bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition and preservation of fluvio‐tidal shallow‐marine sandstones: A re‐evaluation of the Neoproterozoic Jura Quartzite (western Scotland)
Authors: Levell Bruce K. , Johnson Howard D. , Collins Daniel S. , van Cappelle Marijn
Published: June 2019

The 2 to 5 km thick, sandstone‐dominated (>90%) Jura Quartzite is an extreme example of a mature Neoproterozoic sandstone, previously interpreted as a tide‐influenced shelf deposit and herein re‐interpreted within a fluvio‐tidal deltaic depositional model. Three issues are addressed: (i) evidence for the re‐interpretation from tidal shelf to tidal delta; (ii) reasons for vertical facies uniformity; and (iii) sand supply mechanisms to form thick tidal‐shelf sandstones. The predominant facies (compound cross‐bedded, coarse‐grained sandstones) represents the lower parts of metres to tens of metres high, transverse fluvio‐tidal bedforms with superimposed smaller bedforms. Ubiquitous erosional surfaces, some with granule–pebble lags, record erosion of the upper parts of those bedforms. There was selective preservation of the higher energy, topographically‐lower, parts of channel‐bar systems. Strongly asymmetrical, bimodal, palaeocurrents are interpreted as due to associated selective preservation of fluvially‐enhanced ebb tidal currents. Finer‐grained facies are scarce, due largely to suspended sediment bypass. They record deposition in lower‐energy environments, including channel mouth bars, between and down depositional‐dip of higher energy fluvio‐ebb tidal bars. The lack of wave‐formed sedimentary structures and low continuity of mudstone and sandstone interbeds, support deposition in a non‐shelf setting. Hence, a sand‐rich, fluvial–tidal, current‐dominated, largely sub‐tidal, delta setting is proposed. This new interpretation avoids the problem of transporting large amounts of coarse sand to a shelf. Facies uniformity and vertical stacking are likely due to sediment oversupply and bypass rather than balanced sediment supply and subsidence rates. However, facies evidence of relative sea level changes is difficult to recognise, which is attributed to: (i) the areally extensive and polygenetic nature of the preserved facies, and (ii) a large stored sediment buffer that dampened response to relative sea‐level and/or sediment supply changes. Consideration of preservation bias towards high‐energy deposits may be more generally relevant, especially to thick Neoproterozoic and Lower Palaeozoic marine sandstones.
Molecular phylogeny ofHimalopsyche(Trichoptera, Rhyacophilidae)
Authors: Hjalmarsson Anna E. , Graf Wolfram , Vitecek Simon , Jähnig Sonja C. , Cai Qinghua , Sharma Subodh , Tong Xiaoli , Li Fengqing , Shah Deep Narayan , Shah Ram Devi Tachamo , Pauls Steffen U.
Published: June 2019

Species of the genusHimalopsyche(Trichoptera, Rhyacophilidae) inhabit alpine to montane environments in Central and East Asia and North America. Diversity of the genus is concentrated primarily in the Himalayas and surrounding mountain ranges. Phylogenetic hypotheses have hitherto been proposed based on morphological data. Here, we present the first molecular phylogeny ofHimalopsychebased on six gene fragments, using three methods of phylogenetic inference. Based on the phylogenetic analyses, we re‐evaluated species groups suggested by previous authors based on adult male morphology. We found that the previously defined groups are largely supported by molecular evidence as well as larval and adult morphology. However, we modify the species groups so thatHimalopsyche phryganeaandHimalopsyche lepchaconstitute monotypic groups, and so that thetibetanagroup andanomalagroupsensuSchmid & Botosaneanu are merged to a single group, here defined as thetibetanagroup. Thus, we propose thatHimalopsychecan be divided into five groups:kuldschensisgroup,lepchagroup,navasigroup,phryganeagroup, andtibetanagroup. We also provide a biogeographic synthesis ofHimalopsychedistributions.
Thoracic high resolution CT using the modified VetMousetrap™ device is a feasible method for diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers
Authors: Holopainen Saila , Rautala Elina , Lilja‐Maula Liisa , Lohi Hannes , Rajamäki Minna M. , Lappalainen Anu K.
Published: June 2019

Canine idiopathic pulmonary fibrosis is a chronic, progressive interstitial lung disease particularly prevalent in West Highland White Terriers. In the present prospective pilot study, we evaluated the feasibility of modified VetMousetrap™ device in high resolution CT to detect idiopathic pulmonary fibrosis in West Highland White Terriers. Twelve awake West Highland White Terriers with canine idiopathic pulmonary fibrosis and 24 clinically healthy West Highland White Terriers were scanned using a helical dual slice scanner utilizing VetMousetrap™ device without or with minimal chemical restraint with butorphanol. Three evaluators blindly assessed the images for image quality and the presence of canine idiopathic pulmonary fibrosis related imaging findings such as ground glass opacity and reticular opacities. Additionally, the attenuation of the lung was quantified with ImageJ software using histogram analysis of density over the lung fields. Computed tomography was successfully completed and motion artifact ranked in statistical analysis barely noticeable to mild in all dogs. The agreement between imaging findings and clinical status was very good with overall κ value 0.91 and percentage of agreement of 94%. There was also very good intraobserver (κrange = 0.79‐0.91) and interobserver agreement (κ = 0.94). Moderate to severe ground glass opacity was present in all affected dogs. In the ImageJ analysis, a significant difference in lung attenuation between the study groups was observed. We conclude that modified VetMousetrap™ device is applicable in diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers avoiding anesthetic risk in these often severely hypoxic patients.
The Effects of Leucine-Enriched Branched-Chain Amino Acid Supplementation on Recovery After High-Intensity Resistance Exercise
Authors: Osmond Adam D. , Directo Dean J. , Elam Marcus L. , Juache Gabriela , Kreipke Vince C. , Saralegui Desiree E. , Wildman Robert , Wong Michael , Jo Edward
Published: June 2019

