Selection by AZT and Rapid Replacement in the Absence of Drugs of HIV Type 1 Resistant to Multiple Nucleoside Analogs

We studied the intrahost evolution and dynamics of a multidrug-resistant HIV-1, which contains an insertion of two amino acids (aa) and several aa changes within the reverse transcriptase (RT) gene. From an individual receiving intermittent therapy, sequences of 231 full-length molecular clones of HIV-1 RT were obtained from serum-derived viruses at 12 consecutive time points over a period of 6 years, 17 to 20 clones per time point. In the 3.5-year period prior to the first course of therapy, only wild-type (wt) viruses were found. As soon as 6 months after the start of zidovudine (AZT) monotherapy, all viruses contained an insertion of two aa between positions 68 and 69 of the RT and aa changes at positions 67 and 215, a combination conferring resistance to multiple nucleoside analogs. After termination of therapy, the insertion mutants were rapidly and completely replaced by the wt viruses. In turn, the insertion mutants replaced the wt viruses after initiation of therapy with 3TC, d4T, and saquinavir. After termination of triple therapy, the wt viruses completely replaced the mutants within 1 month, which is markedly faster than has been observed earlier for the replacement of AZT-resistant viruses. Fast replacements of the mutant virus populations after termination of therapy indicate gross competitive disadvantage of the insertion mutant in the absence of therapy, which we estimated by using several models. The insertion mutants attained high virus loads, demonstrating that virus load cannot be used as a direct measure of virus fitness

Cardiovascular biochemical risk factors among women with spontaneous preterm delivery

ObjectiveTo determine whether women delivering preterm have unfavorable cardiovascular profiles as compared with women who deliver at term. MethodsA prospective observational cohort study enrolled 165 women with spontaneous preterm delivery (sPTD) at 24(+0) and 36(+6) gestational weeks in three perinatal care centers in The Netherlands between August 2012 and August 2014. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine were measured within 24hours after delivery. Lipids and cardiovascular biochemical risk factors were compared between women with sPTD and an external comparison group of 30 women with term delivery via analysis of covariance. ResultsMean gestational age at delivery was 30.73.6weeks in the sPTD group and 40.31.3weeks in the reference group. Data were adjusted for body mass index, age, and center. As compared with the reference group, total cholesterol and LDL-cholesterol levels were lower and glucose levels were higher among women with sPTD. ConclusionAn association between sPTD and unfavorable lipids and cardiovascular biochemical risk factors was not established. The higher levels of glucose in the sPTD group might be due to increased insulin resistance, which is associated with a higher risk of sPTD

Development and Evaluation of a Proficiency-based and Simulation-based Surgical Skills Training for Technical Medicine Students

Objective: Surgical graduate training to achieve practice-ready students is needed, yet is often lacking. This study developed and evaluated a proficiency-based, simulation-based course for basic surgical skills at graduate level. Learning outcomes were measured at the level of knowledge and skills and evaluated with a post-course questionnaire after students’ clinical rotations.Methods: The surgical skills course was anchored to surgical patient flow and covered topics and skills related to pre-, intra-, and post-operative care, including case-based medical reasoning, patient safety, infection management, operating theatre etiquette, scrubbing and donning, instrument handling, local anaesthesia, excision of tissue, and suturing. Students were assessed on knowledge and procedural skills.Results: 155 graduate Technical Medicine students from academic years 2015-2016 and 2016-2017 entered this 10-week, 3 ECTS credits graduate Surgical Skills course. Pass rates of the knowledge test were 78%, and 87% for the procedural skill assessment. Graduate students reached proficiency level in a simulation-based basic surgical skills course. Students stated to go with confidence to the operating room and felt competent in performing four basic surgical skills.Conclusion: Based on this study, we recommend that proficiency-based training using simulation should be standard in surgical curricula before students are allowed to practice on patients

Motion tracking to support surgical skill feedback and evaluation

Introduction & Aims Performance evaluation of technical surgical skill is done by direct observation by expert surgeons. This is time intensive, costly, and requires training of assessors. Motion tracking could complement direct observation to provide immediate feedback during training and to support objective performance assessment. A recent study by Ahmed et al. (2017) showed that expert feedback combined with validated metrics resulted in greater performance improvement for novices. However, current motion tracking methods are expensive, non-portable, or very sensitive to disturbances from the environment. We hypothesize that combining technologies solves these limitations. The goal of the current study was to design a wireless, low-cost motion tracking system to support 1) real-time individual performance feedback and 2) objective assessment of technical surgical skills. Description An iterative, research-based design process with rapid prototyping was followed. First, we performed a needs assessment with a literature review and survey to a broad range of surgeons to identify relevant motion parameters. Second, various prototypes using an Inertial Measurement Unit (IMU) and a Leap motion sensor were tested in an authentic surgical environment for 1) robustness and 2) accuracy. Outcomes Twelve surgeons (experience range = 2 - 27 years) from five different hospitals and a range of surgical specialties completed the survey and rated ‘precision of movement’ and ‘minimizing unnecessary movements’ as most important motion parameters of surgical skill. Furthermore, unnecessary or excessive movements and secondary tissue damage were reported as most common errors. The final prototype can be seen in Figure 1. The IMU is embedded in a sleeve and detects fine motor skills such as small hand movements, tremors, and strokes. The Leap Motion sensors complement this with infrared tracking of the hand in 3D space and time. The devices proved robust under changing lighting and gowning conditions. Accuracy of motion tracking was however influenced by instrument use. Discussion Our device offers the possibility for immediate performance feedback aiding trainees’ self-assessment during training. By discriminating good from poor performers in training early on, training can be adapted to an individual trainee’s needs and facilitate deliberate practice. Future research includes expert benchmarking and parameter selection. Motion tracking analysis complements subjective assessment that is prone to bias and reduces assessors’ workload. Novelty of methodology Motion tracking to support surgical skill assessment is not yet common practice. The device offers a robust, affordable, and wearable alternative to current motion tracking devices

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: A randomized controlled trial - BARTrial

Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. Methods: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. Results: Composite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for th

Ventilation area measured with eit in order to optimize peep settings in mechanically ventilated patients

INTRODUCTION. Electrical Impedance Tomography (EIT) is a non-invasive imaging technique, which can be used to visualize ventilation. Ventilation will be measured by impedance changes due to ventilation. OBJECTIVES. The aim of this study was to optimize PEEP settings based on the ventilation area of EIT images during a decremental PEEP trial. METHODS. After a recruitment maneuver, a decremental PEEP trial was performed in 10 mechanically ventilated post cardiac surgery patients. Ventilation area, blood gases, FRC and compliance were measured at each PEEP level. The ventilation area was defined as the surface of ventilation at one lung slice measured with EIT and was expressed as percentage of its maximum obtained during a recruitment maneuver (RM). RESULTS. The amount of ventilated pixels during the RM is set as 100 %. Figure 1 shows the amount of ventilated pixels as percentage compared to its maximum during the RM. The ventilation area was significantly smaller at 5 and 0 PEEP compared to its maximum at both the dependent and non-dependent lung. Also PaO2/FiO2 and FRC were significantly lower at these PEEP levels. (Figure presented) Bars represent the mean + SD. Black = dependent lung region, White = non-dependent lung region. *

