The response of many biomedical systems can be modelled using a linear combination of damped exponential functions. The approximation parameters, based on equally spaced samples, can be obtained ...using Prony's method and its variants (e.g. the matrix pencil method). This paper provides a tutorial on the main polynomial Prony and matrix pencil methods and their implementation in MATLAB and analyses how they perform with synthetic and multifocal visual-evoked potential (mfVEP) signals. This paper briefly describes the theoretical basis of four polynomial Prony approximation methods: classic, least squares (LS), total least squares (TLS) and matrix pencil method (MPM). In each of these cases, implementation uses general MATLAB functions. The features of the various options are tested by approximating a set of synthetic mathematical functions and evaluating filtering performance in the Prony domain when applied to mfVEP signals to improve diagnosis of patients with multiple sclerosis (MS).
The code implemented does not achieve 100%-correct signal approximation and, of the methods tested, LS and MPM perform best. When filtering mfVEP records in the Prony domain, the value of the area under the receiver-operating-characteristic (ROC) curve is 0.7055 compared with 0.6538 obtained with the usual filtering method used for this type of signal (discrete Fourier transform low-pass filter with a cut-off frequency of 35 Hz).
This paper reviews Prony's method in relation to signal filtering and approximation, provides the MATLAB code needed to implement the classic, LS, TLS and MPM methods, and tests their performance in biomedical signal filtering and function approximation. It emphasizes the importance of improving the computational methods used to implement the various methods described above.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Objective
To evaluate the in vivo and in vitro responses to nOle e 1 in allergic rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree pollen (OL) confirmed by ...nasal allergen provocation test (NAPT).
Methods
Twelve subjects with AR, 12 with LAR and 12 subjects as control group (CG) were selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic cationic protein (ECP) and tryptase were measured in nasal lavages before and after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation studies were carried out.
Results
All AR (12/12) and 10/12 (83%) of LAR had a +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%); 8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019 and P = 0.001, respectively).
Conclusion
Both AR and LAR had a similar in vivo response to nOle e 1 with release of inflammatory mediators. Specific basophil activation with OL and nOle e 1 was observed in LAR confirming previous data obtained with dust mites.
Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. ...Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.
Here we provide a theoretical framework describing the generation of the fast jet ejected vertically out of a liquid when a bubble, resting on a liquid–gas interface, bursts. The self-consistent ...physical mechanism presented here explains the emergence of the liquid jet as a consequence of the collapse of the gas cavity driven by the low capillary pressures that appear suddenly around its base when the cap, the thin film separating the bubble from the ambient gas, pinches. The resulting pressure gradient deforms the bubble which, at the moment of jet ejection, adopts the shape of a truncated cone. The dynamics near the lower base of the cone, and thus the jet ejection process, is determined by the wavelength
$\unicodeSTIX{x1D706}^{\ast }$
of the smallest capillary wave created during the coalescence of the bubble with the atmosphere which is not attenuated by viscosity. The minimum radius at the lower base of the cone decreases, and hence the capillary suction and the associated radial velocities increase, with the wavelength
$\unicodeSTIX{x1D706}^{\ast }$
. We show that
$\unicodeSTIX{x1D706}^{\ast }$
increases with viscosity as
$\unicodeSTIX{x1D706}^{\ast }\propto Oh^{1/2}$
for
$Oh\lesssim O(0.01)$
, with
$Oh=\unicodeSTIX{x1D707}/\sqrt{\unicodeSTIX{x1D70C}R\unicodeSTIX{x1D70E}}$
the Ohnesorge number,
$R$
the bubble radius and
$\unicodeSTIX{x1D70C}$
,
$\unicodeSTIX{x1D707}$
and
$\unicodeSTIX{x1D70E}$
indicating respectively the liquid density, viscosity and interfacial tension coefficient. The velocity of the extremely fast and thin jet can be calculated as the flow generated by a continuous line of sinks extending along the axis of symmetry a distance proportional to
$\unicodeSTIX{x1D706}^{\ast }$
. We find that the jet velocity increases with the Ohnesorge number and reaches a maximum for
$Oh=Oh_{c}$
, the value for which the crest of the capillary wave reaches the vertex of the cone, and which depends on the Bond number
$Bo=\unicodeSTIX{x1D70C}gR^{2}/\unicodeSTIX{x1D70E}$
. For
$Oh>Oh_{c}$
, the jet is ejected after a bubble is pinched off; in this regime, viscosity delays the formation of the jet, which is thereafter emitted at a velocity which is inversely proportional to the liquid viscosity.
