Recruiting, advertising and marketing strategies in all-volunteer force nations case studies of Canada, Australia, the United Kingdom, and the United States

http://archive.org/details/recruitingdverti109452442

Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells

Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid pharmacokinetics in pre-clinical neuroblastoma models. Here we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance retinoic acid action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signaling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans

The liposomal delivery of hydrophobic oxidovanadium complexes imparts highly effective cytotoxicity and differentiating capacity in neuroblastoma tumour cells

Oxidovanadium complexes with organic ligands are well known to have cytotoxic or differentiating capabilities against a range of cancer cell types. Their limited use in clinical testing though has resulted largely from uncertainties about the long-term toxicities of such complexes, due in part to the speciation to vanadate ions in the circulation. We hypothesised that more highly stable complexes, delivered using liposomes, may provide improved opportunities for oxidovanadium applications against cancer. In this study we sourced specifically hydrophobic forms of oxidovanadium complexes with the explicit aim of demonstrating liposomal encapsulation, bioavailability in cultured neuroblastoma cells, and effective cytotoxic or differentiating activity. Our data show that four ethanol-solubilised complexes with amine bisphenol, aminoalcohol bisphenol or salan ligands are equally or more effective than a previously used complex bis(maltolato)oxovanadium(V) in neuroblastoma cell lines. Moreover, we show that one of these complexes can be stably incorporated into cationic liposomes where it retains very good bioavailability, apparently low speciation and enhanced efficacy compared to ethanol delivery. This study provides the first proof-of-concept that stable, hydrophobic oxidovanadium complexes retain excellent cellular activity when delivered effectively to cancer cells with nanotechnology. This offers the improved prospect of applying oxidovanadium-based drugs in vivo with increased stability and reduced off-target toxicity.</p

Sea ice working group (SIP)

The sea ice is a crucial component of the polar climate system, and has an impact on albedo, heat and gas ex- change, primary productivity and car- bon export, atmospheric and ocean circulation, freshwater budget, ocean stratification, and deep water mass for- mation. It is therefore critical that it is correctly specified as a forcing or pre- dicted as a feedback in modeling stud- ies

Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival

The authors aim to develop siRNA therapeutics for cancer that can be administered systemically to target tumors and retard their growth. The efficacy of systemic delivery of siRNA to tumors with nanoparticles based on lipids or polymers is often compromised by their rapid clearance from the circulation by the liver. Here, multifunctional cationic and anionic siRNA nanoparticle formulations are described, termed receptor‐targeted nanocomplexes (RTNs), that comprise peptides for siRNA packaging into nanoparticles and receptor‐mediated cell uptake, together with lipids that confer nanoparticles with stealth properties to enhance stability in the circulation, and fusogenic properties to enhance endosomal release within the cell. Intravenous administration of RTNs in mice leads to predominant accumulation in xenograft tumors, with very little detected in the liver, lung, or spleen. Although non‐targeted RTNs also enter the tumor, cell uptake appears to be RGD peptide‐dependent indicating integrin‐mediated uptake. RTNs with siRNA against MYCN (a member of the Myc family of transcription factors) in mice with MYCN‐amplified neuroblastoma tumors show significant retardation of xenograft tumor growth and enhanced survival. This study shows that RTN formulations can achieve specific tumor‐targeting, with minimal clearance by the liver and so enable delivery of tumor‐targeted siRNA therapeutics

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis:Design and rationale

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.Trial registration: ClinicalTrials.gov Identifier: NCT05946044.</p

The need for fresh blood: understanding organizational age inequality through a vampiric lens

YesThis article argues that older age inequality within and across working life is the result of vampiric forms and structures constitutive of contemporary organizing. Rather than assuming ageism occurs against a backdrop of neutral organizational processes and practices, the article denaturalizes (and in the process super-naturalizes) organizational orientations of ageing through three vampiric aspects: (un)dying, regeneration and neophilia. These dimensions are used to illustrate how workplace narratives and logics normalize and perpetuate the systematic denigration of the ageing organizational subject. Through our analysis it is argued that older workers are positioned as inevitable ‘sacrificial objects’ of the all-consuming immortal organization. To challenge this, the article explicitly draws on the vampire and the vampiric in literature and popular culture to consider the possibility of subverting existing notions of the ‘older worker’ in order to confront and challenge the subtle and persistent monstrous discourses that shape organizational life

The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities

Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures