Trends in Well-Being Among Youth in Australia, 2017-2022

Importance: Little is known about temporal trends in children's well-being and how the COVID-19 pandemic may have influenced the well-being of young Australians. Certain demographic groups may be more vulnerable to experiencing declines in well-being. Objective: To examine well-being trends over 6 consecutive years among South Australian students and explore the influence of sociodemographic characteristics. Design, setting, and participants: Longitudinal analyses of annual (2017 to 2022) cross-sectional data of students in grades 4 through 9 (n = 40 392 to 56 897 per year) attending South Australian government schools from the Well-being and Engagement Collection (WEC) census. Exposures: Calendar year (2017-2022) and sociodemographic characteristics (sex, school grade, parental education, language spoken at home, residential region) from school enrollment records. Main outcomes and measures: Students self-reported life satisfaction, optimism, happiness, cognitive engagement, emotional regulation, perseverance, worry, and sadness. Results: Over 6 years (2017 to 2022), a total of 119 033 students (mean [SD] age, 12.1 y; 51.4% male) participated in this study. Most well-being measures declined over time, with consistent worsening of well-being from 2020 onward. For example, compared with 2017, sadness was 0.26 (95% CI, 0.25-0.27) points higher in 2020 (standardized mean difference [SMD], 0.27) and remained elevated by more than 0.26 points (SMD, 0.27) in 2021 and 2022. At almost every time point, greatest well-being was reported by students of male sex (except cognitive engagement and perseverance), in earlier school grades, with highest parental education, speaking a language other than English at home, and residing in outer regional and remote settings (for satisfaction, optimism, and emotional regulation). Sociodemographic differences in well-being were generally consistent over time; however, sex differences widened from 2020 for all indicators except cognitive engagement and perseverance. For example, between 2017 and 2022, sadness increased by 0.27 (95% CI, 0.25-0.29) more points among females than males (SMD, 0.28). Conclusions and relevance: In this longitudinal analysis of annual census data, there were downward trends in students' well-being, especially since 2020. The largest sociodemographic disparities were observed for students of female sex, those in later school grades, and those with lowest parental education. Urgent and equitable support for the well-being of all young people, particularly those facing disparity, is imperative.Dorothea Dumuid, Ben Singh, Jacinta Brinsley, Rosa Virgara, Rachel G. Curtis, Sally Brinkman, Carol A. Mahe

Changes in diet, activity, weight, and wellbeing of parents during COVID-19 lockdown

The COVID-19 pandemic has dramatically impacted lifestyle behaviour as public health initiatives aim to “flatten the curve”. This study examined changes in activity patterns (physical activity, sedentary time, sleep), recreational physical activities, diet, weight and wellbeing from before to during COVID-19 restrictions in Adelaide, Australia. This study used data from a prospective cohort of Australian adults (parents of primary school-aged children; n = 61, 66% female, aged 41±6 years). Participants wore a Fitbit Charge 3 activity monitor and weighed themselves daily using Wi-Fi scales. Activity and weight data were extracted for 14 days before (February 2020) and 14 days during (April 2020) COVID-19 restrictions. Participants reported their recreational physical activity, diet and wellbeing during these periods. Linear mixed effects models were used to examine change over time. Participants slept 27 minutes longer (95% CI 9–51), got up 38 minutes later (95% CI 25–50), and did 50 fewer minutes (95% CI -69–-29) of light physical activity during COVID-19 restrictions. Additionally, participants engaged in more cycling but less swimming, team sports and boating or sailing. Participants consumed a lower percentage of energy from protein (-0.8, 95% CI -1.5–-0.1) and a greater percentage of energy from alcohol (0.9, 95% CI 0.2–1.7). There were no changes in weight or wellbeing. Overall, the effects of COVID-19 restrictions on lifestyle were small; however, their impact on health and wellbeing may accumulate over time. Further research examining the effects of ongoing social distancing restrictions are needed as the pandemic continues.Rachel G. Curtis, Timothy Olds, Ty Ferguson, Franc¸ois Fraysse, Dorothea Dumuid, Adrian Esterman ... et al

