The negative impact of traditional laparoscopic surgery (TLS) on surgeons has been well-established. Prevalence rates of discomfort and injury between 73% and 90% are regularly cited to support this, with robot-assisted laparoscopic surgery (RALS) often being presented as the solution. The purpose of this study was to systematically review pain studies of TLS and RALS surgeons, to consider the difference in the reported strain in general and concerning specific sites of the body. PubMed, Embase, and Cochrane databases were searched in October 2019. The resulting articles were screened to ensure the full text was available in English, original data were presented, the study contained pain statistics for TLS or RALS, and the study had a long-term rather than an intra-operative focus. Quality was assessed using the SUrvey Reporting GuidelinE (SURGE). Results from studies were analyzed in two stages for TLS and RALS according to each anatomic region. A total of 1354 papers were found, from which 28 papers won of larger, high-quality, homogenous studies, especially concerning injuries experienced by RALS surgeons, to overcome the limitations of heterogeneity and bias. The management of cholecysto-choledocholithiasis is controversial with the risks and benefits of one versus two-stage approaches debated. This study aims to perform decision analysis of minimally invasive laparo-endoscopic approaches. An advanced decision tree was constructed to compare pre, intra and post-operative ERCP and laparoscopic common bile duct exploration in terms of primary ductal clearance and significant complications for patients intended to undergo laparoscopic cholecystectomy. Transition probabilities were calculated from randomised controlled trials following a comprehensive literature search. Model uncertainties were extensively tested through deterministic and probabilistic Monte Carlo sensitivity analysis. Utility outcomes were 1 and 0.5 for successful primary clearance without and with complications, respectively, and 0 for failure of primary clearance of the duct. Twenty-one studies (n = 2697) were included in the analysis. At base case analysis, a laparo-endoscopic rendezvous appgement of cholecysto-choledocholithiasis is superior to two-stage, in terms of primary clearance of the duct and risk of operative morbidity. Laparo-endoscopic rendezvous approach could offer marginal additional benefit but more high-quality randomised controlled trials are needed.One-stage approach to the management of cholecysto-choledocholithiasis is superior to two-stage, in terms of primary clearance of the duct and risk of operative morbidity. Laparo-endoscopic rendezvous approach could offer marginal additional benefit but more high-quality randomised controlled trials are needed. To demonstrate the feasibility and safety of PTE-RV performed in a single session. This is a retrospective review of a prospective database on ERCP between January 2014 and December 2018. PTE-RV was performed in case of second ERCP failure. Technical success was defined as the establishment of an intestinal access to the biliary tract using a PTE-RV procedure allowing an immediate internal biliary drainage. Safety endpoints included intra-operative complications, morbidity and mortality occurring within 30days after the procedure. Eighty-four patients (44M/40F) with a median age of 69years (range 40-91years) underwent combined PTE-RV. The PTE-RVs were successfully performed in the same session in 80 subjects, resulting in an overall technical success rate of 95.2%. Adverse events were observed in 19% (16/84) of cases. The mortality rate within 30days after the procedure was 9.5%. Percutaneous transhepatic-endoscopic rendezvous technique is feasible in a single session with acceptable level of risk. A randomized trial is required to compare EUBD and PTE-RV.Percutaneous transhepatic-endoscopic rendezvous technique is feasible in a single session with acceptable level of risk. A randomized trial is required to compare EUBD and PTE-RV. Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. HG106 compound library inhibitor In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O -benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. Our in vitro study demonstrated that sequential treatment of O -Benzylguanine with either LY2385219 or cells.A modeling and simulation approach was used for quantitative comparison of a new generation HER2 antibody drug conjugate (ADC, PF-06804103) with trastuzumab-DM1 (T-DM1). To compare preclinical efficacy, the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of PF-06804103 and T-DM1 was determined across a range of mouse tumor xenograft models, using a tumor growth inhibition model. The tumor static concentration was assigned as the minimal efficacious concentration. PF-06804103 was concluded to be more potent than T-DM1 across cell lines studied. TSCs ranged from 1.0 to 9.8 µg/mL (n = 7) for PF-06804103 and from 4.7 to 29 µg/mL (n = 5) for T-DM1. Two experimental models which were resistant to T-DM1, responded to PF-06804103 treatment. A mechanism-based target mediated drug disposition (TMDD) model was used to predict the human PK of PF-06804103. This model was constructed and validated based on T-DM1 which has non-linear PK at doses administered in the clinic, driven by binding to shed HER2. Non-linear PK is predicted for PF-06804103 in the clinic and is dependent upon circulating HER2 extracellular domain (ECD) concentrations. The models were translated to human and suggested greater efficacy for PF-06804103 compared to T-DM1. In conclusion, a fit-for-purpose translational PK/PD strategy for ADCs is presented and used to compare a new generation HER2 ADC with T-DM1.