The role of the genetic counsellor: a systematic review of research evidence

In Europe, genetic counsellors are employed in specialist genetic centres or other specialist units. According to the European Board of Medical Genetics, the genetic counsellor must fulfil a range of roles, including provision of information and facilitation of psychosocial adjustment of the client to their genetic status and situation. To evaluate the extent to which genetic counsellors fulfil their prescribed roles, we conducted a systematic review of the published relevant scientific evidence. We searched five relevant electronic databases (Medline, CINAHL, SocIndex, AMED and PsychInfo) using relevant search terms and handsearched four subject-specific journals for research-based papers published in English between 1 January 2000 and 30 June 2013. Of 419 potential papers identified initially, seven satisfied the inclusion criteria for the review. Themes derived from the thematic analysis of the data were: (i) rationale for genetic counsellors to provide care, (ii) appropriate roles and responsibilities and (iii) the types of conditions included in the genetic counsellor caseload. The findings of this systematic review indicate that where genetic counsellors are utilised in specialist genetic settings, they undertake a significant workload associated with direct patient care and this appears to be acceptable to patients. With the burden on genetic services, there is an argument for the increased use of genetic counsellors in countries where they are under-utilised. In addition, roles undertaken by genetic counsellors in specialist genetic settings could be adapted to integrate genetic counsellors into multi-disciplinary teams in other specialisms

TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Measurements of the Temperature and E-Mode Polarization of the CMB from 500 Square Degrees of SPTpol Data

We present measurements of the $E$-mode polarization angular auto-power spectrum ($EE$) and temperature-$E$-mode cross-power spectrum ($TE$) of the cosmic microwave background (CMB) using 150 GHz data from three seasons of SPTpol observations. We report the power spectra over the spherical harmonic multipole range $50 < \ell \leq 8000$, and detect nine acoustic peaks in the $EE$ spectrum with high signal-to-noise ratio. These measurements are the most sensitive to date of the $EE$ and $TE$ power spectra at $\ell > 1050$ and $\ell > 1475$, respectively. The observations cover 500 deg$^2$, a fivefold increase in area compared to previous SPTpol analyses, which increases our sensitivity to the photon diffusion damping tail of the CMB power spectra enabling tighter constraints on \LCDM model extensions. After masking all sources with unpolarized flux $>50$ mJy we place a 95% confidence upper limit on residual polarized point-source power of $D_\ell = \ell(\ell+1)C_\ell/2\pi <0.107\,\mu{\rm K}^2$ at $\ell=3000$, suggesting that the $EE$ damping tail dominates foregrounds to at least $\ell = 4050$ with modest source masking. We find that the SPTpol dataset is in mild tension with the $\Lambda CDM$ model ($2.1\,\sigma$), and different data splits prefer parameter values that differ at the $\sim 1\,\sigma$ level. When fitting SPTpol data at $\ell < 1000$ we find cosmological parameter constraints consistent with those for $Planck$ temperature. Including SPTpol data at $\ell > 1000$ results in a preference for a higher value of the expansion rate (H_0 = 71.3 \pm 2.1\,\mbox{km}\,s^{-1}\mbox{Mpc}^{-1} ) and a lower value for present-day density fluctuations ($\sigma_8 = 0.77 \pm 0.02$).Comment: Updated to match version accepted to ApJ. 34 pages, 17 figures, 6 table

In Vivo Islet Protection by a Nuclear Import Inhibitor in a Mouse Model of Type 1 Diabetes

Insulin-dependent Type 1 diabetes (T1D) is a devastating autoimmune disease that destroys beta cells within the pancreatic islets and afflicts over 10 million people worldwide. These patients face life-long risks for blindness, cardiovascular and renal diseases, and complications of insulin treatment. New therapies that protect islets from autoimmune destruction and allow continuing insulin production are needed. Increasing evidence regarding the pathomechanism of T1D indicates that islets are destroyed by the relentless attack by autoreactive immune cells evolving from an aberrant action of the innate, in addition to adaptive, immune system that produces islet-toxic cytokines, chemokines, and other effectors of islet inflammation. We tested the hypothesis that targeting nuclear import of stress-responsive transcription factors evoked by agonist-stimulated innate and adaptive immunity receptors would protect islets from autoimmune destruction.Here we show that a first-in-class inhibitor of nuclear import, cSN50 peptide, affords in vivo islet protection following a 2-day course of intense treatment in NOD mice, which resulted in a diabetes-free state for one year without apparent toxicity. This nuclear import inhibitor precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from autoimmune diabetes-prone, non-obese diabetic (NOD) mice that develop T1D. Moreover, in this widely used model of human T1D we noted attenuation of pro-inflammatory cytokine and chemokine production in immune cells.These results indicate that a novel form of immunotherapy that targets nuclear import can arrest inflammation-driven destruction of insulin-producing beta cells at the site of autoimmune attack within pancreatic islets during the progression of T1D

Measurements of B-mode polarization of the cosmic microwave background from 500 square degrees of SPTpol data

