Acute kidney injury in Staphylococcus aureus bacteraemia: a recurrent events analysis.

OBJECTIVES: To estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects. METHODS: We performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions. RESULTS: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001-1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01-1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28-2.42), septic shock (HR 3.28, 95% CI 2.31-4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08-2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05-3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91-6.23). DISCUSSION: The incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.

Two-Year Results of a Five-Year Personalized Integrative Obesity Coaching Program (IBO) Based upon a Systems Health Perspective and an Evolutionary Longitudinal Study Approach.

This study presents the outcomes of a 5-year personalized integrative coaching program for adults with obesity (body mass index BMI ≥ 30 kg/m2), based upon a systems health perspective, during the first 2 years. This longitudinal study, which had an evolutionary design, included all adults who enrolled in the program. Health-related quality of life (HRQoL) was measured with the Short Form-36 (SF-36), and physical outcomes included weight, waist circumference, aerobic capacity, lipid profile, and HbA1c. Subsequently, participants completed questionnaires (e.g., the Symptom Checlist-90 (SCL-90) and the Checklist Individual Strength (CIS)). Seventy-nine adults with a mean BMI of 39.5 kg/m2 (SD 5.3) were included. Forty-four participants completed 2 years in the program. Compared to baseline, there were significant improvements in the SF-36 subscales 'physical functioning' (MD 9.9 points, 95% CI: 2.1-17.5, p = 0.013) and 'general health perceptions' (MD 9.3 points, 95% CI 2.9-15.7, p = 0.006). Furthermore, significant improvements in physical outcomes and psychosocial questionnaires (e.g., weight loss (MD 3.5 kg, 95% CI: 1.2-5.7, p = 0.003), waist circumference (MD 5.1 cm, 95% CI: 2.4-7.8, p < 0.001), and CIS fatigue (MD 6.8, 95% CI: 3.1-10.5, p = 0.001) were observed. This study highlights the importance of a systems health perspective supporting the development of a personalized integrative coaching program for adults with obesity in a 'real-world' setting.

The minimal important change (MIC) and minimal clinically important difference (MCID) of the patient and observer scar assessment scale (POSAS) 2.0.

BACKGROUND: The Patient and Observer Scar Assessment Scale (POSAS) is frequently used to assess scar quality after burns. It is important to be aware of the minimal important change (MIC) and the minimal clinically important difference (MCID) to establish if a POSAS score represents a clinically relevant change or difference. The aim of this study is to explore the MIC and MCID of POSAS version 2.0. METHODS: This prospective study included 127 patients with deep dermal burns that underwent split thickness skin grafting with a mean age of 44 years (range 0 - 87) and total body surface area burned of 10 % (range 0.5 - 55). POSAS data was obtained for one burn scar area at three, six, and 12 months after split skin grafting. At the second and third visits, patients rated the degree of clinical change in scar quality in comparison to the previous visit. At 12 months, they completed the POSAS for a second burn scar area and rated the degree of clinical difference between the two scar areas. Two anchor-based methods were used to determine the MIC and MCID. RESULTS: MIC values of the patient POSAS ranged from - 0.59 to - 0.29 between three and six months and from - 0.75 to - 0.38 between six and 12 months follow-up. Both had a poor discriminatory value. MCID values ranged from - 0.39 and - 0.08, with a better discriminatory value. CONCLUSION: Results suggest that patients consider minor differences (less than 0.75 on the 1-10 scale) in POSAS scores as clinically important scar quality changes. MCID values can be used to evaluate the effects of burn treatment and perform sample-size calculations.

Four-dimensional computed tomography as first-line imaging in primary hyperparathyroidism, a retrospective comparison to conventional imaging in a predominantly single adenoma population.

BACKGROUND: To determine the use of four-dimensional CT as first-line imaging compared to the traditional combination of ultrasound and [99mTc]Tc-Sestamibi SPECT. MATERIALS AND METHODS: Retrospective review of preoperative imaging in patients with primary hyperparathyroidism, who underwent parathyroidectomy between 2012 and 2021. In one group, the combination ultrasound and [99mTc]Tc-Sestamibi SPECT was used as first-line imaging (n = 54), in the other group four-dimensional CT was the first-line imaging modality (n = 51). Sensitivity and positive predictive value were calculated on patient, lateralisation and localisation level. The need for additional imaging was also assessed for both groups. RESULTS: Four-dimensional CT had a significantly higher sensitivity compared to the combination of ultrasound/[99mTc]Tc-Sestamibi SPECT on patient and localisation level (70.6% vs. 51.9%, p = 0.049 and 60.8% vs. 35.2%, p = 0.009 respectively). Sensitivity for lateralisation also appeared higher, but did not reach significance (62.7% vs. 44.4%, p = 0.060). Positive predictive value was not significantly higher for four-dimensional CT compared to ultrasound and [99mTc]Tc-Sestamibi SPECT (88.9% vs. 85.7% for lateralisation and 86.1% vs. 67.9% for localisation respectively). Additional imaging was required in 14 patients with four-dimensional CT as first-line imaging (27.4%) consisting of 2 ultrasound/[99mTc]Tc-Sestamibi SPECT and 13 [18F]fluorocholine PET/CT, compared to 24 patients with ultrasound/[99mTc]Tc-Sestamibi SPECT as first-line imaging (44.4%), requiring 22 four-dimensional CT and 9 [18F]fluorocholine PET/CT. CONCLUSIONS: Four-dimensional CT as the sole first-line parathyroid imaging modality had higher sensitivity than the combination of ultrasound and [99mTc]Tc-Sestamibi SPECT, therefore requiring fewer additional procedures. Although the most costly, [18F]fluorocholine PET/CT was the most effective technique to localise parathyroid adenoma in case all other imaging was negative.

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Effectiveness of tranexamic acid in burn patients undergoing surgery - a systematic review and meta-analysis.

BACKGROUND: Reducing blood loss during excisional surgery in burn patients remains a challenge. Tranexamic acid during surgery can potentially reduce blood loss. The use of tranexamic acid during excisional surgery in burn patients has recently been described in a review and meta-analysis. However, quality assessment on studies included was not performed and this review did not apply independent reviewers. Quality assessment of studies investigating the effectiveness of tranexamic acid in burn patients is crucial before concusions can be drawn. Therefore, we conducted a systematic review and meta-analysis of the literature investigating the effectiveness of tranexamic acid in burn patients undergoing surgery. METHODS: A systematic review and meta-analysis of the literature was conducted. The study was pre-registered in PROSPERO database (CRD42023396183). RESULTS: Five studies including two randomised controlled trials (RCTs) with a total of 303 patients were included. Risk of bias of the included studies was moderate to high. Individual results of the studies were heterogeneous. In three studies of moderate quality the administration of tranexamic acid resulted in a reduction of blood loss per unit excised area, accounting as moderate level of evidence. In two low-quality studies and one moderate quality study the administration of tranexamic acid resulted in a reduction of transfused packed Red Blood Cells (pRBC's), accounting for moderate level of evidence. Postoperative haemoglobin levels were higher after tranexamic acid administration in one study, accounting for insufficient evidence. Meta-analysis pooling overall blood loss from two separate RCTs failed to detect a statistically significant reduction. Substantial heterogeneity was observed. CONCLUSIONS: Moderate level of evidence indicates that tranexamic acid reduces blood loss per unit of excised area and transfusion of packed Red Blood Cells. Results indicate that tranexamic acid can be beneficial in burn patients undergoing surgery. More high-quality research is needed to confirm these results. Future studies should focus on the dosing of tranexamic acid, the administration approaches, and even consider combining these approaches. TRIAL REGISTRATION: PROSPERO: CRD42023396183.

Tunable Neuromorphic Switching Dynamics via Porosity Control in Mesoporous Silica Diffusive Memristors.

In response to the growing need for efficient processing of temporal information, neuromorphic computing systems are placing increased emphasis on the switching dynamics of memristors. While the switching dynamics can be regulated by the properties of input signals, the ability of controlling it via electrolyte properties of a memristor is essential to further enrich the switching states and improve data processing capability. This study presents the synthesis of mesoporous silica (mSiO2) films using a sol-gel process, which enables the creation of films with controllable porosities. These films can serve as electrolyte layers in the diffusive memristors and lead to tunable neuromorphic switching dynamics. The mSiO2 memristors demonstrate short-term plasticity, which is essential for temporal signal processing. As porosity increases, discernible changes in operating currents, facilitation ratios, and relaxation times are observed. The underlying mechanism of such systematic control was investigated and attributed to the modulation of hydrogen-bonded networks within the porous structure of the silica layer, which significantly influences both anodic oxidation and ion migration processes during switching events. The result of this work presents mesoporous silica as a unique platform for precise control of neuromorphic switching dynamics in diffusive memristors.

Timing of surgery in acute deep partial-thickness burns: A study protocol.

