bluuebunny/crossref_metadata_2025_split huggingface dataset:
Firing rate models for gamma oscillations
Authors: Keeley Stephen , Byrne Áine , Fenton André , Rinzel John 
Published: April 2019

Gamma oscillations are readily observed in a variety of brain regions during both waking and sleeping states. Computational models of gamma oscillations typically involve simulations of large networks of synaptically coupled spiking units. These networks can exhibit strongly synchronized gamma behavior, whereby neurons fire in near synchrony on every cycle, or weakly modulated gamma behavior, corresponding to stochastic, sparse firing of the individual units on each cycle of the population gamma rhythm. These spiking models offer valuable biophysical descriptions of gamma oscillations; however, because they involve many individual neuronal units they are limited in their ability to communicate general network-level dynamics. Here we demonstrate that few-variable firing rate models with established synaptic timescales can account for both strongly synchronized and weakly modulated gamma oscillations. These models go beyond the classical formulations of rate models by including at least two dynamic variables per population: firing rate and synaptic activation. The models’ flexibility to capture the broad range of gamma behavior depends directly on the timescales that represent recruitment of the excitatory and inhibitory firing rates. In particular, we find that weakly modulated gamma oscillations occur robustly when the recruitment timescale of inhibition is faster than that of excitation. We present our findings by using an extended Wilson-Cowan model and a rate model derived from a network of quadratic integrate-and-fire neurons. These biophysical rate models capture the range of weakly modulated and coherent gamma oscillations observed in spiking network models, while additionally allowing for greater tractability and systems analysis. NEW & NOTEWORTHY Here we develop simple and tractable models of gamma oscillations, a dynamic feature observed throughout much of the brain with significant correlates to behavior and cognitive performance in a variety of experimental contexts. Our models depend on only a few dynamic variables per population, but despite this they qualitatively capture features observed in previous biophysical models of gamma oscillations that involve many individual spiking units.
Genome-wide Analysis of Common Copy Number Variation and Epithelial Ovarian Cancer Risk
Authors: Reid Brett M. , Permuth Jennifer B. , Chen Y. Ann , Fridley Brooke L. , Iversen Edwin S. , Chen Zhihua , Jim Heather , Vierkant Robert A. , Cunningham Julie M. , Barnholtz-Sloan Jill S. , Narod Steven , Risch Harvey , Schildkraut Joellen M. , Goode Ellen L. , Monteiro Alvaro N. , Sellers Thomas A. 
Published: April 2019

AbstractBackground:Germline DNA copy number variation (CNV) is a ubiquitous source of genetic variation and remains largely unexplored in association with epithelial ovarian cancer (EOC) risk.Methods:CNV was quantified in the DNA of approximately 3,500 cases and controls genotyped with the Illumina 610k and HumanOmni2.5M arrays. We performed a genome-wide association study of common (&gt;1%) CNV regions (CNVRs) with EOC and high-grade serous (HGSOC) risk and, using The Cancer Genome Atlas (TCGA), performed in silico analyses of tumor-gene expression.Results:Three CNVRs were associated (P &lt; 0.01) with EOC risk: two large (∼100 kb) regions within the 610k set and one small (&lt;5 kb) region with the higher resolution 2.5M data. Large CNVRs included a duplication at LILRA6 (OR = 2.57; P = 0.001) and a deletion at CYP2A7 (OR = 1.90; P = 0.007) that were strongly associated with HGSOC risk (OR = 3.02; P = 8.98 × 10−5). Somatic CYP2A7 alterations correlated with EGLN2 expression in tumors (P = 2.94 × 10−47). An intronic ERBB4/HER4 deletion was associated with reduced EOC risk (OR = 0.33; P = 9.5 × 10−2), and somatic deletions correlated with ERBB4 downregulation (P = 7.05 × 10−5). Five CNVRs were associated with HGSOC, including two reduced-risk deletions: one at 1p36.33 (OR = 0.28; P = 0.001) that correlated with lower CDKIIA expression in TCGA tumors (P = 2.7 × 10−7), and another at 8p21.2 (OR = 0.52; P = 0.002) that was present somatically where it correlated with lower GNRH1 expression (P = 5.9 × 10−5).Conclusions:Though CNV appears to not contribute largely to EOC susceptibility, a number of low-to-common frequency variants may influence the risk of EOC and tumor-gene expression.Impact:Further research on CNV and EOC susceptibility is warranted, particularly with CNVs estimated from high-density arrays.
ЕКСТРЕНА ПРОФІЛАКТИКА ЗАРАЖЕННЯ HCV – РЕАЛЬНІСТЬ І ПЕРСПЕКТИВИ
Authors: Bondarenko A. M. 
Published: April 2019

