429 research outputs found

    Comparison of Manual Versus Automated Data Collection Method for an Evidence-based Nursing Practice Study

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    OBJECTIVE: The objective of this study was to investigate and improve the use of automated data collection procedures for nursing research and quality assurance. METHODS: A descriptive, correlational study analyzed 44 orthopedic surgical patients who were part of an evidence-based practice (EBP) project examining post-operative oxygen therapy at a Midwestern hospital. The automation work attempted to replicate a manually-collected data set from the EBP project. RESULTS: Automation was successful in replicating data collection for study data elements that were available in the clinical data repository. The automation procedures identified 32 false negative patients who met the inclusion criteria described in the EBP project but were not selected during the manual data collection. Automating data collection for certain data elements, such as oxygen saturation, proved challenging because of workflow and practice variations and the reliance on disparate sources for data abstraction. Automation also revealed instances of human error including computational and transcription errors as well as incomplete selection of eligible patients. CONCLUSION: Automated data collection for analysis of nursing-specific phenomenon is potentially superior to manual data collection methods. Creation of automated reports and analysis may require initial up-front investment with collaboration between clinicians, researchers and information technology specialists who can manage the ambiguities and challenges of research and quality assurance work in healthcare

    Mutant LRRK2 in lymphocytes regulates neurodegeneration via IL-6 in an inflammatory model of Parkinson\u27s disease

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    Mutations in a number of genes contribute to development of Parkinson\u27s disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system. Here, using two chimeric mouse models, we demonstrate that: 1) the replacement of mutant LRRK2 with wt form of the protein in T- and B-lymphocytes diminishes LPS-mediated inflammation and rescues the SNpc DA neuron loss in the mutant LRRK2 brain; 2) the presence of G2019S or R1441G LRRK2 mutation in lymphocytes alone is sufficient for LPS-induced DA neuron loss in the genotypically wt brain; and 3) neutralization of peripheral IL-6 overproduction prevents the SNpc DA neuron loss in LPS-treated mutant LRRK2 mice. These results represent a major paradigm shift in our understanding of PD pathogenesis and suggest that immune dysfunction in some forms of familial PD may have primacy over the CNS as the initiating site of the disorder

    Modelling multiscale aspects of colorectal cancer

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    Colorectal cancer (CRC) is responsible for nearly half a million deaths annually world-wide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network. We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole

    A 6,000-year record of environmental change from the eastern Pacific margin of central Mexico

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    The transition from the mid- to late-Holocene in MesoAmerica saw increasing complexity in spatial patterns of change. Records from the western part of the region are sparse, with lacustrine sequences affected by long term anthropogenic disturbance or lacking chronological resolution. Here, we present a continuous palaeoecological and geochemical record from Laguna de Juanacatlán, a remote lake in the mountains of the western TMVB. Diatom assemblages, XRF scanning data and bulk organic geochemistry from a well-dated, 7.25-m laminated sequence were combined with summary pollen data from a 9-m partially laminated core to provide a continuous record of catchment and lake ecosystem changes over the last c. 6,000 years. Relatively humid conditions prevailed prior to c. 5.1 cal ka, which supported dense oak-pine forest cover around a deep, stratified lake. A trend towards drier conditions began c. 5.1 cal ka, intensifying after 4.0 cal ka, consistent with weakening of the North American Monsoon. Between 3.0 and 1.2 cal ka, lower lake levels and variable catchment run-off are consistent with increasing ENSO influence observed in the Late Holocene in the neotropics. From 1.2 to 0.9 cal ka, a marked change to catchment stability and more intense stratification reflected drier conditions and / or reduced rainfall variability and possibly warmer temperatures. After 0.9 cal ka, conditions were wetter, with an increase in catchment disturbance associated with the combined effects of climate and human activity. In recent decades, the lake ecosystem has changed markedly, possibly in response to recent climate change as well as local catchment dynamics

    Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus.

