Miracle-dz/UniFAR-FTUs huggingface dataset:
Stochastic sensitivity analysis for timing and amplitude of pressure waves in the arterial system

In the field of computational hemodynamics, sensitivity quantification of pressure and flow wave dynamics has received little attention. This work presents a novel study of the sensitivity of pressure‐wave timing and amplitude in the arterial system with respect to arterial stiffness. Arterial pressure and flow waves were simulated with a one‐dimensional distributed wave propagation model for compliant arterial networks. Sensitivity analysis of this model was based on a generalized polynomial chaos expansion evaluated by a stochastic collocation method. First‐order statistical sensitivity indices were formulated to assess the effect of arterial stiffening on timing and amplitude of the pressure wave and backward‐propagating pressure wave in the ascending aorta, at the maximum pressure and inflection point in the systolic phase. Only the stiffness of aortic arteries was found to significantly influence timing and amplitude of the backward‐propagating pressure wave, whereas other large arteries in the systemic tree showed marginal impact. Furthermore, the ascending aorta, aortic arch, thoracic aorta, and infrarenal abdominal aorta had the largest influence on amplitude, whereas only the thoracic aorta influenced timing. Our results showed that the non‐intrusive polynomial chaos expansion is an efficient method to compute statistical sensitivity measures for wave propagation models. These sensitivities provide new knowledge in the relative importance of arterial stiffness at various locations in the arterial network. Moreover, they will significantly influence clinical data collection and effective composition of the arterial tree for in‐silico clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.
A unified method for estimating pressure losses at vascular junctions

In reduced‐order (0D/1D) blood or respiratory flow models, pressure losses at junctions are usually neglected. However, these may become important where velocities are high and significant flow redirection occurs. Current methods for estimating losses rely on relatively complex empirical equations that are only valid for specific junction geometries and flow regimes. In pulsatile multi‐directional flows, switching between empirical equations upon reversing flow may introduce unrealistic discontinuities in simulated haemodynamic waveforms. Drawing from work by Bassett et al. (SAE Trans 112:565‐583, 2003), we therefore developed a unified method (Unified0D) for estimating loss coefficients that can be applied to any junction (i.e. any number of branches at any angle) and any flow regime. Discontinuities in simulated waveforms were avoided by extending Bassett et al.'s control volume‐based method to incorporate a ‘pseudodatum’ supplier branch, an imaginary effective vessel containing all inflow to the junction. Energy exchange between diverging flow streams was also accounted for empirically. The formulation was validated using high resolution computational fluid dynamics in a wide range flow conditions and junction configurations. In a pulsatile 1D simulation exhibiting transitions between four different flow regimes, the new formulation produced smooth transitions in calculated pressure losses. Copyright © 2015 John Wiley & Sons, Ltd.
Predictors of response to cyclo-oxygenase-2 inhibitors in osteoarthritis: pooled results from two identical trials comparing etoricoxib, celecoxib, and placebo.

OBJECTIVE Nonsteroidal anti-inflammatory drug (NSAID) responses in osteoarthritis (OA) are highly variable, often requiring multiple medication changes. We sought to determine pre-randomization predictors of response to NSAIDs in OA. METHODS Data were pooled from two identical 26-week double-blind, randomized flare design trials comparing etoricoxib 30 mg/day (N=475), celecoxib 200 mg/day (N=488), and placebo (N=244) in patients with OA of the hip or knee. This analysis was limited to the 12-week placebo-controlled period. Response at Week 12 was defined using Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Factors were analyzed using logistic regression and included age, race, gender, body mass index, index joint, screening (pre-washout) and baseline (post-washout) Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain, physical function, and stiffness, and patient global assessment of disease status, prior NSAID/coxib or acetaminophen use, American Rheumatology Association functional class, and disease duration. RESULTS We found that screening WOMAC physical function was the only factor that predicted response in all treatment groups; worse function was associated with lower odds of achieving an OMERACT-OARSI response at 12 weeks (odds ratio 0.84 placebo; 0.87 etoricoxib; 0.89 celecoxib; P<0.05 for all). However, the differences in WOMAC physical function between responders and nonresponders were small (∼5 mm on a 100-mm scale). No factor discriminated between the ability to predict placebo response from active treatment response. CONCLUSIONS Lower levels of physical function decreased the odds of a response to NSAID treatment in OA, although the clinical significance is unknown given the small differences between responders and nonresponders. No other measured baseline variables consistently predicted response in these studies, which may reflect the known individual variability in NSAID response.
Cognitive Behavioral Intervention for Individuals with Severe Mental Illness Who Have a Substance Misuse Problem