Проаналізовано стан проблеми екстреної профілактики HCV-інфекції при парентеральному контакті потерпілого з джерелом збудника в результаті «нещасного випадку» або «аварії» на виробництві (в медичній установі). Зазначено, що ця проблема не вирішується вже протягом майже 20 років, а екстрена профілактика HCV-інфекції взагалі заперечується або фактично забороняється, що відображено в офіційних нормативних документах сучасної адміністративної медицини більшості країн навіть з розвиненою економікою. Досі навіть не простежується тенденції до вирішення цієї проблеми, незважаючи на усю її актуальність, високий ризик серйозних наслідків і те, що ця проблема передусім безпосередньо стосується медичних працівників, які складають більшість потерпілих і виявляються заручниками ситуації, залишаючись наодинці з проблемою інфікування і розвитку гострої HCV-інфекції. Замість реальної допомоги потерпілим офіційною медициною пропонується просто «пильно очікувати» розвитку гострої HCV-інфекції з ризиком хронізації на рівні 50-90 %! Фактично це усвідомлена й узаконена бездіяльність.
Але також протягом більше 20 років невирішеною залишається і проблема лікування гострої HCV-інфекції, навіть незважаючи на появу в останні декілька років високоефективних противірусних препаратів прямої дії та їх комбінацій. Стан проблеми досі перебуває на стадії «серйозної стурбованості» без яких-небудь практичних рішень. Є тільки рекомендації, що зводяться в основному до офіційно узаконеного очікування «самовільного одужання» або ж очікування розвитку хронічної HCV-інфекції. Наявність уривчастих і розпливчатих рекомендацій з етіотропної терапії гострого гепатиту С також не вирішує проблему і наполегливо рекомендує потерпілому, а тепер вже пацієнтові, самостійно чи разом з його лікарем вирішити питання про індивідуальну противірусну терапію. І тут офіційна медицина, медичні установи, де сталися «нещасні випадки», і страхові компанії знову залишаються збоку і вже постраждалий медпрацівник як пацієнт повинен вирішувати проблему також самостійно! Тому в той же час дивною виглядає і пасивність самих медпрацівників, і їх «мовчазна згода» замість активної позиції в ініціації вирішення проблеми, що безпосередньо стосується їх здоров’я і, правда у віддаленій перспективі, – навіть життя.
Така ситуація повністю абсурдна і, навіть, злочинна, а, отже, вимагає невідкладного вирішення проблеми! За наявності широкого й ефективного арсеналу поки що досить ефективних противірусних препаратів таку бездіяльність з боку офіційної медицини і з боку самих медпрацівників можна вважати неприпустимим.
Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation
Authors: Mohanakumar Sheyanth , Telinius Niklas , Kelly Benjamin , Lauridsen Henrik , Boedtkjer Donna , Pedersen Michael , de Leval Marc , Hjortdal Vibeke 
Published: April 2019

Background:
The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve the lymphatic circulation. We aimed to assess lymphatic function and morphology in patients with a univentricular circulation.

Methods:
The functional state of lymphatic vessels in the lower extremities of patients with a Fontan circulation (n=10) was investigated using the novel technique near-infrared fluorescence imaging and compared with an age-, sex-, and weight-matched control group of healthy volunteers (n=10). The lymphatic morphology was described using T2-weighted magnetic resonance imaging, and microvascular permeability was estimated by strain gauge plethysmography.

Results:

The Fontan patients had 17% lower lymphatic pumping pressure (50±3.1 mm Hg) compared with controls (60±2.8 mm Hg;
P
=0.0341) and a 62% higher contraction frequency (0.8±0.1 min
−1
) compared with the healthy controls (0.5±0.1 min
−1
;
P
=0.0432). Velocity by which the lymph is moved and refill time after manual emptying of the lymphatic vessels showed no differences between the 2 groups. The thoracic duct was elongated 10% (
P
=0.0409) and with an abnormal course in the Fontan patients compared with normal. No difference in microvascular permeability was found between the 2 groups.

