bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators to physical activity among children, adolescents, and young adults with cystic fibrosis: a systematic review and thematic synthesis of qualitative research
Authors: Denford Sarah , van Beurden Samantha , O'Halloran Paul , Williams Craig Anthony
Published: February 2020

Objectives

Physical activity is widely recommended in the treatment and management of cystic fibrosis (CF). Despite the numerous physical and psychological benefits, many young people with CF are not achieving the recommended levels of physical activity. The aim of this systematic review was to identify and synthesise available qualitative investigations exploring the motives for, barriers to and facilitators of physical activity among young people with CF.

Methods

The following six electronic databases were systematically searched: Applied Social Sciences Index and Abstracts (ASSIA), CINAH, EMBASE, MEDLINE, MEDLINE-in-process, PsycINFO up to August 2019. Keywords were used to identify qualitative research that explored engagement in physical activity among young people with CF. Titles and abstracts were screened by two independent reviewers, and potentially relevant articles were retrieved in full. Articles were eligible for inclusion if they employed any qualitative method and recruited participants under the age of 24 years with CF. Risk of bias of included studies was assessed via the Critical Appraisal Skills Programme. Results were synthesised using a thematic approach.

Results

Seven studies met our inclusion criteria and were included in the review. Overall, studies were of moderate to high quality. Thematic synthesis identified nine main themes that encompass motives for, barriers to and facilitators of physical activity among young people with CF. These were (1) Perceptions of physical activity. (2) Value attributed to physical activity. (3) Social influences. (4) Competing priorities. (5) Fluctuating health. (6) Normality. (7) Control beliefs. (8) Coping strategies. (9) Availability of facilities. Previous reviews have been unable to identify intervention characteristics that influence physical activity behaviour.

Conclusions

This review provides detailed information on the physical (biological—clinical), psychological, social and environmental influences on physical activity behaviour, thus providing numerous targets for future interventions. This in turn could facilitate promotion of physical activity among young people with CF.
Older LGBT+ health inequalities in the UK: setting a research agenda
Authors: Westwood Sue , Willis Paul , Fish Julie , Hafford-Letchfield Trish , Semlyen Joanna , King Andrew , Beach Brian , Almack Kathryn , Kneale Dylan , Toze Michael , Becares Laia
Published: February 2020

Lesbian, gay, bisexual and trans+ (LGBT+) people report poorer health than the general population and worse experiences of healthcare particularly cancer, palliative/end-of-life, dementia and mental health provision. This is attributable to: (a) social inequalities, including ‘minority stress’; (b) associated health-risk behaviours (eg, smoking, excessive drug/alcohol use, obesity); (c) loneliness and isolation, affecting physical/mental health and mortality; (d) anticipated/experienced discrimination and (e) inadequate understandings of needs among healthcare providers. Older LGBT+ people are particularly affected, due to the effects of both cumulative disadvantage and ageing. There is a need for greater and more robust research data to support growing international and national government initiatives aimed at addressing these health inequalities. We identify seven key research strategies: (1) Production of large data sets; (2) Comparative data collection; (3) Addressing diversity and intersectionality among LGBT+ older people; (4) Investigation of healthcare services’ capacity to deliver LGBT+ affirmative healthcare and associated education and training needs; (5) Identification of effective health promotion and/or treatment interventions for older LGBT+ people, and subgroups within this umbrella category; (6) Development of an (older) LGBT+ health equity model; (7) Utilisation of social justice concepts to ensure meaningful, change-orientated data production which will inform and support government policy, health promotion and healthcare interventions.
Abstinence-contingent wage supplements to promote drug abstinence and employment: a randomised controlled trial
Authors: Holtyn August F , Toegel Forrest , Subramaniam Shrinidhi , Jarvis Brantley P , Leoutsakos Jeannie-Marie , Fingerhood Michael , Silverman Kenneth
Published: February 2020

Background

Poverty, unemployment and substance abuse are inter-related problems. This study evaluated the effectiveness of abstinence-contingent wage supplements in promoting drug abstinence and employment in unemployed adults in outpatient treatment for opioid use disorder.

Methods

A randomised controlled trial was conducted in Baltimore, MD, from 2014 to 2019. After a 3-month abstinence initiation and training period, participants (n=91) were randomly assigned to a usual care control group that received employment services or to an abstinence-contingent wage supplement group that received employment services plus abstinence-contingent wage supplements. All participants were invited to work with an employment specialist to seek employment in a community job for 12 months. Abstinence-contingent wage supplement participants could earn training stipends for working with the employment specialist and wage supplements for working in a community job, but had to provide opiate and cocaine-negative urine samples to maximise pay.

Results

Abstinence-contingent wage supplement participants provided significantly more opiate and cocaine-negative urine samples than usual care control participants (65% vs 45%; OR=2.29, 95% CI 1.22 to 4.30, p=0.01) during the 12-month intervention. Abstinence-contingent wage supplement participants were significantly more likely to have obtained employment (59% vs 28%; OR=3.88, 95% CI 1.60 to 9.41, p=0.004) and lived out of poverty (61% vs 30%; OR=3.77, 95% CI 1.57 to 9.04, p=0.004) by the end of the 12-month intervention than usual care control participants.

