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Objectives: Farmers are faced with many stressors, along with numerous barriers to accessing traditional forms of mental health support. The ifarmwell online intervention was co-designed with farmers and is informed by Acceptance and Commitment Therapy to equip farmers with transferable coping strategies, particularly to help them cope with circumstances beyond their control. We aimed to evaluate the effect of ifarmwell on farmers’ short- and long-term distress and mental wellbeing. Methods: Australian farmers (21–73 years) who registered on www.ifarmwell.com.au completed measures at the commencement of module 1 (N = 228), the end of the intervention (N = 77) and 6-months post-intervention (N = 61). Primary outcomes included distress (Kessler Psychological Distress Scale) and mental wellbeing (Mental Health Continuum – Short Form). We also examined the relationship between distress, mental wellbeing, neuroticism (Quickscales-R) and ACT-based psychological mechanisms; psychological inflexibility (Acceptance and Action Questionnaire-II), cog-nitive fusion (Cognitive Fusion Questionnaire), believability of automatic thoughts (Automatic Thoughts Questionnaire-B), coping via acceptance (4 items from the situational COPE) and mind-fulness (Five Facet Mindfulness Questionnaire-Short Form). Secondary outcomes of acceptability (Client Satisfaction Questionnaire-8) and usability (System Usability Scale) were also explored. Results: Pre- to post-intervention, farmers’ distress decreased and mental wellbeing increased. These effects were maintained at 6-month follow-up. Changes in these outcomes were greatest for participants who entered the intervention with high baseline distress (^β= −0.59, 95%CI =[−0.70, −0.47]) and low mental wellbeing (^β= −0.33, 95%CI = [−0.47, −0.19]). Decreases in distress and increases in mental wellbeing were associated with decreases in psychological inflexibility, cognitive fusion, and believability of thoughts, and increases in coping via acceptance and mindfulness. Levels of satisfaction (M = 26.92/32) and usability (M = 84.70/100) were high, and 94.6% of participants said they would recommend ifarmwell to a friend in need of similar advice and tools. Conclusions: ifarmwell is an effective and usable intervention that is likely to help farmers reduce their levels of distress and improve their mental wellbeing, by improving their psychological flexibility, ability to focus on the present and accept things beyond their control, as well as by reducing the extent to which they believe unhelpful thoughts. Refereed/Peer-reviewed

Two parallel versions (A and B) of the Oxford Cognitive Screen (OCS) were developed in the United Kingdom (UK) as a stroke-specific screen of five key cognitive domains commonly affected post-stroke. We aimed to develop the Australian versions A and B (OCS-AU), including Australian cut-scores indicative of impairment. We hypothesised there to be no difference in performance between the UK and Australian normative data cohorts.Our multidisciplinary expert panel used the UK pre-defined process to develop the OCS-AU versions A and B. We then conducted a cross-sectional normative study. We purposively recruited community-dwelling, Australian-born, and educated adults; with no known cognitive impairment; representative of age, sex, education level, and living location; at seven sites (four metropolitan, three regional) across four Australian states. Participants completed one or both OCS-AU versions in a randomised order. Australian cohorts were compared with the corresponding UK cohorts for demographics using Pearson's chi-squared test for sex and education, and Welch two-sample t test for age. For the cut-scores indicating cognitive impairment, the fifth (95th) percentiles and group mean performance score for each scored item were compared using Welch two-sample t tests. The pre-defined criteria for retaining OCS cut-scores had no statistically significant difference in either percentile or group mean scores for each scored item.Participants (n = 83) were recruited: fifty-eight completed version A [age (years) mean = 61,SD = 15; 62% female], 60 completed version B [age (years) mean = 62,SD = 13, 53% female], and 35 completed both [age (years) mean = 64,SD = 11, 54% female]. Education was different between the cohorts for version B (12 years, p = 0.002). Cut-scores for all 16 scored items for the OCS-AU version B and 15/16 for version A met our pre-defined criteria for retaining the OCS cut scores.The OCS-AU provides clinicians with an Australian-specific, first-line cognitive screening tool for people after stroke. Early screening can guide treatment and management.

Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 ( ω-3) PUFAs and astaxanthin, may be a safe and effective alternative treatment.This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers.Healthy adults (n = 235, 40-65 y old, BMI18.5 to35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0-100). Outcomes were assessed at baseline, 3 mo, and 6 mo.Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: -5.18; 95% CI: -10.0, -0.32; P = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: -6.45; 95% CI: -12.1, -0.9 and -4.67; 95% CI: -9.26, -0.05, respectively; P 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups.Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA.This trial was registered at clinicaltrials.gov as NCT03483090.

