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The COVID-19 pandemic triggered a migration of workforces to work from home. A key issue for academics was the implications for the ability to carve out ‘thinking time’ to engage in what we term sustained knowledge work, the type of work essential for producing research. We administered an employee survey to academics from seven Australian and seven Canadian Universities, receiving over 3000 responses. We report on both quantitative and qualitative findings from the survey, with a particular emphasis on the latter. The two countries displayed broadly similar patterns in responses, but these patterns were gendered in specific ways. We distinguished between episodic and sustained knowledge work and found the shift of the location for sustained knowledge work from the workplace to the home affected academics unevenly, with disproportionate negative impacts on women. There are implications for all knowledge workers: while gendered, domestic norms continue to exist, the sustained knowledge work that is critical to career advancement can become especially problematic for women knowledge workers.

AIM: Many adolescents who meet diagnostic criteria for an eating disorder do not self-identify as having a problem and may consequently be less likely to seek help. Extant research investigating self-identification has been limited to specific populations (ie, girls meeting criteria for bulimic-type eating disorders). This study investigated how self-identification varied across sex, eating disorder diagnoses, and the presence of extreme eating behaviours, and how self-identification was related to help-seeking in adolescents. METHODS: Participants included 1002 Australian school students (75.5% female, Mage = 15.14 years, SD = 1.40) who met DSM-5 diagnostic criteria for an eating disorder. An online survey assessed self-identification of having a body image problem, as well as sex, eating disorder diagnosis, extreme eating behaviours, help-seeking for a body image problem, and other potential correlates of self-identification (demographics, psychological distress, social function, weight and shape concerns). RESULTS: Approximately, 2 in 3 adolescents with an eating disorder self-identified as having a body image problem. Girls who met criteria for a major eating disorder diagnosis, and those engaging in extreme eating behaviours, were more likely to self-identify. When adjusting for covariates, only sex remained significantly associated with self-identification. Adolescents who self-identified were 2.71 times more likely to seek help for a body image problem, adjusting for covariates. CONCLUSIONS: Public health strategies ought to promote awareness regarding the different ways that body image problems might manifest among both girls and boys, as well as the potential gravity of such problems. Awareness among parents, teachers and primary care providers should also be considered.

BACKGROUND:: Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient. METHODS:: A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring. Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index >/=30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12-24 months of age. Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model. RESULTS:: The study included 85 509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98-1.06) and 1.20 (95% CI: 0.98-1.47) for hypertensive disorders; 1.09 (95% CI: 1.01-1.18) and 1.23 (95% CI: 1.07-1.43) for preeclampsia; 1.04 (95% CI: 0.97-1.13) and 1.24 (95% CI: 0.86-1.79) for diabetes; 1.08 (95% CI: 1.05-1.11) and 1.19 (95% CI: 1.12-1.26) for overweight; 1.12 (95% CI: 1.08-1.17) and 1.16 (95% CI: 0.97-1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P = 0.027). CONCLUSIONS:: Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ1–40 and not on the more pathogenic Aβ1–42. Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aβ levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman’s rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aβ1–40 and Aβ1–42 levels (beta=0.163, P<0.001; beta=0.446, P<0.001).This held in subjective memory complainers (SMC) (Aβ1–40; beta=0.208, P=0.017; Aβ1–42; beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) groups. In SMC, increased frequency of the APOE-ε4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ε4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=−0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR)=7.0, 95% confidence interval (CI)=2.1-23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (P<0.0001, test for trend), and regardless of signs of chronic solar damage. In contrast, no association with BRAF-negative melanomas was found (OR=1.0, 95% CI=0.6-1.6). No characteristics of subjects or melanomas, including age, nevus count, pigmentation, and melanoma thickness or location on chronically or intermittently sun-exposed body sites, substantially modified this association, although results could be affected by the small numbers in some categories. This study confirms that the known MC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations.

Copper K- edge EXAFS data for six polycrystalline cubic cluster compounds, {Cu-8[ S2P(OR)(2)](6)(mu(8)- S)} with R= Et, Pr-n, Pr-i, Bu-n, Bu-i and Am-i, show that the architecture of their Cu-8(S2P)(2)S cores is fairly rigid and independent of both length and branching of the alkyl chain, and that the structure of the cluster is maintained in acetone solution. Solid- state P-31 CP-MAS and static Cu-65 NMR data for {Cu-8[S2P(O-n Pr)(2)] 6(mu(8)- S)} and {Cu-8[S2P(OEt)(2)](6) mu(8)- S)} show similarities in the icosahedral O,O'- dialkyldithiophosphate shells and in the `cubic' copper cores in these cluster compounds. The crystal structure of {Cu-8[S2P(O-n Pr)(2)](6) (mu(8)- S)} was resolved using single- crystal X- ray diffraction., authorCount :8

