Demarcation without Dogmas

This paper reviews how research on the demarcation problem has developed, starting from Popper's criterion of falsifiability and ending with recent naturalistically oriented approaches. The main differences between traditional and contemporary approaches to the problem are explicated in terms of six postulates called the traditional assumptions. It is argued that all of the assumptions can be dismissed without giving up on the demarcation problem and that doing so might benefit further discussions on pseudoscience. Four present-day research movements on evaluating the boundaries of science are introduced: (1) philosophy of pseudoscience, (2) social epistemology of dissent, (3) agnotology, and (4) evaluation of expertise. Researchers working within these areas have abandoned some or all traditional assumptions.Peer reviewe

Demarcation without Dogmas

This paper reviews how research on the demarcation problem has developed, starting from Popper's criterion of falsifiability and ending with recent naturalistically oriented approaches. The main differences between traditional and contemporary approaches to the problem are explicated in terms of six postulates called the traditional assumptions. It is argued that all of the assumptions can be dismissed without giving up on the demarcation problem and that doing so might benefit further discussions on pseudoscience. Four present-day research movements on evaluating the boundaries of science are introduced: (1) philosophy of pseudoscience, (2) social epistemology of dissent, (3) agnotology, and (4) evaluation of expertise. Researchers working within these areas have abandoned some or all traditional assumptions.Peer reviewe

New Classes of Distributed Time Complexity

A number of recent papers -- e.g. Brandt et al. (STOC 2016), Chang et al. (FOCS 2016), Ghaffari & Su (SODA 2017), Brandt et al. (PODC 2017), and Chang & Pettie (FOCS 2017) -- have advanced our understanding of one of the most fundamental questions in theory of distributed computing: what are the possible time complexity classes of LCL problems in the LOCAL model? In essence, we have a graph problem $\Pi$ in which a solution can be verified by checking all radius-$O(1)$ neighbourhoods, and the question is what is the smallest $T$ such that a solution can be computed so that each node chooses its own output based on its radius-$T$ neighbourhood. Here $T$ is the distributed time complexity of $\Pi$. The time complexity classes for deterministic algorithms in bounded-degree graphs that are known to exist by prior work are $\Theta(1)$, $\Theta(\log^* n)$, $\Theta(\log n)$, $\Theta(n^{1/k})$, and $\Theta(n)$. It is also known that there are two gaps: one between $\omega(1)$ and $o(\log \log^* n)$, and another between $\omega(\log^* n)$ and $o(\log n)$. It has been conjectured that many more gaps exist, and that the overall time hierarchy is relatively simple -- indeed, this is known to be the case in restricted graph families such as cycles and grids. We show that the picture is much more diverse than previously expected. We present a general technique for engineering LCL problems with numerous different deterministic time complexities, including $\Theta(\log^{\alpha}n)$ for any $\alpha\ge1$, $2^{\Theta(\log^{\alpha}n)}$ for any $\alpha\le 1$, and $\Theta(n^{\alpha})$ for any $\alpha <1/2$ in the high end of the complexity spectrum, and $\Theta(\log^{\alpha}\log^* n)$ for any $\alpha\ge 1$, $\smash{2^{\Theta(\log^{\alpha}\log^* n)}}$ for any $\alpha\le 1$, and $\Theta((\log^* n)^{\alpha})$ for any $\alpha \le 1$ in the low end; here $\alpha$ is a positive rational number

Diagnostic accuracy of contrast-enhanced CT for neck abscesses : A systematic review and meta-analysis of positive predictive value

Objectives To review the diagnostic accuracy of contrast-enhanced computed tomography (CT) in differentiating abscesses from cellulitis in patients with neck infections, using surgical findings as the reference standard. Materials and methods Previous studies in the last 32 years were searched from PubMed and Embase. Because of partial verification bias (only positive abscess findings are usually verified surgically), sensitivity and specificity estimates are unreliable, and we focused on positive predictive value (PPV). For all studies, PPV was calculated as the proportion of true positives out of all positives on imaging. To estimate pooled PPV, we used both the median with an interquartile range and a model-based estimate. For narrative purposes, we reviewed the utility of common morphological CT criteria for abscesses, such as central hypodensity, the size of the collection, bulging, rim enhancement, and presence of air, as well as sensitivity and specificity values reported by the original reports. Results 23 studies were found reporting 1453 patients, 14 studies in children (771 patients), two in adults (137 patients), and seven including all ages (545 patients). PPV ranged from 0.67 to 0.97 in individual studies, had a median of 0.84 (0.79–0.87), and a model-based pooled estimate of 0.83 (95% confidence interval 0.80–0.85). Most morphological CT criteria had considerable overlap between abscesses and cellulitis. Conclusions The pooled estimate of PPV is 0.83 for diagnosing neck abscesses with CT. False positives may be due to limited soft tissue contrast resolution. Overall, none of the morphological criteria seem to be highly accurate for differentiation between abscess and cellulitis.© 2022 Hagelberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.fi=vertaisarvioitu|en=peerReviewed

Microfluidic preparation and optimization of sorafenib-loaded poly(ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.Peer reviewe

