Mammary-carcinoma cells in mouse liver: infiltration of liver tissue and interaction with Kupffer cells.

Interactions between TA3 mammary-carcinoma cells and liver cells were studied with the electron microscope in mouse livers that had been perfused with a defined medium containing the tumour cells. Infiltration of liver tissue by the TA3 cells proceeded in the following steps. First, numerous small protrusions were extended through endothelial cells and into hepatocytes. Next, some cells had larger processes deeply indenting hepatocytes. Finally a few tumour cells became located outside the blood vessels. Two variant cell lines, TA3/Ha and TA3/St, differing in cell coat and surface charge, did not differ in the extent of infiltration. TA3/Ha cells were often encircled by thin processes of liver macrophages (Kupffer cells). Encircled cells were initially intact, but later some of them degenerated. These observations suggest that TA3/Ha cells were phagocytized by the Kupffer cells. Encirclement appeared to be inhibited after only 30 min, when many cells were still partly surrounded. Encirclement of TA3/St was much less frequent. After injection of tumour cells intra-portally in vivo, similar results were obtained, which demonstrated the validity of the perfused liver model. TA3/Ha cells formed much fewer tumour nodules in the liver than TA3/St cells

Cyber Security: China and Russia\u27s Erosion of 21st Century United States\u27 Hegemony

With Russia and China emerging as challengers to U.S. hegemony, the use of cyber warfare could tilt the current balance of power in either of their favors. Using various methods, hackers can acquire sensitive information and destroy online infrastructures. In the development of cyber warfare, China has become a seasoned veteran with computer virus operations dating back to 199714. Russia has emerged as a cyber aggressor, as seen in Russia’s cyber attacks on several countries in the last decade. This paper argues that, with the growth of foreign cyber technology, the probability of cyberspace being used as a military front by state or non-state actors against the United States increases

Phase Behavior of Bent-Core Molecules

Recently, a new class of smectic liquid crystal phases (SmCP phases) characterized by the spontaneous formation of macroscopic chiral domains from achiral bent-core molecules has been discovered. We have carried out Monte Carlo simulations of a minimal hard spherocylinder dimer model to investigate the role of excluded volume interations in determining the phase behavior of bent-core materials and to probe the molecular origins of polar and chiral symmetry breaking. We present the phase diagram as a function of pressure or density and dimer opening angle $\psi$. With decreasing $\psi$, a transition from a nonpolar to a polar smectic phase is observed near $\psi = 167^{\circ}$, and the nematic phase becomes thermodynamically unstable for $\psi < 135^{\circ}$. No chiral smectic or biaxial nematic phases were found.Comment: 4 pages Revtex, 3 eps figures (included

The Basics of Water Waves Theory for Analogue Gravity

This chapter gives an introduction to the connection between the physics of water waves and analogue gravity. Only a basic knowledge of fluid mechanics is assumed as a prerequisite.Comment: 36 pages. Lecture Notes for the IX SIGRAV School on "Analogue Gravity", Como (Italy), May 201

Observation of negative-frequency waves in a water tank: A classical analogue to the Hawking effect?

The conversion of positive-frequency waves into negative-frequency waves at the event horizon is the mechanism at the heart of the Hawking radiation of black holes. In black-hole analogues, horizons are formed for waves propagating in a medium against the current when and where the flow exceeds the wave velocity. We report on the first direct observation of negative-frequency waves converted from positive-frequency waves in a moving medium. The measured degree of mode conversion is significantly higher than expected from theory

Cost-effectiveness of Internet Interventions Compared With Treatment as Usual for People With Mental Disorders: Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: The economic costs of mental disorders for society are huge. Internet-based interventions are often coined as cost-effective alternatives to usual care, but the evidence is mixed. Objective: The aim was to review the literature on the cost-effectiveness of internet interventions for mental disorders compared with usual care and to provide an estimate of the monetary benefits of such interventions compared with usual care. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted, which included participants with symptoms of mental disorders; investigated a telephone- or internet-based intervention; included a control condition in the form of treatment as usual, psychological placebo, waiting list control, or bibliotherapy; reported outcomes on both quality of life and costs; and included articles published in English. Electronic databases such as PubMed (including MEDLINE), Embase, Emcare, PsycINFO, Web of Science, and the Cochrane Library were used. Data on risk of bias, quality of the economic evaluation, quality-adjusted life years, and costs were extracted from the included studies, and the incremental net benefit was calculated and pooled. Results: The search yielded 6226 abstracts, and 37 studies with 14,946 participants were included. The quality of economic evaluations of the included studies was rated as moderate, and the risk of bias was high. A random-effects approach was maintained. Analyses suggested internet interventions were slightly more effective than usual care in terms of quality-adjusted life years gain (Hedges g=0.052, 95% CI 0.010-0.094; P=.02) and equally expensive (Hedges g=0.002, 95% CI −0.080 to 0.84; P=.96). The pooled incremental net benefit was US $255 (95$91 to US $419; P=.002), favoring internet interventions over usual care. The perspective of the economic evaluation and targeted mental disorder moderated the results. Conclusions: The findings indicate that the cost-effectiveness of internet interventions for mental disorders compared with a care-as-usual approach is likely, but generalizability to new studies is poor given the substantial heterogeneity. This is the first study in the field of mental health to pool cost-effectiveness outcomes in an aggregate data meta-analysis

SETBP1 variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder

Germline de novo SETBP1 variants cause clinically distinct and heterogeneous neurodevelopmental disorders. Heterozygous missense variants at a hotspot encoding a canonical degron lead to SETBP1 accumulation and Schinzel-Giedion syndrome (SGS), a rare severe developmental disorder involving multisystem malformations. Heterozygous loss-of-function variants result in SETBP1 haploinsufficiency disorder which is phenotypically much milder than SGS. Following an initial description of four individuals with atypical SGS carrying heterozygous missense variants adjacent to the degron, a few individual cases of variants outside the degron were reported. Due to the lack of systematic investigation of genotype-phenotype associations of different types of SETBP1 variants, and limited understanding of the roles of the gene in brain development, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remain elusive, imposing challenges for diagnosis and patient care. Here, we present a comprehensive investigation of the largest cohort to-date of individuals carrying SETBP1 missense variants outside the degron (n=18, including one in-frame deletion). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS and SETBP1 haploinsufficiency disorder, and primarily characterised by intellectual disability, epilepsy, speech and motor impairment. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding and transcription. In contrast to SGS and SETBP1 haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care and aetiology of SETBP1-related disorders

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care. Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests. Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer