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"Harris, Chris"
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Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis
We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.
Journal Article
Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis
There is a paucity of evidence surrounding the optimal antifungal therapy for use in chronic pulmonary aspergillosis (CPA) and the duration of therapy remains unclear. We retrospectively evaluated treatment outcomes, including change in quality of life scores (St George's Respiratory Questionnaire (QoL)), weight and Aspergillus IgG at 6 and 12 months following initiation of therapy in a cohort of 206 CPA patients referred to the UK National Aspergillosis Centre (NAC), Manchester between April 2013 and March 2015. One hundred and forty-two patients (69%) were azole naïve at presentation and 105 (74%) (Group A) were commenced on itraconazole, 27 (19%) on voriconazole, and 10 (7%) were not treated medically. The remainder (64 patients, 31%) had previously trialled, or remained on, azole therapy at inclusion (Group B) of whom 46 (72%) received itraconazole, 16 (25%) voriconazole, and 2 (3%) posaconazole. Initial therapy was continued for 12 months in 78 patients (48%) of those treated; the azole was changed in 62 (32%) patients and discontinued in 56 (29%) patients for adverse reactions (32, 57%), azole resistance (11, 20%), clinical failure (8, 14%) or clinical stability (5, 9%). Azole discontinuation rates were higher in Group B than in Group A (42% vs. 22%, p = 0.003). For all patients who survived, weight increased (median of 62.2Kg at baseline, to 64.8 at 12 months), mean Aspergillus IgG declined from 260 (baseline) to 154 (12 months) and QoL improved from 62.2/100 (baseline) to 57.2/100 (12 months). At 12 months, there was no difference in median survival between Groups A and B (95% vs. 91%, p = 0.173). The rate of emergence of resistance during therapy was 13% for itraconazole compared to 5% for voriconazole. Bronchial artery embolization was done in 9 (4.4%) patients and lobectomy in 7 (3.2%). The optimal duration of azole therapy in CPA is undetermined due to the absence of evidenced based endpoints allowing clinical trials to be undertaken. However we have demonstrated itraconazole and voriconazole are modestly effective for CPA, especially if given for 12 months, but fewer than 50% of patients manage this duration. This suggests extended therapy may be required for demonstrable clinical improvement.
Journal Article
Somatic mutation of CDKN1B in small intestine neuroendocrine tumors
Matthew Meyerson and colleagues report whole-exome and whole-genome sequencing of 55 small intestine neuroendocrine tumors. They identify recurrent somatic mutations in
CDKN1B
, implicating cell cycle dysregulation in the pathogenesis of these tumors.
The diagnosed incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, and the underlying genomic mechanisms have not yet been defined. Using exome- and genome-sequence analysis of SI-NETs, we identified recurrent somatic mutations and deletions in
CDKN1B
, the cyclin-dependent kinase inhibitor gene, which encodes p27. We observed frameshift mutations of
CDKN1B
in 14 of 180 SI-NETs, and we detected hemizygous deletions encompassing
CDKN1B
in 7 out of 50 SI-NETs, nominating p27 as a tumor suppressor and implicating cell cycle dysregulation in the etiology of SI-NETs.
Journal Article
Now what? : a math tale
Follow along as Puppy tries again and again and finally figures out how blocks of different shapes and sizes can fit together to build a bed that's just the right size for a snooze.
Book
Improved Atlantic winter blocking in a climate model
Most climate models underestimate the frequency of Atlantic blocking. Horizontal resolution is often cited as the main culprit due to poorly resolved small‐scale variability whose upscale effects help to maintain blocks. However, recent studies show that blocking errors are also largely attributable to the large scale climatological bias of the model. Furthermore, modest resolution models can contain enough variability to generate greatly improved blocking frequency if they are corrected to account for time‐mean bias. Here we show greatly improved simulations of Atlantic winter blocking frequency in a coupled ocean–atmosphere climate model. A reduction of the mean bias, due to an improved simulation of the Atlantic Ocean, is a key element of the improvement.
Key Points
Atlantic blocking deficit is caused by Atlantic SST error
Atlantic SST errors are corrected in our improved model
Atlantic blocking is much improved
Journal Article
I'm just no good at rhyming, and other nonsense for mischievous kids and immature grownups
\"An illustrated collection of comically irreverent rhyming poems for readers of all ages, ranging in topic from avocados and anacondas to zombies and zebras (dressed like ghosts)\"-- Provided by publisher
Book
Real-time 3D analysis during electron tomography using tomviz
The demand for high-throughput electron tomography is rapidly increasing in biological and material sciences. However, this 3D imaging technique is computationally bottlenecked by alignment and reconstruction which runs from hours to days. We demonstrate real-time tomography with dynamic 3D tomographic visualization to enable rapid interpretation of specimen structure immediately as data is collected on an electron microscope. Using geometrically complex chiral nanoparticles, we show volumetric interpretation can begin in less than 10 minutes and a high-quality tomogram is available within 30 minutes. Real-time tomography is integrated into tomviz, an open-source and cross-platform 3D data analysis tool that contains intuitive graphical user interfaces (GUI), to enable any scientist to characterize biological and material structure in 3D.
High-throughput electron tomography has been challenging due to time-consuming alignment and reconstruction. Here, the authors demonstrate real-time tomography with dynamic 3D tomographic visualization integrated in tomviz, an open-source 3D data analysis tool.
Journal Article