Search

Background and study aims: Lynch syndrome (LS) is a hereditary autosomal dominant condition, with an increased lifetime risk of developing malignancies including colorectal cancer (CRC). Current guidelines differ in recommended colonoscopy-surveillance intervals from 1 to 2 years. Although colonoscopy is considered a safe procedure, there are risks of severe adverse events (SAEs), such as perforation and bleeding, as well as adverse events (AEs), such as abdominal discomfort and post-colonoscopy gastrointestinal infections. Colonoscopy-related bleeding and perforation rates have been reported 0.17% and 0.11%, respectively. However, there are insufficient data regarding complications of colonoscopy-surveillance for LS patients. This study aims to investigate the risk of AEs among LS patients during colonoscopy in the Stockholm region. Patients and methods: This retrospective cohort study includes 351 LS patients undergoing endoscopic surveillance at the Karolinska University Hospital, August 1989 – April 2021. Data from endoscopic surveillance colonoscopies were extracted from patients' medical records. Results: Of 1873 endoscopies in 351 LS patients, 12 complications (AEs) were documented within 30 days (0.64%) and with a total of 3 bleedings (SAEs, 0.16%). No perforations were identified. Conclusion: Colonoscopy surveillance for LS patients shows a comparatively low risk of AEs per-examination. Colonoscopy complications per-patient, including both SAEs and AEs, show a significantly higher risk. Colonoscopy complications only including SAEs, show a comparatively low risk. Understanding the lifetime risk of surveillance-related colonoscopy complications is important when designing targeted surveillance programmes. [ABSTRACT FROM AUTHOR]

Patients with acute brain injury are vulnerable to secondary deterioration, which may go undetected by traditional monitoring. However, multimodal neuromonitoring of brain tissue oxygen tension (PbtO2) and energy metabolism may be able to detect such episodes. We report a retrospective, observational study of 94 patients with aneurysmal subarachnoid haemorrhage (SAH) or traumatic brain injury (TBI) who underwent multimodal neuromonitoring during admission. We examined the co-occurrence of pathological neuromonitoring values: elevated intracranial pressure (ICP, > 20 mmHg), inadequate cerebral perfusion pressure (CPP, < 60 mmHg), brain hypoxia (PbtO2 < 20 mmHg), and metabolic crisis (lactate/pyruvate ratio > 40 and a glucose level < 0.2 mmol/L in cerebral microdialysate). Mixed effects linear regression demonstrated significant associations between abnormal ICP/CPP, cerebral hypoxia and metabolic crisis. However, brain hypoxia occurred in 40% and 31% of observations in patients with SAH and TBI, respectively, despite normal concurrent values of ICP. Similarly, metabolic crisis was observed in 8% and 16% of measurements for SAH and TBI, respectively, despite a normal ICP. The pattern was identical for CPP. In conclusion, although all neuromonitoring variables are interrelated, brain hypoxia and metabolic crisis are common despite an absence of abnormalities in conventional monitoring. Multimodal neuromonitoring may help identify such episodes and guide individualised treatment. [ABSTRACT FROM AUTHOR]

This paper delves into the experiences and protective factors contributing to integration of highly skilled African immigrants (HSAIs) into the Quebec labour market. Despite the Canadian government's considerable efforts to attract and retain skilled immigrants to promote its economic prosperity, challenges persist for these individuals as they navigate the complexities of the Canadian labour market. While most of the existing studies have focused on these challenges, this paper centers on the key protective factors for the success of HSAIs in Quebec. Drawing on in-depth semi-structured interviews (n = 16) with HSALs, this paper uncovers the multifaceted landscape of labour market integration for HSAIs. The findings reveal that, although a majority of participants encounter barriers preventing them from fully utilizing their skills, education, and experience, they often overcome these barriers by leveraging protective factors such as being in high-demand job sectors, receiving familial support, benefiting from social networks, possessing bilingual proficiency, and engaging in mentorship programmes. This paper highlights the urgent need for evidence-based policies to ensure employment opportunities commensurate with the academic qualifications and professional skills for highly skilled immigrants in Canada, particularly HSAIs. These policies should not only recognize protective factors but also prioritize building resilience and addressing systemic labour market barriers. [ABSTRACT FROM AUTHOR]

The integration of highly skilled immigrants into the Canadian labor market is a complex endeavor, fraught with challenges that necessitate the adoption of various resilience strategies. This study delves into the impact of resilience on the well-being of highly skilled African immigrants (HSAI) navigating the Quebec labor market. This research draws on Ungar's (2012) ecological perspective of resilience and Siegelman's well-being theory to provide an explanation about the impact of HSAIs' resilience on their well-being. Drawing on semi-structured interviews with 16 HSAI participants (9 Anglophone and 7 Francophone HSAIs), the research unveils the nuanced dynamics of resilience and well-being during the labor market integration (LMI) process. While personal resilience is evident in educational pursuits and workplace adaptation, a crucial revelation emerges—the toll these adaptive strategies take on HSAIs' wellbeing. The findings underscore the need for targeted policies aimed at supporting the well-being of highly skilled African immigrants during the labor market integration process. Enhancing awareness and accessibility of tailored mental health resources is crucial. Integrating these considerations into policy frameworks can create a more supportive process for highly skilled African immigrants in Quebec. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive. Methods: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3). Results: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct. Conclusion: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging. ClinicalTrials.gov number, NCT03318380. [ABSTRACT FROM AUTHOR]

Creating and sustaining a positive school climate is not done in isolation but requires continuous ongoing work by several people within the school, and one of the most important actors are the teachers. In order to fulfil this very important task, the teachers need to collaborate with colleagues at school in an organized manner. In this study, we aim to explore and analyse teachers' perspectives on how their teacher team might be linked to their school climate work, and what team characteristics facilitate their work to create and maintain a positive and supportive climate within their school. To understand teachers' comprehension of their team, we applied a social psychology framework, using social interdependence theory and the concept of psychological safety. Data were collected by means of 14 semi-structured focus group interviews with 73 teachers from two compulsory schools in southeast Sweden. The findings revealed that teachers perceived the team as the most significant support structure when it comes to school climate work. According to them, the team was associated with shared responsibility, support and help, as well as safety and an open climate. By elucidating teachers' insider perspectives regarding their working conditions aligned to their work with school climate, we conclude that well-functioning teacher teams are experienced as a safe place to work on creating and maintaining a positive school climate. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore changes in symptoms of eating disorders, compulsive exercise, and depression, between two assessments 12 months apart, among elite gymnasts. Method: Factors related to the development of mental health symptoms in male and female Swedish national team gymnasts were investigated using baseline and 1-year follow-up scores in two subscales of the Eating Disorders Inventory 3; drive for thinness and body dissatisfaction, two subscales of the Compulsive Exercise Test; avoidance and rule-driven behavior and exercise for weight control, and the Montgomery-Åsberg Depression Rating Scale-Self report (MADRS-S). Linear mixed models were used to investigate the influence of drive for thinness, exercise for weight control, avoidance and rule-driven behavior, and MADRS-S on body dissatisfaction. Results: Body dissatisfaction increased from baseline to the follow-up assessment, while drive for thinness and depression remained stable. Symptoms of eating disorders and depression were generally low in this group of elite gymnasts at both assessments. Drive for thinness, exercise for weight control, and symptoms of depression were associated with body dissatisfaction. Discussion: Our findings indicate that there were no significant changes over time in eating disorders and depression symptoms but significant associations with body dissatisfaction. Furthermore, we found independent effects of drive for thinness, exercise for weight control and symptoms of depression for body dissatisfaction. [ABSTRACT FROM AUTHOR]

Purpose: Riot Control Agents (RCAs) are chemicals used in law enforcement for non-lethal riot control and use in conflicts between states that violates the Chemical Weapons Convention. OPCW's Scientific Advisory Board has identified sixteen potential RCAs including capsaicinoids, CS, and CR. RCAs may be misused for criminal purposes, so methods for detecting such misuse are needed. This study therefore evaluates the feasibility of a rapid, high throughput screening method of RCAs on surfaces (particularly clothing surfaces) by Direct Analysis in Real Time with a thermal desorption unit coupled to high-resolution mass spectrometry (DART-TD-HRMS). Methods: A broadly applicable method for detecting potential RCAs was developed and tested on cotton fabric samples sprayed with self-defence sprays from an in-house reference stock. The feasibility of detecting RCAs by direct analysis of surface wipe samples placed in the DART source was also investigated. Results: The method detected all sixteen RCAs and contaminated clothing were successfully screened for active agents in a reference collection of self-defence sprays. A pilot study also showed that RCAs can be detected by holding a sample directly in front of the DART source. Conclusion: DART-TD-HRMS enables rapid and simple screening of RCAs on fabric samples enabling a high sample throughput. [ABSTRACT FROM AUTHOR]

Due to their natural history and ecological attributes, turtles are excellent organisms for studies of heavy metal contamination. Turtles have a large geographical distribution, occupy different aquatic habitats, and occupy various trophic levels. The present study investigated mercury bioaccumulation in the carnivorous chelonian Chelus fimbriata (Matamata turtle) and Hg biomagnification in relation to its aquatic food chain in the middle Rio Negro, AM-Brazil. Tissue samples of muscle, carapace and claws were collected from 26 C. fimbriata individuals, as well as collections of autotrophic energy sources found in the turtle's aquatic habitat area. The samples were collected in February-March/2014 and analyzed for THg concentrations and carbon (δ13C) and nitrogen (δ15N) stable isotopes. The highest THg levels were found in claws (3780 ng.g−1), carapace (3622 ng.g−1) and muscle (403 ng.g−1), which were found to be significantly different [F(2.73) = 49.02 p < 0.01]. However, THg concentrations in muscle tissue were below the consumption threshold indicated by the WHO and Brazilian Health Ministry. The average δ13C and δ15N values in Matamata samples were −31.7‰ and 11.9‰, respectively. The principal energy source sustaining the food chain of C. fimbriata was found to be terrestrial shrubs, with smaller contributions from emergent aquatic herbaceous plants and algae, while δ15N values showed its trophic position to be two levels above the autotrophic energy sources. There was a positive correlation between THg and turtle size, while a significant relationship was found between THg and δ15N, showing strong biomagnification in the food chain of C. fimbriata: y = 0.21x + 0.46; r2 = 0.45; p < 0.001, for which the slope presented a value of 0.21. [ABSTRACT FROM AUTHOR]

Discoveries in the field of genomics have revealed that non-coding genomic regions are not merely "junk DNA", but rather comprise critical elements involved in gene expression. These gene regulatory elements (GREs) include enhancers, insulators, silencers, and gene promoters. Notably, new evidence shows how mutations within these regions substantially influence gene expression programs, especially in the context of cancer. Advances in high-throughput sequencing technologies have accelerated the identification of somatic and germline single nucleotide mutations in non-coding genomic regions. This review provides an overview of somatic and germline non-coding single nucleotide alterations affecting transcription factor binding sites in GREs, specifically involved in cancer biology. It also summarizes the technologies available for exploring GREs and the challenges associated with studying and characterizing non-coding single nucleotide mutations. Understanding the role of GRE alterations in cancer is essential for improving diagnostic and prognostic capabilities in the precision medicine era, leading to enhanced patient-centered clinical outcomes. [ABSTRACT FROM AUTHOR]

This article explores one central assumption that is guiding large portions of contemporary (analytic) moral philosophy: the idea that moral philosophy has to be forward-looking and action-guiding. By paying attention to a number of examples, it is argued that this guiding assumption flies in the face of important aspects of actual moral life. Moral situations are not (always) of the nature that we can plan for them, and reason about them in advance. Rather, the moral reality, or the moral contexts, are often such that the moral situation is created in the scene, and hence something that is only available to reflect upon in hindsight. There are, at least, two central reasons why this is so: The first is that the sense, meaning, of the actions and the concepts we use in reflection about them, are not locked beforehand, and our understanding of them are formed in the process. The second reason is that moral situations come about in a responsive, rather than planned, way. That is, we discover our moral world by means of our reactive interactions, rather than in theoretical reflection that aims to produce "anticipated beliefs." Thus, this article suggests a way of exploring morality's backward-looking nature that does not misrepresent moral reality. [ABSTRACT FROM AUTHOR]

We investigate using the GIRAFE cold-atom gravimeter during an airborne gravity survey for improving gravity field and quasigeoid modelling. The study is conducted over the Bay of Biscay, France. Geoid/quasigeoid determination is usually a major challenge over such coastal areas due to scarce and inconsistent gravity data. In a first step, the GIRAFE dataset is analysed and compared with available surface gravity data as well as with global altimetry models from UCSD and DTU. The comparisons indicate that the DTU model is better than the UCSD model within around 10 km from the coastline. Furthermore, recent satellite altimeter missions significantly improve the altimetry models in coastal areas. A significant bias (− 4.00 mGal) in shipborne data is also found from this comparison. In a second step, eight quasigeoid solutions are calculated to evaluate the contribution of GIRAFE data. This contribution reaches 3 cm in terms of height anomaly for DTU21 while being much larger for UCSDv31 and shipborne data. Finally, the quasigeoid solutions are validated using GNSS-levelling data. The results indicate that using GIRAFE data improves by approximately 50% the quality of quasigeoid models over land near the coast. The highest accuracy, around 1 cm, is achieved when GIRAFE data are merged with refined gravity data. Importantly, the standard deviation is just 1.2 cm when compared with GNSS-levelling points if using only GIRAFE data over marine areas, which is very close to the 1 cm goal of geoid/quasigeoid model determination in modern geodesy. This study thus confirms the benefits of performing airborne gravity survey using quantum sensors. [ABSTRACT FROM AUTHOR]

Objective: Current breast cancer risk prediction scores and algorithms can potentially be further improved by including molecular markers. To this end, we studied the association of circulating plasma proteins using Proximity Extension Assay (PEA) with incident breast cancer risk. Subjects: In this study, we included 1577 women participating in the prospective KARMA mammographic screening cohort. Results: In a targeted panel of 164 proteins, we found 8 candidates nominally significantly associated with short-term breast cancer risk (P < 0.05). Similarly, in an exploratory panel consisting of 2204 proteins, 115 were found nominally significantly associated (P < 0.05). However, none of the identified protein levels remained significant after adjustment for multiple testing. This lack of statistically significant findings was not due to limited power, but attributable to the small effect sizes observed even for nominally significant proteins. Similarly, adding plasma protein levels to established risk factors did not improve breast cancer risk prediction accuracy. Conclusions: Our results indicate that the levels of the studied plasma proteins captured by the PEA method are unlikely to offer additional benefits for risk prediction of short-term overall breast cancer risk but could provide interesting insights into the biological basis of breast cancer in the future. [ABSTRACT FROM AUTHOR]

The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (p = 0.23). At a median follow-up of 3.5 months (range, 0.39–10.92), the estimated 3 month and 6 month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. 78 unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64; p = 0.001). [ABSTRACT FROM AUTHOR]

Objective: The objective was to investigate 10-year mortality, causes of death and cardiovascular comorbidity in idiopathic normal pressure hydrocephalus (iNPH) and to evaluate their mutual associations. Methods: This prospective cohort study included 176 CSF-shunted iNPH patients, and 368 age- and sex-matched controls. At inclusion, participants were medically examined, had blood analyzed and answered a questionnaire. The vascular comorbidities investigated were smoking, diabetes, body mass index, blood pressure (BP), hyperlipidemia, kidney function, atrial fibrillation and, cerebro- and cardiovascular disease. Results: Survival was observed for a mean period of 10.3 ± 0.84 years. Shunted iNPH patients had an increased risk of death compared to controls (hazard ratio (HR) = 2.5, 95% CI 1.86–3.36; p < 0.001). After 10 years, 50% (n = 88) of iNPH patients and 24% (n = 88) of the controls were dead (p < 0.001). The risk of dying from cardiovascular disease, falls and neurological diseases were higher in iNPH (p < 0.05). The most common cause of death in iNPH was cardiovascular diseases (14% vs 7% for controls). Seven out of nine iNPH dying from falls had subdural hematomas. Systolic BP (HR = 0.985 95% CI 0.972–0.997, p = 0.018), atrial fibrillation (HR = 2.652, 95% CI 1.506–4.872, p < 0.001) and creatinine (HR = 1.018, 95% CI 1.010–1.027, p < 0.001) were independently associated with mortality for iNPH. Discussion: This long-term and population-matched cohort study indicates that in spite of CSF-shunt treatment, iNPH has shorter life expectancy. It may be important to treat iNPH in supplementary ways to reduce mortality. Both cardiovascular comorbidities and lethal falls are contributing to the excess mortality in iNPH and reducing these preventable risks should be an established part of the treatment plan. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article published in the European Journal of Epidemiology. It states that there were errors in Table 2 and Table 3 of the article, and provides the correct values for the data. The article discusses the impact of organised colorectal cancer screening on age-specific population incidences in Sweden. The correction notice also includes estimated impact data on incident colorectal cancer cases in Stockholm-Gotland, Sweden, based on difference-in-difference estimations. The document provides information on the methodology used for the estimations and includes rate differences, confidence intervals, and p-values. [Extracted from the article]

The mechanical properties of natural snow play a crucial role in understanding glaciers, avalanches, polar regions, and snow-related constructions. Research has concentrated on how the mechanical properties of snow vary, primarily with its density; the integration of cutting-edge techniques like micro-tomography with traditional loading methods can enhance our comprehension of these properties in natural snow. This study employs μ CT imaging and uniaxial compression tests, along with the Digital Volume Correlation (DVC) to investigate the density-dependent material properties of natural snow. The data from two snow samples, one initially non-compressed (test 1) and the other initially compressed (test 2), were fed into Burger's viscoelastic model to estimate the material properties. μ CT imaging with 801 projections captures the three-dimensional structure of the snow initially and after each loading step at -18 ∘ C, using a constant deformation rate (0.2 mm/min). The relative density of the snow, ranging from 0.175 to 0.39 (equivalent to 160–360 kg/m 3 ), is determined at each load step through binary image segmentation. Modulus and viscosity terms, estimated from Burger's model, exhibit a density-dependent increase. Maxwell and Kelvin–Voigt moduli range from 0.5 to 14 MPa and 0.1 to 0.8 MPa, respectively. Viscosity values for the Maxwell and Kelvin–Voigt models vary from 0.2 to 2.9 GPa-s and 0.2 to 2.3 GPa-s within the considered density range, showing an exponent between 3 and 4 when represented as power functions. Initial grain characteristics for tests 1 and 2, obtained through image segmentation, reveal an average Specific Surface Area (SSA) of around 55 1/mm and 40 1/mm, respectively. The full-field strain distribution in the specimen at each load step is calculated using the DVC, highlighting strong strain localization indicative of non-homogeneous behavior in natural snow. These findings not only contribute to our understanding of natural snow mechanics but also hold implications for applications in fields such as glacier dynamics and avalanche prediction. [ABSTRACT FROM AUTHOR]

Teachers have a major impact on students' social cognition and behaviors, and previous research has found that students who have positive relationships with their teachers tend to be less bullied by their peers. However, this line of research is limited in that it has been (a) Dominated by cross-sectional studies and (b) Treated bullying victimization as a global construct without differentiating among its different forms (i.e., verbal, physical, and relational). The links might be reciprocal but further studies are needed to investigate the directionality. Therefore, this study aimed to examine the longitudinal associations between student–teacher relationship quality and two forms of bullying victimization, namely verbal and relational victimization. Three waves of data from 1885 Swedish fourth- through sixth-grade students were analyzed with cross-lagged panel models. The findings showed that the student–teacher relationship quality predicted and was predicted by verbal and relational victimization. Our findings thus underscore the importance of striving for caring, warm, supportive, and respectful student–teacher relationships as a component of schools' prevention efforts. [ABSTRACT FROM AUTHOR]

Despite the significance of snow in various cryospheric, polar, and construction contexts, more comprehensive studies are required on its mechanical properties. In recent years, the utilization of μ CT has yielded valuable insights into snow analysis. Our objective is to establish a methodology for mapping density-dependent material properties for dry manufactured snow within the density range of 400–600 kg/m 3 utilizing μ CT imaging and step-wise, quasi-static, mechanical loading. We also aim to investigate the variations in the structural parameters of snow during loading. The three-dimensional (3D) structure of snow is captured using μ CT with 801 projections at the beginning of the experiments and at the end of each loading step. The sample is compressed at a temperature of − 18 o C using a constant rate of deformation (0.2 mm/min) in multiple steps. The relative density of the snow is determined at each load step using binary image segmentation. It varies from 0.44 in the beginning to nearly 0.65 at the end of the loading, which corresponds to a density range of 400–600 kg/m 3 . The estimated modulus and viscosity terms, obtained from the Burger's model, show an increasing trend with density. The values of the Maxwell and Kelvin–Voigt moduli were found to range from 60 to 320 MPa and from 6 to 40 MPa, respectively. Meanwhile, the viscosity values for the Maxwell and Kelvin–Voigt models varied from 0.4 to 3.5 GPa-s, and 0.3–3.2 GPa-s, respectively, within the considered density range. In addition, Digital Volume Correlation (DVC) was used to calculate the full-field strain distribution in the specimen at each load step. The image analysis results show that, the particle size and specific surface area (SSA) do not change significantly within the studied range of loading and densities, while the sphericity of the particles is increased. The grain diameter ranges from approximately 100 μ m to nearly 400 μ m, with a mode of nearly 200 μ m. The methodology presented in this study opens up a path for an extensive statistical analysis of the material properties by experimenting more snow samples. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) incurs a significant disease burden globally. Organised CRC screening programmes have been widely implemented for early detection and prevention. To understand the public health impact of these programmes, quantitative evidence of changes in overall and age-specific population incidences is fundamental. We aimed to provide such evidence by exploiting a time lag in the implementation of organised screening in Sweden: two out of 21 regions (these two regions comprise nearly 20% of the total Swedish population) have offered organised screening since 2008; the other regions have offered CRC screening since 2021. Using registry data on diagnosed CRC cases and socio-demographics for all regions in Sweden over the period 1970–2019, Bayesian structural time series modelling and difference-in-differences were applied to analyse the impact of screening on age-specific population incidences over time (CRC cases per 100.000 persons/year). After inviting birth-year cohorts aged 60–69 years for stool-based testing, the incidence rate in the 70–74-year age group decreased significantly over time, with an average reduction of − 44·40 (95% CI − 58·15 to − 31·31) from 2011 to 2019 in the intervention regions. In the overall population aged 60–74 years, there was a net incidence decrease of − 7·99 (95% CI − 13·85 to − 2·39) since the initiation of organised screening in the intervention regions (2008–2019). Organised CRC screening for 60–69-year-olds generated a change in age-specific incidence patterns with a long-lasting incidence decrease in the 70–74-year-old population, implying reductions in the excess mortality and burden of the disease. [ABSTRACT FROM AUTHOR]

There is growing interest in the use of neurointerventions to reduce the risk that criminal offenders will reoffend. Commentators have raised several ethical concerns regarding this practice. One prominent concern is that, when imposed without the offender’s valid consent, neurointerventions might infringe offenders’ right to bodily integrity. While it is commonly held that we possess a moral right to bodily integrity, the extent to which this right would protect against such neurointerventions is as-yet unclear. In this paper, we will assess whether, why, and how severely three forms of neurointervention might infringe the right to bodily integrity. We show that the severity of the infringement of the right to bodily integrity differs across different forms of neurointervention. Moreover, we argue that mental and behavioral effects of neurointerventions could in some cases be relevant to determining the severity of infringements of the right to bodily integrity. [ABSTRACT FROM AUTHOR]

Background: Neonatal effects of late intrauterine and early postpartum exposure to lithium through mother's own milk are scarcely studied. It is unclear whether described symptoms in breastfed neonates are caused by placental lithium transfer or postnatal exposure to lithium through breastfeeding. We aimed to investigate lithium clearance and neonatal morbidity in breastfed infants with high versus low serum lithium concentrations at birth. Methods: This retrospective study focused on breastfed infants to women treated with lithium during and after pregnancy, born between 2006 and 2021 in Stockholm, Sweden. Information on serum lithium concentrations and adverse neonatal outcomes was obtained from medical records. Neonatal symptoms and lithium clearance were compared between a high exposure group (HEG, lithium concentrations ≥ 0.6 meq/l) and a low exposure group (LEG, < 0.6 meq/l). Results: A total of 25 infant-mother dyads were included. Median lithium serum concentration at birth was 0.90 meq/l in the HEG as compared with 0.40 meq/l in the LEG (p < 0.05). The difference was still significant at follow-up (0.20 meq/l vs 0.06 meq/l, p < 0.05), despite reduction in maternal dose. The rate of neonatal symptoms was 85.7% in HEG and 41.2% in LEG (p = 0.08) at birth and 28.6% vs 11.8% at follow-up (p = 0.55). Furthermore, 28.6% of infants in HEG were admitted to neonatal care, vs 5.9% in LEG (p = 0.19). Two infants in the HEG had therapeutic lithium levels at follow-up. All infants with symptoms at follow-up were either in the HEG or exposed to additional psychotropic medication. Conclusions: Neonatal symptoms are common after late intrauterine lithium exposure, however transient, treatable and mostly mild. In this study, a high lithium concentration at birth was a risk factor for an increased lithium level at follow-up. Polypharmacy may constitute an additional risk factor. This study suggests that the late intrauterine exposure to lithium might add to the adverse effects in lithium-exposed, breastfed infants. Consequently we recommend breastfed infants with therapeutic lithium concentrations at birth to be followed up promptly to avoid lithium toxicity. [ABSTRACT FROM AUTHOR]

