Association between COPD exacerbations and lung function decline during maintenance therapy

Acknowledgements: Writing and editorial support was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI). Funding: This study was funded by AstraZeneca.Data availability statement: Data may be obtained from a third party and are not publicly available. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the Optimum Patient Care Research Database (www.opcrd.co.uk). The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 5/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd. com. Access to OCPRD can be made via the OCPRD website(https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email [email protected]. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS19879).Peer reviewedPublisher PD

Intracellular Calcium Disturbances Induced by Arsenic and Its Methylated Derivatives in Relation to Genomic Damage and Apoptosis Induction

Arsenic and its methylated derivatives are contaminants of air, water, and food and are known as toxicants and carcinogens. Arsenic compounds are also being used as cancer chemotherapeutic agents. In humans, inorganic arsenic is metabolically methylated to mono-, di-, and trimethylated forms. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In recent years, the correlation between arsenic exposure, cytotoxicity and genotoxicity, mutagenicity, and tumor promotion has been established, as well as the association of arsenic exposure with perturbation of physiologic processes, generation of reactive oxygen species, DNA damage, and apoptosis induction. Trivalent forms of arsenic have been found to induce apoptosis in several cellular systems with involvement of membrane-bound cell death receptors, activation of caspases, release of calcium stores, and changes of the intracellular glutathione level. It is well known that calcium ion deregulation plays a critical role in apoptotic cell death. A calcium increase in the nuclei might lead to toxic effects in the cell. In this review, we highlight the relationship between induced disturbances of calcium homeostasis, genomic damage, and apoptotic cell death caused by arsenic and its organic derivatives

Quasinormal modes of massive charged flavor branes

We present an analysis and classification of vector and scalar fluctuations in a D3/D7 brane setup at finite termperature and baryon density. The system is dual to an N=2 supersymmetric Yang-Mills theory with SU(N_c) gauge group and N_f hypermultiplets in the fundamental representation in the quenched approximation. We improve significantly over previous results on the quasinormal mode spectrum of D7 branes and stress their novel physical interpretation. Amongst our findings is a new purely imaginary scalar mode that becomes tachyonic at sufficiently low temperature and baryon density. We establish the existence of a critical density above which the scalar mode stays in the stable regime for all temperatures. In the vector sector we study the crossover from the hydrodynamic to the quasiparticle regime and find that it moves to shorter wavelengths for lower temperatures. At zero baryon density the quasinormal modes move toward distinct discrete attractor frequencies that depend on the momentum as we increase the temperature. At finite baryon density, however, the trajectories show a turning behavior such that for low temperature the quasinormal mode spectrum approaches the spectrum of the supersymmetric zero temperature normal modes. We interpret this as resolution of the singular quasinormal mode spectrum that appears at the limiting D7 brane embedding at vanishing baryon density.Comment: 56 pages, 40 figure

Virtual environment navigation with look-around mode to explore new real spaces by people who are blind

Background. This paper examines the ability of people who are blind to construct a mental map and perform orientation tasks in real space by using Nintendo Wii technologies to explore virtual environments. The participant explores new spaces through haptic and auditory feedback triggered by pointing or walking in the virtual environments and later constructs a mental map, which can be used to navigate in real space. Methods. The study included 10 participants who were congenitally or adventitiously blind, divided into experimental and control groups. The research was implemented by using virtual environments exploration and orientation tasks in real spaces, using both qualitative and quantitative methods in its methodology. Results. The results show that the mode of exploration afforded to the experimental group is radically new in orientation and mobility training; as a result 60% of the experimental participants constructed mental maps that were based on map model, compared to only 30% of the control group participants. Conclusion. Using technology that enabled them to explore and to collect spatial information in a way that does not exist in real space influenced the ability of the experimental group to construct a mental map based on the map model

Soil erosion and sediment transport in Tanzania: Part I – sediment source tracing in three neighbouring river catchments

Water bodies in Tanzania are experiencing increased siltation, which is threatening water quality, ecosystem health, and livelihood security in the region. This phenomenon is caused by increasing rates of upstream soil erosion and downstream sediment transport. However, a lack of knowledge on the contributions from different catchment zones, land-use types, and dominant erosion processes, to the transported sediment is undermining the mitigation of soil degradation at the source of the problem. In this context, complementary sediment source tracing techniques were applied in three Tanzanian river systems to further the understanding of the complex dynamics of soil erosion and sediment transport in the region. Analysis of the geochemical and biochemical fingerprints revealed a highly complex and variable soil system that could be grouped in distinct classes. These soil classes were unmixed against riverine sediment fingerprints using the Bayesian MixSIAR model, yielding proportionate source contributions for each catchment. This sediment source tracing indicated that hillslope erosion on the open rangelands and maize croplands in the mid-zone contributed over 75% of the transported sediment load in all three river systems during the sampling time-period. By integrating geochemical and biochemical fingerprints in sediment source tracing techniques, this study demonstrated links between land use, soil erosion and downstream sediment transport in Tanzania. This evidence can guide land managers in designing targeted interventions that safeguard both soil health and water quality

“We will change whether we want it or not”: Soil erosion in Maasai land as a social dilemma and a challenge to community resilience

