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The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children’s reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to evaluate a partial hypothesis. With Bayesian evidence synthesis, these cohorts can still contribute to the aggregated results.

01 juni 2021, Item does not contain fulltext

13 februari 2019, Contains fulltext : 237232.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 238668.pdf (Publisher’s version ) (Open Access), PURPOSE: The presence of extensive ductal carcinoma in situ (DCIS) adjacent to HER2-positive invasive breast cancer (IBC) is often a contra-indication for breast-conserving surgery, even in case of excellent treatment response of the invasive component. Data on the response of DCIS to neoadjuvant systemic treatment (NST) are limited. Therefore, we estimated the response of adjacent DCIS to NST-containing HER2-blockade in HER2-positive breast cancer patients and assessed the association of clinicopathological and radiological factors with response. METHODS: Pre-NST biopsies were examined to determine presence of DCIS in all women with HER2-positive IBC treated with trastuzumab-containing NST +/- pertuzumab between 2004 and 2017 in a comprehensive cancer center. When present, multiple DCIS factors, including grade, calcifications, necrosis, hormone receptor, and Ki-67 expression, were scored. Associations of clinicopathological and radiological factors with complete response were assessed using logistic regression models. RESULTS: Adjacent DCIS, observed in 138/316 patients with HER2-positive IBC, was eradicated after NST in 46% of patients. Absence of calcifications suspicious for malignancy on pre-NST mammography (odds ratio (OR) 3.75; 95% confidence interval (95% CI) 1.72-8.17), treatment with dual HER2-blockade (OR 2.36; 95% CI 1.17-4.75), a (near) complete response on MRI (OR 3.55; 95% CI 1.31-9.64), and absence of calcifications (OR 3.19; 95% CI 1.34-7.60) and Ki-67 > 20% in DCIS (OR 2.74; 95% CI 1.09-6.89) on pre-NST biopsy were significantly associated with DCIS response. CONCLUSIONS: As DCIS can respond to NST containing HER2-blockade, the presence of extensive DCIS in HER2-positive breast cancer before NST should not always indicate a mastectomy. The predictive factors we found could be helpful when considering breast-conserving surgery in these patients.

The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children's reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to eva

Background: Challenging Behaviour (CB) occurs in up to 80% of nursing home residents with dementia. Identifying stressors causing CB is difficult (as residents themselves cannot indicate what is experienced as stressful), thereby hampering the psychosocial approach. Nowadays, stress-related biomedical variables, such as (aberrant) physical activity, skin temperature, heart activity, and skin conductance, can be measured continuously and relatively easily using wearable sensors. Next to validation of algorithms (i.e. the relationship between wearable data and CB), it is of utmost importance to consider the different values, attitudes, and needs of all stakeholders involved to successfully develop, apply and implement this technology. Objective: To identify the values, needs, and attitudes of multiple stakeholders regarding wearables in the care of people with dementia and CB. Method: A qualitative study was conducted, in which a real-life context was created in a Dutch nursing home. Two residents with CB wore the Empatica E4 wristband for three half-days. Multiple stakeholders (i.e., eight involved nurses and eight informal caregivers) were interviewed. Subsequently, results were used for designing two focus groups. The first focus group included formal (n=6) and informal (n=6) caregivers. The second focus group consisted of community-dwelling people with dementia (n=7) and their informal caregivers (n=5) and case managers (n=2). Results: Stakeholders accepted the wearable as a supportive technology in the care of people with dementia and CB. Expected value, user comfort, need for information, and design (including customizability and stigmatization) were important themes. During the focus groups, explicit recommendations were given by the participants with respect to the wearables’ design. Conclusion: In order to enhance the adoption of wearable sensors in CB and dementia on an individual level, inform

This paper reports the detection of the inflammatory and sepsis-related biomarker, interleukin-6 (IL-6), in human blood plasma using functionalized screen-printed electrodes (SPEs) in conjunction with a thermal detection methodology, termed heat-transfer method (HTM). SPEs are functionalized with antibodies specific for IL-6 through electrodeposition of a diazonium linking group and N'-ethylcarbodiimide hydrochloride (EDC) coupling, which was tracked through the use of cyclic voltammetry and Raman spectroscopy. The functionalized SPEs are mounted inside an additively manufactured flow cell and connected to the HTM device. We demonstrate the ability to detect IL-6 at clinically relevant concentrations in PBS buffer (pH = 7.4) with no significant interference from the similarly sized sepsis-related biomarker procalcitonin (PCT). The limit of detection (3s) of the system is calculated to correspond to 3.4 ± 0.2 pg mL-1 with a working range spanning the physiologically relevant concentration levels in both healthy individuals and patients with sepsis, indicating the sensitivity of the sensor is suitable for the application. Further experiments helped provide a proof-of-application through the detection of IL-6 in blood plasma with no significant interference observed from PCT or the constituents of the medium. Due to the selectivity, sensitivity, straightforward operation, and low cost of production, this sensor platform has the potential for use as a traffic light sensor for the multidetection of inflammatory biomarkers for the diagnosis of sepsis and other conditions in which the rapid testing of blood biomarkers has vital clinical application.

