Personalised airway clearance techniques are commonly recommended to augment mucus clearance in chronic suppurative lung diseases. It is unclear what current literature tells us about how airway ...clearance regimens should be personalised. This scoping review explores current research on airway clearance technique in chronic suppurative lung diseases, to establish the extent and type of guidance in this area, identify knowledge gaps and determine the factors which physiotherapists should consider when personalising airway clearance regimens.
Systematic searching of online databases (MEDLINE, EMBASE, CINAHL, PEDro, Cochrane, Web of Science) was used to identify full-text publications in the last 25 years that described methods of personalising airway clearance techniques in chronic suppurative lung diseases. Items from the TIDieR framework provided
categories which were modified based on the initial data to develop a "Best-fit" framework for data charting. The findings were subsequently transformed into a personalisation model.
A broad range of publications were identified, most commonly general review papers (44%). The items identified were grouped into seven personalisation factors: physical, psychosocial, airway clearance technique (ACT) type, procedures, dosage, response and provider. As only two divergent models of ACT personalisation were found, the personalisation factors identified were then used to develop a model for physiotherapists.
The personalisation of airway clearance regimens is widely discussed in the current literature, which provides a range of factors that should be considered. This review summarises the current literature, organising findings into a proposed airway clearance personalisation model, to provide clarity in this field.
The West Antarctic Peninsula (WAP) is a rapidly warming region, with
substantial ecological and biogeochemical responses to the observed change
and variability for the past decades, revealed by ...multi-decadal observations
from the Palmer Antarctica Long-Term Ecological Research (LTER) program. The
wealth of these long-term observations provides an important resource for
ecosystem modeling, but there has been a lack of focus on the development
of numerical models that simulate time-evolving plankton dynamics over the
austral growth season along the coastal WAP. Here, we introduce a
one-dimensional variational data assimilation planktonic ecosystem model (i.e., the
WAP-1D-VAR v1.0 model) equipped with a model
parameter optimization scheme. We first demonstrate the modified and newly
added model schemes to the pre-existing food web and biogeochemical
components of the other ecosystem models that WAP-1D-VAR model was adapted
from, including diagnostic sea-ice forcing and trophic interactions specific
to the WAP region. We then present the results from model experiments where
we assimilate 11 different data types from an example Palmer LTER growth
season (October 2002–March 2003) directly related to corresponding model
state variables and flows between these variables. The iterative data
assimilation procedure reduces the misfits between observations
and model results by 58 %, compared to before optimization, via an optimized set of
12 parameters out of a total of 72 free parameters. The optimized model results
capture key WAP ecological features, such as blooms during seasonal sea-ice
retreat, the lack of macronutrient limitation, and modeled variables and
flows comparable to other studies in the WAP region, as well as several
important ecosystem metrics. One exception is that the model slightly
underestimates particle export flux, for which we discuss potential
underlying reasons. The data assimilation scheme of the WAP-1D-VAR model
enables the available observational data to constrain previously poorly
understood processes, including the partitioning of primary production by
different phytoplankton groups, the optimal chlorophyll-to-carbon ratio of
the WAP phytoplankton community, and the partitioning of dissolved organic
carbon pools with different lability. The WAP-1D-VAR model can be
successfully employed to link the snapshots collected by the available data
sets together to explain and understand the observed dynamics along the
coastal WAP.
Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. ...Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/-) have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood.
In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission.
These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset.
An inverse food-web model for the western Antarctic Peninsula (WAP) pelagic food web was constrained with data from Palmer Long Term Ecological Research (PAL-LTER) project annual austral summer ...sampling cruises. Model solutions were generated for 2 regions with Adélie penguin Pygoscelis adeliae colonies presenting different population trends (a northern and a southern colony) for a 12 yr period (1995–2006). Counter to the standard paradigm, comparisons of carbon flow through bacteria, microzooplankton, and krill showed that the diatom–krill–top predator food chain is not the dominant pathway for organic carbon exchanges. The food web is more complex, including significant contributions by microzooplankton and the microbial loop. Using both inverse model results and network indices, it appears that in the northern WAP the food web is dominated by the microbial food web, with a temporal trend toward its increasing importance. The dominant pathway for the southern WAP food web varies from year to year, with no detectable temporal trend toward dominance of microzooplankton versus krill. In addition, sensitivity analyses indicated that the northern colony of Adélie penguins, whose population size has been declining over the past 35 yr, appears to have sufficient krill during summer to sustain its basic metabolic needs and rear chicks, suggesting the importance of other processes in regulating the Adélie population decline.
