A Redesigned Benders Decomposition Approach for Large-Scale In-Transit Freight Consolidation Operations

The growth in online shopping and third party logistics has caused a revival of interest in finding optimal solutions to the large scale in-transit freight consolidation problem. Given the shipment date, size, origin, destination, and due dates of multiple shipments distributed over space and time, the problem requires determining when to consolidate some of these shipments into one shipment at an intermediate consolidation point so as to minimize shipping costs while satisfying the due date constraints. In this paper, we develop a mixed-integer programming formulation for a multi-period freight consolidation problem that involves multiple products, suppliers, and potential consolidation points. Benders decomposition is then used to replace a large number of integer freight-consolidation variables by a small number of continuous variables that reduces the size of the problem without impacting optimality. Our results show that Benders decomposition provides a significant scale-up in the performance of the solver. We demonstrate our approach using a large-scale case with more than 27.5 million variables and 9.2 million constraints

Nonperturbative dynamics of reheating after inflation: A review

Our understanding of the state of the universe between the end of inflation and big bang nucleosynthesis (BBN) is incomplete. The dynamics at the end of inflation are rich and a potential source of observational signatures. Reheating, the energy transfer between the inflaton and Standard Model fields (possibly through intermediaries) and their subsequent thermalization, can provide clues to how inflation fits in with known high-energy physics. We provide an overview of our current understanding of the nonperturbative, nonlinear dynamics at the end of inflation, some salient features of realistic particle physics models of reheating, and how the universe reaches a thermal state before BBN. In addition, we review the analytical and numerical tools available in the literature to study preheating and reheating and discuss potential observational signatures from this fascinating era.Kavli Institute for Cosmology, CambridgeUnited States. Dept. of Energy (Contract Number DE-SC00012567)Massachusetts Institute of Technology. Center for Theoretical Physic

Cystic tumor of the atrioventricular node of the heart appears to be the heart equivalent of the solid cell nests (ultimobranchial rests) of the thyroid

We studied a series of 10 solid cell nests (SCNs) of the thyroid and a case of cystic tumor of the atrioventricular node (CTAVN) of the heart and reviewed the literature. The CTAVN and SCNs appeared as cystic and/or solid (squamoid) structures mainly composed of polygonal or oval cells (main cells) admixed with occasional clear cells (neuroendocrine and C cells). Main cells were immunoreactive for simple and stratified epithelial-type cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. Neuroendocrine (and C) cells were positive for simple-type cytokeratins, carcinoembryonic antigen, calcitonin, chromogranin, synaptophysin, and thyroid transcription factor-1. Our data support the hypothesis that the CTAVN of the heart and the SCNs of the thyroid are identical structures that represent the same lesional process. The assumption that CTAVN is a ultimobranchial heterotopia fits with the known role of cardiac neural crest cells in cardiovascular development

Relationship between antimicrobial prescribing and antimicrobial resistance among UTI patients at Buraidah Central Hospital, Saudi Arabia

Most of the decisions regarding diagnosis and treatment are based on laboratory test results. Urinary tract infections (UTIs) are among the most common infections in humans. The changing antimicrobial sensitivity in UTI requires appropriate antibiotics. Antimicrobial resistance is an emerging problem in the Kingdom of Saudi Arabia where the complete reversal of antimicrobial resistance is difficult due to irrational use of antibiotics. Objectives: This study aimed to determine the most common bacterial agents causing UTI in different seasons among patients who were admitted to Buraidah Central Hospital (BCH), Saudi Arabia. The study also evaluated the link between prescribing and resistance toward antimicrobials. Materials and Methods: A 6-month retrospective study was conducted among adult patients who were admitted to the inpatient department at BCH. A total of 379 files were collected from microbiological laboratory for inpatients. Results: Most UTI-causing bacteria prevailed in the same season. Of 15 bacterial strains, 12 were significantly correlated with 20 (of a total of 40) antibiotics that were used. Most bacteria were gram-negative. Gram-negative bacilli including Escherichia coli, Klebsiella spp., and Pseudomonadaceae and gram-positive Enterococcus faecalis were most frequently causing UTIs. Conclusion: Overall prevalence of antibiotic resistance was negative in bacterial isolates. However, the relationship between antimicrobial prescribing and antimicrobial resistance was significantly negative among UTI patients in BCH, Saudi Arabia

Future of Management of Multiple Sclerosis in the Middle East: A Consensus View from Specialists in Ten Countries

The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high in the Middle East and is rising, particularly among women. While the characteristics of the disease and the response of patients to disease-modifying therapies are generally comparable between the Middle East and other areas, significant barriers to achieving optimal care for MS exist in these developing nations. A group of physicians involved in the management of MS in ten Middle Eastern countries met to consider the future of MS care in the region, using a structured process to reach a consensus. Six key priorities were identified: early diagnosis and management of MS, the provision of multidisciplinary MS centres, patient engagement and better communication with stakeholders, regulatory body education and reimbursement, a commitment to research, and more therapy options with better benefit-to-risk ratios. The experts distilled these priorities into a single vision statement: “Optimization of patient-centred multidisciplinary strategies to improve the quality of life of people with MS.” These core principles will contribute to the development of a broader consensus on the future of care for MS in the Middle East

The barriers, motives, perceptions, and attitudes toward research among radiology practitioners and interns in Saudi Arabia: a cross-sectional study

