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Recently proved successful for variants of the vehicle routing problem (VRP) involving time windows, genetic algorithms have not yet shown to compete or challenge current best search techniques in solving the classical capacitated VRP. A new hybrid genetic algorithm to address the capacitated VRP is proposed. The basic scheme consists in concurrently evolving two populations of solutions to minimize total travelled distance using genetic operators combining variations of key concepts inspired from routing techniques and search strategies used for a time variant of the problem to further provide search guidance while balancing intensification and diversification. Results from a computational experiment over common benchmark problems report the proposed approach to be very competitive with the best-known methods. Keywords: vehicle routing problems; heuristics

Many heuristics and meta-heuristics problem-solving methods have been proposed so far to solve the NP-hard multi-satellite collection scheduling problem (m-SatCSP). In particular, genetic algorithms (GAs), well-suited for large scale problems, its simplicity and low cost implementation have been pervasive. However, most contributions largely emphasise simple variant or basic GA principles promotion, overlooking prior problem structure exploitation or potential problem-solving benefits that may be conveyed from similar combinatorial optimisation problems such as the vehicle routing problem with time windows (VRPTW). In fact, despite some recognised similarity with VRPTW and early investigation on limited exact methods, few efforts have been successfully reported to adapt efficient advanced special-purpose problem-solving techniques to m-SatCSP. In this paper, a VRPTW-based hybrid genetic algorithm is proposed to tackle the single objective static m-SatCSP. The advocated approach combines and adapts well-known routing heuristics knowledge with standard genetic operator principles to efficiently explore promising search regions, manage constraint handling and improve solution quality. The hybrid strategy co-evolves two populations of solution plan individuals, maximising expected collection value while concurrently densifying collection paths to minimise orbit demand. Computational results show the approach to be cost-effective and competitive in comparison to some recent methods inspired from the best reported m-SatCSP heuristics. [ABSTRACT FROM AUTHOR]

Abstract Background Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions. Methods A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response. Results The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events. Conclusion VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.

Background: Morocco faces a substantial public health challenge due to diabetes mellitus, affecting 12.4% of adults in 2023. The Moroccan population makes extensive use of phytotherapy and traditional medicine to address the difficulties this chronic condition poses. The aim of this study is to document the use of medicinal plants in traditional medicine for managing type 2 diabetes in the provinces of the Casablanca-Settat region., Methods: The study employed a semi-structured questionnaire for data collection. A study was conducted between August 1st and September 30th, 2023, and 244 individuals diagnosed with diabetes were invited to take part in the research, all of whom used at least one medicinal plant to manage type 2 diabetes, by visiting primary healthcare facilities in Morocco. The analysis included the use of Relative Frequency of Citation (RFC) to scrutinize the data., Results: A total of 47 plant species belonging to 25 families were documented. Notably, the Apiaceae, Lamiaceae, and Fabaceae families were frequently mentioned in the context of treating type 2 diabetes in Morocco. Prominent among the cited plant species were Sesamum indicum L., Lepidium sativum L., followed by Foeniculum vulgare Mill., and Rosmarinus officinalis L. Seeds emerged as the plant part most commonly mentioned, with infusion being the prevailing preparation method and oral consumption being the most frequently depicted method of administration., Conclusion: This research underscores the practicality of incorporating traditional medicine into the healthcare framework of the Casablanca-Settat region. The findings not only offer valuable documentation but also have a vital function in safeguarding knowledge regarding the utilization of medicinal plants in this locality. Moreover, they provide opportunities to delve deeper into the phytochemical and pharmacological potential of these plants., (© 2024. The Author(s).)

Different tests are used to evaluate the aerobic capacity of a person. This study aims to investigate the gender and Body Mass Index (BMI) difference in aerobic capacity measured by using shuttle and Spartacus test. The study was conducted on 230 high school students (135 girls and 95 boys) followed their study in public establishment in kenitra city (Morocco). All participants were classified according to their gender (male vs. female) and their BMI (normal weight vs. overweight-obese) and performed the both test of shuttle and Spartacus. Running speed at the last completed stage, run time, maximum heart rate (max HR) max HR and perceived exertion were measured and analyzed. For each test, VO2max was estimated by using the proposed equation. There was significant BMI difference in the measured parameters (p<0.001). Difference in VO2max between male and female remained significant with high-speed level in boys. A significant difference between males and females (p < 0.001) was observed in shuttle test. Participants with normal weight or physical activity had good aerobic capacity. Compared to the Shuttle test, the Spartacus provides a 11.5% higher final speed (11.2 vs. 9.7km/h) and a total test time 2.3 times longer (11.3vs. 4.9 min) (p < 0.001). Our study underlines the interest of the Spartacus test and is preliminary. Indeed, these results must now be replicated in a larger sample of obese adolescents.

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The present study aims to provide a global and regional estimate of the prevalence of COPD based on spirometry according to the two most widely used diagnostic criteria of COPD: fixed ratio (FR) and lower limit of normal (LLN)., Methods: We conducted a systematic review of the literature according to PRISMA guidelines. MEDLINE, Web of Sciences, and Scopus databases were searched to identify studies on the spirometry-based prevalence of COPD in individuals aged 40 years and older. The meta-analysis was performed using MedCalc 19 software., Results: In total, 42 of the 3393 studies reviewed were eligible for inclusion. The overall prevalence of COPD in people aged 40 years and older was 12.64% (95% CI 10.75%-14.65%) and 7.38% (95% CI 5.47% - 9.55%) based on FR and LLN criteria, respectively. By gender, men had a higher prevalence of COPD compared to women (15.47%; 95% CI 12.22%-19.02% for men versus 8.79%; 95% CI 6.94%-10.82% for women). Using the LLN criteria, the prevalence of COPD in both sexes was almost identical (8.67%; 95% CI 8.44%- 8.90% for men and 8.00%; 95% CI 6.42% - 9.73% for women). We reported a high prevalence of COPD among smokers and the elderly by both definitions of airway obstruction. Regional prevalence estimates using the FR definition indicate that the highest COPD prevalence was recorded in the Americas and the lowest was recorded in the Eastern Mediterranean region. Using the LLN definition, the highest prevalence was recorded in the Southeast Asian region and the lowest prevalence was recorded in the American region. The most common COPD stage was stage II, with a prevalence of 50.46%. The results indicate a huge lack of prevalence data in the African and Eastern Mediterranean region. The results were given using a random-effect model due to the high heterogeneity between studies., Conclusion: Results show that the prevalence of COPD differs according to the diagnostic criteria used. In addition, management and prevention strategies targeting risk factors for COPD are certainly needed to reduce the global burden of this chronic respiratory disease., (© 2024. The Author(s).)

Introduction: tuberculosis is a public health problem in Morocco. This study aims to examine the epidemiological profile as well as the evolutionary and diagnostic features of tuberculosis in Settat, Morocco., Methods: we conducted a retrospective descriptive and analytical study of data from the medical records of TB patients managed at the Diagnostic Centre for Tuberculosis and Respiratory Diseases in Settat, Morocco from 1 st January 2015 to 31 December 2019., Results: we identified 1270 cases of tuberculosis. Lung involvement was more common than extrapulmonary involvement. Ganglionic tuberculosis mainly occurred in patients with extrapulmonary tuberculosis. Severe forms included tuberculous meningitis (10 cases) and miliary tuberculosis (10 cases). Diagnosis was bacteriologically confirmed in the majority of patients (84.09%). Extreme ages and female sex were mainly affected by extrapulmonary tuberculosis. Recovery was reported in 35.12% of patients and its rate was higher in pulmonary TB patients than in extrapulmonary TB patients (62.18% vs 0.37%; P<0.001). Patients with pulmonary tuberculosis (19.33% vs 10.81%; P<0.001) were mainly lost to follow-up. Death occurred to almost the same extent in patients with pulmonary and extrapulmonary tuberculosis (2.52% vs. 2.56%)., Conclusion: efforts on all fronts are still needed if the country is to achieve the goal of eliminating TB by 2030., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Mohamed Chahboune et al.)

The Souss region in Morocco is known nationally and internationally for its essential knowledge of traditional herbal medicine and the cultural heritage of nutrition. The endemic species Argania spinosa (L.) Skeels is an important crucial plant used by the local population to treat many diseases and prepare some authentic foods. To identify the therapeutic uses of the Argan tree [Argania spinosa (L.) Skeels] and their benefits in preparing authentic foods, the survey was conducted using semi-structured questionnaires. We have achieved 450 interviews with traditional health practitioners and knowledgeable villagers. In the region of Chtouka Aït Baha and Tiznit (Western Anti-Atlas). In parallel with this survey, we collected some old local manuscripts from conventional practitioners in the region. The data obtained were analyzed using specific ethnobotanical indices such as Use Value (UV), Fidelity Level (FL), and Relative Frequency of Citation (RFC). In parallel, we analyzed the nutritional value of some authentic foods derived the argan oil (Amlou, Tagoulla, and Labsis). All 450 interviewees use the argan oil in food or for the preparation of their authentic foods derived (Amlou, Tagoulla, and Labsis); among them, 100 persons use Argan, in addition to food, in the treatment of various diseases with UV and RFC at 1.94 and 0.22, respectively. Among eight treated diseases by argan tree, the treatment of skin and subcutaneous diseases had a very highly significant value of the FL index (98%). Similarly, the analysis of the manuscripts collected in the study area revealed an ancient therapeutic use of the argan tree. The results also show that the Argan oil extracted from the seed is used to prepare authentic foods with significant nutritional value, especially Amlou.