Conclusion

Abstinence-contingent wage supplements can promote drug abstinence and employment.

Trial registration number

ClinicalTrials.gov
NCT02487745
.
Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes
Authors: Krenn Martin , Wagner Matias , Hotzy Christoph , Graf Elisabeth , Weber Sandrina , Brunet Theresa , Lorenz-Depiereux Bettina , Kasprian Gregor , Aull-Watschinger Susanne , Pataraia Ekaterina , Stogmann Elisabeth , Zimprich Alexander , Strom Tim M , Meitinger Thomas , Zimprich Fritz
Published: February 2020

Background

The genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can be translated into a diagnostic setting. To bridge this gap, we assessed the diagnostic outcomes of exome sequencing (ES) in NAFE.

Methods

112 deeply phenotyped patients with NAFE were included in the study. Diagnostic ES was performed, followed by a screen to detect variants of uncertain significance (VUSs) in 15 well-established focal epilepsy genes. Explorative gene prioritisation was used to identify possible novel candidate aetiologies with so far limited evidence for NAFE.

Results

ES identified pathogenic or likely pathogenic (ie, diagnostic) variants in 13/112 patients (12%) in the genes DEPDC5, NPRL3, GABRG2, SCN1A, PCDH19 and STX1B. Two pathogenic variants were microdeletions involving NPRL3 and PCDH19. Nine of the 13 diagnostic variants (69%) were found in genes of the GATOR1 complex, a potentially druggable target involved in the mammalian target of rapamycin (mTOR) signalling pathway. In addition, 17 VUSs in focal epilepsy genes and 6 rare variants in candidate genes (MTOR, KCNA2, RBFOX1 and SCN3A) were detected. Five patients with reported variants had double hits in different genes, suggesting a possible (oligogenic) role of multiple rare variants.

Conclusion

This study underscores the molecular heterogeneity of NAFE with GATOR1 complex genes representing the by far most relevant genetic aetiology known to date. Although the diagnostic yield is lower compared with severe early-onset epilepsies, the high rate of VUSs and candidate variants suggests a further increase in future years.
PhenX: Host: Social/Cognitive measures for tobacco regulatory research
Authors: Piper Megan E , Brown Darigg C , Hendershot Tabitha P , Swan Gary E
Published: February 2020

A working group (WG) of experts from diverse fields related to nicotine and tobacco addiction was convened to identify elements and measures from the Host: Social/Cognitive domain to include in the Tobacco Regulatory Research Collection in the PhenX Toolkit, a catalogue of measures for biomedical research. This paper describes the methods used to identify, select, approve and include measures in the toolkit with potential relevance to users of both conventional and newer tobacco products, such as electronic cigarettes (e-cigarettes). In addition to 25 complementary measures primarily focused on cigarette use already present in the PhenX Toolkit, the WG recommended 11 additional social/cognitive measures focused on children and adult users or potential users of tobacco products. Of these, 10 were self-administered measures: frequency of communication with parents about smoking, quality of communication with parents about smoking, susceptibility to tobacco use, behaviour economics/purchase behaviour, motivation to quit (both single and multi-item measures), hedonic tone or response to pleasurable situations, multigroup ethnic identity, peer and family influence on smoking, attentional control and house rules about tobacco use. The remaining selected measure was computer based (distress tolerance). Although validated tools for use in the Host: Social/Cognitive realm are available, much remains to be done to develop, standardise and validate the tools for application to users of e-cigarettes and other non-combusted tobacco products, non-English language speakers and adolescents.
PhenX: Agent measures for tobacco regulatory research
Authors: O'Connor Richard , Watson Clifford H , Swan Gary E , Nettles Destiney S , Geisler Rebecca C , Hendershot Tabitha P
Published: February 2020

The current paper describes the PhenX (Phenotypes and eXposures) Toolkit Tobacco Regulatory Research Agent specialty area and the Agent Working Group’s (WG’s) 6-month consensus process to identify high-priority, scientifically supported measures for cross-study comparison and analysis. Eleven measures were selected for inclusion in the Toolkit. Eight of these are interviewer-administered or self-administered protocols: history of switching to lower tar and nicotine cigarettes, passive exposures to tobacco products, tobacco brand and variety (covering cigars, cigarettes and smokeless tobacco separately), tobacco product adulteration (vent-blocking or filter-blocking) and tobacco warning label exposure and recall. The remaining three protocols are either laboratory-based or visual inspection-based: measurement of nicotine content in smoked or smokeless tobacco products and the physical properties of these two classes of products. Supplemental protocols include a biomarker of exposure and smoking topography. The WG identified the lack of standard measurement protocols to assess subjective ratings of tobacco product flavours and their appeal to consumers as a major gap. As the characteristics of tobacco products that influence perception and use are tobacco regulatory research priorities, the reliable assessment of flavours remains an area requiring further development.
Postanaesthetic brachial compartmental syndrome in a horse
Authors: Louro Luís Filipe , Fernández‐Flores Francisco Flores , Bautista Oscar Diaz‐Delgado , Senior Mark
Published: February 2020