Evidence from model organisms and clinical trials reveals that the random insertion of retrovirus-based vectors in the genome of long-term repopulating hematopoietic cells may increase self-renewal or initiate malignant transformation. Clonal dominance of nonmalignant cells is a particularly interesting phenotype as it may be caused by the dysregulation of genes that affect self-renewal and competitive fitness. We have accumulated 280 retrovirus vector insertion sites (RVISs) from murine long-term studies resulting in benign or malignant clonal dominance. RVISs (22.5%) are located in or near (up to 100 kb [kilobase]) to known proto-oncogenes, 49.6% in signaling genes, and 27.9% in other or unknown genes. The resulting insertional dominance database (IDDb) shows substantial overlaps with the transcriptome of hematopoietic stem/progenitor cells and the retrovirus-tagged cancer gene database (RTCGD). RVISs preferentially marked genes with high expression in hematopoietic stem/progenitor cells, and Gene Ontology revealed an overrepresentation of genes associated with cell-cycle control, apoptosis signaling, and transcriptional regulation, including major "stemness" pathways. The IDDb forms a powerful resource for the identification of genes that stimulate or transform hematopoietic stem/progenitor cells and is an important reference for vector biosafety studies in human gene therapy.

Severe combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of immunoglobulin (Ig) and T-cell receptor (TCR) gene segments. Inactivating mutations in RAG1 or RAG2 lead to a developmental block at early checkpoints in B- and T-cell development. SCID can be cured by hematopoietic stem cell transplantation, but an HLA-matched donor is not always available. For two types of SCID, ADA- SCID and X-linked SCID, gammaretrovirus-based gene therapy has proven a successful treatment. For my thesis, several aspects of T-cell development and gene therapy were studied. A feature all forms of SCID have in common, is the occurrence of a block in T-cell development. Therefore, one of the studies in my thesis aimed at gaining more detailed knowledge of normal human T-cell development. Subsets corresponding to consecutive stages of human T- cell development were isolated and their gene expression profile was correlated to the T-cell receptor (TCR) gene rearrangement status. This analysis resulted in the identification of candidate factors involved in regulation of TCR gene rearrangements. In one of the X-linked SCID gene therapy trials using hematopoietic stem cells, lymphoproliferations were observed in four patients. In two cases, insertion of the therapeutic vector was found near the T- ALL oncogene LMO2. We found that gammaretrovirus-driven overexpression LMO2, but not the therapeutic IL2RG gene resulted in a block in human T-cell development. HIV-based vectors have been shown to have a more favorable integration pattern then gammaretroviruses, and self-inactivating (SIN) versions of this transfer system have been developed. We tested the feasibility of RAG gene therapy using HIV-based SIN vectors. We evaluated RAG1 and RAG2 gene transfer into hematopoietic stem cells usin

Si-29, Al-27, H-1 and Na-23 solid-state magic-angle spinning (MAS) nuclear magnetic resonance (NMR) has been used to relate nominal composition, bonding character and compressive strength properties in aluminosilicate inorganic polymers (AIPs). The Si-29 chemical shift varies systematically with Si-to-Al ratio, indicating that the immediate structural environment of Si is altering with nominal composition. Fast H-1 MAS and Si-29 T (SiH)/T-1 rho relaxation measurements demonstrated that occluded pore H2O mobility within the disordered cavities is slow in comparison with H2O mobility characteristics observed within the ordered channel structures of zeolites. The Al-27 MAS NMR data show that the Al coordination remains predominantly 4-coordinate. In comparison with the Si-29 MAS data, the corresponding Al-27 MAS line shapes are relatively narrow, suggesting that the AlO4 tetrahedral geometry is largely unperturbed and the dominant source of structural disorder is propagated by large distributions of Si-O bond angles and bond lengths. Corresponding Na-23 MAS and multiple-quantum MAS NMR data indicate that Na speciation is dominated by distributions of hydration states; however, more highly resolved Na-23 resonances observed in some preparations supported the existence of short-range order. New structural elements are proposed to account for the existence of these Na resonances and an improved model for the structure of AIPs has also been proposed.

To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin- cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Ddelta2-Ddelta3 rearrangement occurs at the most immature CD34+CD38-CD1a- stage. TCRB rearrangement starts at the CD34+CD38+CD1a- stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTalpha) expression pattern show that human TCRbeta-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before.