Vitamin D and respiratory health Hughes, D.A; Norton, R
Clinical and experimental immunology,
October 2009, Letnik:
158, Številka:
1
Journal Article
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Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or ...treatment of a wide range of diseases. In this brief review the known effects of vitamin D on immune function are described in relation to respiratory health. Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defence mechanisms against respiratory pathogens. Population-based studies showing an association between circulating vitamin D levels and lung function provide strong justification for randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases to assess both efficacy and optimal dosage.
We introduce an electro-optic hardware platform for nonlinear activation functions in optical neural networks. The optical-to-optical nonlinearity operates by converting a small portion of the input ...optical signal into an analog electric signal, which is used to intensity -modulate the original optical signal with no reduction in processing speed. Our scheme allows for complete nonlinear on-off contrast in transmission at relatively low optical power thresholds and eliminates the requirement of having additional optical sources between each of the layers of the network Moreover, the activation function is reconfigurable via electrical bias, allowing it to be programmed or trained to synthesize a variety of nonlinear responses. Using numerical simulations, we demonstrate that this activation function significantly improves the expressiveness of optical neural networks, allowing them to perform well on two benchmark machine learning tasks: learning a multi-input exclusive-OR (XOR) logic function and classification of images of handwritten numbers from the MNIST dataset. The addition of the nonlinear activation function improves test accuracy on the MNIST task from 85% to 94%.
Introduction
Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The ...beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.
Methods
EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference.
Results
Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46–0.87
I
2
34%,
p
= 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23–0.68,
I
2
= 0%,
p
= 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD −2.39 95% CI −4.86 to 0.08
I
2
= 0%,
p
= 0.06) or change in 6MWT distance (WMD 9.06 95% CI −35.68, 53.81
I
2
= 88%,
p
= 0.69) was observed.
Conclusions
Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.
Synchronous acceleration and thinning of southeast (SE) Greenland glaciers during the early 2000s was the main contributor that resulted in the doubling of annual discharge from the ice sheet. We ...show that this acceleration was followed by a synchronized and widespread slowdown of the same glaciers, in many cases associated with a decrease in thinning rates, and we propose that ice sheet–ocean interactions are the first‐order regional control on these recent mass changes. Sea surface temperature and mooring data show that the preceding dynamic thinning coincides with a brief decline in the cold East Greenland Coastal Current (EGCC) and East Greenland Current. We suggest this decline was partly induced by a reduction in ice sheet runoff, which allowed warm water from the Irminger Current to reach the SE Greenland coast. A restrengthening of the cold waters coincides with the glaciers' subsequent slowdown. We argue that this warming and subsequent cooling of the coastal waters was the cause of the glaciers' dynamic changes. We further suggest that the restrengthening of the EGCC resulted in part from cold water input by increased glacier calving during the speedup and increased ice sheet runoff. We hypothesize that the main mechanism for ice sheet mass loss in SE Greenland is highly sensitive to ocean conditions and is likely subject to negative feedback mechanisms.
A twofold decrease to an unexplored scale of 5 nm was produced in Cu by applying a large sliding load in liquid nitrogen. Statistical and universal scaling analyses of deformation induced high angle ...boundaries, dislocation boundaries, and individual dislocations observed by high resolution electron microscopy reveal that dislocation processes still dominate. Dislocation based plasticity continues far below the transition suggested by experiment and molecular dynamics simulations, with a limit below 5 nm. Very high strength metals may emerge based on this enhanced structural refinement.
Networks of ground-based hydro-meteorological observations are frequently sparse in developing countries and the situation is not improving. Part of the reason is the lack of resources available in ...countries which have more pressing economic and social issues. However, these are also the very countries where improved estimates of water resource availability are required. While hydrological models have the potential to provide the necessary information, without adequately accurate climate (rainfall, evaporation, etc.) input information, it is extremely difficult to establish models and generate representative water resource availability information. This paper reports on a preliminary analysis of the potential for using satellite derived rainfall data through a comparison with available gauge data for four basins in the southern Africa region. It is clear that the satellite data cannot be used directly in conjunction with historical gauge data. Specifically, the satellite data do not reflect the strong influences on precipitation of topography in some of the basins. However, the prospects of applying relatively straightforward adjustments are promising and further assessments appear to be justified.
•We review 40years of the use of the Pitman model in the context of IAHS PUB.•Some of the Pitman model developments anticipated PUB, others learned from PUB.•Recent developments are aligned with ...uncertainty issues that emerged during PUB.•More efforts are required to make use of new hydrological (EO) data products.•Key differences are associated with the emphasis on the practical use of the model.
The 40th anniversary of the initial development of the Pitman rainfall-runoff (developed in South Africa and widely applied throughout southern Africa) approximately coincides with the end of the IAHS PUB programme and the start of a new decade focussing on hydrological change (Panta Rhei) and society. The paper reviews the developments and applications of the Pitman model in the context of the appropriate outcomes of PUB and the proposed future directions of Panta Rhei. The focus of development of the Pitman model has been dominated by practical applications, while PUB was largely dominated by science issues. While some of the PUB principles have been applied with the Pitman model, there are others that are deemed inappropriate for practical modelling and others that would almost certainly benefit the Pitman model applications in the future. The paper includes discussions of the model structure, input data, parameters and output evaluations – all in the context of uncertainty. The capabilities of the model to address societal development impacts are also discussed and a brief example of an uncertainty approach to applying the model is provided. The conclusions are that some developments of the Pitman model anticipated more recent international developments, while others have not been ignored even if further efforts are required to effectively implement them. Perhaps the largest gap in applying uncertainty principles in practice is how to use them in water resources decision making.
Analog machine learning hardware platforms promise to be faster and more energy efficient than their digital counterparts. Wave physics, as found in acoustics and optics, is a natural candidate for ...building analog processors for time-varying signals. Here, we identify a mapping between the dynamics of wave physics and the computation in recurrent neural networks. This mapping indicates that physical wave systems can be trained to learn complex features in temporal data, using standard training techniques for neural networks. As a demonstration, we show that an inverse-designed inhomogeneous medium can perform vowel classification on raw audio signals as their waveforms scatter and propagate through it, achieving performance comparable to a standard digital implementation of a recurrent neural network. These findings pave the way for a new class of analog machine learning platforms, capable of fast and efficient processing of information in its native domain.
A quantitative microstructural analysis is presented for pure polycrystalline nickel (99.99%) cold rolled to reductions from 70 to 98% (
ε
vM 1.4–4.5). Applying transmission electron microscopy (TEM) ...techniques, key structural parameters, such as spacing between dislocation boundaries and high angle boundaries, as well as the misorientations across their boundaries, have been measured and analyzed. Application of scaling and similitude hypotheses to these microstructural parameters and their distributions revealed that the structures maintain a similar character with increasing strain. This similarity indicates that the measured parameters capture the important features of the structure. Scaling and similitude provide governing principles for structure formation. Based on this structural information and a detailed description of the morphology, structural parameters are identified, strength determining parameters chosen, and strength–structural relationships discussed. The suggestion is then made that two strengthening contributions should be considered: (i) dislocation strengthening due to the presence of low angle boundaries and (ii) grain boundary strengthening due to medium to high angle boundaries. The calculated individual strength contributions evolve differently with the strain and their addition leads to flow stress values and hardening rates in good agreement with those observed experimentally. No saturation of the calculated or experimental flow stress was observed.
Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 ...mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure.
We obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR).
Pre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy.
Genomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.
•We analyzed mechanisms of resistance to PARP inhibitor/platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.•Genomic reversion to functional BRCA1/2 protein was identified in one-half of patients.•Up-regulation of DNA end resection was identified as a resistance mechanism in two additional patients.•RAD51 foci assessed by immunohistochemistry correlated with clinical response to PARP inhibitor/platinum.•RAD51 focus staining warrants further exploration as a biomarker for clinical use.
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