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Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed.

The main purpose of this article is to elaborate on the limitations of using frequency-domain passivity theories in analyzing grid-inverter interactions within the low-frequency range. It primarily covers three levels of limitations: 1) the limitations and selection criteria of two kinds of passivity index, 2) potential conflicts between different passivity index tuning methods, and 3) the relationship between the frequency range of negative passivity index and system stability robustness. The findings suggest that caution should be exercised when applying passivity theory, particularly in the low-frequency range.

A multifunctional grid-forming control method based on a disturbance observer structure is proposed for grid converters. The proposed method has several different control modes, including the grid-forming, grid-following, and current control modes. The proposed method does not require any separate synchronization loop as it is incorporated in the disturbance observer. Links to existing control methods are shown and tuning recommendations are provided based on small-signal stability analysis. Furthermore, robustness against the inductance error in the grid-forming mode is analytically shown. Experiments with a 12.5-kVA converter are used to assess power-tracking performance. The method is shown to have excellent dynamic performance regardless of grid strength and to provide seamless switching between grid-forming and grid-following modes. In addition, the effect of grid voltage sags and grid-frequency deviations is studied.

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Upconversion luminescence (UCL) has great potential for highly sensitive biosensing due to its unique wavelength shift properties. The main limitation of UCL is its low quantum efficiency, which is typically compensated using low-noise detectors and high-intensity excitation. In this work, we demonstrate surface plasmon polariton (SPP)-enhanced UCL for biosensing applications. SPPs are excited by using a gold grating. The gold grating is optimized to match the SPP resonance with the absorption wavelength of upconverting nanoparticles (UCNPs). Functionalized UCNPs conjugated with antibodies are immobilized on the surface of the fabricated gold grating. We achieve an UCL enhancement up to 65 times at low excitation power density. This enhancement results from the increase in the absorption cross section of UCNPs caused by the SPP coupling on the grating surface. Computationally, we investigated a slight quenching effect in the emission process with UCNPs near gold surfaces. The experimental observations were in good agreement with the simulation results. The work enables UCL-based assays with reduced excitation intensity that are needed, for example, in scanning-free imaging.

Job resources are known to be key drivers of work engagement, but surprisingly, little is known about the relative importance of specific job resources in comparison to one another. We investigated the relative importance of eight job resources both cross-sectionally and over a 3-year time period. We hypothesized that job resources at the task level are “universally” important and contribute relatively more to work engagement than other types of job resources. We employed dominance analyses to a large cross-sectional data set (N= 11,468 from 87 organizations), focusing specifically on 11 jobs, and to a two-wave data set (N= 2,334). Three job resources emerged as the most important both for concurrent and future work engagement across the jobs and samples: skill discretion, job feedback, and team empowerment. Practically, this study suggests that interventions to enhance work engagement could focus on increasing skill discretion and job feedback and on building team empowerment.JEL:L200 Firm Objectives, Organization, and Behavior: General

This article discusses the very common moral guideline “Punch up, do not kick down.” Our approach is based on humanistic ethics, and through rigorous philosophical analysis, we will show that while the guideline is commendable and well-intentioned, it does not work as a universal rule and should not be used as an ideological tool. Due to the complexity of our social reality and the fluid nature of hierarchies, there may be cases when punching up is problematic, and kicking down is acceptable. Our theoretical addition to the current ethics of humor is that we propose humor should be evaluated in terms of inclusivity and exclusivity as well. In this, Charles Taylor’s concept of strong evaluation will be indispensable.

