bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective sweep-width for barrier missions against an evasive target
Authors: Rowling Steven J
Published: October 2019

An effective sweep-width, to be used in predicting the performance of a barrier patrol against a smart, evasive intruder is defined. Following Washburn’s example for a two-dimensional area search, the nominal sweep-width of the searcher is reduced to account for the target’s evasive ability. The formulation presented here allows for the barrier to be either stationary or advancing. Two different definitions are offered for an effective sweep-width: one that focuses solely on the probability of detecting the intruder and one that includes deterrence as a form of success for the searcher.
Microneedle System for Transdermal Drug and Vaccine Delivery: Devices, Safety, and Prospects
Authors: He Xiaoxiang , Sun Jingyao , Zhuang Jian , Xu Hong , Liu Ying , Wu Daming
Published: October 2019

Microneedle (MN) delivery system has been greatly developed to deliver drugs into the skin painlessly, noninvasively, and safety. In the past several decades, various types of MNs have been developed by the newer producing techniques. Briefly, as for the morphologically, MNs can be classified into solid, coated, dissolved, and hollow MN, based on the transdermal drug delivery methods of “poke and patch,” “coat and poke,” “poke and release,” and “poke and flow,” respectively. Microneedles also have other characteristics based on the materials and structures. In addition, various manufacturing techniques have been well-developed based on the materials. In this review, the materials, structures, morphologies, and fabricating methods of MNs are summarized. A separate part of the review is used to illustrate the application of MNs to deliver vaccine, insulin, lidocaine, aspirin, and other drugs. Finally, the review ends up with a perspective on the challenges in research and development of MNs, envisioning the future development of MNs as the next generation of drug delivery system.
The development of a new variable stiffness soft gripper
Authors: Tang Zhijie , Lu Jiaqi , Wang Zhen , Ma Gaoqian
Published: October 2019

A new variable stiffness four-finger soft gripper with a combination of rigid and soft structures is designed. The combination of rigid and soft structures is one of the methods to improve the performance of soft grippers. Grasping motion is achieved by the rigid structure of the screw and the connecting rod. Soft gripper uses human finger-like structure made of silicone, and the air pressure and the rigidity of the soft fingers can be adjusted by the air pump. The soft gripper overcomes the inability of a rigid gripper to easily and safely grasp soft and brittle objects and the inability of a completely soft gripper to exert sufficiently high forces to achieve effective grasping. Grasping force can be improved by increasing the stiffness of the finger and the driving stroke of screw. The variable grasping force allows the soft gripper to grasp different shape objects, specially soft and brittle objects.
Characteristics and outcome of patients set up on high-flow oxygen therapy at home
Authors: Dolidon Samuel , Dupuis Johann , Molano Valencia Luis-Carlos , Salaün Mathieu , Thiberville Luc , Muir Jean-François , Cuvelier Antoine , Patout Maxime
Published: October 2019

Background:

High-flow oxygen therapy (HFOT) is increasingly used for acute respiratory failure. Few data support its use at home for the treatment of chronic respiratory failure. Our aim was to report the pattern of the use of long-term HFOT in our center and the outcome of patients setup on long-term HFOT.

Methods:

A retrospective monocentric study including all patients setup on long-term HFOT between January 2011 and April 2018 in Rouen University Hospital was carried out. Patients were divided into two groups, patients with hypoxemic respiratory failure treated with nasal HFOT (nHFOT) and tracheotomized patients treated with tracheal HFOT (tHFOT).

Results:

A total of 71 patients were established on long-term HFOT. Out of these 43 (61%) were included in the nHFOT group and 28 (39%) were included in the tHFOT group. In the nHFOT group, underlying respiratory diseases were interstitial lung disease ( n = 15, 35%), pulmonary hypertension ( n = 12, 28%), lung cancer ( n = 9, 21%), and chronic airway disease ( n = 7, 16%). In the tHFOT group, the number of admissions for exacerbation decreased by −0.78 per year (–2 to 0) ( p = 0.045). In total, 51 (72%) patients were discharged to their homes and 20 (28%) went to a post-acute re-enablement facility. Median survival following HFOT was 7.5 months. Survival was significantly lower in the nHFOT group with a median survival of 3.6 months whereas median survival was not reached in the tHFOT group ( p < 0.001). Monthly costs associated with home delivery of HFOT were €476 (296–533) with significant differences in costs between the nHFOT group of €520 (408–628) and costs in the tHFOT group of €296 (261–475) ( p < 0.001).

