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Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).
Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.
Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
Emotion dysregulation is a risk factor for the development of a variety of psychopathologic outcomes. In children, irritability, or dysregulated negative affect, has been the primary focus, as it predicts later negative outcomes even in very young children. However, dysregulation of positive emotion is increasingly recognized as a contributor to psychopathology. Here we used an exploratory factor analysis and defined four factors of emotion dysregulation: irritability, excitability, sadness, and anhedonia, in the preschool-age psychiatric assessment collected in a sample of 302 children ages 3–5 years enriched for early onset depression. The irritability and excitability factor scores defined in preschoolers predicted later diagnosis of mood and externalizing disorders when controlling for other factor scores, social adversity, maternal history of mood disorders, and externalizing diagnoses at baseline. The preschool excitability factor score predicted emotion lability in late childhood and early adolescence when controlling for other factor scores, social adversity, and maternal history. Both excitability and irritability factor scores in preschoolers predicted global functioning into the teen years and early adolescence, respectively. These findings underscore the importance of positive, as well as negative, affect dysregulation as early as the preschool years in predicting later psychopathology, which deserves both further study and clinical consideration.
22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.
Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.
This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.
The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.
The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.
This article discusses the contingencies and complexities of CRISPR. It outlines key problems regarding off-target effects and replication of experimental work that are important to consider in light of CRISPR’s touted ease of use and diffusion. In light of literature on the sociotechnical dimensions of the life sciences and biotechnology and literature on former bioweapons programs, this article argues that we need more detailed empirical case studies of the social and technical factors shaping CRISPR and related gene-editing techniques in order to better understand how they may be different from other advances in biotechnology — or whether similar features remain. This information will be critical to better inform intelligence practitioners and policymakers about the security implications of new gene-editing techniques.
In this study, we report the characterization of a 304L stainless steel cylindrical projectile produced by additive manufacturing. The projectile was compressively deformed using a Taylor Anvil Gas Gun, leading to a huge strain gradient along the axis of the deformed cylinder. Spatially resolved neutron diffraction measurements on the HIgh Pressure Preferred Orientation time-of-flight diffractometer (HIPPO) and Spectrometer for Materials Research at Temperature and Stress diffractometer (SMARTS) beamlines at the Los Alamos Neutron Science CEnter (LANSCE) with Rietveld and single-peak analysis were used to quantitatively evaluate the volume fractions of the α, γ, and ε phases as well as residual strain and texture. The texture of the γ phase is consistent with uniaxial compression, while the α texture can be explained by the Kurdjumov–Sachs relationship from the γ texture after deformation. This indicates that the material first deformed in the γ phase and subsequently transformed at larger strains. The ε phase was only found in volumes close to the undeformed material with a texture connected to the γ texture by the Shoji–Nishiyama orientation relationship. This allows us to conclude that the ε phase occurs as an intermediate phase at lower strain, and is superseded by the α phase when strain increases further. We found a proportionality between the root-mean-squared microstrain of the γ phase, dominated by the dislocation density, with the α volume fraction, consistent with strain-induced martensite α formation. Knowledge of the sample volume with the ε phase from the neutron diffraction analysis allowed us to identify the ε phase by electron back scatter diffraction analysis, complementing the neutron diffraction analysis with characterization on the grain level.
NGC 604 is by far the brightest HII nebula in the nearby spiral galaxy M33. The gas in this region has about the same metallicity as the gas in the Large Magellanic Cloud (Diaz et al. 1987). In this respect the physical conditions in this nebula may resemble those in 30 Doradus. A one arcmin field centred on the eastern part of the ionized nebula has been observed in CO(2-1) and CO(1-0) using the IRAM 30m antenna and the OVRO interferometer. In CO(1-0) the IRAM and the OVRO data have been combined to produce high resolution maps including the emission at low spatial frequencies. A CO(1-0) map at 7″ resolution (about 25 pc for the distance of M33) has been obtained; maps in both transitions at 12″ resolution have also been produced. The distribution of total line emission (see Figure 1) is characterized by two prominent clouds plus diffuse emission. These clouds are resolved with typical virial masses of a few 105 M⊙. The peak brightness is 8K and the velocity width ΔV1/2 8 km s-1. The CO(2-1)/CO(1-0) brightness temperature ratio is 0.7. Based on LVG models (e.g. Castet et al., 1990) we conclude that the density must be about or at least 1000 cm-3. The virial mass to CO luminosity ratio for these clouds is identical to the one for Galactic GMCs (Solomon et al., 1987). These two molecular clouds are located on the edge of an HI concentration along the HI ridge of a M33 spiral arm feature. From the comparison of sensitive radio continuum VLA maps and an Hα map (Viallefond et al., in preparation) we observe the counterpart of these gas concentrations in the distribution of the extinction; we conclude that one of the two molecular clouds, the brightest on the CO map in Figure 1, must be located inside the ionized halo of NGC 604; the position of this cloud also coincides with the peak of brightness on the near infrared map for the H2 lines obtained by Israel et al. (1990); part of the HI may be photodissociated molecular gas. We suggest that the intense radiation field in NGC 604 compensates the metallicity deficiency to give a NH2/WCO ratio similar to the Galactic one. The diffuse emission is detected over the entire field. The velocity fields as observed with the CO, the HI (data from Deul and van der Hulst, 1988), and the Hα (e.g. Hippelein and Fried, 1984) lines are very similar, the main characteristic is an East-West gradient unrelated with the general rotation of M33. High velocity molecular gas is also detected as a faint blue shifted wing of about 25 km s-1 on the global CO profile; its spatial distribution is diffuse. Finally double peaked profiles are observed in the vicinity of a large optical and radio continuum loop known to be associated with the presence of a Wolf-Rayet star. Obviously the kinematics is perturbed by the recent vigorous formation of massive stars in this unusually bright star forming region of M33.
Oceanographic instruments suspended beneath the Amery Ice Shelf, East Antarctica, have recorded sporadic pressure decreases of 10–20 dbar over a few days at three sites where basal marine ice growth is expected. We attribute these events to flotation due to platelet ice accretion on the instrument moorings. Some events were transient, rapidly returning to pre-event pressures, probably through dislodgement of loosely attached crystals. Driven by these pressure changes, temperatures recorded by the shallowest instruments (within 20 m of the shelf base) tracked in situ freezing temperatures during the events. These observations provide indirect evidence for the presence of frazil ice in the sub-ice-shelf mixed layer and for active marine ice accretion. At one site we infer that a dense layer of platelet ice ˜1.5 m thick was accreted to the ice shelf over a 50 day period. Following some permanent abrupt pressure decreases (which we interpret as due to the lodgement of the uppermost instrument at the ice-shelf base), altered background trends in pressure suggest compaction rates of 3–4 m a–1 for the accreted basal platelet layer. Attachment of platelet ice and resulting displacement of moorings has ramifications for project design and instrument deployment, and implications for interpretation of oceanographic data from sub-ice-shelf environments.
We report on the present status of the Lawrence Livermore AMS spectrometer, including sample throughput and progress towards routine 1% measurement capability for 14C, first results on other isotopes and experience with a multisample high-intensity ion source.
In 1969 radiocarbon dating facilities were established at the National Physical Research Laboratory of the C.S.I.R. in Pretoria (25° 43′ S Lat, 28° 21′ E Long; alt 1500 m). The counters are situated in an underground room built of selected concrete and covered by ca. 12 m earth. In this room, the nucleonic component of cosmic radiation is practically absent and the meson flux is reduced by a factor of 3.5 as compared to the surface at sea level in Groningen, Netherlands. A neutron monitor which registers 30 cpm on the surface, counts ca. 0.1 cpm in the underground room.
The palynological sequence of the Hula L07 core was previously correlated with the global oxygen isotope stages 3–5, based on a radiocarbon age determination and comparison with other Levantine paleoclimatological curves. An attempt was made to validate this correlation with Th/U dating. Unlike typical European peat, which is acidic, the soil pH of the Hula peat is mildly basic. Not only does this contribute to the oxidation of palynomorphs, but it also helps to preserve the carbonate material that can be a variable mixture of allogenic, endogenic, and authigenic components. Each component may represent a different degree of uranium series disequilibrium. The thorium (232Th) concentrations of the carbonate are low. Total digestion or acid leach of the sample may not always enable the proper correction for initial thorium. The dating derived from a NaOH-extraction of the organic material, while giving apparently better ages, also suffers from the presence of the carbonate admixture. It appears that, while 14C dating can be considered suitable for the younger portions of the core, techniques based upon the U-series may not be as efficacious in dating this important record of climatic change.
The LMC star R84 (-HDE 269227 -BR 18) belongs to the group of Ofpe/WN stars believed to be closely related to the Luminous Blue Variables. Support for such a relation comes from the spectral resemblance of these stars to AG Car during visual minimum, and from the observed outburst of the Ofpe/WN star R127.
The spectral analysis of R84 presented here is based on model calculations with the NLTE comoving-frame code described by Wessolowski et al. (1988) and references therein. The helium model atom was represented by 28 levels and hydrogen by 9 levels. The free model parameters were varied until the observed line profiles and the absolutely calibrated and dereddened continuum flux were reproduced. The comparison of the theoretical continuum flux distribution with the observed one yields a reddening of EB-V =0.1.
The diagnositic possibilities for identifying the ionizing source in symbiotic systems are explored. As possible sources we consider hot blackbodies and accretion discs. It turns out that main sequence accretors and hot blackbodies may have the same appearance in both, emission line and continuum flux distribution. However, UV continuum indices of models containing an accretion disc around a white dwarf are confined to a very small region, separated from main sequence accretors and blackbodies. Furthermore, if symbiotic systems containing a white dwarf accretor exist, they might be recognizable by strong emission in Fe X λ6374.
A model for a symbiotic system is presented which is not spherically symmetrical. The system consists of a cool, mass losing giant and a hot star. The stellar wind from the cool star is radiatively ionized by the hot companion, and the resulting nebular lines are emitted mainly close to the cool star. Due to the elliptical orbit, the line fluxes change with time because of the varying separation of the stars. The line profiles vary from symmetrical to asymmetrical, depending on the angle between the line of sight and the axis of symmetry. The calculated line profiles are compared with observed UV lines of the symbiotic star HBV 475.
In their study on C/N/O abundances in red giants, planetary nebulae, novae and symbiotic stars Nussbaumer, Schild, Schmid and Vogel (1988: Astron.Astrophys.198, 179) pointed out that among symbiotic stars HM Sge is quite exceptional, in that its C/N/O abundance ratios rather resemble those of novae and not of symbiotic stars.
In 1975 HM Sge brightened within a few months by at least 4m. The object has been observed in radio, visual, X-ray, and since 1978 with IUE. Here we show the changing level of activity in the UV. Figure 1 gives the FES (IUE fine error sensor) counts, representing an integrated flux at visual wavelengths. This flux shows a general decline with a secondary maximum in 1982. – Our mFES is at variance with the visual magnitude estimates given by Munari and Whitelock (1989: Mon.Not.Roy.astr.Soc. 237, 45p). They report high brightness up to at least the end of 1984.
The most commonly advocated models for explaining the outburst of symbiotic systems are thermonuclear runaways, modulated mass accretion through a disc, or accretion disc instabilities. We show that the onset of a strong stellar wind on the cool component can also produce the observed increase in luminosity.
Recently, large-scale trials of behavioural interventions have failed to show improvements in pregnancy outcomes. They have, however, shown that lifestyle support improves maternal diet and physical activity during pregnancy, and can reduce weight gain. This suggests that pregnancy, and possibly the whole periconceptional period, represents a ‘teachable moment’ for changes in diet and lifestyle, an idea that was made much of in the recent report of the Chief Medical Officer for England. The greatest challenge with all trials of diet and lifestyle interventions is to engage people and to sustain this engagement. With this in mind, we propose a design of intervention that aims simultaneously to engage women through motivational conversations and to offer access to a digital platform that provides structured support for diet and lifestyle change. This intervention design therefore makes best use of learning from the trials described above and from recent advances in digital intervention design.
Transition-metal dichalcogenides (TMDCs) are compounds consisting of a transition-metal M (Ti, Hf, Zr, V, Nb, Ta, Mo, W, Tc, Re, Pd, Pt) and chalcogen atoms X (S, Se, Te). There are approximately 60 compounds in the metal chalcogenide family, and two-thirds of them are in the form of layered structures where the in-plane bonds are strong (covalent), and the out-of-plane bonds are weak (van der Waals). This provides a means to mechanically or chemically thin (exfoliate) these materials down to a single atomic two-dimensional (2D) layer. While graphene, the 2D form of graphite, is metallic, the layered metal chalcogenides cover a wide range of electrical properties, from true metals (NbS2) and superconductors (TaS2) to semiconductors (MoS2) with a wide range of bandgaps and offsets. Multiple techniques are currently being developed to synthesize large-area monolayers, including alloys, and lateral and vertical heterostructures. The wide range of properties and the ability to tune them on an atomic scale has led to numerous applications in electronics, optoelectronics, sensors, and energy. This article provides an introduction to TMDCs, serving as a background for the articles in this issue of MRS Bulletin.
Dairy farms are under pressure to increase productivity while reducing environmental impacts. Effective fertilizer management practices are critical to achieve this. In the present study the effect of timing and rate of nitrogen (N) fertilizer application on pasture production and N losses, either via direct leaching of fertilizer N or indirectly through consumption of N in pasture and subsequent excretion via dairy cow grazing, was modelled. The Agricultural Production Systems Simulator (APSIM) was first tested with experimental data from N fertilizer response experiments conducted on a well-drained soil in the Waikato region of New Zealand. The model was then used in a 20-year simulation to investigate the effect of fertilizer management on the impacts on potential N leaching losses. Year-to-year variability was assessed by incorporating 20 years of climate data into the model. Modelling indicated that N fertilization at rates of 140 and 220 kg N/ha/year, applied in four split applications and avoiding application in winter months, could increase pasture yield on average by 2·2–3·0 t dry matter (DM)/ha (25–38%). There were some significant amounts of direct leaching in some years, related to environmental conditions. The maximum loss was as high as 61 kg N/ha at an N application rate of 220 kg N/ha/year, in a year with low pasture production and high rainfall following fertilizer application. In general, however, the risk of direct N leaching from applied fertilizer was low. It seems the main effect of N fertilization is to increase the risk of indirect N leaching, due to increased N intake and excretion. The modelling indicated that the major contribution to increased indirect N leaching risk was from the extra DM grown (more urine deposited per ha). Increased N concentration in the pasture due to fertilization and the resultant extra partitioning of excretal N to urine had only a minor effect on indirect leaching losses. The exception was N fertilizer applied in late winter/early spring (July), where fertilizer N (55 kg/ha) increased pasture N concentration by c. 25%, suggesting that the N concentration in urine patch areas could increase from c. 550 to 840 kg N/ha. Further measurements are required to test the hypothesis developed from the modelling that the main effect of N fertilizer on urinary N leaching is by increasing DM production rather than increasing pasture N concentration.
Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription–polymerase chain reaction. During October 2011–September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December–May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season.
In Chile, while dog rabies has decreased markedly over the last 30 years, bat rabies is still reported frequently. In order to shed new light on the spatiotemporal trends of these reports, we analysed active and passive data from years 1985 and 2012, which included 61 076 samples from 289 counties of Chile. We found that from 1994 to 2012, more than 15 000 bat samples were submitted for diagnostics through passive surveillance, 9·5% of which tested positive for rabies. By contrast, the prevalence of infection was only ~0·4% among the nearly 12 000 bat samples submitted through active surveillance. We found that the prevalence of dog rabies dropped steadily over the same period, with just a single confirmed case since 1998. None of the 928 samples from wild animals, other than bats, were positive for rabies. Although there has been only one confirmed case of human rabies in Chile since 1985, and a single confirmed case in a dog since 1998, bats remain a reservoir for rabies viruses. While active surveillance indicates that rabies prevalence is low in bat colonies, the high proportion of positive bats submitted through passive surveillance is a concern. To prevent human rabies, local public health agencies should increase research on the basic ecology of bats and the role of stray dogs and cats as potential rabies amplifiers.