed at restoring brain function. The electrical stimulator helps the patient to perform rehabilitation exercises and the brain computer interface system and an electrooculography device are used to determine if the exercises are executed properly. Laboratory tests on healthy people led to system validation from technical point of view. The clinical tests are in progress, but the preliminary results of the clinical tests have highlighted the good satisfaction degree of patients, the quick accommodation with the proposed therapy, and rapid progress for each user rehabilitation.
A Randomized Controlled Trial of Chinese Patent Medicine Xiao’er Biantong Granules in the Treatment of Functional Constipation in Children
Authors: Cai Qiu-han , Ma Rong , Hu Si-yuan , Li Xin-min , Xiang Xi-xiong , Ding Ying , He Ping , Han Xin-min , Chang Ke , Zhang Wei , Xue Zheng , Wang Xue-feng , Zhong Cheng-liang , Yang Na
Published: April 2018

Objective. To confirm the effect and safety of Xiao’er Biantong (XEBT) granules for treating chronic constipation in children. Methods. This randomized, double‐blind, multicenter study enrolled 480 children with age of 1–14 years who had FC. All of them were randomly assigned to receive either XEBT granules or its placebo in the ratio of 3 : 1. The primary efficacy outcome was the frequency of spontaneous bowel movements (SBM) for 14 days, and secondary outcomes were effectual time, score of main symptoms, effect of constipation, disappearance rate of accompanying symptoms, and recurrence rate. We also observed the adverse event (AE) and adverse drug reaction (ADR) to evaluate safety. Results. The sociodemographic characteristics and efficiency data were comparable in the two groups at baseline. The mean values of SBM for 14 days were 8.89 and 5.63 in the XEBT group and the placebo group, respectively, and there were 86.87% and 30.91% subjects in two groups up to SBM ≥ 3/week, respectively. There were significant differences between the two groups. The effects in the XEBT group on median effectual time of defecation, main symptom score, disappearance rate of symptoms, and the differences were significant. The conclusions based on full analysis set (FAS) and per protocol set (PPS) were consistent. Nine AEs were reported, of which 7 were in the XEBT group (2.02%) while 2 were in the placebo group (1.77%). There were no significant differences in the occurrence rate of AE and ADR between the two groups. Conclusions. Xiao’er Biantong granules have superior efficacy compared to the placebo for the treatment of functional constipation in children and are well tolerated.