389 research outputs found
A voice for change? Trust relationships between ombudsmen, individuals and public service providers
There has been a debate for years about what the role of the ombudsman is. This article examines a key component of the role, to promote trust in public services and government. To be able to do this, however, an ombudsman needs to be perceived as legitimate and be trusted by a range of stakeholders, including the user. This article argues that three key relationships in a person’s complaint journey can build trust in an institution, and must therefore be understood as a system. The restorative justice framework is adapted to conceptualize this trust model as a novel approach to understanding the institution from the perspective of its users. Taking two public sector ombudsmen as examples, the article finds that voice and trust need to be reinforced through the relationships in a consumer journey to manage individual expectations, prevent disengagement, and thereby promote trust in the institution, in public service providers, and in government
A Spaetzle-like role for Nerve Growth Factor β in vertebrate immunity to Staphylococcus aureus
Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity
Perceptions of postnatal depression across countries and cultures: from a TransCultural Study of PostNatal Depression (TCS-PND)
Objectives
The qualitative study was conducted within the international
“Transcultural study of postnatal depression (PND)” in 17 centres
located in 13 different countries. The aim was to explore
perceptions of PND by lay and professional key informants,
specifically regarding description of symptoms, awareness of this
pathology and of possible care.
Methods
Broad areas of inquiry and open-ended probes were developed by
the TCS-PND research group during international workshops to
obtain data comparable between countries on perceptions of
PND. A non-random convenience sampling method was used to
recruit postpartum mothers for focus groups, and fathers and
grandmothers for interviews. Influential healthcare planners and
clinicians were interviewed as professional key informants in each
centre. Within sites, transcripts of focus groups and interviews
underwent a process of text analysis in the original language until
exhaustive theme extraction was achieved. Themes (in English)
from all the centres were combined into broader categories and
after consensus discussions these categories were revalidated.
Results and discussion
Qualitative data were supplemented in each centre with sociodemographic
data to address the issues of: (i) whether perceptions
of PND are related to some specific cultural perception of mental
heath and/or of status of parenthood and (ii) how high or low
levels of general care and specificity of health policy relate to
differences in perception of needs for care. Data collected using
the same probes and methodology in different countries and
cultures has enabled a comparative analysis of perceptions of
PND. In addition it has shown that, although not described with
the same words, PND is a well-recognised condition by recent
mothers in all countries in this study. Data on focus groups and
interviews from selected countries are given in the following
abstracts to illustrate some similarities and differences in
perceptions between countries
Expression of naive/memory (CD45RA/CD45RO) markers by peripheral blood CD4+ and CD8+ T cells in children with asthma
On the projection of future fire danger conditions with various instantaneous/mean-daily data sources
Fire danger indices are descriptors of fire potential in a large area, and combine a few variables that affect the initiation, spread and control of forest fires. The Canadian Fire Weather Index (FWI) is one of the most widely used fire danger indices in the world, and it is built upon instantaneous values of temperature, relative humidity and wind velocity at noon, together with 24 hourly accumulated precipitation. However, the scarcity of appropriate data has motivated the use of daily mean values as surrogates of the instantaneous ones in several studies that aimed to assess the impact of global warming on fire. In this paper we test the sensitivity of FWI values to both instantaneous and daily mean values, analyzing their effect on mean seasonal fire danger (seasonal severity rating, SSR) and extreme fire danger conditions (90th percentile, FWI90, and FWI>30, FOT30), with a special focus on its influence in climate change impact studies. To this aim, we analyzed reanalysis and regional climate model (RCM) simulations, and compared the resulting instantaneous and daily mean versions both in the present climate and in a future scenario. In particular, we were interested in determining the effect of these datasets on the projected changes obtained for the mean and extreme seasonal fire danger conditions in future climate scenarios, as given by a RCM. Overall, our results warn against the use of daily mean data for the computation of present and future fire danger conditions. Daily mean data lead to systematic negative biases of fire danger calculations. Although the mean seasonal fire danger indices might be corrected to compensate for this bias, fire danger extremes (FWI90 and specially FOT30) cannot be reliably transformed to accommodate the spatial pattern and magnitude of their respective instantaneous versions, leading to inconsistent results when projected into the future. As a result, we advocate caution when using daily mean data and strongly recommend the application of the standard definition for its calculation as closely as possible. Threshold-dependent indices derived from FWI are not reliably represented by the daily mean version and thus can neither be applied for the estimation of future fire danger season length and severity, nor for the estimation of future extreme events.The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement 243888 (FUME Project). J.F. acknowledges nancial support from the Spanish R&D&I programme through grant CGL2010-22158-C02 (CORWES project).
The ESCENA project (200800050084265) of the Spanish \Strategic action on energy and
climate change" provided the WRF RCM simulation used in this study. We acknowledge three anonymous referees for their useful comments that helped to improve the original manuscript
Functionally reversible impacts of disturbances on lake food webs linked to spatial and seasonal dependencies
Increasing human impact on the environment is causing drastic changes in disturbance regimes and how they prevail over time. Of increasing relevance is to further our understanding on biological responses to pulse disturbances (short duration) and how they interact with other ongoing press disturbances (constantly present). Because the temporal and spatial contexts of single experiments often limit our ability to generalize results across space and time, we conducted a modularized mesocosm experiment replicated in space (five lakes along a latitudinal gradient in Scandinavia) and time (two seasons, spring and summer) to generate general predictions on how the functioning and composition of multitrophic plankton communities (zoo-, phyto- and bacterioplankton) respond to pulse disturbances acting either in isolation or combined with press disturbances. As pulse disturbance, we used short-term changes in fish presence, and as press disturbance, we addressed the ongoing reduction in light availability caused by increased cloudiness and lake browning in many boreal and subarctic lakes. First, our results show that the top-down pulse disturbance had the strongest effects on both functioning and composition of the three trophic levels across sites and seasons, with signs for interactive impacts with the bottom-up press disturbance on phytoplankton communities. Second, community composition responses to disturbances were highly divergent between lakes and seasons: temporal accumulated community turnover of the same trophic level either increased (destabilization) or decreased (stabilization) in response to the disturbances compared to control conditions. Third, we found functional recovery from the pulse disturbances to be frequent at the end of most experiments. In a broader context, these results demonstrate that top-down, pulse disturbances, either alone or with additional constant stress upon primary producers caused by bottom-up disturbances, can induce profound but often functionally reversible changes across multiple trophic levels, which are strongly linked to spatial and temporal context dependencies. Furthermore, the identified dichotomy of disturbance effects on the turnover in community composition demonstrates the potential of disturbances to either stabilize or destabilize biodiversity patterns over time across a wide range of environmental conditions
A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity
De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.
Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability
Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study
Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved
- …