Network Design for the Traffic Assignment Problem with Mixed-Integer Frank-Wolfe

We tackle the network design problem for centralized traffic assignment, which can be cast as a mixed-integer convex optimization (MICO) problem. For this task, we propose different formulations and solution methods in both a deterministic and a stochastic setting in which the demand is unknown in the design phase. We leverage the recently proposed Boscia framework, which can solve MICO problems when the main nonlinearity stems from a differentiable objective function. Boscia tackles these problems by branch-and-bound with continuous relaxations solved approximately with Frank-Wolfe algorithms. We compare different linear relaxations and the corresponding subproblems solved by Frank-Wolfe, and alternative problem formulations to identify the situations in which each performs best. Our experiments evaluate the different approaches on instances from the Transportation Networks library and highlight the suitability of the mixed-integer Frank-Wolfe algorithm for this problem. In particular, we find that the Boscia framework is particularly applicable to this problem and that a mixed-integer linear Frank-Wolfe subproblem performs well for the deterministic case, while a penalty-based approach, with decoupled feasible regions for the design and flow variables, dominates other approaches for stochastic instances with many scenarios

Emerging topics in FXTAS

This paper summarizes key emerging issues in fragile X-associated tremor/ataxia syndrome (FXTAS) as presented at the First International Conference on the FMR1 Premutation: Basic Mechanisms & Clinical Involvement in 2013

Epidemiologic and Environmental Investigation of a Recreational Water Outbreak Caused by Two Genotypes of Cryptosporidium Parvum in Ohio in 2000

In August 2000, the Ohio Department of Health requested assistance to investigate a cryptosporidiosis outbreak with more than 700 clinical case-patients. An epidemiologic and environmental investigation was conducted. Stool specimens, pool water, and sand filter samples were analyzed. A community-based case-control study showed that the main risk factor was swimming in pool A (odds ratio [OR] = 42, 95% confidence interval [CI] = 12.3-144.9). This was supported by results of polymerase chain reaction (PCR) analysis, which showed the presence of both the human and bovine genotypes of Cryptosporidium parvum in case-patients and samples from the filter of pool A. A pool-based case-control study indicated that the highest risk was related to exposure to pool water via the mouth (OR = 5.1, 95% CI = 2.1-12.5) or to pool sprinklers (OR = 2.5, 95% CI = 1.3-4.7). Fecal accidents at the pool were documented. Records indicated that the pool met local health regulations. The outbreak, caused by co-infection with two C. parvum genotypes (human and bovine), underscores the need for concerted action to improve public health policies for recreational water facilities and enhanced education regarding the potential for disease transmission through pools

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1

peer reviewedThe incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitute an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for Magnetic Resonance Imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity towards gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease of TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1 targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate recognition domain of gal-1. Keywords: galectin-1, thyroid cancer, peptides, diagnosis, ultrasmall superparamagnetic particles of iron oxide, phage displa

Advances in ecotechnological methods for diffuse nutrient pollution control: wicked issues in agricultural and urban watersheds

Considerable time and funding have been committed to tackling nonpoint source (NPS) pollution in agricultural and urban watersheds . Notwithstanding all these efforts, the water quality in many AUWs has not significantly improved. Diffuse nutrient pollution involves the movement of these pollutants between soil and water. Excessive diffuse pollution has been accepted as one of the main causes of failure to attain favorable environmental conditions in freshwater systems. Recently, several technologies and practices have been implemented to manage diffuse pollution, namely: a) source reduction, b) pollutant retention over the movement process; c) nutrient recycling, and d) purification and restoration of the eutrophic water bodies. This paper synthesized the existing knowledge of key methods to tackle diffuse pollution from AUWs. Furthermore, the predominant purification mechanisms and impacting factors are explored, allowing a comprehensive and critical understanding of different control strategies to improve the management of diffuse pollution. Therefore, potential approaches for strengthening the performance of control technologies for diffuse pollution treatment and remediation are discussed. Although adopting source reduction strategies (e.g., the “4R” approach: right rate, right time, right source, and right placement of nutrients) could efficiently decrease surface runoff and pollutant levels, they may not stop runoff from entering nearby streams. Consequently, comprehensive treatment of agricultural runoff still requires extra process retention strategies. Overall, the findings of this paper showed that treatment system design and operational and environmental factors played crucial but variable roles in diffuse pollution treatment. Moreover, the results showed that combining or integrating constructed wetlands with other control technologies could enhance the comprehensive purification of diffuse pollution compared to using a single method. This review proposes a systematic approach for diffuse pollution control based on three components (water, soil and microbiota) and maximizing the regulating services of agroecosystems via land use/cover types. The current review contributes to the documentation of existing research trends. It sheds light on diffuse pollution control approaches in AUWs, and further encourages the development of this vital field

A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants

Background The red junglefowl, the wild outgroup of domestic chickens, has historically served as a reference for genomic studies of domestic chickens. These studies have provided insight into the etiology of traits of commercial importance. However, the use of a single reference genome does not capture diversity present among modern breeds, many of which have accumulated molecular changes due to drift and selection. While reference-based resequencing is well-suited to cataloging simple variants such as single-nucleotide changes and short insertions and deletions, it is mostly inadequate to discover more complex structural variation in the genome. Methods We present a pangenome for the domestic chicken consisting of thirty assemblies of chickens from different breeds and research lines. Results We demonstrate how this pangenome can be used to catalog structural variants present in modern breeds and untangle complex nested variation. We show that alignment of short reads from 100 diverse wild and domestic chickens to this pangenome reduces reference bias by 38%, which affects downstream genotyping results. This approach also allows for the accurate genotyping of a large and complex pair of structural variants at the K feathering locus using short reads, which would not be possible using a linear reference. Conclusions We expect that this new paradigm of genomic reference will allow better pinpointing of exact mutations responsible for specific phenotypes, which will in turn be necessary for breeding chickens that meet new sustainability criteria and are resilient to quickly evolving pathogen threats

2022 Canadian Cardiovascular Society Guideline for Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction in Adults

This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients with routine measurement of estimated glomerular filtration rate, urinary albumin-creatinine ratio, glycosylated hemoglobin (A1c), and documentation of left ventricular ejection fraction (LVEF) when evaluating symptoms of HF. For patients with HF, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy for the reduction of hospitalization for HF when LVEF is \u3e 40% and for the reduction of all-cause and CV mortality, hospitalization for HF, and renal protection when LVEF is ≤ 40%. In patients with albuminuric chronic kidney disease, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy to reduce all-cause and CV mortality, nonfatal myocardial infarction, and hospitalization for HF. We provide recommendations and algorithms for the selection of glucagon-like peptide-1 receptor agonists and SGLT2i for patients with type 2 diabetes and either established atherosclerotic CV disease or risk factors for atherosclerotic CV disease to reduce all-cause and CV mortality, nonfatal stroke, and for the prevention of hospitalization for HF and decline in renal function. We offer practical advice for safe use of these diabetes-associated agents with profound cardiorenal benefits

Comparison of empirically derived and model-based estimates of key population HIV incidence and the distribution of new infections by population group in sub-Saharan Africa

Background: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates.Methods: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios.Results: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15–39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15–29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%–11.7%), both much lower than the 25% reported by UNAIDS.Conclusion: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.</div

Measuring HIV acquisitions among partners of key populations: estimates from HIV transmission dynamic models

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models.SETTING: One hundred seventy-eight settings (106 countries).METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020.RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29).CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.</p