Summary
Mucosal‐associated invariant T (MAIT) cells and Vδ2+ γδ T cells are anti‐bacterial innate‐like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control ...of infection. However, the role of ILLs in community‐acquired pneumonia (CAP) is unknown. Using sputum samples from a well‐characterized CAP cohort, MAIT cell and Vδ2+ T cell abundance was determined by quantitative polymerase chain reaction (qPCR). Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and Vδ2+ T cells was inferred by 16S rRNA sequencing. MAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and Vδ2+ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology; however, there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon (IFN)‐α, IFN‐γ, and sputum neutrophil abundance, while Vδ2+ T cell abundance was associated with CXCL11 and IFN‐γ. Therefore, MAIT and Vδ2+ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.
Mucosal‐associated invariant T (MAIT) cells and Vδ2+ γδ T cells are innate‐like lymphocytes that are abundant in humans in blood and at mucosal surfaces, including the lungs. They provide rapid effector responses upon activation by specific ligands produced by a broad range of bacteria, including numerous pulmonary pathogens. Here we show that MAIT and Vδ2+ γδ T cells can be detected in sputum in patients with community acquired pneumonia, where they may contribute to improved clinical outcome.
Background
Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses.
Methods
We examined ...changes in motivation, coping and acceptance among 78 men with chronic haemophilia‐related joint pain. Using cross‐lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes.
Results
Changes in motivation to self‐manage pain influenced later changes in pain coping, consistent with the motivational model of pain self‐management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance.
Conclusions
Based on the findings, a combined model of changes in pain self‐management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain.
Significance
This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self‐management; and tests of behavioural versus motivational models of pain acceptance.
The importance of mechanical wear in the behavioral ecology and energetics of small organisms is an open question. We investigated wear in leaf-cutter ants, Atta cephalotes, because their cutting ...technique can be imitated and the leaves are the main energy source for the colony. We found that a razor-sharp (50-nm radius) "Vblade" that cuts leaves between the first and second mandibular teeth was dulled (~ 10-µm radius) and often nearly worn away on foragers. We found that the force required to cut standard leaves, using mandibles removed from foragers cutting in the wild, varied by a factor of 2.5 with tooth wear, defined as the difference between pupal and actual tooth length. We also found that wear significantly reduced the cutting rate. From the distribution of wear among the cutting foragers, we estimated that the wild colony would have spent 44% less of both energy and time making the observed cuts if the cutters' mandibles had all been pristine. Finally, wear correlated with behavioral differences—foragers with the most worn 10% of mandibles almost exclusively carried rather than cut. This previously unreported form of task partitioning suggests that eusociality may extend useful lifespans by making it possible to switch tasks as skills decline. We developed a model, assuming that ants do work at a constant rate proportional to their mass, to predict the cutting rate from head width, tooth wear, and force to cut leaves with a scalpel (R= 0.62), and we used this estimate to argue that the partitioning of cutting and carrying was sub-optimal but better than random. Wear's strong effect on performance may promote wear-avoiding behavior and wear-resistant mandible composition; it may affect leaf selection and worker lifespan and it raises the possibility that wear is a similarly important constraint for many other small organisms.
– Objective: This paper reports the impact of oral health on the quality of life (QOL) of Southern European, dentate older adults, living independently in Melbourne, Australia. Participants were ...recruited through ethnic social clubs and interviewed about oral health, general health, socio‐demographics, and QOL using the Medical Outcomes Study Short‐Form 12 (SF‐12). The SF‐12’s physical and mental health component summary scores (PCS and MCS, respectively) were computed. The Oral Health Impact Profile (OHIP‐14) assessed the specific impact of oral health on QOL. Participants were also given a clinical oral examination.
