bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of paramedic rapid sequence intubation and survival in out-of-hospital stroke
Authors: Fouche Pieter Francsois , Smith Karen , Jennings Paul Andrew , Boyle Malcolm , Bernard Stephen
Published: May 2019

Introduction

Ambulance transport of patients with stroke is common, with rapid sequence intubation (RSI) to secure the airway used regularly. Randomised controlled trial evidence exists to support the use of RSI in traumatic brain injuries (TBIs), but it is not clear whether the RSI evidence from TBI can be applied to the patient with stroke. To this end, we analysed a retrospective stroke dataset to compare survival of patients with RSI compared with patients that did not receive RSI.

Methods

This study was a retrospective analysis of 10 years of in-hospital and out-of-hospital data for all patients with stroke attended by Ambulance Victoria, in Victoria Australia. Generalised boosted logistic regression was used to predict propensity scores, with initial vital signs, age and demographic variables as well as measures of illness severity and comorbidity included in the prediction model. This analysis employed a 1:1 nearest-neighbour matching which was applied to generate a dataset from which we calculated the OR of survival to hospital discharge of patients receiving RSI versus no-RSI. The sensitivity of these results to unmeasured confounding was assessed with deterministic sensitivity analysis.

Results

The propensity score-matched cohort showed a decreased survival for RSI in strokes with an OR 0.61 (95% CI 0.45 to 0.82; p=0.001) when compared with no-RSI. A subgroup analysis showed no significant survival difference for ischaemic strokes: OR 0.66 (95% CI 40 to 1.07; p=0.09). The survival for haemorrhagic stroke was OR 0.60 (95% CI 0.41 to 0.90; p=0.01) lesser for RSI. Results were likely robust to unmeasured confounding and missing data.

Conclusions

Our retrospective analysis shows a decrease in survival when RSI is utilised by paramedics for stroke. Since RSI is commonly used for strokes, controlled trial evidence to support this practice is urgently needed.
‘A disastrous blow’: psychiatric risk, social indicators and medical authority in abortion reform in post-war Britain
Authors: Crook Sarah
Published: May 2019

The Second World War lent impetus to the creation of new models and explanatory frameworks of risk, encouraging a closer reading of the relationship between individual psychiatric disorder and social disarray. This article interrogates how conceptions of psychiatric risk were animated in debates around abortion reform to forge new connections between social conditions and psychiatric vulnerability in post-war Britain. Drawing upon the arguments that played out between medical practitioners, I suggest that abortion reform, culminating in the 1967 Abortion Act, was both a response to and a stimulus for new ideas about the interaction between social aetiologies and medical pathologies; indeed, it became a site in which the medical and social domains were recognised as mutually constitutive. Positioned in a landscape in which medical professionals were seeking to assert their authority and to defend their areas of practice, abortion reform offered new opportunities for medical professionals to intervene in the social sphere under the guise of risk to women’s mental health. The debate in medical journals around the status of issues that were seen to bridge the social and the medical were entangled with increasing anxiety about patient agency and responsibility. These concerns were further underscored as conversations about psychiatric risk extended towards considerations of the potential impact on women’s existing families, bringing domestic conditions and the perceived psychosocial importance of family life into relief within medical journals. This article, then, argues that conceptions of psychiatric risk, as refracted through the creation of new synapses connecting the social and the medical domains, were critical to medical debates over abortion reform in post-war Britain.
Glycated hemoglobin (HbA1c) and outcome following endovascular thrombectomy for ischemic stroke
Authors: Diprose William K , Wang Michael T M , McFetridge Andrew , Sutcliffe James , Barber P Alan
Published: May 2019

Background

In ischemic stroke, increased glycated hemoglobin (HbA1c) and glucose levels are associated with worse outcome following thrombolysis, and possibly, endovascular thrombectomy.

Objective

To evaluate the association between admission HbA1c and glucose levels and outcome following endovascular thrombectomy.

Methods

Consecutive patients treated with endovascular thrombectomy with admission HbA1c and glucose levels were included. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0–2 at 3 months. Secondary outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3), early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) score ≥8 points, or NIHSS score of 0–1 at 24 hours), symptomatic intracerebral hemorrhage (sICH), and mortality at 3 months.

Results

223 patients (136 (61%) men; mean±SD age 64.5±14.6) were included. The median (IQR) HbA1c and glucose were 39 (36-45) mmol/mol and 6.9 (5.8–8.4) mmol/L, respectively. Multiple logistic regression analysis demonstrated that increasing HbA1c levels (per 10 mmol/mol) were associated with reduced functional independence (OR=0.76; 95% CI 0.60–0.96; p=0.02), increased sICH (OR=1.33; 95% CI 1.03 to 1.71; p=0.03), and increased mortality (OR=1.26; 95% CI 1.01 to 1.57; p=0.04). There were no significant associations between glucose levels and outcome measures (all p>0.05).

Conclusions

HbA1c levels are an independent predictor of worse outcome following endovascular thrombectomy. The addition of HbA1c to decision-support tools for endovascular thrombectomy should be evaluated in future studies.
Deaths from smoking and from HIV/AIDS among gay and bisexual men in California, 2005–2050
Authors: Max Wendy B , Stark Brad B , Sung Hai-Yen , Offen Naphtali B
Published: May 2019

Introduction

Deaths from HIV/AIDS have long been of concern to the gay community, but less attention has focused on smoking-attributable deaths despite the relatively high smoking rates among gay and bisexual men. This study compared deaths from HIV/AIDS with smoking-attributable deaths among California gay and bisexual men from 2005 to 2050.

Methods

Smoking-attributable fractions (SAFs) were estimated using smoking prevalence for gay and bisexual men from the 2011–2014 California Health Interview Surveys and published relative risks of death. Smoking-attributable deaths were calculated by multiplying the SAFs by deaths among gay and bisexual men. Deaths from HIV/AIDS among men who have sex with men was obtained from the California Department of Public Health. Future deaths from smoking and HIV/AIDS were projected using regression equations based on time trends.

Results

From 2005 to 2014, smoking caused over 6800 deaths among gay and bisexual men, while nearly 9500 died from HIV/AIDS. Mortality from both causes has been falling, but deaths from HIV/AIDS have been falling more rapidly. Projections suggest that in the mid-2040s, more gay/bisexual men will die from smoking than from HIV/AIDS.

Conclusion

Smoking will surpass HIV/AIDS as a cause of death among gay and bisexual men in California within a few decades. The lesbian, gay, bisexual and transgender (LGBT) community was highly effective in drawing attention and resources to the fight against HIV/AIDS, saving untold lives by hastening effective treatments. Lessons learnt in the fight against AIDS should be used to help fight the tobacco epidemic.
Hardening or softening? An observational study of changes to the prevalence of hardening indicators in Victoria, Australia, 2001–2016
Authors: Brennan Emily , Greenhalgh Elizabeth M , Durkin Sarah J , Scollo Michelle M , Hayes Linda , Wakefield Melanie A
Published: May 2019

Background

The hardening hypothesis predicts that as smoking prevalence declines, remaining smokers will be more heavily addicted to nicotine and/or less interested in quitting. We tested this hypothesis in a population exposed to a comprehensive tobacco control programme over a 16-year period.

Methods

Annual cross-sectional surveys randomly sampled adults (aged 26+) in the state of Victoria, Australia, between 2001 and 2016. Until 2010, participants were recruited through random digit dialling to landline telephones; from 2011, sampling frames also included mobile phones. Logistic regressions assessed changes over time in the prevalence of smoking and each hardening indicator; additional models examined interactions by sex, age, education and socioeconomic status.

Results

Smoking prevalence declined significantly between 2001 and 2016 (20.1%–13.0%), as did the prevalence of seven hardening indicators: daily smoking, heavy consumption, no quit attempt in the past 5 years or past 12 months, no intention to quit in the next 6 months or next 30 days, and happiness to keep smoking. In addition, the proportion of smokers defined as ‘hardcore’ decreased from 17.2% to 9.1%. On the whole, hardening indicators decreased to a similar extent among demographic subgroups.

Conclusions

These results are inconsistent with the hardening hypothesis. Rather, they suggest that a comprehensive tobacco control programme that combines provision of cessation support to individual smokers with implementation of population-level interventions to drive all smokers towards quitting, can successfully reduce both smoking prevalence and levels of dependence and desire to keep smoking among the remaining population of smokers.
Disparities in current cigarette smoking among US adults, 2002–2016
Authors: Agaku Israel T , Odani Satomi , Okuyemi Kolawole S , Armour Brian
Published: May 2019

Background

To assess disparities in current (past 30 days) cigarette smoking among US adults aged ≥ 18 years during 2002–2016.

Methods

Nine indicators associated with social disadvantage were analysed from the 2002 to 2016 National Survey on Drug Use and Health: education, annual family income, sex, race/ethnicity, urbanicity, serious psychological distress, health insurance, public assistance, and employment status. Using descriptive and multivariable analyses, we measured trends in smoking overall and within the assessed variables. We also evaluated effect of interactions on disparities and estimated the excess number of smokers attributable to disparities.

Results

During 2002–2016, current cigarette smoking prevalence declined overall (27.5%–20.7%; p trend < 0.01), and among all subgroups except Medicare insurees and American Indians/Alaska Natives (AI/ANs). Overall inequalities in cigarette smoking grew even wider or remained unchanged for several indicators during the study period. In 2016, comparing groups with the least versus the most social advantage, the single largest disparity in current smoking prevalence was seen by race/ethnicity (prevalence ratio = 5.1, AI/ANs vs Asians). Education differences alone explained 38.0% of the observed racial/ethnic disparity in smoking prevalence. Interactions were also present; compared with the population-averaged prevalence among all AI/AN individuals (34.0%), prevalence was much higher among AI/ANs with <high school diploma (53.0%), unemployed (58.0%), or with serious psychological distress (66.9%). The burden of smoking attributable to race/ethnic disparities in smoking prevalence was an estimated 27.6 million smokers.

Conclusions

Overall smoking inequality increased or remained unchanged because of slower declines in smoking prevalence among disadvantaged groups. Targeted interventions among high-risk groups can narrow disparities.
Male smoking reduction behaviour in response to China’s 2015 cigarette tax increase
Authors: Yu Lingwei , Cohen Joanna E , Hoe Connie , Yang Tingzhong , Wu Dan
Published: May 2019

Objective

This study aims to evaluate Chinese male smokers’ responses to China’s 2015 6% ad valorem and RMB0.1 specific excise tax increase per cigarettes pack.

Methods

A male population-based cross-sectional survey with multistaged stratified sampling was employed to collect data in six cities in China. Descriptive methods and logistic models were used to assess responses and associated factors following the cigarette tax increase among male Chinese smokers.

Results

Among a potential sample of 6500 Chinese males, 6010 individuals were contacted and 5782 participants completed the questionnaires. Of the 2852 current smokers, 60.7% (95% CI: 58.9 to 62.5) did not think cigarettes were expensive, 77.9% (95% CI: 76.4 to 79.5) reported no reduction in smoking in response to the 2015 tax increase and 21.3% (95% CI: 19.8 to 22.8) were not aware of the cigarette tax increase. Smokers who were occasional smokers, intended to quit and thought cigarettes expensive were more likely to report reducing cigarette smoking following the tax increase, while those who had higher household income per capita, smoked more cigarettes, and purchased more expensive cigarettes were less likely to report reducing cigarette consumption.

Conclusions

About one in five male Chinese smokers reported reduction in smoking following China’s 2015 cigarette tax increase. This is a relatively large impact given the very modest tax increase. Even with the 2015 increase, the excise tax represents only 36.3% of the cigarette price in China. Tax increases are needed to achieve the WHO’s recommended level of 70%.
Multiple stable isotopes identify sediment organic matter as the primary nutritional source to American brook lamprey larvae along a stream gradient
Authors: Evans Thomas M. , Weber Amy M.
Published: May 2019

Multiple stable isotope ratios (δ2H, δ13C, δ15N, and δ34S) of American brook lamprey (Lethenteron appendix) ammocoetes and their potential sources were measured along a stream gradient. Isotopic ratios were successful at differentiating three potential sources: terrestrial organic matter (TOM; upland plants), sediment organic matter (SOM; benthic organic material), and algae. Bayesian mixing models (MixSIAR) utilizing δ13C, δ15N, and δ34S estimated ammocoetes were highly reliant on SOM at all sites (>95%), but inclusion of δ2H increased the importance of both algae and model uncertainty. Ammocoete δ2H was more depleted than anticipated even after lipid extraction and after accounting for trophic water contributions, suggesting δ2H in consumer tissues (especially for long-lived animals) is still incompletely understood. Model sensitivity testing with trophic fractionation values did not substantially change the results. Regardless of the mixing model investigated, none indicated more algae in ammocoete diets in downstream rather than upstream sites, in contrast with expectations about river productivity. Stable isotopes suggest SOM, and not algae, is nutritionally most important to ammocoetes, even in downstream reaches of rivers.
Quantitative PCR enumeration of vcgC and 16S rRNA type A and B genes as virulence indicators for environmental and clinical strains of Vibrio vulnificus in Galveston Bay oysters
Authors: Çam Sedat , Brinkmeyer Robin , Schwarz John R.
Published: May 2019

Oysters from a reef in Galveston Bay, Texas, USA, were screened for more virulent clinical strains versus less virulent environmental strains of Vibrio vulnificus using a combination of quantitative PCR assays for the virulence correlating gene (clinical variant, vcgC) and 16S rRNA types A and B (type A = environmental, type B = clinical). The combination of vcgC and 16S rRNA type B loci to determine clinical type strains was suitable, as indicated by the strong correlation (R2 = 0.98; p < 0.001) between these gene counts over time and their relative proportion (up to 93.8% and 94.3%, respectively) to vvhA genes used to quantify all strains of V. vulnificus. A strong seasonal shift of V. vulnificus strain types was observed. Environmental strains (16S rRNA type A) predominated from April to mid-June as salinities increased from 22 to 27 PSU (practical salinity unit) and temperatures rose 20 to 28 °C, with peak gene quantities of 16 812 ± 56 CFU/g. As temperatures increased to ≥30 °C from mid-June to September and salinities rose above 27 PSU, clinical strains (16S rRNA type B; vcgC) predominated with peak quantities 31 868 ± 287 and 32 360 ± 178 CFU/g, respectively.
Strong legacy effect of peat composition on physicochemical properties of reclamation coversoil
Authors: Calver Teri , Yarmuch Marty , Conway Alexandra J. , Stewart Katherine
Published: May 2019

Incorporation of salvaged peat in soil cover designs for oil sands mine reclamation is a common practice. However, current peat salvage practices do not differentiate between peatland types or the botanical composition of peat. In this study, we characterized the botanical composition of natural peat and coversoil on reclaimed sites and examined the influence of botanical composition on the physicochemical characteristics of reclaimed coversoil. Peat samples were collected from 15 natural peatlands (bog, poor fen, and rich fen) and peat coversoils were sampled from six reclaimed sites in the Athabasca oils sands region. The botanical compositions (Sphagnum, wood Sphagnum, woody, and woody/moss herbaceous) of all samples were determined. We found that natural peatland types had different physicochemical properties, primarily driven by Sphagnum-dominated samples with a high carbon:nitrogen (C:N) ratio and low total exchange capacity (TEC) when compared with samples dominated by more woody/moss herbaceous material. Similarly, we found that coversoil with Sphagnum-dominated peat compared with woody/moss herbaceous peat had lower TEC, pH, and total nitrogen values and higher C:N ratios (∼40 vs. 20 for Sphagnum and woody/moss herbaceous, respectively). Our results indicate that physicochemical properties driven by botanical composition remain in coversoil 5 yr after placement.
Recovering Truncated Streaming Event Log Using Coupled Hidden Markov Model
Authors: Sarno Riyanarto , Sungkono Kelly Rossa
Published: May 2019

Process discovery is a technique for obtaining process model based on traces recorded in the event log. Nowadays, information systems produce streaming event logs to record their huge processes. The truncated streaming event log is a big issue in process discovery because it inflicts incomplete traces that make process discovery depict wrong processes in a process model. Earlier research suggested several methods for recovering the truncated streaming event log and none of them utilized Coupled Hidden Markov Model. This research proposes a method that combines Coupled Hidden Markov Model with Double States and the Modification of Viterbi–Backward method for recovering the truncated streaming event log. The first layer of states contains the transition probability of activities. The second layer of states uses patterns for detecting traces which have a low appearance in the event log. The experiment results showed that the proposed method recovered appropriately the truncated streaming event log. These results also have proven that the accuracies of recovered traces obtained by the proposed method are higher than those obtained by the Hidden Markov Model and the Coupled Hidden Markov Model.
Balancing the Degree of Exploration and Exploitation of Swarm Intelligence Using Parallel Computing
Authors: Tilahun Surafel Luleseged
Published: May 2019

The two basic search behaviors used in metaheuristic algorithms in general and swarm intelligence in particular are exploration and exploitation. Exploration refers to searching the unexplored area of the feasible region while exploitation refers to the search of the neighborhood of a promising region. The success of these algorithms highly depends on how these two search behaviors are balanced. Increasing the number of initial solutions indeed increase the performance of the algorithm over the expense of the runtime. Different exploration and exploitation adjustments are used in different metaheuristic algorithms. To well balance the degree of exploration and exploitation, which ultimately leads to finding good solutions, needs a careful implementation and sufficient runtime. However, the runtime is another issue which has been a bottleneck for different application, especially for high dimensional, highly constrained and expensive objective function cases. Using parallel computing to overcome this limitation has been a central research issue in the study of metaheuristic algorithms. The three basic parallelization approaches used are the parallel move model which is a master slave model where solutions will be distributed to different processors for updating, parallel multi start model which uses several updating methods for the solutions in parallel and move acceleration method, which refers to a parallel implementation with parallelizing the objective function. There is no specific parallelization used towards balancing of exploration and exploitation is mentioned. Hence, in this paper a parallel implementation of swarm intelligence in general and two algorithms, namely particle swarm optimization and prey predator algorithm, in particular will be discussed. The parallelization proposed is aimed to merge the parallel move model and the parallel multi start model with the aim of adjusting the degree of exploration and exploitation. Experimental study based on ten benchmark problems from constrained as well as unconstrained problems will be used for simulation. It will be shown that the parallelization with specific distribution of exploration and exploitation runs better and efficiently compared to the serial and also the parallel version without exporation/exploitation adjustment.
Learning to Get Literal
Authors: Miller Craig S. , Settle Amber
Published: May 2019

We investigate conditions in which novices make some reference errors when programming. We asked students from introductory programming courses to perform a simple code-writing task that required constructing references to objects and their attributes. By experimentally manipulating the nature of the attributes in the tasks, from identifying attributes (e.g.,
title
or
label
) to descriptive attributes (e.g.,
calories
or
texture
), the study revealed the relative frequencies with which students mistakenly omit the name of an identifying attribute while attempting to reference its value. We explain how these reference-point shifts are consistent with the use of metonymy, a form of figurative expression in human communication. Our analysis also reveals how the presentation of examples can affect the construction of the reference in the student’s solution. We discuss plausible accounts of the reference-point errors and how they may inform a model of reference construction. We suggest that reference-point errors may be the result of well-practiced habits of communication rather than misconceptions of the task or what the computer can do.
Heat therapy improves soleus muscle force in a model of ischemia-induced muscle damage
Authors: Kim Kyoungrae , Reid Blake A. , Ro Bohyun , Casey Caitlin A. , Song Qifan , Kuang Shihuan , Roseguini Bruno T.
Published: May 2019

Leg muscle ischemia in patients with peripheral artery disease (PAD) leads to alterations in skeletal muscle morphology and reduced leg strength. We tested the hypothesis that exposure to heat therapy (HT) would improve skeletal muscle function in a mouse model of ischemia-induced muscle damage. Male 42-wk-old C57Bl/6 mice underwent ligation of the femoral artery and were randomly assigned to receive HT (immersion in a water bath at 37°C, 39°C, or 41°C for 30 min) or a control intervention for 3 wk. At the end of the treatment, the animals were anesthetized and the soleus and extensor digitorum longus (EDL) muscles were harvested for the assessment of contractile function and examination of muscle morphology. A subset of animals was used to examine the impact of a single HT session on the expression of genes involved in myogenesis and the regulation of muscle mass. Relative soleus muscle mass was significantly higher in animals exposed to HT at 39°C compared with the control group (control: 0.36 ± 0.01 mg/g versus 39°C: 0.40 ± 0.01 mg/g, P = 0.024). Maximal absolute force of the soleus was also significantly higher in animals treated with HT at 37°C and 39°C (control: 274.7 ± 6.6 mN; 37°C: 300.1 ± 7.7 mN; 39°C: 299.5 ± 10 mN, P < 0.05). In the soleus, but not the EDL muscle, a single session of HT enhanced the mRNA expression of myogenic factors as well as of both positive and negative regulators of muscle mass. These findings suggest that the beneficial effects of HT are muscle specific and dependent on the treatment temperature in a model of PAD.