Conclusions:
Patients with a Fontan circulation have an impaired lymphatic pumping capacity and morphologically changed thoracic duct. Our results indicate a challenged lymphatic vasculature in the Fontan circulation and may play a role in the pathogenesis of the complications that are seen in Fontan patients.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03379805.
Long‐Term Outcomes Following Heart Team Revascularization Recommendations in Complex Coronary Artery Disease
Authors: Patterson Tiffany , McConkey Hannah Z.R. , Ahmed‐Jushuf Fiyyaz , Moschonas Konstantinos , Nguyen Hanna , Karamasis Grigoris V. , Perera Divaka , Clapp Brian R. , Roxburgh James , Blauth Christopher , Young Christopher P. , Redwood Simon R. , Pavlidis Antonis N. 
Published: April 2019

Background

The Heart Team (
HT
) comprises integrated interdisciplinary decision making. Current guidelines assign a Class Ic recommendation for an
HT
approach to complex coronary artery disease (
CAD
). However, there remains a paucity of data in regard to hard clinical end points. The aim was to determine characteristics and outcomes in patients with complex
CAD
following
HT
discussion.

Methods and Results

This observational study was conducted at St Thomas’ Hospital (London, UK). Case mixture included unprotected left main, 2‐vessel (including proximal left anterior descending artery)
CAD
, 3‐vessel
CAD
, or anatomical and/or clinical equipoise.
HT
strategy was defined as optimal medical therapy (
OMT
) alone,
OMT
+percutaneous coronary intervention (
PCI
), or
OMT
+coronary artery bypass grafting. From April 2012 to 2013, 51
HT
meetings were held and 398 cases were discussed. Patients tended to have multivessel
CAD
(74.1%), high SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) scores (median, 30; interquartile range, 23–39), and average age 69±11 years. Multinomial logistic regression analysis performed to determine variables associated with
HT
strategy demonstrated decreased likelihood of undergoing
PCI
compared with
OMT
in older patients with chronic kidney disease and peripheral vascular disease. The odds of undergoing coronary artery bypass grafting compared with
OMT
decreased in the presence of cardiogenic shock and left ventricular dysfunction and increased in younger patients with 3‐vessel
CAD
. Three‐year survival was 60.8% (84 of 137) in the
OMT
cohort, 84.3% (107 of 127) in the
OMT
+
PCI
cohort, and 90.2% in the
OMT
+coronary artery bypass grafting cohort (92 of 102).

Conclusions

In our experience, the
HT
approach involved a careful selection process resulting in appropriate patient‐specific decision making and good long‐term outcomes in patients with complex
CAD
.
Effect of Cumulative Case Volume on Procedural and Clinical Outcomes in Endovascular Thrombectomy
Authors: Kim Byung Moon , Baek Jang-Hyun , Heo Ji Hoe , Kim Dong Joon , Nam Hyo Suk , Kim Young Dae 
Published: April 2019

Background and Purpose—
The effect of endovascular thrombectomy (EVT) cumulative case volume (EVT-CCV) on outcomes of acute stroke patients has not been studied. This study investigated whether EVT-CCV was associated with outcomes.

Methods—

We identified all patients who underwent EVT for anterior circulation large vessel occlusion. Patients who met enrollment criteria were grouped into 5 based on the number of previous cases at each hospital. The number of cases that were recruited from each hospital and then assigned to each group (n) was designed to increase by the function of 10×2
(n-1)
; group 1 consisted of cases 1 to 10 at each hospital, group 2 was cases 11 to 30, group 3 was cases 31 to 70, group 4 was cases 71 to 150, and group 5 was cases ≥151. We tested whether EVT-CCV group was associated with procedural and clinical outcomes.

