New Zealand's location and orography result in strongly-contrasting regional climates that are highly sensitive to variations in atmospheric circulation. Coupled with numerous remnant fragments of ...native forest, containing several long-lived tree species, this makes New Zealand ideally suited to multi-centennial investigation of changes in atmospheric circulation, at annual resolution. The potential of three such species (
Agathis australis,
Halocarpus biformis,
Libocedrus bidwillii) was investigated. Mean sea level pressure (MSLP) composite mapping (1950–1992) was used to develop hypothesised relationships between tree-ring master chronologies and selected regional atmospheric circulation indices. The strongest multi-species relationship identified was with the Southern Oscillation Index (SOI), for a three-season window starting in the austral winter (JJA) prior to growth initiation. The stationarity of hypothesised relationships was tested using additional MSLP composite mapping (1901–1950) and split-record regression analysis, including investigation of the stationarity of relationships at the respective poles of the relevant circulation indices. Significant stationarity issues were encountered, leading, in particular, to the rejection of
L. bidwillii as an atmospheric circulation proxy. Split-record calibration and verification was used to develop regression-based transfer functions for stationary relationships, but only the bivariate relationship between
A. australis and the SOI passed additional nineteenth century verification tests. The derived 400-year SOI reconstruction suggests that the twentieth century may have been the most robust ENSO century. There is also evidence of decadal-scale periodicity in ENSO robustness from the mid-eighteenth century, possibly following a relatively quiescent seventeenth century. More generally, the results reinforce the imperative of explicitly addressing stationarity in palaeoclimatology. They also demonstrate the utility of gridded products (e.g. HadSLP2) and compositing, especially in the context of hypothesis generation.
Anecdotal evidence suggests that death may be heralded by phenomena which seem to comfort dying persons and prepare them spiritually for death. Medical practitioners have been slow to recognize these ...end of life experiences (ELEs) and there has been little research into the way carers respond when patients try to talk about phenomena they have experienced, and how these ELEs influence the carers' work. A pilot study with a palliative care team revealed that patients regularly report these phenomena as an important part of their dying process, and that the experiences are far broader than the traditional image of an apparition at the end of the bed. The study suggested that many Palliative Carers are not trained to help them recognize the wider implications of ELEs, or to deal with difficult questions or situations, which arise from them. Many ELEs may go unreported because of this. The pilot study also suggested that ELEs are not drug-induced, and that patients would rather talk to nurses than doctors about their experiences. There are many subjective phenomena in common between ELEs and near death experiences suggesting that they may form part of a single process.
Increased numbers of macrophages and neutrophils in the lung is a key feature of chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic agent in the airways of COPD patients ...is leukotriene (LT)B(4) and is released by macrophages. The present study examines the role and mechanism of Ca(2+) in platelet-activating factor (PAF)-stimulated LTB(4) release from human lung macrophages. Macrophages were isolated from lung tissue of subjects undergoing lung resection surgery and monocyte-derived macrophages (MDM) were obtained from nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated with PAF and LTB(4) release and Ca(2+)(i) was measured. Lung macrophages and MDM released LTB(4) following stimulation with PAF (mean effective concentration: 0.08+/-0.06 microM (n = 5) versus 0.17+/-0.12 microM (n = 17), respectively). Compared with MDM, lung macrophages released approximately eight-fold more LTB(4). Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB(4) release was abrogated by ethylene glycol tetraacetic acid suggesting a role for extracellular Ca(2+). This was substantiated by using store-operated channel blockers econazole, SK&F96365 and Gd(3+). However, econazole and SK&F96365 were more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could attenuate this response. These data suggest that platelet-activating factor-stimulated leukotriene B(4) release from human lung macrophages is mediated, in part, by Ca(2+) influx through receptor- but not voltage-operated Ca(2+) channels.
Maternal endometrial leukaemia inhibitory factor (LIF) is required for successful implantation in mice. Mice with homozygous deletions in this gene fail to support implantation. The localization of ...immunoreactive LIF and the concentration of the mRNA encoding human LIF in normal endometrium during the menstrual cycle were investigated. The amount of RNA was low or undetectable in the proliferative phase but increased by approximately six times in the mid- to late secretory phase. The protein can only be detected by immunocytochemistry in glandular epithelium in the mid- or late secretory phase. To investigate the possible target for the endometrial LIF, we undertook reverse transcription-PCR analysis of early human embryos to determine whether they contain the mRNA encoding the LIF receptor. This study indicated that at the time of implantation in humans, the maternal endometrium produces LIF and that the blastocyst expresses LIF receptor mRNA and therefore may be capable of responding to this signal.
A recent development in text compression is a 'block sorting' algorithm which permutes the input text according to a special sort procedure and processes the permuted text with Move-To-Front (MTF) ...and a final statistical compressor. The technique combines good speed with excellent compression performance. This paper investigates the fundamental operation of the algorithm and presents some improvements based on that analysis. Although block sorting is clearly related to previous compression techniques, it appears that it is best described by techniques derived from work by Shannon on the prediction and entropy of English text. A simple model is developed which relates the compression to the proportion of zeros after the MTF stage. (Original abstract)
The inflammatory cytokine IL-36γ is increased in COPD lungs, whereas its endogenous inhibitor IL-36 receptor antagonist (IL-36RA) is reduced. IL-36 receptor signalling drives neutrophilic ...inflammation. Macrophages are critical in modulating lung inflammation and clearance of bacteria but the effect of IL-36γ on macrophages is not fully understood.To understand how IL-36γ affected macrophage function, non-smoker(NSm) and COPD monocyte-derived macrophages (MDM) were cultured with 100ng IL-36γ. IL-36γ reduced phagocytosis of H.influenzae by 23% in COPD MDM (p<0.01,n=13) but there was no effect on NSm MDM. Cytokine concentrations were measured in MDM supernatants by ELISA. IL-36γ did not affect IL-6, CXCL1 or CXCL8 secretion. Small airway fibroblasts (SAF) are a known effector cell of IL-36γ. To assess cross-talk between cell types, SAF supernatants were transferred onto MDM and cytokines measured in MDM supernatants. Untreated SAF did not stimulate MDM, however IL-36γ-treated SAF caused increased IL-6 (NT SAF vs IL36γ SAF: 2.8±0.4 vs 49.6±13.1ng/ml), CXCL1 (3.4±1.5 vs 14.1±4.9ng/ml) and CXCL8 (13.9±3.4 vs 53.3±11.0ng/ml) secretion from MDM.Lung macrophages are a major source of IL-36RA. IL36RN expression was measured in monocytes and MDM. COPD monocytes had lower IL36RN expression than NSm (NSm:1.52±0.38 vs COPD:0.32±0.12ng/ml, p<0.01, n=8), suggesting an innate pre-disposition towards low IL-36RA in COPD. IL36RN expression increased on monocyte differentiation to MDM, with NSm MDM having 5-fold higher IL36RN expression than COPD MDM (p<0.01). To investigate the mechanism regulating IL-36RA expression, MDM were incubated with PIK75 (PI3K inhibitor), UO0126 (ERK inhibitor), VX745 (p38 inhibitor), SP600125 (JNK inhibitor) and TPCA1 (NF-κB inhibitor) for 24h and IL36RN measured. Only PIK75 increased IL36RN expression (NT:0.63±0.33, PIK75:1.63±0.75, p<0.05, n=11), indicating that PI3K signalling mediates its reduced expression in COPD.This study demonstrates that IL-36γ causes a cascade of inflammation and impairs bacterial clearance in COPD. As IL-36γ is secreted in response to viral stimuli, the effects of IL-36γ described above could be important in pathogenesis of COPD exacerbations and secondary bacterial infection. IL36RN is reduced in COPD macrophages, which may be due to PI3K expression which is increased in COPD: Further work is needed to identify how this pathway regulates IL36RN to identify a potential drug target.
COPD is a heterogenous disease and there is ongoing need to identify biomarkers for treatable endotypes. Nasosorption is a non-invasive and safe way of sampling the respiratory tract to obtain ...undiluted endothelial lining fluid. This study investigates whether nasosorption can be used to characterise COPD.Nasosorption was performed on 23 non-smokers and 32 COPD patients and MSD (Mesoscale Discovery) used to measure an array of cytokines. IL-4 (NSm:3.06±1.49ng/ml, COPD:0.07±0.03ng/ml), IL-5 (NSm:8.2±2.51ng/ml, COPD:2.03±0.66ng/ml), IL-6 (NSm:20.00±2.73ng/ml, COPD:12.89±2.73ng/ml), CXCL-8 (NSm:4729.2±703.7ng/ml, COPD:2378.3±404.6ng/ml) and IFNγ (NSm:108.37±46.81ng/ml, COPD: 12.93±11.17ng/ml) were significantly lower in COPD than non-smokers. Eotaxin was higher in COPD (NSm:2.90±0.57ng/ml, COPD:6.53±1.12ng/ml). The COPD cohort was further analysed to look at commonly identified clinical phenotypes. Nasal eotaxin was raised in the high blood eosinophil cohort (>300cells/100µl) compared to low eosinophil cohort (7.93±2.66ng/ml vs 2.91±1.14ng/ml, p<0.05), but other TH2 cytokines such as IL-4, IL-5, IL-13 did not differ. 16% of COPD patients had co-existing bronchiectasis. These patients had significantly higher nasal IL-7 (109.7±6.0ng/ml vs 56.9±7.9ng/ml, p<0.05), CXCL10 (4446.0±1540.0ng/ml vs 949.5±237.7ng/ml, p<0.01), CXCL11 (6.41±5.32ng/ml vs 0.30±0.9ng/ml, p<0.01) and CCL17 (56.1±6.8ng/ml vs 32.3±4.1ng/ml, p<0.05). Comparing frequent (≥2 exacerbations/year) against infrequent exacerbators (<2/year) there were non-significant trends of increased IL-6 (15.7±4.1ng/ml vs 7.68±2.81ng/ml) and reduced IL-13 (8.8±3.1ng/ml vs 17.9±3.9ng/ml) and IL-33(63.8±23.2ng/ml vs 144.1±63.1ng/ml) in frequent exacerbators.16 COPD patients were sampled at exacerbation and >4 weeks after recovery. IFNγ was higher during exacerbation than on recovery (729.6±591.2ng/ml vs 2.2±1.3ng/ml, p<0.05), with a trend towards higher levels in viral vs non-viral exacerbations. Other markers known to be associated with viral infections such as IFNα, CXCL10 and TSLP were non-significantly increased in viral vs non-viral exacerbations. There was also a trend towards eotaxin levels being raised during exacerbation, with higher levels in non-bacterial rather than bacterial exacerbations (Non-bact:4.02±2.57ng/ml, Bact: 3.46±1.48ng/ml, p<0.05).We show that nasosorption may identify differences in inflammatory profiles in COPD. As a non-invasive test, its potential for qualifying exacerbations in a less stable patient is particularly relevant. A larger study is needed to cohort COPD phenotypes based on nasal inflammation and assess its use as a diagnostic test during exacerbations.
All sleep stages contain epochs with high-amplitude electrophysiological phasic events, alternating with quieter “core periods.” High-amplitude and core state properties cannot be disentangled with ...PET and fMRI. Here from high temporal resolution magnetoencephalography data, regional changes in neuronal activity were extracted during core periods in different frequency bands for each sleep stage and waking. We found that gamma-band activity increases in precuneus during light sleep (stages 1/2) and in the left dorso–medial prefrontal cortex (L-DMPFC) during deep sleep (stages 3/4). The L-DMPFC activated area expands laterally during rapid eye movement (REM) sleep, into a volume of about 5 cm
3 bounded by regions attributed to Theory of Mind (ToM) and default systems, both involved in introspection. Gamma band activity in this area was higher during REM sleep than other sleep stages and active wakefulness. There is a tantalizing correspondence between increased wide-band activity (dominated by low frequencies) in early non-REM (NREM) sleep stages and increases in gamma-band activity in late NREM and REM periods that we attribute to a lateral disinhibition mechanism. The results provide a description of regional electrophysiological changes in awake state, light and deep sleep, and REM sleep. These changes are most pronounced in the L-DMPFC and the other areas around the dorsal midline that are close to, but do not overlap with areas of the default and ToM systems, suggesting that the DMPFC, particularly in the left hemisphere, plays an important role in late NREM stages, in REM and possibly in dreaming.
Reprints the third part of an excerpt of an article first published in this journal Dec 1913; v.12 n.48, documenting the steady increase in the mortality from cancer in NZ. Refers to the possible ...link between cancer and certain diets among creoles and aboriginal tribes of Sierra Leone. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
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