Abstract There have been considerable advances in the use of psychological treatments for individuals with psychosis in the last 20 years or so. This paper describes an ongoing study in which these treatment approaches are being modified and combined for use with a particularly challenging client group–those with a diagnosis of schizophrenia who have a comorbid drug or alcohol problem. Prevalence rates for such individuals with “dual diagnosis” are high, with surveys indicating that from 20%-60% of clients with schizophrenia may have a substance use problem. More importantly, there is evidence that clinical outcomes are worse for this group and that persons in treatment present many difficulties for services, for example, frequent hospital admissions, violence, engagement problems, and noncompliance. Although there are accounts and evaluations of integrated treatment strategies in the U.S. (Drake et al., 1989; 1991), there is little published work from the UK demonstrating an integration of treatments targeted at both the mental health and substance use problems.
Incorporating the ACGME Educational Competencies Into Morbidity and Mortality Review Conferences

Background: The Accreditation Council for Graduate Medical Education (ACGME) mandates that residents be trained in six core educational competencies. Practice-based learning and improvement (PBLI), one of the six competencies, is defined as the investigation and evaluation of one's own patient care. Morbidity and Mortality Conference, a frequently used venue to review the clinical outcome of hospitalized patients, provides the opportunity to teach and assess PBLI. Description: We report an approach to Morbidity and Mortality Conference that includes a systematic analysis of the ACGME core competencies and their application to a clinical case, a regular review of the factors that defines high-quality patient care, and a focused discussion of the PBLI competency. Evaluation: Preliminary data indicate that our residents preferred this revised method for conducting Morbidity and Mortality Conference. Conclusion: Our adaptation to Morbidity and Mortality Conference provides a systematic review of the core competencies and their relevance to clinical decision making, with the ultimate goal of improving patient care.
Considering the Impact on Overall Patient Health When Choosing Antipsychotic Therapy

Schizophrenia is a chronic and debilitating illness characterized by behaviors that markedly impair social and occupational functioning. Atypical antipsychotic medications have greatly improved outcomes for patients with these psychiatric disorders. Unfortunately, many patients do not respond adequately to therapy because of treatment-limiting adverse events, (AEs) which also limit therapeutic adherence. It is now widely accepted that the “real-world” clinical effectiveness of an atypical antipsychotic depends on its safety and tolerability as much as its efficacy. A number of clinical studies have shown that certain atypical antipsychotics are associated with unwanted sedation and a significant risk of weight gain, diabetes, and dyslipidemia. The risk of hyperprolactinemia is also significantly elevated with some atypical antipsychotics. To minimize the risk of adversely impacting overall patient health, each patient's metabolic and cardiovascular risk profile, as well as the potential impact of sedation on his or her quality of life, should be evaluated before beginning therapy and regularly thereafter.J Am Psychiatr Nurses Assoc, 2007; 13(S5), S23-S28. DOI: 10.1177/1078390307299810
Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets

The bicuspid aortic valve (BAV) is the most common congenital valvular defect and a major risk factor for secondary calcific aortic valve disease. While hemodynamics is presumed to be a potential contributor to this complication, the validation of this theory has been hampered by the limited knowledge of the mechanical stress abnormalities experienced by BAV leaflets and their dependence on the heterogeneous BAV fusion patterns. The objective of this study was to compare computationally the regional and temporal fluid wall shear stress (WSS) and structural deformation characteristics in tricuspid aortic valve (TAV), type‐0, and type‐I BAV leaflets. Arbitrary Lagrangian–Eulerian fluid‐structure interaction models were designed to simulate the flow and leaflet dynamics in idealized TAV, type‐0, and type‐I BAV geometries subjected to physiologic transvalvular pressure. The regional leaflet mechanics was quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI), temporal shear gradient (TSG), and stretch. The simulations identified regions of WSS overloads and increased WSS bidirectionality (174% increase in temporal shear magnitude, 0.10 increase in OSI on type‐0 leaflets) in BAV leaflets relative to TAV leaflets. BAV leaflets also experienced larger radial deformations than TAV leaflets (4% increase in type‐0 BAV leaflets). Type‐I BAV leaflets exhibited contrasted WSS environments marked by WSS overloads on the non‐coronary leaflet and sub‐physiologic WSS levels on the fused leaflet. This study provides important insights into the mechanical characteristics of BAV leaflets, which may further our understanding of the role played by hemodynamic forces in BAV disease. Copyright © 2016 John Wiley & Sons, Ltd.
A Controlled Trial of a Condom Promotion at a Jail: Lessons Learned

Because arrestees are at high-risk for HIV/STDs, we evaluated a ten minute, skills-based condom promotion at the Jefferson Parish Correctional Center. Arrestees were assigned to an intervention or control group based on the week of their first booking. For recidivists, data were compared between the first and second visits. At follow-up, the intervention group was as likely as the control group to have reported condom use, to have reported a similar number of sex partners, and for males, to have a positive test for urethritis. Because of these results, we cannot recommend condom promotions such as the one in this study; however, we showed that a skills-based condom promotion is feasible in jail settings.
Postoperative Visual Loss: A Review of the Current Literature

Molly E. Gilbert University of Illinois Eye and Ear Infirmary, Department of Neuro-Ophthalmology, Chicago, IL, USA Visual loss after nonocular surgery is a relatively uncommon complication, however reports of postoperative visual loss have been increasing over the last ten to fifteen years.1−6 Interest in understanding and quantifying postoperative visual loss (POVL) has been growing for two reasons. The first is the devastating impact it has on the quality of life for the patients who, in many cases, are undergoing elective surgery. The second reason is the medicolegal implications of visual loss occurring after nonocular surgery. Two large retrospective studies have determined that the incidence of ischemic optic neuropathy (ION) after nonocular surgery is approximately 1/60,000–1/125, 000.7,8 The incidence of all causes of POVL has been observed to be as high as 4.5% in cardiac surgery.9 In spine surgery reported incidences are as high as 0.2%. 4 Determining the actual overall incidence of all causes of POVL is difficult since it is not known what percentage of cases are reported. A wide variety of surgical interventions have been associated with POVL. The most commonly reported settings include cardiopulmonary bypass 9−11 and lumbar spine surgery.4,12,13 It has also been associated with surgeries such as neck dissection,14,15 abdominal procedures, hip surgery, cholecystectomy, parathyroidectomy, prostate surgery, pleurodesis, and rotator cuff surgery.16−23 There are several causes of POVL after nonocular surgery (Table 1). Anterior and posterior ischemic optic neuropathies are most frequently described. Posterior ION (PION) is a more common presentation than anterior ION (AION). 2,3 In addition, central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) have been noted, particularly in cases with ocular or orbital compression.24−26 Cortical blindness is another cause of POVL.4,27,28 A variety of factors have been identified that contribute to various causes of POVL. Some of the factors are intrinsic to the patient and may be thought of as predisposing factors. Other risks are related more directly to surgery and anesthesia and can be thought of as precipitating factors (Table 2).
Integration of element specific persistent homology and machine learning for protein‐ligand binding affinity prediction