Conclusions:

The use of long-term HFOT allows very severe patients to be discharged at a reasonable cost from acute care facilities. The reviews of this paper are available via the supplementary material section.
3-D magnetic graphene balls as sorbents for cleaning oil spills
Authors: Tao Tao , Li Guangyao , He Yanli , Yang Xiufang
Published: October 2019

A 3-D magnetic graphene ball (MGB) material was prepared using cellulose as the carbon source. Carbon-encapsulated iron nanoparticles (CEINs) were first prepared by hydrothermal carbonization of cellulose powder at 180°C. Then, the prepared CEINs were catalytically graphitized to graphene-encapsulated iron nanoparticles (GEINs) at 900°C. Finally, GEINs were treated in carbon dioxide at 700°C, during which the iron core was oxidized to magnetite (Fe3O4) nanoparticles, and graphene shells were peeled off from the iron cores to form graphene nanoplatelets. The graphene nanoplatelets consist of 1–10 layers graphene with the in-plane size of 20–30 nm. The prepared 3-D MGB was investigated for the removal of oil from water, which demonstrated outstanding adsorption performance and excellent recyclability.
Noninvasive measurement of cell/colony motion using image analysis methods to evaluate the proliferative capacity of oral keratinocytes as a tool for quality control in regenerative medicine
Authors: Hoshikawa Emi , Sato Taisuke , Kimori Yoshitaka , Suzuki Ayako , Haga Kenta , Kato Hiroko , Tabeta Koichi , Nanba Daisuke , Izumi Kenji
Published: October 2019

Image-based cell/colony analyses offer promising solutions to compensate for the lack of quality control (QC) tools for noninvasive monitoring of cultured cells, a regulatory challenge in regenerative medicine. Here, the feasibility of two image analysis algorithms, optical flow and normalised cross-correlation, to noninvasively measure cell/colony motion in human primary oral keratinocytes for screening the proliferative capacity of cells in the early phases of cell culture were examined. We applied our software to movies converted from 96 consecutive time-lapse phase-contrast images of an oral keratinocyte culture. After segmenting the growing colonies, two indices were calculated based on each algorithm. The correlation between each index of the colonies and their proliferative capacity was evaluated. The software was able to assess cell/colony motion noninvasively, and each index reflected the observed cell kinetics. A positive linear correlation was found between cell/colony motion and proliferative capacity, indicating that both algorithms are potential tools for QC.
Acute Kidney Injury in Critically Ill Children and Subsequent Chronic Kidney Disease
Authors: Hessey Erin , Perreault Sylvie , Dorais Marc , Roy Louise , Zappitelli Michael
Published: October 2019

Background:

The progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children.

Objectives:

We aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge.

Design:

Retrospective cohort study using chart collection and administrative data.

Setting:

Two-center study in Montreal, Canada.

Patients:

Children (≤18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease.

Measurements:

Acute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ≥1 CKD diagnostic code or ≥1 CKD-specific medication prescription.

Methods:

Chart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association.

Results:

A total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively ( P < .001).

Limitations:

Results may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further.

Conclusions:

Acute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.
Novel dynamic stabilization method for medial instability of the first metatarsophalangeal joint
Authors: Koós Zoltán , Sisák Krisztián
Published: October 2019

Medial collateral ligament injury of the first metatarsophalangeal (MTP) joint is rare. If it is missed, chronic instability and traumatic hallux valgus develop, requiring surgical treatment. Different methods have been reported in the limited available literature aiming to restore the balance between the lateral and medial stabilizers by tightening the medial joint capsule with or without additional tendon graft. Our described method utilizes a suture button device (Mini TightRope, Arthrex, Naples, Florida) for reconstruction. This device applies tension to hold the hallux in the correct position, providing stability. Relevant diagnostic regimen, surgical technique, and postoperative care are described, along with a case of a handball player who underwent this procedure. He continues to perform at the same level 38 months postoperatively. Mini TightRope fixation for chronic medial first MTP instability has not been reported. It does not require postoperative immobilization and allows faster return to sport, so it seems superior to other methods when treating athletes.
Gender Bias and Venture Funding: Discussing Bias in the Entrepreneurship Classroom
Authors: Michaelis Timothy L. , Pollack Jeffrey M. , Mulvey Paul , Ritter Beth M. , Carr Jon C.
Published: October 2019

