What do children who stutter and their parents expect from therapy and are their hopes aligned?

Currently there are few published reports exploring what it is that children and their parents wish to see change or happen as part of therapy. A process of eliciting hopes or expectations for therapy using Solution Focused Brief Therapy (de Shazer, 1985) is routinely used at the Michael Palin Centre (MPC) with children who stutter and their parents. This qualitative study aimed to explore what children who stutter and their parents expect from therapy and whether their hopes are aligned

Articulation rate and its relationship to disfluency type, duration, and temperament in preschool children who stutter.

The purpose of this study was to examine the relationship between articulation rate, frequency and duration of disfluencies of different types, and temperament in preschool children who stutter (CWS). In spontaneous speech samples from 19 children CWS (mean age = 3:9; years: months), we measured articulation rate, the frequency and duration of (a) sound prolongations; (b) soundsyllable repetitions; (c) single syllable whole word repetitions; and (d) clusters. Temperament was assessed with the Children’s Behavior Questionnaire (Rothbart et al., 2001). There was a significant negative correlation between articulation rate and average duration of sound prolongations (p\u3c0.01), and between articulation rate and frequency of stuttering-like disfluencies (SLDs) (p\u3c0.05). No other relationships proved statistically significant. Results do not support models of stuttering development that implicate particular characteristics of temperament as proximal contributors to stuttering; however, this is likely due to the fact that current methods, including the ones used in the present study, do not allow for the identification of a functional relationship between temperament and speech production. Findings do indicate that for some CWS, relatively longer sound prolongations co-occur with relatively slower speech rate, which suggests that sound prolongations, across a range of durations, may represent a distinct type of SLD, not just in their obvious perceptual characteristics, but in their potential influence on overall speech production at multiple levels

Ascites induces modulation of α6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma

Interactions between cancer cells and the surrounding medium are not fully understood. In this study, we demonstrate that ascites induces selective changes in the expression of integrins and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) in ovarian cancer cells. We hypothesise that this change of integrin and uPA/uPAR expression triggers signalling pathways responsible for modulating phenotype-dependent functional changes in ovarian cancer cells. Human ovarian surface epithelial (HOSE) cell lines and epithelial ovarian cancer cell lines were treated with ascites for 48 h. Ascites induced upregulation of α6 integrin, without any change in the expression of αv, β1 and β4 integrin subunits. Out of the four ovarian cancer cell lines studied, ascites induced enhancement in the expression of uPA/uPAR in the more invasive OVCA 433 and HEY cell lines without any change in the noninvasive OVHS1 and moderately invasive PEO.36 cell lines. On the other hand, no change in the expression of α6 integrin or uPAR, in response to ascites, was observed in HOSE cells. In response to ascites, enhancement in proliferation and in adhesion was observed in all four ovarian cancer cell lines studied. In contrast, no significant increase in proliferation or adhesion by ascites was observed in HOSE cells. Ascites-induced expression of uPA/uPAR correlated with the increased invasiveness of HEY and OVCA 433 cell lines but was not seen in OVHS1, PEO.36 and HOSE cell lines. Upregulation of α6 integrin and uPA/uPAR correlated with the activation of Ras and downstream Erk pathways. Ascites-induced activation of Ras and downstream Erk can be inhibited by using inhibitory antibodies against α6 and β1 integrin and uPAR, consistent with the inhibition of proliferation, adhesion and invasive functions of ovarian cancer cell lines. Based on these findings, we conclude that ascites can induce selective upregulation of integrin and uPA/uPAR in ovarian cancer cells and these changes may modulate the functions of ovarian carcinomas

Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis

Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3±0.5 ml (mean±s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer

A Measurement of the CMB Temperature Power Spectrum and Constraints on Cosmology from the SPT-3G 2018 TT/TE/EE Data Set

We present a sample-variance-limited measurement of the temperature power spectrum ($TT$) of the cosmic microwave background (CMB) using observations of a $\sim\! 1500 \,\mathrm{deg}^2$ field made by SPT-3G in 2018. We report multifrequency power spectrum measurements at 95, 150, and 220GHz covering the angular multipole range $750 \leq \ell < 3000$. We combine this $TT$ measurement with the published polarization power spectrum measurements from the 2018 observing season and update their associated covariance matrix to complete the SPT-3G 2018 $TT/TE/EE$ data set. This is the first analysis to present cosmological constraints from SPT $TT$, $TE$, and $EE$ power spectrum measurements jointly. We blind the cosmological results and subject the data set to a series of consistency tests at the power spectrum and parameter level. We find excellent agreement between frequencies and spectrum types and our results are robust to the modeling of astrophysical foregrounds. We report results for $\Lambda$CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra $A_\mathrm{L}$, the effective number of neutrino species $N_{\mathrm{eff}}$, the primordial helium abundance $Y_{\mathrm{P}}$, and the baryon clumping factor due to primordial magnetic fields $b$. We find that the SPT-3G 2018 $T/TE/EE$ data are well fit by $\Lambda$CDM with a probability-to-exceed of $15\%$. For $\Lambda$CDM, we constrain the expansion rate today to $H_0 = 68.3 \pm 1.5\,\mathrm{km\,s^{-1}\,Mpc^{-1}}$ and the combined structure growth parameter to $S_8 = 0.797 \pm 0.042$. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either data set are within $<1\,\sigma$ of each other. (abridged)Comment: 35 Pages, 17 Figures, 11 Table

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies

Flaring Stars in a Non-targeted mm-wave Survey with SPT-3G

We present a flare star catalog from four years of non-targeted millimeter-wave survey data from the South Pole Telescope (SPT). The data were taken with the SPT-3G camera and cover a 1500-square-degree region of the sky from $20^{h}40^{m}0^{s}$ to $3^{h}20^{m}0^{s}$ in right ascension and $-42^{\circ}$ to $-70^{\circ}$ in declination. This region was observed on a nearly daily cadence from 2019-2022 and chosen to avoid the plane of the galaxy. A short-duration transient search of this survey yields 111 flaring events from 66 stars, increasing the number of both flaring events and detected flare stars by an order of magnitude from the previous SPT-3G data release. We provide cross-matching to Gaia DR3, as well as matches to X-ray point sources found in the second ROSAT all-sky survey. We have detected flaring stars across the main sequence, from early-type A stars to M dwarfs, as well as a large population of evolved stars. These stars are mostly nearby, spanning 10 to 1000 parsecs in distance. Most of the flare spectral indices are constant or gently rising as a function of frequency at 95/150/220 GHz. The timescale of these events can range from minutes to hours, and the peak $\nu L_{\nu}$ luminosities range from $10^{27}$ to $10^{31}$ erg s$^{-1}$ in the SPT-3G frequency bands

A Measurement of Gravitational Lensing of the Cosmic Microwave Background Using SPT-3G 2018 Data

We present a measurement of gravitational lensing over 1500 deg$^2$ of the Southern sky using SPT-3G temperature data at 95 and 150 GHz taken in 2018. The lensing amplitude relative to a fiducial Planck 2018 $\Lambda$CDM cosmology is found to be $1.020\pm0.060$, excluding instrumental and astrophysical systematic uncertainties. We conduct extensive systematic and null tests to check the robustness of the lensing measurements, and report a minimum-variance combined lensing power spectrum over angular multipoles of $50<L<2000$, which we use to constrain cosmological models. When analyzed alone and jointly with primary cosmic microwave background (CMB) spectra within the $\Lambda$CDM model, our lensing amplitude measurements are consistent with measurements from SPT-SZ, SPTpol, ACT, and Planck. Incorporating loose priors on the baryon density and other parameters including uncertainties on a foreground bias template, we obtain a $1\sigma$ constraint on $\sigma_8 \Omega_{\rm m}^{0.25}=0.595 \pm 0.026$ using the SPT-3G 2018 lensing data alone, where $\sigma_8$ is a common measure of the amplitude of structure today and $\Omega_{\rm m}$ is the matter density parameter. Combining SPT-3G 2018 lensing measurements with baryon acoustic oscillation (BAO) data, we derive parameter constraints of $\sigma_8 = 0.810 \pm 0.033$, $S_8 \equiv \sigma_8(\Omega_{\rm m}/0.3)^{0.5}= 0.836 \pm 0.039$, and Hubble constant $H_0 =68.8^{+1.3}_{-1.6}$ km s$^{-1}$ Mpc$^{-1}$. Using CMB anisotropy and lensing measurements from SPT-3G only, we provide independent constraints on the spatial curvature of $\Omega_{K} = 0.014^{+0.023}_{-0.026}$ (95% C.L.) and the dark energy density of $\Omega_\Lambda = 0.722^{+0.031}_{-0.026}$ (68% C.L.). When combining SPT-3G lensing data with SPT-3G CMB anisotropy and BAO data, we find an upper limit on the sum of the neutrino masses of $\sum m_{\nu}< 0.30$ eV (95% C.L.)

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination