Examine the effectiveness of specific modes of exercise training in non-specific chronic low back pain (NSCLBP).
Network meta-analysis (NMA).
MEDLINE, CINAHL, SPORTDiscus, EMBASE, CENTRAL.
Exercise ...training randomised controlled/clinical trials in adults with NSCLBP.
Among 9543 records, 89 studies (patients=5578) were eligible for qualitative synthesis and 70 (pain), 63 (physical function), 16 (mental health) and 4 (trunk muscle strength) for NMA. The NMA consistency model revealed that the following exercise training modalities had the highest probability (surface under the cumulative ranking (SUCRA)) of being best when compared with true control: Pilates for pain (SUCRA=100%; pooled standardised mean difference (95% CI): -1.86 (-2.54 to -1.19)), resistance (SUCRA=80%; -1.14 (-1.71 to -0.56)) and stabilisation/motor control (SUCRA=80%; -1.13 (-1.53 to -0.74)) for physical function and resistance (SUCRA=80%; -1.26 (-2.10 to -0.41)) and aerobic (SUCRA=80%; -1.18 (-2.20 to -0.15)) for mental health. True control was most likely (SUCRA≤10%) to be the worst treatment for all outcomes, followed by therapist hands-off control for pain (SUCRA=10%; 0.09 (-0.71 to 0.89)) and physical function (SUCRA=20%; -0.31 (-0.94 to 0.32)) and therapist hands-on control for mental health (SUCRA=20%; -0.31 (-1.31 to 0.70)). Stretching and McKenzie exercise effect sizes did not differ to true control for pain or function (p>0.095; SUCRA<40%). NMA was not possible for trunk muscle endurance or analgesic medication. The quality of the synthesised evidence was low according to Grading of Recommendations Assessment, Development and Evaluation criteria.
There is low quality evidence that Pilates, stabilisation/motor control, resistance training and aerobic exercise training are the most effective treatments, pending outcome of interest, for adults with NSCLBP. Exercise training may also be more effective than therapist hands-on treatment. Heterogeneity among studies and the fact that there are few studies with low risk of bias are both limitations.
Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate ...genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why historical candidate gene studies did not achieve their primary aims is inadequate statistical power. However, the considerable efforts embodied in these early studies unquestionably set the stage for current successes in genomic approaches to schizophrenia.
Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations ...(CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for SCZ CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with SCZ using a Swedish national sample (4719 cases and 5917 controls). High-confidence CNV calls were generated using genotyping array intensity data, and their effect on risk of SCZ was measured. Our data confirm increased burden of large, rare CNVs in SCZ cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio=4.16, P=0.018), previously associated with autism and mental retardation but not SCZ. Intriguingly, gene set association analyses implicate biological pathways previously associated with SCZ through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500 kb) in genes present in the postsynaptic density, in genomic regions implicated via SCZ genome-wide association studies and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry--genome-wide screens for CNVs, common variation and exonic variation--are converging on similar sets of pathways and/or genes.
Development of the African Middle Stone Age (MSA) before 300 thousand years ago (ka) raises the question of how environmental change influenced the evolution of behaviors characteristic of early
We ...use temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie Basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a dramatically different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. As early as 615 ka, aspects of Acheulean technology in this region imply that greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.
ABSTRACT We present 0 4 resolution extinction-independent distributions of star formation and dust in 11 star-forming galaxies (SFGs) at z = 1.3-3.0. These galaxies are selected from sensitive ...blank-field surveys of the 2′ × 2′ Hubble Ultra-Deep Field at λ = 5 cm and 1.3 mm using the Karl G. Jansky Very Large Array and Atacama Large Millimeter/submillimeter Array. They have star formation rates (SFRs), stellar masses, and dust properties representative of massive main-sequence SFGs at z ∼ 2. Morphological classification performed on spatially resolved stellar mass maps indicates a mixture of disk and morphologically disturbed systems; half of the sample harbor X-ray active galactic nuclei (AGNs), thereby representing a diversity of z ∼ 2 SFGs undergoing vigorous mass assembly. We find that their intense star formation most frequently occurs at the location of stellar-mass concentration and extends over an area comparable to their stellar-mass distribution, with a median diameter of 4.2 1.8 kpc. This provides direct evidence of galaxy-wide star formation in distant blank-field-selected main-sequence SFGs. The typical galactic-average SFR surface density is 2.5 M yr−1 kpc−2, sufficiently high to drive outflows. In X-ray-selected AGN where radio emission is enhanced over the level associated with star formation, the radio excess pinpoints the AGNs, which are found to be cospatial with star formation. The median extinction-independent size of main-sequence SFGs is two times larger than those of bright submillimeter galaxies, whose SFRs are 3-8 times larger, providing a constraint on the characteristic SFR (∼300 M yr−1) above which a significant population of more compact SFGs appears to emerge.
