During nasal continuous positive airway pressure (nCPAP) treatment in neonates, leakage is inevitable and can lead to reduced distending pressure in the lungs of the infant. In current practice, ...neither leakage nor expiratory flow is measured, which makes it difficult to assess if exhalation is through the device or entirely through leakages.
To examine if infants treated with nCPAP exhale through the CPAP system.
Secondary data analyses from the ToNIL trial on leakages during nCPAP treatment. We retrospectively examined respiratory curves for the 50 infants included in the trial, using NI LabVIEW 2015. Each infant was measured with both prongs and nasal masks. A flow recording was classified as exhalation through the system if more than 50% of all expirations showed reverse flow, each for a minimum duration of 0.1 s.
50 infants were included, born with a mean gestational age (GA) of 34 weeks, median birth weight of 1948 g and mean age at measurement 6.5 days. Inclusion criteria were CPAP treatment and a postmenstrual age (PMA) of 28-42 weeks.
In our measurements, 32/50 infants exhaled through the CPAP system in at least one recording with either nasal mask or prongs. Leakages exceeding 0.3 L/min were seen in 97/100 recordings.
During nCPAP treatment, infants can exhale through the CPAP system and leakage was common. Measuring expiratory flows and leakages in clinical settings could be valuable in optimising CPAP treatment of infants.
NCT03586856.
Primary lung adenocarcinoma remains a deadly disease. Gene-expression phenotypes (GEPs) in adenocarcinoma have potential to provide clinically relevant disease stratification for improved prognosis ...and treatment prediction, given appropriate clinical and methodologic validation.
2,395 transcriptional adenocarcinoma profiles were assembled from 17 public cohorts and classified by a nearest centroid GEP classifier into three subtypes: terminal respiratory unit (TRU), proximal-proliferative, and proximal-inflammatory, and additionally scored by five transcriptional metagenes representing different biologic processes, including proliferation. Prognostic- and chemotherapy-predictive associations of the subtypes were analyzed by univariate and multivariate analysis using overall survival or distant metastasis-free survival as endpoints.
Overall, GEPs were associated with patient outcome in both univariate and multivariate analyses, although not in all individual cohorts. The prognostically relevant division was between TRU- and non-TRU-classified cases, with expression of proliferation-associated genes as a key prognostic component. In contrast, GEP classification was not predictive of adjuvant chemotherapy response. GEP classification showed stability to random perturbations of genes or samples and alterations to classification procedures (typically <10% of cases/cohort switching subtype). High classification variability (>20% of cases switching subtype) was observed when removing larger or entire fractions of a single subtype, due to gene-centering shifts not addressable by the classifier.
In a large-scale evaluation, we show that GEPs add prognostic value to standard clinicopathologic variables in lung adenocarcinoma. Subject to classifier refinement and confirmation in prospective cohorts, GEPs have potential to affect the prognostication of adenocarcinoma patients through a molecularly driven disease stratification.
The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although ...spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy.
We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the CDKN2A locus, and NRAS/BRAF mutation screening.
The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001).
Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
The Spirit framework is designed for atomic-scale spin simulations of magnetic systems with arbitrary geometry and magnetic structure, providing a graphical user interface with powerful ...visualizations and an easy-to-use scripting interface. An extended Heisenberg-type spin-lattice Hamiltonian including competing exchange interactions between neighbors at arbitrary distances, higher-order exchange, Dzyaloshinskii-Moriya and dipole-dipole interactions is used to describe the energetics of a system of classical spins localized at atom positions. A variety of common simulation methods are implemented including Monte Carlo and various time evolution algorithms based on the Landau-Lifshitz-Gilbert (LLG) equation of motion. These methods can be used to determine static ground-state and metastable spin configurations, sample equilibrium and finite-temperature thermodynamical properties of magnetic materials and nanostructures, or calculate dynamical trajectories including spin torques induced by stochastic temperature or electric current. Methods for finding the mechanism and rate of thermally assisted transitions include the geodesic nudged elastic band method, which can be applied when both initial and final states are specified, and the minimum mode-following method when only the initial state is given. The lifetimes of magnetic states and rates of transitions can be evaluated within the harmonic approximation of transition-state theory. The framework offers performant central processing unit (CPU) and graphics processing unit (GPU) parallelizations. All methods are verified and applications to several systems, such as vortices, domain walls, skyrmions, and bobbers are described.
