Engineering cytokine therapeutics.

Cytokines have pivotal roles in immunity, making them attractive as therapeutics for a variety of immune-related disorders. However, the widespread clinical use of cytokines has been limited by their short blood half-lives and severe side effects caused by low specificity and unfavourable biodistribution. Innovations in bioengineering have aided in advancing our knowledge of cytokine biology and yielded new technologies for cytokine engineering.

Lower Risk of Recurrence with a Higher Induction Dose of Mesalazine and Longer Duration of Treatment in Ulcerative Colitis: Results from the Dutch, Non-Interventional, IMPACT Study.

Background And Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes.

Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.

Markerless Real-Time 3-Dimensional kV Tracking of Lung Tumors During Free Breathing Stereotactic Radiation Therapy.

Purpose: Accurate verification of tumor position during irradiation could reduce the probability of target miss. We investigated whether a commercial gantry-mounted 2-dimensional (2D) kilo-voltage (kV) imaging system could be used for real-time 3D tumor tracking during volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Markerless tumor tracking on kV fluoroscopic images was validated using a life-like moving thorax phantom and subsequently performed on kV images continuously acquired before and during free-breathing VMAT lung SBRT.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial.

Importance: It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS).

Objective: To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days.

Design, Setting, And Participants: Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation.

Reliability and Reproducibility of Neuromelanin-Sensitive Imaging of the Substantia Nigra: A Comparison of Three Different Sequences.

Background: Neuromelanin-sensitive MRI (NM-MRI) of the substantia nigra provides a noninvasive way to acquire an indirect measure of dopamine functioning. Despite the potential of NM-MRI as a candidate biomarker for dopaminergic pathology, studies about its reproducibility are sparse.

Purpose: To assess the test-retest reproducibility of three commonly used NM-MRI sequences and evaluate three analysis methods.

Stem cell therapy for neurological disorders.

Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden globally. The scope of treatment options for neurological disease is limited, and drug approval rates for improved treatments remain poor when compared with other therapeutic areas. Stem cell therapy provides hope for many patients, but should be tempered with the realisation that the scientific and medical communities are still to fully unravel the complexities of stem cell biology, and to provide satisfactory data that support the rational, evidence-based application of these cells from a therapeutic perspective.

High-velocity impact of solid objects on Non-Newtonian Fluids.

We investigate which property of non-Newtonian fluids determines the deceleration of a high-speed impacting object. Using high-speed camera footage, we measure the velocity decrease of a high-speed spherical object impacting a typical Newtonian fluid (water) as a reference and compare it with a shear thickening fluid (cornstarch) and a shear thinning viscoelastic fluid (a weakly cross-linked polymer gel). Three models describing the kinetic energy loss of the object are considered: fluid inertia, shear thickening and viscoelasticity.

Comparing causes of death of Hodgkin lymphoma and breast cancer patients between medical records and cause-of-death statistics.

Objective: Obtaining accurate data about causes of death may be difficult in patients with a complicated disease history, including cancer survivors. This study compared causes of death derived from medical records (COD) with causes of death derived from death certificates (COD) as processed by Statistics Netherlands of patients primarily treated for Hodgkin lymphoma (HL) or breast cancer (BC).

Methods: Two hospital-based cohorts comprising 1,215 HL patients who died in the period 1980-2013 and 714 BC patients who died in the period 2000-2013 were linked with cause-of-death statistics files.

Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS).

Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy.

Design, Setting, And Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands.

Clinical evaluation of [I]FP-CIT SPECT scans on the novel brain-dedicated InSPira HD SPECT system: a head-to-head comparison.

The InSPira HD system, a novel brain-dedicated SPECT scanner, allows for imaging with a high spatial resolution. Here, we tested whether this scanner can be used to image the dopamine transporter adequately. Therefore, striatal phantom and patient data acquired on the InSPira were compared head-to-head with the well-validated brain-dedicated NeuroFocus system.

An automated approach to the classification of impact spatter and cast-off bloodstain patterns.