ABSTRACT
We report on precise Doppler measurements of L231-32 (TOI-270), a nearby M dwarf (d = 22 pc, M⋆ = 0.39 M⊙, R⋆ = 0.38 R⊙), which hosts three transiting planets that were recently discovered ...using data from the Transiting Exoplanet Survey Satellite (TESS). The three planets are 1.2, 2.4, and 2.1 times the size of Earth and have orbital periods of 3.4, 5.7, and 11.4 d. We obtained 29 high-resolution optical spectra with the newly commissioned Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations (ESPRESSO) and 58 spectra using the High Accuracy Radial velocity Planet Searcher (HARPS). From these observations, we find the masses of the planets to be 1.58 ± 0.26, 6.15 ± 0.37, and 4.78 ± 0.43 M⊕, respectively. The combination of radius and mass measurements suggests that the innermost planet has a rocky composition similar to that of Earth, while the outer two planets have lower densities. Thus, the inner planet and the outer planets are on opposite sides of the ‘radius valley’ – a region in the radius-period diagram with relatively few members – which has been interpreted as a consequence of atmospheric photoevaporation. We place these findings into the context of other small close-in planets orbiting M dwarf stars, and use support vector machines to determine the location and slope of the M dwarf (Teff < 4000 K) radius valley as a function of orbital period. We compare the location of the M dwarf radius valley to the radius valley observed for FGK stars, and find that its location is a good match to photoevaporation and core-powered mass-loss models. Finally, we show that planets below the M dwarf radius valley have compositions consistent with stripped rocky cores, whereas most planets above have a lower density consistent with the presence of a H-He atmosphere.
Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), ...nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960–2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr−1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr−1. Over the period 2013–2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000–2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m−2 (5–95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m−2), CO2 (34.3 mW m−2), and NOx (17.5 mW m−2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m−2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.
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•Global aviation warms Earth's surface through both CO2 and net non-CO2 contributions.•Global aviation contributes a few percent to anthropogenic radiative forcing.•Non-CO2 impacts comprise about 2/3 of the net radiative forcing.•Comprehensive and quantitative calculations of aviation effects are presented.•Data are made available to analyze past, present and future aviation climate forcing.
A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with ...schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams-Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 × 10⁻⁶. This was largely explained by enrichment for members of the N-methyl-D-aspartate receptor (NMDAR) (P=4.24 × 10⁻⁶) and neuronal activity-regulated cytoskeleton-associated protein (ARC) (P=3.78 × 10⁻⁸) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia.
1. Fundamental ecological research is both intrinsically interesting and provides the basic knowledge required to answer applied questions of importance to the management of the natural world. The ...100th anniversary of the British Ecological Society in 2013 is an opportune moment to reflect on the current status of ecology as a science and look forward to high-light priorities for future work. 2. To do this, we identified 100 important questions of fundamental importance in pure ecology. We elicited questions from ecologists working across a wide range of systems and disciplines. The 754 questions submitted (listed in the online appendix) from 388 participants were narrowed down to the final 100 through a process of discussion, rewording and repeated rounds of voting. This was done during a two-day workshop and thereafter. 3. The questions reflect many of the important current conceptual and technical pre-occupations of ecology. For example, many questions concerned the dynamics of environmental change and complex ecosystem interactions, as well as the interaction between ecology and evolution. 4. The questions reveal a dynamic science with novel subfields emerging. For example, a group of questions was dedicated to disease and micro-organisms and another on human impacts and global change reflecting the emergence of new subdisciplines that would not have been foreseen a few decades ago. 5. The list also contained a number of questions that have perplexed ecologists for decades and are still seen as crucial to answer, such as the link between population dynamics and life-history evolution. 6. Synthesis. These 100 questions identified reflect the state of ecology today. Using them as an agenda for further research would lead to a substantial enhancement in understanding of the discipline, with practical relevance for the conservation of biodiversity and ecosystem function.
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After ...follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.
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