Sjögren's syndrome Delaleu, Nicolas; Jonsson, Roland; Koller, Markus M.
European journal of oral sciences,
04/2005, Letnik:
113, Številka:
2
Journal Article
Recenzirano
Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands, primarily the salivary and lacrimal glands. It has been suggested that exogenous agents may trigger SS in ...genetically predisposed individuals. However, at present, the etiology of SS is far from being understood, and no direct evidence for any of these triggers has been presented. The salivary and lacrimal glands from patients with SS harbor unique and highly selected T‐ and B‐cell populations. Disturbance in glandular cell apoptosis may be one possible explanation for the sicca symptoms in SS. However, discrepancies between glandular destruction and salivary flow give rise to processes causing glandular dysfunction preceding or triggering glandular cell destruction. Recent reports suggested autoantibodies inhibiting neuronal innervation of acinar cells and defective water transport to be implicated in salivary secretion deficiency observed in SS. Several types of autoantibodies have been suggested to contribute to the pathogenesis of SS. However, how the tolerance to these structures is broken down is unknown at present. Studies on B‐cell activating factor indicated that diminished apoptosis and disturbed B‐cell maturation could be responsible for the occurrence of autoreactive B‐cells and B‐cell hyperreactivity. B‐cell activation may also provide a basis for lymphoma development observed in up to 5% of the patients with SS.
Aim
Medijet nasal continuous positive airway pressure (CPAP) generators are a family of devices developed from the Benveniste valve. Previous studies have shown that the in vitro performance of the ...Medijet disposable generator was similar to the Neopuff resistor system. We hypothesised that resistance would be the main mechanism of CPAP generation in the Medijet disposable generator.
Methods
The in vitro performance of the Medijet reusable and disposable systems, the Neopuff resistor system and the Benveniste and Infant Flow nonresistor systems were investigated using static and dynamic bench tests.
Results
Large differences in performance were found between the different systems. The disposable Medijet demonstrated high resistance, low pressure stability and high imposed work of breathing. The results also showed that encapsulating the Benveniste valve changed it into a resistor system.
Conclusion
The main mechanism of CPAP generation for the disposable Medijet generator was resistance. The Medijet device family showed increasing resistance with each design generation. The high resistance of the Medijet disposable generator could be of great value when examining the clinical importance of pressure stability. Our results suggest that this device should be used cautiously in patients where pressure‐stable CPAP is believed to be clinically important.
For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. ...We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.
We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.
Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.
We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular ...origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles.
We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay.
Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation.
We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.
Yoga has shown promise as a treatment for depression and anxiety. The present pilot study investigated the feasibility of an eight-week grouptreatment integrating emotion-focused psychoeducation, ...compassion-focused therapy, and Virya yoga for depression and anxiety in primary healthcare.
Patients seeking treatment for depression and anxiety in a primary healthcare centre completed either an integrative group-treatment (N = 14) or treatment as usual (TAU, N = 17). Outcome measures were analysed pre- and posttreatment. Correlations in the intervention group were investigated between treatment outcomes and amount of yoga practice between sessions.
Large within-group effect sizes on all outcome measures were found at posttreatment. Symptom reduction did not differ between groups (p = 0.155). Improvement in alexithymia correlated significantly (p < 0.05) with amount of yoga practice between sessions.
Integrating yoga with a psychological group-treatment is a somewhat feasible approach to treatment for depression and anxiety in primary healthcare.
•Combining yoga with psychological group-treatment for depression and anxiety shows promise in primary healthcare.•Both treatment conditions provided similar improvements in symptoms of anxiety and depression.•Reductions in alexithymia correlated with amount of yoga practice between sessions.•Reductions in anxiety symptoms correlated with increased self-compassion.
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