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Human tissue three-dimensional (3D) organoid cultures have the potential to reproduce in vitrothe physiological properties and cellular architecture of the organs from which they are derived. The ability of organoid cultures derived from human stomach, liver, kidney, and colon to metabolically activate three dietary carcinogens, aflatoxin B1(AFB1), aristolochic acid I (AAI), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was investigated. In each case, the response of a target tissue (liver for AFB1; kidney for AAI; colon for PhIP) was compared with that of a nontarget tissue (gastric). After treatment cell viabilities were measured, DNA damage response (DDR) was determined by Western blotting for p-p53, p21, p-CHK2, and γ-H2AX, and DNA adduct formation was quantified by mass spectrometry. Induction of the key xenobiotic-metabolizing enzymes (XMEs) CYP1A1, CYP1A2, CYP3A4, and NQO1 was assessed by qRT-PCR. We found that organoids from different tissues can activate AAI, AFB1, and PhIP. In some cases, this metabolic potential varied between tissues and between different cultures of the same tissue. Similarly, variations in the levels of expression of XMEs were observed. At comparable levels of cytotoxicity, organoids derived from tissues that are considered targets for these carcinogens had higher levels of adduct formation than a nontarget tissue.

High-volume manufacturing of microstructures is essential for the uptake of the related scientific results for commercial use and also if hundreds or thousands of devices with repeatable performance are needed during the large-scale experimental research. Polydimethyl siloxane (PDMS) is one of the most widely used materials for academia to prepare microfluidic test devices. This has also motivated the development of roll-to-roll imprinting towards the fabrication of PDMS-based devices at high volumes. The gas bubble entrapping during the replication process has remained an issue resulting in defects in the microstructure. Performing imprinting in vacuum is a well-known method to avoid bubbles but it has not been applied in roll-to-roll processing. In this work we demonstrated a reduced ambient pressure roll to roll imprinting process using PDMS silicone elastomer as imprint resist. We observed the reduction in the number of bubble-originated defects in individual micro-features from 100 % to < 1 % when the ambient pressure was reduced from 1 atm to 1/8 atm. [2023-0063]

IMPORTANCE: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. OBJECTIVE: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. MAIN OUTCOMES AND MEASURES: The main outcomes were 4-year local recurrence and overall survival rates. RESULTS: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P &lt; .001), with lower non–cancer-related mortality (13.8% vs 6.3%; P &lt; .001). CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

An online survey of 200 participants was conducted on the experiences of sharing material and immaterial artifacts, focusing on interaction with non-media content types. The survey included six categories of sharing: music preferences, travel plans, sports activities, apartments and vehicles, virtual items in online games, and dietary preferences. The study identified factors that motivate participation in content-mediated interaction: discovery, curating self, connectedness, collaboration, enjoyment, and instrumental motivations, as a set of six motivating factors driving contemporary sharing practices. The authors consolidated findings from earlier work on motivations to share personal content, validating the set of motivating factors with the six selected non-media types of content. The results suggest that both extrinsic and intrinsic motivations affect content sharing practices. Furthermore, motivating factors were mapped to the reported positive and negative experiences, in order to understand their relation and to discuss their capacity to guide user experience design.

Background: The burden associated with the treatment of patients with multiple myeloma (MM) is expected to increase due to the aging population. Thus, policymakers and clinicians need a holistic view of the healthcare resource use (HCRU) and costs associated with MM and its treatment for informed decision making. However, nationwide information on HCRU and costs due to MM is scarce in Finland. The aim of this study was to determine healthcare resource utilization, patterns of service use and associated costs among Finnish patients with MM during the first 5 years from their first diagnosis and at end of life. Methods: Data on patients newly diagnosed with MM and receiving treatment for it in Finland in 2015–2019 was sourced from comprehensive nationwide registers. Data on all-cause and MM-specific HCRU including inpatient stays, outpatient visits and contacts, emergency care visits and home care were obtained separately from specialized and primary care registers. HCRU costs were assessed by multiplying the numbers of primary and specialized care contacts by respective national unit costs. For reimbursed outpatient medication and reimbursed sick leave, data on actual costs were collected. All registry data were linked via unique personal identifiers, and follow-up time was up to 5 years. Results: Altogether, 1615 patients were included in the analyses. In the 5-year follow-up period, patients had on average 96 healthcare contacts per patient-year (PPY) and the mean all-cause healthcare costs were €46,000 PPY. Around 47% of these costs originated from reimbursed outpatient medication and the rest from healthcare contacts. Over half (60%) of the contacts occurred in primary care but most of the costs were associated with specialized care. Additionally, 29% of contacts were MM-specific, but they were responsible for 58% of the costs. The HCRU was highest during the first year after diagnosis, levelled off during the follow-up and then increased significantly during the last year of patients’ lives. The number of all-cause healthcare contacts PPY was approximately 53% higher, and the respective costs were 5% higher during the last year of a patient’s life when compared with the first year after diagnosis. During the last 12 months (N= 417) and 6 months (N= 505) of life and during palliative care (N= 145), the most common healthcare contact was home care. Conclusions: During active treatment, MM is primarily treated in the specialized care setting, with outpatient medication and visits to specialized care being the main cost drivers. These results can be utilized to estimate the need for care and expected costs over time due to MM and in health economic evaluations concerning MM.

Purpose: The COVID-19 pandemic has been associated with an increased prevalence of domestic violence (DV). It has been proposed that the mitigation efforts—such as lockdown, social distancing, or stay-at-home orders—simultaneously increase the risk of DV while limiting the possibilities for seeking help. In this study, we explored the effects of the pandemic on shelter services.Method: The data consist of shelter use data and regular reports from 29 shelters in Finland. In a mixed-method study, we analyzed how shelter service use during the COVID-19 pandemic in Finland was predicted by the stringency of government actions. Furthermore, to gain additional depth on the topic, we carried out a qualitative analysis of the common issues raised by the staff in regular shelter reports.Results: We found the stringency of government actions—as measured by the comparative composite value of the Stringency Index—to causally predict shelter use during the pandemic. The major finding of our qualitative analysis is that the pandemic has affected shelters at three levels: victim, professional, and organization.Conclusion: As shelter reports indicate, the pandemic affected clients depending on how they perceive the pandemic, receive help, and the changes in their everyday lives at the shelter. At the professional level, COVID-19 affected the practices and content of work with clients, as well as the personal experience and well-being of staff. At the organizational level, there was a need to reconsider the preparedness and organization of work.

The phase-locked loop (PLL) is a commonly used synchronization control method for grid-tied inverters. The PLL-synchronized inverters tend to have poor stability robustness with weak grid interconnections, especially when the PLL is designed with a high control bandwidth. To tackle this challenge, this article proposes an enhanced q-axis voltage-integral damping control, which not only stabilizes PLL-synchronized inverters in weak grids but also lifts the restriction on PLL bandwidth. This superior feature enables inverters to operate stably in ultraweak grids and with a superior transient response. The experimental tests confirm the performance of the method with 400-Hz PLL bandwidth under a short-circuit ratio of 1.28 of the grids.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

This article discusses four ways of understanding the concept of humor: 1) in terms of necessary and sufficient conditions, as 2) a cluster concept, 3) an interpretive concept, and 4) a dual character concept. We peruse both historical and contemporary research on humor, but instead of asking “What is humor?,” we draw conclusions regarding what humor research tells us of the ways to conceptualize humor. The main merits and shortcomings of different approaches are explicated. We suggest that the increased awareness of conceptual options will help the field of humor research to construct ever better theories on the elusive subject matter.

The next-generation Versatile Video Coding (VVC) standard introduces a new Multi-Type Tree (MTT) block partitioning structure that supports Binary-Tree (BT) and Ternary-Tree (TT) splits in both vertical and horizontal directions. This new approach leads to five possible splits at each block depth. It thereby improves the coding efficiency of VVC over that of the preceding High Efficiency Video Coding (HEVC) standard, which only supports Quad-Tree (QT) partitioning with a single split per block depth. However, MTT also has brought a considerable impact on encoder computational complexity. This paper proposes a two-stage learning-based technique to tackle the complexity overhead of MTT in VVC intra encoders. In our scheme, the input block is first processed by a Convolutional Neural Network (CNN) to predict its spatial features through a vector of probabilities describing the partition at each $4\times 4$ edge. Subsequently, a Decision Tree (DT) model leverages this vector of spatial features to predict the most likely splits at each block. Finally, based on this prediction, only the $N$ most likely splits are processed by the Rate-Distortion (RD) process of the encoder. In order to train our CNN and DT models on a wide range of image contents, we also propose a public VVC frame partitioning dataset based on existing image dataset encoded with the VVC reference software encoder. Our solution relying on the top-3 configuration reaches 47.4% complexity reduction for a negligible bitrate increase of 0.79%. A top-2 configuration enables a higher complexity reduction of 70.4% for 2.49% bitrate loss. These results emphasize a better trade-off between VTM intra-coding efficiency and complexity reduction compared to the state-of-the-art solutions. The source code of the proposed method and the training dataset are made publicly available at GitHub.

Variable reactors have been a vital component of power networks for decades, where they have been used as fault-current limiting devices or for reactive power compensation. Traditionally, modifying the inductance of predominantly mechanically operated variable reactors requires seconds to minutes. In contrast, virtual air gap (VAG) reactors can change the inductance within milliseconds, potentially improving power system stability. Existing dynamic models of VAG reactors cannot capture the entire system dynamics, limiting their applicability for simulations in the time-domain. This research presents two dynamic VAG reactor models, one with and one without core losses. The models capture all significant system dynamics using electromagnetic principles and VAG reactor flux linkage behavior. The proposed models were experimentally validated using a small VAG reactor. Over a broad operating range, both models accurately reproduce the dynamic behavior, transient response, and dominant harmonics of the small VAG reactor. Consequently, the models may be used for a variety of applications, such as time-domain simulations, harmonic analysis, and the development of suitable controllers for VAG reactors. In addition, engineers may use the core loss omitting model as a VAG reactor design tool, as the actual reactor is not required for modeling.

Heating is the most energy-intensive sector worldwide as well as in Europe and Finland. About 37% of the heat produced in Finland is still produced with fossil fuels, including 5.5% with fossil fuel oil (FFO). Phasing out FFO from the energy mix in compliance to Finnish carbon neutrality target is complicated because of the decentralized use all over the country, especially in rural Finland. There have been policies and financial instruments targeted for replacement of FFO-fired heating systems, but the rate of heating system renovation has been slow as there are still about 300,000 FFO and gas-fired heating systems nationwide. In this study, we conducted a survey of homeowners with FFO heating systems and asked about their willingness to renovate their heating system. In addition, we asked them to prioritize their sustainability criteria and we ranked them using the analytical hierarchy process (AHP). The first part of the results show that younger homeowners are more interested in more sustainable modes of heating. Further, the results also show that the willingness to undergo an FFO heating system renovation is higher among respondents with university degrees compared to respondents with high-school and upper secondary educations. The second part of the results show that the economy and environment were given the equally highest priority ratings compared to technological and social criteria. However, older and university degree-educated respondents emphasized environmental criteria, climate change and renewable energy indicators more than their younger and high-school graduate counterparts.

Increased gut permeability and gut inflammation have been linked to the development of type 1 diabetes. Little is known on whether and how intake of different foods is linked to these mechanisms in infancy. We investigated whether the amount of breast milk and intake of other foods are associated with gut inflammation marker concentrations and permeability. Seventy-three infants were followed from birth to 12 months of age. Their diet was assessed with structured questionnaires and 3-day weighed food records at the age of 3, 6, 9, and 12 months. Gut permeability was assessed with the lactulose/mannitol test and fecal calprotectin and human ß-defensin-2 (HBD-2) concentrations were analyzed from stool samples at the age of 3, 6, 9, and 12 months. The associations between foods and gut inflammation marker concentrations and permeability were analyzed using generalized estimating equations. Gut permeability and gut inflammation marker concentrations decreased during the first year of life. Intake of hydrolyzed infant formula (P= 0.003) and intake of fruits and juices (P= 0.001) were associated with lower intestinal permeability. Intake of fruits and juices (P< 0.001), vegetables (P< 0.001), and oats (P= 0.003) were associated with lower concentrations of HBD-2. Higher intake of breast milk was associated with higher fecal calprotectin concentrations (P< 0.001), while intake of fruits and juices (P< 0.001), vegetables (P< 0.001), and potatoes (P= 0.007) were associated with lower calprotectin concentrations. Higher intake of breast milk may contribute to higher calprotectin concentration, whereas several complementary foods may decrease gut permeability and concentrations of calprotectin and HBD-2 in infant gut.

