Decentralisation in times of crisis: asset or liability? The case of Germany and Italy during Covid-19

How did the legal and political-administrative relationship between central and local governments of two decentralised states shape their response to COVID-19? Literature and theories on decentralisation argue that federal and decentralised states are less able to respond to crises in a coordinated manner due to their perceived greater susceptibility to political conflict. Situated within this theoretical debate and based on the analysis of legal acts, political decisions, and relevant national news media articles between March and August 2020 in Germany and Italy, this research note shows that, counterintuitively, more decentralisation does not necessarily translate into more legal and political stress during pandemic management. In responding to the COVID-19 pandemic, Germany, a highly decentralised state, experienced less legal and political tensions than the less decentralised Italy. The key to understanding this variation lies in different institutional arrangements, complemented by the specific political cultures of both states

Assessing the effectiveness of EU humanitarian aid. The cases of Myanmar, Lebanon, Mozambique

The socioeconomic impacts of COVID-19 have been felt worldwide, but especially in low-income countries. In these contexts, the effects of the global crisis have exacerbated the need for humanitarian assistance. While humanitarian programmes have become more critical, ensuring their effectiveness remains a challenge. The thesis investigates the factors that may affect humanitarian aid programmes’ effectiveness by looking at the European Union (EU), one of the top donors worldwide. Therefore, the two research questions are, firstly: why does the effectiveness of EU humanitarian aid programmes vary?; and secondly: What are the factors causing this variation? The research is meaningful because it addresses a critical, current challenge and because it also attempts to fill a gap in EU foreign policy literature by empirically assessing the external effectiveness of the EU ‘on the ground’ in contexts of wars and natural crises. It also assesses the relationship that it has with United Nations (UN) agencies and Non-Government Organizations (NGOs) in the field, in a sector, humanitarian aid, that has been overlooked as part of development aid. Following a precise definition of effectiveness and based on empirical data gathered through official reports, documents and interviews with UN, NGO, and EU officials, the thesis seeks to answer to the research questions by formulating three hypotheses on the factors that could influence the effectiveness and by empirically assessing them in the context of Myanmar, Lebanon and Mozambique, between 2015 and 2017. The hypotheses include: the EU Member States internal cohesiveness and coordination with Directorate-General for European Civil Protection and Humanitarian Aid Operations (DG ECHO) on the ground; delegation and coordination in the field between DG ECHO and UN agencies/NGOs; the national authorities’ attitude vis-à-vis EU humanitarian aid programmes. The research finds that the last two factors can be particularly decisive in the effectiveness of the programmes and proposes a formula for effectiveness. It suggests that EU humanitarian aid programmes should focus on resilience and preparedness, that the agents involved should closely coordinate, and the use of new technologies to speed up processes should be increased. Finally, the thesis suggests pathways to generalise these findings to non-EU humanitarian and to development actors, such as the World Bank

A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype

Britain avoids talking about COVID-19 deaths. that’s a mistake

How has the UK government acknowledged and talked about COVID-19 deaths? In an extract from their new report, Katharine M Millar, Yuna Han, Katharina Kuhn, Martin Bayly and Irene Morlino (LSE) warn that the current focus on ‘recovery’ and ‘inevitable’ deaths risks alienating sections of society, and suggest how it can do better. Pandemics present a ... Continue

Confronting the COVID-19 pandemic: grief, loss, and social order

This research addresses the challenge the 2019- 2020 COVID-19 pandemic (COVID-19) presents to social order as a result of mass grieving and loss. It places a particular emphasis on the UK response and lessons that can be learnt for further ‘waves’. A tendency for research to look at technocratic policy responses has led to the overlooking of the social impact that pandemics produce. This study, in contrast, employs a qualitative, comparative methodology to examine four key cases – the UK, Italy, South Korea, and Germany – from 1 January to 31 July 2020, as well as the UK during the 1918-19 influenza epidemic – to examine the politics of COVID-9 as a mass death event. Our research finds that the narrative framing of the pandemic as a particular type of crisis; the ways that deaths have been recorded and managed; and the manner in which loss has been mourned and commemorated vary across cases. This variance, the research suggests, has implications for the ways that societies may respond, particularly in the medium- and longterm. Recommendations are made for governments responding to future ‘waves’ of the virus in relation to communicating loss to the public, and commemorating deaths in a manner that supports social cohesion and prepares the public for future crises

Functional characterization of a novel truncating mutation in Lamin A/C gene in a family with a severe cardiomyopathy with conduction defects