NEW & NOTEWORTHY This is the first study to comprehensively examine the impact of temperature and muscle fiber type composition on the adaptations to repeated heat stress in a model of ischemia-induced muscle damage. Exposure to heat therapy (HT) at 37°C and 39°C, but not at 41°C, improved force development of the isolated soleus muscle. These results suggest that HT may be a practical therapeutic tool to restore muscle mass and strength in patients with peripheral artery disease.
Surf Zone Mapping Using Multirotor Unmanned Aerial Vehicle Imagery
Authors: Che Mat Norhalim , Tahar Khairul Nizam
Published: May 2019

Surf zone is a sand area that stretches inside a breaking wave to limit the rise and fall of waves on the beach. Advanced technology in the geomatics field offers a fast and accurate solution to produce surf zone maps. The demand for surf zone map is increasing during the monsoon season, especially at coastal areas. Nowadays, the Unmanned Aerial Vehicle (UAV) or drone has become popular platform in the geospatial and surveying field. The aim of this study is to produce surf zone 3D surface mapping by using a multirotor Unmanned Aerial Vehicle. There are four phases in this study which are image acquisition, UAV image processing, photogrammetric results, and analysis. The image acquisition was solely obtained using a multirotor UAV based on the photogrammetric concept. The acquired UAV images were processed using commercial software with a specific workflow. Photogrammetric products such as digital elevation model, orthophoto, contour, and surf map zone were produced. The analyses of these results were conducted based on different epochs on the selected months. The accuracy for northing, easting, and height coordinates was 1.026m, 0.838m, and 0.419m, respectively. It can be concluded that the UAV was able to produce a surf zone map with reliable accuracy. This platform is very useful for fast decision making, especially during disaster incidents.
Seasonal and Regional Differences in Extreme Rainfall Events and Their Contribution to the World’s Precipitation: GPM Observations
Authors: Kumar Shailendra , Silva Yamina , Moya-Álvarez Aldo S. , Martínez-Castro Daniel
Published: May 2019

In the present study, five-year of precipitation features (PFs) datasets, based on Global Precipitation Measurement (GPM), are used to investigate the global and regional characteristics of extreme rainfall events (EREs). The EREs are defined based on the PFs area, depth (maximum height of radar reflectivity), and the rain rate and called them largest, deepest, and intense EREs, respectively. The EREs are divided into top 10%, 1%, 0.1%, and 0.01% based on their frequency of occurrences. It is observed that occurrences of EREs belonging to less than top 0.01% EREs follow the tropical rainfall climatology over the tropics based on all the parameters. Subtropical oceanic areas consist of a higher frequency of largest EREs, whereas tropical land areas consist of the higher number of deepest EREs. The most intense EREs (top 0.01%) are uniformly distributed over tropical areas and subtropical oceans, and spatial distribution shows that a deepest ERE belongs to intense EREs in the tropical land areas. Large differences between the precipitation contribution from the largest and deepest EREs are seen; for example, the top 1% of largest EREs contribute to ∼80.7% of Earth’s precipitation, whereas the corresponding percentage for deepest EREs is only 53%. On the regional and seasonal scale, South Asia (SAsia) and South America (SA) nearly show common features, as oceanic and land areas consist of largest and deepest EREs, respectively, and contribute to higher precipitation. Subtropical latitudes over South America, including Sierra de Cordoba and La Plata basin, consist of deepest and intense EREs and match with those of the Indo-Gangetic plain over South Asia, which also shows the similar characteristics. EREs based on various parameters are strongly linked over SAsia compared to SA. For example, the largest top 10% EREs have a higher probability to be part of the top 10% deepest and intense EREs over SAsia. The seasonal and regional water budget reveals different characteristics, as in the southern hemisphere, the deeper EREs contribute to the higher fraction of rainfall, but over SAsia, the shallower EREs could also contribute to significant rainfall.
Nonsingular Fast Terminal Sliding Mode Tracking Control for a Class of Uncertain Nonlinear Systems
Authors: Chen Siyi , Liu Wei , Huang Huixian
Published: May 2019

Aiming at the tracking control problem of a class of uncertain nonlinear systems, a nonsingular fast terminal sliding mode control scheme combining RBF network and disturbance observer is proposed. The sliding mode controller is designed by using nonsingular fast terminal sliding mode and second power reaching law to solve the problem of singularity and slow convergence in traditional terminal sliding mode control. By using the universal approximation of RBF network, the unknown nonlinear function of the system is approximated, and the disturbance observer is designed by using the hyperbolic tangent nonlinear tracking differentiator (TANH-NTD) to estimate the interference of the system and enhance the robustness of the system. The stability of the system is proved by the Lyapunov principle. The numerical simulation results show that the method can shorten the system arrival time, improve the tracking accuracy, and suppress the chattering phenomenon.
IL12 Abrogates Calcineurin-Dependent Immune Evasion during Leukemia Progression
Authors: Rabe Jennifer L. , Gardner Lori , Hunter Rae , Fonseca Jairo A. , Dougan Jodi , Gearheart Christy M. , Leibowitz Michael S. , Lee-Miller Cathy , Baturin Dmitry , Fosmire Susan P. , Zelasko Susan E. , Jones Courtney L. , Slansky Jill E. , Rupji Manali , Dwivedi Bhakti , Henry Curtis J. , Porter Christopher C.
Published: May 2019

Exploitation of the immune system has emerged as an important therapeutic strategy for acute lymphoblastic leukemia (ALL). However, the mechanisms of immune evasion during leukemia progression remain poorly understood. We sought to understand the role of calcineurin in ALL and observed that depletion of calcineurin B (CnB) in leukemia cells dramatically prolongs survival in immune-competent but not immune-deficient recipients. Immune-competent recipients were protected from challenge with leukemia if they were first immunized with CnB-deficient leukemia, suggesting robust adaptive immunity. In the bone marrow (BM), recipients of CnB-deficient leukemia harbored expanded T-cell populations as compared with controls. Gene expression analyses of leukemia cells extracted from the BM identified Cn-dependent significant changes in the expression of immunoregulatory genes. Increased secretion of IL12 from CnB-deficient leukemia cells was sufficient to induce T-cell activation ex vivo, an effect that was abolished when IL12 was neutralized. Strikingly, recombinant IL12 prolonged survival of mice challenged with highly aggressive B-ALL. Moreover, gene expression analyses from children with ALL showed that patients with higher expression of either IL12A or IL12B exhibited prolonged survival. These data suggest that leukemia cells are dependent upon calcineurin for immune evasion by restricting the regulation of proinflammatory genes, particularly IL12.

Significance:

This report implicates calcineurin as an intracellular signaling molecule responsible for immune evasion during leukemia progression and raises the prospect of re-examining IL12 as a therapeutic in leukemia.
mTORC2 Suppresses GSK3-Dependent Snail Degradation to Positively Regulate Cancer Cell Invasion and Metastasis
Authors: Zhang Shuo , Qian Guoqing , Zhang Qian-Qian , Yao Yuying , Wang Dongsheng , Chen Zhuo G. , Wang Li-Jing , Chen Mingwei , Sun Shi-Yong
Published: May 2019

mTOR complex 1 (mTORC1) positively regulates cell invasion and metastasis by enhancing translation of Snail. A connection between mTOR complex 2 (mTORC2) and cell invasion and metastasis has also been suggested, yet the underlying biology or mechanism is largely unknown and thus is the focus of this study. Inhibition of mTOR with both mTOR inhibitors and knockdown of key components of mTORC, including rictor, Sin1, and raptor, decreased Snail protein levels. Inhibition of mTOR enhanced the rate of Snail degradation, which could be rescued by inhibition of the proteasome. Critically, inhibition of mTORC2 (by knocking down rictor) but not mTORC1 (by knocking down raptor) enhanced Snail degradation. Therefore, only mTORC2 inhibition induces Snail proteasomal degradation, resulting in eventual Snail reduction. Interestingly, inhibition of GSK3 but not SCF/β-TrCP rescued the Snail reduction induced by mTOR inhibitors, suggesting GSK3-dependent, but SCF/β-TrCP–independent proteasomal degradation of Snail. Accordingly, mTOR inhibitors elevated E-cadherin levels and suppressed cancer cell migration and invasion in vitro and metastasis in vivo. Collectively, this study reveals that mTORC2 positively regulates Snail stability to control cell invasion and metastasis.

Significance:

These findings delineate a new regulation mechanism of Snail, an important master regulator of epithelial–mesenchymal transition and invasion in cancers.
The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis
Authors: Taylor Sarah E. , O'Connor Caitlin M. , Wang Zhizhi , Shen Guobo , Song Haichi , Leonard Daniel , Sangodkar Jaya , LaVasseur Corinne , Avril Stefanie , Waggoner Steven , Zanotti Kristine , Armstrong Amy J. , Nagel Christa , Resnick Kimberly , Singh Sareena , Jackson Mark W. , Xu Wenqing , Haider Shozeb , DiFeo Analisa , Narla Goutham
Published: May 2019

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma–specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule–mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations.

Significance:

This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.

See related commentary by Haines and Huang, p. 4009
Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts
Authors: Mer Arvind S. , Ba-Alawi Wail , Smirnov Petr , Wang Yi X. , Brew Ben , Ortmann Janosch , Tsao Ming-Sound , Cescon David W. , Goldenberg Anna , Haibe-Kains Benjamin
Published: May 2019

Identifying robust biomarkers of drug response constitutes a key challenge in precision medicine. Patient-derived tumor xenografts (PDX) have emerged as reliable preclinical models that more accurately recapitulate tumor response to chemo- and targeted therapies. However, the lack of computational tools makes it difficult to analyze high-throughput molecular and pharmacologic profiles of PDX. We have developed Xenograft Visualization & Analysis (Xeva), an open-source software package for in vivo pharmacogenomic datasets that allows for quantification of variability in gene expression and pathway activity across PDX passages. We found that only a few genes and pathways exhibited passage-specific alterations and were therefore not suitable for biomarker discovery. Using the largest PDX pharmacogenomic dataset to date, we identified 87 pathways that are significantly associated with response to 51 drugs (FDR < 0.05). We found novel biomarkers based on gene expressions, copy number aberrations, and mutations predictive of drug response (concordance index > 0.60; FDR < 0.05). Our study demonstrates that Xeva provides a flexible platform for integrative analysis of preclinical in vivo pharmacogenomics data to identify biomarkers predictive of drug response, representing a major step forward in precision oncology.

