Differences in Obstetric Care Between Japan and the US: A Qualitative Analysis of Blogs

Aim To investigate patient-reported differences in obstetric care between Japan and the US by characterizing the information Japanese immigrants and expatriates share online

Do regular timetables help to reduce delays in tram networks? It depends!

In public transit planning, regularity of timetables is seen as an important means to improve capacity efficiency by assuring an even trip distribution, as well as to improve product attractiveness and appreciation. This paper focuses on examining whether a regular timetable can also help to reduce network delay, especially resulting from inevitable small disturbances. Following the formulation of a mathematical optimization approach, we propose a number of conditions a network has to fulfill for timetable regularity to have a delay reducing impact. A set of three network properties is identified, which consists of (a) the sharing of resources between tram lines, (b) a low variability of driving times, and (c) the non-redundancy of the network's central resources. To test the impact of these properties, a series of optimization and simulation experiments is conducted on models of the tram network of the cities of Cologne, Germany, and Montpellier, France. Small disturbances are introduced to the simulated operations to check whether the presence of all three properties is necessary for a network to benefit from a regular timetable. The results show that while with all properties present a regular timetable can indeed help to reduce delays resulting from small disturbances, the non-compliance with any one of the conditions nullifies the impact of regularity on the result

A disjunctive program formulation to generate regular public transit timetables adhering to prioritized planning requirements

Timetable regularity, that is, equability of headways, is an important measure for service quality in high frequency public transit systems, assuring an evenly distributed passenger load as well as improving product attractiveness. However, to be feasible during daily operation a timetable may also have to adhere to other planning requirements, such as departure time coordination with other service providers or deliberately short headways to reduce the passenger load of follow-up vehicles. In this article, a disjunctive program formulation combining aspects of two previous optimization models is proposed, to generate regular public transit timetables adhering to planning requirements. The modeled requirements not only allow for the consideration of feasibility constraints from daily operations, but also for the consideration of simultaneous departures for transfer connections, an objective traditionally opposed to regularity. To show its applicability the approach is applied to two models of artificial transit networks as well as to models of the public transit network of Cologne, Germany. The results show that the proposed formulation can be used to generate timetables for network instances of realistic size in acceptable time. For networks consisting of multiple connected components it is shown that a decomposition approach can significantly reduce run times

Tandem Isotope Therapy with 225Ac- and 177Lu-PSMA-617 in a Murine Model of Prostate Cancer.

Radionuclide therapy targeting prostate-specific membrane antigen (PSMA) is a promising option for metastatic castration-resistant prostate cancer. Clinical experience using 177Lu or 225Ac has demonstrated encouraging treatment responses; however, responses are not durable. Dual-isotope combinations, or tandem approaches, may improve tolerability while retaining a high tumor dose. In this study, we directly compared α- versus β-particle treatment, as well as a combination thereof, at different stages of disease in a murine model of disseminated prostate cancer. Methods: First, to determine comparable injected activities from 177Lu- and 225Ac-PSMA-617, ex vivo biodistribution studies were performed at 5 time points after treatment of C4-2 subcutaneous tumor-bearing NSG mice. To establish a more representative model of metastatic prostate cancer, NSG mice were inoculated with luciferase-expressing C4-2 cells in the left ventricle, leading to disseminated visceral and bone lesions. At either 3 or 5 wk after inoculation, the mice were treated with equivalent tumor dose-depositing activities of 177Lu- or 225Ac-PSMA-617 alone or in combination (35 MBq of 177Lu, 40 kBq of 225Ac, or 17 MBq of 177Lu + 20 kBq 225Ac; 10/group). Disease burden was assessed by weekly bioluminescence imaging. Treatment efficacy was evaluated using whole-body tumor burden and overall survival. Results: The ex vivo biodistribution studies revealed that 35 MBq of 177Lu and 40 kBq of 225Ac yield equivalent absorbed tumor doses in a subcutaneous C4-2 model. The disease burden of mice treated at 3 wk after inoculation (microscopic disease) with 177Lu was not significantly different from that of untreated mice. However, 225Ac-PSMA-617 both as a single agent and in combination with 177Lu (17 MBq of 177Lu + 20 kBq of 225Ac) were associated with significant whole-body tumor growth retardation and survival benefit (overall survival, 8.3 wk for nontreatment, 9.4 wk for 177Lu, 15.3 wk for 225Ac alone, and 14.1 wk for tandem therapy). When treated at 5 wk after inoculation (macroscopic disease), all treatment groups showed retarded tumor growth and improved survival, with no significant differences between 225Ac alone and administration of half the 225Ac activity in tandem with 177Lu (overall survival, 7.9 wk for nontreatment, 10.3 wk for 177Lu, 14.6 wk for 225Ac alone, and 13.2 wk for tandem therapy). Conclusion: Treatment of a disseminated model of prostate cancer with simultaneous 225Ac- and 177Lu-PSMA-617 results in significantly decreased tumor growth compared with 177Lu, which was ineffective as a single agent against microscopic lesions. Mice treated later in the disease progression and bearing macroscopic, millimeter-sized lesions experienced significant tumor growth retardation and survival benefit in both monoisotopic and tandem regimens of 177Lu and 225Ac. Although the greatest benefits were observed with the single agent 225Ac, the tandem arm experienced no significant difference in disease burden or survival benefit, suggesting that the reduced activity of 225Ac was adequately compensated in the tandem arm. The superior therapeutic efficacy of 225Ac in this model suggests a preference for α-emitters alone, or possibly in combination, in the microscopic disease setting

Dynamic covalent single chain nanoparticles based on hetero Diels-Alder chemistry

We introduce the fully reversible folding of single chain nanoparticles (SCNPs) based on covalent hetero Diels-Alder (HDA) chemistry. A cyclopentadiene (Cp)-protected cyanodithioester ( CDTE) monomer is designed and copolymerized with methyl methacrylate (MMA) via RAFT polymerization. The polymer chains are folded and subsequently unfolded by exploiting the reversible nature of the HDA reaction

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of $^{177}Lu$-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p 28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT