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The increased development in automated driving systems (ADS) has opened up significant opportunities to revolutionize mobility and to set the path for technologies, such as electrification. The proposed methodology is a simulation model backed by a multi-objective optimization algorithm. This research investigates the adoption of future technologies in earthmoving application and explores its implications on the design of future machine concepts in terms of equipment size. The shift from “elephant to ants” in the machine selection, resulted in improved feasibility.

Probabilistic analysis is used to assess the safety of structures by taking into account uncertainties that may affect structural performance in order to prevent failure of structure, which can lead to injuries or loss of life as well as financial losses. A part of Terminal 2E at Roissy- Charles de Gaulle Airport in Paris collapsed in 2004 and resulted in four casualties. The terminal is a large and complex structure consisting of three main parts: a main building, a boarding area and an isthmus connecting these two buildings. The boarding area, where the collapse occurred, has a length of 650 m and consists of 10 shells stiffened by curved steel girders (ties) braced to the two sides and held away from the shell by means of regular steel struts. The purpose of this paper is to conduct a risk analysis of the terminal using probabilistic approach in order to study the effect of uncertainty on material properties and loads on the values of flexural moment and long-term deflection so the structural safety of the terminal can be verified. Therefore, a nonlinear finite element model of the terminal was carried out using Ansys software. Subsequently, sensitivity analysis was performed by using a combination of Response Surface Method (RSM) and Monte Carlo Simulation (MCS). After that, the ratio of reinforcement required was calculated based on the results of the flexural moment values so the structural safety of the terminal can be finally verified. The obtained results show the importance of conducting probabilistic analysis to assess the structural safety of complex structures by understanding structural behavior when the uncertainty on material properties and loads is taken into account.

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age-adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.

Purpose Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. Methods The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. Results Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. Conclusion This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources. Electronic supplementary material The online version of this article (10.1007/s00345-019-02872-x) contains supplementary material, which is available to authorized users.

Introduction Bladder cancer is the fourth most commonly diagnosed cancer among males worldwide. Recent advances in radiation delivery have increased the importance of bladder preserving strategies using radiotherapy, while also improving patient’s quality of life. However, the outcome of radiotherapy depends on the radiosensitivity of both the patient and his/her tumour. Recent developments in radiobiology have highlighted the importance of the assessment of radiation-induced DNA double-strand breaks (DSB) repair kinetics in predicting radiosensitivity of both normal and cancerous tissues. Indeed, after irradiation, several proteins (ATM, γH2AX, etc.) involved in the signalling and repair of DNA DSB relocalize as nuclear foci. The purpose of this study is to characterise the radiosensitivity of bladder cell lines, based on their capacity to repair radio-induced DNA damage. Material and methods Four human bladder cell lines were used in this study: T24, UM-UC3, RT4 and SVHUC. Clonogenic assay was performed to study cell survival after irradiation: cells were irradiated with doses ranging from 0 to 10 Gy and their capacity to form colonies was assessed. Immunofluorescent analysis using anti-pATM and anti-γH2AX antibodies was then performed to assess DNA DSB signalling and repair kinetics after a 2Gy irradiation. Finally, we performed the three-dimensional (3D) sphere formation assay to assess the effect of irradiation on cancer/stem progenitor cells. Irradiated cells with doses ranging from 0 to 10 Gy were embedded in Matrigel and their capacity to form spheres was assessed. Results and discussions RT4 was found to have the highest survival rate after irradiation, followed by T24, UM-UC3 and SVHUC according to the clonogenic assay results. Immunofluorescence results were consistent with cell survival as RT4 showed the fastest DSB recognition and repair kinetics while SVHUC had a much slower rate. Furthermore, the capacity of cells to recognise radio-induced DNA damage was found to have the best correlation with their survival. Lastly, the sphere formation ability of the different cell lines showed a differential response to increasing irradiation doses. Conclusion We were able to radiobiologically characterise 4 human bladder cell lines by assessing their survival and capacity to repair radio-induced DNA damage. Moreover, we showed the differential effects of radiation on cancer stem/progenitor cells. The results highlighted the importance of DNA DSB signalling through the ATM protein and its role in cell survival after irradiation.

Creep and shrinkage strains of concrete can have prejudicial consequences in prestressed structures built by phases. But these uncontrolled strains appear, with values often clearly more important than the expected ones. In fact, there is not yet a physical explanation perfectly satisfactory of creep and the codified descriptions of this phenomenon are always unreliable.

The steel structure is a type of construction that is very developed in civil engineering. In the phase of survey and then of execution and installation of a metal work, the phase of conception is often the place of discontinuities that prevents the global optimization of material steel. In our survey, we used the traditional approach of optimization that is essentially based on the minimization of the weight of the structure, while taking advantages of plastic properties of steel in the case of a bending structure. It has been permitted because of to the relation found between the areas of the sections of the steel elements and the plastic moment of these sections. These relations have been drawn for different types of steel. In order to take advantages of the linear programming, a simplification has been introduced in transforming these relation to linear relations, which permits us to use simple methods as the simplex theorem. This procedure proves to be very interesting in the first phases of the survey and give very interesting results.

BACKGROUND.: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS.: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (.25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS.: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25. CONCLUSIONS.: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Tumor clonogenic cell content is believed to play an important role in the outcome of radiotherapy. However, there is no proven method to assess the number of clonogens in human tumors accurately. All currently available assays employ in vitro plating efficiency or in vivo TD50 (the average number of cells needed to induce tumors in 50% of injected mice) to estimate the tumor clonogenic ability. In this study, a monolayer mass primary culture system was used to estimate the clonogenic cell fraction in human tumors. For this purpose, 25 growth curves were performed for 25 tumor specimens derived from 21 head and neck and 4 cervical squamous cell carcinomas. The exponential portion of each growth curve was extrapolated through the ordinate (day 0) to estimate the clonogenic cell fraction; this method is only an estimate because it assumes no lag phase before exponential growth of clonogenic cells. The mean clonogenic cell fraction, expressed as clonogens/tumor cells inoculated, was relatively low (mean: 0.71%, range: 0.11–9.28), and the variation was wide (coefficient of variation=148%). On the other hand, the doubling time of the growing population was 1.46 days and exhibited a very narrow range (0.98–2.24, coefficient of variation=24%). The mean and range of clonogenic cell fraction were found to be in agreement with published values of soft agar colony forming efficiencies in both murine and human tumors. However, further investigation is necessary to determine how accurately this method measures the relative clonogenic cell content in human tumors. Clinical correlations between clonogenic cell fraction values and the response to radiotherapy are still too early to determine.

To investigate vocal changes in patients following the neck irradiation for non-laryngeal tumors sparing the glottic region. Fifteen patients were enrolled for the study. Phonatory effort and voice evaluation were reported. Perceptual evaluation and acoustic analysis were performed. Men/women ratio was 6/9. The mean age was 54 years with a range from 24 to 84. The most common primary site of tumor was the nasopharynx and tongue. The mean phonatory effort was significantly greater in the irradiated group versus controls (0.54 vs. 0.08 with a P value 0.01). Fifteen percent reported their voice as being poor and almost 85% as being fair. All the parameters of the GRABS perceptual evaluation were significantly worse in the irradiated group. There were no statistically significant differences between all the acoustic variables in both groups except for an decrease in the Habitual pitch in the irradiated patients. Radiation therapy to head and neck region can affect voice even if the radiation beams spare the vocal folds.

Desmoid tumors of the female pelvis are rare. The efficacy of the available treatment modalities in improving survival and decreasing recurrence remains controversial. A 32-year-old woman presented with an asymptomatic large ischeorectal mass. Computed tomography scan revealed a large tumor adherent to the pubic bone and impinging on the bladder neck and the rectum. Aggressive surgical removal of the mass including partial osteotomy of the pubic bone was followed by radiotherapy. The patient is still alive 6 years later with no evidence of disease. Aggressive surgical management followed by radiotherapy is an acceptable means of treatment of locally invasive desmoid tumor of the female pelvis.

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.

Gastrointestinal lymphomas are almost exclusively of a non-Hodgkin's type. The Western form is characterized by a higher incidence of stomach location (50%), a MALT type (mucosa associated lymphoid tissue) (40%), a B-cell type (90%), and a high grade (55%). Chronic infection with Helicobacter pylori is an important risk factor. Mediterranean lymphomas form a particular clinical and pathological entity with diffuse involvement of the small bowel and are frequently being associated with a chronic malabsorption disorder. Eradication of Helicobacter pylori in early gastric lymphomas, and the use of tetracyclines in early Mediterranean lymphomas, have been shown to induce durable remissions. For more advanced gastric lymphomas, treatment usually consists of anthracyclin-based chemotherapy followed by involved field radiotherapy. Surgery is usually reserved for complications such as perforation or bleeding, or in some selected cases for salvage after failure of non-surgical therapy. For intestinal lymphomas, surgical resection whenever feasible, followed by anthracyclin-based chemotherapy is the most common treatment. Radiotherapy is usually reserved for consolidation in some clinical situations. The most commonly found prognostic factors are stage, grade, and tumor bulk. Treatment results vary with the presence of adverse prognostic factors and the used treatment combination. In general, patients with favorable disease receiving combined therapy have a 5-year relapse free survival (RFS) approaching 90%, whereas those with unfavorable disease have a RFS of 40-50%.

This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy.One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years.Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues.Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site.

e22084 Background: The status of the axillary lymph nodes (ALN) in early (stage I and II) breast cancer (BC) patients remains the single most important determinant of overall survival (OS). While the absolute number of positive ALN has been demonstrated to have a significant prognostic impact, new emerging data supports the role of axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. Methods: We conducted a single-center retrospective review of 1,255 BC patients and analyzed 930 patients with early BC admitted to American University of Beirut Medical Center between 1983 and 2001. Data included age at diagnosis, type of mastectomy, ALN involvement, use of chemotherapy, hormonal therapy, post-operative radiation therapy, tumor size, histological type and grade, lympho-vascular invasion status, hormonal receptor status, and Her-2/neu overexpression and the calculated ALNR (number of positive ALN / total number of excised ALN). Patients were subdivided into 3 groups according to ALNR value (< 0.25, 0.25–0.49, 0.50–1.00). The status of the axillary lymph nodes was analyzed with respect to 5- and 10-year OS. Results: On univariate analysis both the absolute number of positive ALN and the ALNR were significant predictors of OS .The 5- year OS of patients with ALNRs of < 0.25, 0.25–0.49 and 0.50–1.00 was 88%, 72% and 65 % respectively and the 10-year OS was 83%,54% and 51 % respectively . On multivariate analysis only the ALNR remained an independent predictor of overall survival, with a 2.7- and 3.16-fold risk of dying at ALNRs of 0.25 and 0.5, respectively. Conclusions: Our study demonstrated that the ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes. ALNR may aid in subdividing patients with positive ALN into low and high risk groups, with potential implications on their subsequent adjuvant management. No significant financial relationships to disclose.

Between 1976 and 1986, we treated with curative intent, 108 patients with inoperable esophageal cancer. Eighty-three patients (77%) were treated with radiation therapy alone with a mean total dose of 61 Gy and 25 (23%) patients were treated with induction chemotherapy followed by radiotherapy. Actuarial survival, site of failure, sequellae of treatment, and prognostic factors were analysed in this retrospective study. Survival rates at 2, 3 and 5 years were 23, 16 and 9%, respectively. Local failure occurred in more than 61% of documented failures. Patients with tumor located in the upper third of the esophagus, or with total tumor stenosis or poor performance status had low results, but the difference was not statistically significant. Patients treated according to CT scan plans had a 43% 3-year survival rate; this difference is statistically significant (P = 0.0001). Induction chemotherapy improved one year local control and survival rate (60%), but no long term survival benefit was observed. We conclude that inoperable esophageal cancer can be treated successfully by radiotherapy with a curative intent. We also discuss the role that CT scan planning can play in the effective treatment of these patients.

Between June 1986 and December 1988, 149 patients with AIDS-related Kaposi's sarcoma were treated by cutaneous irradiation in our department. According to Mitsuyasu's staging, 34 patients (23 p. 100) were stage I, 82 (55 p. 100) stage II and 33 (22 p. 100) stage IV; no stage III was reported. Fifty eight patients (39 p. 100) had previously presented with one or several opportunistic infections. Ninety four patients (63 p. 100) had previously received treatment with interferon in 85 (57 p. 100) and/or Velbe in 43 (29 p. 100). 319 cutaneous localisations were treated, 59 p. 100 by extended cutaneous irradiation, using 4 and/or 8 MeV electron beam energy, and 41 p. 100 by localized irradiation, using 45 kVX-ray energy, 2.5 Gy/fraction, 4 times a week by split course 20 Gy then 10 Gy two weeks later. Twenty patients (13 p. 100) with oedema of the lower limbs were treated, using 4 MV photon therapy with bolus, and 3 (2 p. 100) were treated for lesions in the ENT regions. Only 131 patients were evaluable (257 localisations); 62 p. 100 obtained complete remission and 31 p. 100 partial remission after a mean period of 1.5 months (0.5-3 months). The overall tolerance was acceptable. The complications were epidermitis with some necrosis (8 p. 100), exudative epidermitis (26 p. 100), moderate epidermitis (63 p. 100) and slight reactions in 4 p. 100. The mean recurrence time was 5 1/2 months.

5163 Introduction: This study prospectively compares weekly Cis-platinum to weekly Paclitaxel as concurrent chemotherapy with radiotherapy in patients with locally advanced cervical cancer. Methods...

Electron beam irradiation of the entire skin surface was used to treat 25 patients with mycosis fungoides from 1977 to January 1988. A plexiglas screen was used to reduce the energy of the 8 MeV beam of a Sagittaire linear accelerator to 4 MeV. A total dose of 30 Gy was delivered in 12 fractions over days. This series includes 17 men and 8 women with a mean age of 44 years (range 13-78 years) and a mean follow-up of 34 months (range 6-92 months). The following-up staging system was used: stage A: superficial lesions covering less than 50 p. 100 of the body surface; stage B: superficial lesions covering more than 50 p. 100 of the body surface; stage C: tumors of the skin, lymph nodes and/or visceral organs, Sezary's syndrome. All stage A patients achieved complete remission. One developed recurrent disease in a very limited area 17 months after radiation therapy. No stage A patient died of mycosis fungoides. 6/9 stage B patients achieved complete remission; 4 of these developed recurrent disease localized to the skin 6 to 13 months after electron therapy. These recurrences were controlled by topical nitrogen mustard, puva therapy or localized irradiation. 1 patient showed no response and died of cutaneous mycosis fungoides. 5/10 stage C patients obtained complete remission but all relapsed within a mean period of 7 months. 4/5 of the patients not responding to electron therapy died of their disease and one is alive 16 months after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)