In this contribution, molecularly imprinted polymers (MIPs) were electropolymerised onto screen-printed carbon electrodes (SPCEs) to develop specific sensors for thermal detection of yeast. A laboratory yeast strain free of interferents was used to optimise the polymerisation procedure, whereas yeast in a complex mixture (yeast for baking) was employed to produce the final sensors and demonstrate proof-of-application. Two different electropolymerisation methods were employed, cyclic voltammetry and chronoamperometry respectively; the electrochemical methodology allows for controlled deposition and the ability to tailor the polymer surface to the required application. Infrared spectroscopy and scanning electron microscopy confirmed that the methods led to different structures; with cyclic voltammetry a high surface area was achieved, whereas for chronoamperometry a dense film was formed. Subsequently, these functionalised electrodes were inserted into a home-made thermal device that can measure the selective binding of yeast cells to the MIP layer via monitoring the thermal resistance (R ) at the solid–liquid interface. The results of the measurements showed that MIP-functionalised electrodes produced, according to both methods, a significant response in thermal signal for the MIP-functionalised electrode, which was not the case for the reference Non-Imprinted Polymer (NIP)-functionalised electrode. This demonstrated that thermal analysis can be employed for the detection of yeast, even in a complex sample such as food. To our knowledge, this is the first report of MIPs electropolymerised onto screen-printed electrodes for the thermal detection of fungi. The proposed approach enables the fast production of low-cost electrodes using a simple manufacturing procedure compatible with a portable device, implying high commercial potential. In the future, this could be adapted to a broad range of microorganisms including bacteria. th

Electrospun nylon 6,6 fibers incorporating polypyrrole (PPy) molecular-imprinted polymers (MIPs) were produced for the selective detection of d-glucose using a thermal detection methodology. PPy MIPs were produced using a facile bulk synthesis approach and electrospun into intricate fibrous scaffolds giving a highly mass-producible sensing interface. The maximum incorporation of MIPs and greatest sensing performance was found to be 12.1 wt % in conjunction with the heat-transfer method (HTM), a low-cost and simple thermal detection method that measures changes in the thermal resistance at the solid-liquid interface. It is demonstrated that a 12.1% incorporation of MIPs into electrospun fibers produces the widest working linear range with a limit of detection of 0.10 ± 0.01 mM. There were no observed changes in the measured thermal resistance response to incubation with a series of structurally similar compounds, providing evidence toward the selectivity of the platform. Additionally, the sensing platform exhibited a linear working response to glucose samples in artificial sweat solutions in the biologically relevant range. This is the first report of the incorporation of MIPs into nylon 6,6 fibers for the detection of glucose and points toward the possibility of developing mass-producible electrospun fibers embedded with low-cost recognition elements of improved thermal and chemical stability for the application of wearable sensor technology.

Background The clinical benefit of approved therapies in patients (pts) with metastatic colorectal cancer (mCRC) who progress on first- and second-line chemotherapy (FOLFOX and FOLFIRI) is limited. In pts with chemotherapy-refractory RAS wild type mCRC, antibodies targeting EGFR offer a monotherapy response rate of approximately 20% and a progression-free survival (PFS) of 4 months (Price 2014). HER2 is a validated target in gastric and breast cancers, with HER2 amplification occurring in ∼3–5% of pts with mCRC. Tucatinib (TUC), recently approved in multiple regions for HER2+ metastatic breast cancer, is a tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR. In pt-derived xenograft models of HER2+ mCRC, the combination of TUC + trastuzumab (TRAS) showed significantly greater antitumor activity compared with either agent alone (Kulukian 2020). The MOUNTAINEER trial was initiated to evaluate the efficacy and safety of TUC in combination with TRAS in pts with HER2+ RAS wild-type mCRC. Interim analysis of the initial 26 pts enrolled in MOUNTAINEER demonstrated an objective response rate (ORR) of 52.2% (12 partial responses [PRs] in 23 evaluable pts), median duration of response of 10.4 months, with a median PFS of 8.1 months and a median overall survival (OS) of 18.7 months (Strickler 2019). Based on these results, the trial was expanded to enable better estimation of ORR and safety. Trial design MOUNTAINEER (NCT03043313) is an open-label, pivotal phase 2 trial that initially consisted of a single cohort of up to 45 pts (Cohort A) treated with TUC (300 mg PO BID) and TRAS (8 mg/kg IV followed by 6 mg/kg IV every 3 weeks). The trial was expanded to include an additional 70 pts randomized 4:3 into 2 cohorts: Cohort B (N=40) who will receive TUC + TRAS, and Cohort C (N=30) who will receive TUC monotherapy. Pts in Cohort C will be treated with TUC (300 mg PO BID) with the option to crossover to TUC + TRAS if an objective response is not

It is well known nowadays that radioactivity can destroy the living cells it interacts with. it is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. however, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medi- cal applications. here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. in brachytherapy (BT), the radioactive sources are used for internal radiation treatment. current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomog- raphy, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. radioactive seed localization (rSl) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of rSl in a clinic through our experi- ences at the netherlands cancer institute.

