Comparing internal migration across the countries of Latin America: A multidimensional approach.

While considerable progress has been made in understanding the way particular aspects of internal migration, such as its intensity, age profile and spatial impact, vary between countries around the world, little attention to date has been given to establishing how these dimensions of migration interact in different national settings. We use recently developed measures of internal migration that are scale-independent to compare the overall intensity, age composition, spatial impact, and distance profile of internal migration in 19 Latin American countries. Comparisons reveal substantial cross-national variation but cluster analysis suggests the different dimensions of migration evolve systematically to form a broad sequence characterised by low intensities, young ages at migration, unbalanced flows and high friction of distance at lower levels of development, trending to high intensities, an older age profile of migration, more closely balanced flows and lower friction of distance at later stages of development. However, the transition is not linear and local contingencies, such as international migration and political control, often distort the migration-development nexus, leading to unique migration patterns in individual national contexts

Global Demography Expert Survey on the Drivers and Consequences of Demographic Change

Insight into the future of the world population is key for policy planning. At present, several organisations engage in developing global long-term population projections and provide varied results in terms of projected population size and structures. This diversity demonstrates that there is a need to reflect on the ingredients that feed into the projections. For this reason, the JRC, IIASA and the UN Population Division launched a survey where experts were asked to assess the validity and relevance of alternative arguments about the forces that could shape future fertility, mortality, and migration trends in the country of their choice. The results of the survey highlight that experts almost unanimously support the roles played by urbanisation, reductions in child mortality, greater educational attainment, and employment opportunities for women in decreasing fertility in high fertility countries. At the same time, life expectancy is expected to continue increasing across world regions, with the most significant improvements projected by experts in current 'low mortality' countries. Experts on migration mostly agree that climate change will lead to a rise in immigration. However, there is less agreement on the forces driving emigration. As a broad conclusion, the expert opinions seem to indicate that demographic challenges of the future do not necessarily have demographic solutions, and will instead necessitate improved adaptive capacities among all societies

Ukraine's population future after the Russian Invasion

This report analyses the effect of the Russian Invasion on the longer-term future of Ukraine?s population size and structure. The qualitative scenarios spanning a range of possible migration futures are translated into quantitative population projections using a multistate population model which shows the evolution of the size and age-sex composition of Ukraine?s population up to 2052. Under the most pessimistic scenario of Long war, low return scenario we project a decline of 30 of the population. The difference of in population decline across the four considered migration scenarios matches the uncertainty in the UN projections suggesting that migration will be similarly important as fertility and mortality in driving population change in Ukraine following the war

The role of c-FLIP splice variants in urothelial tumours

Deregulation of apoptosis is common in cancer and is often caused by overexpression of anti-apoptotic proteins in tumour cells. One important regulator of apoptosis is the cellular FLICE-inhibitory protein (c-FLIP), which is overexpressed, for example, in melanoma and Hodgkin's lymphoma cells. Here, we addressed the question whether deregulated c-FLIP expression in urothelial carcinoma impinges on the ability of death ligands to induce apoptosis. In particular, we investigated the role of the c-FLIP splice variants c-FLIPlong (c-FLIPL) and c-FLIPshort (c-FLIPS), which can have opposing functions. We observed diminished expression of the c-FLIPL isoform in urothelial carcinoma tissues as well as in established carcinoma cell lines compared with normal urothelial tissues and cells, whereas c-FLIPS was unchanged. Overexpression and RNA interference studies in urothelial cell lines nevertheless demonstrated that c-FLIP remained a crucial factor conferring resistance towards induction of apoptosis by death ligands CD95L and TRAIL. Isoform-specific RNA interference showed c-FLIPL to be of particular importance. Thus, urothelial carcinoma cells appear to fine-tune c-FLIP expression to a level sufficient for protection against activation of apoptosis by the extrinsic pathway. Therefore, targeting c-FLIP, and especially the c-FLIPL isoform, may facilitate apoptosis-based therapies of bladder cancer in otherwise resistant tumours

Defective airway intraflagellar transport underlies a combined motile and primary ciliopathy syndrome caused by IFT74 mutations

Ciliopathies are inherited disorders caused by defective cilia. Mutations affecting motile cilia usually cause the chronic muco-obstructive sinopulmonary disease primary ciliary dyskinesia (PCD) and are associated with laterality defects, while a broad spectrum of early developmental as well as degenerative syndromes arise from mutations affecting signalling of primary (non-motile) cilia. Cilia assembly and functioning requires intraflagellar transport of cargos assisted by IFT-B and IFT-A adaptor complexes. Within IFT-B, the N-termini of partner proteins IFT74 and IFT81 govern tubulin transport to build the ciliary microtubular cytoskeleton. We detected a homozygous 3 kb intragenic IFT74 deletion removing the exon 2 initiation codon and 40 N-terminal amino acids in two affected siblings. Both had clinical features of PCD with bronchiectasis, but no laterality defects. They also had retinal dysplasia and abnormal bone growth, with a narrowed thorax and short ribs, shortened long bones and digits and abnormal skull shape. This resembles short-rib thoracic dysplasia, a skeletal ciliopathy previously linked to IFT defects in primary cilia, not motile cilia. Ciliated nasal epithelial cells collected from affected individuals had reduced numbers of shortened motile cilia with disarranged microtubules, some mis-orientation of the basal feet, and disrupted cilia structural and IFT protein distributions. No full length IFT74 was expressed, only truncated forms that were consistent with N-terminal deletion and inframe translation from downstream initiation codons. In affinity purification mass spectrometry, exon 2-deleted IFT74 initiated from the nearest inframe downstream methionine 41 still interacts as part of the IFT-B complex, but only with reduced interaction levels and not with all its usual IFT-B partners. We propose that this is a hypomorphic mutation with some residual protein function retained, that gives rise to a non-lethal primary skeletal ciliopathy combined with defective motile cilia and PCD

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa

Does Consideration and Assessment of Effects on Health Equity Affect the Conclusions of Systematic Reviews? A Methodology Study

INTRODUCTION: Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. METHODS: We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. RESULTS: Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. CONCLUSION: The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews

Equity-oriented toolkit for health technology assessment and knowledge translation: application to scaling up of training and education for health workers

Human resources for health are in crisis worldwide, especially in economically disadvantaged areas and areas with high rates of HIV/AIDS in both health workers and patients. International organizations such as the Global Health Workforce Alliance have been established to address this crisis. A technical working group within the Global Health Workforce Alliance developed recommendations for scaling up education and training of health workers. The paper will illustrate how decision-makers can use evidence and tools from an equity-oriented toolkit to scale up training and education of health workers, following five recommendations of the technical working group. The Equity-Oriented Toolkit, developed by the World Health Organization Collaborating Centre for Knowledge Translation and Health Technology Assessment in Health Equity, has four major steps: (1) burden of illness; (2) community effectiveness; (3) economic evaluation; and (4) knowledge translation/implementation. Relevant tools from each of these steps will be matched with the appropriate recommendation from the technical working group