The Complexity of Routing with Few Collisions

We study the computational complexity of routing multiple objects through a network in such a way that only few collisions occur: Given a graph $G$ with two distinct terminal vertices and two positive integers $p$ and $k$, the question is whether one can connect the terminals by at least $p$ routes (e.g. paths) such that at most $k$ edges are time-wise shared among them. We study three types of routes: traverse each vertex at most once (paths), each edge at most once (trails), or no such restrictions (walks). We prove that for paths and trails the problem is NP-complete on undirected and directed graphs even if $k$ is constant or the maximum vertex degree in the input graph is constant. For walks, however, it is solvable in polynomial time on undirected graphs for arbitrary $k$ and on directed graphs if $k$ is constant. We additionally study for all route types a variant of the problem where the maximum length of a route is restricted by some given upper bound. We prove that this length-restricted variant has the same complexity classification with respect to paths and trails, but for walks it becomes NP-complete on undirected graphs

Estimating the Survival of Patients With Lung Cancer: What Is the Best Statistical Model?

Objectives: Investigating the survival of patients with cancer is vitally necessary for controlling the disease and for assessing treatment methods. This study aimed to compare various statistical models of survival and to determine the survival rate and its related factors among patients suffering from lung cancer. Methods: In this retrospective cohort, the cumulative survival rate, median survival time, and factors associated with the survival of lung cancer patients were estimated using Cox, Weibull, exponential, and Gompertz regression models. Kaplan-Meier tables and the log-rank test were also used to analyze the survival of patients in different subgroups. Results: Of 102 patients with lung cancer, 74.5% were male. During the follow-up period, 80.4% died. The incidence rate of death among patients was estimated as 3.9 (95% confidence [CI], 3.1 to 4.8) per 100 person-months. The 5-year survival rate for all patients, males, females, patients with non-small cell lung carcinoma (NSCLC), and patients with small cell lung carcinoma (SCLC) was 17%, 13%, 29%, 21%, and 0%, respectively. The median survival time for all patients, males, females, those with NSCLC, and those with SCLC was 12.7 months, 12.0 months, 16.0 months, 16.0 months, and 6.0 months, respectively. Multivariate analyses indicated that the hazard ratios (95% CIs) for male sex, age, and SCLC were 0.56 (0.33 to 0.93), 1.03 (1.01 to 1.05), and 2.91 (1.71 to 4.95), respectively. Conclusions: Our results showed that the exponential model was the most precise. This model identified age, sex, and type of cancer as factors that predicted survival in patients with lung cancer

Global Air Quality and COVID-19 Pandemic : Do We Breathe Cleaner Air?

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has challenged most countries worldwide. It was quickly recognized that reduced activities (lockdowns) during the Coronavirus Disease of 2019 (COVID-19) pandemic produced major changes in air quality. Our objective was to assess the impacts of COVID-19 lockdowns on groundlevel PM2.5, NO2, and O-3 concentrations on a global scale. We obtained data from 34 countries, 141 cities, and 458 air monitoring stations on 5 continents (few data from Africa). On a global average basis, a 34.0% reduction in NO2 concentration and a 15.0% reduction in PM2.5 were estimated during the strict lockdown period (until April 30, 2020). Global average O-3 concentration increased by 86.0% during this same period. Individual country and continent-wise comparisons have been made between lockdown and business-as-usual periods. Universally, NO2 was the pollutant most affected by the COVID-19 pandemic. These effects were likely because its emissions were from sources that were typically restricted (i.e., surface traffic and non-essential industries) by the lockdowns and its short lifetime in the atmosphere. Our results indicate that lockdown measures and resulting reduced emissions reduced exposure to most harmful pollutants and could provide global-scale health benefits. However, the increased O-3 may have substantially reduced those benefits and more detailed health assessments are required to accurately quantify the health gains. At the same, these restrictions were obtained at substantial economic costs and with other health issues (depression, suicide, spousal abuse, drug overdoses, etc.). Thus, any similar reductions in air pollution would need to be obtained without these extensive economic and other consequences produced by the imposed activity reductions.Peer reviewe

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Whole exome sequencing of a consanguineous family identifies the possible modifying effect of a globally rare AK5 allelic variant in celiac disease development among Saudi patients.

Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small intestine, is known to occur in both sporadic and familial forms. Together HLA and Non-HLA genes can explain up to 50% of CD's heritability. In order to discover the missing heritability due to rare variants, we have exome sequenced a consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern. We have identified a rare homozygous insertion c.1683_1684insATT, in the conserved coding region of AK5 gene that showed classical AR model segregation in this family. Sequence validation of 200 chromosomes each of sporadic CD cases and controls, revealed that this extremely rare (EXac MAF 0.000008) mutation is highly penetrant among general Saudi populations (MAF is 0.62). Genotype and allelic distribution analysis have indicated that this AK5 (c.1683_1684insATT) mutation is negatively selected among patient groups and positively selected in the control group, in whom it may modify the risk against CD development [p<0.002]. Our observation gains additional support from computational analysis which predicted that Iso561 insertion shifts the existing H-bonds between 400th and 556th amino acid residues lying near the functional domain of adenylate kinase. This shuffling of amino acids and their H-bond interactions is likely to disturb the secondary structure orientation of the polypeptide and induces the gain-of-function in nucleoside phosphate kinase activity of AK5, which may eventually down-regulates the reactivity potential of CD4+ T-cells against gluten antigens. Our study underlines the need to have population-specific genome databases to avoid false leads and to identify true candidate causal genes for the familial form of celiac disease

Whole exome sequencing of a consanguineous family identifies the possible modifying effect of a globally rare <i>AK5</i> allelic variant in celiac disease development among Saudi patients - Fig 3

<p>(A) Nucleotide sequence Alignment of human and primate adenylate kinase 5 genes. (B) Phylogenetic tree of the human adenylate kinases.</p

Genotype and allelic distribution of <i>AK5</i>,c.1683_1684insATT variant between celiac sporadic patients and controls, as well as their risk prediction for celiac disease.

<p>Genotype and allelic distribution of <i>AK5</i>,c.1683_1684insATT variant between celiac sporadic patients and controls, as well as their risk prediction for celiac disease.</p