bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotropic silicon etch characteristics in a purely inductively coupled SF6 plasma
Authors: Panduranga Parashara , Abdou Aly , Ren Zhong , Pedersen Rasmus H. , Nezhad Maziar P.
Published: November 2019

The characteristics of isotropic etching of silicon in a purely inductively coupled SF6 plasma are quantitatively studied. Since the etch results are strongly dependent on mask features, the authors investigated both large area and narrow trench etch characteristics. Circles of diameter 500 μm were used as a proxy for unpatterned surfaces and etched for different durations to establish the material etch rate and surface roughness. The average etch rate using the chosen recipe was found to be 2.27 μm/min. Arrays of narrow trenches ranging from 8 to 28 μm were also etched to analyze the effect of trench size on etch rate and degree of anisotropy. The etch rate of the trenches was found to strongly decrease with decreasing trench width. The results demonstrate that isotropic SF6 etch can be readily used as a replacement for more exotic silicon vapor phase etch chemistries such as XeF2.
Optical characterization of inhomogeneous thin films containing transition layers using the combined method of spectroscopic ellipsometry and spectroscopic reflectometry based on multiple-beam interference model
Authors: Ohlídal Ivan , Vohánka Jiří , Buršíková Vilma , Ženíšek Jaroslav , Vašina Petr , Čermák Martin , Franta Daniel
Published: November 2019

This paper presents the results of the optical characterization of inhomogeneous thin films of polymer-like SiOxCyHz and non-stoichiometric silicon nitride SiNx. An efficient method combining variable angle spectroscopic ellipsometry and spectroscopic reflectometry applied at the near-normal incidence based on the multiple-beam interference model is utilized for this optical characterization. The multiple-beam interference model allows us to quickly evaluate the values of ellipsometric parameters and reflectance of the inhomogeneous thin films, which exhibit general profiles of their optical constants. The spectral dependencies of the optical constants of the inhomogeneous SiOxCyHz and SiNx thin films are determined using the Campi–Coriasso dispersion model. The profiles of the optical constants of these films can also be determined. Furthermore, the transition layers at the lower boundaries of the characterized films are also taken into account. Spectral dependencies of the optical constants of these transition layers are also determined using the Campi–Coriasso dispersion model.
Eliminating etch stop in high-density magnetic tunnel junction patterning using high-temperature CO/NH3 plasma etching
Authors: Satake Makoto , Abe Takahiro , Ichino Takamasa , Suyama Makoto , Kawaguchi Tadayoshi , Yamada Masaki , Matsumoto Eiji , Maeda Kenji , Yokogawa Kenetsu
Published: November 2019

Increasing the process temperature in CO/NH3 plasma etching has been investigated to suppress an etch stop in high-density magnetic tunnel junction stack (MTJ stack) patterning with a Ta mask. In a previous study, the occurrence of an etch stop was observed when using a 100 nm space pattern; specifically, the etching depth was unchanged with the 100 nm space pattern when the etching time was increased, although when wider spaces were used, the etching depth increased proportionally. In this study, differences in the etch stop depth with 100 nm space patterns were examined by changing the electrode temperature from 120 to 300 °C. The etch stop depth became deeper as the electrode temperature was increased and it was found that a high-temperature CO/NH3 process was an effective way to prevent the etch stop effect. However, at 300 °C, the MTJ stack's thickness was observed to expand, which may induce a deterioration of the junction's magnetic properties. A scanning transmission electron microscope image and an energy dispersive x-ray spectroscopy image of the MTJ stack revealed that nitridation of the MTJ stack was the reason of its expansion in thickness. Moreover, pure N2 plasma irradiation of the MTJ stack clearly indicated that this thickness expansion occurred for an electrode temperature of over 265 °C. Finally, the results demonstrate that, for a CO/NH3 process with an electrode temperature of 250 °C, it is possible to etch a 52-nm-thick MTJ stack without either etch stop or film thickness expansion occurring.
Multiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut Microbiota
Authors: Lomeli Barbara K. , Galbraith Hal , Schettler Jared , Saviolakis George A. , El-Amin Wael , Osborn Blaire , Ravel Jacques , Hazleton Keith , Lozupone Catherine A. , Evans Ronald J. , Bell Stacie J. , Ochsner Urs A. , Jarvis Thale C. , Baqar Shahida , Janjic Nebojsa
Published: November 2019

CRS3123 is a novel small molecule that potently inhibits methionyl-tRNA synthetase of
Clostridioides difficile
, inhibiting
C. difficile
toxin production and spore formation. CRS3123 has been evaluated in a multiple-ascending-dose placebo-controlled phase 1 trial.
Substrate Use Prioritization by a Coculture of Five Species of Gut Bacteria Fed Mixtures of Arabinoxylan, Xyloglucan, β-Glucan, and Pectin
Authors: Liu Yafei , Heath Anne-Louise , Galland Barbara , Rehrer Nancy , Drummond Lynley , Wu Xi-Yang , Bell Tracey J. , Lawley Blair , Sims Ian M. , Tannock Gerald W.
Published: November 2019

