A 21‐year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

AbstractObjectivesGallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival.MethodsThe National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub‐stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log‐rank and Cox's regression analyses.ResultsOf 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow‐up of 22 months, 288 (25.8%) had died of GBC. Five‐year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease‐specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013).ConclusionsIn the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered

The Kinetics of Specific Immune Responses in Rhesus Monkeys Inoculated with Live Recombinant BCG Expressing SIV Gag, Pol, Env, and Nef Proteins

AbstractDevelopment of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette–Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV

Phospho-Ser784-VCP is required for DNA damage response and is associated with poor prognosis of chemotherapy-treated breast cancer

Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for DNA damage response (DDR), which influences treatment response by directing cancer cell fate. This process is orchestrated by valosin-containing protein (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential and pleiotropic effects of VCP in global proteostasis, it remains challenging practically to understand and target its DDR-specific functions. We describe a DNA-damage-induced phosphorylation event (Se

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm.METHODS: The study cohort comprised children (n = 128) with birthweight &lt;1500 g or gestational age &lt; 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models.RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02).CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.</p

A Multidimensional PERMA-H Positive Education Model, General Satisfaction of School Life, and Character Strengths Use in Hong Kong Senior Primary School Students: Confirmatory Factor Analysis and Path Analysis Using the APASO-II

The multidimensional PERMA-H positive education model provided evaluation and education framework for the theoretical and practice development of positive psychology in schools. Character strengths use mediates the association of strength knowledge and well-being. Using the Assessment Program for Affective and Social Outcomes (2nd Version) (APASO-II), the Subjective Happiness Scale, and the Physical Health Subscale of the PERMA-profiler, a multidimensional measure of PERMA-H was validated using confirmatory factor analysis in the context of a positive education program evaluation in senior primary school students. The association of PERMA-H measurements with school well-being as measured by general satisfaction of school life, and levels of depression and anxiety, and the mediation mechanism of character strengths use in such association were studied using path analysis. A cross-sectional sample of 726 senior primary school students (i.e., grade 4–6) aged 8–13 from the two primary schools completed a baseline evaluation questionnaire of a positive education program. Satisfactory internal reliability of the scales was obtained with Cronbach's alpha coefficients &lt; 0.70. The scales were generally positively and moderately inter-correlated, except for level of anxiety and depression symptoms which was negative. Good psychometric properties of APASO-II were evidenced from the factor structure of sub-scale scores conforming to six factors of the PERMA-H model by confirmatory factor analysis. Path analyses showed that the APASO-II factors together with measures of subject happiness and positive health as the multidimensional PERMA-H model of positive education differentially predicted general satisfaction of school life, level of anxiety and depression, and character strengths use. Character strengths use mediated the relationship of Positive Engagement with general satisfaction of school life. Positive education utilizes knowledge and research findings from positive psychology in schools to produce intended positive outcomes like enhanced well-being and reduced level of depression in students. This study provided a solid foundation for related scientific research and the understanding of the multidimensional framework of positive psychology concepts. Systematic promotion and longitudinal evaluation of positive education at the institutional level in Hong Kong can be achieved with the use of APASO-II and the positive education scales of subjective happiness and physical health

Measuring the Magnetic Field Amplitude of rf Radiation by the Quasistatic Magnetic Field Effect in Organic Light-Emitting Diodes

Electron paramagnetic resonance (EPR) is a versatile tool to probe spin physics in organic semiconductor materials. A common method used to detect the spin-½ paramagnetic resonance in organic light-emitting diodes (OLEDs) is to measure the device resistance under EPR conditions, i.e., to record electrically detected magnetic resonance (EDMR). Here, we present ultralow-frequency EDMR experiments on OLEDs that exhibit a qualitatively new line shape because of a quasistatic magnetic field effect: the modulation of the static ultrasmall field-effect magnetoresistance arising from the magnetic field amplitude B1 of the radio frequency (rf) radiation. The disappearance of spin-½ Zeeman resonances of individual charge carriers in the OLED, i.e., the resonances at magnetic fields where the Zeeman splitting matches the photon energy of the incident rf radiation, coincides with the emergence of the quasistatic effect. We discuss the origin of this quasistatic magnetic field effect, its characteristic line shape in terms of the magnetic field dependence, the influence of experimental parameters, and the application potential with regards to EDMR experiments. The EDMR line shape can be inferred numerically from the magnetoresistance measurements. This approach enables a unique means of determining the drive-field strength B1 in EDMR under driving conditions where alternative methods employing an analysis of the Zeeman resonance—such as power broadening and Rabi flopping—are not applicable

Capacity of countries to reduce biological invasions

The extent and impacts of biological invasions on biodiversity are largely shaped by an array of socio-economic and environmental factors, which exhibit high variation among countries. Yet, a global analysis of how these factors vary across countries is currently lacking. Here, we investigate how five broad, country-specific socio-economic and environmental indices (Governance, Trade, Environmental Performance, Lifestyle and Education, Innovation) explain country-level (1) established alien species (EAS) richness of eight taxonomic groups, and (2) proactive or reactive capacity to prevent and manage biological invasions and their impacts. These indices underpin many aspects of the invasion process, including the introduction, establishment, spread and management of alien species. They are also general enough to enable a global comparison across countries, and are therefore essential for defining future scenarios for biological invasions. Models including Trade, Governance, Lifestyle and Education, or a combination of these, best explained EAS richness across taxonomic groups and national proactive or reactive capacity. Historical (1996 or averaged over 1996–2015) levels of Governance and Trade better explained both EAS richness and the capacity of countries to manage invasions than more recent (2015) levels, revealing a historical legacy with important implications for the future of biological invasions. Using Governance and Trade to define a two-dimensional socio-economic space in which the position of a country captures its capacity to address issues of biological invasions, we identified four main clusters of countries in 2015. Most countries had an increase in Trade over the past 25 years, but trajectories were more geographically heterogeneous for Governance. Declines in levels of Governance are concerning as they may be responsible for larger levels of invasions in the future. By identifying the factors influencing EAS richness and the regions most susceptible to changes in these factors, our results provide novel insights to integrate biological invasions into scenarios of biodiversity change to better inform decision-making for policy and the management of biological invasions

Damage costs from invasive species exceed management expenditure in nations experiencing lower economic activity

Financial disclosure The InvaCost project was funded by the French National Research Agency (ANR-14-CE02-0021), the BNP-Paribas Foundation Climate Initiative, the AXA Research Fund Chair of Invasion Biology of University Paris Saclay and by the BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios (AlienScenarios; BMBF/PT DLR 01LC1807C). M.K. received funding from the European Union's Horizon 2020 research programme under a Marie Skłodowska-Curie grant agreement 899546. C.J.A.B. acknowledges the Australian Research Council (CE170100015) for support. A.B. acknowledges Azim Premji University's grants programme (UNIV-RC00326) for support.Peer reviewe

Early protein intake predicts functional connectivity and neurocognition in preterm born children

© 2021, The Author(s). Nutritional intake can promote early neonatal brain development in very preterm born neonates (\u3c 32 weeks’ gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p \u3c 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children