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Funder: Aarhus Universitets Forskningsfond; Id: http://dx.doi.org/10.13039/501100002739, Funder: Health Data Research UK; Id: http://dx.doi.org/10.13039/501100023699, Funder: Jabbs Foundation; Id: http://dx.doi.org/10.13039/501100016132, Funder: National Institute of Health Research Biomedical Research Centre, Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.

SUMMARYCancers often display immune escape, but the mechanisms and potential for reversibility are incompletely understood. Epigenetic dysregulation has been implicated in the immune escape of various cancer types. We have identified the epigenetic modifier SET and MYND-domain containing protein 3 (SMYD3) as a mediator of immune escape in human papilloma virus (HPV)- negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor prognosis and low response to immunotherapy with pembrolizumab, a programmed-death-1 (PD-1) targeting antibody. SMYD3 loss increased the sensitivity of HNSCC cancer cells to IFN-β, resulting in upregulation of type I IFN response and antigen presentation machinery genes. We found that SMYD3 regulates the transcription of Ubiquitin-Like PHD And RING Finger Domain- Containing Protein 1 (UHRF1), a key epigenetic reader of trimethylated lysine 9 on histone H3 (H3K9me3), which binds to H3K9me3-enriched promoters of key immune-related genes and silences their expression. SMYD3 further maintains the repression of immune-related genes through the deposition of H4K20me3 within the gene body regions of these genes. In an anti-PD-1 immune checkpoint resistant syngeneic mouse model of HPV-negative HNSCC, Smyd3 depletion induced influx of CD8+ T-cells, upregulated PD-L1 and MHC class I molecules, and increased sensitivity to anti-PD-1 therapy. SMYD3 overexpression was associated with decreased CD8 T-cell infiltration in tumor samples from patients with HPV-negative HNSCC, and was associated with poor response to pembrolizumab. Overall, these data highlight a previously unreported function of SMYD3 as a master epigenetic regulator of anti-tumor immune response in HPV-negative HNSCC and provide a rationale for translational approaches combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in this devastating disease.

Including millimeter-wave (mm-wave) data in multi-wavelength studies of the variability of active galactic nuclei (AGN) can provide insights into AGN physics that are not easily accessible at other wavelengths. We demonstrate in this work the potential of cosmic microwave background (CMB) telescopes to provide long-term, high-cadence mm-wave AGN monitoring over large fractions of sky. We report on a pilot study using data from the SPTpol instrument on the South Pole Telescope (SPT), which was designed to observe the CMB at arcminute and larger angular scales. Between 2013 and 2016, SPTpol was used primarily to observe a single 500 deg^2 field, covering the entire field several times per day with detectors sensitive to radiation in bands centered at 95 and 150 GHz. We use SPT 150 GHz observations to create AGN light curves, and we compare these mm-wave light curves to those at other wavelengths, in particular gamma-ray and optical. In this Letter, we focus on a single source, PKS 2326-502, which has extensive, day-timescale monitoring data in gamma-ray, optical, and now mm-wave between 2013 and 2016. We find PKS 2326-502 to be in a flaring state in the first two years of this monitoring, and we present a search for evidence of correlated variability between mm-wave, optical R band, and gamma-ray observations. This pilot study is paving the way for AGN monitoring with current and upcoming CMB experiments such as SPT-3G, Simons Observatory, and CMB-S4, including multi-wavelength studies with facilities such as VRO-LSST., Comment: 9 pages, 3 figures, accepted to Astrophysical Journal Letters

