We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose
Chronic obstructive pulmonary disease (COPD) is frequently associated with various comorbidities. However, the proportion of COPD patients with dementia has not been adequately ...examined. This retrospective cohort study investigated the association between COPD and dementia by using a nationwide population‐based database in Taiwan.
Methods
Data were retrieved from the Taiwanese National Health Insurance Research Database and analyzed using multivariate Cox proportional hazards regression models to assess the effects of COPD on the risk of dementia after adjusting for demographic characteristics and comorbidities.
Results
The COPD cohort exhibited a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline than did the non‐COPD cohort (P < 0.0001). After adjusting for covariates, the COPD patients exhibited a 1.27‐fold higher risk of developing dementia (hazard ratio 1.27, 95% confidence interval 1.20–1.36). The incidence rate was higher in patients with frequent acute exacerbations than in the non‐COPD patients regardless of whether a hospital admission or emergency room visit was required (hazard ratio 196.8 vs. 41.7, 95% confidence intervals 145.9–265.5 and 22.3–78.0).
Conclusion
This study shows that COPD is associated with a subsequent higher risk of dementia after adjusting for comorbidities. Specifically, the association between COPD and dementia is greater in patients with more frequent acute exacerbation events of COPD.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The epoch of re-ionization is a milestone of cosmological structure formation, marking the birth of the first objects massive enough to yield large numbers of ionizing photons. Measurements of the ...cosmic microwave background (CMB) Doppler effect from ionizing bubbles embedded in large-scale velocity streams - known as the patchy kinetic Sunyaev-Zel'dovich (kSZ) effect - can be used to constrain the duration of re-ionization. Using new multi-frequency data from the South Pole Telescope (SPT), we show that the ionized fraction evolved relatively rapidly. We combine the SPT constraint on the duration of re-ionization with the Wilkinson Microwave Anisotropy Probe measurement of the integrated optical depth to probe the cosmic ionization history. We find that re-ionization ended with 95% confidence at z > 7.2 under the assumption of no tSZ-CIB correlation, and z > 5.8 when correlations are allowed. These CMB observations complement other observational probes of the epoch of re-ionization such as the red-shifted 21 cm line and narrow-band surveys for Lyalpha-emitting galaxies.
Here, we present a sample-variance-limited measurement of the temperature power spectrum (TT) of the cosmic microwave background using observations of a ~1500 deg2 field made by the SPT-3G in 2018. ...We report multifrequency power spectrum measurements at 95, 150, and 220 GHz covering the angular multipole range 750 ≤ ℓ < 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 dataset. 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 dataset 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 Λ CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra AL, the effective number of neutrino species Neff, the primordial helium abundance YP, and the baryon clumping factor due to primordial magnetic fields b. We find that the SPT-3G 2018 TT/TE/EE data are well fit by Λ CDM with a probability to exceed of 15%. For Λ CDM, we constrain the expansion rate today to H0 = 68.3 ± 1.5 km s–1 Mpc–1 and the combined structure growth parameter to S8 = 0.797 ± 0.042. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either dataset are within <1σ of each other. The addition of temperature data to the SPT-3G TE/EE power spectra improves constraints by 8–27% for each of the Λ CDM cosmological parameters. When additionally fitting AL, Neff, or Neff + YP, the posteriors of these parameters tighten by 5–24%. In the case of primordial magnetic fields, complete TT/TE/EE power spectrum measurements are necessary to break the degeneracy between b and ns, the spectral index of primordial density perturbations. We report a 95% confidence upper limit from SPT-3G data of b<1.0. The cosmological constraints in this work are the tightest from SPT primary power spectrum measurements to date and the analysis forms a new framework for future SPT analyses.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP ...inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial.
To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term ‘HRD test’; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC.
A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype.
Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
•Homologous recombination repair deficiency (HRD) is a common feature of high-grade serous gynaecological cancers (HGSC).•Currently, the clinical validity of HRD tests in ovarian cancer is best assessed in terms of PARPi benefit.•Germline and somatic BRCA mutation and genomic instability tests help to predict likely magnitude of benefit from a PARPi.•Existing HRD tests fail to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies.•HRD is a dynamic entity and better biomarkers that capture current homologous recombination proficiency status are needed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
We study the relation between obscuration and supermassive black hole (SMBH) accretion using a large sample of hard X-ray selected active galactic nuclei (AGNs). We find a strong decrease in ...the fraction of obscured sources above the Eddington limit for dusty gas (
log
λ
Edd
≳
−
2
) confirming earlier results, and consistent with the radiation-regulated unification model. This also explains the difference in the Eddington ratio distribution functions (ERDFs) of type 1 and type 2 AGNs obtained by a recent study. The break in the ERDF of nearby AGNs is at
log
λ
Edd
*
=
−
1.34
±
0.07
. This corresponds to the
λ
Edd
where AGNs transition from having most of their sky covered by obscuring material to being mostly devoid of absorbing material. A similar trend is observed for the luminosity function, which implies that most of the SMBH growth in the local universe happens when the AGN is covered by a large reservoir of gas and dust. These results could be explained with a radiation-regulated growth model, in which AGNs move in the
N
H
–
λ
Edd
plane during their life cycle. The growth episode starts with the AGN mostly unobscured and accreting at low
λ
Edd
. As the SMBH is further fueled,
λ
Edd
,
N
H
and the covering factor increase, leading the AGN to be preferentially observed as obscured. Once
λ
Edd
reaches the Eddington limit for dusty gas, the covering factor and
N
H
rapidly decrease, leading the AGN to be typically observed as unobscured. As the remaining fuel is depleted, the SMBH goes back into a quiescent phase.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted) We present measurements of secondary cosmic microwave background (CMB) anisotropies and cosmic infrared background (CIB) fluctuations ...using data from the South Pole Telescope (SPT) covering the complete 2540 deg super(2) SPT-SZ survey area. Data in the three SPT-SZ frequency bands centered at 95, 150, and 220 GHz, are used to produce six angular power spectra (three single-frequency auto-spectra and three cross-spectra) covering the multipole range 2000 < l < 11,000 (angular scales 5' > ~ straighttheta > ~ 1'). These are the most precise measurements of the angular power spectra at l > 2500 at these frequencies. The main contributors to the power spectra at these angular scales and frequencies are the primary CMB, CIB, thermal and kinematic Sunyaev-Zel'dovich effects (tSZ and kSZ), and radio galaxies. We include a constraint on the tSZ power from a measurement of the tSZ bispectrum from 800 deg super(2) of the SPT-SZ survey. We measure the tSZ power at 143 GHz to be ... mu K super(2) and the kSZ power to be ... mu K super(2). The data prefer positive kSZ power at 98.1% CL. We measure a correlation coefficient of ... between sources of tSZ and CIB power, with xi < 0 disfavored at a confidence level of 99.0%. The constraint on kSZ power can be interpreted as an upper limit on the duration of reionization. When the post-reionization homogeneous kSZ signal is accounted for, we find an upper limit on the duration Delta z < 5.4 at 95% CL.
We present spectral and timing properties of the newly discovered X-ray transient source, MAXI J1535-571, which is believed to be a Galactic X-ray binary containing a black hole candidate (BHC) as ...the primary object. Since its discovery on 2017 September 2, it has been monitored regularly in multi-wavelength bands by several satellites. We use archival data of the Swift (XRT and BAT) and MAXI (GSC) satellite instruments to study accretion flow dynamics of the source during the outburst. During its outburst, the source became very bright in the sky with a maximum observed flux of 5 Crab in the 2-10 keV GSC band. Similar to other transient BHCs, it also shows signatures of low-frequency quasi-periodic oscillations (QPOs) during the outburst. Spectral data of different instruments are fitted with the transonic flow, solution-based two-component advective flow model fits file to find the direct accretion flow parameters. The evolution of spectral states and their transitions are understood from the model-fitted physical flow parameters and nature of QPOs. We also estimate the probable mass of the black hole from our spectral analysis as 7.9-9.9 M or 8.9 1.0 M .
Periodontal disease encompasses gingivitis and periodontitis, which exerts systemic effects. We conducted a population-based study to evaluate the association between periodontal disease and the risk ...of cancer.
We used insurance claims data from 1997 to 2010, accessing a database of 1 million randomly selected insurants in Taiwan. All patients were older than 20 and newly diagnosed with periodontitis between 1 January 1997 and 31 December 2010. The comparison cohort comprised patients older than 20, who were newly diagnosed with gingivitis in the same period. Both cohorts were followed until a cancer diagnosis, lost to follow-up, death, termination of insurance, or the end of 2010.
The incidence rate of cancer was 1.14 times higher in the study cohort than in the comparison cohort confidence interval (CI) = 1.11-1.17. The adjusted hazard ratio (HR) was 1.05 (95% CI = 1.00-1.11). A multivariable analysis showed that the periodontitis patients exhibited an elevated risk of developing oral cancer (adjusted HR = 1.79, 95% CI = 1.42-2.25).
The findings indicated that patients in the periodontitis cohort exhibited a higher risk of developing oral cancer than those in the gingivitis cohort.
TROPICAL CYCLONES AND CLIMATE CHANGE ASSESSMENT Knutson, Thomas; Camargo, Suzana J.; Chan, Johnny C. L. ...
Bulletin of the American Meteorological Society,
10/2019, Volume:
100, Issue:
10
Journal Article
Peer reviewed
Open access
An assessment was made of whether detectable changes in tropical cyclone (TC) activity are identifiable in observations and whether any changes can be attributed to anthropogenic climate change. ...Overall, historical data suggest detectable TC activity changes in some regions associated with TC track changes, while data quality and quantity issues create greater challenges for analyses based on TC intensity and frequency. A number of specific published conclusions (case studies) about possible detectable anthropogenic influence on TCs were assessed using the conventional approach of preferentially avoiding type I errors (i.e., overstating anthropogenic influence or detection). We conclude there is at least low to medium confidence that the observed poleward migration of the latitude of maximum intensity in the western North Pacific is detectable, or highly unusual compared to expected natural variability. Opinion on the author team was divided on whether any observed TC changes demonstrate discernible anthropogenic influence, or whether any other observed changes represent detectable changes. The issue was then reframed by assessing evidence for detectable anthropogenic influence while seeking to reduce the chance of type II errors (i.e., missing or understating anthropogenic influence or detection). For this purpose, we used a much weaker “balance of evidence” criterion for assessment. This leads to a number of more speculative TC detection and/or attribution statements, which we recognize have substantial potential for being false alarms (i.e., overstating anthropogenic influence or detection) but which may be useful for risk assessment. Several examples of these alternative statements, derived using this approach, are presented in the report.
Full text
Available for:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
