The acceleration of inertial particles in a homogeneous shear flow may vigorously respond to the intense flow structures induced by the mean shear. In this study, by direct numerical simulation (DNS) ...of particle-laden shear flow, we observe the statistical properties of those accelerations, and then we assessed the recently proposed simulation approach in which the effect of intermittency on residual scales is linked directly with coarsely resolved flow turbulence. First, we focused on the acceleration statistics of fluid particles in a homogeneous shear flow. Consistent with previous findings in homogenous isotropic turbulence, the norm and the direction of fluid acceleration in shear flow are shown to be conditioned by the dynamics of intermittent long-lived vortical structures. The averaged acceleration norm of the fluid particle exhibits a pseudo-cyclic behaviour, which is a signature of the periodic action of the largest confined vortices against the mean shear. The long correlation time of the acceleration norm, of the order of the integral time, the high level of fluctuations of the acceleration norm (very close to the magnitude of the mean norm of acceleration) and the log-normality in its statistical distribution reflect the impact of intense flow structures in shear flow. The presence of these zones results also in highly non-Gaussian statistics of the acceleration of a fluid particle and its velocity increments at small time lags. Contrary to the acceleration norm, the acceleration direction of a fluid particle is observed to be short, of the order of the Kolmogorov time, and to be statistically independent of the acceleration norm. The short-time correlation of the acceleration direction is attributed usually to effects of centripetal forces in intense vorticity filaments. We suggest that, in homogeneous shear turbulence, there may be a supplementary effect on the acceleration direction: the vortex, stretched by the mean shear, may exert the preferential direction of fluid particle acceleration. As evidence, our DNS shows that fluid particles are accelerated preferentially in the direction of longitudinal vortical tubes, effectively stretched by the imposed mean shear. Concerning simulations with heavy point-wise particles, it is shown that, when the inertia of a particle is not high, its acceleration closely follows all the aforementioned properties of the fluid particle acceleration. Particularly, an inertial particle is also entrained by accelerating motion in the direction of the effectively stretched vortical tubes. Although with increasing Stokes number of the inertial particle, the effects of strong intermittency in the flow are filtered, it is shown that the alignment of the particle acceleration direction with vortical tubes is amplified – particles with higher inertia respond to solicitations of stronger vortical structures. An alternative to the Maxey (
J. Fluid Mech.
, vol. 174, 1987, pp. 441–465) preferential sweeping mechanism is discussed in this paper. When the shear turbulence is under-resolved, we employed the large-eddy simulation (LES) equations with a forcing term on the smallest resolved scales in order to simulate stochastically the effects of the dynamics on the residual scales. The forcing term is expressed with two independent stochastic processes, one for its norm and another for its direction. While the norm of acceleration is modelled using Pope’s log-normal process with the integral time for correlation, its direction is modelled in the framework of an Ornstein–Uhlenbeck process on the unit sphere. Consistently with our DNS, the latter process contains two presumed times: the homogeneous strain rate is specified as typical time of relaxation towards the direction of resolved vorticity, and the Kolmogorov time is presumed as a typical time of the diffusion process on the unit sphere. The high efficiency of this approach is demonstrated in prediction of the small-scale dynamics observed in DNS, even in the case when the shear length scale is not resolved by LES.
Abstract Per- and poly-fluorinated compounds constitute a wide group of fluorocarbon chemicals with widespread industrial applications, ranging from non-stick coating in cookware to water ...surfactants, from fire-fighting foams to water-repellent coatings on textiles. Presently, over 12,000 PFAS are known worldwide. In recent years, extensive research has focused on investigating the biological effects of these molecules on various organisms, including humans. Here, we conducted in silico simulations to examine the potential binding of a representative selection of PFAS to various human proteins known to be involved in chemical transportation and accumulation processes. Specifically, we targeted human serum albumin (HSA), transthyretin (TTR), thyroxine binding protein (TBG), fatty acid binding proteins (FABPs), organic anion transporters (OATs), aiming to assess the potential for bioaccumulation. Molecular docking simulations were employed for this purpose, supplemented by molecular dynamics (MD) simulations to account for protein flexibility, when necessary. Our findings indicate that so-called “legacy PFAS” such as PFOA or PFOS exhibit a higher propensity for interaction with the analysed human protein targets compared to newly formulated PFAS, characterised by higher branching and hydrophilicity, and possibly a higher accumulation in the human body.
Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to ...their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients. Therefore, this study aimed to describe current anesthesia practices across Europe for infants undergoing surgery for NEC.
Cross-sectional survey study.
Anesthesiologists working in centers where surgery for NEC is performed across Europe.
A 46-item questionnaire assessing protocols for anesthesia practice, preoperative care, intraoperative care, postoperative care, and the respondent's opinion on the adequacy of anesthetic care for patients with NEC in their center.
Out of the 173 responding anesthesiologists from 31 countries, approximately a third had a written standard protocol for anesthetic care in infants. Three quarters of the respondents screened all patients with NEC preoperatively, and a third structurally performed preoperative multidisciplinary consultation. For induction of general anesthesia, most respondents opted for intravenous anesthesia (n = 73, 43%) or a combination of intravenous and inhalation anesthesia (n = 57, 33%). For intravenous induction, they mostly used propofol (n = 58, 44%), followed by midazolam (n = 43, 33%) and esketamine (n = 42, 32%). For maintenance of anesthesia, inhalation anesthetic agents were more commonly used (solely: n = 71, 41%; in combination: n = 37, 22%), almost exclusively with sevoflurane. Postoperative analgesics mainly included paracetamol and/or morphine. Sixty percent of the respondents (n = 104) considered their anesthetic care for patients with NEC adequate. Suggestions for further improvement mainly revolved around monitoring, protocols, and collaboration.
Anesthesia practice for infants undergoing surgery for NEC was highly variable. Most respondents considered the provided anesthetic care for patients with NEC adequate, but also recognized opportunities for further improvement, especially with regards to monitoring, protocols, and interdisciplinary collaboration.
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•Anesthesia practice for preterm infants with NEC is highly variable.•Sixty percent of anesthesiologists are satisfied with current anesthetic care for NEC.•Advances in monitoring, protocols, and collaboration may drive further improvement.
Background:: ZD6474 selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor and epidermal growth factor receptor. The safety, tolerability and ...pharmacokinetics of ZD6474 were assessed in a phase I dose-escalation study of patients with advanced solid tumors.
Patients and methods:: Adult patients with tumors refractory to standard treatments received once-daily oral ZD6474 (50–600mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed.
Results:: Seventy-seven patients were treated at doses of 50mg (n=9), 100mg (n=19), 200mg (n=8), 300mg (n=25), 500mg (n=8), and 600mg (n=8). Adverse events were generally mild, and the most common dose-limiting toxicities (DLT) were diarrhea (n=4), hypertension (n=4), and rash (n=3). The incidence of most adverse events appeared to be dose-dependant. In the 500mg/day cohort, 3/8 patients experienced DLT and this dose was therefore considered to exceed the maximum tolerated dose. Pharmacokinetic analysis confirmed that ZD6474 was suitable for once-daily oral dosing.
Conclusions:: Once-daily oral dosing of ZD6474 at 300mg/day is generally well tolerated in patients with advanced solid tumors, and this dose is being investigated in phase II trials.
Newborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in ...these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects. Despite the widely recognized importance of pain management, pain assessment in neonates has thus far proven to be a challenge. As self-report, the gold standard for pain assessment, is not possible in neonates, other methods are needed. Several observational pain scales have been developed, but these often rely on snapshot and largely subjective observations and may fail to capture pain in certain conditions. Incorporation of biomarkers alongside observational pain scores holds promise in enhancing pain assessment and, by extension, optimizing pain treatment and neonatal outcomes. This review explores the possibilities of integrating biomarkers in pain assessment in the NICU.
The functionalization of single-walled carbon nanotubes (SWCNTs) via microwave-assisted grafting reactions enables efficient multidecoration in a single step. A novel water-soluble SWCNT platform was ...prepared via the simple 1,3-dipolar cycloaddition of azomethine ylides under dielectric heating. Thanks to a single grafting reaction the CNT surface binds in a 1 : 1 ratio an amino acidic β-cyclodextrin (β-CD) derivative and the DOTAMA moiety (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid monoamide). This novel "one shot" synthesis, compared with multistep functionalizations, preserves the SWCNT's structural integrity (TEM images). Besides thermogravimetric analyses, the determination of the amount of β-CD and DOTA moieties grafting onto the SWCNT's surface was performed on the basis of phenolphthalein and gadolinium complexation, respectively.
Rehabilitation is currently the preferred first-line treatment for thoracic outlet syndrome (TOS). When physiotherapy fails, the next treatment option is usually surgery - a complex procedure with ...potential complications.