We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work uses 500 deg² of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: 52 < ℓ < 2301. Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz × 95 GHz, 95 GHz × 150 GHz, and 150 GHz × 150 GHz. B-mode power is detected at very high significance; we find P(BB < 0) = 5.8 × 10⁻⁷¹, corresponding to a 18.1σ detection of power. With a prior on the galactic dust from Planck, WMAP and BICEP2/Keck observations, the SPTpol B-mode data can be used to set an upper limit on the tensor-to-scalar ratio, r < 0.44 at 95% confidence (the expected 1σ constraint on r given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit Λ CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor A_(lens), the data prefer A_(lens) = 1.17 ± 0.13. These data are currently the most precise measurements of B-mode power at ℓ > 320

Measurements of B-mode Polarization of the Cosmic Microwave Background from 500 Square Degrees of SPTpol Data

We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work uses 500 deg$^2$ of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: $52 < \ell < 2301$. Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz x 95 GHz, 95 GHz x 150 GHz, and 150 GHz x 150 GHz. B-mode power is detected at very high significance; we find $P(BB < 0) = 5.8 \times 10^{-71}$, corresponding to a $18.1 \sigma$ detection of power. An upper limit is set on the tensor-to-scalar ratio, $r < 0.44$ at 95% confidence (the expected $1 \sigma$ constraint on $r$ given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit $\Lambda$CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = $1.17 \pm 0.13$. These data are currently the most precise measurements of B-mode power at $\ell > 320$.Comment: 16 pages, 4 figures, Submitted to PR

Constraints on cosmological parameters from the 500 deg2 SPTPOL lensing power spectrum

We present cosmological constraints based on the cosmic microwave background (CMB) lensing potential power spectrum measurement from the recent 500 deg2 SPTpol survey, the most precise CMB lensing measurement from the ground to date. We fit a flat ΛCDM model to the reconstructed lensing power spectrum alone and in addition with other data sets: baryon acoustic oscillations (BAO), as well as primary CMB spectra from Planck and SPTpol. The cosmological constraints based on SPTpol and Planck lensing band powers are in good agreement when analyzed alone and in combination with Planck full-sky primary CMB data. With weak priors on the baryon density and other parameters, the SPTpol CMB lensing data alone provide a 4% constraint on ${\sigma }_{8}{{\rm{\Omega }}}_{m}^{0.25}=0.593\pm 0.025$. Jointly fitting with BAO data, we find ${\sigma }_{8}=0.779\pm 0.023$, ${{\rm{\Omega }}}_{m}={0.368}_{-0.037}^{+0.032}$, and ${H}_{0}={72.0}_{-2.5}^{+2.1}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, up to $2\sigma$ away from the central values preferred by Planck lensing + BAO. However, we recover good agreement between SPTpol and Planck when restricting the analysis to similar scales. We also consider single-parameter extensions to the flat ΛCDM model. The SPTpol lensing spectrum constrains the spatial curvature to be ${{\rm{\Omega }}}_{K}=-0.0007\pm 0.0025$ and the sum of the neutrino masses to be $\sum {m}_{\nu }\lt 0.23$ eV at 95% C.L. (with Planck primary CMB and BAO data), in good agreement with the Planck lensing results. With the differences in the signal-to-noise ratio of the lensing modes and the angular scales covered in the lensing spectra, this analysis represents an important independent check on the full-sky Planck lensing measurement

Optimal CMB Lensing Reconstruction and Parameter Estimation with SPTpol Data

We perform the first simultaneous Bayesian parameter inference and optimal reconstruction of the gravitational lensing of the cosmic microwave background (CMB), using 100 deg$^2$ of polarization observations from the SPTpol receiver on the South Pole Telescope. These data reach noise levels as low as 5.8 $\mu$K-arcmin in polarization, which are low enough that the typically used quadratic estimator (QE) technique for analyzing CMB lensing is significantly sub-optimal. Conversely, the Bayesian procedure extracts all lensing information from the data and is optimal at any noise level. We infer the amplitude of the gravitational lensing potential to be $A_\phi\,{=}\,0.949\,{\pm}\,0.122$ using the Bayesian pipeline, consistent with our QE pipeline result, but with 17\% smaller error bars. The Bayesian analysis also provides a simple way to account for systematic uncertainties, performing a similar job as frequentist "bias hardening," and reducing the systematic uncertainty on $A_\phi$ due to polarization calibration from almost half of the statistical error to effectively zero. Finally, we jointly constrain $A_\phi$ along with $A_{\rm L}$, the amplitude of lensing-like effects on the CMB power spectra, demonstrating that the Bayesian method can be used to easily infer parameters both from an optimal lensing reconstruction and from the delensed CMB, while exactly accounting for the correlation between the two. These results demonstrate the feasibility of the Bayesian approach on real data, and pave the way for future analysis of deep CMB polarization measurements with SPT-3G, Simons Observatory, and CMB-S4, where improvements relative to the QE can reach 1.5 times tighter constraints on $A_\phi$ and 7 times lower effective lensing reconstruction noise.Comment: 27 pages, 14 figures, accompanying software package available at https://cosmicmar.com/CMBLensing.j