Possible reasons for the growth of peace studies in the 1980s

Peace movements in many different forms and degrees have been present throughout history. But advocacy of peace studies in educational institutions is quite a recent phenomenon. While a few groups have advocated peace studies since the 1950s, a preponderance of curricular materials and literature did not appear until the 1980s (Scott, 1984)

Caring for the older person with cognitive impairment in hospital: Qualitative analysis of nursing personnel reflections on fall events

Aims and objectives To explore nurse and nursing assistant reflections on the care of older patients with cognitive impairment who have experienced a fall. Background While there are evidence‐based clinical guidelines for the prevention and management of falls and for the care of older people with cognitive impairment, the falls rates for older people with cognitive impairment are three times as high as those without. Design Critical incident technique. Methods Eleven registered and two enrolled nurses and four assistants in nursing working in one subacute and two acute wards within two hospitals of a tertiary level health service in south‐east Queensland. Individual semistructured interviews focused on two past events when a patient with cognitive impairment had fallen in hospital: one when there was minimal harm and the second when there was significant harm. Thematic analysis was undertaken. The COREQ checklist was followed. Results Three themes emerged from 23 reflective accounts of fall events: “direct observation is confounded by multiple observers” and “knowing the person has cognitive impairment is not enough,” and “want to rely on the guideline but unsure how to enact it.” While participants were aware of the falls prevention policy and techniques available to prevent falls, the implementation of these was challenging due to the complexity of care required by the older person with cognitive impairment. Conclusions Falls prevention for older people with cognitive impairment is complex and belies the simple application of policy. Relevance to clinical practice To reduce falls, nurses can involve the family to support “knowing the patient” to enable prediction of impulsive actions; shift the focus of in‐service from lectures to specific case presentations, with collaborative analysis on person‐focused strategies to prevent falls in older people with cognitive impairment; and reconsider the sitter role from simple observer to assistant, focused on ambulation and supporting independence in activities of daily living.Full Tex

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

Osteoarthritis (OA) is characterised by loss of articular cartilage, synovial membrane dysfunction and subchondral sclerosis. Few studies have used a global approach to stratify equine synovial fluid (SF) molecular profiles according to OA severity. SF was collected from 58 metacarpophalangeal (MCP) and metatarsophalangeal joints of racing Thoroughbred horses (Hong Kong Jockey Club; HKJC) and 83 MCP joints of mixed breed horses from an abattoir and equine hospital (biobank). Joints were histologically and macroscopically assessed for OA severity. For proteomic analysis, native SF and SF loaded onto ProteoMiner™ equalisation columns, to deplete high abundant proteins, were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification. Validation of selected differentially expressed proteins was undertaken using clinical SF collected during diagnostic investigations. Native SF metabolites were analysed using 1D 1 H Nuclear Magnetic Resonance (NMR). 1,834 proteins and 40 metabolites were identified in equine SF. Afamin levels decreased with synovitis severity and four uncharacterised proteins decreased with OA severity. Gelsolin and lipoprotein binding protein decreased with OA severity and apolipoprotein A1 levels increased for mild and moderate OA. Within the biobank, glutamate levels decreased with OA severity and for the HKJC cohort, 2-aminobutyrate, alanine and creatine increased with severity. Proteomic and metabolomic integration was undertaken using linear regression via Lasso penalisation modelling, incorporating 29 variables (R 2 =0.82) with principal component 2 able to discriminate advanced OA from earlier stages, predominantly driven by H9GZQ9, F6ZR63 and alanine. Combining biobank and HKJC datasets, discriminant analysis of principal components modelling prediction was good for mild OA (90%). This study has stratified equine OA using both metabolomic and proteomic SF profiles and identified a panel of markers of interest which may be applicable to grading OA severity. This is also the first study to undertake computational integration of NMR metabolomic and LC-MS/MS proteomic datasets of any biological system

Synthesis and characterization of a series of nickel(II) alkoxide precursors and their utility for Ni(0) nanoparticle production

A series of nickel(ii) aryloxide ([Ni(OAr)2(py)x]) precursors was synthesized from an amide-alcohol exchange using [Ni(NR2)2] in the presence of pyridine (py). The H-OAr selected were the mono- and di-ortho-substituted 2-alkyl phenols: alkyl = methyl (H-oMP), iso-propyl (H-oPP), tert-butyl (H-oBP) and 2,6-di-alkyl phenols (alkyl = di-iso-propyl (H-DIP), di-tert-butyl (H-DBP), di-phenyl (H-DPhP)). The crystalline products were solved as solvated monomers and structurally characterized as [Ni(OAr)2(py)x], where x = 4: OAr = oMP (1), oPP (2); x = 3: OAr = oBP (3), DIP (4); x = 2: OAr = DBP (5), DPhP (6). The excited states (singlet or triplet) and various geometries of 1-6 were identified by experimental UV-vis and verified by computational modeling. Magnetic susceptibility of the representative compound 4 was fit to a Curie Weiss model that yielded a magnetic moment of 4.38(3)μB consistent with a Ni2+ center. Compounds 1 and 6 were selected for decomposition studied under solution precipitation routes since they represent the two extremes of coordination. The particle size and crystalline structure were characterized using transmission electron microscopy (TEM) and powder X-ray diffraction (PXRD). The materials isolated from 1 and 6 were found by TEM to form irregular shape nanomaterials (8-15 nm), which by PXRD were found to be Ni0 hcp (PDF: 01-089-7129) and fcc (PDF: 01-070-0989), respectively