IMPORTANCE: Spontaneous adverse reaction reports of sudden hearing loss have been observed, and a population-based cohort study conducted in Israel showed an increase in the incidence of sudden sensorineural hearing loss (SSNHL) following vaccination with messenger RNA COVID-19 vaccine BNT162b2 (Pfizer-BioNTech). However, in this setting, the possibility of confounding remained. OBJECTIVE: To assess a potential association between COVID-19 vaccinations and SSNHL. DESIGN, SETTING, AND PARTICIPANTS: This register-based country-wide retrospective cohort study of 5.5 million Finnish residents was conducted from January 1, 2019, to April 20, 2022, and included all individuals who were identified from the population information system who were alive or born during the study period except individuals who had SSNHL during 2015 to 2018 according to specialized care derived diagnosis codes for SSNHL (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code H91.2) as a primary or secondary diagnosis. EXPOSURES: The a priori primary risk period was 0 to 54 days following each COVID-19 vaccination. The risk periods for different vaccine doses did not overlap so that a later vaccine exposure ended the previous risk period. The secondary risk period was from 55 days following each COVID-19 vaccination until a subsequent COVID-19 vaccination. A secondary analysis included a risk time from 0 to 54 days following a positive polymerase chain reaction test result for SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The incidences of SSNHL following COVID-19 vaccination were compared with the incidences before the COVID-19 epidemic in Finland. The Poisson regression model included calendar time, age, sex, diabetes, cardiovascular disease, other chronic diseases, and the number of visits in primary health care. RESULTS: For the 5.5 million Finnish residents included in the study, the comparison time comprised 6.5 million person-years, the primary risk time of 1.7 million person-years, and the secondary risk time of 2.1 million person-years. Before the COVID-19 epidemic in Finland, 18.7/100 000 people received a diagnosis of SSNHL annually. The study data suggested no increased risk for SSNHL following any COVID-19 vaccination. In particular, adjusted incidence rate ratios with 95% confidence intervals for the BNT162b2 vaccine’s 3 doses were 0.8 (95% CI, 0.6-1.0), 0.9 (95% CI, 0.6-1.2), and 1.0 (95% CI, 0.7-1.4), respectively. There was no association between SARS-CoV-2 infection and an increased incidence of SSNHL. CONCLUSIONS AND RELEVANCE: The results of this cohort study show no evidence of an increased risk of SSNHL following COVID-19 vaccination. The study accounted for previous disease and other potential confounding factors. These results are based on diagnosis codes in specialized care but still need to be verified in settings that are capable of evaluating the degree of hearing loss.

An analytical plate bending model is used in a novel measurement method that is being developed for feedback control of material properties in paper manufacturing. The model involves an efficient material model for paper yet allowing a selected level of material complexity. In this study, the effects of the simplifications are studied by comparing the results with a discretized model applied in finite element methods. The boundary conditions required for specifying the censoring location in the real system proves to be challenging and a specific combined load distribution might be necessary to apply the developed model.

Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to NOTCH inhibitors, which corresponded to high expression of NOTCH receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.

This qualitative study includes nine semi-structured interviews with cybersecurity experts from different security-related organizations who are familiar with cybersecurity exercises. Its contribution to cybersecurity workforce development focuses on organizational learning rather than individual skills development and relevant competencies. It was found that the utilization of thematic analysis methods develop individual readiness and expertise. It also enhances the maturity of an organization's processes, roles, communication, and exercise capabilities. Moreover, the exercises increase social trust between individuals and organizations through business-to-business cooperation. However, there were several barriers and challenges in utilizing learned skills and competencies within an organization, including a need to increase the capacity of staff members who participate in the exercise.

Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle’s behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard 1H NMR experiments. We optimized the hydrolysis conditions to degrade the PSi, providing mobility to the molecules for NMR detection. The NMR parameters were also optimized by relaxation delay and the number of scans to provide reliable NMR spectra. With an internal standard, we quantitatively analyzed the surficial amine groups and their sequential modification of polyethylene glycol. Our investigation provides a reliable, fast, and straightforward method in quantitative analysis of the surficial modification characterization of PSi requiring a small amount of sample.

ABSTRACTWhile society benefits from Arctic shipping, it is necessary to recognize that ship operations in Arctic waters pose significant risks to people, the environment, and property. To support the management of those risks, this article presents a comprehensive approach addressing both short-term operational risks, as well as risks related to long-term extreme ice loads. For the management of short-term operational risks, an extended version of the Polar Operational Limit Assessment Risk Indexing System (POLARIS) considering the magnitude of the consequences of potential adverse events is proposed. For the management of risks related to long-term extreme ice loads, guidelines are provided for using existing analytical, numerical, and semi-empirical methods. In addition, to support the design of ice class ship structures, the article proposes a novel approach that can be used in the conceptual design phase for the determination of preliminary scantlings for primary hull structural members.

The youngest time interval of the Cretaceous Period is known as the Maastrichtian, in reference to the shallow-marine strata outcropping in the area surrounding the city of Maastricht, in the Netherlands-Belgium border region. While the type-Maastrichtian strata have yielded a wealth of paleontological data, comparatively little geochemical work has so far been carried out on this succession. To date, age assessment of the type-Maastrichtian, and stratigraphic correlation with sections elsewhere, have largely been based on biostratigraphy and preliminary attempts at cyclostratigraphy. However, these techniques are hampered by bio-provincialism and the presence of stratigraphic gaps in the succession, respectively. In recent years, stable carbon isotope stratigraphy has proven to be a powerful tool for correlating Upper Cretaceous strata on a global scale. When integrated with biostratigraphy, carbon isotope stratigraphy can be used to test the synchroneity of biological and climatic events across the globe and to reconcile inter-regional biostratigraphic schemes. Therefore, we have generated the first high-resolution bulk stable carbon isotope stratigraphy for the type-Maastrichtian, using an extensive sample set acquired within the context of the Maastrichtian Geoheritage Project spanning approximately 100 meters of stratigraphy at the Hallembaye and former ENCI quarries. In combination with bulk major and trace element data generated using µXRF, this record presents the first high-resolution chemostratigraphic survey for the type-Maastrichtian. The µXRF-based element profiles through the type-Maastrichtian succession reveal variable fluxes of terrigenous input into this carbonate system over time, marking three distinct stratigraphic sequences, separated by sequence boundaries at the Froidmont, Lichtenberg and Vroenhoven horizons. In addition, the carbon isotope profile records the Campanian–Maastrichtian Boundary Event (CMBE) and the Mid-Maastrichtian Event (MME) in the Maastrichtian type area for the first time. Our refined age model allows for global correlation between the type-Maastrichtian sequence and Maastrichtian successions worldwide and places the abundant paleontological records from the type-Maastrichtian in a global context.

Disadvantaged migrant populations face risk factors that can affect their oral health amongst other health issues. The purpose of this study was to explore the oral care needs of these populations and to identify the obstacles they might encounter in accessing dental care.

AbstractMany geotechnical problems involve pavements in Algerian arid regions; the main among them being related to the scarcity of standard materials. Recently, numerous studies were carried out on the valorization of Saharan local materials for pavement design. In this context, dune sand, tuff and quarry waste are promising alternatives. In this study, the design of experiments was used to optimize formulations to meet the current unconfined compressive strength (UCS) recommendations according to grading distribution. For the studied local material, the use of UCScriterion extended the valid domain of formulations to poorly graded materials where the amount of dune sand could reach 54.5%. An optimal formulation was proposed and tested, composed of 46% dune sand, 36% tuff, 11% quarry waste and 7% water, fulfilling all current recommendations related to the pavement design in the Sahara region. Finally, the results show that the design of experiments can be a useful tool to optimize mixture formulations and valorize local materials such as dune sand.

We extend the algebraic construction of finite dimensional varying exponent Lp(·)space norms, defined in terms of Cauchy polynomials to a more general setting, including varying exponent Lp(·)spaces. This boils down to reformulating the Musielak–Orlicz or Nakano space norm in an algebraic fashion where the infimum appearing in the definition of the norm should become a (uniquely attained) minimum. The latter may easily fail, as turns out, and in this connection we examine the Fatou type semicontinuity conditions on the modulars. Norms defined by ODEs are applied in studying such semicontinuity properties of Lp(·)space norms with p(·)unbounded.

This review discusses the current data on predictive and prognostic biomarkers in oligometastatic NSCLC and discusses whether biomarkers identified in other stages and widespread metastatic disease can be extrapolated to the oligometastatic disease (OMD) setting. Research is underway to explore the prognostic and predictive value of biological attributes of tumor tissue, circulating cells, the tumor microenvironment, and imaging findings as biomarkers of oligometastatic NSCLC. Biomarkers that help define true OMD and predict outcomes are needed for patient selection for oligometastatic treatment, and to avoid futile treatments in patients that will not benefit from locoregional treatment. Nevertheless, these biomarkers are still in the early stages of development and lack prospective validation in clinical trials. Furthermore, the absence of a clear definition of OMD contributes to a heterogeneous study population in which different types of OMD are mixed and treatment strategies are different. Multiple tissue-based, circulating, and imaging features are promising regarding their prognostic and predictive role in NSCLC, but data is still limited and might be biased owing to the inclusion of heterogeneous patient populations. Larger homogeneous and prospective series are needed to assess the prognostic and predictive role of these biomarkers. As obtaining tissue can be difficult and is invasive, the most promising tools for further evaluation are liquid biopsies and imaging-based biomarkers as these can also be used for longitudinal follow-up.

Background: Accurate response evaluation is necessary to select complete responders (CRs) for a watch-and-wait approach. Deep learning may aid in this process, but so far has never been evaluated for this purpose. The aim was to evaluate the accuracy to assess response with deep learning methods based on endoscopic images in rectal cancer patients after neoadjuvant therapy. Methods: Rectal cancer patients diagnosed between January 2012 and December 2015 and treated with neoadjuvant (chemo)radiotherapy were retrospectively selected from a single institute. All patients underwent flexible endoscopy for response evaluation. Diagnostic performance (accuracy, area under the receiver operator characteristics curve (AUC), positive- and negative predictive values, sensitivities and specificities) of different open accessible deep learning networks was calculated. Reference standard was histology after surgery, or long-term outcome (>2 years of follow-up) in a watch-and-wait policy. Results: 226 patients were included for the study (117(52%) were non-CRs; 109(48%) were CRs). The accuracy, AUC, positive- and negative predictive values, sensitivity and specificity of the different models varied from 0.67–0.75%, 0.76–0.83%, 67–74%, 70–78%, 68–79% to 66–75%, respectively. Overall, EfficientNet-B2 was the most successful model with the highest diagnostic performance. Conclusions: This pilot study shows that deep learning has a modest accuracy (AUCs 0.76-0.83). This is not accurate enough for clinical decision making, and lower than what is generally reported by experienced endoscopists. Deep learning models can however be further improved and may become useful to assist endoscopists in evaluating the response. More well-designed prospective studies are required.

The goal of this project was to create an up‐to‐date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher‐level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. These multidisciplinary European guidelines provide an up‐to‐date comprehensive evidence‐based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitropermeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (Papp) of 2.37 × 10−6 cm/s, over the 1.66 × 10−6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.