For deep partial-thickness burns no consensus on the optimal treatment has been reached due to conflicting study outcomes with low quality evidence. Treatment options in high- and middle-income countries include conservative treatment with delayed excision and grafting if needed; and early excision and grafting. The majority of timing of surgery studies focus on survival rather than on quality of life. This study protocol describes a study that aims to compare long-term scar quality, clinical outcomes, and patient-reported outcomes between the treatment options. A multicentre prospective study will be conducted in the three Dutch burn centres (Rotterdam, Beverwijk, and Groningen). All adult patients with acute deep-partial thickness burns, based on healing potential with Laser Doppler Imaging, are eligible for inclusion. During a nine-month baseline period, standard practice will be monitored. This includes conservative treatment with dressings and topical agents, and excision and grafting of residual defects if needed 14-21 days post-burn. The subsequent nine months, early surgery is advocated, involving excision and grafting in the first week to ten days post-burn. The primary outcome compared between the two groups is long-term scar quality assessed by the Patient and Observer Scar Assessment Scale 3.0 twelve months after discharge. Secondary outcomes include clinical outcomes and patient-reported outcomes like quality of life and return to work. The aim of the study is to assess long-term scar quality in deep partial-thickness burns after conservative treatment with delayed excision and grafting if needed, compared to early excision and grafting. Adding to the ongoing debate on the optimal treatment of these burns. The broad range of studied outcomes will be used for the development of a decision aid for deep partial-thickness burns, to fully inform patients at the point of consent to surgery and support optimal person-centred care.

Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial.

Importance: Lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use. Objective: To determine whether the judicious use of a syndromic polymerase chain reaction (PCR)-based panel for rapid testing of CAP in the emergency department (ED) leads to faster, more accurate microbiological test result-based treatment. Design, Setting, and Participants: This parallel-arm, single-blinded, single-center, randomized clinical superiority trial was conducted between September 25, 2020, and June 21, 2022, in the ED of Haukeland University Hospital, a large tertiary care hospital in Bergen, Norway. Adult patients who presented to the ED with suspected CAP were recruited. Participants were randomized 1:1 to either the intervention arm or standard-of-care arm. The primary outcomes were analyzed according to the intention-to-treat principle. Intervention: Patients randomized to the intervention arm received rapid syndromic PCR testing (BioFire FilmArray Pneumonia plus Panel; bioMérieux) of LRT samples and standard of care. Patients randomized to the standard-of-care arm received standard microbiological diagnostics alone. Main Outcomes and Measures: The 2 primary outcomes were the provision of pathogen-directed treatment based on a microbiological test result and the time to provision of pathogen-directed treatment (within 48 hours after randomization). Results: There were 374 patients (221 males [59.1%]; median (IQR) age, 72 [60-79] years) included in the trial, with 187 in each treatment arm. Analysis of primary outcomes showed that 66 patients (35.3%) in the intervention arm and 25 (13.4%) in the standard-of-care arm received pathogen-directed treatment, corresponding to a reduction in absolute risk of 21.9 (95% CI, 13.5-30.3) percentage points and an odds ratio for the intervention arm of 3.53 (95% CI, 2.13-6.02; P < .001). The median (IQR) time to provision of pathogen-directed treatment within 48 hours was 34.5 (31.6-37.3) hours in the intervention arm and 43.8 (42.0-45.6) hours in the standard-of-care arm (mean difference, -9.4 hours; 95% CI, -12.7 to -6.0 hours; P < .001). The corresponding hazard ratio for intervention compared with standard of care was 3.08 (95% CI, 1.95-4.89). Findings remained significant after adjustment for season. Conclusions and Relevance: Results of this randomized clinical trial indicated that routine deployment of PCR testing for LRT pathogens led to faster and more targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard, time-consuming, laboratory-based diagnostics. Trial Registration: ClinicalTrials.gov Identifier: NCT04660084.

Association between work sick-leave absenteeism and SARS-CoV-2 notifications in the Netherlands during the COVID-19 epidemic.

