Migration and The Equilibrium Prevalence of Infectious Diseases

This paper models how migration both influences and responds to differences in disease prevalence between cities and shows how the possibility of migration away from high-prevalence areas affects long-run steady state disease prevalence. We develop a dynamic framework where migration responds to the prevalence of disease, to the costs of migration and to the costs of living. The model explores how pressure for migration in response to differing equilibrium levels of disease prevalence generates differences in city characteristics such as land rents. Competition for scarce housing in low-prevalence areas can create segregation, with disease concentrated in high-prevalence ”sinks”. We show that policies affecting migration costs affect the steady-state disease prevalences across cities. In particular, migration can reduce steady-state disease incidence in low-prevalence areas while having no impact on prevalence in high-prevalence areas. This suggests that, in some circumstances, public health measures may need to avoid discouraging migration away from high disease areas

Escaping infectious diseases through migration? Quarantine measures under incomplete information about infection risk

This paper explores the implications for public policy of the fact that individuals have incomplete but private information about their exposure to infectious disease when they make migration decisions. In a 2-period model we study conditions under which the presence of quarantine measures may lead to inefficient outcomes by strengthening individuals' interest in migration to escape centres of disease and thereby imposing negative externalities on other uninfected individuals. We show first that when the disease has an epicentre, the marginal migrant imposes a net negative externality. Secondly, quarantine policies may sometimes encourage migration instead of discouraging it. Thirdly, even when they succeed in discouraging migration, quarantine policies may lower social welfare, and even increase overall disease incidence, if they go too far, thereby discouraging those intra-marginal migrants for whom private benefits exceed private costs by more than the negative externality they impose on others

Complexity of Bradley-Manna-Sipma Lexicographic Ranking Functions

In this paper we turn the spotlight on a class of lexicographic ranking functions introduced by Bradley, Manna and Sipma in a seminal CAV 2005 paper, and establish for the first time the complexity of some problems involving the inference of such functions for linear-constraint loops (without precondition). We show that finding such a function, if one exists, can be done in polynomial time in a way which is sound and complete when the variables range over the rationals (or reals). We show that when variables range over the integers, the problem is harder -- deciding the existence of a ranking function is coNP-complete. Next, we study the problem of minimizing the number of components in the ranking function (a.k.a. the dimension). This number is interesting in contexts like computing iteration bounds and loop parallelization. Surprisingly, and unlike the situation for some other classes of lexicographic ranking functions, we find that even deciding whether a two-component ranking function exists is harder than the unrestricted problem: NP-complete over the rationals and $\Sigma^P_2$-complete over the integers.Comment: Technical report for a corresponding CAV'15 pape

Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates

Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. Although the majority of affected individuals survive 3-5 years following diagnosis, some subgroups experience a more rapidly progressing form, surviving less than 1 year, and other subgroups experience slowly progressing forms, surviving nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to the case for humans, variation in survival within the mSOD1 mouse has been well documented, but different progression rates have not been investigated. The present study identifies two subgroups of B6SJL mSOD1(G93A) mice with different disease progression rates, a fast progression group (FPG) and slow progression group, as evidenced by differences in the rate of motor function decline. In addition, increased disease-associated gene expression within the FPG facial motor nucleus confirmed the presence of a more severe phenotype. We hypothesize that a more severe disease phenotype could be the result of 1) an earlier onset of axonal disconnection with a consistent degeneration rate or 2) a more severe or accelerated degenerative process. We performed a facial nerve transection axotomy in both mSOD1 subgroups prior to disease onset as a method to standardize the axonal disconnection. Instead of leading to comparable gene expression in both subgroups, this standardization did not eliminate the severe phenotype in the FPG facial nucleus, suggesting that the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups are representative of the rapid and slow disease phenotypes often experienced in ALS

Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays

Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. Several viruses encode proteins containing bZIP domains, including four that encode bZIPs lacking significant homology to any human protein. We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. The arrays recapitulated reported viral−human interactions and also uncovered new associations. MEQ and HBZ interacted with multiple human partners and had unique interaction profiles compared to any human bZIPs, whereas K-bZIP and BZLF1 displayed homospecificity. New interactions detected included HBZ with MAFB, MAFG, ATF2, CEBPG, and CREBZF and MEQ with NFIL3. These were confirmed in solution using circular dichroism. HBZ can heteroassociate with MAFB and MAFG in the presence of MARE-site DNA, and this interaction is dependent on the basic region of HBZ. NFIL3 and MEQ have different yet overlapping DNA-binding specificities and can form a heterocomplex with DNA. Computational design considering both affinity for MEQ and specificity with respect to other undesired bZIP-type interactions was used to generate a MEQ dimerization inhibitor. This peptide, anti-MEQ, bound MEQ both stably and specifically, as assayed using coiled-coil arrays and circular dichroism in solution. Anti-MEQ also inhibited MEQ binding to DNA. These studies can guide further investigation of the function of viral and human bZIP complexes.National Institutes of Health (U.S.) (NIH Award GM067681)National Science Foundation (U.S.) (NSF Award 0216437

The Financial Burden of Non-Communicable Chronic Diseases in Rural Nigeria: Wealth and Gender Heterogeneity in Health Care Utilization and Health Expenditures

Objectives Better insights into health care utilization and out-of-pocket expenditures for non-communicable chronic diseases (NCCD) are needed to develop accessible health care and limit the increasing financial burden of NCCDs in Sub-Saharan Africa. Methods A household survey was conducted in rural Kwara State, Nigeria, among 5,761 individuals. Data were obtained using biomedical and socio-economic questionnaires. Health care utilization, NCCD-related health expenditures and distances to health care providers were compared by sex and by wealth quintile, and a Heckman regression model was used to estimate health expenditures taking selection bias in health care utilization into account. Results The prevalence of NCCDs in our sample was 6.2%. NCCD-affected individuals from the wealthiest quintile utilized formal health care nearly twice as often as those from the lowest quintile (87.8% vs 46.2%, p = 0.002). Women reported foregone formal care more often than men (43.5% vs. 27.0%, p = 0.058). Health expenditures relative to annual consumption of the poorest quintile exceeded those of the highest quintile 2.2-fold, and the poorest quintile exhibited a higher rate of catastrophic health spending (10.8% among NCCD-affected households) than the three upper quintiles (4.2% to 6.7%). Long travel distances to the nearest provider, highest for the poorest quintile, were a significant deterrent to seeking care. Using distance to the nearest facility as instrument to account for selection into health care utilization, we estimated out-of-pocket health care expenditures for NCCDs to be significantly higher in the lowest wealth quintile compared to the three upper quintiles. Conclusions Facing potentially high health care costs and poor accessibility of health care facilities, many individuals suffering from NCCDs—particularly women and the poor—forego formal care, thereby increasing the risk of more severe illness in the future. When seeking care, the poor spend less on treatment than the rich, suggestive of lower quality care, while their expenditures represent a higher share of their annual household consumption. This calls for targeted interventions that enhance health care accessibility and provide financial protection from the consequences of NCCDs, especially for vulnerable populations

Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis

Introduction: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. Methods: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. Results: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2–8.7) years and 5.7 (IQR 4.8–8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). Conclusions: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup

Evidence for the involvement of tetrahydrofolate in the demethylation of nicotine by Nicotiana plumbaginifolia cell-suspension cultures.

The conversion of nicotine to nornicotine by Nicotiana plumbaginifolia Viv. cells was investigated by analysing the redistribution of label during feeding experiments with (R,S)-[[2]H-methyl]nicotine, (R,S)-[[13]C-methyl]nicotine and (R,S)-[[14]C-methyl]nicotine, and the results show that the N-methyl group of nicotine can be recycled into primary metabolism. Nuclear magnetic resonance (NMR) analysis of ethanolic extracts of cells grown in the presence of (R,S)-[[13]C-methyl]nicotine, using [1]H-[13]C correlation spectroscopy (HMQC, HMBC), revealed the presence of [3-[13]C]serine and [[13]C-methyl]methionine. Label was also identified in a cysteinyl derivative and in several methoxylated compounds, but no evidence was obtained with either NMR or ion-trap mass spectrometry for the presence of any intermediate between nicotine and nornicotine. However, experiments with (R,S)-[[14]C-methyl] nicotine indicated that 70-75% of the metabolised label was released as carbon dioxide. These results are consistent with a pathway in which the oxidative hydrolysis of the nicotine methyl produces an unstable intermediate, N'-hydroxymethylnornicotine, that breaks down spontaneously to nornicotine and formaldehyde, with the formaldehyde being metabolised either directly to formate and carbon dioxide, or through the tetrahydrofolate-mediated pathways of one-carbon metabolism. However since the key intermediate, N-hydro xymethylnornicotine, could not be detected, the possibility of a direct methyl group transfer to tetrahydrofolate cannot be excluded

Migration outflows and optimal migration policy: rules versus discretion

We study the effects of more open borders on return migration and show that migrants are more likely to return to the origin country when migration rules are softened, because this implies that they could more easily re-migrate if return migration is unsuccessful. As a result, softening migration rules leads to lower net inflows than is generally acknowledged. We show that if government follows rules to shape the optimal migration policy, it will choose more open “borders” than were its behaviour to be discretionary. However, this requires an appropriate commitment technology. We show that electoral accountability may be a solution to the commitment problem. As a matter of fact, observed softer immigration rules in western countries suggest the effectiveness of such a mechanism.info:eu-repo/semantics/publishedVersio

Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth

BACKGROUND: An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease. METHODS: In a large case-control study nested in the populations of Denmark, Norway, Sweden, and Finland of 4.4 million children, we studied the association of birth order and seasonal variation of birth with subsequent risk for CNS tumours. We identified 3983 children from the national cancer registries, and information on exposure was obtained from the high-quality national administrative health registries. We investigated the association between childcare attendance during the first 2 years of life and the risk for CNS tumours in a subset of Danish children with CNS tumours, using information from the Danish Childcare database. RESULTS: We observed no association between birth order and risk of CNS tumours overall (odds ratio (OR) for second born or later born vs first born, 1.03; 95% confidence interval (CI), 0.96-1.10) or by histological subgroup, and children with CNS tumours did not show a seasonal variation of birth that was distinct from that of the background population. Childcare attendance compared with homecare showed a slightly increased OR (1.29; 95% CI, 0.90-1.86) for CNS tumours, with the highest risk observed in children attending a crèche. The strongest association was observed for embryonal CNS tumours. We found no effect of age at enrolment or duration of enrolment in childcare. CONCLUSION: These results do not support the hypothesis that the burden of exposure to infectious disease in early childhood has an important role in the aetiology of paediatric CNS tumours