Results: A total of 603 eligible older adults volunteered; 308 were from Greek background and 295 were from Italian background. Mean age was 67.7 years (SD 6.2), with 63.7% being female. The PCS score had a mean value of 45.8 (SD 11.8), and MCS had a mean of 47.8 (SD 5.7). PCS was associated with, periodontal status, chronic health condition, self‐perceived oral health needs, self‐assessed oral health status, oral health impact score and the interaction between gender and level of education F(11 552) = 10.57; P < 0.0001. These independent variables accounted for 16% of the variance in PCS. The multivariate model predicting MCS had only one significant variable (self‐reported gingival bleeding), explaining 1.5% of the variance. The OHIP‐14 ranged from 0 to 48 with a mean score of 5.6 (SD 9.3). The model predicting OHIP‐14 contained four significant variables: perceived oral health treatment needs, number of missing natural teeth, reports of having to sip liquid to help swallow food, and gender F(4576) = 33.39; P < 0.0001, and explained 18% of the variance. The results demonstrated a negative association between oral health indicators and both the oral health‐related QOL and the physical component of the SF‐12.
Conclusion: The present findings support a growing recognition of the importance of oral health as a mediator of QOL. However, the self‐selected sample and modest predictive power of the multivariate models suggest that further research is needed to expand this explanatory model.
Summary
Background Vitamin E (α-tocopherol) is thought to have a role in prevention of atherosclerosis, through inhibition of oxidation of low-density lipoprotein. Some epidemiological studies have ...shown an association between high dietary intake or high serum concentrations of α-tocopherol and lower rates of ischaemic heart disease. We tested the hypothesis that treatment with a high dose of α-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease.
Methods In this double-blind, placebo-controlled study with stratified randomisation, 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days (range 3-981). 1035 patients were assigned α-tocopherol (capsules containing 800 IU daily for first 546 patients; 400 IU daily for remainder); 967 received identical placebo capsules. The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal Ml alone.
Findings Plasma α-tocopherol concentrations (measured in subsets of patients) rose in the actively treated group (from baseline mean 34·2 μmol/L to 51·1 μmol/L with 400 IU daily and 64·5 μmol/L with 800 IU daily) but did not change in the placebo group. α-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal Ml (41 vs 64 events; relative risk 0·53 95% Cl 0·34-0·83; p=0·005). The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal Ml (14 vs 41; 0·23 0·11-0·47; p=0·005); however, there was a non-significant excess of cardiovascular deaths in the α-tocopherol group (27 vs 23; 1·18 0·62-2·27; p=0·61). All-cause mortality was 36 of 1035 α-tocopherol-treated patients and 27 of 967 placebo recipients.
Interpretation We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis, α-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment. The effect of α-tocopherol treatment on cardiovascular deaths requires further study.
BackgroundPeople living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a ...marker of risk for cancer among HIV-infected virally suppressed patients.MethodsA nested case control study design was pursued with 17 cancer cases and 73 controls (PLWH without cancer)ouidentified among the US Military HIV Natural History Study cohort, and were matched for CD4 + count, duration of HIV infection, and viral suppression. Cells were obtained from PLWH on an average of 12 months prior to clinical cancer diagnosis. Expression of inhibitory receptors (PD-1, CD160, CD244, Lag-3, and TIGIT), and transcription factors (T-bet, Eomesodermin, TCF-1, and (TOX) was measured on CD8 +T cells from that early time point.ResultsWe found that cases have increased expression of PD-1 +CD160+CD244+ (‘triple positive’) on total and effector CD8 + compared with controls (p=0.02). Furthermore, CD8 +T cells that were both PD-1 +CD160+CD244+ and T-betdimEomeshi were significantly elevated in cases at time point before cancer detection, compared with controls without cancer (p=0.008). This was driven by the finding that transcriptional factor profile of cells was altered in cancers compared with controls. Triple-positive cells were noted to retain the ability for cytotoxicity and cytokine secretion mediated by expression of CD160 and PD-1, respectively. However, triple-positive cells demonstrated high expression of TOX-1, a transcription factor associated with T cell exhaustion.ConclusionIn conclusion, we have found a subset of dysfunctional CD8 +T cells, PD-1 +CD160+CD244+T-betdimEomeshi, that is elevated 12 months before cancer diagnosis, suggesting that peripheral T cell alterations may serve as a biomarker of increased cancer risk among PLWH.
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