Genome structure and transcriptional regulation of human coronavirus NL63

BACKGROUND: Two human coronaviruses are known since the 1960s: HCoV-229E and HCoV-OC43. SARS-CoV was discovered in the early spring of 2003, followed by the identification of HCoV-NL63, the fourth member of the coronaviridae family that infects humans. In this study, we describe the genome structure and the transcription strategy of HCoV-NL63 by experimental analysis of the viral subgenomic mRNAs. RESULTS: The genome of HCoV-NL63 has the following gene order: 1a-1b-S-ORF3-E-M-N. The GC content of the HCoV-NL63 genome is extremely low (34%) compared to other coronaviruses, and we therefore performed additional analysis of the nucleotide composition. Overall, the RNA genome is very low in C and high in U, and this is also reflected in the codon usage. Inspection of the nucleotide composition along the genome indicates that the C-count increases significantly in the last one-third of the genome at the expense of U and G. We document the production of subgenomic (sg) mRNAs coding for the S, ORF3, E, M and N proteins. We did not detect any additional sg mRNA. Furthermore, we sequenced the 5' end of all sg mRNAs, confirming the presence of an identical leader sequence in each sg mRNA. Northern blot analysis indicated that the expression level among the sg mRNAs differs significantly, with the sg mRNA encoding nucleocapsid (N) being the most abundant. CONCLUSIONS: The presented data give insight into the viral evolution and mutational patterns in coronaviral genome. Furthermore our data show that HCoV-NL63 employs the discontinuous replication strategy with generation of subgenomic mRNAs during the (-) strand synthesis. Because HCoV-NL63 has a low pathogenicity and is able to grow easily in cell culture, this virus can be a powerful tool to study SARS coronavirus pathogenesis

Imaging Behind the Plaque:Improved Blood Flow Quantification Using an Iterative Scheme for Active Attenuation Correction

Objective: Blood flow quantification using high frame-rate (HFR), contrast-enhanced ultrasound followed by particle image velocimetry (PIV), termed echoPIV, allows the study of blood flow phenomena in diseased arteries before and after treatment. However, acoustic shadows caused by atherosclerotic plaques may lead to incomplete flow quantification. As a global increase in transmit pressure to compensate for the attenuation would lead to contrast agent destruction in unattenuated areas, this article proposes a method to locally enhance the signal amplitude, thereby improving flow quantification accuracy. Methods: The acoustic pressure was locally increased by adjusting the transmit apodization of the transducer elements using a proportional integral controller coupled to an acoustic model based on the Rayleigh integral. These iterative adjustments were performed prior to the HFR recording. This iterative scheme for active attenuation correction (ISAAC) was applied in vitro on phantoms with different levels of attenuation. A PIV analysis was then performed on each of the recorded HFR datasets. Results: Without ISAAC, using a driving voltage of 11.2V, the mean errors in velocity estimates were below 20% for attenuation values up to 6.4 dB. Using ISAAC, the errors were reduced to less than 10% for attenuation values up to 8.5 dB and to less than 20% for attenuation up to 10.6 dB. Conclusion: The proposed iterative scheme for attenuation correction was shown to compensate effectively for acoustic signal loss in acoustic shadows. ISAAC led to an improved accuracy in echoPIV-derived flow velocities.</p

Comparison of segmentation software packages for in-hospital 3D print workflow

Purpose: In-hospital three-dimensional (3D) printing of patient-specific pathologies is increasingly being used in daily care. However, the efficiency of the current conversion from image to print is often obstructed due to limitations associated with segmentation software. Therefore, there is a need for comparison of several clinically available tools. A comparative study has been conducted to compare segmentation performance of Philips IntelliSpace Portal(®) (PISP), Mimics Innovation Suite (MIS), and DICOM to PRINT(®) (D2P). Approach: These tools were compared with respect to segmentation time and 3D mesh quality. The dataset consisted of three computed tomography (CT)-scans of acetabular fractures (ACs), three CT-scans of tibia plateau fractures (TPs), and three CTA-scans of abdominal aortic aneurysms (AAAs). Independent-samples [Formula: see text]-tests were performed to compare the measured segmentation times. Furthermore, 3D mesh quality was assessed and compared according to representativeness and usability for the surgeon. Results: Statistically significant differences in segmentation time were found between PISP and MIS with respect to the segmentation of ACs ([Formula: see text]) and AAAs ([Formula: see text]). Furthermore, statistically significant differences in segmentation time were found between PISP and D2P for segmentations of AAAs ([Formula: see text]). There were no statistically significant differences in segmentation time for TPs. The accumulated mesh quality scores were highest for segmentations performed in MIS, followed by D2P. Conclusion: Based on segmentation time and mesh quality, MIS and D2P are capable of enhancing the in-hospital 3D print workflow. However, they should be integrated with the picture archiving and communication system to truly improve the workflow. In addition, these software packages are not open source and additional costs must be incurred