Early palliative care for solid and blood cancer patients and caregivers: Quantitative and qualitative results of a long-term experience as a case of value-based medicine

Introduction: Cancer patients and their caregivers have substantial unmet needs, that negatively impact the clinical outcome and quality of life. However, interventions aimed to address such needs are still suboptimal, failing to answer the recent healthcare call for the adoption of value-based models of care. In the case of incurable oncologic and hematologic cancers, a value-based model of care should plan advanced care on patients' needs and include the quality of death as an outcome. The integration of early palliative care into standard oncologic care for patients with advanced cancers represents a recent innovative model of assistance whose benefits for patients and caregivers are now widely recognized. The key elements underlying the reasons behind these benefits are the multidisciplinary collaboration (teamwork), an honest and empathetic communication between the early palliative care team, the patient, and the caregiver (rapport building), and the ability to detect changes in the physical/psychosocial wellbeing of the patient, along the whole disease trajectory (constant monitoring). Methods: This community case study documents the quantitative and qualitative results of a long term clinical and research experience in delivering early palliative care service to address both solid and blood cancer patients' and their primary caregivers' needs. Results: Data showed decreased use of chemotherapy, blood transfusions and referral to intensive care units near the end of life; increased life expectancy; improved symptom burden and mood; increased frequency of goals-of-care and advanced care planning conversations. Hope perception among bereaved caregivers was associated with resilience and realistic expectations raising from honest communication with the early palliative care team and appreciation toward the model. Patients and caregivers perceived the possibility of a good death as realistic and not as an unlikely event as it was for patients and caregivers on standard oncologic care only. Gratitude expressions toward the model and the team were frequently identified in their reports and positively associated with communication and spirituality. Conclusions: These findings are discussed in the context of an updated literature review regarding value-based care and suggest that early palliative care integrated into standard oncology care may be considered as an effective model of value-based care

Determination of the binding epitope of RGD-peptidomimetics to \u3b1v\u3b23 and \u3b1IIb\u3b23 integrin-rich intact cells by NMR and computational studies

NMR experiments (transferred NOE and Saturation Transfer Difference) were used to shed light on the binding epitope of RGD peptidomimetics 1-3 with integrins \u3b1v\u3b23 and \u3b1IIb\u3b23, expressed on the membrane of ECV304 bladder cancer cells and human platelets, respectively. The NMR results were supported by docking calculations in the active sites of \u3b1v\u3b23 and \u3b1IIb\u3b23 integrin receptors and were compared to the results of competitive \u3b1v\u3b23 receptor binding assays and competitive ECV304 cell adhesion experiments. While cis RGD ligand 1 interacts mainly with the \u3b1 integrin subunit through its basic guanidine group, trans RGD ligands 2 and 3 are able to interact with both the \u3b1 and \u3b2 integrin subunits via an electrostatic clam

Release of DNA from Dermanyssus gallinae during the Biting Process

none10noDermanyssus gallinae is a hematophagous ectoparasitic mite that usually infests poultry, but is also known for occasionally attacking other animals and humans. It represents a major problem for poultry systems all over the world, with detrimental effects for both production and animal welfare. Despite the significance of D. gallinae, very little is known about the biting process to date. Therefore, this study has aimed to verify if mite DNA is injected into the host skin during the blood meal. Mite DNA has been detected by seminested PCR from infested chicken skin and quantified by real-time PCR. Furthermore, its localization within the host tissue has been checked by fluorescent in situ hybridization. Results showed that a very little amount of D. gallinae DNA can be released by mites, suggesting that the latter do not introduce whole or partially destroyed cells into the host, but rather it injects traces of nucleic acids, possibly together with merocrine secretions.Pugliese, Nicola; Raele, Donato Antonio; Schiavone, Antonella; Cafiero, Maria Assunta; Potenza, Lucia; Samarelli, Rossella; Circella, Elena; Vasco, Ilaria; Pennuzzi, Germana; Camarda, AntonioPugliese, Nicola; Raele, Donato Antonio; Schiavone, Antonella; Cafiero, Maria Assunta; Potenza, Lucia; Samarelli, Rossella; Circella, Elena; Vasco, Ilaria; Pennuzzi, Germana; Camarda, Antoni

Release of {DNA} from Dermanyssus gallinae during the Biting Process

: Dermanyssus gallinae is a hematophagous ectoparasitic mite that usually infests poultry, but is also known for occasionally attacking other animals and humans. It represents a major problem for poultry systems all over the world, with detrimental effects for both production and animal welfare. Despite the significance of D. gallinae, very little is known about the biting process to date. Therefore, this study has aimed to verify if mite DNA is injected into the host skin during the blood meal. Mite DNA has been detected by seminested PCR from infested chicken skin and quantified by real-time PCR. Furthermore, its localization within the host tissue has been checked by fluorescent in situ hybridization. Results showed that a very little amount of D. gallinae DNA can be released by mites, suggesting that the latter do not introduce whole or partially destroyed cells into the host, but rather it injects traces of nucleic acids, possibly together with merocrine secretions

Stigma of Palliative Care among Patients with Advanced Cancer and Their Caregivers on Early Palliative Care

Simple Summary Early palliative care represents a successful model of care for advanced cancer patients and their caregivers. Yet, early palliative care provision remains confined to the last weeks of life. Among the possible reasons, the stigma associated with the name "palliative care" seems to have a prominent role. The present study aimed to investigate the perception of palliative care that a sample of 78 patients and 110 caregivers had before their referral to the early palliative care service. The results suggest on which levels it is necessary to intervene to overcome the stigma. From a policy perspective, it is clear that broad education is needed to ensure a more widespread understanding of the essence of anticipated palliative care. The early referral to palliative care (PC) represents a successful value-based model with proven benefits regarding the quality of life and clinical outcomes for advanced cancer patients and their caregivers. Yet, its provision remains typically confined to the last weeks of life as per the historical, late PC model. The stigma according to which PC represents end-of-life care has been identified as the root of the problem. To explore the presence and effects of the stigma in a clinical context, we surveyed 78 patients and 110 caregivers (mean age: 71.7 and 60.7, respectively) on early PC to study what their perception of PC was before their direct experience. The responses were analyzed through a qualitative descriptive approach. The participants explicitly mentioned a lack of knowledge about PC (53% of the sample), which they identified also among physicians and the population (13%); an identification of PC with the late PC model (53%); and a detrimental reaction to the proposal of an early PC referral (83%). However, the participants explicitly mentioned that a direct experience of early PC allowed for an acquired awareness of early PC meaning and benefits (52%), as well as a comprehension of its differences with late PC (34%); the regret for the delayed referral (8%); the perception of the word "palliative" as a barrier (21%); and the belief that early PC should be part of the cancer routine practice (25%). A comprehensive multi-level intervention is necessary for a widespread understanding of the essence of anticipated PC

Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model

Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production. Moreover, increased plasma OPN correlated with higher BM fibrosis grade and inferior overall survival in MF patients. To understand whether OPN is a druggable target in MF, we assessed putative inhibitors of OPN expression in vitro and identified ERK1/2 as a major regulator of OPN production. Increased OPN plasma levels were associated with BM fibrosis development in the Romiplostim-induced MF mouse model. Moreover, ERK1/2 inhibition led to a remarkable reduction of OPN production and BM fibrosis in Romiplostim-treated mice. Strikingly, the antifibrotic effect of ERK1/2 inhibition can be mainly ascribed to the reduced OPN production since it could be recapitulated through the administration of anti-OPN neutralizing antibody. Our results demonstrate that OPN is a novel druggable target in MF and pave the way to antifibrotic therapies based on the inhibition of ERK1/2-driven OPN production or the neutralization of OPN activity

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells

IntroductionDespite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity.MethodsIn this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs).ResultsActivated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature.ConclusionThese data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio