Radiotherapy of choroidal metastases.

Abstract Purpose: This retrospective study was undertaken to clarify the role of high energy external beam radiation therapy (EBRT) and to determine its safety and efficacy on local control and visual acuity in patients suffering from choroidal metastases (CM). Materials and methods: The records of 58 consecutive patients treated with EBRT between 1970 and 1993 were analyzed. The female to male ratio was 2.9 and the median age was 59 years (range 40–81 years). Thirty-six patients (62%) had unilateral CM and 22 patients had bilateral CM. The mean number of lesions per eye was two. Retinal detachment was present in 65% of cases. The primary tumour (PT) was breast carcinoma for 38 patients (75%), lung carcinoma for 10 patients (17%) and gastrointestinal, genitourinary or unknown PT for the remaining 10 patients. The median interval of time between the PT and the CM was 55 months (range 0–228 months). All patients were treated with megavoltage irradiation. The median prescribed dose was 35.5 Gy (range 20–53 Gy) normalized at a 2 Gy per fraction schedule with an a/b value of 10 Gy. Various techniques were used and whenever possible the lens was spared. Ten patients with unilateral disease were treated in both eyes. Results: The tumour response was slow. When assessed after 3 months or more, the complete response rate was 53% with significantly better results for doses higher than 35.5 Gy (72 versus 33%; P = 0.009). Visual acuity was improved or stabilized in 62% of patients, with also significantly better results when doses higher than 35.5 Gy (P = 0.014) were administered. Amongst 26 patients with unilateral CM who had no elective contralateral irradiation, three developed metastasis in the opposite eye versus none of the 10 patients who had bilateral irradiation. Five complications occurred (three cataracts, one retinopathy and one glaucoma). Conclusion: Radiation therapy is an efficient and safe palliative treatment for choroidal metastases and it helps the preservation of vision. Thus, there is a major impact on the quality of life in a group of patients with an almost uniformly fatal prognosis. Both tumour response and visual acuity are significantly improved if doses higher than 35.5 Gy are administered. Whenever possible, a lens sparing technique should be used. Ó 1998 Elsevier Science Ireland Ltd

A case of morgagnian cataract mimicking an iris tumor

Purpose: To report, with the aid of original imaging, an unusual differential diagnosis of an iris tumor. Observations: A 60-year-old Caucasian man visited our clinic with a large amelanotic iris mass in the left eye in the absence of concomitant extraocular inflammation or neoplastic evidence. The patient reported an ocular trauma caused by a wire 5 years prior to his visit, which resolved after a short course of antibiotic eye drops. Orbital magnetic resonance imaging with contrast enhancement was consistent with an iris tumor; ultrasound biomicroscopy indicated a semi-solid, mid-stromal iris formation continuous with the lens. Surgical inspection was performed. Surgery showed the presence of a hypermature cataract with a fine break in the anterior capsule of the lens covered by the iris surface. The liquefied cortex infiltrated the iris without diffusing into the aqueous humor. Conclusions and Importance: A so-called morgagnian cataract developed, likely following a penetrating ocular wound. The progressive, slow infiltration of the iris stroma by the crystalline matrix mimicked the appearance of an amelanotic iris tumor

Microfluidic converging/diverging channels optimised for homogeneous extensional deformation

In this work we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field

Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation

Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the anti-proliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, Cdk-4, Cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment

Do institutional arrangements make a difference to transport policy and implementation? Lessons for Britain

This paper describes local government decision-making in transport in three areas of the UK, London, West Yorkshire and Edinburgh, in which major changes in local government decision-making structures have taken place over the last decade, and between which arrangements are now very different. The research discusses whether institutional change has had a beneficial or adverse effect, and whether any of the current structures provides a more effective framework for policy development and implementation. The results show that although the sites share a broadly common set of objectives there are differences in devolved responsibilities and in the extent to which various policy options are within the control of the bodies charged with transport policy delivery. The existence of several tiers of government, coupled with the many interactions required between these public sector bodies and the predominantly private sector public transport operators appears to create extra transactional barriers and impedes the implementation of the most effective measures for cutting congestion. There is, however, a compelling argument for the presence of an overarching tier of government to organise travel over a spatial scale compatible with that of major commuter patterns. The extent to which such arrangements currently appear to work is a function of the range of powers and the funding levels afforded to the co-ordinating organisation

Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD-95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD-95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K+ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage-dependent K+ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease

Total and High Molecular Weight Adiponectin and Hepatocellular Carcinoma with HCV Infection

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades

Spintronic Majority Gates

In this paper we present an overview of two types of majority gate devices based on spintronic phenomena. We compare the spin torque majority gate and the spin wave majority gate and describe work on these devices. We discuss operating conditions for the two device concepts, circuit implication and how these reflect on materials choices for device implementation

Responding to the need of postgraduate education for Planetary Health: Development of an online Master's Degree

Data availability statement: The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.Copyright © 2022 O'Callaghan-Gordo, Moreno, Bosque-Prous, Castro-Sanchez, Dadvand, Guzmán, García-Juanatey, Gascon, Grau, Jordana, Lowe, March, Medina, Mélon, Navas, Núñez Casal, Ruiz-Mallén, Sánchez-Valdivia, Tonne, Triguero-Mas, Zografos and Antó. . Planetary Health has emerged as a new approach to respond to the existential risks that the clime and global environmental crises pose to human societies. As stated by various stakeholders, the challenges involved in Planetary Health are of such magnitude that education must be at the forefront to obtain a meaningful response. Universities and higher education institutions have been specifically called to embed the concept of planetary stewardship in all curricula and train the next generation of researchers and change makers as a matter of urgency. As a response to this call, the Universitat Oberta de Catalunya (UOC), the Universitat Pompeu Fabra (UPF), and the Barcelona Institute for Global Health (ISGlobal) developed the first online and asynchronous Master in Science (MSc) in Planetary Health. The aim of the programme is to train a new generation of academics and professionals who understand the challenges of Planetary Health and have tools to tackle them. This article describes the development of the curriculum of this MSc, presents the main characteristics of the programme and discusses some of the challenges encountered in the development of the programme and its implementation. The design of this MSc was based on: the alignment of the programme with the principles for Planetary Health education with a focus on human health; a multi-, inter-, and trans-disciplinary approach; the urgency to respond to the Anthropocene challenges; and the commitment to the 2030 Agenda. The MSc was recognized as an official degree by the Agency for Quality of the Catalan University System, included in the European Quality Assurance Register for Higher Education, and the Spanish National Academic Coordination body in April 2021 and launched in October 2021. There are currently more than 50 students enrolled in the program coming from a broad range of disciplines and geographic locations. The information presented in this article and the discussion on challenges encountered in developing and implementing the programme can be useful for those working in the development of similar programs.Spanish Ministry of Science and Innovation and State Research Agency through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S); Generalitat de Catalunya through the CERCA Program