Modified Mamdani-fuzzy inference system for predicting the cost overrun of construction projects

Cost overruns are a common worldwide problem in the construction industry; improved proactive risk management and cost control are much needed. Several models have been proposed, but all have weaknesses, particularly in data demands and the severity of critical risks or uncertainties associated with expert judgment. In response, this study develops a new 3-part model based on the Mamdani-type fuzzy inference system (FIS) to predict the cost overrun of construction projects. The first part assesses the weight of each expert, evaluating the severity of cost overrun factors. The second part contains a list of 40 in-built cost overrun factors and their degree of severity, while the third part establishes the relationships of every factor's occurrence probability and severity to predict the cost overrun of a specific project. The severity of each factor is assessed based on a survey of 31 randomly selected experts in the Saudi Arabian construction industry. The model is demonstrated on two completed projects in Saudi Arabia. For each project, this involves a group of project-based experts rating the probability of occurrence of each factor on that project and applying this to the factor severity list to obtain a predicted cost overrun (PCO) for the whole project. The model is validated for robustness by sensitivity analysis comparing the predicted and actual whole project cost overrun and shown to be of practical value in assessing critical risks and predicting the likely amount of cost overrun. The model is equally applicable in the early project stages.</p

A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms

Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were SBNEN, G1/G2 NEN, initial tumour diagnosis, stage IV NEN, positivity on 68Ga somatostatin analogue PET/CT, eligible for surgery, and 177Lu peptide receptor radionuclide therapy (PRRT). Blood samples for NETest were collected longitudinally. Progression-free survival (PFS) and overall survival (OS) were calculated. NETest results were assessed prior to surgery and during clinical follow-up. Results: A surgical cohort of 39 SBNEN patients met eligibility criteria. Thirty-two patients underwent ileal resection and 7 right hemicolectomy. The mean number of 177Lu PRRT cycles was 4. Mortality was nil. Surgical morbidity was 10.3%. Transient grade 1/2 toxicity occurred in 41% (PRRT). NETest scores (n=9 patients) decreased in 100% following treatment and correlated with diminished tumour volume and disease stabilization following surgery and PRRT. Median follow-up: 78 months. Median PFS and OS: 42.7 and 110 months, respectively. Progression-free survival at 1-, 3-, and 5-years was 79.4%, 57.1% and 40.5%, respectively. Overall survival at 1-, 3-, and 5-years was 97.4%, 97.4%, and 94.1%, respectively. Conclusions: Surgery combined with 177Lu PRRT is safe and provides favourable PFS and OS in selected patients with advanced SBNEN. Liquid biopsy (NETest) has the potential to accurately delineate disease status

Neoadjuvant peptide receptor radionuclide therapy and modified multivisceral transplantation for an advanced small intestinal neuroendocrine neoplasm: an updated case report

Small intestinal neuroendocrine neoplasms (SINEN) frequently metastasise to regional lymph nodes, and surgery is the mainstay of therapy for such patients. However, despite the possible use of advanced surgical techniques, the resection of both primary and locoregional diseases is not always attainable. Intestinal and multivisceral transplantation has been performed in a small number of patients with conventionally nonresectable, slow-growing tumours threatening the mesenteric root but has remained controversial. The use of donor skin in “sentinel flaps” in transplantation theoretically offers advantages in tailoring immunosuppression and monitoring for rejection. We represent (with extended followup) the first case of a patient with inoperable extensive mesenteric metastases from SI-NEN, who underwent neoadjuvant peptide receptor radionuclide therapy before a modified multivisceral transplant with a concomitant vascularised sentinel forearm flap. At 48 months after transplantation, our patient remained at full physical activity with no evidence of disease recurrence on either tumour biochemistry or radiological imaging

Prevalence of Allergic Disorders among Primary School-Aged Children in Madinah, Saudi Arabia: Two-Stage Cross-Sectional Survey

There are limited data on the epidemiology of allergic disorders in Saudi Arabia. Such data are needed for, amongst other things, helping to plan service provision at a time when there is considerable investment taking place in national healthcare development. We sought to estimate the prevalence of atopic eczema, allergic rhinitis and asthma in primary school children in Madinah, Saudi Arabia.We conducted a two-stage cross-sectional survey of schoolchildren in Madinah. Children were recruited from 38 randomly selected schools. Questionnaires were sent to the parents of all 6,139 6-8 year old children in these schools. These parental-completed questionnaires incorporated questions from the International Study of Asthma and Allergies in Childhood (ISAAC), which had previously been validated for use in Arab populations. We undertook descriptive analyses, using the Generalized Estimating Equation (GEE) to calculate 95% confidence intervals. The overall response rate was 85.9% (n = 5,188), 84.6% for girls and 86.2% for boys, respectively. Overall, parents reported symptoms suggestive of a history of eczema in 10.3% (95%CI 9.4, 11.4), rhinitis in 24.2% (95%CI 22.3, 26.2) and asthma in 23.6% (95%CI 21.3, 26.0) of children. Overall, 41.7% (95%CI 39.1, 44.4) of children had symptoms suggestive of at least one allergic disorder, with a substantial minority manifesting symptoms indicative of co-morbid allergic disease. Comparison of these symptom-based prevalence estimates with reports of clinician-diagnosed disease suggested that the majority of children with eczema and asthma had been diagnosed, but only a minority (17.4%) of children had been diagnosed with rhinitis. International comparisons indicated that children in Madinah have amongst the highest prevalence of allergic problems in the world.Symptoms indicative of allergic disease are very common in primary school-aged children in Madinah, Saudi Arabia, with figures comparable to the highest risk regions in the world

FDG uptake by prosthetic arterial grafts in large vessel vasculitis Is not specific for active disease

OBJECTIVES: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV). BACKGROUND: The role of (18)F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) in the management of LVV remains to be defined. Although [(18)F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied. METHODS: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [(18)F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [(18)F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUVmax) was calculated. Periprosthetic [(18)F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA). RESULTS: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUVmax was 4.21 ± 1.46. Median periprosthetic [(18)F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [(18)F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [(18)F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment. CONCLUSIONS: Significant [(18)F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

PET/MRI technique role in Alzheimer disease

Abstract Background Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT measurements, illuminating the possibility of early trial termination which implicates significant potential time and resource savings. Methods Primary lesion maximum standardised uptake value (SUVmax) was determined twice from preoperative FDG-PET/CTs in 45 ovarian cancer patients. Differences in SUVmax were assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis (N = 45) was compared with the group-sequential analysis strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. Results When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis and the final analysis. Other partitions did not suggest early stopping after adjustment for multiple testing due to one influential outlier and our small sample size. Conclusions Group-sequential testing may enable early stopping of a trial, allowing for potential time and resource savings. The testing strategy must, though, be defined at the planning stage, and sample sizes must be reasonably large at interim analysis to ensure robustness against single outliers. Group-sequential testing may have a place in accuracy and agreement studies

Neglected Tropical Diseases of the Middle East and North Africa: Review of Their Prevalence, Distribution, and Opportunities for Control

The neglected tropical diseases (NTDs) are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA) region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11