Results—

Nine hundred fifty-five patients fulfilled the enrollment criteria. Recanalization and good outcome positively correlated with EVT-CCV group (
P
<0.001 [correlation coefficient,
r
=0.122] for recanalization;
P
=0.002 [
r
=0.099] for good outcome), whereas symptomatic intracranial hemorrhage and mortality negatively correlated (
P
=0.039 [
r
=–0.067] for symptomatic intracranial hemorrhage;
P
=0.016 [
r
=–0.078] for mortality). EVT-CCV group was independently associated with recanalization (odds ratio, 1.182; 95% CI, 1.029–1.358) and good outcome (odds ratio, 1.187; 95% CI, 1.053–1.337).

Conclusions—
With increased EVT-CCV, recanalization and good outcome increased, whereas symptomatic intracranial hemorrhage and mortality decreased. Increased EVT-CCV was independently associated with recanalization and good outcome.
Use of High-Resolution Numerical Models and Statistical Approaches to Understand New Zealand Historical Wind Speed and Gust Climatologies
Authors: Turner Richard , Safaei Pirooz Amir A. , Flay Richard G. J. , Moore Stuart , Revell Mike 
Published: April 2019

AbstractThis paper describes how a combination of high-resolution numerical modeling, a robust homogenization algorithm, and local pressure observations have been used to understand and reconcile time series of daily, seasonal, and annual peak wind gusts recorded at observing sites in the Cook Strait region of New Zealand. The homogenization algorithm consists of corrections for the relocation of masts, changes in instrumentations, data acquisition and signal processing, surrounding surface roughness, and measurement heights. In addition, a statistical method, penalized maximal F test (PMFT), was used to assess the homogeneity of the wind speed time series and detect and eliminate all remaining, undocumented, artificial (i.e., nonclimatic) breakpoints. A three-dimensional time-dependent computational fluid dynamics (CFD) simulation was carried out using the Gerris model to characterize the turbulence environment at the mast sites and to estimate topographic speedup effects. Trends in magnitudes and frequencies of the homogenized seasonal and annual peak wind gusts are evaluated and presented for the Cook Strait region. The pressure gradients between pairs of stations were used to study the correlation between the gust wind speeds and the pressure field. A high-resolution convection-resolving numerical weather prediction model [the New Zealand Convective-Scale Model (NZCSM)] was employed to aid the interpretation of results and analyze wind trends. The trend in gust speeds is also shown to be consistent with larger-scale NCEP–NCAR reanalysis pressure trends. The homogenization algorithm showed promising results in eliminating the artificial breakpoints and trends. Overall, strong correlations were found between the homogenized gust speeds, the pressure field across the region, and NZCSM predictions.
Air–Sea Momentum Fluxes during Tropical Cyclone Olwyn
Authors: Voermans Joey J. , Rapizo Henrique , Ma Hongyu , Qiao Fangli , Babanin Alexander V. 
Published: April 2019

AbstractObservations of wind stress during extreme winds are required to improve predictability of tropical cyclone track and intensity. A common method to approximate the wind stress is by measuring the turbulent momentum flux directly. However, during high wind speeds, wave heights are typically of the same order of magnitude as instrument heights, and thus, turbulent momentum flux observations alone are insufficient to estimate wind stresses in tropical cyclones, as wave-induced stresses contribute to the wind stress at the height of measurements. In this study, wind stress observations during the near passage of Tropical Cyclone Olwyn are presented through measurements of the mean wind speed and turbulent momentum flux at 8.8 and 14.8 m above the ocean surface. The high sampling frequency of the water surface displacement (up to 2.5 Hz) allowed for estimations of the wave-induced stresses by parameterizing the wave input source function. During high wind speeds, our results show that the discrepancy between the wind stress and the turbulent stress can be attributed to the wave-induced stress. It is observed that for > 1 m s−1, the wave-induced stress contributes to 63% and 47% of the wind stress at 8.8 and 14.8 m above the ocean surface, respectively. Thus, measurements of wind stresses based on turbulent stresses alone underestimate wind stresses during high wind speed conditions. We show that this discrepancy can be solved for through a simple predictive model of the wave-induced stress using only observations of the turbulent stress and significant wave height.
Process of Decline in Activities of Daily Living of Older Chinese People Prior to Death: Evidence From Three Cohorts
Authors: Zhang Wenjuan , Feldman Marcus W. , Du Peng 
Published: April 2019