Maternal Diabetes and Risk of Childhood Cancer in the Offspring

An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry-based setting. With a case-control design, we aimed to explore whether maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population-based registries, we analyzed a total of 2,029 cases, i.e. persons with childhood cancer diagnosed under the age of 20?years between years 1996-2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modelling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14-1.54) compared to the offspring of the non-diabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36-1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05-1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04-1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk-reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation. This article is protected by copyright. All rights reserved.Peer reviewe

Evaluation of the effects of nanoprecipitation process parameters on the size and morphology of poly(ethylene oxide)-block-polycaprolactone nanostructures

Nanoprecipitation is a straightforward method for the production of block copolymer nanoparticles for drug delivery applications. However, the effects of process parameters need to be understood to optimize and control the particle size distribution (PSD). To this end, we investigated the effects of material and process factors on PSD and morphology of nanoparticles prepared from an amphiphilic diblock copolymer, poly(ethylene oxide)-block-polycaprolactone. Using a Design of Experiments approach, we explored the joint effects of molecular weight, block length ratios, water volume fraction, stirring rate, polymer concentration and organic phase addition rate on hydrodynamic size and polydispersity index of the nanostructures and created statistical models explaining up to 94 % of the variance in hydrodynamic diameter. In addition, we performed morphological characterization by cryogenic transmission electron microscopy and showed that increasing the process temperature may favor the formation of vesicles from these polymers. We showed that the effects of process parameters are dependent on the polymer configuration and we found that the most useful parameters to fine-tune the PSD are the initial polymer concentration and the stirring rate. Overall, this study provides evidence on the joint effects of material and process parameters on PSD and morphology, which will be useful for rational design of formulation-specific optimization studies, scale-up and process controls.Peer reviewe

Use of fertility drugs in early onset female cancer survivors –A Finnish register-based study on 8,929 survivors

Advances in multimodality cancer treatments have increased the risk of long-term complications in early onset cancer survivors. For female cancer survivors these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of this study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRR) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A sub-classification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95 % CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counselling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years. This article is protected by copyright. All rights reserved.Peer reviewe

Emission reduction potential of different types of Finnish buildings through energy retrofits

Energy retrofitting of buildings shows great potential in reducing CO2 emissions. However, most retrofitting studies only focus on a single building type. This paper shows the relative potential in six Finnish building types, to identify possible focus areas for future retrofits in Finland. Data from previous optimization studies was used to provide optimal cases for comparison. Energy demand of the buildings was generated through dynamic simulation with the IDA-ICE software. The cases were compared according to emissions reduction, investment and life cycle cost. It was found that, in all buildings, it was possible to reduce emissions cost-neutrally by 20% to 70% in buildings with district heating and by 70% to 95% using heat pumps. Single-family homes with oil or wood boilers switching to heat pumps had the greatest emission reduction potential. More stringent requirements for energy efficiency could be mandated during building renovation

Diagnostic performance of short noncontrast biparametric 3‑T MRI for tonsillar infections : comparison with a full protocol including contrast‑enhanced sequence

Background We investigated whether a short, 5-min magnetic resonance imaging (MRI) protocol consisting of only axial T2-weighted and diffusion-weighted imaging (DWI) sequences can discriminate between tonsillar infections, peritonsillar abscesses and deeply extending abscesses in a retrospective, blinded, multireader setting. Methods We included patients sent by emergency physicians with suspected pharyngotonsillar infections who underwent emergency neck 3-T MRI from April 1 2013 to December 31 2018. Three radiologists (with 10−16 years of experience) reviewed the images for abscesses and their extension into deep neck spaces. Data were reviewed first using only axial T2-weighted Dixon images and DWI (short protocol) and second including other sequences and contrast-enhanced T1-weighted Dixon images (full protocol). Diagnostic accuracy, interobserver agreement, and reader confidence were measured. Surgical findings and clinical course served as standard of reference. Results The final sample consisted of 52 patients: 13 acute tonsillitis with no abscesses, 19 peritonsillar abscesses, and 20 deeply extending abscesses. Using the short protocol, diagnostic accuracy for abscesses across all readers was good-to-excellent: sensitivity 0.93 (95% confidence interval 0.87−0.97), specificity 0.85 (0.70−0.93), accuracy 0.91 (0.85−0.95). Using the full protocol, respective values were 0.98 (0.93−1.00), 0.85 (0.70−0.93), and 0.95 (0.90−0.97), not significantly different compared with the short protocol. Similar trends were seen with detecting deep extension. Interobserver agreement was similar between protocols. However, readers had higher confidence in diagnosing abscesses using the full protocol. Conclusions Short MRI protocol showed good-to-excellent accuracy for tonsillar abscesses. Contrast-enhanced images improved reader confidence but did not affect diagnostic accuracy or interobserver agreement. Relevance statement Short protocol consisting only of T2-weighted Dixon and DWI sequences can accurately image tonsillar abscesses, which may improve feasibility of emergency neck MRI. Key points • The short 3-T MRI protocol (T2-weighted images and DWI) was faster (5 min) than the full protocol including T1-weighted contrast-enhanced images (24 min). • The short 3-T MRI protocol showed good diagnostic accuracy for pharyngotonsillar abscesses. • Contrast-enhanced sequences improved reader confidence but did not impact diagnostic accuracy or interobserver agreement.© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.fi=vertaisarvioitu|en=peerReviewed