This study addresses the question as to how bacterial species, characteristic of the human gut microbiota, collectively utilize mixtures of plant polysaccharides such as are found in dietary fiber. Five bacterial species with the capacity to degrade polymers and/or produce acidic fermentation products detectable in human feces were used in the experiments. The bacteria showed preferential use of certain polysaccharides over others for growth, and this influenced their fermentation output qualitatively. These kinds of studies are essential in developing concepts of how the gut microbial community shares habitat resources, directly and indirectly, when presented with mixtures of polysaccharides that are found in human diets. The concepts are required in planning dietary interventions that might correct imbalances in the functioning of the human microbiota so as to support measures to reduce metabolic conditions such as obesity.
Anoxygenic Phototrophs Span Geochemical Gradients and Diverse Morphologies in Terrestrial Geothermal Springs
Authors: Hamilton Trinity L. , Bennett Annastacia C. , Murugapiran Senthil K. , Havig Jeff R.
Published: November 2019

There is a long and rich history of literature on phototrophs in terrestrial geothermal springs. These studies have revealed sulfide, pH, and temperature are the main constraints on phototrophy. However, the taxonomic and physiological diversity of anoxygenic phototrophs suggests that, within these constraints, specific geochemical parameters determine the distribution and activity of individual anoxygenic phototrophic taxa. Here, we report the recovery of sequences affiliated with characterized anoxygenic phototrophs in sites that range in pH from 2 to 9 and in temperature from 31°C to 71°C. Transcript abundance indicates anoxygenic phototrophs are active across this temperature and pH range. Our data suggest sulfide is not a key determinant of anoxygenic phototrophic taxa and underscore a role for photoheterotrophy in terrestrial geothermal ecosystems. These data provide the framework for high-resolution sequencing and
in situ
activity approaches to characterize the physiology of specific anoxygenic phototrophic taxa across a broad range of temperatures and pH.
When “evaporites” are not formed by evaporation: The role of temperature and pCO2 on saline deposits of the Eocene Green River Formation, Colorado, USA
Authors: Demicco Robert V. , Lowenstein Tim K.
Published: November 2019

Halite precipitates in the Dead Sea during winter but re-dissolves above the thermocline upon summer warming, “focusing” halite deposition below the thermocline (Sirota et al., 2016, 2017, 2018). Here we develop an “evaporite focusing” model for evaporites (nahcolite + halite) preserved in a restricted area of the Eocene Green River Formation in the Piceance Creek Basin of Colorado, USA. Nahcolite solubility is dependent on partial pressure of carbon dioxide (pCO2) as well as temperature (T), so these models covary with both T and pCO2. In the lake that filled the Piceance Creek Basin, halite, nahcolite or mixtures of both could have precipitated during winter cooling, depending on the CO2 content in different parts of the lake. Preservation of these minerals occurs below the thermocline (>∼25 m) in deeper portions of the basin. Our modeling addresses both: (1) the restriction of evaporites in the Piceance Creek Basin to the center of the basin without recourse to later dissolution and (2) the variable mineralogy of the evaporites without recourse to changes in lake water chemistry. T from 20 to 30 °C and pCO2 between 1800 and 2800 ppm are reasonable estimates for the conditions in the Piceance Creek Basin paleolake. Other evaporites occur in the center of basins but do not extend out to the edges of the basin. Evaporite focusing caused by summer-winter T changes in the solubility of the minerals should be considered for such deposits and variable pCO2 within the evaporating brines also needs to be considered if pCO2 sensitive minerals are found.
Subduction, mantle metasomatism, and gold: A dynamic and genetic conjunction
Authors: Groves David I. , Zhang Liang , Santosh M.
Published: November 2019

Global gold deposit classes are enigmatic in relation to first-order tectonic scale, leading to controversial genetic models and exploration strategies. Traditionally, hydrothermal gold deposits that formed through transport and deposition from auriferous ore fluids are grouped into specific deposit types such as porphyry, skarn, high- and low-sulfidation–type epithermal, gold-rich volcanogenic massive sulfide (VMS), Carlin-type, orogenic, and iron-oxide copper-gold (IOCG), and intrusion-related gold deposits (IRGDs). District-scale mineral system approaches propose interrelated groups such as porphyry Cu-Au, skarn Cu-Au-Ag, and high-sulfidation Au-Ag. In this study, the temporal evolution of subduction-related processes in convergent margins was evaluated to propose a continuum of genetic models that unify the various types of gold deposits. At the tectonic scale of mineral systems, all hydrothermal gold deposits are interrelated in that they formed progressively during the evolution of direct or indirect subduction-related processes along convergent margins. Porphyry-related systems formed initially from magmatic-hydrothermal fluids related to melting of fertile mantle to initiate calc-alkaline to high-K felsic magmatism in volcanic arcs directly related to subduction. Formation of gold-rich VMS systems was related to hydrothermal circulation driven by magmatic activity during rifting of oceanic arcs. Orogenic gold deposits formed largely through fluids derived from devolatilization of the downgoing slab and overlying sediment wedge during late transpression in the orogenic cycle. Carlin-type deposits, IRGDs, and some continental-arc porphyry systems formed during the early stages of orogenic collapse via fluids directly or indirectly related to hybrid magmatism from melting of lithosphere that was metasomatized and gold-fertilized by earlier fluid release from subduction zones near margins of continental blocks. The IOCGs were formed during postorogenic asthenosphere upwelling beneath such subduction-related metasomatized and fertilized lithospheric blocks via fluid release and explosive emplacement of volatile-rich melts. Thus, importantly, subduction is clearly recognized as the key unifying dynamic factor in gold metallogenesis, with subduction-related fluids or melts providing the critical ore components for a wide variety of gold-rich deposit types.
ICON 2019—International Scientific Tendinopathy Symposium Consensus: There are nine core health-related domains for tendinopathy (CORE DOMAINS): Delphi study of healthcare professionals and patients
Authors: Vicenzino Bill , de Vos Robert-Jan , Alfredson Hakan , Bahr Roald , Cook Jill L , Coombes Brooke K , Fu Siu Ngor , Gravare Silbernagel Karin , Grimaldi Alison , Lewis Jeremy S , Maffulli Nicola , Magnusson SP , Malliaras Peter , Mc Auliffe Sean , Oei Edwin H G , Purdam Craig , Rees Jonathan D , Rio Ebonie Kendra , Scott Alex , Speed Cathy , Akker-Scheek Inge van den , Weir Adam , Wolf Jennifer Moriatis , Zwerver Johannes
Published: November 2019

