571 research outputs found
Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: an additional barrier to non viral gene delivery
Transparent Carbon Disclosures:depth in Carbon-reporting of Dutch listed and non-listed companies
Climate change is seen as one of the most relevant challenges for the next coming years, politically and economically. The Dutch government has set targets to reduce national carbon emissions according to the commitments made in Paris in 2015. Since companies substantially contribute to the level of carbon emissions, it is necessary to monitor their carbon emissions to see whether they fulfil their commitments. This research shows to what extent companies in the Netherlands (listed, non-listed family owned and a reference group we refer to as non-listed other companies) report their strategies, implementation and performance regarding carbon emissions and reduction. We find, not surprisingly, that on average listed companies are far more transparent than non-listed companies. Non-listed family owned companies are apparently not active or even not willing to be transparent about their carbon policy. However, we do find that several non-listed companies that score high in the Dutch Transparency Benchmark (non-listed other companies) are just as transparent about carbon emissions as AEX-listed companies that must report due to market regulation. Furthermore, we find that most carbon disclosures are still of a mainly qualitative nature. This could imply that firmsβ carbon disclosures are at present mostly a means of storytelling rather than a means of thorough analysis on how climate change risk might affect them and how they have to respond to mitigate these financial and societal risks
National Improvement of Waiting Times:First Results From the Dutch Head and Neck Audit
ObjectiveTimely treatment initiation in head and neck cancer (HNC) care is of great importance regarding survival, oncological, functional, and psychological outcomes. Therefore, waiting times are assessed in the Dutch Head and Neck Audit (DHNA). This audit aims to assess and improve the quality of care through feedback and benchmarking. For this study, we examined how waiting times evolved since the start of the DHNA.Study DesignProspective cohort study.SettingNational multicentre study.MethodsThe DHNA was established in 2014 and reached national coverage of all patients treated for primary HNC in 2019. DHNA data on curative patients from 2015 to 2021 was extracted on national (benchmark) and hospital level. We determined 3 measures for waiting time: (1) the care pathway interval (CPI, first visit to start treatment), (2) the time to treatment interval (TTI, biopsy to start treatment), and (3) CPI-/TTI-indicators (percentage of patients starting treatment β€30 days). The Dutch national quality norm for the CPI-indicator is 80%.ResultsThe benchmark median CPI and TTI improved between 2015 and 2021 from 37 to 26 days and 37 to 33 days, respectively. Correspondingly, the CPI- and TTI-indicators, respectively, increased from 39% to 64% and 35% to 40% in 2015 to 2021. Outcomes for all hospitals improved and dispersion between hospitals declined. Four hospitals exceeded the 80% quality norm in 2021.ConclusionWaiting times improved gradually over time, with 4 hospitals exceeding the quality standard in 2021. On the hospital-level, process improvement plans have been initiated. Systematic registration, auditing, and feedback of data support the improvement of quality of care
Π₯ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ Π²Π·ΡΠΎΡΠ»ΡΡ Π±ΠΎΠ»ΡΠ½ΡΡ Ρ ΡΠ°ΡΠΊΠΎΠΌΠ°ΠΌΠΈ ΠΌΡΠ³ΠΊΠΈΡ ΡΠΊΠ°Π½Π΅ΠΉ
Π ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΎΠ±ΡΠΈΠ΅ ΠΏΡΠΈΠ½ΡΠΈΠΏΡ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ Π²Π·ΡΠΎΡΠ»ΡΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΡΠ°ΡΠΊΠΎΠΌΠ°ΠΌΠΈ ΠΌΡΠ³ΠΊΠΈΡ
ΡΠΊΠ°Π½Π΅ΠΉ. Π ΠΎΠ»Ρ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΡΠΈ ΡΡΠΎΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΈ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
Π»Π΅Ρ ΠΏΠΎΠ²ΡΡΠ°Π΅ΡΡΡ. HΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ°ΠΌΠΈ ΡΠ²Π»ΡΡΡΡΡ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ ΠΈ ΠΈΡΠΎΡΡΠ°ΠΌΠΈΠ΄, ΠΏΡΠΈΡΠ΅ΠΌ Ρ ΠΎΠ±ΠΎΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΎΡ Π΄ΠΎΠ·Ρ. Π₯ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΡΠΈΠΌΠ΅Π½ΡΡΡ ΠΊΠ°ΠΊ ΡΠ»Π΅ΠΌΠ΅Π½Ρ ΡΠ°Π΄ΠΈΠΊΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΊΠ°ΠΊ ΠΏΠ°Π»Π»ΠΈΠ°ΡΠΈΠ²Π½ΡΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΡΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΏΡΠΎΡΠ΅ΡΡΠ΅. ΠΡΠΈ ΡΠ°Π±Π΄ΠΎΠΌΠΈΠΎΡΠ°ΡΠΊΠΎΠΌΠ΅ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½Π° ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ ΠΏΡΠΈ Π»ΡΠ±ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.Chemotherapy has an increasing role in the therapy of soft tissue sarcomas. Meanwhile, chemotherapy of these tumors is frequently considered in general without taking into account the peculiar clinical features of various subtypes. Doxorubicin and ifosfamide are the most active drugs in the treatment of soft tissue sarcomas. Chemotherapy could be used both for radical and for palliative treatment. For rhabdomyosarcoma, chemotherapy is effective in all the stages of such disease
Support for Redistribution in Western Europe: Assessing the role of religion
Previous sociological studies have paid little attention to religion as a central determinant of individual preferences for redistribution. In this article we argue that religious individuals, living in increasingly secular societies, differ in political preferences from their secular counterparts. Based on the theory of religious cleavages, we expect that religious individuals will oppose income redistribution by the state. Furthermore, in contexts where the polarization between religious and secular individuals is large, preferences for redistribution will be lower. In the empirical analysis we test our predictions in a multilevel framework, using data from the European Social Survey 2002β2006 for 16 Western European countries. After controlling for a wide range of individual socio-economic factors and for welfare-state policies, religion plays and important explanatory role. We find that both Catholics and Protestants strongly oppose income redistribution by the state. The cleavage between religious and secular individuals is far more important than the difference between denominations. Using a refined measure of religious polarization, we also find that in more polarized context the overall level of support for redistribution is lower
The perceived legitimacy of a basic income among Finnish food aid recipients
Discussions on the pros and cons of a basic income (BI) have remained mainly at the 'systemic level'. Based on survey and interview data, this study provides a 'bottom-up' perspective on the legitimacy of the idea of a basic income among people queuing in breadlines in Helsinki in late 2016, who are assumed to be affected positively by this benefit. While general support for the idea is high, not everyone supports an unconditional BI. Despite the likely 'objective interest', a BI does not seem to be supported by food aid recipients any more than by the general population as measured by a previous study. Besides interests, normative beliefs and perceptions of deservingness seem of importance for legitimacy too, especially among those not supporting a BI. Doubts regarding a BI are to some extent connected to wishes to limit the social citizenship of some of the persons in the breadlines.Peer reviewe
Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
Presenilin 1 (PS1) interacts with telencephalin (TLN) and the amyloid precursor protein via their transmembrane domain (Annaert, W.G., C. Esselens, V. Baert, C. Boeve, G. Snellings, P. Cupers, K. Craessaerts, and B. De Strooper. 2001. Neuron. 32:579β589). Here, we demonstrate that TLN is not a substrate for Ξ³-secretase cleavage, but displays a prolonged half-life in PS1β/β hippocampal neurons. TLN accumulates in intracellular structures bearing characteristics of autophagic vacuoles including the presence of Apg12p and LC3. Importantly, the TLN accumulations are suppressed by adenoviral expression of wild-type, FAD-linked and D257A mutant PS1, indicating that this phenotype is independent from Ξ³-secretase activity. Cathepsin D deficiency also results in the localization of TLN to autophagic vacuoles. TLN mediates the uptake of microbeads concomitant with actin and PIP2 recruitment, indicating a phagocytic origin of TLN accumulations. Absence of endosomal/lysosomal proteins suggests that the TLN-positive vacuoles fail to fuse with endosomes/lysosomes, preventing their acidification and further degradation. Collectively, PS1 deficiency affects in a Ξ³-secretaseβindependent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes
Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy
Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and FrΓΌhsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy
Short of drugs?:Call upon Operations and Supply Chain Management
Purpose: This βimpact pathwaysβ paper argues that operations and supply chain management (OSCM) could help address the worsening drug shortage problem in high-income countries. This significant societal problem poses difficult challenges to stakeholders given the complex and dynamic nature of drug supply chains. OSCM scholars are well positioned to provide answers, introducing new research directions for OSCM in the process. Design/methodology/approach: To substantiate this, we carried out a review of stakeholder reports from six European countries and the academic literature. Findings: There is little academic research and no fundamental agreement among stakeholders about causes of shortages. Stakeholders have suggested many government measures, but little evidence exists on their comparative cost-effectiveness. Originality/value: We discuss three pathways of impactful research on drug shortages to which OSCM could contribute: (1) Developing an evidence-based system view of drug shortages; (2) Studying the comparative cost-effectiveness of key government interventions; (3) Bringing supply chain risk management into the government and economics perspectives and vice versa. Our study provides a baseline for future COVID-19-related research on this topic
- β¦