BACKGROUND: Alternative data sources for surveillance have gained importance in maintaining coronavirus disease 2019 (COVID-19) situational awareness as nationwide testing has drastically decreased. Therefore, we explored whether rates of sick-leave from work are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) notification trends and at which lag, to indicate the usefulness of sick-leave data for COVID-19 surveillance. METHODS: We explored trends during the COVID-19 epidemic of weekly sick-leave rates and SARS-CoV-2 notification rates from 1 June 2020 to 10 April 2022. Separate time series were inspected visually. Then, Spearman correlation coefficients were calculated at different lag and lead times of zero to four weeks between sick-leave and SARS-CoV-2 notification rates. We distinguished between four SARS-CoV-2 variant periods, two labour sectors and overall, and all-cause sick-leave versus COVID-19-specific sick-leave. RESULTS: The correlation coefficients between weekly all-cause sick-leave and SARS-CoV-2 notification rate at optimal lags were between 0.58 and 0.93, varying by the variant period and sector (overall: 0.83, lag -1; 95% CI [0.76, 0.88]). COVID-19-specific sick-leave correlations were higher than all-cause sick-leave correlations. Correlations were slightly lower in healthcare and education than overall. The highest correlations were mostly at lag -2 and -1 for all-cause sick-leave, meaning that sick-leave preceded SARS-CoV-2 notifications. Correlations were highest mostly at lag zero for COVID-19-specific sick-leave (coinciding with SARS-CoV-2 notifications). CONCLUSION: All-cause sick-leave might offer an earlier indication and evolution of trends in SARS-CoV-2 rates, especially when testing is less available. Sick-leave data may complement COVID-19 and other infectious disease surveillance systems as a syndromic data source.

Trailing-edge far-field noise and noise source characterization in high inflow turbulence conditions.

Airframe noise currently is a bottle neck in various applications, e.g., wind energy, maritime applications, and aircraft. Airframe noise is significantly increased by the presence of inflow turbulence. High inflow turbulence influences the boundary layer and wall-pressure fluctuations close to the trailing edge of airfoils. In this research, measurements of boundary layer and wall-pressure fluctuations near the trailing edge of an airfoil are conducted to investigate how the inflow turbulence affects the trailing-edge noise generation mechanism. Far-field noise measurements of additional three airfoils are shown to understand the role of the airfoil geometry in the dominant noise source for the cases of inflow turbulence and to generalize the observed increase in trailing-edge noise. Inflow turbulence leads to an increase in both the wall-pressure spectrum and spanwise correlation length. Trailing-edge noise increases due to the inflow turbulence in the entire frequency range at least 2 dB up to more than 15 dB for all the cases. The contribution of leading- and trailing-edge noise to the total noise varies with the airfoil geometry and inflow velocity, with the trailing-edge noise dominating in a larger frequency range for the thickest airfoil and for lower velocities.

Opportunities for personalised follow-up in breast cancer: the gap between daily practice and recurrence risk.

PURPOSE: Follow-up guidelines barely diverge from a one-size-fits-all approach, even though the risk of recurrence differs per patient. However, the personalization of breast cancer care improves outcomes for patients. This study explores the variation in follow-up pathways in the Netherlands using real-world data to determine guideline adherence and the gap between daily practice and risk-based surveillance, to demonstrate the benefits of personalized risk-based surveillance compared with usual care. METHODS: Patients with stage I-III invasive breast cancer who received surgical treatment in a general hospital between 2005 and 2020 were selected from the Netherlands Cancer Registry and included all imaging activities during follow-up from hospital-based electronic health records. Process analysis techniques were used to map patients and activities to investigate the real-world utilisation of resources and identify the opportunities for improvement. The INFLUENCE 2.0 nomogram was used for risk prediction of recurrence. RESULTS: In the period between 2005 and 2020, 3478 patients were included with a mean follow-up of 4.9 years. In the first 12 months following treatment, patients visited the hospital between 1 and 5 times (mean 1.3, IQR 1-1) and received between 1 and 9 imaging activities (mean 1.7, IQR 1-2). Mammogram was the prevailing imaging modality, accounting for 70% of imaging activities. Patients with a low predicted risk of recurrence visited the hospital more often. CONCLUSIONS: Deviations from the guideline were not in line with the risk of recurrence and revealed a large gap, indicating that it is hard for clinicians to accurately estimate this risk and therefore objective risk predictions could bridge this gap.

Higher-valency pneumococcal conjugate vaccines in older adults, taking into account indirect effects from childhood vaccination: a cost-effectiveness study for the Netherlands.

BACKGROUND: New 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined. METHODS: We used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement. RESULTS: Indirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20. CONCLUSIONS: For long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use.

Aetiology of bioethanol related burn accidents: A qualitative study.

BACKGROUND: Since insight into the motivation of behaviour in bioethanol related burn accidents is lacking, this study aimed to qualitatively examine influencing factors in bioethanol related burn accidents. In order to identify target points for effective burn prevention. METHODS: Patients previously admitted with bioethanol related acute non-intentional burn injury to the three Dutch burn centres were eligible. One interviewer conducted fourteen semi-structured interviews. Interviews were transcribed and coded by two independent researchers. Conclusions were drawn based on generalised statements on the concerned topics. RESULTS: Four overall themes in influencing factors were found, namely 1) motivation; including non-designated use and impaired judgement, 2) knowledge and education; including unknown product and properties and information overload, 3) risk perception; including poor recognisability of risks and preferred trial and error and 4) thresholds; including easy availability and unclear liability. CONCLUSION: Trust in consumers may be over-estimated, as proper use cannot be expected. To prevent future bioethanol related burn incidents, thresholds for obtaining and using bioethanol should be increased, safe alternatives to ignite open fires and wood stoves should be provided and knowledge and warnings should be improved.

Correction: π-Facial selectivity in the Diels-Alder reaction of glucosamine-based chiral furans and maleimides.

Correction for 'π-Facial selectivity in the Diels-Alder reaction of glucosamine-based chiral furans and maleimides' by Cornelis H. M. van der Loo et al., Org. Biomol. Chem., 2023, 21, 1888-1894, https://doi.org/10.1039/D2OB02221D.

Development of an in vitro setup for flow studies in a stented carotid artery bifurcation.

To investigate flow conditions in a double-layered carotid artery stent, a bench-top in vitro flow setup including a bifurcation phantom was designed and fabricated. The geometry of the tissue-mimicking phantom was based on healthy individuals. Two identical phantoms were created using 3D-printing techniques and molding with PVA-gel. In one of them, a clinically available CGuard double-layer stent was inserted. Measurements were performed using both continuous and pulsatile flow conditions. Blood flow studies were performed using echoPIV: a novel ultrasound-based technique combined with particle image velocimetry. A maximum deviation of 3% was visible between desired and measured flow patterns. The echoPIV measurements showed promising results on visualization and quantification of blood flow in and downstream the stent. Further research could demonstrate the effects of a double-layered stent on blood flow patterns in a carotid bifurcation in detail.

Dynamic Computed Tomography Angiography for capturing vessel wall motion: A phantom study for optimal image reconstruction.

BACKGROUND: Reliably capturing sub-millimeter vessel wall motion over time, using dynamic Computed Tomography Angiography (4D CTA), might provide insight in biomechanical properties of these vessels. This may improve diagnosis, prognosis, and treatment decision making in vascular pathologies. PURPOSE: The aim of this study is to determine the most suitable image reconstruction method for 4D CTA to accurately assess harmonic diameter changes of vessels. METHODS: An elastic tube (inner diameter 6 mm, wall thickness 2 mm) was exposed to sinusoidal pressure waves with a frequency of 70 beats-per-minute. Five flow amplitudes were set, resulting in increasing sinusoidal diameter changes of the elastic tube, measured during three simulated pulsation cycles, using ECG-gated 4D CTA on a 320-detector row CT system. Tomographic images were reconstructed using one of the following three reconstruction methods: hybrid iterative (Hybrid-IR), model-based iterative (MBIR) and deep-learning based (DLR) reconstruction. The three reconstruction methods where based on 180 degrees (half reconstruction mode) and 360 degrees (full reconstruction mode) raw data. The diameter change, captured by 4D CTA, was computed based on image registration. As a reference metric for diameter change measurement, a 9 MHz linear ultrasound transducer was used. The sum of relative absolute differences (SRAD) between the ultrasound and 4D CTA measurements was calculated for each reconstruction method. The standard deviation was computed across the three pulsation cycles. RESULTS: MBIR and DLR resulted in a decreased SRAD and standard deviation compared to Hybrid-IR. Full reconstruction mode resulted in a decreased SRAD and standard deviations, compared to half reconstruction mode. CONCLUSIONS: 4D CTA can capture a diameter change pattern comparable to the pattern captured by US. DLR and MBIR algorithms show more accurate results than Hybrid-IR. Reconstruction with DLR is >3 times faster, compared to reconstruction with MBIR. Full reconstruction mode is more accurate than half reconstruction mode.

Plant-based production of a protective vaccine antigen against the bovine parasitic nematode Ostertagia ostertagi.

The development of effective recombinant vaccines against parasitic nematodes has been challenging and so far mostly unsuccessful. This has also been the case for Ostertagia ostertagi, an economically important abomasal nematode in cattle, applying recombinant versions of the protective native activation-associated secreted proteins (ASP). To gain insight in key elements required to trigger a protective immune response, the protein structure and N-glycosylation of the native ASP and a non-protective Pichia pastoris recombinant ASP were compared. Both antigens had a highly comparable protein structure, but different N-glycan composition. After mimicking the native ASP N-glycosylation via the expression in Nicotiana benthamiana plants, immunisation of calves with these plant-produced recombinants resulted in a significant reduction of 39% in parasite egg output, comparable to the protective efficacy of the native antigen. This study provides a valuable workflow for the development of recombinant vaccines against other parasitic nematodes.