Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes

Barriers and facilitators to physical activity among children, adolescents, and young adults with cystic fibrosis: A systematic review and thematic synthesis of qualitative of research

This is the final version. Available from BMJ Publishing Group via the DOI in this record.Availability of data and material: All data relevant to the study are included in the article or uploaded as supplementary information.Objectives: Physical activity is widely recommended in the treatment and management of cystic fibrosis (CF). Despite the numerous physical and psychological benefits, many young people with CF are not achieving the recommended levels of physical activity. The aim of this systematic review was to identify and synthesise available qualitative investigations exploring the motives for, barriers to and facilitators of physical activity among young people with CF. Methods: The following six electronic databases were systematically searched: ASSIA, CINAH, EMBASE, MEDLINE, MEDLINE-in-process, PsycINFO up to August 2019. Keywords were used to identify qualitative research that explored engagement in physical activity among young people with CF. Titles and abstracts were screened by two independent reviewers, and potentially relevant articles were retrieved in full. Articles were eligible for inclusion if they employed any qualitative method and recruited participants under the age of 24 years with CF. Risk of bias of included studies were assessed via the Critical Appraisal Skills Program. Results were synthesised using a thematic approach. Results: Seven studies met our inclusion criteria and were included in the review. Overall, studies were of moderate to high quality. Thematic synthesis identified nine main themes that encompass motives for, barriers to and facilitators of physical activity among young people with CF. These were 1) perceptions of physical activity, 2) value attributed to physical activity, 3) social influences, 4) competing priorities, 5) fluctuating health, 6) normality, 7) control beliefs, 8) coping strategies, and 9) availability of facilities. Previous reviews have been unable to identify intervention characteristics that influence physical activity behaviour. Conclusions: This review provides detailed information on the physical (biological – clinical), psychological, social, and environmental influences on physical activity behaviour, thus providing numerous targets for future interventions. This in turn could facilitate promotion of physical activity among young people with CF.Cystic Fibrosis TrustVertex Pharmaceutical

Spitzer-IRS Spectroscopy of the Prototypical Starburst Galaxy NGC7714

We present observations of the starburst galaxy NGC 7714 with the Infrared Spectrograph IRS on board the Spitzer Space Telescope. The spectra yield a wealth of ionic and molecular features that allow a detailed characterization of its properties. NGC 7714 has an HII region-like spectrum with strong PAH emission features. We find no evidence for an obscured active galactic nucleus, and with [NeIII]/[NeII]~0.73, NGC7714 lies near the upper end of normal-metallicity starburst galaxies. With very little slicate absorption and a temperature of the hottest dust component of 340K, NGC 7714 is the perfect template for a young, unobscured starburstComment: To appear in the special ApJSS issue on early results from Spitze

Models of the Morphology, Kinematics, and Star Formation History of the Prototypical Collisional Starburst System: NGC 7714/7715 = Arp 284

(abridged) We present new N-body, hydrodynamical simulations of the interaction between the starburst galaxy NGC 7714 and its post-starburst companion NGC 7715, focusing on the formation of the collisional features, including: 1) the gas-rich star forming bridge, 2) the large gaseous loop (and stellar tails) to the west of the system, 3) the very extended HI tail to the west and north of NGC 7714, and 4) the partial stellar ring in NGC 7714. Our simulations confirm the results of earlier work that an off-center inclined collision between two disk galaxies is almost certainly responsible for the peculiar morphologies of this system. However, we have explored a wider set of initial galaxy and collisional encounter parameters than previously, and have found a relatively narrow range of parameters that reproduce all the major morphologies of this system. The simulations suggest specific mechanisms for the development of several unusual structures. We find that the complex gas bridge has up to four distinct components, with gas contributed from two sides of NGC 7715, as well as from NGC 7714. The observed gas-star offset in this bridge is accounted for in the simulations by the dissipative evolution of the gas. The models also indicate that the low surface brightness HI tail to the far west of NGC 7714 is the end of the NGC 7715 countertail, curved behind the two galaxies. Spectral evolutionary models of the NGC 7714 core by Lan\c{c}on et al. suggest the possibility of multiple starbursts in the last 300 Myr. Our hydrodynamic models suggest that bursts could be triggered by induced ring-like waves, and a post-collision buildup of gas in the core of the galaxy.Comment: 24 pages, 20 figures, accepted for ApJ Supp

New Observations of Extra-Disk Molecular Gas in Interacting Galaxy Systems, Including a Two-Component System in Stephan's Quintet

We present new CO (1 - 0) observations of eleven extragalactic tails and bridges in nine interacting galaxy systems, almost doubling the number of such features with sensitive CO measurements. Eight of these eleven features were undetected in CO to very low CO/HI limits, with the most extreme case being the NGC 7714/5 bridge. This bridge contains luminous H II regions and has a very high HI column density (1.6 X 10^21 cm^-2 in the 55" CO beam), yet was undetected in CO to rms T(R)* = 2.4 mK. The HI column density is higher than standard H2 and CO self-shielding limits for solar-metallicity gas, suggesting that the gas in this bridge is metal-poor and has an enhanced N(H2)/I(CO) ratio compared to the Galactic value. Only one of the eleven features in our sample was unambiguously detected in CO, a luminous HI-rich star formation region near an optical tail in the compact group Stephan's Quintet. We detect CO at two widely separated velocities in this feature, at ~6000 km/s and ~6700 km/s. Both of these components have HI and H-alpha counterparts. These velocities correspond to those of galaxies in the group, suggesting that this gas is material that has been removed from two galaxies in the group. The CO/HI/H-alpha ratios for both components are similar to global values for spiral galaxies.Comment: 39 pages, Latex, 15 figures, Astronomical Journal, in pres

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation

AbstractAn appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies.From the Clinical EditorExisting in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities

Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors

AbstractPatient-derived xenograft (PDX) tumor models have emerged as a new approach to evaluate the effects of cancer drugs on patients’ personalized tumor grafts enabling to select the best treatment for the cancer patient and providing a new tool for oncology drug developers. Here, we report that human tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX tumors. We xenografted human primary and metastatic tumor samples into immunodeficient mice and found that a fraction of PDX tumors generated from patients’ samples of breast, colon, pancreatic, bladder and renal cancer were histologically similar to lymphocytic neoplasms. Moreover, we found that the first passage of breast and pancreatic cancer PDX tumors after initial transplantation of the tumor pieces from the same human tumor graft could grow as a lymphocytic tumor in one mouse and as an adenocarcinoma in another mouse. Whereas subcutaneous PDX tumors resembling human adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid tumors, formation of B-cell tumor may evolve in a wide range of PDX tumor models. Although PDX tumor models show great promise in the development of personalized therapy for cancer patients, our results suggest that confidence in any given PDX tumor model requires careful screening of lymphocytic markers

The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)

Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention. Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff. Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision. Conclusions: We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes

A nearby GRB host prototype for z~7 Lyman-break galaxies: Spitzer-IRS and X-shooter spectroscopy of the host galaxy of GRB031203

Gamma-ray burst (GRB) host galaxies have been studied extensively in optical photometry and spectroscopy. Here we present the first mid-infrared spectrum of a GRB host, HG031203. It is one of the nearest GRB hosts at z=0.1055, allowing both low and high-resolution spectroscopy with Spitzer-IRS. Medium resolution UV-to-K-band spectroscopy with the X-shooter spectrograph on the VLT is also presented, along with Spitzer IRAC and MIPS photometry, as well as radio and sub-mm observations. These data allow us to construct a UV-to-radio spectral energy distribution with almost complete spectroscopic coverage from 0.3-35 micron of a GRB host galaxy for the first time, potentially valuable as a template for future model comparisons. The IRS spectra show strong, high-ionisation fine structure line emission indicative of a hard radiation field in the galaxy, suggestive of strong ongoing star-formation and a very young stellar population. The selection of HG031203 via the presence of a GRB suggests that it might be a useful analogue of very young star-forming galaxies in the early universe, and hints that local BCDs may be used as more reliable analogues of star-formation in the early universe than typical local starbursts. We look at the current debate on the ages of the dominant stellar populations in z~7 and z~8 galaxies in this context. The nebular line emission is so strong in HG031203, that at z~7, it can reproduce the spectral energy distributions of z-band dropout galaxies with elevated IRAC 3.6 and 4.5 micron fluxes without the need to invoke a 4000A break.Comment: Published in ApJ. 9 pages, 6 figures, emulateapj styl

Program analysis is harder than verification: A computability perspective

We study from a computability perspective static program analysis, namely detecting sound program assertions, and verification, namely sound checking of program assertions. We first design a general computability model for domains of program assertions and correspond- ing program analysers and verifiers. Next, we formalize and prove an instantiation of Rice\u2019s theorem for static program analysis and verifica- tion. Then, within this general model, we provide and show a precise statement of the popular belief that program analysis is a harder prob- lem than program verification: we prove that for finite domains of pro- gram assertions, program analysis and verification are equivalent prob- lems, while for infinite domains, program analysis is strictly harder than verification