Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants

AbstractSeveral studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FOv. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n115) were randomly allocated to 5 ml/d FO (1·2 g/dn-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker ofn-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P&lt;0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sex×group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95 % CI 0·4, 21·8;P=0·04) higher after FO compared with SO supplementation among boys only. The sex×group interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P=0·03). The results were supported by sex-specific dose–response associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (bothP&lt;0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further.</jats:p

Severe Obesity in Young Women and Reproductive Health: The Danish National Birth Cohort

Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother and child.From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level

A feminist new materialist experiment: exploring what else gets produced through encounters with children’s news media

In this paper we are concerned to grapple with the ways in which real world issues directly impact children’s lives, and ask what else gets produced through encounters with children’s global news media specifically within the contexts of the UK and Norway. Our aim is to experiment with worldling practices as a means to open up generative possibilities to encounter and reconfigure difficult knowledges. We take two contemporary events: the 2017 Grenfell Tower fire tragedy in London, and the 2018 Marjory Stoneman high school shooting massacre in Florida, as a means to attend to ways in which affects are materialised across multiple times and spaces. News reports of these harrowing events, alongside what they produced, in terms of child activism, racism and toxic masculinity, provided a catalyst for a feminist new materialist experiment in generating other knowledges through material-affective-embodied encounters. Newspapers, glue, sticky tape, string, torches, bags and a cartridge for a firearm undertook important work within a speculative workshop, where a small number of early childhood researchers came together to be open to multiple and experimental ways of (k)not-knowing in order to formulate collectively shared problems. Following Manning (2016) we recognise that to avoid getting stuck in familiar ways of thinking and doing we need to undertake research differently. We wondered how might the re-materialisation of these events (through objects, artefacts, sounds and images) shift our thinking about childhood in other directions. We dwell upon the affective work that these high-profile news events perform, and how they might become rearticulated through affective encounters with materiality. Attending to how these events worked on us involves staying with the trouble (Haraway, 2016) as it becomes reignited, mutated and amplified across time and in different contexts. Our goal is to generate other possibilities that seek to reconfigure the ‘image of the child’. By resisting comforts of recognition, reflection and identification we reach beyond what we think we know about how children are in the world, and instead argue for their entanglement with difficult knowledges through, ours and their, world-making practices

A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and <i>TOP2A</i> gene amplification

ᅟ: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6 % of these tumors had TOP2A copy gain and 2.0 % had loss of TOP2A when compared to adjacent normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5 % had a ratio ≥ 1.5 consistent with gene amplification and 2.6 % had a ratio ≤ 0.8 suggesting gene deletions. Based on these observations and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio ≥ 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon’s two-stage minimax design). Every nine weeks, response is measured by computed tomography imaging and evaluated according to RECIST 1.1. The primary end-point of the study is progression-free survival. TRIAL REGISTRATION: Eudract no. 2013-001648-79

Mortality and HRQoL in ICU patients with delirium : Protocol for 1-year follow-up of AID-ICU trial

Background Intensive care unit (ICU)-acquired delirium is frequent and associated with poor short- and long-term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU-acquired delirium. Agents intervening against Delirium in the ICU (AID-ICU) is an international, multicentre, randomised, blinded, placebo-controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU-acquired delirium. The current pre-planned one-year follow-up study of the AID-ICU trial population aims to explore the effects of haloperidol on one-year mortality and health related quality of life (HRQoL). Methods The AID-ICU trial will include 1000 participants. One-year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox-regression and visualized by Kaplan-Meier curves tested for significance using the log-rank test. We will obtain HRQoL data using the EQ-5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value. Results We expect to publish results of this study in 2022. Conclusion We expect that this one-year follow-up study of participants with ICU-acquired delirium allocated to haloperidol vs. placebo will provide important information on the long-term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.Peer reviewe

Fully Automatic Whole-Volume Tumor Segmentation in Cervical Cancer

Uterine cervical cancer (CC) is the most common gynecologic malignancy worldwide. Whole-volume radiomic profiling from pelvic MRI may yield prognostic markers for tailoring treatment in CC. However, radiomic profiling relies on manual tumor segmentation which is unfeasible in the clinic. We present a fully automatic method for the 3D segmentation of primary CC lesions using state-of-the-art deep learning (DL) techniques. In 131 CC patients, the primary tumor was manually segmented on T2-weighted MRI by two radiologists (R1, R2). Patients were separated into a train/validation (n = 105) and a test- (n = 26) cohort. The segmentation performance of the DL algorithm compared with R1/R2 was assessed with Dice coefficients (DSCs) and Hausdorff distances (HDs) in the test cohort. The trained DL network retrieved whole-volume tumor segmentations yielding median DSCs of 0.60 and 0.58 for DL compared with R1 (DL-R1) and R2 (DL-R2), respectively, whereas DSC for R1-R2 was 0.78. Agreement for primary tumor volumes was excellent between raters (R1-R2: intraclass correlation coefficient (ICC) = 0.93), but lower for the DL algorithm and the raters (DL-R1: ICC = 0.43; DL-R2: ICC = 0.44). The developed DL algorithm enables the automated estimation of tumor size and primary CC tumor segmentation. However, segmentation agreement between raters is better than that between DL algorithm and raters.publishedVersio

Shifts Between Sugar Kelp and Turf Algae in Norway: Regime Shifts or Fluctuations Between Different Opportunistic Seaweed Species?

Around year 2000, sugar kelp (Saccharina latissima) forests were observed to disappear in southern parts of Norway, being replaced by mats of turf algae (i.e., filamentous ephemeral algae) loaded with sediments. Among more than 600 stations covering 35 000 km of coastline, about 80% on the Skagerrak coast and about 40% on the North Sea coast were dominated by turf. Various types of turf algae replaced S. latissima in a discontinuous pattern. This large spatial scale event was reported as a possible irrevocable regime shift, not caused by a single factor but related to multiple stressors, where eutrophication and ocean warming were proposed to be the most important. Recent observations have however, revealed that the seabed state has flipped back and forth between sugar kelp and turf algae in several areas and on temporal scales spanning from seasons to years. The relative abundance of S. latissima at monitoring sites at the Norwegian southern coast has fluctuated dramatically during the last 12 years, varying from sparse to common at several of these sites. In 2016, sugar kelp abundance had increased in more than half of the sites, compared to earlier years. Our monitoring data as well as other field observations and field experiments question the regime shift paradigm. Although traditionally considered as a perennial macrophyte, several of our studies indicate that sugar kelp possesses many of the characteristic traits of an opportunistic species, such as high dispersal potential and colonization rate, which enables the species to rapidly colonize available substrate. However, where turf algae persist, space for recolonization of sugar kelp will most likely be minor. In this paper we explore the spatial and temporal shift dynamic between sugar kelp and turf algae based on monitoring data and other studies. Based on a synthesis of mapped fluctuations between the two states, and studies on sugar kelps recolonization abilities, we discuss prerequisites and drivers for an irrevocable regime shift or a continuation of natural fluctuations, as well as possible mitigation actions

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM