Sustained release vaccine platforms for enhanced humoral immunity

Vaccines aim to modulate the immune system to elicit a sufficiently robust, yet targeted, immune response with specifiable immune cell phenotypes.1,2 Failure of a single vaccine administration to elicit such a response likely arises from inappropriate temporal control over antigen/adjuvant presentation and immune cell activation.2 Recent work demonstrates the potential for sustained, low-level presentation of antigens and adjuvants for just over a week to yield more potent and long-lasting immunity.3 Please download the file below for full content

High-affinity anion binding by steroidal squaramide receptors

Exceptionally powerful anion receptors have been constructed by placing squaramide groups in axial positions on a steroidal framework. The steroid preorganizes the squaramide NH groups such that they can act cooperatively on a bound anion, while maintaining solubility in nonpolar media. The acidic NH groups confer higher affinities than previously-used ureas or thioureas. Binding constants exceeding 1014?M?1 have been measured for tetraethylammonium salts in chloroform by employing a variation of Cram’s extraction procedure. The receptors have also been studied as transmembrane anion carriers in unilamellar vesicles. Unusually their activities do not correlate with anion affinities, thus suggesting an upper limit for binding strength in the design of anion carrier

The promotion of homebased physical activity for people with lung and cancer cachexia, a qualitative study of healthcare professionals, patients and carers

Purpose There is some evidence of the benefits of physical activity (PA) in patients with lung cancer; however, there is a lack of understanding of acceptable PA for patients with established cachexia and how to facilitate sustainable behaviour change to promote PA. Therefore, this study explored the views of healthcare professionals (HP), patients with lung cancer and cachexia, and their carers on preferences for, barriers and facilitators of homebased PA. Methods This qualitative study involved ten telephone interviews with HPs and face-to-face interviews with seven patients with lung cancer and cachexia and their carers. Interviews were transcribed and analysed thematically. The Capability, Opportunity, Motivation and Behaviour (COM-B) model was used as a framework for the thematic cross-group analysis. Results The types of homebased PA suggested by patients with lung cancer and cachexia (n = 7), their carers (n = 7) and HPs (n = 10) were functional, flexible, individualised and initially of short duration and low intensity. PA was influenced by themes within physical and psychological Capability, physical and social Opportunities as well as automatic and reflective Motivation. Conclusion Based on a behaviour change theory, principles to promote homebased PA were developed. These principles need to be integrated into tools to promote PA in people with lung cancer and weight loss. Implications for Cancer Survivors The application of the proposed principles by clinicians will promote physical activity, enhancing the function and wellbeing of patients with lung cancer and reducing burden on carers. Introductio

Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes

Thiourea isosteres as anion receptors and transmembrane transporters

Compounds containing cyanoguanidine and 3-amino-1,2,4-benzothiadiazine-1,1-dioxide have been studied as anion receptors and transporters. Significant affinity for oxo-anions was observed in organic solution and the receptors were found to function as transmembrane chloride/nitrate antiporters with transport rates enhanced in the presence of valinomycin–K+ complex.<br/

A randomized, controlled trial of endovenous thermal ablation using the 810-nm wavelength laser and the ClosurePLUS radiofrequency ablation methods for superficial venous insufficiency of the great saphenous vein

BackgroundGreat saphenous vein (GSV) incompetence is the most common cause of superficial venous insufficiency. Radiofrequency catheter ablation (RFA) is superior to conventional ligation and stripping, and endovenous laser treatment (EVL) has emerged as an effective alternative to RFA. This randomized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results.MethodsBetween June 2006 and May 2008, patients with symptomatic primary venous insufficiency due to GSV incompetence were randomized to RFA or EVL. Patients with bilateral disease were randomized for treatment of the first leg and received the alternative method on the other. Pretreatment examination included a leg assessment using the Venous Clinical Severity Score (VCSS) and CEAP classification. Patients completed the Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2). RFA was performed with the ClosurePlus system (VNUS Medical Technologies, Sunnyvale, Calif). EVL was performed with the EVLT system (AngioDynamics Inc, Queensbury, NY). Early (1-week and 1-month) postoperative results of pain, bruising, erythema, and hematoma were recorded. Duplex ultrasound (DU) imaging was used at 1 week and 1 year to evaluate vein status. VCSS scores and CEAP clinical class were recorded at each postoperative visit, and quality of life (QOL) using CIVIQ2 was assessed at 1 month and 1 year.ResultsThe study enrolled 118 patients (141 limbs): 46 (39%) were randomized to RFA and 48 (40%) to EVL, and 24 (20%) had bilateral GSV incompetence. At 1 week, one patient in the RFA group had an open GSV and was deemed a failure. More bruising occurred in the EVL group (P = .01) at 1 week, but at 1 month, there was no difference in bruising between groups. At 1 year, DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients (P = .002). The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL (P = .002), but there was no difference between groups at 1 month (P = .07) and 1 year (P = .9). Overall QOL mean score improved over time for all patients (P < .001). CEAP clinical class scores of ≥3 were recorded in 21 RFA (44%) and 24 EVL patients (44%) pretreatment, but at 1-year, 9 RFA (19%) and 12 EVL patients (24%) had scores of ≥3 (P < .001). This represented a significant improvement in all patients compared with baseline.ConclusionBoth methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency. EVL is associated with greater bruising and discomfort in the perioperative period but may provide a more secure closure over the long-term than RFA

Near-Infrared Monitoring of Volatiles in Frozen Lunar Simulants While Drilling

In Situ Resource Utilization (ISRU) focuses on using local resources for mission consumables. The approach can reduce mission cost and risk. Lunar polar volatiles, e.g. water ice, have been detected via remote sensing measurements and represent a potential resource for both humans and propellant. The exact nature of the horizontal and depth distribution of the ice remains to be documented in situ. NASA's Resource Prospector mission (RP) is intended to investigate the polar volatiles using a rover, drill, and the RESOLVE science package. RP component level hardware is undergoing testing in relevant lunar conditions (cryovacuum). In March 2015 a series of drilling tests were undertaken using the Honeybee Robotics RP Drill, Near-Infrared Volatile Spectrometer System (NIRVSS), and sample capture mechanisms (SCM) inside a 'dirty' thermal vacuum chamber at the NASA Glenn Research Center. The goal of these tests was to investigate the ability of NIRVSS to monitor volatiles during drilling activities and assess delivery of soil sample transfer to the SCMs in order to elucidate the concept of operations associated with this regolith sampling method

Funnel plots, performance variation and the Myocardial Infarction National Audit Project 2003–2004

BACKGROUND: Clinical governance requires health care professionals to improve standards of care and has resulted in comparison of clinical performance data. The Myocardial Infarction National Audit Project (a UK cardiology dataset) tabulates its performance. However funnel plots are the display method of choice for institutional comparison. We aimed to demonstrate that funnel plots may be derived from MINAP data and allow more meaningful interpretation of data. METHODS: We examined the attainment of National Service Framework standards for all hospitals (n = 230) and all patients (n = 99,133) in the MINAP database between 1(st )April 2003 and 31(st )March 2004. We generated funnel plots (with control limits at 3 sigma) of Door to Needle and Call to Needle thrombolysis times, and the use of aspirin, beta-blockers and statins post myocardial infarction. RESULTS: Only 87,427 patients fulfilled criteria for analysis of the use of secondary prevention drugs and 15,111 patients for analysis by Door to Needle and Call to Needle times (163 hospitals achieved the standards for Door to Needle times and 215 were within or above their control limits). One hundred and sixteen hospitals fell outside the 'within 25%' and 'more than 25%' standards for Call to Needle times, but 28 were below the lower control limits. Sixteen hospitals failed to reach the standards for aspirin usage post AMI and 24 remained below the lower control limits. Thirty hospitals were below the lower CL for beta-blocker usage and 49 outside the standard. Statin use was comparable. CONCLUSION: Funnel plots may be applied to a complex dataset and allow visual comparison of data derived from multiple health-care units. Variation is readily identified permitting units to appraise their practices so that effective quality improvement may take place

Volatiles Loss from Water Bearing Regolith Simulant at Lunar Environments

Permanently shadowed craters at the lunar poles contain water, ~5 wt% according to LCROSS. Interest in water for ISRU applications. Desire to 'ground truth' water using surface prospecting; e.g. Resource Prospector (RP) & RESOLVE. How to access subsurface water resources and accurately measure quantity; Excavation operations and exposure to lunar environment may affect the results A series a ground based dirty thermal vacuum tests are being conducted to better understand the subsurface sampling operations: Sample removal and transfer, Volatiles loss during sampling operations, Concept of operations, Instrumentation. This presentation covers: The capabilities of the VF-13 Thermal Vacuum Chamber (Tvac). The Resource Prospector TVAC hardware. The summary and results of 5 years of RP volatiles tests; 43 viable sample

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.</p