The liver has evolved to maintain tissue homeostasis and a state of immune-unresponsiveness in the face of constant exposure to food-derived and commensal microbial products entering through the portal circulation. This is achieved by the unique properties of cells residing in the liver that function to dampen adaptive immune responses. Here we will survey the unique features of the liver microenvironment that contribute to this general state of immune-tolerance and render the liver particularly “hospitable” to incoming metastatic cancer cells. The diverse cell types and unique liver ECM, which collectively control the progression of metastasis and can act to curtail or promote the process, will be described and recent insight into their respective roles highlighted.
BACKGROUND Assessing the gap between rich and poor is important to monitor inequalities in health. Identifying the contribution to that gap can help policymakers to develop interventions towards decreasing that difference. OBJECTIVE To quantify the wealth inequalities in health preventive measures (bed net use, vaccination, and contraceptive use) to determine the demographic and socioeconomic contribution factors to that inequality using a decomposition analysis. METHODS Data from the 2015 Immunisation, Malaria and AIDs Indicators Survey were used. The total sample included 6946 women aged 15–49 years. Outcomes were use of insecticide-treated nets (ITN), child vaccination, and modern contraception use. Wealth Index was the exposure variable and age, marital status, place of residence, region, education, occupation, and household wealth index were the explanatory variables. Wealth inequalities were assessed using concentration indexes (Cindex). Wagstaff-decomposition analysis was conducted to assess the determinants of the wealth inequality. RESULTS The Cindex was −0.081 for non-ITN, −0.189 for lack of vaccination coverage and −0.284 for non-contraceptive use, indicating a pro-poor inequality. The results revealed that 88.41% of wealth gap for ITN was explained by socioeconomic factors, with education and wealth playing the largest roles. Lack of full vaccination, socioeconomic factors made the largest contribution, through the wealth variable, whereas geographic factors came next. Finally, the lack of contraceptive use, socioeconomic factors were the main explanatory factors, but to a lesser degree than the other two outcomes, with wealth and education contributing most to explaining the gap. CONCLUSION There was a pro-poor inequality in reproductive and child preventive measures in Mozambique. The greater part of this inequality could be attributed to wealth, education, and residence in rural areas. Resources should be channeled into poor and non-educated rural communities to tackle these persistent inequities in preventive care.
Background Home delivery is associated with a high risk of maternal and neonatal mortality. The prevalence and factors associated with home delivery have been studied retrospectively among women in Ethiopia. However, no national studies have assessed pregnant women’s preferences for home delivery. Objective To assess factors associated with preferences for home delivery among pregnant women in Ethiopia. Methods We analysed a sample of 678 pregnant women derived from the 2019 performance monitoring for action cross-sectional survey. The association between pregnant women’s preferences for home delivery and several individual, household, healthcare, and community factors were explored through log-Poisson regression with robust variance. Results The weighted prevalence of pregnant women’s preferences for home delivery in Ethiopia was 33%. Pregnant women between the ages of 15–19 years (PR = 2.3; 95% CI: 1.43–4.00) had a higher preference for home delivery compared to those above 34 years. Those who had no Antenatal care (ANC) visit in the current pregnancy (PR = 1.5; 95% CI: 1.11–2.11), multipara women (PR = 1.8; 95% CI: 1.19–2.92) those who did not discuss place of delivery with their partners (PR = 1.5; 95% CI: 1.18–2.10), did not participate in a community-based program called ‘1 to 5’ network meetings (PR = 4.5; 95% CI: 1.09–18.95), and those who perceived low community support for facility delivery (PR = 2.2; 95% CI: 1.53–3.20) had a higher prevalence of home delivery preference compared to their references. Conclusions A significant proportion of pregnant women preferred home deliveries in Ethiopia. Household and community supporting factors such as not discussing place of delivery with a partner, not participating in women developmental army meetings, and perceived low community support were associated with preference for home delivery. Interventions should address these factors to increase facility deliveries in Ethiopia.
Background Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. Description Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69–96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. Conclusion It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.
As is well known, for plasmas of high density and modest temperature, the classical kinetic theory needs to be extended. Such extensions can be based on the Schrödinger Hamiltonian, applying a Wigner transform of the density matrix, in which case the Vlasov equation is replaced by the celebrated Wigner–Moyal equation. Extending the treatment to more complicated models, we investigate aspects such as spin dynamics (based on the Pauli Hamiltonian), exchange effects (using the Hartree–Fock approximation), Landau quantization, and quantum relativistic theory. In the relativistic theory, we first study cases where the field strength is well-beyond Schwinger critical field. Both weakly relativistic theory (gamma factors close to unity) and strongly relativistic theory are investigated, using assumptions that allow for a separation of electron and positron states. Finally, we study the so-called Dirac–Heisenberg–Wigner (DHW) formalism, which is a fully quantum relativistic theory, allowing for field strengths of the order of the Schwinger critical field or even larger. As a result, the quantum kinetic theory is extended to cover phenomena such as Zitterbewegung and electron–positron pair creation. While the focus of this review is on the quantum kinetic models, we illustrate the theories with various applications throughout the manuscript.
Background Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. Methods In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. Results From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. Conclusions Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. Trial registration NCT02136147, May 12, 2014.
Purpose Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein–Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC. Methods Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real-time PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry. Results Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16. Conclusion These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.
Bacteria often reside in sessile communities called biofilms, where they adhere to a variety of surfaces and exist as aggregates in a viscous polymeric matrix. Biofilms are resistant to antimicrobial treatments, and are a major contributor to the persistence and chronicity of many bacterial infections. Herein, we determined that the CpxA-CpxR two-component system influenced the ability of enteropathogenic Yersinia pseudotuberculosis to develop biofilms. Mutant bacteria that accumulated the active CpxR~P isoform failed to form biofilms on plastic or on the surface of the Caenorhabditis elegans nematode. A failure to form biofilms on the worm surface prompted their survival when grown on the lawns of Y. pseudotuberculosis . Exopolysaccharide production by the hms loci is the major driver of biofilms formed by Yersinia . We used a number of molecular genetic approaches to demonstrate that active CpxR~P binds directly to the promoter regulatory elements of the hms loci to activate the repressors of hms expression and to repress the activators of hms expression. Consequently, active Cpx-signalling culminated in a loss of exopolysaccharide production. Hence, the development of Y. pseudotuberculosis biofilms on multiple surfaces is controlled by the Cpx-signalling, and at least in part this occurs through repressive effects on the Hms-dependent exopolysaccharide production.
To achieve clinical impact in daily oncological practice, emerging AI-based cancer imaging research needs to have clearly defined medical focus, AI methods, and outcomes to be estimated. AI-supported cancer imaging should predict major relevant clinical endpoints, aiming to extract associations and draw inferences in a fair, robust, and trustworthy way. AI-assisted solutions as medical devices, developed using multicenter heterogeneous datasets, should be targeted to have an impact on the clinical care pathway. When designing an AI-based research study in oncologic imaging, ensuring clinical impact in AI solutions requires careful consideration of key aspects, including target population selection, sample size definition, standards, and common data elements utilization, balanced dataset splitting, appropriate validation methodology, adequate ground truth, and careful selection of clinical endpoints. Endpoints may be pathology hallmarks, disease behavior, treatment response, or patient prognosis. Ensuring ethical, safety, and privacy considerations are also mandatory before clinical validation is performed. The Artificial Intelligence for Health Imaging (AI4HI) Clinical Working Group has discussed and present in this paper some indicative Machine Learning (ML) enabled decision-support solutions currently under research in the AI4HI projects, as well as the main considerations and requirements that AI solutions should have from a clinical perspective, which can be adopted into clinical practice. If effectively designed, implemented, and validated, cancer imaging AI-supported tools will have the potential to revolutionize the field of precision medicine in oncology.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Background No previous systematic review has quantitatively compared the effects of resistance training, endurance training, or concurrent training on hormonal adaptations in children and adolescents. Objective was to examine the effects of exercise training and training type on hormonal adaptations in children and adolescents. Methods A systematic literature search was conducted in the following databases: PubMed, Web of Science, and EBSCO. Eligibility criteria were: population: healthy youth population sample (mean age < 18 years); intervention: resistance training, endurance training, or concurrent training (> 4 weeks duration); comparison: control group; outcome: pre- and post-levels of hormones and cytokines; and study design: randomized and non-randomized controlled trials. We used a random-effect model for the meta-analysis. The raw mean difference in hormones from baseline to post-intervention was presented alongside 95% confidence intervals (CI). Further, the certainty of evidence quality and the risk of bias were assessed. Results A total of 3689 records were identified, of which 14 studies were eligible for inclusion. Most studies examined adolescents with fewer studies on children (age < 12 years, N = 5 studies) and females (N = 2 studies). Nine exercise training programs used endurance training, five studies used resistance training, and no eligible study used concurrent training. The meta-analysis showed no significant effect of exercise training on testosterone (MD = 0.84 nmol/L), cortisol (MD = − 17.4 nmol/L), or SHBG (MD = − 5.58 nmol/L). Subgroup analysis showed that resistance training significantly increased testosterone levels after training (MD = 3.42 nmol/L) which was not observed after endurance training (MD = − 0.01 nmol/L). No other outcome differed between training types. Exercise training resulted in small and non-significant changes in GH (MD = 0.48 ng/mL, p = 0.06) and IGF-I (MD = − 22.90 ng/mL, p = 0.07). GH response to endurance training may be age-dependent and evident in adolescents (MD = 0.59 ng/mL, p = 0.04) but not when children and adolescents are pooled (MD = 0.48 ng/mL, p = 0.06). Limited evidence exists to conclude on IL-6 and TNF-α effects of exercise training. Assessments of GRADE domains (risk of bias, consistency, directness, or precision of the findings) revealed serious weaknesses with most of the included outcomes (hormones and cytokines). Conclusions This systematic review suggests that exercise training has small effects on hormonal concentrations in children and adolescents. Changes in testosterone concentrations with training are evident after resistance training but not endurance training. GH's response to training may be affected by maturation and evident in adolescents but not children. Further high-quality, robust training studies on the effect of resistance training, endurance training, and concurrent training are warranted to compare their training-specific effects. Registration: PROSPERO: CRD42021241130.
Malevolent creativity refers to employing creative processes for one's own selfish gain, often combined with detrimental effects on others. Sex differences in malevolent or negative creativity are to be expected due to the established finding that males are higher in the Dark Triad traits. However, the only previous study of this issue, using a sample of Indian students, did not find a sex difference. Here, we administered the Malevolent Creativity Behaviour Scale (MCBS) to a sample of 1619 Sudanese students, and found a small sex difference in that females rated themselves higher. Reasons for the finding are explored, including possible problems with the MCBS instrument.
Net CO2 emissions from the production of quicklime can be reduced by introducing renewable solid fuels or sustainably produced electricity for heating of the process. This paper reports the results of a study examining the effects of new heat sources on quicklime surface reaction products and on quicklime microstructure. Limestone was heated to 1100 °C and 1350 °C in high CO2 atmosphere under three conditions: i) an ash mixture representing conventional coal and a solid biofuel (olive pomace); ii) olive pomace ash, and iii) no ash representing an electrically heated process. The ash-quicklime interfaces of the samples were analyzed for elemental composition and microstructure using SEM-EDX. Multi-component chemical equilibrium calculations were used to assess the stable chemical phases in the interface. Coal-olive pomace ash mixture resulted in coarsening of the quicklime microstructure; this effect was less severe compared to that of pure olive pomace ash. The calculations indicated that the potassium in olive pomace ash was bound to Si- and Al-rich coal ash phases. Exposure to potassium-rich olive pomace ash resulted in severe coarsening of the quicklime microstructure. The difference was most obvious at 1,350 °C, and was probably the result of intrusion of a potassium-rich salt melt. For limestone without ash, the quicklime showed enhanced sintering and reduced porosity at the higher temperature, in agreement with previous studies. Interface reactions and microstructure coarsening, here most apparent for the case with olive pomace, could be problematic in industrial quicklime production since they may contribute to decreased available CaO and reactivity.
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