Context: Of the 3 branched-chain amino acids (BCAA), leucine has arguably received the most attribution for the role of BCAA supplementation in alleviating symptoms of exercise-induced muscle damage and facilitation of acute performance recovery. Purpose: To examine whether enrichment of a standard BCAA supplement with additional leucine or a standalone leucine (LEU) supplement differentially affects exercise-induced muscle damage and performance recovery compared with a standard BCAA supplement. Methods: A total of 22 recreationally active male and female subjects were recruited and assigned to consume a BCAA, leucine-enriched BCAA (LBCAA), or LEU supplement for 11 d. On the eighth day, subjects performed eccentric-based resistance exercise (ECRE). Lower-body mean average and peak power, plasma creatine kinase, soreness, and pain threshold were measured before and 24, 48, and 72 h after ECRE. Results: LEU showed decreased mean average power (P = .02) and mean peak power (P = .01) from baseline to 48 h post-ECRE, whereas LBCAA and BCAA only trended toward a reduction at 24 hours post-ECRE. At 48 h post-ECRE, BCAA showed greater recovery of mean peak power than LEU (P = .04). At 24 h post-ECRE, LEU demonstrated a greater increase in plasma creatine kinase from baseline than BCAA (P = .04). Area under the curve for creatine kinase was greater in LEU than BCAA (P = .02), whereas BCAA and LBCAA did not differ. Only LEU demonstrated increased soreness during rest and under muscular tension at 24 and 48 h post-ECRE (P < .05). Conclusions: LBCAA failed to afford any advantages over a standard BCAA supplement for postexercise muscle recovery, whereas a LEU supplement was comparatively ineffective.
The Temporal Relationship Between Exercise, Recovery Processes, and Changes in Performance
Authors: Skorski Sabrina , Mujika Iñigo , Bosquet Laurent , Meeusen Romain , Coutts Aaron J. , Meyer Tim
Published: June 2019

Physiological and psychological demands during training and competition generate fatigue and reduce an athlete’s sport-specific performance capacity. The magnitude of this decrement depends on several characteristics of the exercise stimulus (eg, type, duration, and intensity), as well as on individual characteristics (eg, fitness, profile, and fatigue resistance). As such, the time required to fully recover is proportional to the level of fatigue, and the consequences of exercise-induced fatigue are manifold. Whatever the purpose of the ensuing exercise session (ie, training or competition), it is crucial to understand the importance of optimizing the period between exercise bouts in order to speed up the regenerative processes and facilitate recovery or set the next stimulus at the optimal time point. This implies having a fairly precise understanding of the fatigue mechanisms that contribute to the performance decrement. Failing to respect an athlete’s recovery needs may lead to an excessive accumulation of fatigue and potentially “nonfunctional overreaching” or to maladaptive training. Although research in this area recently increased, considerations regarding the specific time frames for different physiological mechanisms in relation to exercise-induced fatigue are still missing. Furthermore, recommendations on the timing and dosing of recovery based on these time frames are limited. Therefore, the aim of this article is to describe time courses of recovery in relation to the exercise type and on different physiological levels. This summary supports coaches, athletes, and scientists in their decision-making process by considering the relationship of exercise type, physiology, and recovery.
Session RPE During Prolonged Exercise Training
Authors: Fusco Andrea , Knutson Christine , King Charles , Mikat Richard P. , Porcari John P. , Cortis Cristina , Foster Carl
Published: June 2019

Purpose: Although the session rating of perceived exertion (sRPE) is primarily a marker of internal training load (TL), it may be sensitive to external TL determining factors, such as duration and volume. Thus, sRPE could provide further information on accumulated fatigue not available from markers of internal TL. Therefore, the purpose of this study was to investigate sRPE during heavy training bouts at relatively constant intensity. Methods: Eleven university swimmers performed a high-volume training session consisting of 4 × 10 × 100-yd (4 × 10 × 91.4 m). Repetition lap time and heart rate were measured for each repetition and averaged for each set. Blood lactate concentration was measured after each set. At the end of each set, a 10-minute rest period was allowed, during which sRPE values were obtained, as if the training bout had ended. Results: There were no differences between sets for lap time (P = .096), heart rate (P = .717), and blood lactate concentration (P = .466), suggesting that the subjects were working at the same external and internal intensity. There was an increase (P = .0002) in sRPE between sets (first 4 [1.2], second 5 [1.3], third 7 [1.3], and fourth 8 [1.5]), suggesting that even when maintaining the same intensity, the perception of the entire workload increased with duration. Conclusions: Increases in duration, although performed with a consistent internal and external intensity, influences sRPE. These findings support the concept that sRPE may provide additional information on accumulated fatigue not available from other markers of TL.
Acute Exercise and Emotion Recognition in Young Adolescents
Authors: Brand Serge , Gerber Markus , Colledge Flora , Holsboer-Trachsler Edith , Pühse Uwe , Ludyga Sebastian
Published: June 2019