Background/Aims: Truncating LMNA gene mutations occur in many inherited cardiomyopathy cases, but the molecular mechanisms involved in the disease they cause have not yet been systematically investigated. Here, we studied a novel frameshift LMNA variant (p.D243Gfs*4) identified in three members of an Italian family co-segregating with a severe form of cardiomyopathy with conduction defects. Methods: HEK293 cells and HL-1 cardiomyocytes were transiently transfected with either Lamin A or D243Gfs*4 tagged with GFP (or mCherry). D243Gfs*4 expression, cellular localization and its effects on diverse cellular mechanisms were evaluated with western blotting, laser-scanning confocal microscopy and video-imaging analysis in single cells. Results: When expressed in HEK293 cells, GFP- (or mCherry)-tagged LMNA D243Gfs*4 colocalized with calnexin within the ER. ER mislocalization of LMNA D243Gfs*4 did not significantly induce ER stress response, abnormal Ca2+ handling and apoptosis when compared with HEK293 cells expressing another truncated mutant of LMNA (R321X) which similarly accumulates within the ER. Of note, HEK293-LMNA D243Gfs*4 cells showed a significant reduction of connexin 43 (CX43) expression level, which was completely rescued by activation of the WNT/β-catenin signaling pathway. When expressed in HL-1 cardiomyocytes, D243Gfs*4 significantly impaired the spontaneous Ca2+ oscillations recorded in these cells as result of propagation of the depolarizing waves through the gap junctions between non-transfected cells surrounding a cell harboring the mutation. Furthermore, mCh-D243Gfs*4 HL-1 cardiomyocytes showed reduced CX43-dependent Lucifer Yellow (LY) loading and propagation. Of note, activation of β-catenin rescued both LY loading and LMNA D243Gfs*4 -HL-1 cells spontaneous activity propagation. Conclusion: Overall, the present results clearly indicate the involvement of the aberrant CX43 expression/activity as a pathogenic mechanism for the conduction defects associated to this LMNA truncating alteration

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

An Additional Patient With 3q27.3 Microdeletion Syndrome.

The 3q27.3 microdeletion syndrome has been recently delineated in 7 subjects from 5 families sharing a 1.4 Mb smallest region of overlap. This condition appears recognizable by the association of Marfanoid habitus, mild but distinctive facial dysmorphism, intellectual disability, psychosis, and mood disorder. Here, we describe an additional 17-year-old man with an *7.7-Mb deletion encompassing the 3q27.3 microdeletion critical region, previously run undetected at standard karyotyping. The constellation of major clinical findings overlaps with those reported in the 7 previously published patients and thus confirms the existence of a strongly recognizable syndrome linked to imbalance of 3q27.3. The role of AHSG and, possibly, of other genes in determining the3q27.3 microdeletion habitus is discussed by comparison of the deleted segments. The involvement of adjacent loci and genes, such as OPA1 and GP5, may contribute in this patient to novel satellite features, such as optic atrophy and subclinical coagulopathy

Variability in a three-generation family with pierre robin sequence, acampomelic campomelic dysplasia, and intellectual disability due to a novel ∼1 Mb deletion upstream of SOX9, and including KCNJ2 and KCNJ16

Background: Campomelic dysplasia and acampomelic campomelic dysplasia (ACD) are allelic disorders due to heterozygous mutations in or around SOX9. Translocations and deletions involving the SOX9 5′ regulatory region are rare causes of these disorders, as well as Pierre Robin sequence (PRS) and 46,XY gonadal dysgenesis. Genotype-phenotype correlations are not straightforward due to the complex epigenetic regulation of SOX9 expression during development. Methods: We report a three-generation pedigree with a novel ∼1 Mb deletion upstream of SOX9 and including KCNJ2 and KCNJ16, and ascertained for dominant transmission of PRS. Results: Further characterization of the family identified subtle appendicular anomalies and a variable constellation of axial skeletal features evocative of ACD in several members. Affected males showed learning disability. Conclusion: The identified deletion was smaller than all other chromosome rearrangements associated with ACD. Comparison with other reported translocations and deletions involving this region allowed further refining of genotype-phenotype correlations and an update of the smallest regions of overlap associated with the different phenotypes. Intrafamilial variability in this pedigree suggests a phenotypic continuity between ACD and PRS in patients carrying mutations in the SOX9 5′ regulatory region. Birth Defects Research (Part A) 106:61-68, 2016