Significance:

A computational platform for PDX data analysis reveals consistent gene and pathway activity across passages and confirms drug response prediction biomarkers in PDX.

See related commentary by Meehan, p. 4324
CD44 Regulates Formation of Spheroids and Controls Organ-Specific Metastatic Colonization in Epithelial Ovarian Carcinoma
Authors: Sacks Suarez Joelle , Gurler Main Hilal , Muralidhar Goda G. , Elfituri Osama , Xu Hao-Liang , Kajdacsy-Balla Andre A. , Barbolina Maria V.
Published: May 2019

Disseminating epithelial ovarian cancer cells often become assembled into spheroids prior to their arrival at metastatic sites within the peritoneal cavity. Although epithelial ovarian carcinoma (EOC) is the deadliest gynecologic malignancy, the mechanisms regulating formation and metastatic potential of spheroids are poorly understood. We show that expression of a cell surface glycoprotein CD44 is an important contributing factor for spheroid formation and spheroid adhesion to mesothelial cells, and its loss impairs mesenteric metastasis. In contrast, loss of CD44 resulted in significant increase of tumor burden at several locoregional sites, including liver, and unleashed distant metastases to the thoracic cavity. Altogether our studies suggest that CD44 regulates metastatic progression of EOC in an organ-specific manner.

Implications:

Expression of CD44 promotes spheroid formation, mesothelial adhesion, and formation of mesenteric metastasis, but it suppresses development of metastasis to several peritoneal sites, including liver, and the thoracic cavity.
A viola caipira no Dandô: cultura popular e meio ambiente
Authors: Corrêa Jussânia Borges
Published: May 2019

Este artigo investiga o Projeto Dandô - Circuito de Música Dércio Marques, buscando compreender seus significados, bem como o papel da Viola Caipira nesse contexto. O texto discute autores como Geertz (2012), Merriam (1964), Seeger (2008), Blacking (1974), Cambria (2015), Vilela (2013), Brandão (2008, 2009), dentre outros. Foi realizada uma etnografia de dois espetáculos do projeto Dandô em Brasília, com os violeiros João Arruda e Victor Batista, e verificou-se que as músicas apresentadas transmitem um discurso de defesa da cultura popular e do meio ambiente. Este entrelaçamento entre música e natureza nos reporta à Ecomusicologia, que pode oferecer novas abordagens de antigos problemas de música e cultura por meio de estudos conectados a questões ambientais.
Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction
Authors: Ortiz-Sánchez Paula , Villalba-Orero María , López-Olañeta Marina M. , Larrasa-Alonso Javier , Sánchez-Cabo Fátima , Martí-Gómez Carlos , Camafeita Emilio , Gómez-Salinero Jesús M. , Ramos-Hernández Laura , Nielsen Peter J. , Vázquez Jesús , Müller-McNicoll Michaela , García-Pavía Pablo , Lara-Pezzi Enrique
Published: May 2019

Rationale:

RBPs (RNA binding proteins) play critical roles in the cell by regulating mRNA transport, splicing, editing, and stability. The RBP SRSF3 (serine/arginine-rich splicing factor 3) is essential for blastocyst formation and for proper liver development and function. However, its role in the heart has not been explored.

Objective:

To investigate the role of SRSF3 in cardiac function.

Methods and Results:

Cardiac SRSF3 expression was high at mid gestation and decreased during late embryonic development. Mice lacking SRSF3 in the embryonic heart showed impaired cardiomyocyte proliferation and died in utero. In the adult heart, SRSF3 expression was reduced after myocardial infarction, suggesting a possible role in cardiac homeostasis. To determine the role of this RBP in the adult heart, we used an inducible, cardiomyocyte-specific SRSF3 knockout mouse model. After SRSF3 depletion in cardiomyocytes, mice developed severe systolic dysfunction that resulted in death within 8 days. RNA-Seq analysis revealed downregulation of mRNAs encoding sarcomeric and calcium handling proteins. Cardiomyocyte-specific SRSF3 knockout mice also showed evidence of alternative splicing of mTOR (mammalian target of rapamycin) mRNA, generating a shorter protein isoform lacking catalytic activity. This was associated with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and prevents mRNA decapping. Consequently, we found increased decapping of mRNAs encoding proteins involved in cardiac contraction. Decapping was partially reversed by mTOR activation.

Conclusions:

We show that cardiomyocyte-specific loss of SRSF3 expression results in decapping of critical mRNAs involved in cardiac contraction. The molecular mechanism underlying this effect likely involves the generation of a short mTOR isoform by alternative splicing, resulting in reduced 4E-BP1 phosphorylation. The identification of mRNA decapping as a mechanism of systolic heart failure may open the way to the development of urgently needed therapeutic tools.
Echocardiographic Abnormalities and Determinants of 1‐Month Outcome of Stroke Among West Africans in the SIREN Study
Authors: Adeoye Abiodun M. , Ovbiagele Bruce , Akinyemi Joshua O. , Ogah Okechukwu S. , Akinyemi Rufus , Gebregziabher Mulugeta , Wahab Kolawole , Fakunle Adekunle G. , Akintunde Adeseye , Adebayo Oladimeji , Aje Akinyemi , Tiwari Hemant K. , Arnett Donna , Agyekum Francis , Appiah Lambert T. , Amusa Ganiyu , Olunuga Taiwo O. , Onoja Akpa , Sarfo Fred S. , Akpalu Albert , Jenkins Carolyn , Lackland Daniel , Owolabi Lukman , Komolafe Morenikeji , Faniyan Moyinoluwalogo M. , Arulogun Oyedunni , Obiako Reginald , Owolabi Mayowa
Published: May 2019

Background

Little is known about the relationship between echocardiographic abnormalities and outcome among patients with acute stroke. We investigated the pattern and association of baseline echocardiographic variables with 1‐month disability and mortality among patients with stroke in the
SIREN
(Stroke Investigative Research and Education Network) study.

Methods and Results

We enrolled and followed up consecutive 1020 adult patients with acute stroke with baseline transthoracic echocardiography from west Africa. To explore the relationship between echocardiographic variables and 1‐month disability (using modified Rankin scale >3) and fatality, regression models were fitted. Relative risks were computed with 95% CIs. The participants comprised 60% men with a mean age of 59.2±14.6 years. Ischemic stroke was associated with smaller aortic root diameter (30.2 versus 32.5,
P
=0.018) and septal (16.8 versus 19.1,
P
<0.001) and posterior wall thickness at systole (18.9 versus 21.5,
P
=0.004). Over 90% of patients with stroke had abnormal left ventricular (LV) geometry with eccentric hypertrophy predominating (56.1%). Of 13 candidate variables investigated, only baseline abnormal
LV
geometry (concentric hypertrophy) was weakly associated with 1‐month disability (unadjusted relative risk, 1.80; 95%
CI
, 0.97–5.73). Severe
LV
systolic dysfunction was significantly associated with increased 1‐month mortality (unadjusted relative risk, 3.05; 95%
CI
, 1.36–6.83).

Conclusions

Nine of 10 patients with acute stroke had abnormal
LV
geometry and a third had systolic dysfunction. Severe
LV
systolic dysfunction was significantly associated with 1 month mortality. Larger studies are required to establish the independent effect and unravel predictive accuracy of this association.
Prelude to the Skybolt Crisis: The Kennedy Administration's Approach to British and French Strategic Nuclear Policies in 1962
Authors: Jones Matthew
Published: May 2019

The speech delivered by U.S. Secretary of Defense Robert S. McNamara on 16 June 1962 at the University of Michigan in Ann Arbor is often cited for its significance in the enunciation of U.S. nuclear strategy, but the speech also featured passages decrying the existence of separate, national nuclear forces within the North Atlantic Treaty Organization. This article concentrates on the latter dimension of the speech by examining the context of McNamara's remarks and the reactions they provoked, particularly in Great Britain. A vociferous political debate erupted in the United Kingdom over the country's independent nuclear deterrent. The article presents new evidence about McNamara's thinking on independent nuclear forces during this period and shows that the speech had the unintended consequence of complicating Britain's attempts to enter the European Economic Community. The speech and the resulting debate were a crucial part of the sequence of events that produced the Skybolt crisis at the end of 1962.
Camptodontornis gen. nov., a replacement name for the bird genus Camptodontus Li, Gong, Zhang, Yang, and Hou, 2010, a junior homonym of Camptodontus Dejean, 1826
Authors: DEMIRJIAN VAHE
Published: May 2019

Camptodontus yangi Li, Gong, Zhang, Yang, and Hou, 2010 was erected for a complete enantiornithine bird skeleton from the Early Cretaceous Jiufotang Formation in Liaoning, northeastern China (Li et al. 2010). However, the genus name Camptodontus is a junior homonym of the beetle genus Camptodontus Dejean, 1826. Under Article 23.1 of the International Code of Zoological Nomenclature (ICZN 1999) Dejean’s 1826 name has priority.
Bulbotrachystola, a substitute name for Centruroides Breuning, 1940 (Coleoptera Cerambycidae)
Authors: VITALI FRANCESCO , YANEGA DOUG
Published: May 2019

The genus name Centruroides was first introduced by George Marx (in Howard, 1889: 211) for two species of scorpions in the family Buthidae: C. exilicauda (Wood, 1863) and C. luctifer n. sp. The latter species, coming from Indefatigable Is. (Galapagos), lacks a description and has been considered as a nomen nudum and synonym of Centruroides exsul (Meise, 1934) (Lambertz, 2013). Nonetheless, exilicauda Wood (Buthus) is an available and valid species name; thus, Centruroides is available according to the ICZN, 1999, Art. 12.2.5. (“the specific name or names can be unambiguously assigned to a nominal species-group taxon or taxa”).