We report on the findings from an in-class experiment that represents a learning innovation which can enable classroom-based conversations about bias in the domain of entrepreneurship. More specifically, the present learning innovation explores gender bias in venture funding with regard to entrepreneurship. In an introduction to entrepreneurship class, we randomly assigned students to one of the three experimental conditions—students evaluated an executive summary for a venture either written by a woman, or a man, or one in which the gender was neutral (i.e., the control group). Students acted as if they were considering an investment and reported whether, for example, the executive summary was well written as well as how much equity they would want in the venture as a potential investor. Overall, these results provide evidence consistent with the inference that the students sampled in this study did not use gender as a decision-making heuristic when evaluating entrepreneurial opportunities. We discuss the results of our experiment and describe (a) how to replicate this activity, (b) how to discuss this in the classroom, and (c) how to adapt this activity to explore other types of bias (e.g., race, ethnicity, weight-based, etc.).
Provision of Dental Trauma Care in a Remote and Rural Setting
Authors: Gray Crawford , Gupta Varun
Published: October 2019

Advanced oral surgery such as the treatment of fractures of the mandible is difficult to be performed in rural and remote settings. Within India, the bulk of the population reside in the countryside rather than in urban settings, leading to a lack of provision of secondary care services. Within the Chitrakoot Project, a modern, fully equipped dental surgery has evolved, which with the assistance of Indian specialists from secondary care, and visitors from abroad, has become a rural clinic capable of treating mandibular fractures using maxillomandibular fixation.

The concept of training for remote and rural dental surgeons is explored, and three cases are chronicled. The experience in Chitrakoot is something which could be usefully rolled out to suitable rural surgeons to receive training in teaching hospitals, which would improve the provision of acute oral surgery within the rural population of India, and other countries.
Intravenous Iron for the Treatment of Steroid-Refractory Idiopathic Thrombocytopenic Purpura
Authors: Mouabbi Jason , Hadid Tarik , Kafri Zyad
Published: October 2019

Introduction: Idiopathic thrombocytopenic purpura (ITP) is an acquired platelet disorder that is often caused by antibodies against platelet's antigens. Steroids are effective first therapy for ITP. Steroid-refractory ITP is rare and warrant further investigation and treatment. While iron deficiency anemia (IDA) usually presents with thrombocytosis, there are a few reported cases of IDA presenting with unexplained ITP.

Objective: We aim to determine whether the use of intravenous (IV) iron improves platelet count in patients with concomitant steroid-refractory ITP and IDA.

Methods: We identified five patients with IDA who presented to the St. John Hospital and Medical Center between 1/2010 and 12/2017 with unexplained profound thrombocytopenia. They were initially treated with steroids without success. All patients were then treated with a single infusion of iron dextran to replenish their iron stores.

Results: All five patients were African American females of childbearing age and with a history of menorrhagia. All patients had profound iron deficiency defined as iron saturation less than 20% and ferritin less than 15 ng/dL. Four of these patients had profound thrombocytopenia defined as platelets count below 30,000/mm3(table 1). Other causes of thrombocytopenia were ruled out. With IV iron, all patients achieved complete and durable resolution of their thrombocytopenia lasting for at least 6 months (table 2).

Conclusion: The exact mechanism of thrombocytopenia that occurs in patients with IDA is unknown. However, it is suggested that it may be related to the alteration in the activity of iron-dependent enzymes in the cells responsible for megakaryopoiesis and thrombopoiesis. We suggest that patients who present with concomitant steroid-refractory ITP and IDA should receive a trial of IV iron before proceeding with more aggressive therapy such as splenectomy.

Disclosures

No relevant conflicts of interest to declare.
Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma
Authors: Campos-Cabrera Gregorio , Mendez-Garcia Esther , Campos-Cabrera Salvador , Campos-Villagomez Jose-Luis , Campos-Cabrera Virgina
Published: October 2019

Hematological cancer has risk of venous thromboembolism of 28 fold compared to sex and age adjusted incidence in general population (JAMA 2005;293:715-722). This risk increases in patients with MM receiving dexamethasone and immunomodulatory drug. Thus, thromboprophylaxis with aspirin in low risk patients and LMWH or warfarin in high risk patients are recommended (Leukemia 2008;22:414-423). Direct oral anticoagulants are promising due to their convenience and costs-effectiveness in preventing VTE in other settings. They have not been extensively studied in myeloma therapy.

From January of 2010 to December of 2017, 105 with MM received thalidomide and dexamethasone based triplet induction therapy, maintenance with thalidomide and creatinine clearance > 30 mL/min. From those, 23 (21.9%) had only an additional risk factor and were randomized 5:1 to receive 100 mg aspirin or 10 mg rivaroxaban until relapse and need another treatment. Doppler ultrasound was performed every six months or as medical indication in all patients and pulmonary CT scan if EP was suspected.