Objective: The study analyzes the decline in activities of daily living (ADL) prior to death among three cohorts of older Chinese. Method: With data from the Chinese Longitudinal Healthy Longevity Survey, the process of decline in ADL in older people born during the periods 1899–1908, 1909–1918, and 1919–1928 is analyzed using the hierarchical linear model with mixed effects. Results: The remaining survival time has a stronger effect on changes in ADL than chronological age, and there is significant heterogeneity among the older adults in ADL. Conclusion: Decline in ADL is delayed by extending life span. Older people with healthy behaviors, good living conditions in childhood, and age-friendly living environment have long-lasting good ADL during their remaining life span; socioeconomic resources help the older adults with ADL disabilities to survive. Selective effects of mortality and protective effects of socioeconomic resources explain the heterogeneity in ADL and its changes over time.
Ipsilateral metastatic choroidal melanoma responds to systemic immunotherapy
Authors: Morkos Moanes , Jain Puneet , Pavlick Anna C , Finger Paul T 
Published: April 2019

Purpose: To report that metastatic choroidal melanoma (systemic and intraocular) can respond to systemic immunotherapy. Methods: In 2010, a 64-year-old woman with a choroidal melanoma was treated with palladium-103 plaque brachytherapy. Developing 2.5 years later, radiation maculopathy was suppressed with periodic intravitreal anti–vascular endothelial growth factor injections for five additional years. Development of a new, discrete choroidal melanoma in the same eye prompted radiographic imaging of the orbits, abdomen/pelvis, and chest. Multi-organ metastasis in the eye, the liver, and nodes was treated with systemic combination immunotherapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) intravenous every 3 weeks for four cycles followed by nivolumab (3 mg/kg) intravenous every 4 weeks as maintenance. Subsequent ophthalmic and systemic surveillance were performed. Results: All sites of metastases were found to regress on systemic immunotherapy. For example, ophthalmic ultrasound imaging revealed that the intraocular metastasis was reduced from 6.6 to 1.5 mm in thickness. Synchronously, serial radiographic imaging revealed progressive shrinkage and disappearance of hepatic and nodal metastasis (except for one gastrohepatic node). However, combination stereotactic body radiation therapy (30 Gy) with nivolumab maintenance was found to induce a significant reduction in this remaining node. Continued periodic intraocular anti–vascular endothelial growth factor therapy has suppressed her radiation maculopathy resulting in 20/25 vision, now 8 ½ years after initial plaque therapy. Conclusion: This case shows that metastatic choroidal melanoma can present in the same eye as the primary tumor. It also shows that systemic immunotherapy can control both ocular and systemic metastases as well as prolong both life and sight.
Practical Implications of New Antibiotic Agents for the Treatment of Carbapenem-Resistant Enterobacteriaceae
Authors: Bradley Nicole , Lee Yuman 
Published: April 2019

Objective: To provide insight into the practical implications of the use of ceftazidime/avibactam and meropenem/vaborbactam for the management of carbapenem-resistant Enterobacteriaceae (CRE) and to identify strategies for overcoming barriers to the use of these agents in clinical practice. Data sources: A literature search of PubMed was conducted using the following search terms: ceftazidime/avibactam, meropenem/vaborbactam, carbapenem-resistant Enterobacteriaceae, antimicrobial stewardship, and clinical laboratory standards institute. Abstracts from infectious diseases conferences, article bibliographies, and relevant drug monographs were also reviewed. Study selection/data extraction: Relevant English-language studies were considered. Data synthesis: Studies demonstrating the clinical utility of ceftazidime/avibactam and meropenem/vaborbactam over older agents for CRE were summarized. Laboratory challenges, including lack of widespread technology and delays in usable information, and formulary considerations were discussed. Insight was provided into overcoming these challenges and minimizing barriers using infectious diseases pharmacists, antimicrobial stewardship teams, and infection control teams. Relevance to patient care and clinical practice: This review informs clinicians of the potential difficulties of the use of ceftazidime/avibactam and meropenem/vaborbactam in clinical practice and provides tools to overcome these difficulties, thus allowing clinicians to stay at the forefront of CRE treatment. Conclusions: Clinicians treating patients with CRE infections need to be aware of challenges they may face when using ceftazidime/avibactam and meropenem/vaborbactam. Infectious disease (ID) pharmacists and antimicrobial stewardship teams play an important role in minimizing barriers and ensuring appropriate use of these antibiotics.