A 9‐year‐old Irish sports horse gelding was anaesthetised out‐of‐hours for management of digital flexor tendon sheath sepsis after a left hind foot penetration. In the postanaesthetic period, the patient manifested a right forelimb non‐weight bearing lameness. Diagnostic imaging and serum biochemistry were unremarkable. The animal progressively deteriorated and became recumbent. After consultation with the owner, euthanasia was performed on welfare grounds. A postmortem examination was performed to establish the cause of the right forelimb lameness. After excluding all other probable causes of postanaesthetic lameness, it was concluded that the patient manifested a postanaesthetic compartmental syndrome due to haemorrhage associated with the ulnar nerve developed intraoperatively. This case report discusses factors associated with increased anaesthetic‐related mortality in elective surgical procedures performed out‐of‐hours, other causes of postanaesthetic forelimb lameness and diagnosis of, and treatment options for, brachial compartment syndrome.
Low wolverine (Gulo gulo) density in a national park complex of the Canadian Rocky Mountains
Authors: Barrueto M. , Sawaya M.A. , Clevenger A.P.
Published: February 2020

Large carnivores are sensitive to human-caused extirpation due to large home ranges, low population densities, and low reproductive rates. Protected areas help maintain populations by acting as sources, but human-caused mortality, habitat displacement, and edge effects occurring at protected area boundaries may reduce that function. The national parks Banff, Yoho, and Kootenay in the Canadian Rocky Mountains are refugia for large carnivores, including wolverines (Gulo gulo (Linnaeus, 1758)). Despite growing conservation concern, empirical baseline population data for wolverines remain scarce throughout their range, including most of Canada. We hypothesized (i) that in these national parks, wolverine density matched values expected for high-quality habitat, and (ii) that edge effects decreased density towards park boundaries. We conducted systematic non-invasive genetic sampling surveys covering >7000 km2 (2011 and 2013). Using spatial capture–recapture models, we estimated mean (±SE) female (1.5 ± 0.3 and 1.4 ± 0.3 wolverine/1000 km2), male (1.8 ± 0.4 and 1.5 ± 0.3 wolverine/1000 km2), and combined (3.3 ± 0.5 and 3.0 ± 0.4 wolverine/1000 km2) densities for 2011 and 2013, respectively. These estimates were lower than predictions based on density extrapolation from nearby high-quality habitat, and density decreased towards park boundaries. To benefit the population, we recommend creating buffer zones around parks that protect female habitat and prohibit harvest.
SixTrack V and runtime environment
Authors: De Maria R. , Andersson J. , Berglyd Olsen V. K. , Field L. , Giovannozzi M. , Hermes P. D. , Høimyr N. , Kostoglou S. , Iadarola G. , Mcintosh E. , Mereghetti A. , Molson J. , Pellegrini D. , Persson T. , Schwinzerl M. , Maclean E. H. , Sjobak K. N. , Zacharov I. , Singh S.
Published: February 2020

SixTrack is a single-particle tracking code for high-energy circular accelerators routinely used at CERN for the Large Hadron Collider (LHC), its luminosity upgrade (HL-LHC), the Future Circular Collider (FCC) and the Super Proton Synchrotron (SPS) simulations. The code is based on a 6D symplectic tracking engine, which is optimized for long-term tracking simulations and delivers fully reproducible results on several platforms. It also includes multiple scattering engines for beam–matter interaction studies, as well as facilities to run the integrated simulations with external particle matter interaction codes. These features differentiate SixTrack from general-purpose, optics-design software. The code recently underwent a major restructuring to merge the advanced features into a single branch, such as multiple ion species, interface with external codes and high-performance input/output. This restructuring also removed a large number of compilation flags, instead enabling/disabling the functionality with runtime options. In the process, the code was moved from Fortran 77 to Fortran 2018 standard, also allowing and achieving a better modularization. Physics models (beam–beam effects, Radio-Frequency (RF) multipoles, current carrying wires, solenoid and electron lenses) and methods (symplecticity check) have also been reviewed and refined to offer more accurate results. The SixDesk runtime environment allows the user to manage the large batches of simulations required for accurate predictions of the dynamic aperture. SixDesk supports several cluster environments available at CERN as well as submitting jobs to the LHC@Home volunteering computing project, which enables volunteers contributing with their hardware to CERN simulation. SixTrackLib is a new library aimed at providing a portable and flexible tracking engine for single- and multi-particle problems using the models and formalism of SixTrack. The library is able to run in CPUs as well as graphical processing units (GPUs). This contribution presents the status of the code, summarizes the main existing features and provides details about the main development lines SixTrack, SixDesk and SixTrackLib.
Low-Power Passive/Active UHF RFID Tag Transceiver with Frequency Locked On-chip Oscillator
Authors: Han Peiqing , Zhang Zhaofeng , Mei Niansong
Published: February 2020

