159 research outputs found

    The Amplification and Characterization of Mycobacteriophages MyPhage and SolarFlare

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    Bacteriophages are viruses that infect and replicate in bacteria and are being researched for medical applications. MyPhage is a Mycobacteriophage discovered in Anaconda, Montana in May of 2009. The student found the phage in soil from a potted plant. The background of SolarFlare is unknown.https://digitalcommons.mtech.edu/urp_aug_2018/1003/thumbnail.jp

    A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2)

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    Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the brain's metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. However, in depth study of oxygen metabolism with MRI has so far been hindered by the lack of robust methods. One MRI method of mapping CMRO2 is based on the simultaneous acquisition of cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) weighted images during respiratory modulation of both oxygen and carbon dioxide. Although this dual-calibrated methodology has shown promise in the research setting, current analysis methods are unstable in the presence of noise and/or are computationally demanding. In this paper, we present a machine learning implementation for the multi-parametric assessment of dual-calibrated fMRI data. The proposed method aims to address the issues of stability, accuracy, and computational overhead, removing significant barriers to the investigation of oxygen metabolism with MRI. The method utilizes a time-frequency transformation of the acquired perfusion and BOLD-weighted data, from which appropriate feature vectors are selected for training of machine learning regressors. The implemented machine learning methods are chosen for their robustness to noise and their ability to map complex non-linear relationships (such as those that exist between BOLD signal weighting and blood oxygenation). An extremely randomized trees (ET) regressor is used to estimate resting blood flow and a multi-layer perceptron (MLP) is used to estimate CMRO2 and the oxygen extraction fraction (OEF). Synthetic data with additive noise are used to train the regressors, with data simulated to cover a wide range of physiologically plausible parameters. The performance of the implemented analysis method is compared to published methods both in simulation and with in-vivo data (n = 30). The proposed method is demonstrated to significantly reduce computation time, error, and proportional bias in both CMRO2 and OEF estimates. The introduction of the proposed analysis pipeline has the potential to not only increase the detectability of metabolic difference between groups of subjects, but may also allow for single subject examinations within a clinical context

    Escape the welcome cliché

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    The University of Surrey Library and Learning Support Services (LLSS) recognised an increasing need to transform its welcome, induction and orientation activities for students. Past activities have entailed delivering information to students in ways which may have led to information overload and lack of engagement by students with library services. The LLSS have been exploring innovative ways to welcome students to university, moving away from didactic approaches. This paper presents one such innovation produced among a series of activities during 2017/18, an educational escape room, informed by the work of Walsh (2017). This activity invited students to solve a series of themed puzzles in the escape room, introducing them to library services and information literacy (IL) skills to support their studies. This report provides an account of the challenges and positive outcomes encountered in designing the escape room, with a view to sharing good learning and teaching practice

    Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen consumption and effective oxygen diffusivity

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    Dual-calibrated fMRI is a multi-parametric technique that allows for the quantification of the resting oxygen extraction fraction (OEF), the absolute rate of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes during hypercapnic and hyperoxic gas challenges. Here we propose an extension to this methodology that permits the simultaneous quantification of the effective oxygen diffusivity of the capillary network (DC). The effective oxygen diffusivity has the scope to be an informative biomarker and useful adjunct to CMRO2, potentially providing a non-invasive metric of microvascular health, which is known to be disturbed in a range of neurological diseases. We demonstrate the new method in a cohort of healthy volunteers (n = 19) both at rest and during visual stimulation. The effective oxygen diffusivity was found to be highly correlated with CMRO2 during rest and activation, consistent with previous PET observations of a strong correlation between metabolic oxygen demand and effective diffusivity. The increase in effective diffusivity during functional activation was found to be consistent with previously reported increases in capillary blood volume, supporting the notion that measured oxygen diffusivity is sensitive to microvascular physiology

    Alzheimer's genetic risk effects on cerebral blood flow are spatially consistent and proximal to gene expression across the lifespan

