Studi Volume Lalu Lintas di Jalan Raya Narogong Cileungsi, Kabupaten Bogor, Periode Agustus 2011

Survey of traffic volume is one of the simplest methods to obtain traffic data in order to better understand optimalisation andefficiency so that it can minimize vehicle traffic congestion problems on the highway. The method used is based on descriptive andanalytical methods, which is done is to classify the vehicles in classes manually by counting the number of vehicles per time unitbased on class - class. The purpose of the volume of traffic surveys carried out in the classified Narogong Cullinan Road, Bogorregency during the period August, 2011, results that can be found is the degree of saturation of the highway is still in an acceptablelevel. Analysis of traffic flow at the study site is still under the limit congestion. It is suggested that to reduce the traffic density, thetype of heavy vehicles such as out of the factory operates around the study site between the hours of 10:00 pm to 3:00 am

Extrapulmonary poorly differentiated NECs, including molecular and immune aspects

International audiencePatients with extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PD-NECs) have a poor prognosis. Surgery is offered for those with localised disease, but the majority of patients present with advanced disease. Treatment strategies adopted are analogous to that of high grade NECs of the lung, with platinum/etoposide-based regimens advocated in the first-line setting for advanced disease. There is no standard second-line therapy. Research into their molecular and immune pathways may pave the way for novel drug discovery. The molecular drivers of NEC are best identified in small cell lung carcinoma, which present with near universal genomic alterations in TP53 and RB1 . The genetics of EP-PD-NEC remain poorly understood; TP53 , KRAS , PIK3CA/PTEN and BRAF mutations have been identified, with alterations in the BRCA pathway reported additionally in small cell NEC of the cervix and absence of argininosuccinate synthetase 1 expression in NEC of the urinary bladder. The use of cell lines and patient-derived xenografts (PDX) to predict response to treatment in NEC and the emergence of alternative biomarkers, such as circulating tumour cells and cell-free DNA, will also be explored. Despite limited published data on the immune microenvironment of EP-NEC, there are a number of clinical trials investigating the use of immune-targeted agents in this disease category, with conflicting emerging data from studies thus far. This review will summarise the treatment and available molecular and immune data in this under researched diagnosis and may stimulate the direction of future exploratory studies

Updated overall survival and outcomes of long-term survivors from the randomised phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer

BackgroundIn the phase 3, double-blind TOPAZ-1 study, durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) versus placebo plus GemCis in advanced biliary tract cancer (BTC). Updated data from TOPAZ-1, including outcomes in long-term survivors (LTS) are reported here. Methods In TOPAZ-1 (NCT03875235), participants aged ≥18 years with unresectable, locally advanced, or metastatic BTC were randomised 1:1 to durvalumab plus GemCis or placebo plus GemCis (administered intravenously) on a 21-day cycle for up to eight cycles. Durvalumab 1500 mg or placebo was administered on day 1 of each cycle, and GemCis (gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2) was administered on days 1 and 8 of each cycle. After completion of GemCis, durvalumab 1500 mg or placebo were administered once every four weeks until disease progression or other discontinuation criteria were met. Participants were randomly assigned to study treatment using a computer-generated randomisation scheme. Randomisation was stratified by disease status and primary tumour location. Investigators and participants were masked to study treatment. The primary objective was OS. Updated data from TOPAZ-1, with additional follow-up (data cut-off [DCO] February 25, 2022) and data maturity beyond the interim analysis, are reported here. Baseline characteristics, best objective response per RECIST v1.1 (DCO August 11, 2021), and safety were analysed in LTS (participants who survived for ≥18 months after randomisation). Findings In total, 685 participants were randomised (345 [50·4%] were male; 340 [49·6%] were female). For durvalumab plus GemCis (n=341) and placebo plus GemCis (n=344), median (95% CI) follow-up was 23·4 (20·6–25·2) months and 22·4 (21·4–23·8) months. OS hazard ratio (95% CI) for durvalumab plus GemCis versus placebo plus GemCis was 0·76 (0·64–0·91). Kaplan–Meier-estimated 24-month OS rates (95% CIs) were 23·6% (18·7–28·9) and 11·5% (7·6–16·2), respectively. Survival with durvalumab plus GemCis, including long-term survival, was improved in participants with disease control (complete or partial response or stable disease). In total, 39/88 (44·3%) of LTS on durvalumab plus GemCis had an objective response versus 22/65 (33·8%) of LTS in the placebo plus GemCis group. Adverse events with durvalumab plus GemCis were similar to the pre-planned interim analysis. Interpretation Durvalumab plus GemCis demonstrated robust and sustained OS benefit with no new safety signals. Findings continue to support the regimen as a standard of care for untreated advanced BTC. <br/