Protein‐ligand binding is a fundamental biological process that is paramount to many other biological processes, such as signal transduction, metabolic pathways, enzyme construction, cell secretion, and gene expression. Accurate prediction of protein‐ligand binding affinities is vital to rational drug design and the understanding of protein‐ligand binding and binding induced function. Existing binding affinity prediction methods are inundated with geometric detail and involve excessively high dimensions, which undermines their predictive power for massive binding data. Topology provides the ultimate level of abstraction and thus incurs too much reduction in geometric information. Persistent homology embeds geometric information into topological invariants and bridges the gap between complex geometry and abstract topology. However, it oversimplifies biological information. This work introduces element specific persistent homology (ESPH) or multicomponent persistent homology to retain crucial biological information during topological simplification. The combination of ESPH and machine learning gives rise to a powerful paradigm for macromolecular analysis. Tests on 2 large data sets indicate that the proposed topology‐based machine‐learning paradigm outperforms other existing methods in protein‐ligand binding affinity predictions. ESPH reveals protein‐ligand binding mechanism that can not be attained from other conventional techniques. The present approach reveals that protein‐ligand hydrophobic interactions are extended to 40Å away from the binding site, which has a significant ramification to drug and protein design.
Influence of bronchial diameter change on the airflow dynamics based on a pressure‐controlled ventilation system

Bronchial diameter is a key parameter that affects the respiratory treatment of mechanically ventilated patients. In this paper, to reveal the influence of bronchial diameter on the airflow dynamics of pressure‐controlled mechanically ventilated patients, a new respiratory system model is presented that combines multigeneration airways with lungs. Furthermore, experiments and simulation studies to verify the model are performed. Finally, through the simulation study, it can be determined that in airway generations 2 to 7, when the diameter is reduced to half of the original value, the maximum air pressure (maximum air pressure in lungs) decreases by nearly 16%, the maximum flow decreases by nearly 30%, and the total airway pressure loss (sum of each generation pressure drop) is more than 5 times the original value. Moreover, in airway generations 8 to 16, with increasing diameter, the maximum air pressure, maximum flow, and total airway pressure loss remain almost constant. When the diameter is reduced to half of the original value, the maximum air pressure decreases by 3%, the maximum flow decreases by nearly 5%, and the total airway pressure loss increases by 200%. The study creates a foundation for improvement in respiratory disease diagnosis and treatment.
Using 3dRNA for RNA 3‐D Structure Prediction and Evaluation

This unit describes how to use 3dRNA to predict RNA 3‐D structures from their sequences and secondary (2‐D) structures, and how to use 3dRNAscore to evaluate the predicted structures. The predicted RNA 3‐D structures can be used to predict or understand their functions and can also be used to find the interactions between the RNA and other molecules. © 2017 by John Wiley & Sons, Inc.
Novel Utilization of the Bridge during Weaning off Venoarterial ECMO: The Hoffman Clamp Method

Standard practice for weaning patients off venoarterial extracorporeal membrane oxygenation (ECMO) occurs by decreasing pump flows until idle flow is achieved. This method is limited in its use because it is difficult to assess a patient's true potential to successfully come off ECMO when supported by idle flow. We have developed a weaning technique that uses a Hoffman clamp on the bridge to decrease blood flow to the patient beyond idle flow. This method was used to wean eight patients from venoarterial ECMO. No patients weaned with this technique required emergent reinstitution of ECMO. The Hoffman clamp technique has allowed us to safely wean patients off ECMO support while maintaining integrity of the circuit.
Patient Safety Education: What Was, What Is, and What Will Be?

Patient safety is an important topic that has been receiving more attention in the current health care climate. Patient safety as a curriculum topic in medical schools has only become apparent in the late 1990s, and much more needs to be done. This article summarizes patient safety curricular content as it occurred (or did not occur) in medical education circles in the past (pre-1990s), and present. It also makes some recommendations for the future of medical education curricula in the area of patient safety, using a framework for the development of expertise using the Dreyfus educational model.
Self‐Pressurized Rapid Freezing as Cryo‐Fixation Method for Electron Microscopy and Cryopreservation of Living Cells

Reduction or complete prevention of ice crystal formation during freezing of biological specimens is mandatory for two important biological applications: (1) cryopreservation of living cells or tissues for long‐term storage, and (2) cryo‐fixation for ultrastructural investigations by electron microscopy. Here, a protocol that is fast, easy‐to‐use, and suitable for both cryo‐fixation and cryopreservation is described. Samples are rapidly cooled in tightly sealed metal tubes of high thermal diffusivity and then plunged into a liquid cryogen. Due to the fast cooling speed and high‐pressure buildup internally in the confined volume of the metal tubes, ice crystal formation is reduced or completely prevented, resulting in vitrification of the sample. For cryopreservation, however, a similar principle applies to prevent ice crystal formation during re‐warming. A detailed description of procedures for cooling (and re‐warming) of biological samples using this technique is provided. © 2018 by John Wiley & Sons, Inc.
Identification of Human Memory‐Like NK Cells

Our understanding of NK biology is increased dramatically, a product of improved flow‐cytometric techniques for analyzing these cells. NK cells undergo significant changes in repertoire during differentiation. A repeating stimulus, such as a cytomegalovirus infection, may result in accumulation of certain types of highly differentiated NK cells designated as memory‐like, or adaptive NK cells. Adaptive NK cells are capable of rapid expansion and effective response to the recall stimulus. These cells differ significantly from conventional NK cells both functionally and phenotypically. Here we describe an approach for identification and analysis of adaptive NK cells in human peripheral blood. CD57‐positive cells with high expression of activating‐receptor NKG2C, increased expression of KIR receptors, lack of co‐expression with inhibitory receptor NKG2A, and decreased expression of activating receptor NCR3 (NKp30) all characterize this cell type. The flow‐cytometric method described below can identify this NK cell subset on a relatively simple flow cytometer. © 2017 by John Wiley & Sons, Inc.
Intervention Issues Created by Successful Universal Newborn Hearing Screening

Early intervention programs designed for young children with hearing disabilities typically focus on children having severe and profound losses. Amplification for such children is generally recommended at the time of diagnosis (about 2 years old), and parents and children are enrolled in early intervention programs designed to optimize parent/child interaction for language growth. Children with less severe hearing losses are frequently not identified until age 4 or older, and intervention for such children typically begins at school age when the communication sequelae of mild bilateral, unilateral, or fluctuating conductive hearing loss* are already firmly entrenched. The feasibility of universal screening using transient evoked otoacoustic emissions (TEOAE), as demonstrated
Ascomycin and FK506: Pharmacology and Therapeutic Potential as Anticonvulsants and Neuroprotectants

Ascomycin and FK506 are powerful calcium‐dependent serine/threonine protein phosphatase (calcineurin [CaN], protein phosphatase 2B) inhibitors. Their mechanism of action involves the formation of a molecular complex with the intracellular FK506‐binding protein‐12 (FKBP12), thereby acquiring the ability to interact with CaN and to interfere with the dephosphorylation of various substrates. Pharmacological studies of ascomycin, FK506, and derivatives have mainly been focused on their action as immunosuppressants and therapeutic use in inflammatory skin diseases, both in animal studies and in humans. CaN inhibitors have been also proposed for the treatment of inflammatory and degenerative brain diseases. Preclinical studies suggest, however, that ascomycin and its derivatives exhibit additional pharmacological activities. Ascomycin has been shown to have anticonvulsant activity when perfused into the rat hippocampus via microdialysis probes, and ascomycin derivatives may be useful in preventing ischemic brain damage and neuronal death. Their pharmacological action in the brain may involve CaN‐mediated regulation of gamma aminobutyric acid (GABA) and glutamate receptor channels, neuronal cytoskeleton and dendritic spine morphology, as well as of the inflammatory responses in glial cells. FK506 and ascomycin inhibit signaling pathways in astrocytes and change the pattern of cytokine and neurotrophin gene expression. However, brain‐specific mechanisms of action other than CaN inhibition cannot be excluded. CaN is a likely potential target molecule in the treatment of central nervous system (CNS) diseases, so that the therapeutic potential of ascomycin, FK506, and nonimmunosuppressant ascomycin derivatives as CNS drugs should be further explored.