This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC).
Between October 2012 and ...February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) and stathmin immunohistochemistry were performed on FFPE tumour tissue.
Eighteen from 30 (60%) patients had detectable CTCs during study 1 CTC (n = 7), 2 (n = 4), 3 (n = 1), 4 (n = 2), 7 (n = 1), 8 (n = 1), 22 (n = 1), 172 (n = 1) in 7.5 ml blood. Ten from 18 patients had between 50 and 100% of detectable CTCs that were stathmin positive. More CTC-positive than CTC-negative patients had non-endometrioid versus endometrioid histology, tumour size ≥5 versus <5 cm, higher-stage disease and worse survival hazard ratio 3.3, p > 0.05, 95% confidence interval 0.7-16.2. Twenty-one tumour blocks were tested for EpCAM and stathmin immunohistochemistry (IHC). Stathmin tumour immunostaining scores (TIS) on IHC were higher in CTC-positive patients.
CTC enumeration and molecular profiling with stathmin on the CellSearch platform is feasible in aEC. Stathmin TIS on IHC, a known prognostic marker in EC, was associated with CTC positivity.
BackgroundCentral venous access devices (CVADs) are integral to cancer care provision. Despite the high prevalence of CVAD complications in children with cancer, preventative strategies are ...understudied.ObjectiveThe aim of this study was to assess study feasibility, occlusive events, thrombolytic use, adverse events, and direct costs of catheter lock solutions.MethodsA single-center, parallel-group, pilot randomized controlled trial was undertaken at a tertiary-referral pediatric hospital in Australia. Children 18 years or younger with an oncological or malignant hematological condition and a CVAD were eligible. Participants were 1:1 randomized to (1) normal or (2) heparinized (10–100 U/mL; CVAD-type dependent) saline lock solutions.ResultsOf 217 children assessed for eligibility, 61 were recruited and randomized to normal (n = 30; 3850 CVAD days) or heparinized (n = 31; 4036 CVAD days) saline. Eligibility (52%) and recruitment (54%) feasibility targets were not met. Protocol adherence was high (95% assessments), with no attrition. Parent/clinician satisfaction of interventions was high (median, 10/10 clinicians/parents). Complete CVAD occlusion occurred in heparin only (n = 2, 6.7% CVADs; incidence rate IR, 0.49/1000 CVAD days 0.06–1.78). Central venous access device partial occlusion was detected in 23.3% of CVADs in heparin (n = 7; IR, 2.73/1000 CVAD days 1.36–4.87) and 13.8% of CVADs in normal saline (n = 4; IR, 2.59/1000 CVAD days 1.24–4.77). Thrombolytic agents were used in 16.7% heparin (5 CVADs) and 3.5% normal saline (1 CVAD). Adverse events did not differ between groups.ConclusionMultisite randomized controlled trials examining CVAD locks are safe, but strategies and resources to increase recruitment and eligibility are required.Implications for PracticeBoth routine CVAD lock solutions seem safe but may not prevent all forms of CVAD-associated harm.
Background: Early empirical data shows that school-aged children, adolescents and adults are experiencing elevated levels of anxiety and depression during the COVID-19 pandemic. Currently, there is ...very little research on mental health outcomes for young children.
Objectives: To describe the formation of a global collaboration entitled, 'COVID-19 Unmasked'. The collaborating researchers aim to (1) describe and compare the COVID-19 related experiences within and across countries; (2) examine mental health outcomes for young children (1 to 5 years) and caregivers over a 12-month period during the COVID-19 pandemic; (3) explore the trajectories/time course of psychological outcomes of the children and parents over this period and (4) identify the risk and protective factors for different mental health trajectories. Data will be combined from all participating countries into one large open access cross-cultural dataset to facilitate further international collaborations and joint publications.