We sought to establish whether an intensive, multidisciplinary, day-hospital-based rehabilitation programme could reduce the symptoms of TOS after the failure of private-practice physiotherapy and before surgery was considered.
We performed a retrospective, single-centre study of 63 TOS patients admitted to our day hospital for 3 weeks (15 therapy sessions) between 2003 and 2014. The data were extracted from hospital records or gathered in a phone interview.
Immediately after discharge, the observed improvements in hand function were related to lifting a load, reaching a high shelf, sweeping the floor, cleaning windows, and combing hair. Three months after the end of the intensive rehabilitation program, 80% of the patients reported a reduction in their symptoms. Forty-one of the 63 patients were subsequently contacted by phone. The mean time interval between the end of the rehabilitation programme and the phone interview was 4.5 years (median: 3.5 years; range: 1-12 years). Twenty-seven patients (66%) reported a worsening in hand function, and 25% had undergone surgery. Twenty-three patients had kept the same job, 7 had changed jobs after retraining, 4 had stopped working before the programme but were able to return to work afterwards (including one patient in a part-time job), 4 had not returned to work, and 3 received disability benefits.
An intensive, multidisciplinary, hospital-based rehabilitation programme was associated with improvements in the great majority of patients with TOS - even after private-practice physiotherapy had failed.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Adequate pain management for preterm born neonates suffering from the extremely painful disease necrotizing enterocolitis (NEC) is essential, since neonatal exposure to pain is related to negative ...short-term and long-term consequences. The aim of this study was to describe the current pain management and its effectiveness in NEC patients.
In this single-center, retrospective study, neonates (gestational age < 32 weeks and/or birth weight < 1500 g) with NEC Bell's stage II or III were included. Information on pain (based on COMFORTneo and NRS scores) and analgesic therapy was collected and analyzed for the acute disease period.
Of 79 patients included, 74 (94%) received intravenous analgesic therapy: most commonly morphine, fentanyl, and acetaminophen. The median COMFORTneo score was 11 (IQR 10-11), however, 49 patients had at least one COMFORTneo score ≥ 14 indicating pain. Nineteen patients had persistent high pain scores ≥ 14 with a median duration of 7.2 h (IQR 2.8-14.0).
This study showed that despite analgesic therapy, most NEC patients showed signs of pain, and in some, pain persisted for several hours. It suggests that current analgesic therapy frequently failed to prevent pain and existing pain was often insufficiently treated. This supports the urgent need for individualized pain management guidelines for NEC patients.
This study is unique in reporting on pain management in neonates suffering from necrotizing enterocolitis (NEC) during the full acute disease period. Despite analgesic therapy, the majority of NEC patients experience pain, and in some patients, pain persists for several hours. These findings highlight the need for improvement of neonatal pain management in NEC patients, including better pain monitoring and guidelines for individualized analgesic therapy. Improved pain management guidelines may help to prevent short-term and long-term consequences of neonatal exposure to pain, as well as excessive exposure to opioids.
The low sensitivity is the major disadvantage of MRI as compared to PET. Therefore, amplification strategies are necessary for specific pathway labeling. This survey is aimed at exploring different ...routes to the entrapment of Gd(III) chelates in various type of cells at amounts sufficiently large to allow MRI visualization. Namely, the obtained results have been summarized in terms of internalization via i) pinocytosis; ii) phagocytosis; iii) receptors; iv) receptor mediated endocytosis; v) transporters; vi) transmembrane carrier peptides. MRI visualization of cells appears possible when the number of internalized Gd(III) chelates is of the order of 10(7)-10(8)/cell. Pinocytosis shows to be particularly useful for labeling cells that can be incubated for several hours in the presence of high concentrations of Gd-agent. This approach appears very effective for labeling stem cells. Nanoparticles filled with Gd-chelates can be used for an efficient loading of cells endowed with a good phagocytic activity. Entrapment via receptors most often results in receptor mediated endocytosis. Suitably functionalized monomeric and multimeric Gd-chelates can be considered for being internalized by this route as well as supramolecular systems such as those formed between Avidin and biotinylated Gd-complexes. Exploitation of up-regulated transporters of nutrients in tumor cells appears to be a promising route for their differentiation from healthy cells. Finally, properly designed systems entering the cells by means of penetrin-like peptides deserve great attention.
Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There ...is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs).
An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts.
Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients.
Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients.
This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units. Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries. A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU. The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC.
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