Background: The somatic BRAF V600E mutation occurs in 38-64% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory BRAF V600E mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for., Procedure: Multicentric retrospective observational study including patients <18 years treated with VMF alone for refractory BRAF V600E mutated LCH in 13 countries between October 1, 2013 and December 31, 2018., Results: Fifty-seven patients: 56% female, median age 2.1 years (0.2-14.6), median treatment duration 4.1 months (1.4-29.7). Forty-one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence., Conclusions: At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow-up is essential to manage CAEs and screen for possible induced skin tumors., (© 2021 Wiley Periodicals LLC.)

Purpose: Off-label use of vemurafenib (VMF) to treat BRAF V600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated., Patients and Methods: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score., Results: LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 ( P < .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAF V600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P < .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAF V600E clone., Conclusion: VMF seemed safe and effective in children with refractory BRAF V600E -positive LCH. Additional studies are needed to find effective maintenance therapy approaches.

An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ-positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses of Ara-C (1 g/m(2) per day) plus cladribine (9 mg/m(2) per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity., (© 2015 by The American Society of Hematology.)

Background: Mediastinal involvement (MI) in Langerhans cell histiocytosis (LCH) has been rarely reported. Here, we describe the clinical, radiological, and biological presentation, and the outcome of childhood LCH with MI., Method: From the French LCH register, which includes 1,423 patients aged less than 18 years, we retrieved the medical charts of patients with mediastinal enlargement detected on chest X-rays., Results: Thirty-seven patients were retrieved, including 18 males; median age of diagnosis was 0.7 years, and median follow-up time was 6.2 years. The prevalence of MI varied with the age at diagnosis, ranging from 7% below 1 year old to less than 1% at >5 years. Thirteen cases (35%) were diagnosed because of MI-related symptoms, including respiratory distress (N = 4), superior venous cava syndrome (N = 2), and/or cough and polypnea (N = 10). CT scans performed in 32 cases at diagnosis showed tracheal compression (N = 5), cava thrombosis (N = 2), and/or calcification (N = 16). All patients presented multi-system disease at LCH diagnosis, and 35/37 were initially treated with vinblastine and corticosteroids. Death occurred in five cases, due to MI (N = 1) or hematological refractory involvement (N = 4). The overall 5-year survival was 87.1%, and immunodeficiency was not detected as a sequel., Conclusions: MI in LCH mainly occurs in young children, and diagnosis was based on CT showing thymus enlargement and calcifications., (© 2013 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.)

Introduction: Childhood Langerhans cell histiocytosis (LCH) is a rare and poorly understood multisystemic disease. The French National Registry of Childhood Hematopoietic Malignancies (NRCH) has recorded LCH cases of all subtypes since 2000. The present study describes the data on LCH collected on a national scale over a 5-year period., Materials and Methods: The cases were children aged less than 15 years, diagnosed with LCH of any type between 2000 and 2004, and residing in mainland France at the time of diagnosis. Completeness was evaluated by capture-recapture after cross-checking against the database compiled by the French Langerhans Cell Histiocytosis Study Group., Results: Two hundred fifty-eight cases of LCH were registered. The completeness of the NRCH was estimated to be 97%. The annual incidence rate was 4.6/10(6) children aged less than 15 years and the sex ratio was 1.2. Bone and skin were the most commonly involved organs at diagnosis. The incidence rate decreased with age from 15.3/10(6) before 1 year to 2.0/10(6) after 10 years. The disease was mainly unifocal (2.6/10(6)) and rarely disseminated (0.6/10(6)), but disseminated forms predominated in infants. The overall 2-year survival rate was 99% (95%CI: [97; 100]). About 30% of the LCH cases were enrolled in a clinical trial at first onset. No case was treated by radiotherapy., Conclusion: This study evidenced the main features of LCH incidence in the overall population and was consistent with previous studies. The NRCH thus appears to be a very promising tool for further elucidation of LCH., ((c) 2008 Wiley-Liss, Inc.)