We present the first measurements of asteroids in millimeter wavelength (mm) data from the South Pole Telescope (SPT), which is used primarily to study the cosmic microwave background (CMB). We analyze maps of two $\sim270$ deg$^2$ sky regions near the ecliptic plane, each observed with the SPTpol camera $\sim100$ times over one month. We subtract the mean of all maps of a given field, removing static sky signal, and then average the mean-subtracted maps at known asteroid locations. We detect three asteroids$\text{ -- }$(324) Bamberga, (13) Egeria, and (22) Kalliope$\text{ -- }$with signal-to-noise ratios (S/N) of 11.2, 10.4, and 6.1, respectively, at 2.0 mm (150 GHz); we also detect (324) Bamberga with S/N of 4.1 at 3.2 mm (95 GHz). We place constraints on these asteroids' effective emissivities, brightness temperatures, and light curve modulation amplitude. Our flux density measurements of (324) Bamberga and (13) Egeria roughly agree with predictions, while our measurements of (22) Kalliope suggest lower flux, corresponding to effective emissivities of $0.66 \pm 0.11$ at 2.0 mm and $, 21 pages, 9 figures

Author(s): Gupta, N; Reichardt, CL; Ade, PAR; Anderson, AJ; Archipley, M; Austermann, JE; Avva, JS; Beall, JA; Bender, AN; Benson, BA; Bianchini, F; Bleem, LE; Carlstrom, JE; Chang, CL; Chiang, HC; Citron, R; Corbett Moran, C; Crawford, TM; Crites, AT; de Haan, T; Dobbs, MA; Everett, W; Feng, C; Gallicchio, J; George, EM; Gilbert, A; Halverson, NW; Harrington, N; Henning, JW; Hilton, GC; Holder, GP; Holzapfel, WL; Hou, Z; Hrubes, JD; Huang, N; Hubmayr, J; Irwin, KD; Knox, L; Lee, AT; Li, D; Lowitz, A; Luong-Van, D; Marrone, DP; McMahon, JJ; Meyer, SS; Mocanu, LM; Mohr, JJ; Montgomery, J; Nadolski, A; Natoli, T; Nibarger, JP; Noble, GI; Novosad, V; Padin, S; Patil, S; Pryke, C; Ruhl, JE; Saliwanchik, BR; Sayre, JT; Schaffer, KK; Shirokoff, E; Sievers, C; Smecher, G; Staniszewski, Z; Stark, AA; Story, KT; Switzer, ER; Tucker, C; Vanderlinde, K; Veach, T; Vieira, JD; Wang, G; Whitehorn, N; Williamson, R; Wu, WLK; Yefremenko, V; Zhang, L | Abstract: We study the polarization properties of extragalactic sources at 95 and 150 GHz in the SPTpol 500 deg2 survey. We estimate the polarized power by stacking maps at known source positions, and correct for noise bias by subtracting the mean polarized power at random positions in the maps. We show that the method is unbiased using a set of simulated maps with similar noise properties to the real SPTpol maps. We find a flux-weighted mean-squared polarization fraction 〈p2〉= [8.9 ± 1.1] × 10−4 at 95 GHz and [6.9 ± 1.1] × 10−4 at 150 GHz for the full sample. This is consistent with the values obtained for a subsample of active galactic nuclei. For dusty sources, we find 95 per cent upper limits of 〈p2〉95 l 16.9 × 10−3 and 〈p2〉150 l 2.6 × 10−3. We find no evidence that the polarization fraction depends on the source flux or observing frequency. The 1σ upper limit on measured mean-squared polarization fraction at 150 GHz implies that extragalactic foregrounds will be subdominant to the CMB E and B mode polarization power spectra out to at least l ≲ 5700 (l ≲ 4700) and l ≲ 5300 (l ≲ 3600), respectively, at 95 (150) GHz.

We present a search for anisotropic cosmic birefringence in 500 deg$^2$ of southern sky observed at 150 GHz with the SPTpol camera on the South Pole Telescope. We reconstruct a map of cosmic polarization rotation anisotropies using higher-order correlations between the observed cosmic microwave background (CMB) $E$ and $B$ fields. We then measure the angular power spectrum of this map, which is found to be consistent with zero. The non-detection is translated into an upper limit on the amplitude of the scale-invariant cosmic rotation power spectrum, $L(L+1)C_L^{\alpha\alpha}/2\pi < 0.10 \times 10^{-4}$ rad$^2$ (0.033 deg$^2$, 95% C.L.). This upper limit can be used to place constraints on the strength of primordial magnetic fields, $B_{1 \rm Mpc} < 17 {\rm nG} $ (95% C.L.), and on the coupling constant of the Chern-Simons electromagnetic term $g_{a\gamma} < 4.0 \times 10^{-2}/H_I $ (95% C.L.), where $H_I$ is the inflationary Hubble scale. For the first time, we also cross-correlate the CMB temperature fluctuations with the reconstructed rotation angle map, a signal expected to be non-vanishing in certain theoretical scenarios, and find no detectable signal. We perform a suite of systematics and consistency checks and find no evidence for contamination., Comment: 17 pages, 7 figures - new subsection on non-Gaussian foregrounds, conclusions unchanged - updated to match published version on PRD

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 $18.1 ��$ detection of power. An upper limit is set on the tensor-to-scalar ratio, $r < 0.44$ at 95% confidence (the expected $1 ��$ constraint on $r$ given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit $��$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 $\ell > 320$., 16 pages, 4 figures, Submitted to PRD

We present a constraint on the tensor-to-scalar ratio, $r$, derived from measurements of cosmic microwave background (CMB) polarization $B$-modes with "delensing," whereby the uncertainty on $r$ contributed by the sample variance of the gravitational lensing $B$-modes is reduced by cross-correlating against a lensing $B$-mode template. This template is constructed by combining an estimate of the polarized CMB with a tracer of the projected large-scale structure. The large-scale-structure tracer used is a map of the cosmic infrared background derived from Planck satellite data, while the polarized CMB map comes from a combination of South Pole Telescope, BICEP/Keck, and Planck data. We expand the BICEP/Keck likelihood analysis framework to accept a lensing template and apply it to the BICEP/Keck data set collected through 2014 using the same parametric foreground modelling as in the previous analysis. From simulations, we find that the uncertainty on $r$ is reduced by $\sim10\%$, from $��(r)$= 0.024 to 0.022, which can be compared with a $\sim26\%$ reduction obtained when using a perfect lensing template. Applying the technique to the real data, the constraint on $r$ is improved from $r_{0.05} < 0.090$ to $r_{0.05} < 0.082$ (95\% C.L.). This is the first demonstration of improvement in an $r$ constraint through delensing., 23 pages, 11 figures; match published version

We report new measurements of millimeter-wave power spectra in the angular multipole range $2000 \le \ell \le 11,000$ (angular scales $5^\prime \gtrsim \theta \gtrsim 1^\prime$). By adding 95 and 150\,GHz data from the low-noise 500 deg$^2$ SPTpol survey to the SPT-SZ three-frequency 2540 deg$^2$ survey, we substantially reduce the uncertainties in these bands. These power spectra include contributions from the primary cosmic microwave background, cosmic infrared background, radio galaxies, and thermal and kinematic Sunyaev-Zel'dovich (SZ) effects. The data favor a thermal SZ (tSZ) power at 143\,GHz of $D^{\rm tSZ}_{3000} = 3.42 \pm 0.54~ \mu {\rm K}^2$ and a kinematic SZ (kSZ) power of $D^{\rm kSZ}_{3000} = 3.0 \pm 1.0~ \mu {\rm K}^2$. This is the first measurement of kSZ power at $\ge 3\,\sigma$. We study the implications of the measured kSZ power for the epoch of reionization, finding the duration of reionization to be $\Delta z_{re} = 1.0^{+1.6}_{-0.7}$ ($\Delta z_{re}< 4.1$ at 95% confidence), when combined with our previously published tSZ bispectrum measurement., Comment: Submitted to ApJ, 16 pages. (revised portions of the introduction and description of bandpower estimation)

We present a catalog of galaxy cluster candidates detected in 100 square degrees surveyed with the SPTpol receiver on the South Pole Telescope. The catalog contains 89 candidates detected with a signal-to-noise ratio greater than 4.6. The candidates are selected using the Sunyaev-Zel'dovich effect at 95 and 150 GHz. Using both space- and ground-based optical and infrared telescopes, we have confirmed 81 candidates as galaxy clusters. We use these follow-up images and archival images to estimate photometric redshifts for 66 galaxy clusters and spectroscopic observations to obtain redshifts for 13 systems. An additional 2 galaxy clusters are confirmed using the overdensity of near-infrared galaxies only, and are presented without redshifts. We find that 15 candidates (18% of the total sample) are at redshift of $z \geq 1.0$, with a maximum confirmed redshift of $z_{\rm{max}} = 1.38 \pm 0.10$. We expect this catalog to contain every galaxy cluster with $M_{500c} > 2.6 \times 10^{14} M_\odot h^{-1}_{70}$ and $z > 0.25$ in the survey area. The mass threshold is approximately constant above $z = 0.25$, and the complete catalog has a median mass of approximately $ M_{500c} = 2.7 \times 10^{14} M_\odot h^{-1}_{70}$. Compared to previous SPT works, the increased depth of the millimeter-wave data (11.2 and 6.5 $��$K-arcmin at 95 and 150 GHz, respectively) makes it possible to find more galaxy clusters at high redshift and lower mass., 21 pages, 7 figures, associated data available at http://pole.uchicago.edu/public/data/sptsz-clusters. V2 was accepted to the AJ, and includes minor changes requested by the reviewer

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 $D_\ell = \ell(\ell+1)C_\ell/2\pi 1000$ 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 tables

Alterations of the somatotropic system as seen in Growth Hormone Deficiency (GHD) or acromegaly can lead to a variety of mental and physical impairments. Especially the prevalence of psychiatric disorders is elevated and cognitive function is impaired. These changes are paralleled by disturbances of the macroscopic brain tissue architecture and may persist despite achievement of biochemical control. On the other hand strong alterations in GH-secretion and impaired regulatory response to exogenous stimulation have been described in a variety of studies investigating the somatotropic feedback-loop in mood disorders. This reciprocal relationship indicates certain effects of this hormone system in the modulation of neuronal function and an involvement in the pathogenesis of psychiatric disorders.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p

BACKGROUND Quality of life in lung transplant recipients (LTR) is reported to be comparable with that of the general population. However, previous studies have shown that exercise capacity was reduced to 30 - 40 % of normal values. The purpose of this study was to investigate the gap between good self-reported quality of life and reduced exercise capacity in LTR, to describe possible correlations and to compare the results with those of a control group (CG). METHODS 27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11 female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) % 75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/- 4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic disease" self-rating questionnaire. RESULTS Significant differences were shown in objective exercise related variables (peak oxygen consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p < 0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p < 0.01); percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p < 0.01). The rating of subjective quality of life in physical, psychological and social domains of LTR did not differ from values of the CG or of the general population (n = 1143). The quality of life in the physical domain correlated significantly with peak exercise capacity (LTR r = 0.44, p < 0.05; CG r = 0.37; p < 0.05). CONCLUSION Patients 7 months after lung transplantation described their physical, social and psychological quality of life as equally good as the healthy control group. However, peak exercise capacity and oxygen consumption were markedly reduced. To improve physical capacity in the range of daily activities, an exercise training program should be offered to patients after lung transplantation.

The competitive GH receptor antagonist pegvisomant is reported to normalise IGF-1 levels in up to 97 % of acromegalic patients at a maximum dosage of 40 mg/d. Description of Case: We present an acromegalic patient resistant to the recommended maximum GH receptor antagonist dosage. The 60-year-old male patient presenting with typical clinical signs of acromegaly has underwent multiple transsphenoidal surgeries and pituitary irradiation, while currently available pharmacological therapies for acromegaly have been exhausted.Biochemical control of the disease could only be achieved until uptitration of pegvisomant to 60 mg/d which was tolerated well.The current treatment algorithm for acromegaly should be modified to treat cases of persistent and uncontrolled disease.