Background

The absence of any agreed-upon tendon health-related domains hampers advances in clinical tendinopathy research. This void means that researchers report a very wide range of outcome measures inconsistently. As a result, substantial synthesis/meta-analysis of tendon research findings is almost futile despite researchers publishing busily. We aimed to determine options for, and then define, core health-relateddomainsfor tendinopathy.

Methods

We conducted a Delphi study of healthcare professionals (HCP) and patients in a three-stage process. In stage 1, we extracted candidate domains from clinical trial reports and developed an online survey. Survey items took the form: ‘The ‘candidate domain’is important enough to be included as a core health-related domain of tendinopathy’; response options were: agree, disagree, or unsure. In stage 2, we administered the online survey and reported the findings. Stage 3 consisted of discussions of the findings of the survey at the ICON (International Scientific Tendinopathy Symposium Consensus) meeting. We set 70% participant agreement as the level required for a domain to be considered ‘core’; similarly, 70% agreement was required for a domain to be relegated to ‘not core’ (see Results next).

Results

Twenty-eight HCP (92% of whom had >10 years of tendinopathy experience, 71% consulted >10 cases per month) and 32 patients completed the online survey. Fifteen HCP and two patients attended the consensus meeting. Of an original set of 24 candidate domains, the ICON group deemed nine domains to be core. These were: (1) patient rating of condition, (2) participation in life activities (day to day, work, sport), (3) pain on activity/loading, (4) function, (5) psychological factors, (6) physical function capacity, (7) disability, (8) quality of life and (9) pain over a specified time. Two of these (2, 6) were an amalgamation of five candidate domains. We agreed that seven other candidate domainswere notcore domains: range of motion, pain on clinician applied test, clinical examination, palpation, drop out, sensory modality pain and pain without other specification. We were undecided on the other five candidate domains of physical activity, structure, medication use, adverse effects and economic impact.

Conclusion

Nine core domains for tendon research should guide reporting of outcomes in clinical trials. Further research should determine the best outcome measures for each specific tendinopathy (ie, core outcome sets).
Investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial comparing intubating conditions in 25° head-up position and supine: the InSize25 study protocol
Authors: Falempin Anne-Sophie , Pereira Bruno , Binakdane Fatima , Bazin Jean-Etienne , Smirdec Margot
Published: November 2019

Introduction

Difficult airway management during tracheal intubation can lead to severe hypoxic sequelae. Routine intubation practice is to use a strict supine position, whereas a 25° head-up or reverse Trendelenburg position increases efficacy of preoxygenation, seems more comfortable for the anaesthetist and may also provide better intubation conditions in direct laryngoscopy. The 25° head-up position could be used for the whole population rather than only for obese patients, but there is no prospective randomised controlled trial with a robust design and large number of patients comparing strict supine against 25° intubation in operating room. The objective of the InSize25 study is to test the effect of these two patient positions on intubation conditions during laryngoscopy in scheduled surgery on non-obese patients.

Methods and analysis

InSize25 is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial. The InSize25 study will randomise 1000 adult patients scheduled for surgery under general anaesthesia requiring intubation with neuromuscular-blocking drugs, candidates for direct laryngoscopy. The primary outcome variable is the view obtained during the first laryngoscopy without any external manipulation assessed using percentage of glottic opening. Important secondary outcomes are: Cormack-Lehane classification, number of attempts at laryngoscopy and at tracheal intubation, use of ancillary equipment (eg, bougies, alternative laryngoscope blades, videolaryngoscope) and manoeuvres (eg, laryngeal manipulation), comfort score for the anaesthetist, episodes of postinduction hypotension or desaturation and mechanical complications of intubation.

Ethics and dissemination

The trial received appropriate approval from the ‘CPP Sud-Est II’ ethical review board. Informed consent is required. If the 25° head-up position proves superior for tracheal intubation without more complications, it may become the routine-standard intubation position rather than only for use with obese patients. The final results will be published in a peer-reviewed journal.

Trial registration number

Clinicaltrials.gov identifier (NCT03339141).
Mental well-being of international migrants to Japan: a systematic review
Authors: Miller Russell , Tomita Yuri , Ong Ken Ing Cherng , Shibanuma Akira , Jimba Masamine
Published: November 2019

Background

Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages.

Objectives

To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan.

Design

Systematic review

Data sources

PubMed, ProQuest, Web of Science, Ichushi and J-Stage

Eligibility criteria

Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included.

Data extraction and synthesis

Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed.

Results

Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public.

Conclusion

Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change.

PROSPERO registration number

CRD42018108421.
Yoga and Cardiovascular Health Trial (YACHT): a UK-based randomised mechanistic study of a yoga intervention plus usual care versus usual care alone following an acute coronary event
Authors: Tillin Therese , Tuson Claire , Sowa Barbara , Chattopadhyay Kaushik , Sattar Naveed , Welsh Paul , Roberts Ian , Ebrahim Shah , Kinra Sanjay , Hughes A , Chaturvedi Nishi
Published: November 2019

Objective

To determine the effects of yoga practice on subclinical cardiovascular measures, risk factors and neuro-endocrine pathways in patients undergoing cardiac rehabilitation (CR) following acute coronary events.

Design

3-month, two-arm (yoga +usual care vs usual care alone) parallel randomised mechanistic study.

Setting

One general hospital and two primary care CR centres in London. Assessments were conducted at Imperial College London.

Participants

80 participants, aged 35–80 years (68% men, 60% South Asian) referred to CR programmes 2012–2014.

Intervention

A certified yoga teacher conducted yoga classes which included exercises in stretching, breathing, healing imagery and deep relaxation. It was pre-specified that at least 18 yoga classes were attended for inclusion in analysis. Participants and partners in both groups were invited to attend weekly a 6- to 12-week local standard UK National Health Service CR programme.

Main outcome measures

(i) Estimated left ventricular filling pressure (E/e′), (ii) distance walked, fatigue and breathlessness in a 6 min walk test, (iii) blood pressure, heart rate and estimated peak VO2following a 3 min step-test. Effects on the hypothalamus–pituitary–adrenal axis, autonomic function, body fat, blood lipids and glucose, stress and general health were also explored.

Results

25 participants in the yoga + usual care group and 35 participants in the usual care group completed the study. Following the 3-month intervention period, E/e′ was not improved by yoga (E/e′: between-group difference: yoga minus usual care:−0.40 (−1.38, 0.58). Exercise testing and secondary outcomes also showed no benefits of yoga.

Conclusions

In this small UK-based randomised mechanistic study, with 60 completing participants (of whom 25 were in the yoga + usual care group), we found no discernible improvement associated with the addition of a structured 3-month yoga intervention to usual CR care in key cardiovascular and neuroendocrine measures shown to be responsive to yoga in previous mechanistic studies.

Trial registration number

NCT01597960; Pre-results.
Testing quality indicators and proposing benchmarks for physician-staffed emergency medical services: a prospective Nordic multicentre study
Authors: Haugland Helge , Olkinuora Anna , Rognås Leif , Ohlen David , Krüger Andreas
Published: November 2019

Objectives

A consensus study from 2017 developed 15 response-specific quality indicators (QIs) for physician-staffed emergency medical services (P-EMS). The aim of this study was to test these QIs for important characteristics in a real clinical setting. These characteristics were feasibility, rankability, variability, actionability and documentation. We further aimed to propose benchmarks for future quality measurements in P-EMS.

Design

In this prospective observational study, physician-staffed helicopter emergency services registered data for the 15 QIs. The feasibility of the QIs was assessed based on the comments of the recording physicians. The other four QI characteristics were assessed by the authors. Benchmarks were proposed based on the quartiles in the dataset.

Setting

Nordic physician-staffed helicopter emergency medical services.

Participants

16 physician-staffed helicopter emergency services in Finland, Sweden, Denmark and Norway.

Results

The dataset consists of 5638 requests to the participating P-EMSs. There were 2814 requests resulting in completed responses with patient contact. All QIs were feasible to obtain. The variability of 14 out of 15 QIs was adequate. Rankability was adequate for all QIs. Actionability was assessed as being adequate for 10 QIs. Documentation was adequate for 14 QIs. Benchmarks for all QIs were proposed.

Conclusions

All 15 QIs seem possible to use in everyday quality measurement and improvement. However, it seems reasonable to not analyse the QI ‘Adverse Events’ with a strictly quantitative approach because of a low rate of adverse events. Rather, this QI should be used to identify adverse events so that they can be analysed as sentinel events. The actionability of the QIs ‘Able to respond immediately when alarmed’, ‘Time to arrival of P-EMS’, ‘Time to preferred destination’, ‘Provision of advanced treatment’ and ‘Significant logistical contribution’ was assessed as being poor. Benchmarks for the QIs and a total quality score are proposed for future quality measurements.
Prevalence and service assessment of cataract in Tibetan areas of Sichuan Province, China: population-based study
Authors: Jiachu Danba , Jin Ling , Jiang Feng , Luo Li , Zheng Hong , Ji Duo , Yang Jing , Yongcuo Nima , Huang Wenyong , Yi Jinglin , Bright Tess , Yip Jennifer LY , Xiao Baixiang
Published: November 2019

Objectives

To assess the prevalence of visual impairment (VI) and blindness (BL) due to cataract and cataract surgical outcomes in remote dispersed and high-altitude Tibetan areas of China.