A reconfigurable architecture is presented to be compatible with conventional passive operating mode and active mode for ultrahigh frequency (UHF) and radio-frequency identification (RFID) tag. The transceiver with frequency locked on-chip oscillator is proposed to increase the read range of RFID system and the lifetime of tag. The transceiver is fabricated in 0.18[Formula: see text][Formula: see text]m standard CMOS process with the active area of 0.246[Formula: see text]mm2. For passive mode, the sensitivity of tag is [Formula: see text][Formula: see text]dBm. For the active mode, the sensitivity is [Formula: see text][Formula: see text]dBm only consuming 1.2[Formula: see text][Formula: see text]W under the supply voltage of 0.8[Formula: see text]V. The output power is [Formula: see text][Formula: see text]dBm for active transmitting mode and the power consumption is 450[Formula: see text][Formula: see text]W under the supply voltage of 1[Formula: see text]V.
Exterior powers of the standard E6-module: An elementary approach
Authors: Semenov A. M. , Zubkov A. N.
Published: February 2020

For the standard [Formula: see text]-dimensional representation [Formula: see text] of the exceptional group [Formula: see text] of type [Formula: see text] we prove that [Formula: see text] is a Donkin pair if and only if the characteristic of a ground field is greater than [Formula: see text]. We also develop an elementary approach to describe submodule structure of any exterior power of [Formula: see text].
Conjugate subgroups and overgroups of Vn
Authors: Donoven Casey , Olukoya Feyishayo
Published: February 2020

We describe subgroups and overgroups of the generalized Thompson groups [Formula: see text] which arise via conjugation by rational homeomorphisms of Cantor space. We specifically consider conjugating [Formula: see text] by homeomorphisms induced by synchronizing transducers and their inverses. Our descriptions of the subgroups and overgroups use properties of the conjugating transducer to either restrict or augment the action of [Formula: see text] on Cantor space. We also consider a class [Formula: see text] of transducers containing all invertible, initial transducers. We associate to every transducer [Formula: see text] in this class, a group [Formula: see text]. We show that for a certain subclass of [Formula: see text], the groups [Formula: see text] are simple.
State sum invariants for flat virtual links from the chord index
Authors: Lee Kyeonghui , Im Young Ho , Kim Sera
Published: February 2020

We introduce some polynomial invariants for flat virtual links which are similar to the Jones–Kauffman polynomial, the Miyazawa polynomial and the arrow polynomial for virtual link diagrams, and we give several properties and examples.
Nonlinear Dynamic Response of Elastically Supported Stiffened Plates with Initial Stresses and Geometric Imperfections Under Impact Loads
Authors: Ma Niu-Jing , Gu Li-Xiong , Piao Long
Published: February 2020

This paper deals with the nonlinear dynamic response of elastically supported stiffened plates with initial stresses under impact loads. A stiffened plate is assumed to be composed of a plate with some stiffeners, which are treated separately. The plate is modeled by the thin plate theory, whereas the stiffeners are considered as geometrically nonlinear Euler–Bernoulli beams. First, the equations of both the kinetic energies and strain energies of the plate and stiffeners are established. Then, the dynamic equilibrium equations for the stiffened plate are derived as the Lagrange’s equation of the functional. A parametric analysis is performed to evaluate how initial stresses, initial geometric imperfections, elastic supports, impact loads and configuration of stiffeners affect the time-history responses of the stiffened plates. Some useful nonlinear dynamic properties are obtained, which serve as references for engineering design and application.
Kupershmidt-(dual-)Nijenhuis structure on the alternative algebra with a representation
Authors: Sun Qinxiu
Published: February 2020

The aim of this paper is to study Kupershmidt-(dual-)Nijenhuis structures on alternative algebras with representations. The notion of a (dual-)Nijenhuis pair is introduced and it can generate a trivial deformation of an alternative algebra with a representation. We introduce the notion of a Kupershmidt-(dual-)Nijenhuis structure on an alternative algebra with a representation. Furthermore, we verify that Kupershmidt operators and Kupershmidt-(dual-)Nijenhuis structures can give rise to each other under some conditions. Finally, we study the notions of Rota–Baxter–Nijenhuis structures and alternative [Formula: see text]-matrix-Nijenhuis structures. Meanwhile, we investigate the relation between them.
Analysis of interleaved storage via a constant-service queuing system with Markov-chain-driven input
Authors: Hofri Micha
Published: February 2020

A popular means of increasing the effective rate of main storage
accesses in a large computer is a multiplicity of memory modules
accessible in parallel. Although such an organization usually
achieves a net gain in access rate, it also creates new modes of
congestion at the storage controller. This paper analyzes the
variables that describe such a congestion: queue lengths and
delays. A controller that maintains separate register sets to
accommodate the request queue of each module is considered. The
various processors attached to the storage are assumed to generate,
in each memory cycle, a number of access requests with the same
given distribution. The addresses specified by these requests
(reduced to the module index) are further assumed to follow the
states of a first-order Markov chain. The analysis then becomes one
of a single-server queuing system with constant service time and
indexed batch arrival process. Results are derived for several
descriptors of the congestion and thus of the quality of service
offered by such an organization. The aim throughout is to embody
the results in a form readily suitable for numerical
evaluation.
Hasta Luego, Mi Amiga
Authors: Rothwell Trevis J.
Published: February 2020

Looking back fondly on an old friend
Estrogen and calcium handling proteins: new discoveries and mechanisms in cardiovascular diseases
Authors: Jiao Lijuan , Machuki Jeremiah Ong’achwa , Wu Qi , Shi Mingjin , Fu Lu , Adekunle Adebayo Oluwafemi , Tao Xi , Xu Chenxi , Hu Xide , Yin Zeyuan , Sun Hong
Published: February 2020

Estrogen deficiency is considered to be an important factor leading to cardiovascular diseases (CVDs). Indeed, the prevalence of CVDs in postmenopausal women exceeds that of premenopausal women and men of the same age. Recent research findings provide evidence that estrogen plays a pivotal role in the regulation of calcium homeostasis and therefore fine-tunes normal cardiomyocyte contraction and relaxation processes. Disruption of calcium homeostasis is closely associated with the pathological mechanism of CVDs. Thus, this paper maps out and summarizes the effects and mechanisms of estrogen on calcium handling proteins in cardiac myocytes, including L-type Ca2+ channel, the sarcoplasmic reticulum Ca2+ release channel named ryanodine receptor, sarco(endo)plasmic reticulum Ca2+-ATPase, and sodium-calcium exchanger. In so doing, we provide theoretical and experimental evidence for the successful design of estrogen-based prevention and treatment therapies for CVDs.
Gastric bypass in female rats lowers concentrated sugar solution intake and preference without affecting brief-access licking after long-term sugar exposure
Authors: Hyde Kellie M. , Blonde Ginger D. , Bueter Marco , le Roux Carel W. , Spector Alan C.
Published: February 2020

In rodents, Roux-en-Y gastric bypass (RYGB) decreases intake of, and preference for, foods or fluids that are high in sugar. Whether these surgically induced changes are due to decreases in the palatability of sugar stimuli is controversial. We used RYGB and sham-operated (SHAM) female rats to test the influence of prolonged ingestive experience with sugar solutions on the motivational potency of these stimuli to drive licking in brief-access (BA) tests. In experiment 1, RYGB attenuated intake of, and caloric preference for, 0.3 M sucrose during five consecutive, 46-h two-bottle tests (TBTs; sucrose). A second series of TBTs (5 consecutive, 46-h tests) with 1.0 M sucrose revealed similar results, except fluid preference for 1.0 M sucrose also significantly decreased. Before, between, and after the two series of TBTs, two sessions of BA tests (30 min; 10-s trials) with an array of sucrose concentrations (0 and 0.01–1.0 M) were conducted. Concentration-dependent licking and overall trial initiation did not differ between surgical groups in any test. In a similar experimental design in a second cohort of female rats, 0.6 and 2.0 M glucose (isocaloric with sucrose concentrations in experiment 1) were used in the TBTs; 0 and 0.06-2.0 M glucose were used in the BA tests. Outcomes were similar to those for experiment 1, except RYGB rats initiated fewer trials during the BA tests. Although RYGB profoundly affected intake of, and caloric preference for, sugar solutions and, with high concentrations, fluid preference, RYGB never influenced the motivational potency of sucrose or glucose to drive concentration-dependent licking in BA tests.
High-Flow Nasal Cannula: A Promising Oxygen Therapy for Patients with Severe Bronchial Asthma Complicated with Respiratory Failure
Authors: Geng Wanru , Batu Wuliji , You Shuhong , Tong Zhaohui , He Hangyong
Published: February 2020

Severe bronchial asthma complicated with respiratory failure, a common critical illness in respiratory medicine, may be life-threatening. High-flow nasal cannula (HFNC) is a novel oxygen therapy technique developed in recent years. HFNC was applied in this study for treating adult patients with severe bronchial asthma complicated with respiratory failure. Its efficacy was analyzed comparatively to conventional oxygen therapy (COT). HFNC and COT were randomly performed based on conventional treatment. The HFNC group was similar to COT-treated patients in terms of response rate, with no significant difference in efficacy between the two groups. In patients with bronchial asthma, effectively increased PO2 and reduced PCO2 were observed after treatment in both groups. However, HFNC was more efficient than COT in elevating PO2 in patients with severe bronchial asthma complicated with respiratory failure, while no statistically significant difference in PCO2 reduction was found between the two groups. Heart rate (HR) and respiratory rate (RR) between the two groups on admission (0 h) and at 2, 8, 24, and 48 h after admission were compared. Both indicators significantly decreased with time. No significant differences in HR and RR were found between the groups at 0, 2, and 8 h after admission. However, these indicators were significantly lower in the HFNC group compared with the COT group at 24 and 48 h after admission. HFNC could significantly elevate PO2 and reduce HR and RR. Thus, it is a promising option for patients with severe bronchial asthma complicated with respiratory failure.
Using Extended-Release Injectable Aripiprazole for the Successful Treatment of Depressive Symptoms in Bipolar I Disorder
Authors: Kuo Joseph , Lin Shih-Ku
Published: February 2020

Extended-release injectable (ERI) aripiprazole is indicated for schizophrenia and maintenance monotherapy of bipolar I disorder. Clinical trials of aripiprazole failed to exhibit efficacy in the treatment of bipolar depression. It has been suggested that relatively high doses, rapid titration of dose, a high dropout rate, and a high placebo effect might be the reasons of its ineffectiveness. Here, we report a case of a 39-year-old woman with bipolar depression who was successfully treated with ERI aripiprazole.
The Impulsive Model with Pest Density and Its Change Rate Dependent Feedback Control
Authors: Khan Ihsan Ullah , Tang Sanyi
Published: February 2020

