Language and social/emotional problems identified at a universal developmental assessment at 30 months

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GESLA Version 3: A major update to the global higher‐frequency sea‐level dataset

This paper describes a major update to the quasi-global, higher-frequency sea-level dataset known as GESLA (Global Extreme Sea Level Analysis). Versions 1 (released 2009) and 2 (released 2016) of the dataset have been used in many published studies, across a wide range of oceanographic and coastal engineering-related investigations concerned with evaluating tides, storm surges, extreme sea levels, and other related processes. The third version of the dataset (released 2021), presented here, contains double the number of years of data, and nearly four times the number of records, compared to Version 2. The dataset consists of records obtained from multiple sources around the world. This paper describes the assembly of the dataset, its processing, and its format, and outlines potential future improvements

Female leadership in French voluntary associations

Drawing on a recent national survey, this paper focuses on the female representation on executive committees in French voluntary associations. To begin with, we observe that this representation is very unequal according to the different officer positions. It is especially low among presidents. Then we study the relationship between the associations' attributes and the likelihood of women being appointed as executive committee members. We notice that the probabilities that women hold president, treasurer and secretary positions are highly correlated to each other. We find that the proportion of female officers is higher in organizations whose activities pertain to social service, health and humanitarian sectors. It is lower in the oldest associations and it decreases as their geographical area of activity increases and as their budget becomes larger. The probability that associations have female presidents is higher in associations with few volunteers

Origin of Ozone NO(x) in the Tropical Troposphere: A Photochemical Analysis of Aircraft Observations Over the South Atlantic Basin

The photochemistry of the troposphere over the South Atlantic basin is examined by modeling of aircraft observations up to 12-km altitude taken during the TRACE A expedition in September-October 1992. A close balance is found in the 0 to 12-km column between photochemical production and loss Of O3, with net production at high altitudes compensating for weak net loss at low altitudes. This balance implies that O3 concentrations in the 0-12 km column can be explained solely by in situ photochemistry; influx from the stratosphere is negligible. Simulation of H2O2, CH3OOH, and CH2O concentrations measured aboard the aircraft lends confidence in the computations of O3 production and loss rates, although there appears to be a major gap in current understanding of CH2O chemistry in the marine boundary layer. The primary sources of NO(x) over the South Atlantic Basin appear to be continental (biomass burning, lightning, soils). There is evidence that NO(x) throughout the 0 to 12-km column is recycled from its oxidation products rather than directly transported from its primary sources. There is also evidence for rapid conversion of HNO3 to NO(x) in the upper troposphere by a mechanism not included in current models. A general representation of the O3 budget in the tropical troposphere is proposed that couples the large scale Walker circulation and in situ photochemistry. Deep convection in the rising branches of the Walker circulation injects NO(x) from combustion, soils, and lightning to the upper troposphere, leading to O3 production; eventually, the air subsides and net O3 loss takes place in the lower troposphere, closing the O3 cycle. This scheme implies a great sensitivity of the oxidizing power of the atmosphere to NO(x) emissions in the tropics

The statistics of triggered star formation: an overdensity of massive YSOs around Spitzer bubbles

We present a detailed statistical study of massive star formation in the environment of 322 Spitzer mid-infrared bubbles by using the RMS survey for massive Young Stellar Objects (YSOs). Using a combination of simple surface density plots and a more sophisticated angular cross-correlation function analysis we show that there is a statistically significant overdensity of RMS YSOs towards the bubbles. There is a clear peak in the surface density and angular cross-correlation function of YSOs projected against the rim of the bubbles. By investigating the autocorrelation function of the RMS YSOs we show that this is not due to intrinsic clustering of the RMS YSO sample. RMS YSOs and Spitzer bubbles are essentially uncorrelated with each other beyond a normalised angular distance of two bubble radii. The bubbles associated with RMS YSOs tend to be both smaller and thinner than those that are not associated with YSOs. We interpret this tendency to be due to an age effect, with YSOs being preferentially found around smaller and younger bubbles. We find no evidence to suggest that the YSOs associated with the bubbles are any more luminous than the rest of the RMS YSO population, which suggests that the triggering process does not produce a top heavy luminosity function or initial mass function. We suggest that it is likely that the YSOs were triggered by the expansion of the bubbles and estimate that the fraction of massive stars in the Milky Way formed by this process could be between 14 and 30%.Comment: 12 pages, 8 figures. Accepted by MNRAS. This version incorporates minor suggestions by the referee. A version with higher resolution Figure 1 is available upon reques

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: Study design, and baseline urinary, bowel and sexual function and quality of life

Objectives: To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. Materials and Methods: A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. Results: A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49-54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. Conclusion: The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer

Ad5NULL-A20 - a tropism-modified, αvβ6 integrin-selective oncolytic adenovirus for epithelial ovarian cancer therapies

Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for manipulability and tolerance of transgenes. Poor tumour-selectivity, off-target sequestration and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumour selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but non-detectable in healthy tissues. Experimental Design: Ad5NULL-A20 harbours mutations in each major capsid protein to preclude uptake via all native pathways. Tumour-tropism via αvβ6-targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed. Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of pre-existing anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non-tumour-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared to Ad5. Tumour uptake, transgene expression and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20-treated animals demonstrated significantly improved survival compared to those treated with oncolytic Ad5. Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-over-expressing cancers, and exciting platforms for tumour selective over-expression of therapeutic anti-cancer modalities, including immune checkpoint inhibitors

N-Palmitoyl Glycine, a Novel Endogenous Lipid That Acts As a Modulator of Calcium Influx and Nitric Oxide Production in Sensory Neurons

N-arachidonoyl glycine is an endogenous arachidonoyl amide that activates the orphan G protein-coupled receptor (GPCR) GPR18 in a pertussis toxin (PTX)-sensitive manner and produces antinociceptive and antiinflammatory effects. It is produced by direct conjugation of arachidonic acid to glycine and by oxidative metabolism of the endocannabinoid anandamide. Based on the presence of enzymes that conjugate fatty acids with glycine and the high abundance of palmitic acid in the brain, we hypothesized the endogenous formation of the saturated N-acyl amide N-palmitoyl glycine (PalGly). PalGly was partially purified from rat lipid extracts and identified using nano-high-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry. Here, we show that PalGly is produced after cellular stimulation and that it occurs in high levels in rat skin and spinal cord. PalGly was up-regulated in fatty acid amide hydrolase knockout mice, suggesting a pathway for enzymatic regulation. PalGly potently inhibited heat-evoked firing of nociceptive neurons in rat dorsal horn. In addition, PalGly induced transient calcium influx in native adult dorsal root ganglion (DRG) cells and a DRG-like cell line (F-11). The effect of PalGly on the latter cells was characterized by strict structural requirements, PTX sensitivity, and dependence on the presence of extracellular calcium. PalGly-induced calcium influx was blocked by the nonselective calcium channel blockers ruthenium red, 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole (SK&F96365), and La3+. Furthermore, PalGly contributed to the production of NO through calcium-sensitive nitric-oxide synthase enzymes present in F-11 cells and was inhibited by the nitric-oxide synthase inhibitor 7-nitroindazole