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

The structural basis of bacterial manganese import

Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese. However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation. The type II transporter has a tightly closed transmembrane channel due to "extracellular gating" residues that prevent water permeation or ion reflux. Below these residues, the channel contains a hitherto unreported metal coordination site, which is essential for manganese translocation. Mutagenesis of the extracellular gate perturbs manganese uptake, while coordination site mutagenesis abolishes import. These structural features are highly conserved in metal-specific ABC transporters and are represented throughout the kingdoms of life. Collectively, our results define the structure of PsaBC and reveal the features required for divalent cation transport.Stephanie L. Neville, Jennie Sjöhamn, Jacinta A. Watts, Hugo MacDermott-Opeskin, Stephen J. Fairweather, Katherine Ganio, Alex Carey Hulyer, Aaron P. McGrath, Andrew J. Hayes, Tess R. Malcolm, Mark R. Davies, Norimichi Nomura, So Iwata, Megan L. O’Mara, Megan J. Maher, Christopher A. McDevit

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

Selection of antigenically advanced variants of seasonal influenza viruses

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent se

Diversity in collaborative research communities: a multicultural, multidisciplinary thesis writing group in public health

Writing groups for doctoral students are generally agreed to provide valuable learning spaces for Ph.D. candidates. Here an academic developer and the eight members of a writing group formed in a Discipline of Public Health provide an account of their experiences of collaborating in a multicultural, multidisciplinary thesis writing group. We consider the benefits of belonging to such a group for Ph.D. students who are operating in a research climate in which disciplinary boundaries are blurring and where an increasing number of doctoral projects are interdisciplinary in nature; in which both academic staff and students come from enormously diverse cultural and language backgrounds; and in which teamwork, networking and collaboration are prized but not always proactively facilitated. We argue that doctoral writing groups comprising students from diverse cultural and disciplinary backgrounds can be of significant value for postgraduates who wish to collaborate on their own academic development to improve their research writing and communication skills; at the same time, such collaborative work effectively builds an inclusive, dynamic research community.Cally Guerin, Vicki Xafis, Diana V. Doda, Marianne H. Gillam, Allison J. Larg, Helene Luckner, Nasreen Jahan, Aris Widayati and Chuangzhou X

Two-loop O(GF2MH4){\rm O}\left(G_F^2M_H^4\right) corrections to the fermionic decay rates of the Higgs boson

We calculate the dominant ${\rm O}\left(G_F^2M_H^4\right)$ two-loop electroweak corrections to the fermi\-onic decay widths of a heavy Higgs boson in the Standard Model. Use of the Goldstone-boson equivalence theorem reduces the problem to one involving only the physical Higgs boson $H$ and the Goldstone bosons $w^\pm$ and $z$ of the unbroken theory. The two-loop corrections are opposite in sign to the one-loop electroweak corrections, exceed the one-loop corrections in magnitude for $M_H>1114\ {\rm GeV}$, and increase in relative magnitude as $M_H^2$ for larger values of $M_H$. We conclude that the perturbation expansion in powers of $G_FM_H^2$ breaks down for $M_H\approx 1100\ {\rm GeV}$. We discuss briefly the QCD and the complete one-loop electroweak corrections to $H\rightarrow b\bar{b}, \,t\bar{t}$, and comment on the validity of the equivalence theorem. Finally we note how a very heavy Higgs boson could be described in a phenomenological manner.Comment: 24 pages, RevTeX file, 4 figures in a separate compressed uuencoded Postscript file or available by mail on request. Fig. 1 not included see Figs. 1, 2 in Phys. Rev. D 48, 1061 (1993

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer

RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective. Lei et al. show that transcriptionally active estrogen receptor gene (ESR1) fusions identified from late-stage, treatment-refractory estrogen receptor-positive (ER+) breast cancer drive pan-endocrine therapy resistance and metastatic progression. Growth of breast tumors driven by ESR1 fusions at primary and metastatic sties can be suppressed with a CDK4/6 inhibitor