The idea of action threshold depends on the pest density and its change rate is more general and furthermore can produce new modelling techniques related to integrated pest management (IPM) as compared with those that appeared in earlier studies, which definitely bring challenges to analytical analysis and generate new ideas to the state control measures. Keeping this in mind, using the strategies of IPM, we develop a prey-predator system with action threshold depending on the pest density and its change rate, and study its dynamical behavior. We develop new criteria guaranteeing the existence, uniqueness, local and global stability of order-1 periodic solutions. Applying the properties of Lambert W function, the Poincaré map is portrayed for the exact phase set, which is helpful to provide the sufficient conditions for the existence and stability of the interior order-1 periodic solutions and boundary order-1 periodic solution, also confirmed by numerical simulations. It is studied in detail that how and under what conditions the fixed point of Poincaré map and its stability are affected by the newly introduced action threshold. The analytical methods developed in this paper will be very beneficial to study other generalized models with state-dependent feedback control.
Effect of Inflammation on Gingival Mesenchymal Stem/Progenitor Cells’ Proliferation and Migration through Microperforated Membranes: An In Vitro Study
Authors: Al Bahrawy M. , Ghaffar K. , Gamal A. , El-Sayed K. , Iacono V.
Published: February 2020

Background. In the field of periodontal guided tissue regeneration, microperforated membranes have recently proved to be very promising periodontal regenerative tissue engineering tools. Regenerative periodontal approaches, employing gingival mesenchymal stem/progenitor cells in combination with these novel membranes, would occur mostly in inflamed microenvironmental conditions intraorally. This in turn entails the investigation into how inflammation would affect the proliferation as well as the migration dynamics of gingival mesenchymal stem/progenitor cells. Materials and Methods. Clones of human gingival mesenchymal stem/progenitor cells (GMSCs) from inflamed gingival tissues were characterized for stem/progenitor cells’ characteristics and compared to clones of healthy human GMSCs (n=3), to be subsequently seeded on perforated collagen-coated poly-tetra-floro-ethylene (PTFE) membranes with a pore size 0.4 and 3 microns and polycarbonic acid membranes of 8 microns pore size in Transwell systems. The population doubling time and the MTT test of both populations were determined. Fetal bovine serum (FBS) was used as a chemoattractant in the culturing systems, and both groups were compared to their negative controls without FBS. Following 24 hours of incubation period, migrating cells were determined on the undersurface of microperforated membranes and the membrane-seeded cells were examined by scanning electron microscopy. Results. GMSCs demonstrated all predefined stem/progenitor cell characteristics. GMSCs from inflamed gingival tissues showed significantly shorter population doubling times. GMSCs of inflamed and healthy tissues did not show significant differences in their migration abilities towards the chemoattractant, with no cellular migration observed in the absence of FBS. GMSCs from healthy gingival tissue migrated significantly better through larger micropores (8 microns). Scanning electron microscopic images proved the migratory activity of the cells through the membrane pores. Conclusions. Inflammation appears to boost the proliferative abilities of GMSCs. In terms of migration through membrane pores, GMSCs from healthy as well as inflamed gingival tissues do not demonstrate a difference in their migration abilities through smaller pore sizes, whereas GMSCs from healthy gingival tissues appear to migrate significantly better through larger micropores.
Comparing Nursing Student Competence in CPR before and after a Pedagogical Intervention
Authors: Roel Siv , Bjørk Ida Torunn
Published: February 2020

Nursing students must be able to initiate and perform effective cardiopulmonary resuscitation (CPR) when they start their career in nursing. Studies show that students’ competency in CPR is deficient, indicating that better training is necessary during nursing education. This study reports on the differences in nursing students’ competence in CPR before and after a longitudinal pedagogical intervention across the curriculum. Changes in the curriculum were relocation and added testing of CPR skills, inclusion of a course in defibrillation, a knowledge test as stimuli before simulation, and more simulation practice with deteriorating patients. This was a comparative study between two cohorts of students in the bachelor in nursing education. We measured knowledge and compression performance in the students’ final year of education. Students in cohort 2, who received the pedagogical intervention, had a significant higher total knowledge score than students in cohort 1. Students’ mean depth and number of correct compressions was similar. Students in cohort 2 had a significantly higher mean rate of compressions, number of compressions per minute, and mean number of compressions with incorrect hand positions. Although the new curriculum afforded more hands-on practice of CPR, it was not enough to improve the students’ performance to match the demands set out in national and international guidelines.
Design and Conduct of Early Clinical Studies of Immunotherapy: Recommendations from the Task Force on Methodology for the Development of Innovative Cancer Therapies 2019 (MDICT)
Authors: Smoragiewicz Martin , Adjei Alex A. , Calvo Emiliano , Tabernero Josep , Marabelle Aurélien , Massard Christophe , Tang Jun , de Vries Elisabeth G.E. , Douillard Jean-Yves , Seymour Lesley
Published: February 2020

Purpose:

To review key aspects of the design and conduct of early clinical trials (ECT) of immunotherapy agents.

Experimental Design:

The Methodology for the Development of Innovative Cancer Therapies Task Force 2019 included experts from academia, nonprofit organizations, industry, and regulatory agencies. The review focus was on methodology for ECTs testing immune-oncology therapies (IO) used in combination with other IO or chemotherapy.

Results:

Although early successes have been seen, the landscape continues to be very dynamic, and there are ongoing concerns regarding the capacity to test all new drugs and combinations in clinical trials.

Conclusions:

Optimization of drug development methodology is required, taking into account early, late, and lower grade intolerable toxicities, novel response patterns, as well as pharmacodynamic data.
Circuit Survival during Continuous Venovenous Hemodialysis versus Continuous Venovenous Hemofiltration
Authors: Califano Alfonso Maria , Bitker Laurent , Baldwin Ian , Fealy Nigel , Bellomo Rinaldo
Published: February 2020

Background: Continuous renal replacement therapy (CRRT) technique may affect circuit lifespan. A shorter circuit life may reduce CRRT efficacy and increase costs. Methods: In a before-and-after study, we compared circuit median survival time during continuous venovenous hemofiltration (CVVH) versus continuous venovenous hemodialysis (­CVVHD). We performed log-rank mixed effects univariate analysis and Cox mixed effect regression modeling to define predictors of circuit lifespan. Results: We compared 197 ­CVVHD and 97 CVVH circuits in 39 patients. There was no overall difference in circuit lifespan. When no anticoagulation was used, median circuit survival time was shorter for CVVH circuits (5 h, 95% CI 3–7 vs. 10 h, 95% CI 8–13, p < 0.01). Moreover, CVVHD, lower platelets levels, and longer activated partial thromboplastin time independently predicted longer circuit median survival time. Conclusions: CVVHD is associated with longer circuit median survival time than CVVH when no anticoagulation is used and is an independent predictor of circuit survival.
Bone Mineral Density in Patients Suffering from Ménière’s Disease
Authors: Shupak Avi , Faranesh Nabil
Published: February 2020

Introduction: Previous studies have reported an association between reduced bone mineral density and the occurrence of benign paroxysmal positional vertigo, balance impairment, and saccular dysfunction. Furthermore, the results of recent animal studies have raised the possibility that vestibular dysfunction could affect bone remodeling and bone mass. The goal of the study was to compare bone mineral density of patients suffering from definite Ménière’s disease to that of a matched control group. Methods: We conducted a case-control cross-sectional study in a tertiary referral center. The study group included 23 patients suffering from definite Ménière’s disease, and the control group was comprised of 23 patients matched in their race, gender, and age parameters in whom no vestibular pathology could be found. Dual energy X-ray absorptiometry of the femoral head was used for the assessment of bone mineral density. The T and Z scores of the femoral heads’ bone mineral density were compared. Results: The average T scores were –1.53 ± 1.08 in the study and –0.39 ± 0.72 (p = 0.016) in the control groups, and the Z scores were –0.4 ± 0.63 and 0.33 ± 0.31 (p = 0.018), respectively. Seventeen patients (74%) of the study group and 9 (39%) of the control group had T scores less than –1.0, indicating osteopenia/osteoporosis (p = 0.036). Conclusions: The results showed a significant association between Ménière’s disease and reduced bone mineral density of the femoral head. Bone mineral density studies of the weight-bearing bones are warranted in Ménière’s disease for the early diagnosis and treatment of osteopenia/osteoporosis on the one hand and possible benefit of this treatment for the evolution of Ménière’s disease on the other hand.
Detection of Human Papillomavirus Prevalence in Ovarian Cancer by Different Test Systems
Authors: Kisseljova Natalia , Zhordania Kirill , Fedorova Maria , Katargin Alexey , Valeeva Adelina , Pajanidi Julia , Pavlova Larisa , Khvan Olga , Vinokurova Svetlana
Published: February 2020

Background/Aims: High-risk human papillomavirus (HPV) infection is associated with different malignancies, but its role in the pathogenesis of ovarian cancer remains inconclusive. Published studies demonstrated a wide variation (0–50%) in HPV prevalence in ovarian cancer. To evaluate the contribution of detection tests to controversial results in different populations, we determined the presence of HPV DNA in Russian ovarian cancer patients using 10 different PCR-based tests. Methods: Epithelial ovarian adenocarcinomas were tested with 5 general primer sets commonly used for HPV screening of cervical and ovarian cancer and 5 HPV type-specific primers. Results: The use of a single PCR primer set resulted in a wide variation (0–29%) and an underestimation of the incidence of HPV-positive cancers. The combination of MY09/MY11 and GP5+/6+ primers in nested PCR revealed HPV DNA in 53% (18/34) of adenocarcinomas. HPV16 was found in 94% of the HPV-positive cases. In 6/6 positive cases, the active status of HPV16 was demonstrated by RT-PCR detection of E6 and E7 oncogene mRNAs. Conclusion: These findings indicate the need to employ multiple PCR-based tests to detect all HPV-positive patients. The identification of viral DNA and oncogene transcripts in cancerous tissues indicate the possible role of HPV in ovarian carcinogenesis in Russia.
Heart Rate Recovery After Exercise Is Associated With Arrhythmic Events in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Lieve Krystien V.V. , Dusi Veronica , van der Werf Christian , Bos J. Martijn , Lane Conor M. , Stokke Mathis Korseberg , Roston Thomas M. , Djupsjöbacka Aurora , Wada Yuko , Denjoy Isabelle , Bundgaard Henning , Noguer Ferran Roses I. , Semsarian Christopher , Robyns Tomas , Hofman Nynke , Tanck Michael W. , van den Berg Maarten P. , Kammeraad Janneke A.E. , Krahn Andrew D. , Clur Sally-Ann B. , Sacher Frederic , Till Jan , Skinner Jonathan R. , Tfelt-Hansen Jacob , Probst Vincent , Leenhardt Antoine , Horie Minoru , Swan Heikki , Roberts Jason D. , Sanatani Shubhayan , Haugaa Kristina H. , Schwartz Peter J. , Ackerman Michael J. , Wilde Arthur A.M.
Published: February 2020

Background:

Risk stratification in catecholaminergic polymorphic ventricular tachycardia remains ill defined. Heart rate recovery (HRR) immediately after exercise is regulated by autonomic reflexes, particularly vagal tone, and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. Our objective was to evaluate whether HRR after maximal exercise on the exercise stress test (EST) is associated with symptoms and ventricular arrhythmias.

Methods:

In this retrospective observational study, we included patients ≤65 years of age with an EST without antiarrhythmic drugs who attained at least 80% of their age- and sex-predicted maximal HR. HRR in the recovery phase was calculated as the difference in heart rate (HR) at maximal exercise and at 1 minute in the recovery phase (ΔHRR1′).

Results:

We included 187 patients (median age, 36 years; 68 [36%] symptomatic before diagnosis). Pre-EST HR and maximal HR were equal among symptomatic and asymptomatic patients. Patients who were symptomatic before diagnosis had a greater ΔHRR1′ after maximal exercise (43 [interquartile range, 25–58] versus 25 [interquartile range, 19–34] beats/min;
P
<0.001). Corrected for age, sex, and relatedness, patients in the upper tertile for ΔHRR1′ had an odds ratio of 3.4 (95% CI, 1.6–7.4) of being symptomatic before diagnosis (
P
<0.001). In addition, ΔHRR1′ was higher in patients with complex ventricular arrhythmias at EST off antiarrhythmic drugs (33 [interquartile range, 22–48] versus 27 [interquartile range, 20–36] beats/min;
P
=0.01). After diagnosis, patients with a ΔHRR1′ in the upper tertile of its distribution had significantly more arrhythmic events as compared with patients in the other tertiles (
P
=0.045).

Conclusions:

Catecholaminergic polymorphic ventricular tachycardia patients with a larger HRR following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during the first EST off antiarrhythmic drug.
Assessing and Mitigating Bias in Medical Artificial Intelligence
Authors: Noseworthy Peter A. , Attia Zachi I. , Brewer LaPrincess C. , Hayes Sharonne N. , Yao Xiaoxi , Kapa Suraj , Friedman Paul A. , Lopez-Jimenez Francisco
Published: February 2020

Background:

Deep learning algorithms derived in homogeneous populations may be poorly generalizable and have the potential to reflect, perpetuate, and even exacerbate racial/ethnic disparities in health and health care. In this study, we aimed to (1) assess whether the performance of a deep learning algorithm designed to detect low left ventricular ejection fraction using the 12-lead ECG varies by race/ethnicity and to (2) determine whether its performance is determined by the derivation population or by racial variation in the ECG.

Methods:

We performed a retrospective cohort analysis that included 97 829 patients with paired ECGs and echocardiograms. We tested the model performance by race/ethnicity for convolutional neural network designed to identify patients with a left ventricular ejection fraction ≤35% from the 12-lead ECG.

Results:

The convolutional neural network that was previously derived in a homogeneous population (derivation cohort, n=44 959; 96.2% non-Hispanic white) demonstrated consistent performance to detect low left ventricular ejection fraction across a range of racial/ethnic subgroups in a separate testing cohort (n=52 870): non-Hispanic white (n=44 524; area under the curve [AUC], 0.931), Asian (n=557; AUC, 0.961), black/African American (n=651; AUC, 0.937), Hispanic/Latino (n=331; AUC, 0.937), and American Indian/Native Alaskan (n=223; AUC, 0.938). In secondary analyses, a separate neural network was able to discern racial subgroup category (black/African American [AUC, 0.84], and white, non-Hispanic [AUC, 0.76] in a 5-class classifier), and a network trained only in non-Hispanic whites from the original derivation cohort performed similarly well across a range of racial/ethnic subgroups in the testing cohort with an AUC of at least 0.930 in all racial/ethnic subgroups.

Conclusions:

Our study demonstrates that while ECG characteristics vary by race, this did not impact the ability of a convolutional neural network to predict low left ventricular ejection fraction from the ECG. We recommend reporting of performance among diverse ethnic, racial, age, and sex groups for all new artificial intelligence tools to ensure responsible use of artificial intelligence in medicine.