This is the final version. Available on open access from Elsevier via the DOI in this recordSoil erosion is a major environmental challenge that undermines economic development in many regions of the world. While much previous work explored physical processes behind this problem, less attention has been paid to social, cultural, and psychological parameters that make a significant impact on soil erosion through the land use practices that they support. The present paper addresses this gap by conducting a qualitative exploration of agro-pastoralist stakeholders’ experiences of soil erosion in northern Tanzania, using the community resilience framework and the social dilemmas approach as theoretical lenses. Interview data suggests that the factors that make communities vulnerable to soil erosion challenges include the centrality of cattle keeping practice to pastoralists’ cultural identity, lack of social cohesion, lack of alternative livelihood opportunities, and weak governance structures. We argue that the ways towards resolving the dilemma lie in addressing relevant cultural norms, building cohesive and open communities, and strengthening local governance.Natural Environment Research Council (NERC)British Academ

Biomechanical Thresholds Regulate Inflammation through the NF-κB Pathway: Experiments and Modeling

BACKGROUND: During normal physical activities cartilage experiences dynamic compressive forces that are essential to maintain cartilage integrity. However, at non-physiologic levels these signals can induce inflammation and initiate cartilage destruction. Here, by examining the pro-inflammatory signaling networks, we developed a mathematical model to show the magnitude-dependent regulation of chondrocytic responses by compressive forces. METHODOLOGY/PRINCIPAL FINDINGS: Chondrocytic cells grown in 3-D scaffolds were subjected to various magnitudes of dynamic compressive strain (DCS), and the regulation of pro-inflammatory gene expression via activation of nuclear factor-kappa B (NF-kappaB) signaling cascade examined. Experimental evidences provide the existence of a threshold in the magnitude of DCS that regulates the mRNA expression of nitric oxide synthase (NOS2), an inducible pro-inflammatory enzyme. Interestingly, below this threshold, DCS inhibits the interleukin-1beta (IL-1beta)-induced pro-inflammatory gene expression, with the degree of suppression depending on the magnitude of DCS. This suppression of NOS2 by DCS correlates with the attenuation of the NF-kappaB signaling pathway as measured by IL-1beta-induced phosphorylation of the inhibitor of kappa B (IkappaB)-alpha, degradation of IkappaB-alpha and IkappaB-beta, and subsequent nuclear translocation of NF-kappaB p65. A mathematical model developed to understand the complex dynamics of the system predicts two thresholds in the magnitudes of DCS, one for the inhibition of IL-1beta-induced expression of NOS2 by DCS at low magnitudes, and second for the DCS-induced expression of NOS2 at higher magnitudes. CONCLUSIONS/SIGNIFICANCE: Experimental and computational results indicate that biomechanical signals suppress and induce inflammation at critical thresholds through activation/suppression of the NF-kappaB signaling pathway. These thresholds arise due to the bistable behavior of the networks originating from the positive feedback loop between NF-kappaB and its target genes. These findings lay initial groundwork for the identification of the thresholds in physical activities that can differentiate its favorable actions from its unfavorable consequences on joints

In vitro calibration of a system for measurement of in vivo convective heat transfer coefficient in animals

BACKGROUND: We need a sensor to measure the convective heat transfer coefficient during ablation of the heart or liver. METHODS: We built a minimally invasive instrument to measure the in vivo convective heat transfer coefficient, h in animals, using a Wheatstone-bridge circuit, similar to a hot-wire anemometer circuit. One arm is connected to a steerable catheter sensor whose tip is a 1.9 mm × 3.2 mm thin film resistive temperature detector (RTD) sensor. We used a circulation system to simulate different flow rates at 39°C for in vitro experiments using distilled water, tap water and saline. We heated the sensor approximately 5°C above the fluid temperature. We measured the power consumed by the sensor and the resistance of the sensor during the experiments and analyzed these data to determine the value of the convective heat transfer coefficient at various flow rates. RESULTS: From 0 to 5 L/min, experimental values of h in W/(m(2)·K) were for distilled water 5100 to 13000, for tap water 5500 to 12300, and for saline 5400 to 13600. Theoretical values were 1900 to 10700. CONCLUSION: We believe this system is the smallest, most accurate method of minimally invasive measurement of in vivo h in animals and provides the least disturbance of flow

Soil erosion and sediment transport in Tanzania: Part II – sedimentological evidence of phased land degradation

Soil resources in parts of Tanzania are rapidly being depleted by increased rates of soil erosion and downstream sediment transport, threatening ecosystem health, water and livelihood security in the region. However, incomplete understanding to what effect the dynamics of soil erosion and sediment transport are responding to land-use changes and climatic variability are hindering the actions needed to future-proof Tanzanian land-use practices. Complementary environmental diagnostic tools were applied to reconstruct the rates and sources of sedimentation over time in three Tanzanian river systems that have experienced changing land use and climatic conditions. Detailed historical analysis of sediment deposits revealed drastic changes in sediment yield and source contributions. Quantitative sedimentation reconstruction using radionuclide dating showed a 20-fold increase in sediment yield over the past 120 years. The observed dramatic increase in sediment yield is most likely driven by increasing land-use pressures. Deforestation, cropland expansion and increasing grazing pressures resulted into accelerating rates of sheet erosion. A regime shift after years of progressive soil degradation and convergence of surface flows resulted into a highly incised landscape, where high amounts of eroded soil from throughout the catchment are rapidly transported downstream by strongly connected ephemeral drainage networks. By integrating complementary spatial and temporal evidence bases, this study demonstrated links between land-use change, increased soil erosion and downstream sedimentation. Such evidence can guide stakeholders and policy makers in the design of targeted management interventions to safeguard future soil health and water quality