Airway metabolic profiling during Streptococcus pneumoniae infection identifies branched chain amino acids as signatures of upper airway colonisation

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and bacteraemia and is capable of remarkable phenotypic plasticity, responding rapidly to environmental change. Pneumococcus is a nasopharyngeal commensal, but is responsible for severe, acute infections following dissemination within-host. Pneumococcus is adept at utilising host resources, but the airways are compartmentalised and those resources are not evenly distributed. Challenges and opportunities in metabolite acquisition within different airway niches may contribute to the commensal-pathogen switch when pneumococcus moves from nasopharynx into lungs. We used NMR to characterise the metabolic landscape of the mouse airways, in health and during infection. Using paired nasopharynx and lung samples from naïve animals, we identified fundamental differences in metabolite bioavailability between airway niches. Pneumococcal pneumonia was associated with rapid and dramatic shifts in the lung metabolic environment, whilst nasopharyngeal carriage led to only modest change in upper airway metabolite profiles. NMR spectra derived from the nasopharynx of mice infected with closely-related pneumococcal strains that differ in their colonisation potential could be distinguished from one another using multivariate dimensionality reduction methods. The resulting models highlighted that increased branched-chain amino acid (BCAA) bioavailability in nasopharynx is a feature of infection with the high colonisation potential strain. Subsequent analysis revealed increased expression of BCAA transport genes and increased intracellular concentrations of BCAA in that same strain. Movement from upper to lower airway environments is associated with shifting challenges in metabolic resource allocation for pneumococci. Efficient biosynthesis, liberation or acquisition of BCAA is a feature of adaptation to nasopharyngeal colonisation

A robust intracellular metabolite extraction protocol for human neutrophil metabolic profiling

Neutrophils are phagocytic innate immune cells that play essential roles in host defence, but are also implicated in inflammatory diseases such as rheumatoid arthritis (RA) where they contribute to systemic inflammation and joint damage. Transcriptomic analysis of neutrophils has revealed significant changes in gene expression in neutrophils activated in vitro by cytokines and in vivo during inflammation in RA. However, there are no reports on the global metabolomic changes that occur as a consequence of this activation. The aim of this study was to establish protocols for the study of changes in the metabolome of human neutrophils using 1H NMR spectroscopy. Sample preparation and spectral analysis protocols were optimised using neutrophils isolated by Ficoll-Paque, with decreased washing steps and inclusion of a heat-shock step to quench metabolite turnover. Cells were incubated ± PMA for 15 min in HEPES-free media and samples were analysed by NMR using a 700 MHz NMR Avance IIIHD Bruker NMR spectrometer equipped with a TCI cryoprobe. Chenomx, Bruker TopSpin and AMIX software were used to process spectra and identify metabolites. Principal Component Analysis (PCA) and signalling pathway analysis was carried out using Metaboanalyst. Cell number and number of scans (NS) were optimised as >3.6 million cells and 512 NS. 327 spectral bins were defined in the neutrophil spectra, of which 287 (87.7%) were assigned to 110 metabolites that included: amino acids, peptides and analogues; carbohydrates, carbonyls and alcohols; nucleotides, nucleosides and analogues; lipids and lipid-like molecules; benzenoids; and other organic compounds. 43 metabolites changed at least 1.5 fold (increase or decrease) after the addition of PMA for 5 or 15 min. Pathway analysis revealed that PMA affected nicotinate and nicotinamide metabolism, aminoacyl-tRNA biosynthesis and glycolysis, suggesting a redirection of glucose metabolism from glycolysis to the pentose phosphate pathway and production of NADPH for activation of the NADPH oxidase and subsequent respiratory burst. We have developed protocols for the study of human neutrophils by 1H NMR spectroscopy. Importantly, this methodology has sufficient sensitivity and reproducibility to detect changes in metabolite abundance from cell numbers typically collected from clinical samples or experiments with multiple assay conditions

Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid

The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity

Four Weeks of Probiotic Supplementation Alters the Metabolic Perturbations Induced by Marathon Running: Insight from Metabolomics

Few data are available that describe how probiotics influence systemic metabolism during endurance exercise. Metabolomic profiling of endurance athletes will elucidate mechanisms by which probiotics may confer benefits to the athlete. In this study, twenty-four runners (20 male, 4 female) were block randomised into two groups using a double-blind matched-pairs design according to their most recent Marathon performance. Runners were assigned to 28-days of supplementation with a multi-strain probiotic (PRO) or a placebo (PLB). Following 28-days of supplementation, runners performed a competitive track Marathon race. Venous blood samples and muscle biopsies (vastus lateralis) were collected on the morning of the race and immediately post-race. Samples were subsequently analysed by untargeted 1H-NMR metabolomics. Principal component analysis (PCA) identified a greater difference in the post-Marathon serum metabolome in the PLB group vs. PRO. Univariate tests identified 17 non-overlapped metabolites in PLB, whereas only seven were identified in PRO. By building a PLS-DA model of two components, we revealed combinations of metabolites able to discriminate between PLB and PRO post-Marathon. PCA of muscle biopsies demonstrated no discernible difference post-Marathon between treatment groups. In conclusion, 28-days of probiotic supplementation alters the metabolic perturbations induced by a Marathon. Such findings may be related to maintaining the integrity of the gut during endurance exercise