Full quantification of Positron Emission Tomography (PET) requires an arterial input function (AIF) for measurement of certain targets, or using particular radiotracers, or for the quantification of specific outcome measures. The AIF represents the measurement of radiotracer concentrations in the arterial blood plasma over the course of the PET examination. Measurement of the AIF is prone to error as it is a composite measure created from the combination of multiple measurements of different samples with different equipment, each of which can be sources of measurement error. Moreover, its measurement requires a high degree of temporal granularity for early time points, which necessitates a compromise between quality and quantity of recorded samples. For these reasons, it is often desirable to fit models to this data in order to improve its quality before using it for quantification of radiotracer binding in the tissue. The raw observations of radioactivity in arterial blood and plasma samples are derived from radioactive decay, which is measured as a number of recorded counts. Count data have several specific properties, including the fact that they cannot be negative as well as a particular mean-variance relationship. Poisson regression is the most principled modelling strategy for working with count data, as it both incorporates and exploits these properties. However, no previous studies to our knowledge have taken this approach, despite the advantages of greater efficiency and accuracy which result from using the appropriate distributional assumptions. Here, we implement a Poisson regression modelling approach for the AIF as proof-of-concept of its application. We applied both parametric and non-parametric models for the input function curve. We show that a negative binomial distribution is a more appropriate error distribution for handling overdispersion. Furthermore, we extend this approach to a hierarchical non-parametric model which is shown to be highly resilient to missing data. We thus demonstrate that Poisson regression is both feasible and effective when applied to AIF data, and propose that this is a promising strategy for modelling blood count data for PET in future. [ABSTRACT FROM AUTHOR]

Lytic polysaccharide monooxygenases (LPMOs) catalyze the oxidation of β-(1,4)-linked polysaccharides, such as cellulose, in a reaction that requires an electron donor and H2O2 as co-substrate. Several LPMOs include a carbohydrate-binding module (CBM), which promotes action on insoluble substrates. Herein, a fluorescent labeling technique was used to track LPMO action on microcrystalline cellulose and evaluate the impact of CBMs on the distribution of LPMO activity across the fiber surface. Confocal microscopic images revealed that the distribution of oxidized positions on the cellulose surface was CBM-dependent: fluorescent spots were concentrated in reactions with a CBM-containing LPMO whereas they were more dispersed for a CBM-deficient LPMO variant. The more dispersed oxidation pattern for the CBM-free LPMO coincided with the release of fewer soluble reaction products. [ABSTRACT FROM AUTHOR]

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV+ head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus. Here, we evaluate multiple aspects of the memory-like natural killer cell response in human-derived bioengineered environments, including immune cell extravasation, tumor penetration, tumor killing, T cell dependence, virus suppression, and compatibility with retroviral medication. Overall, these results suggest that memory-like natural killer cells are capable of operating without T cell assistance and could simultaneously destroy head and neck cancer cells as well as reduce viral latency. Current biological models for examining cancer immunobiology in a HIV infected context are lacking. Here the authors use a human-derived microphysiological model to represent the HIV immune system and assess the ability of transferred populations of NK cells in the targeting of tumours. [ABSTRACT FROM AUTHOR]

Background: Nephropathic cystinosis is a rare lysosomal storage disorder in which accumulation of cystine and formation of crystals particularly impair kidney function and gradually lead to multi-organ dysfunction. Lifelong therapy with the aminothiol cysteamine can delay the development of kidney failure and the need for transplant. The purpose of our long-term study was to explore the effects of transitioning from immediate release (IR) to extended release (ER) formulation in Norwegian patients in routine clinical care. Methods: We retrospectively analysed data on efficacy and safety in 10 paediatric and adult patients. Data were obtained from up to 6 years before and 6 years after transitioning from IR- to ER-cysteamine. Results: Mean white blood cell (WBC) cystine levels remained comparable between the different treatment periods (1.19 versus 1.38 nmol hemicystine/mg protein) although most patients under ER-cysteamine underwent dose reductions. For the non-transplanted patients, the mean estimated glomerular filtration rate (eGFR) change/year was more pronounced during ER-treatment (− 3.39 versus − 6.80 ml/min/1.73 m2/year) possibly influenced by individual events, such as tubulointerstitial nephritis and colitis. Growth measured by Z-height score tended to develop positively. Four of seven patients reported improvement of halitosis, one reported unchanged and two reported worsened symptoms. Most adverse drug reactions (ADRs) were of mild severity. One patient developed two serious ADRs and switched back to IR-formulation. Conclusions: The results from this long-term retrospective study indicate that switching from IR- to ER-cysteamine was feasible and well tolerated under routine clinical practice. ER-cysteamine allowed satisfactory disease control over the long period considered. [ABSTRACT FROM AUTHOR]

