Highly active iridium(I) complexes for the selective hydrogenation of carbon-carbon multiple bonds

New iridium(I) complexes, bearing a bulky NHC/phosphine ligand combination, have been established as extremely efficient hydrogenation catalysts that can be used at low catalyst loadings, and are compatible with functional groups which are often sensitive to more routinely employed hydrogenation methods

Systematic overview of economic evaluations of health-related rehabilitation

Background: Health related rehabilitation is instrumental in improving functioning and promoting participation by people with disabilities. To make clinical and policy decisions about health-related rehabilitation, resource allocation and cost issues need to be considered. Objectives: To conduct an overview of systematic reviews (SRs) on economic evaluations of health-related rehabilitation. Methods: We searched multiple databases to identify relevant SRs of economic evaluations of health-related rehabilitation. Review quality was assessed by AMSTAR checklist. Results: We included 64 SRs, most of which included economic evaluations alongside randomised controlled trials (RCTs). The review quality was low to moderate (AMSTAR score 5-8) in 35, and high (score 9-11) in 29 of the included SRs. The included SRs addressed various health conditions, including spinal or other pain conditions (n=14), age-related problems (11), stroke (7), musculoskeletal disorders (6), heart diseases (4), pulmonary (3), mental health problems (3), and injury (3). Physiotherapy was the most commonly evaluated rehabilitation intervention in the included SRs (n=24). Other commonly evaluated interventions included multidisciplinary programmes (14); behavioural, educational or psychological interventions (11); home-based interventions (11); complementary therapy (6); self-management (6); and occupational therapy (4). Conclusions: Although the available evidence is often described as limited, inconsistent or inconclusive, some rehabilitation interventions were cost-effective or showed cost-saving in a variety of disability conditions. Available evidence comes predominantly from high income countries, therefore economic evaluations of health-related rehabilitation are urgently required in less resourced settings

The Determination of Total Energy Expenditure During and Following Repeated High-Intensity Intermittent Sprint Work

International Journal of Exercise Science 10(3): 312-321, 2017. The purpose of this study was to examine the variation in oxidative, glycolytic, and post-exercise O2 kinetic contribution during two distinct high-intensity interval training (HIIT) protocols using a 1:1 work-to-rest ratio (30:30 sec) and a 2:1 work-to-rest ratio (30:15 sec). HIIT familiarized males (n =6) and females (n = 8) were recruited for this study. All subject underwent 3 testing session, an incremental maximal exertion treadmill test and 30:30 and 30:15 HIIT protocols in a counterbalanced order. Each HIIT protocol measured oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) to represent oxidative contribution. Capillary blood lactate was also analyzed to represent glycolytic contribution during both HIIT sessions. Repeated-measures ANOVA revealed a relative and absolute significant difference between the oxidative, glycolytic, and post-exercise oxygen kinetics between 30:30 and 30:15 HIIT session. 30:30 displayed a greater contribution from the oxidative system while the 30:15 displayed an increase contribution from the glycolytic system and displayed an increase in EE during the post-exercise oxygen kinetics phase. Results also revealed no significant findings between the two HIIT sessions in regards to absolute EE (30:30 = 258.2 + 43 kcals, 30:15 = 261 + 43.6 kcals). The addition of blood lactate following exercise did display a noteworthy contribution from the glycolytic system. In conclusion, utilizing pulmonary gas exchange in conjunction with blood lactate depicts an acceptable EE estimation during a bout of HIIT

Evolving antimicrobial resistance in a patient receiving palliative OPAT for a vascular graft infection: a case report

Prosthetic vascular graft infection is devastating and frequently fatal. Cure requires removal of the graft and reperfusion by placement of a new graft. However, no evidence based guidelines exist for management where removal of the graft is not possible. We describe a patient who lived in a state of chronic infection suppression through outpatient parenteral antimicrobial therapy (OPAT) over a period of 32 months, and outline the challenges experienced and strategies used to suppress infection in the face of escalating antimicrobial resistance. To date there have been very few reports of OPAT used in the palliative context and this case illustrates the microbiological issues that can arise and the importance of the full OPAT multi-disciplinary team in managing these issues and optimising the patient's quality and length of life

A Novel Method for Assessing Proximal and Distal Forelimb Function in the Rat: the Irvine, Beatties and Bresnahan (IBB) Forelimb Scale

Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences of damage to this level of the spinal cord (Pearse et al., 2005, Gensel et al., 2006, Anderson et al., 2009), as the majority of human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss of forelimb function due to damage to the white matter affecting both descending motor and ascending sensory systems, and to the gray matter containing the segmental circuitry for processing sensory input and motor output for the forelimb. Additionally, a key priority for human patients with cervical SCI is restoration of hand/arm function (Anderson, 2004). Thus, outcome measures that assess both proximal and distal forelimb function are needed. Although there are several behavioral assays that are sensitive to different aspects of forelimb recovery in experimental models of cervical SCI (Girgis et al., 2007, Gensel et al., 2006, Ballerman et al., 2001, Metz and Whishaw, 2000, Bertelli and Mira, 1993, Montoya et al., 1991, Whishaw and Pellis, 1990), few techniques provide detailed information on the recovery of fine motor control and digit movement

Effect of Ti-substitution on the properties of P3 structure Na2/3Mn0.8Li0.2O2 showing a ribbon superlattice

Funding: Faraday Institution (Grant Number(s): FIRG018); Engineering and Physical Sciences Research Council (Grant Number(s): EP/T019298/1, EP/L017008/1, EP/R023751/1); Energimyndigheten (Grant Number(s): 2020-005249); Spring 8 (Grant Number(s): 2019B1604).Oxygen anion redox offers an effective strategy to enhance the energy density of layered oxide positive electrodes for sodium- and lithium-ion batteries. However, lattice oxygen loss and irreversible structural transformations over the first cycle may result in large voltage hysteresis, thereby impeding practical application. Herein, ribbon superstructure ordering of Li/transition-metal-ions was applied to suppress the voltage hysteresis combined with Ti-substitution to improve the cycling stability for P3-Na0.67Li0.2Ti0.15Mn0.65O2. When both cation and anion redox reactions are utilized, Na0.67Li0.2Ti0.15Mn0.65O2 delivers a reversible capacity of 172 mA h g−1 after 25 cycles at 10 mA g−1 between 1.6–4.4 V vs. Na+/Na. Ex-situ X-ray diffraction data reveal that the ribbon superstructure is retained with negligible unit cell volume expansion/contraction upon sodiation/desodiation. The performance as a positive electrode for Li-ion batteries was also evaluated and P3-Na0.67Li0.2Ti0.15Mn0.65O2 delivers a reversible capacity of 180 mA h g−1 after 25 cycles at 10 mA g−1 when cycled vs. Li+/Li between 2.0–4.8 V.Publisher PDFPeer reviewe

Effect of Cu substitution on anion redox behaviour in P3-type sodium manganese oxides

This work was supported by the Faraday Institution (Grant No. FIRG018). The authors gratefully acknowledge support from the Engineering and Physical Sciences Research Council (EPSRC), Grant Nos. EP/L017008/1, EP/R023751/1 and EP/T019298/1.Sodium layered oxides which display oxygen anion redox behaviour are considered promising positive electrodes for sodium-ion batteries because they offer increased specific capacities. However, they suffer from irreversible structural changes resulting in significant capacity loss and limited oxygen redox reversibility. Here the effect of Cu substitution on the electrochemical performance of P3-type sodium manganese oxide is examined by evaluating the structural and electronic structural evolution upon cycling, supported by density functional theory (DFT) calculations. Over the voltage range 1.8–3.8 V vs. Na/Na+, where the redox reactions of the transition metal ions contribute entirely towards the charge compensation mechanism, stable cycling performance is maintained, showing a capacity retention of 90% of the initial discharge capacity of 166 mA h g−1 after 40 cycles at 10 mA g−1. Over an extended voltage range of 1.8–4.3 V vs. Na/Na+, oxygen anion redox is invoked, with a voltage hysteresis of 110 mV and a greater initial discharge capacity of 195 mA h g−1 at 10 mA g−1 is reached. Ex-situ powder x-ray diffraction patterns reveal distortion of the P3 structure to P'3 after charge to 4.3 V, and then transformation to O'3 upon discharge to 1.8 V, which contributes towards the capacity fade observed between the voltage range 1.8–4.3 V. DFT with projected density of states calculations reveal a strong covalency between the copper and oxygen atoms which facilitate both the cationic and anionic redox reactions in P3-type Na0.67Mn0.9Cu0.1O2.Publisher PDFPeer reviewe

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8[superscript +] T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4[superscript +] T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.Bill & Melinda Gates FoundationRagon Institute of MGH, MIT and HarvardNational Institutes of Health (U.S.) (AI091693)National Institutes of Health (U.S.) (AI095109)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32CA180586)Hertz Foundation (Graduate Fellowship)National Science Foundation (U.S.). Graduate Research Fellowshi

Age-dependent changes in autophosphorylation of alpha calcium/calmodulin dependent kinase II in hippocampus and amygdala after contextual fear conditioning

The hippocampus and amygdala are essential brain regions responsible for contextual fear conditioning (CFC). The autophosphorylation of alpha calciumcalmodulin kinase II (αCaMKII) at threonine-286 (T286) is a critical step 3 implicated in long-term potentiation (LTP), learning and memory. However, the changes in αCaMKII levels with aging and training in associated brain regions are not fully understood. Here, we studied how aging and training affect the levels of phosphorylated (T286) and proportion of phosphorylated:total αCaMKII in the hippocampus and amygdala. Young and aged mice, naïve (untrained) and trained in CFC, were analysed by immunohistochemistry for the levels of total and phosphorylated αCaMKII in the hippocampus and amygdala. We found that two hours after CFC training, young mice exhibited a higher level of phosphorylated and increased ratio of phosphorylated:total αCaMKII in hippocampal CA3 stratum radiatum. Furthermore, aged untrained mice showed a higher ratio of phosphorylated:total αCaMKII in the CA3 region of the hippocampus when compared to the young untrained group. No effect of training or aging were seen in the central, lateral and basolateral amygdala regions, for both phosphorylated and ratio of phosphorylated:total αCaMKII. These results show that aging impairs the training-induced upregulation of autophosphorylated (T286) αCaMKII in the CA3 stratum radiatum of the hippocampus. This indicates that distinct age-related mechanisms underlie CFC that may rely more heavily on NMDA receptor-dependent plasticity in young age

Enhanced cycling stability in the anion redox material P3-type Zn-substituted sodium manganese oxide

Funding: Faraday Institution (Grant Number(s): FIRG018), Diamond Light Source (Grant Number(s): SP14239), Engineering and Physical Sciences Research Council (Grant Number(s): EP/L017008/1, EP/R023751/1, EP/T019298/1), SPRing8 (Grant Number(s): 2021A1425).Sodium layered oxides showing oxygen redox activity are promising positive electrodes for sodium‑ion batteries (SIBs). However, structural degradation typically results in limited reversibility of the oxygen redox activity. Herein, the effect of Zn‑doping on the electrochemical properties of P3-type sodium manganese oxide, synthesised under air and oxygen is investigated for the first time. Air‑Na 0.67 Mn 0.9 Zn 0.1 O 2 and Oxy‑Na 0.67 Mn 0.9 Zn 0.1 O 2 exhibit stable cycling performance between 1.8 and 3.8 V, each maintaining 96% of their initial capacity after 30 cycles, where Mn 3+ /Mn 4+ redox dominates. Increasing the voltage range to 1.8‑4.3 V activates oxygen redox. For the material synthesised under air, oxygen redox activity is based on Zn, with limited reversibility. The additional transition metal vacancies in the material synthesised under oxygen result in enhanced oxygen redox reversibility with small voltage hysteresis. These results may assist the development of high‑capacity and structurally stable oxygen redox‑based materials for SIBs.Publisher PDFPeer reviewe