Purpose IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional ...injections in subjects with Peyronie disease. Co-primary outcomes in these identical phase 3 randomized, double-blind, placebo controlled studies included the percent change in the penile curvature abnormality and the change in the Peyronie disease questionnaire symptom bother score from baseline to 52 weeks. Materials and Methods IMPRESS I and II examined collagenase C. histolyticum intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg collagenase C. histolyticum, that is 2 injections per cycle separated by approximately 24 to 72 hours with the second injection of each followed 24 to 72 hours later by penile plaque modeling. Men were stratified by baseline penile curvature (30 to 60 vs 61 to 90 degrees) and randomized to collagenase C. histolyticum or placebo 2:1 in favor of the former. Results Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with collagenase C. histolyticum showed a mean 34% improvement in penile curvature, representing a mean ± SD −17.0 ± 14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean −9.3 ± 13.6 degree change per subject (p <0.0001). The mean change in Peyronie disease symptom bother score was significantly improved in treated men vs men on placebo (−2.8 ± 3.8 vs −1.8 ± 3.5, p = 0.0037). Three serious adverse events (corporeal rupture) were surgically repaired. Conclusions IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease.
The LOFAR Two-metre Sky Survey Shimwell, T. W.; Hardcastle, M. J.; Tasse, C. ...
Astronomy and astrophysics (Berlin),
03/2022, Volume:
659
Journal Article
Peer reviewed
Open access
In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120–168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred ...at approximately 12h45m +44°30′ and 1h00m +28°00′ and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes
I
) maps, where the majority of these have never been detected at radio wavelengths before. At 6″ resolution, our full bandwidth Stokes
I
continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beam
−1
; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2″; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beam
−1
. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > ± 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes
V
) 20″ resolution 120–168 MHz continuum images have a median rms sensitivity of 95 μJy beam
−1
, and we estimate a Stokes
I
to Stokes
V
leakage of 0.056%. Our linear polarisation (Stokes
Q
and Stokes
U
) image cubes consist of 480 × 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beam
−1
at 4′ and 2.2 mJy beam
−1
at 20″; we estimate the Stokes
I
to Stokes
Q
/
U
leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes
I
,
Q
,
U
and
V
images in addition to the calibrated
uv
-data to facilitate the thorough scientific exploitation of this unique dataset.
Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in ...METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and (11)Craclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.
An ecologically and economically disruptive harmful algal bloom (HAB) affected much of the northeast Pacific margin in 2015, during a prolonged oceanic warm anomaly. Caused by diatoms of the genus ...Pseudo‐nitzschia, this HAB produced the highest particulate concentrations of the biotoxin domoic acid (DA) ever recorded in Monterey Bay, California. Bloom inception followed strong upwelling during the spring transition, which introduced nutrients and eliminated the warm anomaly locally. Subsequently, moderate and intermittent upwelling created favorable conditions for growth and accumulation of HAB biomass, which was dominated by a highly toxigenic species, P. australis. High cellular DA concentrations were associated with available nitrogen for DA synthesis coincident with silicate exhaustion. This nutrient influence resulted from two factors: (1) disproportionate depletion of silicate in upwelling source waters during the warm anomaly, the most severe depletion observed in 24 years, and (2) silicate uptake by the dense diatom bloom.
Key Points
The most toxic algal bloom ever recorded in Monterey Bay, California, occurred in spring 2015, during a hiatus in a prolonged warm anomaly
The dense bloom of Pseudo‐nitzschia australis resulted from a strong spring upwelling transition followed by intermittent upwelling
Toxicity was influenced by anomalously low ratios of silicate to nitrate that predisposed the bloom to silicate exhaustion
These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the ...exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.
High-redshift quasars (
z
> 5) that also shine brightly at radio wavelengths are unique signposts of supermassive black hole activity in the early universe. However, bright radio sources at
z
≥ 5 ...are extremely rare and therefore we have started a campaign to search for new high-
z
quasars by combining an optical dropout selection driven by the
g
,
r
, and
z
bands from the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys with low-frequency radio observations from the LOFAR Two-metre Sky Survey (LoTSS). Currently, LoTSS covers a large fraction of the northern sky (∼5720 deg
2
) to such a depth (median noise level ∼83 μJy beam
−1
) that about 30% of the general quasar population is detected − which is a factor of 5–10 more than previous large sky radio surveys such as NVSS and FIRST, respectively. In this paper, we present the discovery of 20 new quasars (and the independent confirmation of four) between 4.9 ≤
z
≤ 6.6. Out of the 24 quasars, 21 satisfy the traditional radio-loudness criterion of
R
=
f
5 GHz
/
f
4400 Å
> 10, with the full sample spanning
R
∼ 6–1000, thereby more than doubling the sample of known radio-loud quasars at
z
≥ 5. Our radio detection requirement strongly decreases the contamination of stellar sources and allows one to select these quasars in a broad redshift range. Despite selecting our quasar candidates using fewer and less conservative colour restrictions, both the optical and near-infrared colours, Ly
α
emission line properties, and dust reddening,
E
(
B
−
V
), measurements of our quasar sample do not deviate from the known radio-quiet quasar population, suggesting similar optical quasar properties of the radio-loud and radio-quiet quasar population at high-
z
. Our campaign demonstrates the potential for discovering new high-
z
quasar populations through next generation radio continuum surveys.
Natural carbon sinks currently absorb approximately half of the anthropogenic CO2 emitted by fossil fuel burning, cement production and land-use change. However, this airborne fraction may change in ...the future depending on the emissions scenario. An important issue in developing carbon budgets to achieve climate stabilisation targets is the behaviour of natural carbon sinks, particularly under low emissions mitigation scenarios as required to meet the goals of the Paris Agreement. A key requirement for low carbon pathways is to quantify the effectiveness of negative emissions technologies which will be strongly affected by carbon cycle feedbacks. Here we find that Earth system models suggest significant weakening, even potential reversal, of the ocean and land sinks under future low emission scenarios. For the RCP2.6 concentration pathway, models project land and ocean sinks to weaken to 0.8 0.9 and 1.1 0.3 GtC yr−1 respectively for the second half of the 21st century and to −0.4 0.4 and 0.1 0.2 GtC yr−1 respectively for the second half of the 23rd century. Weakening of natural carbon sinks will hinder the effectiveness of negative emissions technologies and therefore increase their required deployment to achieve a given climate stabilisation target. We introduce a new metric, the perturbation airborne fraction, to measure and assess the effectiveness of negative emissions.
Background
Lipid levels during pregnancy in women with gestational diabetes mellitus (GDM) have been extensively studied; however, it remains unclear whether dyslipidaemia is a potential marker of ...preexisting insulin resistance.
Objective
To evaluate the relationship between lipid measures throughout pregnancy and GDM.
Search strategy
We searched PubMed‐MedLine and SCOPUS (inception until January 2014) and reference lists of relevant studies.
Selection criteria
Publications describing original data with at least one raw lipid (total cholesterol, high‐density lipoprotein cholesterol HDL‐C, low‐density lipoprotein cholesterol LDL‐C, or triglyceride) measurement during pregnancy in women with GDM and healthy pregnant controls were retained.
Data collection and analysis
Data extracted from 60 studies were pooled and weighted mean difference (WMD) in lipid levels was calculated using random effects models. Meta‐regression was also performed to identify sources of heterogeneity.
Main results
Triglyceride levels were significantly elevated in women with GDM compared with those without GDM (WMD 30.9, 95% confidence interval 95% CI 25.4–36.4). This finding was consistent in the first, second and third trimesters of pregnancy. HDL‐C levels were significantly lower in women with GDM compared with those without GDM in the second (WMD −4.6, 95% CI −6.2 to −3.1) and third (WMD −4.1, 95% CI −6.5 to −1.7) trimesters of pregnancy. There were no differences in aggregate total cholesterol or LDL‐C levels between women with GDM and those without insulin resistance.
Author's conclusions
Our meta‐analysis shows that triglycerides are significantly elevated among women with GDM compared with women without insulin resistance and this finding persists across all three trimesters of pregnancy.
We find two chemically distinct populations separated relatively cleanly in the Fe/H-Mg/Fe plane, but also distinguished in other chemical planes, among metal-poor stars (primarily with metallicities ...) observed by the Apache Point Observatory Galactic Evolution Experiment (APOGEE) and analyzed for Data Release 13 (DR13) of the Sloan Digital Sky Survey. These two stellar populations show the most significant differences in their X/Fe ratios for the -elements, C+N, Al, and Ni. In addition to these populations having differing chemistry, the low metallicity high-Mg population (which we denote "the HMg population") exhibits a significant net Galactic rotation, whereas the low-Mg population (or "the LMg population") has halo-like kinematics with little to no net rotation. Based on its properties, the origin of the LMg population is likely an accreted population of stars. The HMg population shows chemistry (and to an extent kinematics) similar to the thick disk, and is likely associated with in situ formation. The distinction between the LMg and HMg populations mimics the differences between the populations of low- and high- halo stars found in previous studies, suggesting that these are samples of the same two populations.
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