BackgroundResearch and the use of evidence-based practices are imperative to the advancement of diagnostic imaging modalities. The aim of this study was to assess the perceptions and attitudes of radiology practitioners (i.e., Technicians, Technologists or Specialists, and Senior Specialists) and interns in King Abdulaziz Medical Cities (KAMCs), Kingdom of Saudi Arabia, toward research, and to explore the various barriers and obstacles that hinder their research efforts.MethodsA cross-sectional descriptive investigation was carried out from December 2022 to March 2023 among 112-KAMCs’ radiology practitioners and interns, using previously developed and validated questionnaire comprised of five distinct sections, each serving a specific purpose, and with a non-probability convenient sampling technique. Descriptive statistics were generated for participants’ demographics, and chi-square and fisher’s exact tests were used to examine the association between participants’ demographics and their involvement in research.ResultsAmong the 137 KAMCs’ radiology practitioners and interns who were invited to participate, 112 responded and completed the questionnaire, resulting in an overall response rate of 81.75%. Radiology practitioners and interns from various medical imaging subspecialties were found to be involved in research to the extent of 83%, with nearly half (40.9%) of them have had publications, and 53.3% of these publications being either cross-sectional studies or retrospective clinical studies. A lack of time (66.1%), a lack of a professional supervisor support program (50.9%), and deficiency in research skills (45.5%) were common obstacles that may impede the participants’ ability to conduct research. The most common motives for participants to conduct research were the desire to improve their resumes (69.6%), get accepted into postgraduate radiology programs (58%), and improve their research skills (52.7%).ConclusionKAMCs’ radiology practitioners and interns have a positive attitude toward performing research. Despite the high percentage (83%) of those involved in research, the number of publications remains low. A crucial step to advancing the profession’s evidence base is engaging radiology practitioners and interns in research and encouraging radiology practitioner-led research. The study findings can serve as a valuable basis for designing developmental programs aimed at overcoming research obstacles among healthcare professionals in Saudi Arabia

Control of the Intracellular Redox State by Glucose Participates in the Insulin Secretion Mechanism

Background: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. Methodology/Principal Findings: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. Conclusions: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazi

Cten Is Targeted by Kras Signalling to Regulate Cell Motility in the Colon and Pancreas

CTEN/TNS4 is an oncogene in colorectal cancer (CRC) which enhances cell motility although the mechanism of Cten regulation is unknown. We found an association between high Cten expression and KRAS/BRAF mutation in a series of CRC cell lines (p = 0.03) and hypothesised that Kras may regulate Cten. To test this, Kras was knocked-down (using small interfering (si)RNA) in CRC cell lines SW620 and DLD1 (high Cten expressors and mutant for KRAS). In each cell line, Kras knockdown was mirrored by down-regulation of Cten Since Kras signals through Braf, we tested the effect of Kras knockdown in CRC cell line Colo205 (which shows high Cten expression and is mutant for BRAF but wild type for KRAS). Cten levels were unaffected by Kras knockdown whilst Braf knockdown resulted in reduced Cten expression suggesting that Kras signals via Braf to regulate Cten. Quantification of Cten mRNA and protein analysis following proteasome inhibition suggested that regulation was of Cten transcription. Kras knockdown inhibited cell motility. To test whether this could be mediated through Cten, SW620 cells were co-transfected with Kras specific siRNAs and a Cten expression vector. Restoring Cten expression was able to restore cell motility despite Kras knockdown (transwell migration and wounding assay, p<0.001 for both). Since KRAS is mutated in many cancers, we investigated whether this relationship could be demonstrated in other tumour models. The experiments were repeated in the pancreatic cancer cell lines Colo357 & PSN-1(both high Cten expressors and mutant for KRAS). In both cell lines, Kras was shown to regulate Cten and forced expression of Cten was able to rescue loss of cell motility following Kras knockdown in PSN-1 (transwell migration assay, p<0.001). We conclude that, in the colon and pancreas, Cten is a downstream target of Kras and may be a mechanism through which Kras regulates of cell motility

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

This online publication has been corrected. The corrected version first appeared at thelancet.com on June 20, 2019BACKGROUND:Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. METHODS:We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10-54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10-14 years and 50-54 years was estimated from data on fertility in women aged 15-19 years and 45-49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. FINDINGS:From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4-52·0). The TFR decreased from 4·7 livebirths (4·5-4·9) to 2·4 livebirths (2·2-2·5), and the ASFR of mothers aged 10-19 years decreased from 37 livebirths (34-40) to 22 livebirths (19-24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3-200·8) since 1950, from 2·6 billion (2·5-2·6) to 7·6 billion (7·4-7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15-64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9-1·2) in Cyprus to a high of 7·1 livebirths (6·8-7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07-0·09) in South Korea to 2·4 livebirths (2·2-2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3-0·4) in Puerto Rico to a high of 3·1 livebirths (3·0-3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. INTERPRETATION:Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. FUNDING:Bill & Melinda Gates Foundation.Christopher J L Murray ... Azmeraw T Amare ... Habtamu Abera Areri ... Peter S Azzopardi ... Bernhard T Baune ... Liliana G Ciobanu ... Garumma Tolu Feyissa ... Tiffany K Gill ... Ratilal Lalloo ... Zohra S Lassi ... Jean Jacques Noubiap ... Andrew T Olagunju ... Engida Yisma ... et al. (GBD 2017 Population and Fertility Collaborators