Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography Organ-based Tube Current Modulation Technique

Purpose This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol

The Effects of Gantry Tilt on Breast Dose and Image Noise in Cardiac CT

Purpose: This study investigated the effects of tilted-gantry acquisition on image noise and glandular breast dose in females during cardiac computed tomography (CT) scans. Reducing the dose to glandular breast tissue is important due to its high radiosensitivity and limited diagnostic significance in cardiac CT scans. Methods: Tilted-gantry acquisition was investigated through computer simulations and experimental measurements. Upon IRB approval, eight voxelized phantoms were constructed from previously acquired cardiac CT datasets. Monte Carlo simulations quantified the dose deposited in glandular breast tissue over a range of tilt angles. The effects of tilted-gantry acquisition on breast dose were measured on a clinical CT scanner (CT750HD, GE Healthcare) using an anthropomorphic phantom with MOSFET dosimeters in the breast regions. In both simulations and experiments, scans were performed at gantry tilt angles of 0°–30°, in 5° increments. The percent change in breast dose was calculated relative to the nontilted scan for all tilt angles. The percent change in noise standard deviation due to gantry tilt was calculated in all reconstructed simulated and experimental images. Results: Tilting the gantry reduced the breast dose in all simulated and experimental phantoms, with generally greater dose reduction at increased gantry tilts. For example, at 30° gantry tilt, the dosimeters located in the superior, middle, and inferior breast regions measured dose reductions of 74%, 61%, and 9%, respectively. The simulations estimated 0%–30% total breast dose reduction across the eight phantoms and range of tilt angles. However, tilted-gantry acquisition also increased the noise standard deviation in the simulated phantoms by 2%–50% due to increased pathlength through the iodine-filled heart. The experimental phantom, which did not contain iodine in the blood, demonstrated decreased breast dose and decreased noise at all gantry tilt angles. Conclusions: Tilting the gantry reduced the dose to the breast, while also increasing noise standard deviation. Overall, the noise increase outweighed the dose reduction for the eight voxelized phantoms, suggesting that tilted gantry acquisition may not be beneficial for reducing breast dose while maintaining image quality

Tiresias: Predicting Security Events Through Deep Learning

With the increased complexity of modern computer attacks, there is a need for defenders not only to detect malicious activity as it happens, but also to predict the specific steps that will be taken by an adversary when performing an attack. However this is still an open research problem, and previous research in predicting malicious events only looked at binary outcomes (e.g., whether an attack would happen or not), but not at the specific steps that an attacker would undertake. To fill this gap we present Tiresias, a system that leverages Recurrent Neural Networks (RNNs) to predict future events on a machine, based on previous observations. We test Tiresias on a dataset of 3.4 billion security events collected from a commercial intrusion prevention system, and show that our approach is effective in predicting the next event that will occur on a machine with a precision of up to 0.93. We also show that the models learned by Tiresias are reasonably stable over time, and provide a mechanism that can identify sudden drops in precision and trigger a retraining of the system. Finally, we show that the long-term memory typical of RNNs is key in performing event prediction, rendering simpler methods not up to the task

Examining the alcohol-related consequences of adult drinkers who self-report medicating low mood with alcohol: an analysis of the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions survey data.

The aim of this paper is to examine the alcohol-related consequences experienced by adults who experienced a two-week period of low mood and identify as a 'self-mediator' compared to those who do not. Our focus is on assessing whether the conceptualization of alcohol use disorder severity differs across adult drinkers who self-medicate with alcohol during a period of low mood, compared to those who do not. This study used secondary data from the NESARC survey. The analytic sample consisted of 5945 participants who answered questions from the alcohol abuse/dependence (alcohol experiences) section, in the last 12 months. The sample was split into four groups by whether they self-medicated with alcohol or not, and drank alcohol in the last year and their drinking class. The findings indicated that a one factor model was the best fit and all items were a strong indicator of alcohol use disorder. The two-parameter model had the best fit, indicating that the diagnostic criteria were placed as a good fit along a continuum of severity. It was revealed that the hazardous drinking group who self-medicated, experienced more consequences even at low levels of severity. As the self-medicating hazardous drinking group also showed the highest estimates for alcohol use disorder severity, this may indicate that this group are high functioning self-medicators who are trying to regulate their drinking, and may not be as clinically high risk as expected, due to their drinking patterns

The influence of the Drygalski Ice Tongue on the local ocean

ABSTRACT The Drygalski Ice Tongue presents an ~80 km long floating obstacle to alongshore flows in the Victoria Land coastal ocean region of the Western Ross Sea. Here we use oceanographic data from near to the tongue to explore the interplay between the floating glacier and the local currents and stratification. A vessel-based circuit of the glacier, recording ocean temperature and salinity profiles, reveals the southwest corner to be the coldest and most complex in terms of vertical structure. The southwest corner structure beneath the surface warm, salty layer sustains a block of very cold water extending to 200 m depth. In this same location there was a distinct layer at 370 m not seen anywhere else of water at ~−1.93°C. The new observations broadly, but not directly, support the presence of a coherent Victoria Land Coastal Current. The data suggest the northward moving coastal current turns against the Coriolis force and works its way anticlockwise around the glacier, but with leakage beneath the glacier through the highly 'rippled' underside, resulting in a spatially heterogeneous supply to the Terra Nova Bay Polynya region – an important location for the formation of high-salinity shelf water

De Novo Structural Pattern Mining in Cellular Electron Cryotomograms

Electron cryotomography enables 3D visualization of cells in a near-native state at molecular resolution. The produced cellular tomograms contain detailed information about a plethora of macromolecular complexes, their structures, abundances, and specific spatial locations in the cell. However, extracting this information in a systematic way is very challenging, and current methods usually rely on individual templates of known structures. Here, we propose a framework called “Multi-Pattern Pursuit” for de novo discovery of different complexes from highly heterogeneous sets of particles extracted from entire cellular tomograms without using information of known structures. These initially detected structures can then serve as input for more targeted refinement efforts. Our tests on simulated and experimental tomograms show that our automated method is a promising tool for supporting large-scale template-free visual proteomics analysis

Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study.

BACKGROUND: South Africa has a large burden of rifampicin-resistant tuberculosis (RR-TB), with 18,734 patients diagnosed in 2014. The number of diagnosed patients has increased substantially with the introduction of the Xpert MTB/RIF test, used for tuberculosis (TB) diagnosis for all patients with presumptive TB. Routine aggregate data suggest a large treatment gap (pre-treatment loss to follow-up) between the numbers of patients with laboratory-confirmed RR-TB and those reported to have started second-line treatment. We aimed to assess the impact of Xpert MTB/RIF implementation on the delay to treatment initiation and loss to follow-up before second-line treatment for RR-TB across South Africa. METHODS AND FINDINGS: A nationwide retrospective cohort study was conducted to assess second-line treatment initiation and treatment delay among laboratory-diagnosed RR-TB patients. Cohorts, including approximately 300 sequentially diagnosed RR-TB patients per South African province, were drawn from the years 2011 and 2013, i.e., before and after Xpert implementation. Patients with prior laboratory RR-TB diagnoses within 6 mo and currently treated patients were excluded. Treatment initiation was determined through data linkage with national and local treatment registers, medical record review, interviews with health care staff, and direct contact with patients or household members. Additional laboratory data were used to track cases. National estimates of the percentage of patients who initiated treatment and time to treatment were weighted to account for the sampling design. There were 2,508 and 2,528 eligible patients in the 2011 and 2013 cohorts, respectively; 92% were newly diagnosed with RR-TB (no prior RR-TB diagnoses). Nationally, among the 2,340 and 2,311 new RR-TB patients in the 2011 and 2013 cohorts, 55% (95% CI 53%-57%) and 63% (95% CI 61%-65%), respectively, started treatment within 6 mo of laboratory receipt of their diagnostic specimen (p < 0.001). However, in 2013, there was no difference in the percentage of patients who initiated treatment at 6 mo between the 1,368 new RR-TB patients diagnosed by Xpert (62%, 95% CI 59%-65%) and the 943 diagnosed by other methods (64%, 95% CI 61%-67%) (p = 0.39). The median time to treatment decreased from 44 d (interquartile range [IQR] 20-69) in 2011 to 22 d (IQR 2-43) in 2013 (p < 0.001). In 2013, across the nine provinces, there were substantial variations in both treatment initiation (range 51%-73% by 6 mo) and median time to treatment (range 15-36 d, n = 1,450), and only 53% of the 1,448 new RR-TB patients who received treatment were recorded in the national RR-TB register. This retrospective study is limited by the lack of information to assess reasons for non-initiation of treatment, particularly pre-treatment mortality data. Other limitations include the use of names and dates of birth to locate patient-level data, potentially resulting in missed treatment initiation among some patients. CONCLUSIONS: In 2013, there was a large treatment gap for RR-TB in South Africa that varied significantly across provinces. Xpert implementation, while reducing treatment delay, had not contributed substantially to reducing the treatment gap in 2013. However, given improved case detection with Xpert, a larger proportion of RR-TB patients overall have received treatment, with reduced delays. Nonetheless, strategies to further improve linkage to treatment for all diagnosed RR-TB patients are urgently required

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

Visualizing insulin vesicle neighborhoods in β cells by cryo-electron tomography

Subcellular neighborhoods, comprising specific ratios of organelles and proteins, serve a multitude of biological functions and are of particular importance in secretory cells. However, the role of subcellular neighborhoods in insulin vesicle maturation is poorly understood. Here, we present single-cell multiple distinct tomogram acquisitions of β cells for in situ visualization of distinct subcellular neighborhoods that are involved in the insulin vesicle secretory pathway. We propose that these neighborhoods play an essential role in the specific function of cellular material. In the regions where we observed insulin vesicles, a measurable increase in both the fraction of cellular volume occupied by vesicles and the average size (diameter) of the vesicles was apparent as sampling moved from the area near the nucleus toward the plasma membrane. These findings describe the important role of the nanometer-scale organization of subcellular neighborhoods on insulin vesicle maturation