While there is evidence that acute bouts of aerobic and coordinative exercise positively affect attention and executive functions, no study has focused on the impact of acute exercise on facial-emotion processing. A total of 106 adolescents (mean age 13.0 years) were randomly assigned to a group performing either an aerobic exercise session (AER), an aerobic exercise session with coordinative demands (AER+C), or stretching. Before and after the 35-min experimental session, participants completed computerized facial-emotion labeling and emotion-matching tasks. Facial-emotion labeling, but not emotion matching, increased over time, but more so in AER and AER+C conditions. When aerobic exercise is combined with coordinative demands, greater benefits seem to be elicited for some aspects of facial-emotion recognition. Results suggest a new direction for the influence of exercising on dimensions of psychological functioning, namely on emotion processing and social cognition.
Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC
Authors: Barnes Melissa D. , Taracila Magdalena A. , Good Caryn E. , Bajaksouzian Saralee , Rojas Laura J. , van Duin David , Kreiswirth Barry N. , Jacobs Michael R. , Haldimann Andreas , Papp-Wallace Krisztina M. , Bonomo Robert A.
Published: June 2019

Carbapenem-resistant
Enterobacteriaceae
(CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents.
Klebsiella pneumoniae
carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged diazabicyclooctane (DBO) β-lactamase inhibitor that inactivates class A and C β-lactamases and exhibits intrinsic antibiotic and β-lactam “enhancer” activity against
Enterobacteriaceae
.
A Revised Species Concept for OpportunisticMucorSpecies Reveals Species-Specific Antifungal Susceptibility Profiles
Authors: Wagner Lysett , de Hoog Sybren , Alastruey-Izquierdo Ana , Voigt Kerstin , Kurzai Oliver , Walther Grit
Published: June 2019

Recently, the species concept of opportunisticMucor circinelloidesand its relatives has been revised, resulting in the recognition of its classical formae as independent species and the description of new species. In this study, we used isolates of all clinically relevantMucorspecies and performed susceptibility testing using the EUCAST reference method to identify potential species-specific susceptibility patterns.
Inverted Regulation of Multidrug Efflux Pumps, Acid Resistance, and Porins in Benzoate-Evolved Escherichia coli K-12
Authors: Moore Jeremy P. , Li Haofan , Engmann Morgan L. , Bischof Katarina M. , Kunka Karina S. , Harris Mary E. , Tancredi Anna C. , Ditmars Frederick S. , Basting Preston J. , George Nadja S. , Bhagwat Arvind A. , Slonczewski Joan L.
Published: June 2019

Benzoic acid is a common food preservative, and salicylic acid (2-hydroxybenzoic acid) is the active form of aspirin. At high concentrations, benzoic acid conducts a proton across the membrane, depleting the proton motive force. In the absence of antibiotics, benzoate exposure selects against proton-driven multidrug efflux pumps and upregulates porins that admit fermentable substrates but that also allow the entry of antibiotics. Thus, evolution with benzoate and related molecules, such as salicylates, requires a trade-off for antibiotic sensitivity, a trade-off that could help define a stable gut microbiome. Benzoate and salicylate are naturally occurring plant signal molecules that may modulate the microbiomes of plants and animal digestive tracts so as to favor fermenters and exclude drug-resistant pathogens.
Update on adrenal steroid hormone biosynthesis and clinical implications
Authors: Bacila Irina-Alexandra , Elder Charlotte , Krone Nils
Published: June 2019

Steroid biosynthesis is a complex process in which cholesterol is converted to steroid hormones with the involvement of multiple enzymes and cofactors. Inborn conditions affecting adrenal steroidogenesis are relatively common in paediatric practice and have serious implications on patient mortality and morbidity. This paper provides an overview of novel insights into human adrenal steroid biosynthesis. Inborn errors of steroidogenesis associated with congenital adrenal hyperplasia are discussed, with a particular focus on the pathophysiology and clinical features of 21-hydroxylase deficiency. The final section of the review presents more recent findings and clinical implications of adrenal-specific androgen biosynthesis.
Microscopic colitis impacts quality of life in older people
Authors: Ogundipe Olayinka Ayodele , Campbell Amy
Published: June 2019

This report describes a frail 92-year-old woman with dementia who presented with a year’s history of chronic watery non-bloody diarrhoea. She had abdominal bloating, weight loss, faecal urgency, nocturnal stools and developed faecal incontinence. Her serum C reactive peptide and faecal calprotectin were elevated. Flexible sigmoidoscopy was macroscopically normal, but demonstrated histological features of microscopic colitis (MC) in sigmoid colon and rectal biopsies. Polypharmacy was reviewed for possible medication-induced MC. Ranitidine, donepezil and simvastatin were discontinued. She was started on oral budesonide with improvement in the abdominal and bowel symptoms. Stool frequency and consistency normalised, and the faecal incontinence resolved with treatment. The outcomes were an improved quality of life, reduced functional dependency, reduced carer strain and avoidance of premature transition from her home into a long-term/institutional care setting. We briefly review terminology, basic epidemiology, notable associations, the importance of establishing a diagnosis and some treatment considerations for MC.
Skin staining following intravenous iron infusion
Authors: Crowley Clare Margaret , McMahon Gabriela , Desmond Joanna , Imcha Mendinaro
Published: June 2019

This report describes the case of a 36-year-old woman, gravida 3, para 2, at 11 weeks' gestation, who received a ferric carboxymaltose infusion for iron deficiency anaemia after medical management of a miscarriage. The following morning, light brown skin staining was noted at the infusion site, and the staining was present 2 months later at follow-up. Skin staining following intravenous iron infusion is a rare but important side effect. The skin staining is potentially permanent but may fade in time. Such an adverse effect may have cosmetic consequences for the patient.
Perceived physical health in obsessive-compulsive disorder: a protocol for a systematic review and meta-analysis
Authors: Pozza Andrea , Ferretti Fabio , Coluccia Anna
Published: June 2019

Introduction

Obsessive-compulsive disorder (OCD) is a mental health condition associated with severe impairment in a variety of quality of life domains, an increased physical health burden, and a higher risk of general medical conditions and mortality compared with the general population. While there is a large amount of literature on psychological quality of life, a systematic review of perceived physical health in OCD is lacking. A quantitative summary might suggest that policy makers also focus the evaluation on perceived physical health and develop new strategies also aimed at this outcome. The current paper presents a protocol for the first systematic review and meta-analysis aimed at summarising perceived physical health in OCD by specifically examining perceived physical health status, bodily pain and role limitations due to physical problems in patients with OCD compared with controls. The review will also investigate potential demographic and clinical moderators of perceived physical health status (age, gender, OCD severity, publication date, methodological quality).

Methods and analysis

A systematic review and meta-analysis will be conducted according to PRISMA guidelines. Studies will be included if using a clinical group with a current primary diagnosis of OCD established by international standardised criteria, if measuring perceived physical health status, and if using screened or community participants as controls. No publication date or language restriction will be applied. An online systematic search of electronic databases (Scopus, PubMed, PsycINFO, EMBASE, Cochrane Library), and examination of conference proceedings and theses/dissertations will be conducted by independent reviewers. Risk of bias will be assessed through the Newcastle-Ottawa Scale.

Ethics and dissemination

The current review does not require ethics approval. The results will be disseminated through publications in peer-reviewed journals.

PROSPERO registration number

2018 CRD42018106194.
Why do trainees leave hospital-based specialty training? A nationwide survey study investigating factors involved in attrition and subsequent career choices in the Netherlands
Authors: Bustraan Jacqueline , Dijkhuizen Kirsten , Velthuis Sophie , van der Post Rachel , Driessen Erik , van Lith Jan M M , de Beaufort Arnout Jan
Published: June 2019

Objective

To gain insight into factors involved in attrition from hospital-based medical specialty training and future career plans of trainees who prematurely left their specialty training programme.

Design

Nationwide online survey study.

Setting

Postgraduate education of all hospital-based specialties in the Netherlands.

Participants

174 trainees who prematurely left hospital-based medical specialty training between January 2014 and September 2017.

Main outcome measures

Factors involved in trainees’ decisions to leave specialty training and their subsequent career plans.

Results

The response rate was 38%. Of the responders, 25% left their programme in the first training year, 50% in year 2–3 and 25% in year 4–6. The most frequently reported factors involved in attrition were: work-life balance, job content, workload and specialty culture. Of the leaving trainees, 66% switched to another specialty training programme, of whom two-thirds chose a non-hospital-based training programme. Twelve per cent continued their career in a non-clinical role and the remainder had no specific plans yet.

Conclusions

This study provides insight in factors involved in attrition and in future career paths. Based on our findings, possible interventions to reduce attrition are: (1) enable candidates to develop a realistic view on job characteristics and demands, prior to application; (2) provide individual guidance during specialty training, with emphasis on work-life balance and fit with specialty.
UK military helmet design and test methods
Authors: Carr Debra J , Lewis E , Mahoney PF
Published: June 2019

The aim of this paper was to provide the military medical community with an expert summary of military helmets used by HM Armed Forces. The design of military helmets and test methods used to determine the fragmentation and non-ballistic impact protection are discussed. The helmets considered are Parachutist, Combat Vehicle Crewman, Mk6, Mk6A, Mk7 and VIRTUS. The helmets considered provide different levels of fragmentation and non-ballistic impact protection dictated by the materials available at the time of the helmet design and the end-user requirement. The UK Ministry of Defence defines the area of coverage of military helmets by considering external anatomical features to provide protection to the brain and the majority of the brainstem. Established test methods exist to assess the performance of the helmet with respect to the threats; however, these test methods do not typically consider anatomical vulnerability.
Comparison of postmortem inspection procedures for detecting caseous lymphadenitis of Australian sheep and goats
Authors: Pointon Andrew , Hamilton David , Kiermeier Andreas
Published: June 2019

Alternative postmortem inspection procedures for the detection of gross abnormalities due to Caseous Lymphadenitis (CLA) of sheep and goats were compared quantitatively against the current Australian Standard (AS4696). Studies on sheep and goats in Australia during 2016 addressed data gaps regarding current prevalence, combinations of multiple lesions within affected carcases and sensitivity of inspection procedures enabling a comparison of alternative with current procedures. Using these contemporary inspection data from 54 915 sheep and 48 577 goats a desktop study estimated the effect of implementing alternative procedures of reduced palpation from eleven carcase sites to the four sites most commonly affected. Under current procedures it was estimated that 86 sheep and 34 goat carcases with CLA lesions are missed per 10,000 carcases. Under alternative procedures it is estimated that an additional 48.4 sheep and 10.5 goat carcases with CLA lesions would be missed per 10 000 carcases. Of these, 38.2 sheep and 5.6 goat per 10 000 carcases would contain CLA only in routinely discarded, non‐edible tissue sites. Hence, only an additional 10.2 sheep and 4.9 goat carcases per 10 000 inspected, with CLA in edible tissue sites are estimated to be missed. These alternative procedures have now been officially implemented in the Australian domestic standard.
Moose, caribou, and fire: have we got it right yet?
Authors: DeMars C.A. , Serrouya R. , Mumma M.A. , Gillingham M.P. , McNay R.S. , Boutin S.
Published: June 2019

Natural disturbance plays a key role in shaping community dynamics. Within Canadian boreal forests, the dominant form of natural disturbance is fire, and its effects are thought to influence the dynamics between moose (Alces alces (Linnaeus, 1758)) and the boreal ecotype of woodland caribou (Rangifer tarandus caribou (Gmelin, 1788)). Boreal caribou are considered “threatened” and population declines are attributed, at least in part, to disturbance-mediated apparent competition (DMAC) with moose. Here, we tested a primary prediction of the DMAC hypothesis: that moose respond positively to burns within and adjacent to the caribou range. We assessed moose selection for ≤25-year-old burns (when selection is predicted to be strongest) at multiple spatial scales and evaluated whether moose density was correlated with the extent of ≤40-year-old burns (a time frame predicted to negatively affect caribou). Against expectation, moose showed avoidance and low use of ≤25-year-old burns at all scales, regardless of burn age, season, and type of land cover burned. These findings mirrored the demographic response, as we found no correlation between ≤40-year-old burns and moose density. By contradicting the prevailing hypothesis linking fires to caribou population declines, our results highlight the need to understand regional variation in disturbance impacts on caribou populations.
Macroecological approach for scorpions (Arachnida, Scorpiones): β-diversity in Brazilian montane forests
Authors: Foerster S.I.A. , DeSouza A.M. , Lira A.F.A.
Published: June 2019

The montane forests of northeastern Brazil are patches of rainforests, surrounded by xeric vegetation, that originated during the expansion of rainforests in the Pleistocene epoch. Their historical processes make these areas ideal for biogeographical investigations of organisms, particularly in groups with low dispersion and habitat specificity, such as scorpions. We perform a macroecological investigation of the community assembly process of scorpions, disentangling the pattern of β-diversity to test the hypothesis that the similarity in the composition of scorpion fauna in areas of montane forests and coastal rainforests is greater when these localities are geographically close. We also investigated if larger patches of montane forests exhibit a positive species–area relationship. Our results state that species replacement accounts for 71% of the total scorpion β-diversity in montane forest remnants. Additionally, scorpion assemblages were influenced by the spatial arrangement, with a higher similarity between the fauna of montane forests and coastal forests when these areas were geographically close. We did not find a species–area relationship in montane forest patches. The expressive contribution of species replacement to the overall β-diversity may reflect both the high environmental heterogeneity and the historical and independent colonization events that took place in these areas.
Weak Transient Electromagnetic Radiation Signal Detection Method Considering the New Watershed Image Segmentation Algorithm
Authors: Huo Wenjun , Chu Peng , Wang Kai , Fu Liangting , Niu Zhigang , Zhao Jianhua
Published: June 2019

In order to study the detection methods of weak transient electromagnetic radiation signals, a detection algorithm integrating generalized cross-correlation and chaotic sequence prediction is proposed in this paper. Based on the dual-antenna test and cross-correlation information estimation method, the detection of aperiodic weak discharge signals under low signal-to-noise ratio is transformed into the estimation of periodic delay parameters, and the noise is reduced at the same time. The feasibility of this method is verified by simulation and experimental analysis. The results show that under the condition of low signal-to-noise ratio, the integrated method can effectively suppress the influence of 10 noise disturbances. It has a high detection probability for weak transient electromagnetic radiation signals, and needs fewer pulse accumulation times, which improves the detection efficiency and is more suitable for long-distance detection of weak electromagnetic radiation sources.
A Filled Flatten Function Method Based on Basin Deepening and Adaptive Initial Point for Global Optimization
Authors: Liu Junhua , Wang Yuping , Wei Shiwei , Sui Xin , Tong Wuning
Published: June 2019

Currently, there are four drawbacks for filled function methods: (1) too many local optimal solutions result in huge difficulty to search global optimal solutions; (2) difficult to control the parameter(s); (3) difficult to determine the initial point for minimization of filled function; (4) the shallow basins will affect the solution precision during the minimization of the filled function. To overcome these drawbacks, in this paper, we adopt a flatten function to eliminate many local optimal solutions first, and then a new filled function with one parameter is proposed, and its parameter is easy to control. Furthermore, we propose an efficient method for determining initial point of the filled function by using adaptive step size. Moreover, when some basins of the filled function are shallow ones, it will result in inefficiency of searching these basins during the minimization of the filled function. To tackle this issue and make the search for global optimal solutions much easier, we propose a strategy of basin deepening. By integrating these schemes, we propose a new efficient filled flatten function method. Numerical results indicate the efficiency and effectiveness of the proposed filled function methods.
Further Insights Into Time-Integration Method Based on Bernstein Polynomials and Bezier Curve for Structural Dynamics
Authors: Malakiyeh Mohammad Mahdi , Shojaee Saeed , Hamzehei-Javaran Saleh , Tadayon Behrooz
Published: June 2019

In [M. M. Malakiyeh, S. Shojaee and S. Hamzehei-Javaran, Development of a direct time integration method based on Bezier curve and 5th-order Berstein basis function, Comput. Struct. 194 (2108) 15–31] an unconditionally stable implicit time-integration method using the Bezier curve was proposed for solving structural dynamic problems. In this study, a new class of the previous algorithm is presented by using the Bernstein polynomials and the Bezier curve as the interpolation functions for solving the equations of motion with the possibility of using large time steps. The spectral radius, period elongation, amplitude decay and overshooting of the present method are investigated and compared with some other methods. To show the high-performance, robustness and validity of this method, five numerical examples are presented. The theoretical analysis and numerical examples show that the proposed method has low dissipation in the lower modes and high dissipation in the higher modes in comparison with the other methods reported in the literature.
Singular values of large non-central random matrices
Authors: Bryc Włodek , Silverstein Jack W.
Published: June 2019

We study largest singular values of large random matrices, each with mean of a fixed rank [Formula: see text]. Our main result is a limit theorem as the number of rows and columns approach infinity, while their ratio approaches a positive constant. It provides a decomposition of the largest [Formula: see text] singular values into the deterministic rate of growth, random centered fluctuations given as explicit linear combinations of the entries of the matrix, and a term negligible in probability. We use this representation to establish asymptotic normality of the largest singular values for random matrices with means that have block structure. We also deduce asymptotic normality for the largest eigenvalues of a random matrix arising in a model of population genetics.
Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice
Authors: Espinoza-Derout Jorge , Hasan Kamrul M. , Shao Xuesi M. , Jordan Maria C. , Sims Carl , Lee Desean L. , Sinha Satyesh , Simmons Zena , Mtume Norma , Liu Yanjun , Roos Kenneth P. , Sinha-Hikim Amiya P. , Friedman Theodore C.
Published: June 2019

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE−/−) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE−/− mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractional shortening and ejection fraction compared with e-cigarette (0%) and saline. Ventricular transcriptomic analysis revealed changes in genes associated with metabolism, circadian rhythm, and inflammation in e-cigarette (2.4%)-treated ApoE−/− mice. Transmission electron microscopy revealed that cardiomyocytes of mice treated with e-cigarette (2.4%) exhibited ultrastructural abnormalities indicative of cardiomyopathy. Additionally, we observed increased oxidative stress and mitochondrial DNA mutations in mice treated with e-cigarette (2.4%). ApoE−/− mice on e-cigarette (2.4%) had also increased atherosclerotic lesions compared with saline aerosol-treated mice. These results demonstrate adverse effects of e-cigarettes on cardiac function in mice.

NEW & NOTEWORTHY The present study is the first to show that mice exposed to nicotine electronic cigarettes (e-cigarettes) have decreased cardiac fractional shortening and ejection fraction in comparison with controls. RNA-seq analysis reveals a proinflammatory phenotype induced by e-cigarettes with nicotine. We also found increased atherosclerosis in the aortic root of mice treated with e-cigarettes with nicotine. Our results show that e-cigarettes with nicotine lead to detrimental effects on the heart that should serve as a warning to e-cigarette users and agencies that regulate them.
Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma
Authors: Eberle-Singh Jaime A. , Sagalovskiy Irina , Maurer H. Carlo , Sastra Stephen A. , Palermo Carmine F. , Decker Amanda R. , Kim Min Jung , Sheedy Josephine , Mollin Anna , Cao Liangxian , Hu Jianhua , Branstrom Arthur , Weetall Marla , Olive Kenneth P.
Published: June 2019

Purpose:

Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that is broadly chemoresistant, due in part to biophysical properties of tumor stroma, which serves as a barrier to drug delivery for most classical chemotherapeutic drugs. The goal of this work is to evaluate the preclinical efficacy and mechanisms of PTC596, a novel agent with potent anticancer properties in vitro and desirable pharmacologic properties in vivo.

