Deep Neural Network Cloud-Type Classification (DeepCTC) model and its application in evaluating PERSIANN-CCS

Satellite remote sensing plays a pivotal role in characterizing hydrometeorological components including cloud types and their associated precipitation. The Cloud Profiling Radar (CPR) on the Polar Orbiting CloudSat satellite has provided a unique dataset to characterize cloud types. However, data from this nadir-looking radar offers limited capability for estimating precipitation because of the narrow satellite swath coverage and low temporal frequency. We use these high-quality observations to build a Deep Neural Network Cloud-Type Classification (DeepCTC) model to estimate cloud types from multispectral data from the Advanced Baseline Imager (ABI) onboard the GOES-16 platform. The DeepCTC model is trained and tested using coincident data from both CloudSat and ABI over the CONUS region. Evaluations of DeepCTC indicate that the model performs well for a variety of cloud types including Altostratus, Altocumulus, Cumulus, Nimbostratus, Deep Convective and High clouds. However, capturing low-level clouds remains a challenge for the model. Results from simulated GOES-16 ABI imageries of the Hurricane Harvey event show a large-scale perspective of the rapid and consistent cloud-type monitoring is possible using the DeepCTC model. Additionally, assessments using half-hourly Multi-Radar/Multi-Sensor (MRMS) precipitation rate data (for Hurricane Harvey as a case study) show the ability of DeepCTC in identifying rainy clouds, including Deep Convective and Nimbostratus and their precipitation potential. We also use DeepCTC to evaluate the performance of the Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Cloud Classification System (PERSIANN-CCS) product over different cloud types with respect to MRMS referenced at a half-hourly time scale for July 2018. Our analysis suggests that DeepCTC provides supplementary insights into the variability of cloud types to diagnose the weakness and strength of near real-time GEO-based precipitation retrievals. With additional training and testing, we believe DeepCTC has the potential to augment the widely used PERSIANN-CCS algorithm for estimating precipitation

Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. RESULTS: Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. CONCLUSION: Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs

Associations between quality of life and duration and frequency of physical activity and sedentary behaviour: Baseline findings from the WALK 2.0 randomised controlled trial.

While physical and mental health benefits of regular physical activity are well known, increasing evidence suggests that limiting sedentary behaviour is also important for health. Evidence shows associations of physical activity and sedentary behaviour with health-related quality of life (HRQoL), however, these findings are based predominantly on duration measures of physical activity and sedentary behaviour (e.g., minutes/week), with less attention on frequency measures (e.g., number of bouts). We examined the association of HRQoL with physical activity and sedentary behaviour, using both continuous duration (average daily minutes) and frequency (average daily bouts≥10 min) measures. Baseline data from the WALK 2.0 trial were analysed. WALK 2.0 is a randomised controlled trial investigating the effects of Web 2.0 applications on engagement, retention, and subsequent physical activity change. Daily physical activity and sedentary behaviour (duration = average minutes, frequency = average number of bouts ≥10 minutes) were measured (ActiGraph GT3X) across one week, and HRQoL was assessed with the 'general health' subscale of the RAND 36-Item Health Survey. Structural equation modelling was used to evaluate associations. Participants (N = 504) were 50.8±13.1 (mean±SD) years old with a BMI of 29.3±6.0. The 465 participants with valid accelerometer data engaged in an average of 24.0±18.3 minutes and 0.64±0.74 bouts of moderate-vigorous physical activity per day, 535.2±83.8 minutes and 17.0±3.4 bouts of sedentary behaviour per day, and reported moderate-high general HRQoL (64.5±20.0). After adjusting for covariates, the duration measures of physical activity (path correlation = 0.294, p<0.05) and sedentary behaviour were related to general HRQoL (path coefficient = -0.217, p<0.05). The frequency measure of physical activity was also significant (path coefficient = -0.226, p<0.05) but the frequency of sedentary behaviour was not significantly associated with general HRQoL. Higher duration levels of physical activity in fewer bouts, and lower duration of sedentary behaviour are associated with better general HRQoL. Further prospective studies are required to investigate these associations in different population groups over time

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

Fish as Reservoirs and Vectors of Vibrio cholerae

Vibrio cholerae, the etiologic agent of cholera, is autochthonous to various aquatic environments, but despite intensive efforts its ecology remains an enigma. Recently, it was suggested that copepods and chironomids, both considered as natural reservoirs of V. cholerae, are dispersed by migratory waterbirds, thus possibly distributing the bacteria between water bodies within and between continents. Although fish have been implicated in the scientific literature with cholera cases, as far as we know, no study actually surveyed the presence of the bacteria in the fish. Here we show for the first time that fish of various species and habitats contain V. cholerae in their digestive tract. Fish (n = 110) were randomly sampled from freshwater and marine habitats in Israel. Ten different fish species sampled from freshwater habitats (lake, rivers and fish ponds), and one marine species, were found to carry V. cholerae. The fish intestine of Sarotherodon galilaeus harboured ca. 5×103 V. cholerae cfu per 1 gr intestine content—high rates compared with known V. cholerae cfu numbers in the bacteria's natural reservoirs. Our results, combined with evidence from the literature, suggest that fish are reservoirs of V. cholerae. As fish carrying the bacteria swim from one location to another (some fish species move from rivers to lakes or sea and vice versa), they serve as vectors on a small scale. Nevertheless, fish are consumed by waterbirds, which disseminate the bacteria on a global scale. Moreover, V. cholerae isolates had the ability to degrade chitin, indicating a commensal relationship between V. cholerae and fish. Better understanding of V. cholerae ecology can help reduce the times that human beings come into contact with this pathogen and thus minimize the health risk this poses

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Multiple imputation for estimation of an occurrence rate in cohorts with attrition and discrete follow-up time points: a simulation study

<p>Abstract</p> <p>Background</p> <p>In longitudinal cohort studies, subjects may be lost to follow-up at any time during the study. This leads to attrition and thus to a risk of inaccurate and biased estimations. The purpose of this paper is to show how multiple imputation can take advantage of all the information collected during follow-up in order to estimate the cumulative probability <it>P(E) </it>of an event <it>E</it>, when the first occurrence of this event is observed at <it>t </it>successive time points of a longitudinal study with attrition.</p> <p>Methods</p> <p>We compared the performance of multiple imputation with that of Kaplan-Meier estimation in several simulated attrition scenarios.</p> <p>Results</p> <p>In missing-completely-at-random scenarios, the multiple imputation and Kaplan-Meier methods performed well in terms of bias (less than 1%) and coverage rate (range = [94.4%; 95.8%]). In missing-at-random scenarios, the Kaplan-Meier method was associated with a bias ranging from -5.1% to 7.0% and with a very poor coverage rate (as low as 0.2%). Multiple imputation performed much better in this situation (bias <2%, coverage rate >83.4%).</p> <p>Conclusions</p> <p>Multiple imputation shows promise for estimation of an occurrence rate in cohorts with attrition. This study is a first step towards defining appropriate use of multiple imputation in longitudinal studies.</p

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations

Self-reported pediatricians' management of the well-appearing young child with fever without a source: first survey in an European country in the anti-pneumococcal vaccine era

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest a substantially reduced risk of invasive bacterial infection in children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV). To investigate whether the introduction of PCV might affect clinical decision making, we conducted a cross-sectional survey aimed at Italian Pediatric physicians.</p> <p>Results</p> <p>The study included 348 (46.5%) primary care pediatricians; 251 (36.4%) hospital pediatricians, and 139 (20.1%) pediatric residents. In an hypothetical scenario, a well-appearing 12-month-old child with fever without source would be sent home with no therapy by 60.7% (419/690) of physicians if the child was not vaccinated with PCV. The proportion increased to 74.2% (512/690) if the child had received PCV (P < 0.0001). Also, physicians would obtain blood tests less frequently in the vaccinated than in unvaccinated children (139/690 [20.1%] <it>vs</it>. 205/690 [29.7%]; P < 0.0001), and started empiric antibiotic therapy less frequently (3.0% <it>vs</it>. 7.5%; P < 0.0001). In the hypothetical event that white blood cell count was 17,500/μL, a significantly lower proportion of physicians would ask for erythrocyte sedimentation rate (P < 0.017), C reactive protein (P < 0.0001), blood culture (P = 0.022), and urine analysis or dipstick (P = 0.028), if the child had received PCV. Only one third of participants routinely recommended PCV.</p> <p>Conclusion</p> <p>Our data suggest that implementation of educational programs regarding the proper management of the febrile child is needed.</p