In this paper we address the problem faced by a company that needs to decide the number and location of facilities to close in order to reduce the size of their retail distribution network, whilst ...minimising the market share that is lost to their competitor, who is also engaged in a network reduction process. The problem is modelled as a bilevel competitive delocation model and is formulated as a variant of the well-known (r|p)-centroid problem. The formulation takes into account the existence of a certain level of customer loyalty, which implies that customers may decide to visit a more distant facility of their regular provider rather than rely on a closer competitor’s facility. A depth-first search implicit enumeration algorithm is proposed for solving a diverse set of instances of the problem. The analysis of an instance based on a real-life setting, and intensive numerical experimentation, provide evidence of the effectiveness of the algorithm for the solution of real-size problems, and confirm the practical validity of our modelling approach. Our results also highlight the importance of considering spatial loyalty in network restructuring scenarios.
•A novel competitive delocation problem is studied.•Spatially loyalty customers are considered in the model.•A bi-level programming formulation is proposed inspired in the (r|p)-centroid problem.•An exact depth-first search implicit enumeration algorithm is proposed.•Extensive computational experimentation is performed to validate our approach.
Summary
Background
There are few data on corticosteroids (CS)‐sparing strategies for checkpoint inhibitor (ICI)‐induced liver injury (ChILI).
Aim
We aimed to assess the performance of a 2‐step ...algorithm for severe ChILI, based on ICI temporary discontinuation (step‐1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step‐2).
Methods
Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening.
Results
From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti‐PD1, 8(18.2%) anti‐PD‐L1, 3(6.8%) anti‐CTLA‐4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step‐1) and 8/22 (36.4%) based on the degree of necroinflammation (step‐2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non‐improvement patients after ICI discontinuation. CD8+ HLA‐DR expression (p = 0.028), central memory (p = 0.046) were lower in CS‐free managed subjects, but effector‐memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS‐free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed.
Conclusions
An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.
A 2‐step algorithm based on immunotherapy temporary discontinuation and liver biopsy allowed a corticosteroid‐free management in two thirds of cases of severe checkpoint inhibitor‐induced liver injury.
To explore the perceptions that Colombians have about voluntary private health insurance plans (VPHI) in the health system to identify the tensions that exist between the public and private systems.
...A qualitative case study approach with 46 semi structured interviews of patients, healthcare workers, healthcare administrators, decision-makers, and citizens. Interviews were recorded, transcribed, anonymized, digitally stored, and analyzed following grounded theory guidelines.
We developed a paradigmatic matrix that explores how, in a context mediated by both the commodification of health and social stratification, perceptions about the failures in the public health system related to lack of timely care, extensive administrative procedures, and the search for privileged care led to positioning VPHI as a solution to these failures. The interviewees identified three consequences of using VPHI: first, the worsening of problems of timely access to care in the public system; second, higher costs for citizens translated into double payment for technologies and services to which they are entitled; third, the widening of inequity gaps in access to health services between people with similar needs but different payment capacities.
These findings can help decision makers to understand citizens´ perceptions about the implications that VPHI may have in worsening equity gaps in the Colombian health system. It also shows, how VPHI is perceived as a double payment for services covered within social security plans and suggests that the perceived lack of timely access to care in the public systems and the fear that citizens have for themselves or their family members when using suboptimal healthcare are important drivers to purchase these private insurances.
SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes ...Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico.
Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done.
Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus.
Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients.
IceCube is a cubic kilometer neutrino detector located at the south pole. IceProd is IceCube’s internal dataset management system, keeping track of where, when, and how jobs run. It schedules jobs ...from submitted datasets to HTCondor, keeping track of them at every stage of the lifecycle. Many updates have happened in the last years to improve stability and scalability, as well as increase user access. Along the way, the IceProd codebase switched from Python 2 to Python 3.
Background and objective
TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of ...progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d.
Methods
We studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in
TK2
, 9 with mutations in other nuclear genes involved in mitochondrial DNA mtDNA synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics.
Results
We found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the
gluteus maximus
,
gastrocnemius medialis
, and
sartorius
muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features.
Conclusions
By analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.
Background
The coronavirus disease 2019 (COVID-19) pandemic has been a worldwide stress test for health systems. 2 years have elapsed since the description of the first cases of pneumonia of unknown ...origin. This study quantifies the impact of COVID-19 in the screening program of chronic viral infections such as human papillomavirus (HPV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) along the six different pandemic waves in our population. Each wave had particular epidemiological, biological, or clinical patterns.
Methods
We analyzed the number of samples for screening of these viruses from March 2020 to February 2022, the new infections detected in the pandemic period compared to the previous year, the time elapsed between diagnosis and linking to treatment and follow-up of patients, and the percentage of late HIV diagnosis. Moreover, we used the origin of the samples as a marker for quantifying the restoration of activity in primary care.
Results
During the first pandemic year, the number of samples received was reduced by 26.7, 22.6, and 22.5% for molecular detection of HPV or serological HCV and HIV status respectively. The highest decrease was observed during the first wave with 70, 40, and 26.7% for HPV, HCV, and HIV. As expected, new diagnoses also decreased by 35.4, 58.2, and 40.5% for HPV, HCV, and HIV respectively during the first year of the pandemic. In the second year of the pandemic, the number of samples remained below pre-pandemic period levels for HCV (−3.6%) and HIV (−9.3%) but was slightly higher for HPV (8.0%). The new diagnoses in the second year of the pandemic were −16.1, −46.8, and −18.6% for HPV, HCV, and HIV respectively.
Conclusions
Undoubtedly, an important number of new HPV, HCV, and HIV infections were lost during the COVID-19 pandemic, and surveillance programs were disrupted as a consequence of collapse of the health system. It is a priority to reinforce these surveillance programs as soon as possible in order to detect undiagnosed cases before the associated morbidity-mortality increases. New pandemic waves could increase the risk of reversing the achievements made over the last few decades.
Missed opportunities for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) testing remain high. We aimed to ascertain the knowledge of screening guidelines and attitudes of ...non-infectious disease (ID) hospital physicians and assess the impact of a 1-h session on screening rates and diagnoses.
This interventional study consisted of a 1-h training session on HIV and HCV epidemiology and testing guidelines for non-ID physicians. Pre-and post-session questionnaires compared the knowledge of the guidelines and attitudes toward screening before and after the session. Rates of screening and diagnoses were compared in three 6 months periods: before, immediately after, and 24 months ±4 after the session.
A total of 345 physicians from 31 departments participated in these sessions. Before the session, 19.9% (28% medical, 8% surgical) and 17.9% (30% medical, 2.7% surgical) were aware of HIV and HCV testing guidelines, respectively. The willingness to routinely test increased from 5.6 to 22%, whereas not ordering tests decreased from 34.1 to 2.4%. HIV screening rates significantly increased by 20% after the session (7.7 vs. 9.3 tests per 103 patients;
< 0.001), and the effect persisted until the long-term period. The HIV diagnosis rate increased globally (3.6 vs. 5.2 HIV diagnoses per 105 patients;
= 0.157), mainly because of medical services (4.7 vs. 7.7 per 105 patients;
= 0.082). The HCV screening rate increased significantly immediately and in the long term only in medical services (15.7 and 13.6%, respectively). The new active HCV infection rates increased immediately and declined steeply thereafter.
A short session for non-ID physicians can improve HIV/HCV screening, increase diagnosis, and contribute to disease elimination.
IceCube--a neutrino telescope that encompasses a cubic kilometer of Antarctic ice at the South Pole, collecting and processing data from 5,160 optical sensors buried a mile deep in the ...icecap--presents considerable challenges, from overcoming power and bandwidth limitations to simulating the complexities of Antarctic ice, which continue to stretch computing technology. The Web extra at http://youtu.be/ht0e6m6lpz0 is a video simulation of a visualization of the highest energy neutrino ever detected. The 2-PeV neutrino event was detected on Tuesday, 4 December 2012, by the IceCube Neutrino Observatory, a particle-detector telescope buried 1,500 meters deep in the ice at the South Pole. The neutrino was dubbed "Big Bird."
The High-Altitude Water Cherenkov (HAWC) TeV gamma–ray Observatory in México is ready to search and study gamma-ray emission regions, extremely high-energy cosmic-ray sources, and to identify ...transient phenomena. With a better Gamma/Hadron rejection method than other similar experiments, it will play a key role in triggering multi–wavelength and multi–messenger studies of active galaxies (AGN), gamma-ray bursts (GRB), supernova remnants (SNR), pulsar wind nebulae (PWN), Galactic Plane Sources, and Cosmic Ray Anisotropies. It has an instantaneous field-of-view of ∼2 str, equivalent to 15% of the whole sky and continuous operation (24 hours per day). The results obtained by HAWC–111 (111 detectors in operation) were presented on the proceedings of the International Cosmic Ray Conference 2015 and in 1. The results obtained by HAWC–300 (full operation) are now under analysis and will be published in forthcoming papers starting in 2017 (see preliminary results on http://www.hawc-observatory.org/news/). Here we present the HAWC contributions on cosmic ray astrophysics via anisotropies studies, summarizing the HAWC detector and its upgrading by the installation of “outriggers”.
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