Guselkumab is an IL-23 inhibitor approved for moderate-to-severe plaque psoriasis that has demonstrated safety and efficacy in phase III clinical trials
. However, there is scarce data regarding its ...drug survival in clinical practice.
Recent decades have seen a growing acknowledgement of violence against women (VAW) as a serious social and public health problem of epidemic proportions. The prevention of VAW and intimate partner ...violence against women (IPVAW) has become a priority within this context, and includes various prevention strategies such as social participation and helping behaviors. In different countries, conducting research on help-seeking behavior and bystander intervention in cases of VAW is a common practice, but addressing these issues is much less common in Spain. In this context, the objective of this study is to provide a preliminary estimation of the volume of bystanders in cases of IPVAW in Spain between 2005 and 2020 (since the entry into force of Organic Law 1/2004), their willingness to intervene and, in the case of intervention, the type of helping behavior (real or hypothetical) preferred, using the sources (secondary data) available (specifically, survey data, as the surveys of social perception of gender violence and the 2014 and 2019 macro-surveys, and also administrative data, as the database of reports filed). The data analyzed allow us to determine that, in fact, in the cases of IPVAW there are usually persons within the victim’s inner circle who are firsthand witnesses or have been informed by the victim of the existence of this type of violence, but, although the bystanders generally claim they would engage in an active and supportive response, this is in fact not always the case. These results underscore the need to develop intervention programs aimed at IPVAW bystanders to improve their reaction and contribute to the development of helpful and efficient active responses.
Summary
Topology optimization has emerged in the last years as a promising research field with a wide range of applications. One of the most successful approaches, the SIMP method, is based on ...regularizing the problem and proposing a penalization interpolation function. In this work, we propose an alternative interpolation function, the SIMP‐ALL method that is based on the topological derivative concept. First, we show the strong relation in plane linear elasticity between the Hashin‐Shtrikman (H‐S) bounds and the topological derivative, providing a new interpretation of the last one. Then, we show that the SIMP‐ALL interpolation remains always in between the H‐S bounds regardless the materials to be interpolated. This result allows us to interpret intermediate values as real microstructures. Finally, we verify numerically this result and we show the convenience of the proposed SIMP‐ALL interpolation for obtaining auto‐penalized optimal design in a wider range of cases. A MATLAB code of the SIMP‐ALL interpolation function is also provided.
Summary
Background
Patients with moderate‐to‐severe psoriasis treated with adalimumab in daily clinical practice are different from those in clinical trials, and outcomes may differ in different ...geographical settings.
Objectives
To analyse the efficacy, retention of treatment and adverse events in a cohort of such patients at a referral centre in Barcelona, Spain.
Methods
Data from a cohort of 119 consecutive patients treated between January 2008 and March 2013 were retrospectively collected. Drug survival was analysed by the Kaplan–Meier method with log‐rank test and Cox regression.
Results
The mean duration of treatment was 25 months (median 22, range 2–60). The 75% improvement in Psoriasis Area and Severity Index (PASI 75) response rates at 16 weeks, 6 months and 1 year of treatment were 64%, 58% and 53%, respectively (intention‐to‐treat analysis). The corresponding PASI 90 values were 49%, 52% and 50%. Biologic‐naive patients (41%) had significantly higher PASI 75 and PASI 90 response rates at 6 months and 1 year. On multivariate analysis, only PASI 90 response at 6 months was significantly associated with treatment retention (P = 0·0009), with a hazard ratio of 7·3 (95% confidence interval 2·3–23·6). Forty‐eight adverse events (AEs) occurred in 29 patients, and were serious in eight (0·032 events per patient‐year). Paradoxical flares of psoriasis or arthritis were seen in five patients. Infections accounted for seven serious AEs, and were the reason for discontinuation in two patients.
Conclusions
PASI 90 response at 6 months was the only independent variable predicting drug survival on multivariate analysis. Infections, including de novo infection by Mycobacterium tuberculosis, accounted for seven serious AEs.
What's already known about this topic?
There are few reports on the use of adalimumab for the treatment of moderate‐to‐severe psoriasis in clinical practice according to the European Medicines Agency.
Psoriasis Area and Severity Index (PASI) 75% response rates at 16 weeks and 6 months were approximately 60% in a previously published U.K. series.
Male sex and the presence of arthritis have been associated with decreased drug survival in one study.
What does this study add?
Biologic‐naive status and efficacy parameters denoting a good or excellent response appear to be associated with a higher probability of drug survival.
Combination treatment increased PASI response rates at 6 months and might provide an explanation for the relatively high rate of PASI 90 responders in our cohort.
Infections, including de novo infection by Mycobacterium tuberculosis, accounted for most serious adverse events, and paradoxical flares of psoriasis and psoriatic arthritis were relatively frequent.
A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no ...biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse.
One hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR.
NGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r-=-0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) hazard ratio (HR), 17.56; log-rank P-=-0.0014 and HR, 11.33; log-rank P-=-0.0001, respectively. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P-<-0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5-months.
Plasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.