In the forensic discipline of bloodstain pattern analysis, it has been suggested that there is a blurred boundary between characterising the features of a bloodstain pattern and determining the mechanism(s) that led to its deposition. This study proposes that bloodstain pattern classification can become a distinct and logical process by implementing an automated approach. To do this, an automated bloodstain pattern recognition system was developed to enable the distinction of two types of spatter bloodstain patterns.

RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial.

Background: Evidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population.  METHODS/DESIGN: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h.

Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy.

Background: Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes.

Effect of Wetting on Drop Splashing of Newtonian Fluids and Blood.

We investigate the impact velocity beyond which the ejection of smaller droplets from the main droplet (splashing) occurs for droplets of different liquids impacting different smooth surfaces. We examine its dependence on the surface wetting properties and droplet surface tension. We show that the splashing velocity is independent of the wetting properties of the surface but increases roughly linearly with increasing surface tension of the liquid.

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques.

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9.

Differences in optimality index between planned place of birth in a birth centre and alternative planned places of birth, a nationwide prospective cohort study in The Netherlands: results of the Dutch Birth Centre Study.

Objectives: To compare the Optimality Index of planned birth in a birth centre with planned birth in a hospital and planned home birth for low-risk term pregnant women who start labour under the responsibility of a community midwife.

Design: Prospective cohort study.

Setting: Low-risk pregnant women under care of a community midwife and living in a region with one of the 21 participating Dutch birth centres or in a region with the possibility for midwife-led hospital birth.

An eye tracking study of bloodstain pattern analysts during pattern classification.

Bloodstain pattern analysis (BPA) is the forensic discipline concerned with the classification and interpretation of bloodstains and bloodstain patterns at the crime scene. At present, it is unclear exactly which stain or pattern properties and their associated values are most relevant to analysts when classifying a bloodstain pattern. Eye tracking technology has been widely used to investigate human perception and cognition.

An image-processing methodology for extracting bloodstain pattern features.

There is a growing trend in forensic science to develop methods to make forensic pattern comparison tasks more objective. This has generally involved the application of suitable image-processing methods to provide numerical data for identification or comparison. This paper outlines a unique image-processing methodology that can be utilised by analysts to generate reliable pattern data that will assist them in forming objective conclusions about a pattern.

Hepatic parenchymal transection increases liver volume but not function after portal vein embolization in rabbits.

Background: Associating liver partition with portal vein ligation for staged hepatectomy induces more extensive liver hypertrophy than ligation alone; however, the mechanisms underlying the accelerated liver regrowth and the functional quality of the hypertrophic liver are presently elusive. This study, therefore, investigated the effect of parenchymal transection on liver volume and function after portal vein embolization in a standardized rabbit model.

Methods: Twelve rabbits were subjected to portal vein embolization of the cranial liver lobes and randomized between parenchymal transection of the left lateral liver lobe versus no transection (portal vein embolization only).

Comparable liver function and volume increase after portal vein embolization in rabbits and humans.

Background: Portal vein embolization is the gold standard approach to preoperatively enhance the future liver remnant before liver resection. Portal vein embolization is studied in several experimental animal models; however, clinical translation of results is often difficult. We aimed to examine the translational value of the portal vein embolization response in a standardized rabbit model by comparing the volume and function increase with the response seen in patients.

A novel, element-based approach for the objective classification of bloodstain patterns.

The classification of bloodstain patterns has been identified as a challenging part of bloodstain pattern analysis due to the lack of a widely accepted and well-defined methodology and the ambiguity often associated with examining bloodstain patterns. The main aim of this study was to develop an objective, science-based method, for classifying bloodstain patterns, through the development of common language that could be used by BPA experts to describe the appearance of the pattern. This novel approach encourages a shift in the mindset of a BPA analyst by bringing them 'back to the basics' by treating components of a bloodstain pattern as discrete, observable and measurable units.

Understanding the visibility of blood on dark surfaces: A practical evaluation of visible light, NIR, and SWIR imaging.

Bloodstains on dark surfaces are often difficult to detect due to a lack of contrast. Infrared photography is in many cases a solution as it enhances the contrast between blood and background. Still, on some surfaces bloodstains cannot be visualized.