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Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI <18·5 kg/m2 were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VM v. LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or D2O. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI −0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or D2O but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients.
Techniques are presented whereby X-ray spectrographic analyses are carried out on alloys and metallurgical products which enter the Laboratory in the form of drillings, millings, or filings. The techniques described include direct analysis, with and without internal standards. Analysis of high temperature alloys without a aeries of chemically analysed standards by these techniques have greatly extended the usefulness of the X-ray spectrograph.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
We report major new insights from recent research at the Powars II Paleoindian red ocher quarry (48PL330). We salvaged more than 7,000 artifacts from Powars II between 2014 and 2016 by screening redeposited sediment from the talus slope below the intact portion of the site. Clovis artifacts dominate the diagnostic artifact assemblage, including 53 Clovis points, 33 preforms, and artifacts associated with a previously unrecognized blade core industry. We report the first radiocarbon dates from the site, determined from dating bone tools, which indicate Cody-aged use (ca. >10,000 cal BP). Further, salvage efforts discovered a previously unknown toolstone source from which many of the Clovis artifacts were produced. The Powars II Clovis points most resemble early Paleoindian points from the far Northern Plains and were likely both produced and discarded in the red ocher quarry after hunting, as evidenced by preform production and the presence of impact fractures on many used points. Given these production and discard patterns, Powars II holds some of the best evidence archaeologists currently have for Paleoindian ritualism related to hunting.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
Because of the metastability of the 23S level of He I, a variety of effects can change the line strengths from pure recombination values in Seyfert galaxies (see Feldman and MacAlpine 1978). This occurs because the population which builds up in the 23S level can be collisionally excited to the 23P level, enhancing λ10830. The expected ratios of λ10830/λ5876 can be altered by internal or external reddening and vary with temperature, density and optical depth.
Since the very beginning of the Itapetinga 45-ft antenna operations in 1971, there were plans to use it as a southern hemisphere VLBI terminal for high north-south resolution. The first successful VLBI tests were performed on water vapor lines in cooperation with Haystack Observatory in 1978 in one of the last runs using the MkI system. This cooperation led to the construction of a MkII terminal for Itapetinga years later (1981–1983). Astrophysical VLBI runs have been carried out since 1984, with the cooperation of Caltech, producing maps of unique resolution on stronger quasars, especially on 3C273 whose evolution has been followed since then. Recently, Bonn joined the collaboration in astrophysical VLBI programs. Itapetinga also participated successfully in geodetic surveys, and in the Vega-Venus mission, in collaboration with JPL and French organizations CNES, Observatoire de Paris and IGN. Plans for continuation and expansion of the Itapetinga VLBI participation in international efforts depend strongly on support to maintain and upgrade instrumentation at the Brazilian Radio Observatory.
Adélie penguins (Pygoscelis adeliae) are responding to ocean–climate variability throughout the marine ecosystem of the western Antarctic Peninsula (WAP) where some breeding colonies have declined by 80%. Nuclear and mitochondrial DNA (mtDNA) markers were used to understand historical population genetic structure and gene flow given relatively recent and continuing reductions in sea ice habitats and changes in numbers of breeding adults at colonies throughout the WAP. Genetic diversity, spatial genetic structure, genetic signatures of fluctuations in population demography and gene flow were assessed in four regional Adélie penguin colonies. The analyses indicated little genetic structure overall based on bi-parentally inherited microsatellite markers (FST =-0.006–0.004). No significant variance was observed in overall haplotype frequency (mtDNA ΦST =0.017; P=0.112). Some comparisons with Charcot Island were significant, suggestive of female-biased philopatry. Estimates of gene flow based on a two-population coalescent model were asymmetrical from the species’ regional core to its northern range. Breeding Adélie penguins of the WAP are a panmictic population and hold adequate genetic diversity and dispersal capacity to be resilient to environmental change.
Żabińskiite, ideally Ca(Al0.5Ta0.5)(SiO4)O,
was found in a Variscan granitic pegmatite at Piława Górna, Lower Silesia,
SW Poland. The mineral occurs along with (Al,Ta,Nb)- and (Al,F)-bearing
titanites, a pyrochlore-supergroupmineral and a K-mica in compositionally
inhomogeneous aggregates, ∼120 μm × 70 μm in size, in a fractured crystal of
zircon intergrown with polycrase-(Y) and euxenite-(Y). Żabińskiite is
transparent, brittle, brownish, with a white streak, vitreous lustre and a
Mohs hardness of ∼5. The calculated density for the refined crystal is equal
to 3.897 g cm–3, but depends strongly on composition. The mineral
is non-pleochroic, biaxial (–), with mean refractive indices ≥1.89. The
mol.% Ca[Al0.5(Ta,Nb)0.5](SiO4)O; is close
in composition to previously described synthetic material. Żabińskiite is
triclinic (space group symmetry A1) and has unit-cell
parameters a = 7.031(2) Å, b = 8.692(2)
Å,c = 6.561(2) Å, α = 89.712(11)°, β = 113.830(13)°, γ =
90.352(12)° and V = 366.77 (11) Å3. It is
isostructural with triclinic titanite and bond-topologically identical with
titanite and other minerals of the titanite group.Żabińskiite crystallized
along with (Al,Ta,Nb)-bearing titanites at increasing Ti and Nb, and
decreasing Ta activities, almost coevally with polycrase-(Y) and
euxenite-(Y) from Ca-contaminated fluxed melts or early hydrothermal
The concept of information has penetrated almost all areas of human inquiry, from physics, chemistry, and engineering through biology to the social sciences. And yet its status as a physical entity remains obscure. Traditionally, information has been treated as a derived or secondary concept. In physics especially, the fundamental bedrock of reality is normally vested in the material building blocks of the universe, be they particles, strings, or fields. Because bits of information are always instantiated in material degrees of freedom, the properties of information could, it seems, always be reduced to those of the material substrate. Nevertheless, over several decades there have been attempts to invert this interdependence and root reality in information rather than matter. This contrarian perspective is most famously associated with the name of John Archibald Wheeler, who encapsulated his proposal in the pithy dictum ‘it from bit?’ (Wheeler, 1999).
In a practical, everyday sense, information is often treated as a primary entity, as a ‘thing in its own right’ with a measure of autonomy; indeed, it is bought and sold as a commodity alongside gas and steel. In the life sciences, informational narratives are indispensable: biologists talk about the genetic code, about translation and transcription, about chemical signals and sensory data processing, all of which treat information as the currency of activity, the ‘oil’ that makes the ‘biological wheels go round’. The burgeoning fields of genomic and metagenomic sequencing and bioinformatics are based on the notion that informational bits are literally vital. But beneath this familiar practicality lies a stark paradox. If information makes a difference in the physical world, which it surely does, then should we not attribute to it causal powers? However, in physics causation is invariably understood at the level of particle and field interactions, not in the realm of abstract bits (or qubits, their quantum counterparts). Can we have both? Can two causal chains coexist compatibly? Are the twin narratives of material causation and informational causation comfortable bedfellows? If so, what are the laws and principles governing informational dynamics to place alongside the laws of material dynamics?