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    Cerebrovascular dysregulation is a hallmark feature of Alzheimer’s disease (AD), where alterations in cerebral blood flow (CBF) are observed decades prior to symptom onset. Genome-wide association studies (GWAS) show that AD has a polygenic aetiology, providing a tool for studying AD susceptibility across the lifespan. Here, we ascertain whether AD genetic risk effects on CBF previously observed (Chandler et al., 2019) remain consistent across the lifespan. We further provide a causal mechanism to AD genetic risk scores (AD-GRS) effects by establishing spatial convergence between AD-GRS associated regional reductions in CBF and mRNA expression of the proximal AD transcripts using independent data from the Allen Brain Atlas. We analysed grey matter (GM) CBF in a young cohort (N=75; aged 18-35) and an older cohort (N=90; aged 55-85). Critically, we observed that AD-GRS was negatively associated with whole brain GM CBF in the older cohort (standardised β −0.38 [−0.68 – −0.09], P = 0.012), consistent with our prior observation in younger healthy adults (Chandler et al., 2019). We then demonstrate that the regional impact of AD-GRS on GM CBF was spatially consistent across the younger and older samples (r = 0.233, P = 0.035). Finally, we show that CBF across the cortex was related to the regional expression of the genes proximal to SNP’s used to estimate AD-GRS in both younger and older cohorts (ZTWO-TAILED = −1.99, P= 0.047; ZTWO-TAILED = −2.153 P = 0.032, respectively). These observations collectively demonstrate that AD risk alleles have a negative influence on brain vascular function and likely contribute to cerebrovascular changes preceding the onset of clinical symptoms, potentially driven by regional expression of proximal AD risk genes across the brain. Our observations suggest that reduced CBF is an early antecedent of AD and a key modifiable target for therapeutic intervention in individuals with a higher cumulative genetic risk for AD. This study will further enable identification of key molecular processes that underpin AD genetic risk related reductions in CBF that could be targeted decades prior to the onset of neurodegeneration

    Investigating the delivery of health and nutrition interventions for women and children in conflict settings: a collection of case studies from the BRANCH Consortium.

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    Globally, the number of people affected by conflict is the highest in history, and continues to steadily increase. There is currently a pressing need to better understand how to deliver critical health interventions to women and children affected by conflict. The compendium of articles presented in this Conflict and Health Collection brings together a range of case studies recently undertaken by the BRANCH Consortium (Bridging Research & Action in Conflict Settings for the Health of Women and Children). These case studies describe how humanitarian actors navigate and negotiate the multiple obstacles and forces that challenge the delivery of health and nutrition interventions for women, children and adolescents in conflict-affected settings, and to ultimately provide some insight into how service delivery can be improved

    Antibiotic consumption and time to recovery from uncomplicated urinary tract infection

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    BACKGROUND: Randomised trials provide high-quality evidence on the effects of prescribing antibiotics for urinary tract infection (UTI) but may not reflect the effects in those who consume antibiotics. Moreover, they mostly compare different antibiotic types or regimens but rarely include a ‘no antibiotic’ group. AIM: To estimate the effect of antibiotic consumption, rather than prescription, on time to recovery in females with uncomplicated UTI. DESIGN AND SETTING: Secondary analysis of 14-day observational data from a point-of-care test trial for UTI in primary care in England, the Netherlands, Spain, and Wales, which ran from 2012 to 2014. Clinicians treated patients using their own judgement, providing immediate, delayed, or no antibiotic. METHOD: UTI-symptomatic females who either consumed or did not consume antibiotics during a 14-day follow-up were included. Antibiotic consumption was standardised across participants and grouped into either ≤3 or >3 standardised antibiotic days. To account for confounders, a robust propensity score matching analysis was conducted. Adjusted Kaplan–Meier and Cox proportional hazard models were employed to estimate time to recovery and hazard ratios, respectively. RESULTS: A total of n = 333 females who consumed antibiotics and n = 80 females who did not consume antibiotics were identified and included in the study. The adjusted median time to recovery was 2 days longer among patients who did not consume antibiotics (9 days, 95% confidence interval [CI] = 7 to 12) compared with those who did (7 days, 95% CI = 7 to 8). No difference was found between those who consumed ≤3 (7 days, 95% CI = 7 to 8) compared with >3 standardised antibiotic days (7 days, 95% CI = 6 to 9). CONCLUSION: Consuming antibiotics was associated with a reduction in self-reported time to recovery, but more antibiotics exposure was not associated with faster recovery in this study

    Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

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    Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 ± 6.10 vs. 48.90 ± 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 ± 17.31 vs. 136.49 ± 14.48 μmol/100g/min p<0.001) and DC (2.70 ± 0.51 vs. 3.18 ± 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 ± 0.09 vs. 0.39 ± 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression
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