There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who ...wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.
General anesthesia is associated with the development of atelectasis, which may affect lung ventilation. Electrical impedance tomography (EIT) is a noninvasive imaging tool that allows monitoring in ...real time the topographical changes in aeration and ventilation.
To evaluate the pattern of distribution of pulmonary ventilation through EIT before and after anesthesia induction in pediatric patients without lung disease undergoing nonthoracic surgery.
This was a prospective observational study including healthy children younger than 5 years who underwent nonthoracic surgery. Monitoring was performed continuously before and throughout the surgical period. Data analysis was divided into 5 periods: induction (spontaneous breathing, SB), ventilation-5min, ventilation-30min, ventilation-late and recovery-SB. In addition to demographic data, mechanical ventilation parameters were also collected. Ventilation impedance (Delta Z) and pulmonary ventilation distribution were analyzed cycle by cycle at the 5 periods.
Twenty patients were included, and redistribution of ventilation from the posterior to the anterior region was observed with the beginning of mechanical ventilation: on average, the percentage ventilation distribution in the dorsal region decreased from 54%(IC95%:49-60%) to 49%(IC95%:44-54%). With the restoration of spontaneous breathing, ventilation in the posterior region was restored.
There were significant pulmonary changes observed during anesthesia and controlled mechanical ventilation in children younger than 5 years, mirroring the findings previously described adults. Monitoring these changes may contribute to guiding the individualized settings of the mechanical ventilator with the goal to prevent postoperative complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. ...The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL.
ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group.
A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% 95% confidence interval (CI): 42.8% to 59.4% with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP.
In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
•A total of 452 patients with previously untreated PTCL were randomized (1 : 1) to six or eight cycles of A+CHP or CHOP.•The 5-year PFS rates were 51.4% with A+CHP versus 43.0% with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91).•The 5-year OS rates were 70.1% with A+CHP versus 61.0% with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99).•Peripheral neuropathy was resolved or improved in 72% of patients in the A+CHP arm and 78% in the CHOP arm.•The ORR was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP.
Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function ...DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer.
Machine learning algorithms often contain many hyperparameters whose values affect the predictive performance of the induced models in intricate ways. Due to the high number of possibilities for ...these hyperparameter configurations and their complex interactions, it is common to use optimization techniques to find settings that lead to high predictive performance. However, insights into efficiently exploring this vast space of configurations and dealing with the trade-off between predictive and runtime performance remain challenging. Furthermore, there are cases where the default hyperparameters fit the suitable configuration. Additionally, for many reasons, including model validation and attendance to new legislation, there is an increasing interest in interpretable models, such as those created by the decision tree (DT) induction algorithms. This paper provides a comprehensive approach for investigating the effects of hyperparameter tuning for the two DT induction algorithms most often used, CART and C4.5. DT induction algorithms present high predictive performance and interpretable classification models, though many hyperparameters need to be adjusted. Experiments were carried out with different tuning strategies to induce models and to evaluate hyperparameters’ relevance using 94 classification datasets from OpenML. The experimental results point out that different hyperparameter profiles for the tuning of each algorithm provide statistically significant improvements in most of the datasets for CART, but only in one-third for C4.5. Although different algorithms may present different tuning scenarios, the tuning techniques generally required few evaluations to find accurate solutions. Furthermore, the best technique for all the algorithms was the Irace. Finally, we found out that tuning a specific small subset of hyperparameters is a good alternative for achieving optimal predictive performance.
Summary
Moniliophthora perniciosa causes witches’ broom disease of cacao and inflicts symptoms suggestive of hormonal imbalance. We investigated whether infection of the tomato (Solanum lycopersicum) ...model system Micro‐Tom (MT) by the Solanaceae (S)‐biotype of Moniliophthora perniciosa, which causes stem swelling and hypertrophic growth of axillary shoots, results from changes in host cytokinin metabolism.
Inoculation of an MT‐transgenic line that overexpresses the Arabidopsis CYTOKININ OXIDASE‐2 gene (35S::AtCKX2) resulted in a reduction in disease incidence and stem diameter. RNA‐sequencing analysis of infected MT and 35S::AtCKX2 revealed the activation of cytokinin‐responsive marker genes when symptoms were conspicuous.
The expression of an Moniliophthora perniciosa tRNA‐ISOPENTENYL‐TRANSFERASE suggests the production of isopentenyladenine (iP), detected in mycelia grown in vitro. Inoculated MT stems showed higher levels of dihydrozeatin and trans‐zeatin but not iP. The application of benzyladenine induced symptoms similar to infection, whereas applying the cytokinin receptor inhibitors LGR‐991 and PI55 decreased symptoms.
Moniliophthora perniciosa produces iP that might contribute to cytokinin synthesis by the host, which results in vascular and cortex enlargement, axillary shoot outgrowth, reduction in root biomass and an increase in fruit locule number. This strategy may be associated with the manipulation of sink establishment to favour infection by the fungus.
Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to ...the limited treatment options.
To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin-susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC).
Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for blaKPC genes. Clonality was investigated by pulsed-field gel electrophoresis. Resistance to colistin was confirmed by broth microdilution method. Consumption of carbapenems and colistin was expressed as defined daily doses.
In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions.
Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission.
Leishmaniasis is considered a neglected disease, which makes it an unattractive market for the pharmaceutical industry; hence, efforts in the search for biologically active substances are hampered by ...this lack of financial motivation. Thus, in the present study, we report the leishmanicidal activity and the possible mechanisms of action of compounds with promising activity against the species
Leishmania
(
V
.)
braziliensis
, the causative agent of the skin disease leishmaniasis. The natural compound
1a
(piplartine) and the analog
2a
were the most potent against promastigote forms with growth inhibition values for 50% of the parasite population (IC
50
) = 8.58 and 11.25 μM, respectively. For amastigote forms, the ICa
50
values were 1.46 and 16.7 μM, respectively. In the molecular docking study, piplartine showed favorable binding energy (−7.13 kcal/mol) and with 50% inhibition of trypanothione reductase (IC
50
) = 91.1 μM. Preliminary investigations of the mechanism of action indicate that piplartine increased ROS levels, induced loss of cell membrane integrity, and caused accumulation of lipid bodies after 24 h of incubation at its lowest effective concentration (IC
50
), which was not observed for the synthetic analog
2a
. The mode of action for the leishmanicidal activity of piplartine (
1a
) was assigned to involve affinity for the trypanothione reductase of
Leishmania
(
V
.)
braziliensis
TR.
Momentum sharing in imbalanced Fermi systems Hen, O.; Sargsian, M.; Weinstein, L. B. ...
Science (American Association for the Advancement of Science),
10/2014, Letnik:
346, Številka:
6209
Journal Article
Recenzirano
Odprti dostop
The atomic nucleus is composed of two different kinds of fermions: protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority of ...fermions (usually neutrons) to have a higher average momentum. Our high-energy electron-scattering measurements using 12C, 27Al, 56Fe, and 208Pb targets show that even in heavy, neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs. Thus, in neutron-rich nuclei, protons have a greater probability than neutrons to have momentum greater than the Fermi momentum. This finding has implications ranging from nuclear few-body systems to neutron stars and may also be observable experimentally in two-spin–state, ultracold atomic gas systems.
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