Methods: COVID-19 Unmasked is an online prospective longitudinal cohort study. An international steering committee was formed with the aim of starting a global collaboration. Currently, partnerships have been formed with 9 countries (Australia, Cyprus, Greece, the Netherlands, Poland, Spain, Turkey, the UK, and the United States of America). Research partners have started to start data collection with caregivers of young children aged 1-5 years old at baseline, 3-months, 6-months, and 12-months. Caregivers are invited to complete an online survey about COVID-19 related exposure and experiences, child's wellbeing, their own mental health, and parenting.
Data analysis: Primary study outcomes will be child mental health as assessed by scales from the Patient-Reported Outcomes Measurement Information System - Early Childhood (PROMIS-EC) and caregiver mental health as assessed by the Depression Anxiety Stress Scale (DASS-21). The trajectories/time course of mental health difficulties and the impact of risk and protective factors will be analysed using hierarchical linear models, accounting for nested effects (e.g. country) and repeated measures.
This article describes the formation of a global collaboration between 9 countries that are collecting data to examine mental health outcomes for young children (1 to 5 years) and caregivers over a 12-month period during the COVID-19 pandemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption.
The purpose of this study ...was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia.
We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography).
In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function.
We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If.
A randomized clinical trial involving postmenopausal patients with estrogen receptor positive recurrent breast cancer is reported. Of 168 patients entered, 156 were evaluable, of whom 79 received ...oral tamoxifen citrate 10 mg twice daily and 77 oral megestrol acetate 40 mg four times a day. Partial response (PR) plus complete response (CR) rates (both arms, 34%) and time-to-disease progression were similar in both arms. Side effects and toxicity were minimal with both regimens, although more patients who received tamoxifen complained of hot flushes (33% v 11%) and more patients who received megestrol acetate had a 10% or greater weight gain at 6 months from baseline (51% v 19%). On progression of disease, 73 patients who had achieved a CR, PR, or stable response received the alternative hormonal treatment in addition to the original hormonal therapy. Ten of 40 patients (25%) who began treatment with megestrol acetate had a further CR or PR; none of 33 patients originally receiving tamoxifen had a response when megestrol acetate was added. Similarly, patients who received tamoxifen as an addition to their original megestrol acetate treatment also had a significantly longer time to second progression than did those in the comparative arm. It was concluded that as initial hormonal therapy for relapsed patients, either tamoxifen or megestrol acetate can be used with confidence. However, it is suggested that tamoxifen and megestrol acetate should not be used in combination, except for those few occasions when tamoxifen is added as second-line therapy following a completed megestrol acetate response, and the megestrol acetate is continued for its palliative effects on appetite and weight gain. Possible mechanisms behind these results are discussed.
Sediment fluxes in aquatic environments are crucially dependent on bedform dynamics. However, sediment-flux predictions rely almost completely on clean-sand studies, despite most environments being ...composed of mixtures of non-cohesive sands, physically cohesive muds and biologically cohesive extracellular polymeric substances (EPS) generated by microorganisms. EPS associated with surficial biofilms are known to stabilize sediment and increase erosion thresholds. Here we present experimental data showing that the pervasive distribution of low levels of EPS throughout the sediment, rather than the high surficial levels of EPS in biofilms, is the key control on bedform dynamics. The development time for bedforms increases by up to two orders of magnitude for extremely small quantities of pervasively distributed EPS. This effect is far stronger than for physical cohesion, because EPS inhibit sand grains from moving independently. The results highlight that present bedform predictors are overly simplistic, and the associated sediment transport processes require re-assessment for the influence of EPS.
Biologically active, fine‐grained sediment forms abundant sedimentary deposits on Earth's surface, and mixed mud‐sand dominates many coasts, deltas, and estuaries. Our predictions of sediment ...transport and bed roughness in these environments presently rely on empirically based bed form predictors that are based exclusively on biologically inactive cohesionless silt, sand, and gravel. This approach underpins many paleoenvironmental reconstructions of sedimentary successions, which rely on analysis of cross‐stratification and bounding surfaces produced by migrating bed forms. Here we present controlled laboratory experiments that identify and quantify the influence of physical and biological cohesion on equilibrium bed form morphology. The results show the profound influence of biological cohesion on bed form size and identify how cohesive bonding mechanisms in different sediment mixtures govern the relationships. The findings highlight that existing bed form predictors require reformulation for combined biophysical cohesive effects in order to improve morphodynamic model predictions and to enhance the interpretations of these environments in the geological record.
Key Points
Subaqueous bed form dimensions are controlled more by biological than physical cohesion
Existing predictors require reformulation for combined biophysical cohesive effects
Small amounts of substrate biological cohesion act to reduce bed roughness 2 orders of magnitude
Working memory (WM) plays a crucial role in various cognitive tasks from language comprehension to problem-solving. However, its influence on social activities has remained largely unexplored. The ...current two studies on individual differences, a pilot (N = 329) and a pre-registered direct replication (N = 338) study, investigated the relationship between WM and outside-the-lab social interaction by using a listening span task and three social network questionnaires (e.g., how many people a participant had contacted in the past month). The consistent patterns in the two studies were (a) WM recall was positively correlated with social network size, (b) WM recall remained positively correlated with social network size even when accounting for online interactions on WhatsApp and Facebook, and (c) WM recall was positively correlated with social network size by face-to-face interaction. These novel findings would suggest connections between WM and face-to-face social interaction. It was, however, acknowledged that the obtained effect sizes were small, and that further investigation is indeed necessary. In light of this, we also clarify future directions for understanding the relationship between WM and social interaction.
•The current study focuses on everyday social interaction 56 characters•Working memory relates to face-to-face social interaction 57 characters•Working memory does not relate to non-face-to-face social interaction 69 characters•The obtained effect sizes are, however, small, and further research is needed 77 characters
The liquid crystal nonsymmetric dimer, 1-(4-butoxyazobenzene-4′-yloxy)-6-(4-cyanobiphenyl-4′-yl) hexane (CB6OABOBu), shows enantiotropic twist–bend nematic, NTB, and nematic, N, phases. The NTB phase ...has been confirmed using polarized light microscopy, freeze fracture transmission electron microscopy, and X-ray diffraction. The helicoidal pitch in the NTB phase is 18 nm. The NTB–N (TNTBN) and N–I (TNI) transition temperatures are reduced upon UV light irradiation, with the reduction in TNTBN being much larger than that in TNI. An isothermal, reversible NTB–N transition may be driven photochemically. These observations are attributed to a trans–cis photoisomerization of the azobenzene fragment on UV irradiation, with the cis isomers stabilizing the standard nematic phase and the trans isomers stabilizing the NTB phase. The dramatic changes in TNTBN provide evidence that the transition between the normal nematic and twist–bend nematic with spontaneous breaking of chiral symmetry is crucially dependent on the shape of molecular dimers, which changes greatly during the trans–cis isomerization.
U̠t-Ma’in (Kainji, Benue-Congo), spoken in northwestern Nigeria, has two morphosyntactically distinct progressive constructions – the Intransitive Progressive Construction and the Transitive ...Progressive Construction. This paper presents the synchronic structure of each construction, proposed historical sources of the distinct morphological pieces, and a comparison of the U̠t-Ma’in Progressive Constructions with cognate elements from four Kainji language clusters. No single source component has grammaticalized to mark progressive aspect in U̠t-Ma’in. Rather, the combination of several elements created the progressive. Formal changes in several morphosyntactic elements within each of the constructions provide evidence that originally nominalized verb forms are gradually becoming less noun-like and more verb-like. These developments are examples of constructionalization, as the Progressive Constructions exist as new form-meaning pairs distinct from the source. These formal changes also show signs of adjustment, whereby a construction moves toward isomorphism, that is, a one-to-one correspondence between form and meaning. Specifically, various stages of morphological loss are evident in particular lexemes when used in U̠t-Ma’in Progressive Constructions, gradually spreading throughout the lexicon.
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