Design and setting

A cross-sectional study was conducted among people aged 50 and above in Tibetan Autonomous Prefecture of Kandze (TAPK), China, in 2017. The Rapid Assessment of Avoidable Blindness protocol was followed.

Participants

Of 5000 eligible participants, 4764 were examined (response rate 95.3%).

Primary and secondary outcome measures

Cataract VI was defined as lens opacity at visual acuity (VA) levels of <3/60 (Blindness (BL)), ≥3/60 and <6/60 (severe visual impairment (SVI)), ≥6/60 and <6/18 (moderate visual impairment (MVI)), ≥6/18 and <6/12 (early visual impairment (EVI)).

Results

The estimated prevalence of cataract BL was 0.61% (95% CI 0.42 to 0.87). With best corrected VA, the estimated prevalence of SVI from cataract was 0.86% (95% CI 0.63 to 1.17); MVI was 2.39% (95% CI 2.00 to 2.87) and EVI was 5.21% (95% CI 4.61 to 5.87). Women in TAPK had a significantly higher prevalence of cataract BL (0.82%, 95% CI 0.54 to 2.15) than men (0.34%, 95% CI 0.16 to 0.70). Women had lower cataract surgical coverage (CSC) by eyes (60.8%, 95% CI 55.5 to 65.8) compared with men (70.1%; 95% CI 63.7 to 75.7). The prevalence of cataract BL was higher among Tibetan (2.28%; 95% CI 1.98 to 2.62) than Han Chinese (1.01%%; 95% CI 0.54% to 1.87%). Overall CSC by person with BL (by better eye) was 82.0% (95% CI 75.2 to 87.6). Among cataract-operated participants, 71.2% had VA equal to or better than 6/18.

Conclusions

The study detected a low prevalence of VI and BL due to cataract with high CSC in the study area compared with many other places in China. Further actions should be taken to improve cataract surgical outcome.
Advance care planning in COPD: guidance development for healthcare professionals
Authors: Meehan Elaine , Sweeney Catherine , Foley Tony , Lehane Elaine , Burgess Kelleher Art , Hally Ruth M , Shanagher Deirdre , Korn Bettina , Rabbitte Mary , Detering Karen Margaret , Cornally Nicola
Published: November 2019

Objectives

To examine current practices, attitudes and levels of confidence related to advance care planning (ACP) in patients with chronic obstructive pulmonary disease (COPD) among healthcare professionals working in Ireland. This will inform future clinical guidance development.

Methods

A cross-sectional survey of healthcare professionals.

Results

There were 143 participants (109 general practitioners, 25 nurses, 7 physiotherapists and 2 consultant physicians). The majority (82%, n=117) cared for patients with COPD weekly, but only 23% (n=33) had initiated ACP with a patient with COPD over the previous 6 months. Overall, 59% (n=85) answered ≥6 of 8 general knowledge questions correctly. Participants demonstrated positive attitudes towards ACP (mean score 3.6/5.0), but confidence levels were low (2.2/4.0). Most thought ACP was appropriate for patients with severe or very severe COPD (71%, n=101%, and 91%, n=130, respectively) but were unsure or felt that it was not appropriate for those with mild–moderate COPD. However, almost all participants (97%, n=139) stated that if a patient expressed a desire to have ACP discussions, they would comply. Topics most likely to be discussed related to diagnosis and treatment options. Death and end-of-life issues were rarely discussed. The death of a family member or friend and participation in support groups were identified as new ‘triggers’ for initiating ACP.

Conclusions

Targeted education to improve general knowledge and confidence levels among healthcare professionals, together with initiatives to increase public awareness of ACP so that patients themselves might be more inclined to start the discussion, may help increase the uptake of ACP for this patient group.
STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis
Authors: Heichler Christina , Scheibe Kristina , Schmied Anabel , Geppert Carol I , Schmid Benjamin , Wirtz Stefan , Thoma Oana-Maria , Kramer Viktoria , Waldner Maximilian J , Büttner Christian , Farin Henner F , Pešić Marina , Knieling Ferdinand , Merkel Susanne , Grüneboom Anika , Gunzer Matthias , Grützmann Robert , Rose-John Stefan , Koralov Sergei B , Kollias George , Vieth Michael , Hartmann Arndt , Greten Florian R , Neurath Markus F , Neufert Clemens
Published: November 2019

Objective

Cancer-associated fibroblasts (CAFs) influence the tumour microenvironment and tumour growth. However, the role of CAFs in colorectal cancer (CRC) development is incompletely understood.

Design

We quantified phosphorylation of STAT3 (pSTAT3) expression in CAFs of human colon cancer tissue using a tissue microarray (TMA) of 375 patients, immunofluorescence staining and digital pathology. To investigate the functional role of CAFs in CRC, we took advantage of two murine models of colorectal neoplasia and advanced imaging technologies. In loss-of-function and gain-of-function experiments, using genetically modified mice with collagen type VI (COLVI)-specific signal transducer and activator of transcription 3 (STAT3) targeting, we evaluated STAT3 signalling in fibroblasts during colorectal tumour development. We performed a comparative gene expression profiling by whole genome RNA-sequencing of fibroblast subpopulations (COLVI+ vs COLVI–) on STAT3 activation (IL-6 vs IL-11).

Results

The analysis of pSTAT3 expression in CAFs of human TMAs revealed a negative correlation of increased stromal pSTAT3 expression with the survival of colon cancer patients. In the loss-of-function and gain-of-function approach, we found a critical role of STAT3 activation in fibroblasts in driving colorectal tumourigenesis in vivo. With different imaging technologies, we detected an expansion of activated fibroblasts in colorectal neoplasias. Comparative gene expression profiling of fibroblast subpopulations on STAT3 activation revealed the regulation of transcriptional patterns associated with angiogenesis. Finally, the blockade of proangiogenic signalling significantly reduced colorectal tumour growth in mice with constitutive STAT3 activation in COLVI+ fibroblasts.

Conclusion

Altogether our work demonstrates a critical role of STAT3 activation in CAFs in CRC development.
Persisting inequalities in birth outcomes related to neighbourhood deprivation
Authors: Bertens Loes C M , Burgos Ochoa Lizbeth , Van Ourti Tom , Steegers Eric A P , Been Jasper V
Published: November 2019

Introduction

Health inequalities can be observed in early life as unfavourable birth outcomes. Evidence indicates that neighbourhood socioeconomic circumstances influence health. However, studies looking into temporal trends in inequalities in birth outcomes including neighbourhood socioeconomic conditions are scarce. The aim of this work was to study how inequalities in three different key birth outcomes have changed over time across different strata of neighbourhood deprivation.

Methods

Nationwide time trends ecological study with area-level deprivation in quintiles as exposure. The study population consisted of registered singleton births in the Netherlands 2003–2017 between 24 and 41 weeks of gestation. Outcomes used were perinatal mortality, premature birth and small for gestational age (SGA). Absolute rates for all birth outcomes were calculated per deprivation quintile. Time trends in birth outcomes were examined using logistic regression models. To investigate relative inequalities, rate ratios for all outcomes were calculated per deprivation quintile.

Results

The prevalence of all unfavourable birth outcomes decreased over time: from 7.2 to 4.1 per 1000 births for perinatal mortality, from 61.8 to 55.6 for premature birth, and from 121.9 to 109.2 for SGA. Inequalities in all birth outcomes have decreased in absolute terms, and the decline was largest in the most deprived quintile. Time trend analyses confirmed the overall decreasing time trends for all outcomes, which were significantly steeper for the most deprived quintile. In relative terms however, inequalities remained fairly constant.

Conclusion

In absolute terms, inequalities in birth outcomes by neighbourhood deprivation in the Netherlands decreased between 2003 and 2017. However, relative inequalities remained persistent.
Estimating the social value of mechanical thrombectomy randomized trials on an established stroke network
Authors: Rodrigues Gabriel Martins , Haussen Diogo C , Bouslama Mehdi , Rangaraju Srikant , Frankel Michael R , Nogueira Raul G
Published: November 2019

Background

Given the relative strength of prior mechanical thrombectomy (MT) data in face of the perceived poor natural history of emergent large vessel occlusion strokes, randomization to medical therapy during the recent clinical MT trials raised ethical challenges at individual and institutional levels despite overall clinical equipoise.

Methods

In a thrombectomy stroke registry, we compared treatment rates preceding and following the SWIFT-PRIME and DAWN trials. Based on effect sizes of treatment in both trials, we estimated missed opportunities due to randomization to medical therapy and estimated the societal benefit resulting from additional patients who benefited as a result of these studies.

Results

The average monthly thrombectomy rate in the SWIFT-PRIME time window increased from 14.1±4 patients-per-month (ppm) to 23.8±6 ppm (p<0·001). Twelve subjects were enrolled in SWIFT-PRIME and we estimated a missed opportunity of benefiting 2.3 of six subjects randomized to medical therapy. This was offset by providing treatment to an additional 9.7 ppm, resulting in an additional functional benefit to 3.7 ppm. Similarly, the thrombectomy rate in the DAWN window increased from 8.6±4 ppm pre-DAWN to 11.9±3.6 ppm post-DAWN (p<0.01). 38 subjects were enrolled in the DAWN trial with a missed opportunity to benefit eight of 16 subjects randomized to medical therapy. This was offset by the ability to offer MT to an additional 3.3 ppm, bringing definite benefit to an additional 1.65 ppm.

Conclusion

Completion of recent trials resulted in observable increases in rates of thrombectomy, translating to functional benefits that rapidly offset any missed opportunities due to randomization to medical therapy arms.
Assessment of clinical features and determinants of mortality among cancer patients with septic shock of pulmonary origin: a prospective analysis
Authors: Rasheed Maria , Khan Yusra Habib , Mujtaba Ghulam , Mallhi Tauqeer Hussain , Saadullah Malik , Saifullah Amna
Published: November 2019

Background

Pneumonia-associated septic shock (PASS) in patients with cancer inflicts healthcare burden attributed to high morbidity and mortality. Current study was aimed to evaluate the clinical outcomes, microbiological characteristics, risk factors and impact of life-support interventions on 28-day mortality among cancer patients with PASS.

Methods

A prospective observational study was conducted among cancer patients with PASS admitted to intensive care unit (ICU) of ‘Shaukat Khanum Memorial Cancer Hospital’. Data were analysed using appropriate statistical methods.

Results

Out of 100 patients who sought medical care during the study period, 59 (59%) were male and majority had solid tumour than haematological malignancies (68% vs 32%). Nosocomial pneumonia was most frequent (90%) followed by healthcare-associated pneumonia (HCAP) (9%) and community-acquired pneumonia (CAP) (1%). The most common causative pathogen was Pseudomonas aeruginosa, 21 (32%). Overall mortality rate was 76% including 15% hospital and 61% ICU mortality. Sequential Organ Failure Assessment (SOFA) score at first day (HR 3.8; 95% CI 1.7 to 8.9; p=0.002), SOFA score at seventh day (HR 8.9; 95% CI 3.6 to 22.7; p=<0.001), invasive mechanical ventilation (HR 8.0; 95% CI 3.2 to 20; p<0.001) and performance status (HR 5.4; 95% CI 2.5 to 11.3; p<0.001) were found to be independently associated with 28-day mortality. Receiver operating characteristic curve analysis accentuates the excellent predictive accuracy of Cox regression model for mortality indicated by area under the curve of 0.892 (95% CI 0.801 to 0.983, p<0.001).

Conclusion

Our analysis demonstrates substantial mortality associated with PASS among patients with cancer. Timely recognition of patients with high predilection of increased mortality could be of value in improving the disease burden.
What factors reliably predict electronic cigarette nicotine delivery?
Authors: Blank Melissa D , Pearson Jennifer , Cobb Caroline O , Felicione Nicholas J , Hiler Marzena M , Spindle Tory R , Breland Alison
Published: November 2019

Background

The ability of an electronic cigarette (e-cigarette) to deliver nicotine effectively may be dependent on features of the device, the liquid and the user. Some of these features have been examined in previous work (eg, liquid nicotine concentration and puff topography), while others have not (eg, nicotine dependence and demographic characteristics). The purpose of this secondary analysis is to examine such features as predictors of e-cigarette nicotine delivery using a relatively large sample.

Methods

Four studies were combined in which e-cigarette-experienced users (n=63; 89% men; 75% white) and e-cigarette-naïve cigarette smokers (n=67; 66% men; 54% white) took 10 puffs from an eGo-style e-cigarette (~7.3 watts) filled with liquid that had a nicotine concentration of 18, 25 or 36 mg/mL. Thus, held constant across all studies were device features of battery/cartomiser style and power level and the topography parameters of puff number and interpuff interval. Blood was sampled before and after use, and puff topography was measured. Three general linear models were conducted to predict plasma nicotine concentrations (pre–post increase) for: (1) e-cigarette users only, (2) smokers only and (3) both groups combined. Predictor variables included puff duration, puff volume, liquid nicotine concentration, presession plasma nicotine concentration, nicotine dependence score (smokers only), gender and race.

Results

In all models tested, longer puff durations and higher liquid nicotine concentrations were associated significantly with increased nicotine delivery (ps<0.05). For e-cigarette users only, higher presession nicotine concentration was associated significantly with increased nicotine delivery (p<0.05).

Conclusions

Puff duration and liquid nicotine concentration may be among the more important factors to consider as regulators attempt to balance e-cigarette safety with efficacy. These findings should be interpreted in the context of devices with relatively low power output, a variable not studied here but likely also directly relevant to product regulation.
Muscular angiomatosis in a dog
Authors: Marchis Horatiu Silviu , Veiga‐Parga Tamara
Published: November 2019

A 12‐year‐ 4 month‐ old male neutered crossbreed small dog was presented for moderate lameness and a swelling in the tibio‐tarso‐metatarsal area of the left hindlimb. Clinical examination revealed a fluid‐filled mass in the metatarsal and tarsal regions in addition to multiple 5×5×3 cm firm nodules in the tibial region. Histopathological evaluation of the lesion was diagnostic for muscular angiomatosis. Angiomatosis is a non‐neoplastic lesion reported in the veterinary literature as a lesion affecting the skin, bone or as a multisystemic disorder affecting various sites in dogs, cats, cattle and horses. As far as the authors are aware, this is the first reported case of angiomatosis restricted to the skeletal muscle in a dog.
Petrogenesis and tectonic setting of the Huhetaoergai granitic pluton in the northern Ya-Gan Fault zone, northern Alxa, China: constraints from whole-rock geochemistry, zircon U–Pb ages, and Hf isotope compositions
Authors: Xie Fenquan , Wu Qianhong , Wang Lidong , Xiao Wenzhou , Cao Jingya , Shi Zhaoxia , Song Jiajia
Published: November 2019

This study presents a new data set that contains zircon U–Pb ages, whole-rock geochemistry, and Hf isotopes of the Huhetaoergai granitic pluton in the northern Ya-Gan Fault zone, northern Alxa, China. The Huhetaoergai pluton is composed of medium- to coarse-grained biotite monzogranite and coarse-grained biotite monzogranite with K-feldspar megacrysts, with U–Pb zircon ages of 220.5 ± 1.9 Ma and 226.5 ± 2.4 Ma, respectively. Granitoids are I-type granites with high εHf(t) values (9–11.05). These features indicate that the granitoids were generated from partial melting of juvenile crust and experienced an obvious fractional crystallization process. We speculate that the granitoids of the Huhetaoergai pluton were formed in an intraplate extensional environment during the post-collision process, indicating a crustal stretching and thinning event in the northern Ya-Gan Fault zone.
Development of a core SNP panel for cacao (Theobroma cacao L.) identity analysis
Authors: Mahabir Amrita , Motilal Lambert A. , Gopaulchan David , Ramkissoon Saila , Sankar Antoinette , Umaharan Pathmanathan
Published: November 2019