The World Health Organisation (WHO) reported antimicrobial resistance (AMR) as a global threat comparable to terrorism and climate change. The use of antibiotics in veterinary or clinical practice exerts a selective pressure, which accelerates the emergence of antimicrobial resistance. Therefore, there is a clear need to detect antibiotic residues in complex matrices, such as water, food, and environmental samples, in a fast, selective, cost-effective, and quantitative manner. Once problematic areas are identified, can extraction of the antibiotics then be carried out to reduce AMR development. Molecularly imprinted polymer (MIPs) are synthetic recognition elements produced through the biomarker of interest being used as a template in order to manufacture tailor-made ligand selective polymeric recognition sites. They are emerging steadily as a viable alternative to antibiotics, especially given their low-cost, superior thermal and chemical stability that facilitates on-site detection, simplified manufacturing process, and avoiding the use of animals in the production process. In this paper, the authors critically review literature from primarily 2010–2020 on rational design approaches used to develop MIPs for sensing and extraction of antibiotics, providing an outlook on crucial issues that need to be tackled to bring MIPs for antibiotic sensing to the market.

We demonstrate that a novel functionalized interface, where molecularly imprinted polymer nanoparticles (nanoMIPs) are attached to screen-printed graphite electrodes (SPEs), can be utilized for the thermal detection of the cardiac biomarker troponin I (cTnI). The ultrasensitive detection of the unique protein cTnI can be utilized for the early diagnosis of myocardial infraction (i.e., heart attacks), resulting in considerably lower patient mortality and morbidity. Our developed platform presents an innovative route to develop accurate, low-cost, and disposable sensors for the diagnosis of cardiovascular diseases, specifically myocardial infraction. A reproducible and advantageous solid-phase approach was utilized to synthesize high-affinity nanoMIPs (average size = 71 nm) for cTnI, which served as synthetic receptors in a thermal sensing platform. To assess the performance and commercial potential of the sensor platform, various approaches were used to immobilize nanoMIPs onto thermocouples or SPEs: dip coating, drop casting, and a covalent approach relying on electrografting with an organic coupling reaction. Characterization of the nanoMIP-functionalized surfaces was performed with electrochemical impedance spectroscopy, atomic force microscopy, and scanning electron microscopy. Measurements from an in-house designed thermal setup revealed that covalent functionalization of nanoMIPs onto SPEs led to the most reproducible sensing capabilities. The proof of application was provided by measuring buffered solutions spiked with cTnI, which demonstrated that through monitoring changes in heat transfer at the solid-liquid interface, we can measure concentrations as low as 10 pg L-1, resulting in the most sensitive test of this type. Furthermore, preliminary data are presented for a prototype platform, which can detect cTnI with shorter measurement times and smaller sample volumes. The excellent sensor performance, versatility of the nanoMIPs, and reproducible and low-cos

The development of self-cleaning biomimetic surfaces has the potential to be of great benefit to human health, in addition to reducing the economic burden on industries worldwide. Consequently, this study developed a biomimetic wax surface using a moulding technique which emulated the topography of the self-cleaning Gladiolus hybridus (Gladioli) leaf. A comparison of topographies was performed for unmodified wax surfaces (control), biomimetic wax surfaces, and Gladioli leaves using optical profilometry and scanning electron microscopy. The results demonstrated that the biomimetic wax surface and Gladioli leaf had extremely similar surface roughness parameters, but the water contact angle of the Gladioli leaf was significantly higher than the replicated biomimetic surface. The self-cleaning properties of the biomimetic and control surfaces were compared by measuring their propensity to repel Escherichia coli and Listeria monocytogenes attachment, adhesion, and retention in mono- and co-culture conditions. When the bacterial assays were carried out in monoculture, the biomimetic surfaces retained fewer bacteria than the control surfaces. However, when using co-cultures of the bacterial species, only following the retention assays were the bacterial numbers reduced on the biomimetic surfaces. The results demonstrate that such surfaces may be effective in reducing biofouling if used in the appropriate medical, marine, and industrial scenarios. This study provides valuable insight into the antifouling physical and chemical control mechanisms found in plants, which are particularly appealing for engineering purposes.