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    Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is MPDZ Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast medium penetrates into the brain ventricles of mice carrying a Mpdz loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of Mpdz KO mice is substantially higher than in normal mice. These conclusions are supported by ultrastructural evidence, and by immunohistochemistry and cytology data. Our results provide a straightforward and concise explanation for the pathophysiology of Mpdz-linked hydrocephalus

    Infection and Risk of Parkinson\u27s Disease

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    Parkinson\u27s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed

    An Observed Correlation Between Thermal and Non-Thermal Emission in Gamma-Ray Bursts

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    Recent observations by the FermiFermi Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some Gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal γ\gamma-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, EpE_{\rm p} and kTkT, of these two components are correlated via the relation EpTαE_{\rm p} \propto T^{\alpha} which varies from GRB to GRB. We present an interpretation in which the value of index α\alpha indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data

    Impact of COVID-19 on the management and outcomes of ureteric stones in the UK: a multicentre retrospective study

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    Objectives: To determine if management of ureteric stones in the UK changed during the coronavirus disease 2019 (COVID-19) pandemic and whether this affected patient outcomes. Patients and methods: We conducted a multicentre retrospective study of adults with computed tomography-confirmed ureteric stone disease at 39 UK hospitals during a pre-pandemic period (23/3/2019–22/6/2019) and a period during the pandemic (the 3-month period after the first severe acute respiratory syndrome coronavirus-2 case at individual sites). The primary outcome was success of primary treatment modality, defined as no further treatment required for the index ureteric stone. Our study protocol was published prior to data collection. Results: A total of 3735 patients were included (pre-pandemic 1956 patients; pandemic 1779 patients). Stone size was similar between groups (P > 0.05). During the pandemic, patients had lower hospital admission rates (pre-pandemic 54.0% vs pandemic 46.5%, P < 0.001), shorter mean length of stay (4.1 vs 3.3 days, P = 0.02), and higher rates of use of medical expulsive therapy (17.4% vs 25.4%, P < 0.001). In patients who received interventional management (pre-pandemic 787 vs pandemic 685), rates of extracorporeal shockwave lithotripsy (22.7% vs 34.1%, P < 0.001) and nephrostomy were higher (7.1% vs 10.5%, P = 0.03); and rates of ureteroscopy (57.2% vs 47.5%, P < 0.001), stent insertion (68.4% vs 54.6%, P < 0.001), and general anaesthetic (92.2% vs 76.2%, P < 0.001) were lower. There was no difference in success of primary treatment modality between patient cohorts (pre-pandemic 73.8% vs pandemic 76.1%, P = 0.11), nor when patients were stratified by treatment modality or stone size. Rates of operative complications, 30-day mortality, and re-admission and renal function at 6 months did not differ between the data collection periods. Conclusions: During the COVID-19 pandemic, there were lower admission rates and fewer invasive procedures performed. Despite this, there were no differences in treatment success or outcomes. Our findings indicate that clinicians can safely adopt management strategies developed during the pandemic to treat more patients conservatively and in the community

    Tunable Bifunctional Silyl Ether Cross-Linkers for the Design of Acid-Sensitive Biomaterials

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    Responsive polymeric biomaterials can be triggered to degrade using localized environments found in vivo. A limited number of biomaterials provide precise control over the rate of degradation, the release rate of entrapped cargo, and yield a material that is intrinsically non-toxic. Here we design non-toxic acid-sensitive biomaterials based on silyl ether chemistry. A host of silyl ether cross-linkers were synthesized and molded into relevant medical devices including Trojan horse particles, sutures, and stents. The resulting devices were engineered to degrade under acidic conditions known to exist in tumor tissue, inflammatory tissue, and within diseased cells. The implementation of silyl ether chemistry gave precise control over the rate of degradation, and depending upon the steric bulk around the silicon atom, afforded devices that could degrade over the course of hours, days, weeks, or months. These novel materials could be useful for numerous biomedical applications including drug-delivery, tissue repair, and general surgery
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