Abstract In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria ...are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.
Summary
Background
The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI‐responsive oesophageal eosinophilia (PPI‐REE) and eosinophilic oesophagitis (EoE) remain unknown.
Aim
...To compare symptom‐histological and cytokine gene expression in PPI‐REE and EoE patients, at baseline and after specific treatment.
Methods
In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin‐3, IL‐13, and IL‐5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI‐REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids.
Results
Fifty three patients were re‐evaluated on PPI therapy. 23 patients (43%) had PPI‐REE and 30 patients (57%) had EoE. At baseline, eotaxin‐3/IL‐13/IL‐5 gene expression was indistinguishable between EoE and PPI‐REE, excepting increased IL‐5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin‐3/IL‐13 in PPI‐REE, at both oesophageal sites (P ≤ 0.008), and IL‐5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid‐responsive EoE also showed a significant decrease in eotaxin‐3/IL‐5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers.
Conclusions
Baseline cytokine gene expression in PPI‐REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin‐3/Th2‐cytokine gene expression in PPI‐REE, similarly to that seen in steroid‐responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.
ABSTRACT
Small low-mass stars are favourable targets for the detection of rocky habitable planets. In particular, planetary systems in the solar neighbourhood are interesting and suitable for precise ...characterization. The RedDots campaigns seek to discover rocky planets orbiting nearby low-mass stars. The 2018 campaign targeted GJ 1061, which is the 20th nearest star to the Sun. For three consecutive months we obtained nightly, high-precision radial velocity measurements with the HARPS spectrograph. We analysed these data together with archival HARPS data. We report the detection of three planet candidates with periods of 3.204 ± 0.001, 6.689 ± 0.005, and 13.03 ± 0.03 d, which are close to 1:2:4 period commensurability. After several considerations related to the properties of the noise and sampling, we conclude that a fourth signal is most likely explained by stellar rotation, although it may be due to a planet. The proposed three-planet system (and the potential four-planet solution) is long-term dynamically stable. Planet–planet gravitational interactions are below our current detection threshold. The minimum masses of the three planets range from 1.4 ± 0.2 to 1.8 ± 0.3 M⊕. Planet d, with msin i = 1.64 ± 0.24 M⊕, receives a similar amount of energy as Earth receives from the Sun. Consequently it lies within the liquid-water habitable zone of the star and has a similar equilibrium temperature to Earth. GJ 1061 has very similar properties to Proxima Centauri but activity indices point to lower levels of stellar activity.
Deubiquitinases (DUBs) have fundamental roles in the ubiquitin system through their ability to specifically deconjugate ubiquitin from targeted proteins. The human genome encodes at least 98 DUBs, ...which can be grouped into 6 families, reflecting the need for specificity in their function. The activity of these enzymes affects the turnover rate, activation, recycling and localization of multiple proteins, which in turn is essential for cell homeostasis, protein stability and a wide range of signaling pathways. Consistent with this, altered DUB function has been related to several diseases, including cancer. Thus, multiple DUBs have been classified as oncogenes or tumor suppressors because of their regulatory functions on the activity of other proteins involved in tumor development. Therefore, recent studies have focused on pharmacological intervention on DUB activity as a rationale to search for novel anticancer drugs. This strategy may benefit from our current knowledge of the physiological regulatory mechanisms of these enzymes and the fact that growth of several tumors depends on the normal activity of certain DUBs. Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer.
Objective
To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults.
Method
We conducted a systematic review of articles ...published until January 2017. We identified 26 883 potential papers; 1701 full‐text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta‐analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables.
Results
Finally, 41 studies were included, involving participants aged 12–26 years for a systematic review, and 24 articles were included for meta‐analysis. The meta‐analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65).
Conclusion
Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.
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