Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE): study protocol for a randomized controlled trial

Contains fulltext : 97893.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Polycystic liver disease (PLD) is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. METHODS/DESIGN: This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. DISCUSSION: This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01157858

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Contains fulltext : 109282.pdf (publisher's version ) (Open Access)BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405

The SFXC software correlator for Very Long Baseline Interferometry: Algorithms and Implementation

In this paper a description is given of the SFXC software correlator, developed and maintained at the Joint Institute for VLBI in Europe (JIVE). The software is designed to run on generic Linux-based computing clusters. The correlation algorithm is explained in detail, as are some of the novel modes that software correlation has enabled, such as wide-field VLBI imaging through the use of multiple phase centres and pulsar gating and binning. This is followed by an overview of the software architecture. Finally, the performance of the correlator as a function of number of CPU cores, telescopes and spectral channels is shown.Comment: Accepted by Experimental Astronom

Дослідження ефективності управління примежовим шаром на опорній поверхні шляхової структури перспективних транспортних технологій Maglev

Исследованы физические процессы управления пограничным слоем на профилированной поверхности путевой структуры перспективных транспортных технологий. Установлены закономерности влияния параметров управления пограничным слоем на распределение скоростей на путевой структуре.The physical processes of control are investigational by a frontier layer on the profiled surface of the ground structure of perspective transport technologies. Conformities to law of influence of control parameters are set by a frontier layer on distribution of speeds on the ground structure

Глобализация как фактор радикализации трансформации приоритетов социально-экономического развития в посттранзитивних экономиках

Expression of the for khead transcription factor FOXP1 is essential for early B-cell development, whereas down regulation ofFOXP1at the germinal center (GC) stage is required for GC B-cell function. Aberrantly high FOXP1 expression is frequently observed in diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma, being associated with poor prognosis. Here, by gene expression analysis upon ectopic over expression of FOXP1 in primary

Co-visualise the impact of Sickle Cell: How can we use design thinking to investigate and visualise the impact of Sickle Cell?

Background: This study leverages the principles of design thinking and system thinking to investigate and visualise the impact of Sickle Cell. Sickle cell is a genetic disorder that affects millions of people worldwide and disproportionately affects people of African and Caribbean descent. Patients with this condition face a range of physical, emotional, and social challenges due to the unpredictable nature of the disease. The fundamental principle explored in this study is designing for empathy. Design for Sickle Cell (D4SC) initiative was developed to bridge the gap between art, design and science within the Sickle Cell landscape. Aim: This design research project aims to investigate and visualise the condition's impact from a multi-stakeholder perspective by developing art and design prototypes that can inform an innovative Sickle Cell exhibition. Methods: Techniques from social constructionism, phenomenological qualitative research and user-experience research were utilised to create a novel methodology for this small-scale study. The methodology involved a multi-step process combining the double diamond, system thinking, and action research frameworks to gather insights that guided the development of this design research practice. Semi-structured interviews were conducted with Sickle Cell experts consisting of patients, a healthcare practitioner and support staff. Common themes were generated from their experience of the condition's impact. D4SC collaborated with Imperial's Invisible Warrior Project, RCABlack, a PhD Archivist Researcher and Photographer at the Slade School of Fine Art, to develop visual prototypes for the exhibition. Results: The findings from these interviews informed the development of a range of workshops and prototypes. The prototypes were tested by Sickle Cell experts and healthcare designers, who provided feedback on the concept. The results showed that the design outputs and exhibition were well-received and had the potential to improve education and awareness of the condition and promote empathy. Design research in healthcare has the potential to create innovative solutions. With the use of a multidisciplinary approach, it can yield a positive impact. Conclusions: The project highlights the importance of design thinking, system thinking and collaboration in developing innovative healthcare solutions for this complex health condition. The study demonstrates the value of a multi-stakeholder approach to designing for empathy. It shows the potential of visualising the impact of Sickle Cell to promote understanding and awareness of the condition. To facilitate the further advancement of the concepts developed in this study, securing funding an

The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells

Proteomic

Aspiration–sclerotherapy Results in Effective Control of Liver Volume in Patients with Liver Cysts

Purpose To study the extent to which aspiration–sclerotherapy reduces liver volume and whether this therapy results in relief of symptoms. Results Four patients, group I, with isolated large liver cysts, and 11 patients, group II, with polycystic livers, underwent aspiration–sclerotherapy. Average volume of aspirated cyst fluid was 1,044 ml (range 225–2,000 ml) in group I and 1,326 ml (range 40–4,200 ml) in group II. Mean liver volume before the procedure was 2,157 ml (range 1,706–2,841 ml) in group I and 4,086 ml (range 1,553–7,085 ml) in group II. This decreased after the procedure to 1,757 ml (range 1,479–2,187 ml) in group I. In group II there was a statistically significant decrease to 3,347 ml (range 1,249–6,930 ml, P = 0.008). Volume reduction was 17.1% (range −34.7% to −4.1%) and 19.2% (range −53.9% to +2.4%) in groups I and II, respectively. Clinical severity of all symptoms decreased, except for involuntary weight loss and pain in group II. Conclusion Aspiration–sclerotherapy is an effective means of achieving liver volume reduction and relief of symptoms