Five patients received rivaroxaban, 3 males and 2 females, median age of 67.5 years; additional factors were obesity in 4 and DM in one. Aspirin was received by 18 patients, 10 males an 8 females, median age 66.8 years; additional factors were obesity in 10, DM in 5, erythropoietin in 3.

No patient in the Rivaroxaban arm developed thrombosis; bleeding episodes were self-limited to the gums and easy bruising; no major bleeding was detected. One patient in the Aspirin arm, with body mass index of 31.22 kg/m2 as an additional risk factor, developed right iliofemoral DVT without PE; he was changed to rivaroxaban at therapeutic doses for six months with resolution of the DVT and then continue with 10 mg dose; bleeding episodes in all patients were similar to the rivaroxaban arm.

In this small group of patients with a low risk factors with an additional one, that could be in an intermediate risk, the use of rivaroxaban showed a good efficiency and security profiles. Either, rivaroxaban or aspirin could be used in this situations and deserve further investigation.

Disclosures

No relevant conflicts of interest to declare.
Alpha-Granules in Resting Human Platelets Are a Spatially Clustered, Single Major Population
Authors: Pokrovskaya Irina D , Storrie Brian , Yadav Shilpi , Rao Amith , McBride Emma , Aronova Maria , Leapman Richard
Published: October 2019

We interrogated in 3D-space the arrangement of alpha-granules and their proteins within 30 human platelets in order to address two central structure/function questions. First, are alpha-granules based on their size, shape and protein content a single population or not, and second, what implications could organelle frequency and organization within the resting platelet have for platelet biogenesis and membrane fusion events in activated platelets? We used serial block face scanning electron microscopy (SBF-SEM) to render in full platelet volume the ultrastructure of alpha-granules, dense granules, mitochondria, canalicular system (CS), and plasma membrane (PM) in 30 platelets, 10 each from 3 donors. Size and shape were measured for 1488 a-granules. Compositional data were assessed for multiple proteins over hundreds of granules by 3D-structured illumination microscopy (SIM) and serial section cryo-immunogold electron microscopy. Data analysis led to 3 conclusions: 1) Based on size, shape and protein composition, there was one major population of alpha-granules in resting human platelets, 2) Alpha-granules clustered tightly together while dense granules were more peripherally located and distal from one another suggesting a spatial arrangement that in the one case supports compound granule fusion and in the other case rapid fusion with the PM, and 3) Based on the weak relationship between platelet size and organelle number and volume, we inferred that platelet biogenesis is likely relatively imprecise with alpha-granule inclusion being more precisely metered than that of other organelles,. These results provide a strong, informative baseline for a-granule structural properties and suggest a spatial clustering of organelles within the resting platelet that may be functionally significant during platelet activation.

Figure. Figure.

Disclosures

No relevant conflicts of interest to declare.
The human phylome
Authors: Huerta-Cepas Jaime , Dopazo Hernán , Dopazo Joaquín , Gabaldón Toni
Published: October 2019

Background:

Phylogenomics analyses serve to establish evolutionary relationships among organisms and their genes. A phylome, the complete collection of all gene phylogenies in a genome, constitutes a valuable source of information, but its use in large genomes still constitutes a technical challenge. The use of phylomes also requires the development of new methods that help us to interpret them.

Results:

We reconstruct here the human phylome, which includes the evolutionary relationships of all human proteins and their homologs among 39 fully sequenced eukaryotes. Phylogenetic techniques used include alignment trimming, branch length optimization, evolutionary model testing and maximum likelihood and Bayesian methods. Although differences with alternative topologies are minor, most of the trees support the Coelomata and Unikont hypotheses as well as the grouping of primates with laurasatheria to the exclusion of rodents. We assess the extent of gene duplication events and their relationship with the functional roles of the protein families involved. We find support for at least one, and probably two, rounds of whole genome duplications before vertebrate radiation. Using a novel algorithm that is independent from a species phylogeny, we derive orthology and paralogy relationships of human proteins among eukaryotic genomes.

Conclusion:

Topological variations among phylogenies for different genes are to be expected, highlighting the danger of gene-sampling effects in phylogenomic analyses. Several links can be established between the functions of gene families duplicated at certain phylogenetic splits and major evolutionary transitions in those lineages. The pipeline implemented here can be easily adapted for use in other organisms.
ChromaClade: combined visualisation of phylogenetic and sequence data
Authors: Monit Christopher , Goldstein Richard A. , Towers Greg J.
Published: October 2019

Background

Studying site-specific amino acid frequencies by eye can reveal biologically significant variability and lineage-specific adaptation. This so-called ‘sequence gazing’ often informs bioinformatics and experimental research. But it is important to also account for the underlying phylogeny, since similarities may be due to common descent rather than selection pressure, and because it is important to distinguish between founder effects and convergent evolution. We set out to combine phylogenetic and sequence data to produce evolutionarily insightful visualisations.

Results

We present ChromaClade, a convenient tool with a graphical user-interface that works in concert with popular tree viewers to produce colour-annotated phylogenies highlighting residues found in each taxon and at each site in a sequence alignment. Colouring branches according to residues found at descendent tips also quickly identifies lineage-specific residues and those internal branches where key substitutions have occurred. We demonstrate applications of ChromaClade to human immunodeficiency virus and influenza A virus datasets, illustrating cases of conservative, adaptive and convergent evolution.

Conclusions

We find this to be a powerful approach for visualising site-wise residue distributions and detecting evolutionary patterns, especially in large datasets. ChromaClade is available for Windows, macOS and Unix or Linux; program executables and source code are available at github.com/chrismonit/chroma_clade.
Signatures of selection for resistance to Haemonchus contortus in sheep and goats
Authors: Estrada-Reyes Zaira M. , Tsukahara Yoko , Amadeu Rodrigo R. , Goetsch Arthur L. , Gipson Terry A. , Sahlu Tilahun , Puchala Richard , Wang Zaisen , Hart Steve P. , Mateescu Raluca G.
Published: October 2019

Background

Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode,Haemonchus contortus. Host genetic variation for resistance toH. contortusallows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimateFst outliers in three different breeds of sheep and goats exposed toH. contortus.

Results

Our results for sheep populations showed SNPs under selection inC3AR1,CSF3,SOCS2,NOS2,STAT5B,TGFB2andIL2RAgenes using frequentist and Bayesian approaches. For goats, SNPs inCD1D,ITGA9,IL12A,IL13RA1, CD86andTGFB2genes were under selection. Common signatures of selection in both species were observed inNOS2,TGFB2andTLR4genes. Directional selection was present in all SNPs evaluated in the present study.

Conclusions

A total of 13 SNPs within 7 genes of our candidate gene panel related toH. contortusexposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance toH. contortusis likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection againstH. contortusinfection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.
High-throughput sequencing revealed differences of microbial community structure and diversity between healthy and diseased Caulerpa lentillifera
Authors: Liang Zhourui , Liu Fuli , Wang Wenjun , Zhang Pengyan , Sun Xiutao , Wang Feijiu , Kell Heather
Published: October 2019

Background

Caulerpa lentillifera is one of the most important economic green macroalgae in the world. Increasing demand for consumption has led to the commercial cultivation of C. lentillifera in Japan and Vietnam in recent decades. Concomitant with the increase of C. lentillifera cultivation is a rise in disease. We hypothesise that epiphytes or other microorganisms outbreak at the C. lentillifera farm may be an important factor contributing to disease in C. lentillifera. The main aims are obtaining differences in the microbial community structure and diversity between healthy and diseased C. lentillifera and key epiphytes and other microorganisms affecting the differences through the results of high-throughput sequencing and bioinformatics analysis in the present study.

Results

A total of 14,050, 2479, and 941 operational taxonomic units (OTUs) were obtained from all samples using 16S rDNA, 18S rDNA, and internal transcribed spacer (ITS) high-throughput sequencing, respectively. 16S rDNA sequencing and 18S rDNA sequencing showed that microbial community diversity was higher in diseased C. lentillifera than in healthy C. lentillifera. Both PCoA results and UPGMA results indicated that the healthy and diseased algae samples have characteristically different microbial communities. The predominant prokaryotic phyla were Proteobacteria, Planctomycetes, Bacteroidetes, Cyanobacteria, Acidobacteria, Acidobacteria and Parcubacteria in all sequences. Chlorophyta was the most abundant eukaryotic phylum followed by Bacillariophyta based on 18S rDNA sequencing. Ascomycota was the dominant fungal phylum detected in healthy C. lentillifera based on ITS sequencing, whereas fungi was rare in diseased C. lentillifera, suggesting that Ascomycota was probably fungal endosymbiont in healthy C. lentillifera. There was a significantly higher abundance of Bacteroidetes, Cyanobacteria, Bacillariophyta, Ulvales and Tetraselmis in diseased C. lentillifera than in healthy C. lentillifera. Disease outbreaks significantly change carbohydrate metabolism, environmental information processing and genetic information processing of prokaryotic communities in C. lentillifera through predicted functional analyses using the Tax4Fun tool.

Conclusions

Bacteroidetes, Cyanobacteria, Bacillariophyta, Ulvales and Tetraselmis outbreak at the C. lentillifera farm sites was an important factor contributing to disease in C. lentillifera.
Glucose associated NETosis in patients with ST-elevation myocardial infarction: an observational study
Authors: Helseth Ragnhild , Knudsen Eva Cecilie , Eritsland Jan , Opstad Trine Baur , Arnesen Harald , Andersen Geir Øystein , Seljeflot Ingebjørg
Published: October 2019

Background

Neutrophil extracellular traps (NETs) have recently been identified as mediators in atherothrombosis. Although NETosis in general has been suggested to be glucose dependent, the transferability to patients with acute ST-elevation myocardial infarction (STEMI) is unclear. We assessed whether the NETs markers double-stranded deoxyribonucleid acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) associated with plasma glucose and the glucometabolic status in the acute phase and 3 months after a STEMI. We also explored whether an acute glucose load resulted in upregulated NETosis by assessment of peptidylarginine deiminase 4 (PAD4) gene expression.

Methods

In total, 224 STEMI patients were prospectively enrolled and underwent blood sampling acutely (median 16.5 h after PCI) and after 3 months. Glucometabolic status was defined based on the results of an oral glucose tolerance test (OGTT) as normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes (T2DM). dsDNA and MPO-DNA were measured in serum, while PAD4 mRNA was measured in circulating leukocytes by RT-PCR.

Results

dsDNA levels were significantly correlated to plasma glucose both acutely and after 3 months (r = 0.12 and r = 0.17, both p < 0.02), whereas MPO-DNA was not. No associations with the glucometabolic status were encountered for dsDNA and MPO-DNA acutely, but after 3 months dsDNA levels were elevated in patients with IFG and T2DM vs. NGR (428 vs. 371 ng/ml and 408 vs. 371 ng/ml, both p < 0.045). During the acute glucose load after 3 months, dsDNA and MPO-DNA remained unchanged while PAD4 mRNA increased significantly (RQ 0.836 vs. 0.920, p = 0.02).

Conclusions

In this cohort of STEMI patients, levels of dsDNA associated with plasma glucose both in the acute and stable condition. The glucometabolic status was not substantially related to the selected NETs markers, however, an acute glucose load by OGTT performed after 3 months resulted in increased PAD4 expression, suggestive of enhanced NETosis in the aftermath of STEMI.

Trial registration

www.clinicaltrials.gov, NCT00926133. Registered June 23, 2009.
Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs
Authors: Abawi Dawud , Faragli Alessandro , Schwarzl Michael , Manninger Martin , Zweiker David , Kresoja Karl-Patrik , Verderber Jochen , Zirngast Birgit , Maechler Heinrich , Steendijk Paul , Pieske Burkert , Post Heiner , Alogna Alessio
Published: October 2019

Background

Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min− 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min− 1 under various inotropic states.

Methods

We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min− 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax).

Results

CPO showed the best correlation with LV SW min− 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min− 1 (LVPmaxr2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min− 1 (r2 = 0.28).

Conclusion

CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU.
Women’s experience of unplanned out-of-hospital birth in paramedic care
Authors: Flanagan Belinda , Lord Bill , Reed Rachel , Crimmins Gail
Published: October 2019

Background

Healthcare literature describes predisposing factors, clinical risk, maternal and neonatal clinical outcomes of unplanned out-of-hospital birth; however, there is little quality research available that explores the experiences of mothers who birth prior to arrival at hospital.

Methods

This study utilised a narrative inquiry methodology to explore the experiences of women who birth in paramedic care.

Results

The inquiry was underscored by 22 narrative interviews of women who birthed in paramedic care in Queensland, Australia between 2011 and 2016. This data identified factors that contributed to the planned hospital birth occurring in the out-of-hospital setting. Women in this study began their story by discussing previous birth experience and their knowledge, expectations and personal beliefs concerning the birth process. Specific to the actual birth event, women reported feeling empowered, confident and exhilarated. However, some participants also identified concerns with paramedic practice; lack of privacy, poor interpersonal skills, and a lack of consent for certain procedures.

Conclusions

This study identified several factors and a subset of factors that contributed to their experiences of the planned hospital birth occurring in the out-of-hospital setting. Women described opportunities for improvement in the care provided by paramedics, specifically some deficiencies in technical and interpersonal skills.
Acceptability and barriers to implementation of N-of-1 tests in Ethiopia - a qualitative study
Authors: Alemayehu Chalachew , Mitchell Geoff , Nikles Jane , Aseffa Abraham , Clavarino Alexandra
Published: October 2019

Background

Locally produced generic drugs offer a cost–effective alternative to imported drugs to treat patients in Ethiopia. However, due to a lack of bioequivalence testing, additional assurance tests are needed to build trust in cheaper, locally made drugs. By testing bioequivalence of local drugs to gold standard, N-of-1 tests have the potential to promote patient centred quality use of medicines.

Method

We sought to assess the acceptability of, and explore barriers to, conducting N-of-1 tests to evaluate local medicines in a resource limited clinical setting. We conducted a descriptive qualitative study, analysing four focus group discussions and five key informant interviews. Participants were senior drug regulatory authority members, institutional review board members, physicians and patients. All interviews were audio taped and transcribed verbatim. Patient interviews were conducted in Amharic and translated to English prior to analysis. Data analysis used an inductive, thematic process.

Results

Five major themes were identified; (1) Appropriateness of N-of-1 tests to determine the therapeutic equivalence of local drugs, (2) N-of-1 therapeutic equivalence tests: clinical care or research? (3) Ethical and regulatory requirements (IRB), (4) Potential barriers to implementing N-of-1 tests and (5) Possible solutions to identified challenges. The study demonstrated considerable support for using N-of-1 tests for clinical equivalence studies between local and imported medicines, but important impediments were very likely to impact the feasibility of conducting N-of-1 tests in Ethiopia. Key informants from the regulatory authority did not support additional tests of local drugs. There were also mixed opinions regarding ethical requirements for conducting N-of-1 tests. The Institutional Review Board (IRB) members believed that IRB approval was sufficient to conduct N-of-1 tests, however, the regulatory authority members considered that N-of-1 tests constituted a clinical trial, and required approval at the regulatory level.

Conclusion

This study showed that there were key uncertainties that could impact the feasiblity of using N-of-1 testing local drugs in Ethiopia. Therefore, a number of protocol amendments to address contextual threats and regulatory challenges, would be needed before progressing to conducting these tests.
Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools
Authors: Tolksdorf Johanna , Kattan Michael W. , Boorjian Stephen A. , Freedland Stephen J. , Saba Karim , Poyet Cedric , Guerrios Lourdes , De Hoedt Amanda , Liss Michael A. , Leach Robin J. , Hernandez Javier , Vertosick Emily , Vickers Andrew J. , Ankerst Donna P.
Published: October 2019

Background

Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool.

Methods

We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance.

Results

High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004).

Conclusions

We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.
Correction to: Feasibility of identifying important changes in care management resulting from cardiovascular magnetic resonance (CMR) using hospital episode data in patients who activate the primary percutaneous coronary intervention (PPCI) pathway
Authors: Pufulete Maria , Harris Jessica , Dorman Stephen , Cook Lynn , Bucciarelli-Ducci Chiara , Greenwood John P. , Anderson Richard , Brierley Rachel , Reeves Barnaby C.
Published: October 2019

In the original publication of this article [1], the author noted two corrections after publication.
Candidate single nucleotide polymorphisms of irritable bowel syndrome: a systemic review and meta-analysis
Authors: Zhu Shiwei , Wang Ben , Jia Qiong , Duan Liping
Published: October 2019

Background

Genetic factors increase the risk of irritable bowel syndrome (IBS). Analysis of single nucleotide polymorphisms (SNPs) has been used in IBS patients, but the findings are inconsistent. The goal of this review was to synthesize all the published SNPs studies of IBS through meta-analysis to objectively evaluate the relevance of SNPs to IBS risks.

Methods

IBS - related polymorphisms studies from 2000 to 2018 were searched. Pooled odds ratios with a 95% confidence interval for each SNP were evaluated through five genetic models. Ethnicity, ROME criteria and IBS subtypes were defined for subgroup analyze.

Results

Ten relevant genes were evaluated. SNPs rs4263839 and rs6478108 of TNFSF15 associated with an increased risk of IBS; IL6 rs1800795 increased the risk for Caucasian IBS patients which diagnosed by Rome III criteria; and IL23R rs11465804 increased the risk for IBS-C patients. IL10 rs1800896 GG genotype associated with a decreased risk of IBS. No evidence supported the association of GNβ3 rs5443, TNFα rs1800629, and IL10 rs1800871 to IBS in this study.

Conclusions

This meta-analysis presents an in-depth overview for IBS SNPs analysis. It was confirmed that polymorphisms of TNFSF15 associated with increased IBS risk, while IL10 rs1800896 associated with decreased IBS risk. It might offer some insights into polymorphisms of inflammation factors which might affect IBS susceptibility. Moreover, the analysis also emphasizes the importance of diagnostic criteria and phenotype homogeneity in IBS genetic studies.
Patient views about the impact of ulcerative colitis and its management with drug treatment and surgery: a nested qualitative study within the CONSTRUCT trial
Authors: Rapport Frances , Clement Clare , Seagrove Anne C. , Alrubaiy Laith , Hutchings Hayley A. , Williams John G.
Published: October 2019

Background

A nested qualitative interview study within the CONSTRUCT trial was conducted to explore experiences and perceptions of patients with acute severe ulcerative colitis following treatment with infliximab or ciclosporin, surgery, or other medication.

Methods

Two hundred seventy patients with steroid-resistant ulcerative colitis were randomised to either infliximab or ciclosporin. Interviews were conducted with 20 trial participants. Thirty-five data capture events took place in total, 20 interviews conducted 3 months after treatment and a further 15 interviews with the same cohort as second interviews at 12 months.

Results

Disease duration varied but similar stories emerged about how people adjusted to living with ulcerative colitis. Issues raised by patients included; the debilitating effect of the disease on quality of life, living with the unpredictability of symptoms and treatment, dealing with embarrassment and stigma and the desire to share knowledge of the disease with others to combat the private nature of this debilitating illness and bring greater visibility to patient experience of symptoms and outcomes.

Conclusion

Patients were more positive about treatment with infliximab than ciclosporin, mainly due to the cumbersome intravenous regimen required for ciclosporin. Prompt diagnosis is required and early reporting of changes in symptoms is encouraged to ensure appropriate treatment.

Trial registration

This trial is registered with the ISRCTN registry; numberISRCTN22663589. The date of registration was 16/05/2008.
Dose-response association between physical activity and sedentary time categories on ageing biomarkers
Authors: Mañas Asier , del Pozo-Cruz Borja , Rodríguez-Gómez Irene , Leal-Martín Javier , Losa-Reyna José , Rodríguez-Mañas Leocadio , García-García Francisco J. , Ara Ignacio
Published: October 2019

Background

Physical activity and sedentary behaviour have been suggested to independently affect a number of health outcomes. To what extent different combinations of physical activity and sedentary behaviour may influence physical function and frailty outcomes in older adults is unknown. The aim of this study was to examine the combination of mutually exclusive categories of accelerometer-measured physical activity and sedentary time on physical function and frailty in older adults.

Methods

771 older adults (54% women; 76.8 ± 4.9 years) from the Toledo Study for Healthy Aging participated in this cross-sectional study. Physical activity and sedentary time were measured by accelerometry. Physically active was defined as meeting current aerobic guidelines for older adults proposed by the World Health Organization. Low sedentary was defined as residing in the lowest quartile of the light physical activity-to-sedentary time ratio. Participants were then classified into one of four mutually exclusive movement patterns: (1) ‘physically active & low sedentary’, (2) ‘physically active & high sedentary’, (3) ‘physically inactive & low sedentary’, and (4) ‘physically inactive & high sedentary’. The Short Physical Performance Battery was used to measure physical function and frailty was assessed using the Frailty Trait Scale.

Results

‘Physically active & low sedentary’ and ‘physically active & high sedentary’ individuals had significantly higher levels of physical function (β = 1.73 and β = 1.30 respectively; all p < 0.001) and lower frailty (β = − 13.96 and β = − 8.71 respectively; all p < 0.001) compared to ‘physically inactive & high sedentary’ participants. Likewise, ‘physically inactive & low sedentary’ group had significantly lower frailty (β = − 2.50; p = 0.05), but significance was not reached for physical function.

Conclusions

We found a dose-response association of the different movement patterns analysed in this study with physical function and frailty. Meeting the physical activity guidelines was associated with the most beneficial physical function and frailty profiles in our sample. Among inactive people, more light intensity relative to sedentary time was associated with better frailty status. These results point out to the possibility of stepwise interventions (i.e. targeting less strenuous activities) to promote successful aging, particularly in inactive older adults.