Single nucleotide polymorphisms (SNPs) are preferred markers for DNA fingerprinting and diversity studies in cacao (Theobroma cacao L.). Yet, a consensus SNP panel with a minimum number of SNPs for optimal identity analysis is unavailable for cacao. An initial set of 146 SNP panels of varying sizes were assembled based on heterozygosity, linkage disequilibrium (LD), linkage group (LG) distribution, major allele frequency, minor allele frequency (MiAF), polymorphism information content (PIC), and random distribution. These panels were assessed to determine their ability to distinguish among a training set of 155 accessions. The panels with the best separation ability were supplemented with additional SNPs to create 16 designer panels, which separated all 155 accessions. The 16 designer SNP panels were then assessed on a dataset of 1220 accessions coming from 10 ancestral groups. Increasing the number of SNPs generally yielded improved resolution of genetic identities with concomitant reduction of synonymous groups. The number and choice of SNPs were critical factors with LD, MiAF, and PIC being important selection attributes but an even LG distribution was unnecessary. A robust set of 96 SNPs is recommended as a minimal core SNP panel for cacao DNA fingerprinting to the international cacao community.
Assessing the risk of default propagation in interconnected sectoral financial networks
Authors: Barja Adrià , Martínez Alejandro , Arenas Alex , Fleurquin Pablo , Nin Jordi , Ramasco José J. , Tomás Elena
Published: November 2019

Systemic risk of financial institutions and sectoral companies relies on their inter-dependencies. The inter-connectivity of the financial networks has proven to be crucial to understand the propagation of default, as it plays a central role to assess the impact of single default events in the full system. Here, we take advantage of complex network theory to shed light on the mechanisms behind default propagation. Using real data from the BBVA, the second largest bank in Spain, we extract a financial network from customer-supplier transactions among more than$140\text{,}000$140,000companies, and their economic flows. Then, we introduce a computational model, inspired by the probabilities of default contagion, that allow us to obtain the main statistics of default diffusion given the network structure at individual and system levels. Our results show the exposure of different sectors to default cascades, therefore allowing for a quantification and ranking of sectors accordingly. This information is relevant to propose countermeasures to default propagation in specific scenarios.
Spectral analysis of the spin-boson Hamiltonian with two bosons for arbitrary coupling and bounded dispersion relation
Authors: Ibrogimov Orif O.
Published: November 2019

We study the spectrum of the spin-boson Hamiltonian with two bosons for arbitrary coupling [Formula: see text] in the case when the dispersion relation is a bounded function. We derive an explicit description of the essential spectrum which consists of the so-called two- and three-particle branches that can be separated by a gap if the coupling is sufficiently large. It turns out, that depending on the location of the coupling constant and the energy level of the atom (w.r.t. certain constants depending on the maximal and the minimal values of the boson energy) as well as the validity or the violation of the infrared regularity type conditions, the essential spectrum is either a single finite interval or a disjoint union of at most six finite intervals. The corresponding critical values of the coupling constant are determined explicitly and the asymptotic lengths of the possible gaps are given when [Formula: see text] approaches to the respective critical value. Under minimal smoothness and regularity conditions on the boson dispersion relation and the coupling function, we show that discrete eigenvalues can never accumulate at the edges of the two-particle branch. Moreover, we show the absence of the discrete eigenvalue accumulation at the edges of the three-particle branch in the infrared regular case.
Semi-empirical formula for alpha and cluster decay half-lives of superheavy nuclei
Authors: Manjunatha H. C. , Sowmya N. , Nagaraja A. M.
Published: November 2019

We have formulated a semi-empirical formula for alpha decay half-lives and cluster decay half-lives for superheavy nuclei of atomic number range [Formula: see text]. We have compared the logarithmic half-lives produced by the present formula with that of experiments and other formulae, such as universal decay law (UDL) [H. C. Manjunatha and K. N. Sridhar, Eur. Phys. J. A 53, 156 (2017)] and Horoi et al. [Horoi et al., J. Phys. G[Formula: see text] Nucl. Part. Phys. 30, 945 (2004)], Univ [D. Ni and Z. Ren, Phys. Rev. C 74, 014304 (2006)], Royer [G. Royer, J. Phys. G: Nucl. Part. Phys. 26, 1149 (2000)] and VSS [S. A. Gurvitz and G. Kalbermann, Phys. Rev. Lett. 59, 262 (1987)]. The constructed formula produces logarithmic half-lives for alpha and cluster decay (4He,9Be, [Formula: see text]B, [Formula: see text]C, [Formula: see text]N, [Formula: see text]O, [Formula: see text]F, [Formula: see text]Ne, [Formula: see text]Na, [Formula: see text]Mg, [Formula: see text]Al, [Formula: see text]Si, [Formula: see text]P, [Formula: see text]S, [Formula: see text]Cl, [Formula: see text]Ar, [Formula: see text]K and [Formula: see text]Ca) in superheavy nuclei of atomic number range [Formula: see text].