Sensor placement for combined sewer system monitoring in the Besòs river basin

In this paper, a sensor placement methodology for sewer systems monitoring in order to measure direct discharge to the river during intense rainfall events is presented. During these events, Combined Sewer Overflows (CSOs) may occur, causing serious problems of contamination of the corresponding receiving waters. The current national regulation compels sewer systems’ managers to monitor and quantify direct discharge to these receiving waters, in order to track these events. Hence, the selection of the appropriate sensor set in order to monitor the critical outlets of the network is of paramount importance to adequately monitor CSOs and minimize their effect by using the information gathered from these measurements. Here, a methodology considering relevant characteristics of each potential monitoring point —e.g. number of discharges, volume discharged or percentage of polluted mass— is defined to select the final sensor set. The presented methodology is applied to three different combined sewer systems in the Besòs river basin nearby Barcelona city area in Catalonia (Spain), i.e. Granollers, La Llagosta and Montornès systems.Peer ReviewedPostprint (published version

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Whose "successful ageing"?:Lay- and researcher-driven conceptualisations of ageing well

Background and Objectives: To date, there is no consensus definition of successful ageing (SA). In the literature, conceptualisations of SA are generally researcher-driven operational definitions or layperson perspectives. The current study aims to systematically review and compare quantitative operational definitions of SA with qualitative, layperson perspectives of SA. Methods: PubMed, PsycInfo, ISI Web of Knowledge, EmBase and CINAHL databases were searched using the words "successful ageing" and related terms. Peer-reviewed studies positing quantifiable operational definitions of SA were included, as were studies that conducted exploratory qualitative study of layperson perspectives of SA. Results: Marked differences in the focus of SA conceptualizations between researchers and laypersons were revealed. Qualitative studies demonstrated a greater emphasis on psychosocial aspects of SA, such as attitude whilst quantitative studies were generally biomedically focused, e.g. physical functioning/disability. Conclusions: Little concordance in classification of SA is found across the two perspectives such that an individual may be simultaneously classified as unsuccessfully ageing from a biomedical approach and successfully ageing from a layperson perspective. Most studies have been conducted in North America and the UK using non-clinical populations, resulting in limitations on generalizability. Alternative perspectives of SA must be taken into consideration in the practical application of SA

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy.

Pegylation of nanoparticles has been widely implemented in the field of drug delivery to prevent macrophage clearance and increase drug accumulation at a target site. However, the shielding effect of polyethylene glycol (PEG) is usually incomplete and transient, due to loss of nanoparticle integrity upon systemic injection. Here, we have synthesized unique PEG-dendron-phospholipid constructs that form super stealth liposomes (SSLs). A \u3b2-glutamic acid dendron anchor was used to attach a PEG chain to several distearoyl phosphoethanolamine lipids, thereby differing from conventional stealth liposomes where a PEG chain is attached to a single phospholipid. This composition was shown to increase liposomal stability, prolong the circulation half-life, improve the biodistribution profile and enhance the anticancer potency of a drug payload (doxorubicin hydrochloride)

Facilitators and barriers faced by community organizations supporting older adults during the COVID-19 pandemic

Background: During the COVID-19 pandemic, olderadult-focused community organizations played an essential role in supporting the wellbeing of older adults. Supporting older adults during this time required extensive modifications to existing programming but their adaptations during the COVID-19 pandemic are not well documented. The purpose of this study was to understand how older adult-focused community organizations adopted virtual delivery formats during the COVID-19 pandemic and their perspectives of the barriers and facilitators for organizations and older adults. Methods: To understand the changes that were made, we conducted a qualitative environmental scan of community-based services across British Columbia. Online searches were complemented by snowball sampling and key informant interviews. We identified 90 older adult-serving community organizations and interviewed 26. We used reflexive thematic analysis to understand the main strategies. Results: These community organizations described barriers related to older adults’ wellbeing, information technology proficiency, and personal/organizational losses related to changes in program structure. Facilitators for virtual activities and events included inter- and intra-organizational collaboration, intrinsic qualities of program design, physical resources to supporting virtual programming, and availability of technological resources. Organizations described meeting the challenge by increasing the ‘depth’ and ‘breadth’ of their reach. Conclusion: Older adult-focused community organizations recognized the critical role they played for older adults and adapted their resources to meet those needs. Informational technology was quickly and effectively leveraged to promote social interaction for older adults when physical distancing was required during the COVID-19 pandemic. Barriers related to cost, time, and ultimately older adults’ interest in a virtual delivery format were critical limitations. Graphical Abstract

Concept Modelling of Vehicle Joints and Beam-Like Structures through Dynamic FE-Based Methods

This paper presents dynamic methodologies able to obtain concept models of automotive beams and joints, which compare favourably with the existing literature methods, in terms of accuracy, easiness of implementation, and computational loads. For the concept beams, the proposed method is based on a dynamic finite element (FE) approach, which estimates the stiffness characteristics of equivalent 1D beam elements using the natural frequencies, computed by a modal analysis of the detailed 3D FE model of the structure. Concept beams are then connected to each other by a concept joint, which is obtained through a dynamic reduction technique that makes use of its vibration normal modes. The joint reduction is improved through the application of a new interface beam-to-joint element, able to interpolate accurately the nodal displacements of the outer contour of the section, to obtain displacements and rotations of the central connection node. The proposed approach is validated through an application case that is typical in vehicle body engineering: the analysis of a structure formed by three spot-welded thin-walled beams, connected by a joint

A Novel Examination of Successful Aging Trajectories at the End of Life

A successful aging (SA) index was captured in a longitudinal population-based cohort study of individuals aged 75 and older and examined longitudinally using growth mixture modelling (GMM) to identify groups with similar trajectories using decedents' (n = 1,015) last completed interview and up to four previous data collection waves before death. GMM identified a three-class model. Classes were high-functioning, no decline (HN); high-functioning, gradual decline (HG); and low-functioning, steep decline (LS). HN class individuals were significantly younger at death (p < 0.001) and at last interview (p < 0.001), consisted of more men (p < 0.001), and more likely to be married (p < 0.001) compared to HG and LS class individuals. These results demonstrate the different ways in which individuals can experience successful aging at the end of life. This study provides the framework for future research into life-course processes of aging, with important implications for policy and practice