Handwritten signatures are biometric traits at the center of debate in the scientific community. Over the last 40 years, the interest in signature studies has grown steadily, having as its main ...reference the application of automatic signature verification, as previously published reviews in 1989, 2000, and 2008 bear witness. Ever since, and over the last 10 years, the application of handwritten signature technology has strongly evolved and much research has focused on the possibility of applying systems based on handwritten signature analysis and processing to a multitude of new fields. After several years of haphazard growth of this research area, it is time to assess its current developments for their applicability in order to draw a structured way forward. This perspective reports a systematic review of the last 10 years of the literature on handwritten signatures with respect to the new scenario, focusing on the most promising domains of research and trying to elicit possible future research directions in this subject.
Long-tailed unconventional class I myosin, Myosin 1E (MYO1E) and Myosin 1F (MYO1F) are motor proteins that use chemical energy from the hydrolysis of adenosine triphosphate (ATP) to produce ...mechanical work along the actin cytoskeleton. On the basis of their motor properties and structural features, myosins perform a variety of essential roles in physiological processes such as endocytosis, exocytosis, cell adhesion, and migration. The long tailed unconventional class I myosins are characterized by having a conserved motor head domain, which binds actin and hydrolyzes ATP, followed by a short neck with an isoleucine-glutamine (IQ) motif, which binds calmodulin and is sensitive to calcium, and a tail that contains a pleckstrin homology domain (PH), a tail homology 1 domain (TH1), wherein these domains allow membrane binding, a tail homology 2 domain (TH2), an ATP-insensitive actin-binding site domain, and a single Src homology 3 domain (SH3) susceptible to binding proline rich regions in other proteins. Therefore, these motor proteins are able to bind actin, plasma membrane, and other molecules (adaptor, kinases, membrane proteins) that contribute to their function, ranging from increasing membrane tension to molecular trafficking and cellular adhesion. MYO1E and MYO1F function in host self-defense, with a better defined role in innate immunity in cell migration and phagocytosis. Impairments of their function have been identified in patients suffering pathologies ranging from tumoral processes to kidney diseases. In this review, we summarize our current knowledge of specific features and functions of MYO1E and MYO1F in various tissues, as well as their involvement in disease.
Palliative care aims to improve quality of life for people with serious illness and their families. One potential barrier to palliative care uptake is inaccurate knowledge and/or negative beliefs ...among the general population, which may inhibit early interest in, communication about, and integration of palliative care following subsequent illness diagnosis. We explored knowledge and beliefs about palliative care among the general public using nationally-representative data collected in 2018 as part of the cross-sectional Health Information National Trends Survey. Only individuals who had heard of palliative care (n = 1,162, Mage = 51.8, 64% female) were queried on knowledge and beliefs. We examined whether self-assessed level of awareness of palliative care (i.e., knowing a little vs. enough to explain it) was associated with the relative likelihood of having accurate/positive beliefs, inaccurate/negative beliefs, or responding "don't know" to questions about palliative care. Respondents who indicated knowing a lot about palliative care had more accurate versus inaccurate knowledge than those who knew a little on only two of six items and more positive attitudes on only one of three items. In particular, respondents with greater awareness were equally likely to report that palliative care is the same as hospice and requires stopping other treatments, and equally likely to believe that palliative care means giving up and to associate palliative care with death. Those with higher awareness were less likely than those with lower awareness to respond "don't know," but greater awareness was not necessarily associated with having accurate or positive beliefs about palliative care as opposed to inaccurate or negative beliefs. Thus, even members of the general public who perceived themselves to know a lot about palliative care were often no less likely to report inaccurate knowledge or negative beliefs (versus accurate and positive, respectively). Findings suggest a need to improve awareness and attitudes about palliative care.
Redox flow cells for energy conversion Ponce de León, C.; Frías-Ferrer, A.; González-García, J. ...
Journal of power sources,
09/2006, Letnik:
160, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Energy storage technologies provide an alternative solution to the problem of balancing power generation and power consumption. Redox flow cells are designed to convert and store electrical energy ...into chemical energy and release it in a controlled fashion when required. Many redox couples and cell designs have being evaluated. In this paper, redox flow systems are compared in the light of characteristics such as open circuit potential, power density, energy efficiency and charge-discharge behaviour. The key advantages and disadvantages of redox flow cells are considered while areas for further research are highlighted.
We present a general framework for the dimensional reduction, in terms of number of degrees of freedom as well as number of integration points (“hyper-reduction”), of nonlinear parameterized finite ...element (FE) models. The reduction process is divided into two sequential stages. The first stage consists in a common Galerkin projection onto a reduced-order space, as well as in the condensation of boundary conditions and external forces. For the second stage (reduction in number of integration points), we present a novel cubature scheme that efficiently determines optimal points and associated positive weights so that the error in integrating reduced internal forces is minimized. The distinguishing features of the proposed method are: (1) The minimization problem is posed in terms of orthogonal basis vector (obtained via a partitioned Singular Value Decomposition) rather that in terms of snapshots of the integrand. (2) The volume of the domain is exactly integrated. (3) The selection algorithm need not solve in all iterations a nonnegative least-squares problem to force the positiveness of the weights. Furthermore, we show that the proposed method converges to the absolute minimum (zero integration error) when the number of selected points is equal to the number of internal force modes included in the objective function. We illustrate this model reduction methodology by two nonlinear, structural examples (quasi-static bending and resonant vibration of elastoplastic composite plates). In both examples, the number of integration points is reduced three order of magnitudes (with respect to FE analyses) without significantly sacrificing accuracy.
PDF