Background: Langerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas. The present study was designed to further investigate the nature of proliferating cells and the immune mechanisms involved in the LCH granulomas., Methods and Findings: Biopsies (n = 24) and/or blood samples (n = 25) from 40 patients aged 0.25 to 13 y (mean 7.8 y), were studied to identify cells that proliferate in blood and granulomas. We found that the proliferating index of LCs was low ( approximately 1.9%), and we did not observe expansion of a monocyte or dendritic cell compartment in patients. We found that LCH lesions were a site of active inflammation, tissue remodeling, and neo-angiogenesis, and the majority of proliferating cells were endothelial cells, fibroblasts, and polyclonal T lymphocytes. Within granulomas, interleukin 10 was abundant, LCs expressed the TNF receptor family member RANK, and CD4(+) CD25(high) FoxP3(high) regulatory T cells (T-regs) represented 20% of T cells, and were found in close contact with LCs. FoxP3(+) T-regs were also expanded compared to controls, in the blood of LCH patients with active disease, among whom seven out of seven tested exhibited an impaired skin delayed-type hypersensitivity response. In contrast, the number of blood T-regs were normal after remission of LCH., Conclusions: These findings indicate that LC accumulation in LCH results from survival rather than uncontrolled proliferation, and is associated with the expansion of T-regs. These data suggest that LCs may be involved in the expansion of T-regs in vivo, resulting in the failure of the host immune system to eliminate LCH cells. Thus T-regs could be a therapeutic target in LCH.

Background and Objectives: The two main complications of severe chronic neutropenia are fatal sepsis and myelodysplasia/acute leukemia (MDS/AL). Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known., Design and Methods: The French Severe Chronic Neutropenia (SCN) Registry has prospectively collected data since 1994 on 231 patients with various forms of SCN, namely severe congenital neutropenia (n=101), cyclic neutropenia (n=60), glycogen storage disease type Ib (GSDIb) (n=15) and Shwachman-Diamond syndrome (SDS)(n=55). The median overall follow-up is 11.1 years. Parameters of exposure to G-CSF therapy, such as the time averaged dose, follow up after first use of G-CSF, and the cumulative dose, have been recorded., Results: Eight septic deaths occurred, of which 6 among patients with severe congenital neutropenia and 2 in patients with cyclic neutropenia; none of these 8 patients was receiving G-CSF therapy. No septic deaths occurred during G-CSF therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years., Interpretation and Conclusions: Risk factors for MDS/AL were the diagnostic category, the severity of neutropenia, younger age at diagnosis, and strong exposure to G-CSF. MDS/AL only occurred in patients with severe congenital neutropenia and SDS. Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.

Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN). To date, 30 different mutations have been reported, but no correlation has been found with the degree of neutropenia. To address this issue, we analyzed the clinical, hematologic, and molecular characteristics of 81 unrelated patients with SCN (n = 54) or CN (n = 27). We identified mutations in 31 patients, two thirds of whom had sporadic forms. Familial cases were consistent with dominant inheritance. Seventeen novel mutations were identified, showing that the mutational spectrum encompasses not only the region encoding the mature enzyme but also the prodomains and promoter region. Genotype-phenotype analysis strongly suggested that ELA2 mutations correlate with more severe expression of neutropenia, specifically in patients diagnosed with SCN. This study underlines the importance of ELA2 molecular screening to identify patients who may be at particular risk of severe bacterial infections and/or acute myeloid leukemia/myelodysplasia. By phenotypic analysis of affected relatives and carriers of the same ELA2 mutations, we showed that the expression of neutropenia in CN and SCN may be either homogeneous or variable according to the type of mutations, suggesting different pathogenetic mechanisms.

We retrospectively studied 61 patients with GH deficiency (GHD), identified among 589 patients with Langerhans cell histiocytosis (LCH) enrolled in a nationwide survey between 1993 and 2001. Overall, 141 patients in the survey developed diabetes insipidus. The median follow-up of the 61 patients with GHD was 12 yr. The 5- and 10-yr risks of GHD among patients with diabetes insipidus were 34.7 +/- 4.5% and 53.7 +/- 5.2%, respectively. Growth velocity decreased soon after LCH diagnosis in patients who developed GHD, and anterior pituitary height, estimated by magnetic resonance imaging, was significantly reduced relative to patients who remained free of GHD. GH replacement therapy was administered to 47 of the 61 patients with GHD. Among GH-treated patients, median final height (-0.8 SD) was significantly greater than median height at GHD diagnosis (-1.6 SD) but remained below midparental (target) height. Among patients with pituitary involvement, the number of LCH disease episodes appeared not significantly influenced by GHD or GH administration, suggesting an absence of deleterious effect of GH therapy on LCH disease activity.