Objective:To correlate B-mode ultrasound findings to carotid plaque histology.Design:European multicentre study (nine centres).Material and Methods:Clinical presentation and risk factors were recorded and preoperative ultrasound Duplex scanning with special emphasis on B-mode imaging studies was performed in 270 patients undergoing carotid endarterectomy. Perioperatively, macroscopic plaque features were evaluated and the removed specimens were analysed histologically for fibrous tissue, calcification and ‘soft tissue’ (primarily haemorrhage and lipid).Results:Males had more soft tissue than females (p = 0.0006), hypertensive patients less soft tissue than normotensive (p = 0.01) and patients with recent symptoms more soft tissue than patients with earlier symptoms (p = 0.004). There was no correlation between surface description on ultrasound images compared to the surface judged intraoperatively by the surgeon. Echogenicity on B-mode images was inversely related to soft tissue (p = 0.005) and calcification was directly related to echogenicity (p < 0.0001). Heterogeneous plaques contained more calcification than homogeneous (p = 0.003), however, there was no difference in content of soft tissue.Conclusion:Ultrasound B-mode characteristics are related to the histological composition of carotid artery plaques and to patient's history. These results may imply that patients with distant symptoms may be regarded and treated as asymptomatic patients whereas asymptomatic patients with echolucent plaques should be considered for carotid endarterectomy.

Obesity is associated with the metabolic syndrome. However, not all obese individuals have cardiovascular risk factors (CVRF). It is not clear how many abdominally obese individuals are free of CVRF and what distinguishes them from the group of obese individuals with CVRF. In this study, we aimed to assess the associated factors and prevalence of abdominal obesity without CVRF. In our cross-sectional analysis, we included n = 4244 subjects from the Study of Health in Pomerania (SHIP), a population-based study and n = 6671 subjects from the Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study, a representative primary care study in Germany. We defined abdominal obesity by waist-to-height ratio (WHtR) of 0.5 or greater. We assessed how many subjects with abdominal obesity had CVRF based on the definition of the metabolic syndrome. We analysed which conditions were associated with the absence of CVRF in abdominal obesity. In SHIP and DETECT, 2652 (62.5%) and 5126 (76.8%) subjects had a WHtR ≥ 0.5. Among those with a WHtR ≥ 0.5, 9.0% and 13.8% were free of CVRF and 49.9% and 52.7% had at least two CVRF in SHIP and DETECT, respectively. In both studies, after backward elimination, age, male sex, body mass index and high liver enzymes and unemployment were consistently inversely associated with the absence of CVRF. Among abdominally obese subjects, the prevalence of metabolically healthy subjects is low. Conditions consistently associated with the absence of CVRF in abdominal obesity are younger age, female sex, low BMI, and normal liver enzymes, the latter likely reflecting the absence of steatohepatitis.

BACKGROUND Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. METHODS We measured circulating concentrations of cTnI, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. RESULTS Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. CONCLUSIONS Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction.A prospective, nested case-control study.We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort.We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk.In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores.Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.

Leiomyomas, which usually occur multilocular in uterus, can develop even if rarely in other organs with smooth muscle cells. The tumour is considered benign; 2 case reports supports the hypothesis that uterus myoma could metastasize, and in the metastasis sites grow invasively.2 female patients 44 y. and 29 y. old were admitted to our clinic for MPL. Due to increasing tumor size respectively dypnea, they were operated on. Multiple nodules of the left lung in one case, and a mediastinal tumour in the other were resected; resected tumour was histologically examined.In both cases it was a matter of well-differentiated leiomyosarcoma. The mediastinal tumour has already invade the N. phrenicus. Postoperatively there were no complications. Patients discharged in well-doing state, medical control one year later revealed no new growth.Multiple pulmonary leiomyomas are rare, they occur in sexually mature women in coincidence with uterus myoma. Even though many authors assume that MPL is a lung metastasis of benign tumours, the pathogenesis is still hypothetical. Supporting this thesis is the hormone dependence of both the uterine and the pulmonary tumours; against it, is that extrapulmonary locations are too rarely observed. The still open pathogenetical question has no therapeutical consequence. Whenever technically possible, a radical, parenchyma-saving surgical therapy should be the first choice. Otherwise hormon-ablation is a good alternative.

Transcranial Doppler ultrasonography can monitor changes in intracranial blood flow velocity over time in a variety of experimental and clinical settings with excellent temporal resolution. Alterations in arterial carbon dioxide pressure exert a profound influence on blood flow velocity. Such changes exhibit important individual fluctuation depending on respiratory status. This limits the ability of transcranial Doppler to accurately study subtle changes in blood flow velocity, independent of the respiratory state of the subject. Suggested here is a method to control for the respiration artifact on blood flow velocity. The middle cerebral artery of 7 healthy male volunteers was studied with transcranial Doppler under resting conditions, monitoring end-tidal carbon dioxide concentration and blood flow velocity. Hyperventilation was performed both voluntarily and with pharmacological induction by human corticotropin-releasing hormone. These studies were carried out both with and without the use of counterregulation of the end-tidal carbon dioxide concentration via a respiration unit, with an adjustable carbon dioxide-oxygen gas supply preventing significant changes in end-tidal carbon dioxide. The blood flow velocity in the middle cerebral artery during maximal voluntary hyperventilation decreased from baseline values of 100% to 44.4 +/- 4.3% (a 55.6% decrease), and with human corticotropin-releasing hormone-induced involuntary hyperventilation, to 65.1 +/- 5.3% (a 34.9% decrease). With the control method, blood flow velocities during voluntary and pharmacological hyperventilation were 100 +/- 1.6% and 100 +/- 2.8%, respectively. This method allows for control of respiration-induced artifacts during transcranial Doppler monitoring, and can be used to assess the effect of direct or indirect blood flow velocity stimuli independent of respiratory status.

Ob Veranderungen in der Plaquezusammensetzung bei dem Ereignis oder Mechanismus, der eine asymptomatische Karotisplaque in eine symptomatische umwandelt, bedeutsam sind, ist unklar. Die Verwendung hochauflosender Ultraschallgerate ermoglicht eine zunehmend bessere Darstellung arteriosklerotischer Karotisplaques. Ziel unserer Untersuchung war die Frage, ob sich mittels einer computerisierten Texturanalyse Kenngrosen von asymptomatischen und symptomatischen Karotisplaques errechnen lassen.

To evaluate the CO2-induced vasomotor reactivity of the cerebral vasculature, relative changes of blood flow velocity within the middle cerebral artery were measured by transcranial Doppler ultrasonography during normocapnia and various degrees of hypercapnia and hypocapnia. We studied 40 normal individuals and 40 patients with unilateral and 15 patients with bilateral internal carotid artery occlusions. When blood flow velocity changes as percent of normocapnic values were plotted against end-tidal CO2 volume percent, a biasymptotic curve (a tangent-hyperbolic function) gave the best fit of the scattergram. The distance between the upper and lower asymptotes was defined as cerebral vasomotor reactivity. In the normal individuals, mean +/- SD vasomotor reactivity was 85.63 +/- 15.96%. In patients with internal carotid artery occlusions, vasomotor reactivity was significantly lower than normal on both the occluded (mean 45.2%, median 50.4%; p less than 0.0001) and the nonoccluded (mean +/- SD 67.7 + 13.3%, p less than 0.01) sides in the unilateral group and on both sides (mean +/- SD 36.6 +/- 15.9% and 44.9 +/- 24.6%, p less than 0.0001) in the bilateral group. The difference between vasomotor reactivity for symptomatic and asymptomatic unilateral occlusions was also highly significant (mean 37.6% and 62.9%, p less than 0.006). Vasomotor reactivity was also significantly lower in patients with low-flow infarctions on computed tomography than in patients with normal scans (mean +/- SD 36.7 +/- 25% and 60.2 +/- 16.9%, p less than 0.008). A striking association of low-flow infarctions, ischemic ophthalmopathy, and hypostatic transient ischemic attacks was found with vasomotor reactivities of less than 34% or even paradoxical reactions.(ABSTRACT TRUNCATED AT 250 WORDS)