Denitrification in sediments is a key microbial process that removes excess fixed nitrogen, while dissimilatory nitrate reduction to ammonium (DNRA) converts nitrate to ammonium. Although microorganisms are responsible for essential nitrogen (N) cycling, it is not yet fully understood how these microbially mediated processes respond to toxic hydrophobic organic compounds (HOCs) and metals. In this study, we sampled long-term polluted sediment from the outer harbor of Oskarshamn (Baltic Sea), measured denitrification and DNRA rates, and analyzed taxonomic structure and N-cycling genes of microbial communities using metagenomics. Results showed that denitrification and DNRA rates were within the range of a national reference site and other unpolluted sites in the Baltic Sea, indicating that long-term pollution did not significantly affect these processes. Furthermore, our results indicate an adaptation to metal pollution by the N-cycling microbial community. These findings suggest that denitrification and DNRA rates are affected more by eutrophication and organic enrichment than by historic pollution of metals and organic contaminants. [ABSTRACT FROM AUTHOR]

Cryo electron microscopy (cryo-EM) is used by biological research to visualize biomolecular complexes in 3D, but the heterogeneity of cryo-EM reconstructions is not easily estimated. Current processing paradigms nevertheless exert great effort to reduce flexibility and heterogeneity to improve the quality of the reconstruction. Clustering algorithms are typically employed to identify populations of data with reduced variability, but lack assessment of remaining heterogeneity. Here we develope a fast and simple algorithm based on spatial filtering to estimate the heterogeneity of a reconstruction. In the absence of flexibility, this estimate approximates macromolecular component occupancy. We show that our implementation can derive reasonable input parameters, that composition heterogeneity can be estimated based on contrast loss, and that the reconstruction can be modified accordingly to emulate altered constituent occupancy. This stands to benefit conventionally employed maximum-likelihood classification methods, whereas we here limit considerations to cryo-EM map interpretation, quantification, and particle-image signal subtraction. Heterogeneity in structural biology data includes potentially valuable information about binding and dynamics. Here, the authors devise, validate and demonstrate a method to quantify local heterogeneity in 3D reconstructions. [ABSTRACT FROM AUTHOR]

Five specialists share essential books for understanding threats to democracy past and present, and finding ways to guard against them. [ABSTRACT FROM AUTHOR]

Ultrasound imaging has been using microbubble-based ultrasound contrast agents (UCAs) for about 30 years, which enhance ultrasound signals and improve the accuracy of diagnoses. There are currently four major UCAs approved for cardiology and radiology applications, all of which have excellent safety profiles. A technique called subharmonic-aided pressure estimation (SHAPE) has been developed, which uses UCAs to estimate pressure noninvasively. SHAPE has shown promise in diagnosing portal hypertension and monitoring the response to chemotherapy. Ongoing clinical trials are exploring other potential applications for SHAPE. [Extracted from the article]

Most bacteria in the biosphere are predicted to be polylysogens harbouring multiple prophages1–5. In studied systems, prophage induction from lysogeny to lysis is near-universally driven by DNA-damaging agents6. Thus, how co-residing prophages compete for cell resources if they respond to an identical trigger is unknown. Here we discover regulatory modules that control prophage induction independently of the DNA-damage cue. The modules bear little resemblance at the sequence level but share a regulatory logic by having a transcription factor that activates the expression of a neighbouring gene that encodes a small protein. The small protein inactivates the master repressor of lysis, which leads to induction. Polylysogens that harbour two prophages exposed to DNA damage release mixed populations of phages. Single-cell analyses reveal that this blend is a consequence of discrete subsets of cells producing one, the other or both phages. By contrast, induction through the DNA-damage-independent module results in cells producing only the phage sensitive to that specific cue. Thus, in the polylysogens tested, the stimulus used to induce lysis determines phage productivity. Considering the lack of potent DNA-damaging agents in natural habitats, additional phage-encoded sensory pathways to lysis likely have fundamental roles in phage–host biology and inter-prophage competition.Prophage lysogeny-to-lysis transitions are controlled by regulatory modules consisting of transcription factors and partner small proteins that are activated through DNA-damage-independent pathways, including by quorum sensing, and these modules determine inter-prophage competition outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Radiographs of the hand and teeth are frequently used for medical age assessment, as skeletal and dental maturation correlates with chronological age. These methods have been criticized for their lack of precision, and magnetic resonance imaging (MRI) of the knee has been proposed as a more accurate method. The aim of this systematic review is to explore the scientific and statistical evidence for medical age estimation based on skeletal maturation as assessed by MRI of the knee. Materials and methods: A systematic review was conducted that included studies published before April 2021 on living individuals between 8 and 30 years old, with presumptively healthy knees for whom the ossification stages had been evaluated using MRI. The correlation between "mature knee" and chronological age and the risk of misclassifying a child as an adult and vice versa was calculated. Results: We found a considerable heterogeneity in the published studies —in terms of study population, MRI protocols, and grading systems used. There is a wide variation in the correlation between maturation stage and chronological age. Conclusion: Data from published literature is deemed too heterogenous to support the use of MRI of the knee for chronological age determination. Further, it is not possible to assess the sensitivity, specificity, negative predictive value, or positive predictive value for the ability of MRI to determine whether a person is over or under 18 years old. Key Points: • There is an insufficient scientific basis for the use of magnetic resonance imaging of the knee in age determination by skeleton. • It is not possible to assess the predictive value of MRI of the knee to determine whether a person is over or under 18 years of age. [ABSTRACT FROM AUTHOR]

Background: Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored. Objective: The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs. Materials and methods: Eighteen fetal lambs at 107–139 days gestational age (term = 145 days) underwent subdural ICP catheter placement. The brain was imaged in the coronal plane in CEUS mode optimized for SHAPE, while infusing an US contrast agent into the fetal circulation. After SHAPE calibration, saline was infused via the subdural catheter to increase ICP. Five-second SHAPE cine clips were obtained at various ICPs. Subharmonic intensity values of the whole brain and thalami were correlated with ICP values using mixed effects linear regression analyses and the strength of the relationship was evaluated by Spearman's rank-order correlation. Results: Forty-nine experiments produced 723 datapoints, including SHAPE intensity values and mean ICP measurements. There was a statistically significant inverse relationship between SHAPE intensity values and ICP measurements in the whole brain and thalami (median rho value − 0.58 and − 0.56, respectively). Conclusion: SHAPE intensity values of the brain demonstrate an inverse and statistically significant correlation with in vivo ICP measurements in an animal model. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) is associated with increased levels of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid (CSF). Residual symptoms after antibiotic treatment can have deleterious effects on patients and knowledge regarding the pathogenesis linked to prolonged recovery is lacking. In this prospective follow-up study, we investigated the B cell-associated and T helper (Th) cell-associated immune responses in well-characterized patients with LNB and controls. The aims were to assess the kinetics of selected cytokines and chemokines involved in the inflammatory response and to identify potential prognostic markers. We investigated 13 patients with LNB according to a standardized clinical protocol before antibiotic treatment and after 1, 6 and 12 months of follow-up. CSF and blood samples were obtained at baseline and after 1 month. As controls, we used CSF samples from 37 patients who received spinal anesthesia during orthopedic surgery. The CSF samples were analyzed for CXCL10 (Th1-related), CCL22 (Th2-related) and IL-17A, CXCL1 and CCL20 (Th17-related), as well as for the B cell-related cytokines of a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF) and CXCL13. The CSF levels of all the cytokines and chemokines, with the exception of APRIL, were significantly higher at baseline in patients with LNB compared with controls. All the cytokines and chemokines, except for IL-17A were significantly reduced at 1-month follow-up. Patients with quick recovery (< 1 month, n = 3) had significantly lower levels of CCL20 at baseline and lower levels of IL-17A at 1-month follow-up. Patients with time of recovery > 6 months (n = 7) had significantly higher levels of IL-17A at the one-month follow-up. No other cytokines or chemokines were associated with prolonged recovery. Dominating residual symptoms were fatigue, myalgia, radiculitis and/or arthralgia. In this prospective follow-up study of patients with LNB, we found significantly lower levels of CCL20 in those who recovered rapidly, and increased levels of IL-17A in patients with delayed recovery post-treatment. Our findings indicate persistent Th17-driven inflammation in the CSF, possibly contributing to a longer convalescence, and suggest IL-17A and CCL20 as potential biomarker candidates for patients with LNB. [ABSTRACT FROM AUTHOR]

A common goal among fisheries science professionals, stakeholders, and rights holders is to ensure the persistence and resilience of vibrant fish populations and sustainable, equitable fisheries in diverse aquatic ecosystems, from small headwater streams to offshore pelagic waters. Achieving this goal requires a complex intersection of science and management, and a recognition of the interconnections among people, place, and fish that govern these tightly coupled socioecological and sociotechnical systems. The World Fisheries Congress (WFC) convenes every four years and provides a unique global forum to debate and discuss threats, issues, and opportunities facing fish populations and fisheries. The 2021 WFC meeting, hosted remotely in Adelaide, Australia, marked the 30th year since the first meeting was held in Athens, Greece, and provided an opportunity to reflect on progress made in the past 30 years and provide guidance for the future. We assembled a diverse team of individuals involved with the Adelaide WFC and reflected on the major challenges that faced fish and fisheries over the past 30 years, discussed progress toward overcoming those challenges, and then used themes that emerged during the Congress to identify issues and opportunities to improve sustainability in the world's fisheries for the next 30 years. Key future needs and opportunities identified include: rethinking fisheries management systems and modelling approaches, modernizing and integrating assessment and information systems, being responsive and flexible in addressing persistent and emerging threats to fish and fisheries, mainstreaming the human dimension of fisheries, rethinking governance, policy and compliance, and achieving equity and inclusion in fisheries. We also identified a number of cross-cutting themes including better understanding the role of fish as nutrition in a hungry world, adapting to climate change, embracing transdisciplinarity, respecting Indigenous knowledge systems, thinking ahead with foresight science, and working together across scales. By reflecting on the past and thinking about the future, we aim to provide guidance for achieving our mutual goal of sustaining vibrant fish populations and sustainable fisheries that benefit all. We hope that this prospective thinking can serve as a guide to (i) assess progress towards achieving this lofty goal and (ii) refine our path with input from new and emerging voices and approaches in fisheries science, management, and stewardship. [ABSTRACT FROM AUTHOR]