Experimental Design: We assessed the pharmacology, mechanism, and preclinical efficacy of PTC596 in combination with standards of care, using multiple preclinical models of PDA.

Results:

We found that PTC596 has pharmacologic properties that overcome the barrier to drug delivery in PDA, including a long circulating half-life, lack of P-glycoprotein substrate activity, and high systemic tolerability. We also found that PTC596 combined synergistically with standard clinical regimens to improve efficacy in multiple model systems, including the chemoresistant genetically engineered “KPC” model of PDA. Through mechanistic studies, we learned that PTC596 functions as a direct microtubule polymerization inhibitor, yet a prior clinical trial found that it lacks peripheral neurotoxicity, in contrast to other such agents. Strikingly, we found that PTC596 synergized with the standard clinical backbone regimen gemcitabine/nab-paclitaxel, yielding potent, durable regressions in a PDX model. Moreover, similar efficacy was achieved in combination with nab-paclitaxel alone, highlighting a specific synergistic interaction between two different microtubule-targeted agents in the setting of pancreatic ductal adenocarcinoma.

Conclusions:

These data demonstrate clear rationale for the development of PTC596 in combination with standard-of-care chemotherapy for PDA.
Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation
Authors: Pasch Cheri A. , Favreau Peter F. , Yueh Alexander E. , Babiarz Christopher P. , Gillette Amani A. , Sharick Joe T. , Karim Mohammad Rezaul , Nickel Kwangok P. , DeZeeuw Alyssa K. , Sprackling Carley M. , Emmerich Philip B. , DeStefanis Rebecca A. , Pitera Rosabella T. , Payne Susan N. , Korkos Demetra P. , Clipson Linda , Walsh Christine M. , Miller Devon , Carchman Evie H. , Burkard Mark E. , Lemmon Kayla K. , Matkowskyj Kristina A. , Newton Michael A. , Ong Irene M. , Bassetti Michael F. , Kimple Randall J. , Skala Melissa C. , Deming Dustin A.
Published: June 2019

Purpose:

Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed.

Experimental Design:

Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively.

Results:

We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key histologic and molecular features. These cultures were generated from numerous cancers, various biopsy sample types, and in different clinical settings. Next-generation sequencing reveals the presence of subclonal populations within the organoid cultures. These cultures allow for the detection of clonal heterogeneity with a greater sensitivity than bulk tumor sequencing. Optical metabolic imaging of these organoids provides cell-level quantification of treatment response and tumor heterogeneity allowing for resolution of therapeutic differences between patient samples. Using this technology, we prospectively predict treatment response for a patient with metastatic colorectal cancer.

Conclusions:

These studies add to the literature demonstrating feasibility to grow clinical patient-derived organotypic cultures for treatment effectiveness testing. Together, these culture methods and response assessment techniques hold great promise to predict treatment sensitivity for patients with cancer undergoing chemotherapy and/or radiation.
A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis
Authors: Liu Yao , Meng Fanzheng , Wang Jiabei , Liu Mingyang , Yang Guangchao , Song Ruipeng , Zheng Tongsen , Liang Yingjian , Zhang Shugeng , Yin Dalong , Wang Jizhou , Yang Haiyan , Pan Shangha , Sun Bo , Han Jihua , Sun Jing , Lan Yaliang , Wang Yan , Liu Xirui , Zhu Mingxi , Cui Yifeng , Zhang Bo , Wu Dehai , Liang Shuhang , Liu Yufeng , Song Xuan , Lu Zhaoyang , Yang Jingxuan , Li Min , Liu Lianxin
Published: June 2019

Purpose:

As a main rate-limiting subunit of the 2-oxoglutarate dehydrogenase multienzyme complex, oxoglutarate dehydrogenase like (OGDHL) is involved in the tricarboxylic acid cycle, and frequently downregulated in human carcinoma and suppresses tumor growth. However, little is known about the role of OGDHL in human cancer, especially pancreatic cancer. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by OGDHL modulating pancreatic cancer progression.

Experimental Design:

The expression and functional analysis of OGDHL, miR-214, and TWIST1 in human pancreatic cancer tissues, cell lines, and xenograft tumor model were investigated. The correlations between OGDHL and those markers were analyzed.

Results:

OGDHL was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. OGDHL was shown to be negatively regulated by miR-214. TWIST1 upregulation induced miR-214 expression in pancreatic cancer. OGDHL suppressed TWIST1 expression through promoting ubiquitin-mediated proteasomal degradation of HIF1α and regulating AKT pathways. A combination of OGDHL downregulation and TWIST1 and miR-214 overexpression predicted worse prognosis in patients with pancreatic cancer.

Conclusions:

We demonstrated the prognostic value of OGDHL, miR-214, and TWIST1 in pancreatic cancer, and elucidated a novel pathway in OGDHL-regulated inhibition of pancreatic cancer tumorigenesis and metastasis. These findings may lead to new targeted therapy for pancreatic cancer through regulating OGDHL, miR-214, and TWIST1.
Distinguishing Tumor from Associated Fibrosis to Increase Diagnostic Biopsy Yield with Polarization-Sensitive Optical Coherence Tomography
Authors: Hariri Lida P. , Adams David C. , Applegate Matthew B. , Miller Alyssa J. , Roop Benjamin W. , Villiger Martin , Bouma Brett E. , Suter Melissa J.
Published: June 2019

Purpose:

With recent advancements in personalized medicine, biopsies must contain sufficient tumor for histologic diagnosis and molecular testing. However, inadvertent biopsy of tumor-associated fibrosis compromises tumor yield, resulting in delayed diagnoses and/or repeat procedures when additional tumor is needed. The ability to differentiate tumor from fibrosis intraprocedurally during biopsy could significantly increase tumor yield. Polarization-sensitive optical coherence tomography (PS-OCT) is an imaging modality that is endoscope- and/or needle-compatible, and provides large volumetric views of tissue microstructure with high resolution (∼10 μm) while simultaneously measuring birefringence of organized tissues such as collagen. We aim to determine whether PS-OCT can accurately detect and distinguish tumor-associated fibrosis from tumor.

Experimental Design:

PS-OCT was obtained ex vivo in 64 lung nodule samples. PS-OCT birefringence was measured and correlated to collagen content in precisely matched histology, quantified on picrosirius red (PSR) staining.

Results:

There was a strong positive correlation between PS-OCT measurement of birefringent fibrosis and total collagen content by PSR (r = 0.793; P < 0.001). In addition, PS-OCT was able to accurately classify tumor regions with >20% fibrosis from those with low fibrosis (≤20%) that would likely yield higher tumor content (P < 0.0001).

Conclusions:

PS-OCT enables accurate fibrosis detection and can distinguish tumor regions with low fibrosis. PS-OCT has significant potential for clinical impact, as the ability to differentiate tumor from fibrosis could be used to guide intraprocedural tissue sampling in vivo, or for rapid biopsy adequacy assessment ex vivo, to increase diagnostic tumor yield essential for patient care and research.
Talkumpleurodese über dauerhaft implantierten Katheter bei malignem Pleuraerguss
Authors: Keymel Stefanie
Published: June 2019

Ein maligner Pleuraerguss (MPE) wird häufig nicht operativ durch eine Talkumpleurodese behandelt, die typischerweise unter stationären Bedingungen vorgenommen wird. Als Behandlungsalternative kann ein Pleurakatheter (indwelling pleural catheter, IPC) zur intermittierenden Drainage implantiert werden. Dies kann als ambulante Prozedur vorgenommen werden. In einer klinischen multizentrischen Studie im Vereinigten Königreich wurde geprüft, ob die Instillation von Talkum über einen IPC häufiger zu einer Pleurodese führt als Plazebo. Hierfür wurden Patienten mit MPE eingeschlossen, bei denen nach Anlage eines IPC und Drainagetherapie die Lunge nach 10 Tagen entfaltet war. 69 Patienten wurde über den IPC 4g einer Talkumsuspension instilliert, 70 Patienten wurde als Plazebo über den IPC Kochsalzlösung appliziert. Der primäre Endpunkt, die erfolgreiche Pleurodese nach der Randomisierung, wurde bei 30 von 69 (43%) Patienten in der Talkumgruppe und 16 von 70 (23%) Patienten in der Plazebogruppe erreicht, dies war signifikant häufiger in der Talkumgruppe (Hazard ratio 2,20; 95% Konfidenzintervall 1,23-3,92; p = 0,008). Die Lebensqualität und die Symptomatik waren besser in der Talkumgruppe, während die Ergussmenge, die Anzahl der stationären Behandlungstage, die Mortalität oder der Anzahl von unerwünschten Ereignissen zwischen den Gruppen vergleichbar waren.
Der Einfluss des Alters auf die Morbidität und Mortalität bei operablen Lungenkrebspatienten im Stadium I
Authors: Hekmat Khosro
Published: June 2019

Die vorliegende Studie befasst sich mit dem Einfluss des Alters auf die postoperative Morbidität und Mortalität nach Lungenresektion bei Patienten mit einem nicht kleinzelligen Bronchialkarzinom (non-small cell lung carcinoma, NSCLC) im Stadium I. Am Sloan Kettering Cancer Center (USA) wurden in den Jahren 2000-2011 insgesamt 5371 Patienten einer Lungenresektion unterzogen. 2186 Patienten befanden sich im Stadium I eines NSCLC und wurden in die Studie eingeschlossen. Die multivariate Analyse zeigte, dass die Lungendiffusion (DLCO) ein unabhängiger Prädiktor für die Morbidität, Einjahresmortalität und nicht krebsspezifische Mortalität war. Im Gegensatz dazu war die Einsekundenkapazität (FEV1) ein signifikanter Risikofaktor für die krebsspezifische Mortalität. Die vorliegende Studie zeigt die Relevanz der präoperativen Lungenfunktion mit Bestimmung der DLCO und FEV1. Bei älteren Patienten mit Lungenresektion im Stadium I eines NSCLC ist die nicht krebsspezifische Sterblichkeit in der Frühphase nach der Operation bedeutsam.