To determine whether functional lung avoidance based onPatients with stage III non-small cell lung cancer (or oligometastatic disease treated with curative intent) undergoing CCRT with at least a 10 pack-year smoking history were eligible. Patients underwent pretreatmentTwenty-seven patients were randomized before the trial was closed due to slower-than-expected accrual, with 11 randomized to the standard arm and 16 to the avoidance arm. Baseline patient characteristics were well-balanced. At 3 months post-RT, the mean ± SD LCS scores were 17.4 ± 2.8 versus 17.3 ± 6.1 for the standard and avoidance arms, respectively (P = .485). A clinically meaningful, prespecified decline of ≥3 points in the LCS score was observed in 50% (4/8) in the standard arm and 33% (4/12) in the avoidance arm (P = .648). Two patients in each arm developed grade ≥2 radiation pneumonitis, with no grade ≥4 toxicities.Although this trial did not reach full accrual, QOL scores were very similar between arms. Due to the scarcity of

Introduction To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure. Materials and Methods Medical records were systematically reviewed to identify veterans that indicated antimalarial medication use. Linear regression was performed to examine associations between mefloquine/antimalarial exposure and health outcomes. The mefloquine-exposed group was further compared with normative populations for the same health outcomes. Results In the adjusted models, no significant differences were noted between the two exposure groups and the unexposed group for any of the health measures (P-value > 0.05). When compared to normative population samples, the mefloquine-exposed group had poorer health and greater neurobehavioral symptom severity or cognitive complaints. Conclusion This study suggests that mefloquine use by veterans referred for intensive evaluation of their military deployment exposures and health was not associated with increased, long-term, neurocognitive/psychiatric symptoms compared to unexposed veterans.

Blood-based liquid biopsies examining circulating tumour DNA (ctDNA) have increasing applications in non-small cell lung cancer (NSCLC). Limitations in sensitivity remain a barrier to ctDNA replacing tissue-based testing. We hypothesized that testing immediately after starting treatment would yield an increased abundance of ctDNA in plasma because of tumor lysis, allowing for the detection of genetic alterations that were occult in baseline testing.Three prospective cohorts of patients with stage III/IV NSCLC were enrolled. Cohort 1 (C1) contained patients starting platinum doublet chemoradiation (n = 10) and cohort 2 (C2) initiating platinum doublet cytotoxic chemotherapy ± immunotherapy (n = 10). Cohort 3 (C3) contained patients receiving palliative radiation. Two baseline samples were collected. In C1 and C2, subsequent samples were collected 3, 6, 24 and 48 h post initiation of chemotherapy. Patients in C3 had samples collected immediately prior to the next three radiotherapy fractions. Samples were analyzed for ctDNA using the 36-gene amplicon-based NGS Inivata InVisionFirst®-Lung assay.A total of 40 patients were enrolled. Detectable ctDNA was present at baseline in 32 patients (80%), 4 additional patients (50%) had detectable ctDNA in post-treatment samples. Seven patients with detectable ctDNA at baseline (23%) had new genetic alterations detected in post-treatment samples. Mutant molecule numbers increased with treatment in 24 of 31 (77%) pts with detectable ctDNA. ctDNA levels peaked a median of 7 h (IQR:2-26 h) after the initiation of chemotherapy and a median of 2 days (IQR:1-3 days) after radiation was commenced.ctDNA levels increase in the hours to days after starting treatment. ctDNA testing in the acute post-treatment phase can yield results that were not evident in pre-treatment testing. Application of this principle could improve ctDNA utility as an alternate to tissue-based testing and improve sensitivity for the detection of treatment-resistant clones.(NCT03986463).

Results of lipid association analyses

Supplementary Figures S1-S6

Patient and sample clinical characteristics

Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting.Significance:This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.

Materials with specific electromagnetic properties are increasingly used for the realization of passive components. Therefore, electromagnetic characterization is a priority to know these materials properties. This study focuses on the electromagnetic characterization of 10 nm maghemite ferrofluid doped sol-gel using a resonant cavity method. We deposited the sol-gel by dipping/removal on an alumina substrate in order to make measurements on the cavity to determine the complex permittivity and permeability. Two studies were carried out; the first consisted in varying the doped sol-gel thickness of layers of the same concentration in the realization of samples; and the second consisted in varying the volume concentration of ferrofluid according to the matrix dimensions. The first study showed that the dielectric constants do not vary with the thickness of the magnetic sol-gel layers. In the second study, measurements also showed that the gyromagnetic resonance is the same for all samples regardless of the ferrofluid volume concentration.

Objective To determine the association of combined parental preconception overweight and obesity on infant birthweight. Design Retrospective study of fresh in vitro fertilization or intracytoplasmic sperm injection cycles (2009–2017). Setting Repromed, South Australia, assisted reproductive technology clinic. Patients Couples undergoing in vitro fertilization/intracytoplasmic sperm injection insemination with their own gametes and transfer of a fresh single blastocyst (N = 1,778). Intervention(s) None. Main Outcome Measures Parental body mass index (BMI) was recorded prior to cycle initiation. Infant birthweight was recorded at delivery. The impact of parental obesity and their interaction on first singleton term (≥37 weeks’ gestation) birthweight was assessed using linear regressions assessing nonlinearity and a pairwise linear interactions. Results In the base model where parental BMI is assumed linear, there was strong evidence for higher birthweight with increasing maternal BMI (11.2 g per maternal kg/m2; 95% confidence interval, 7.2, 15.1) but not paternal BMI. The inclusion of a pairwise linear interaction indicated that paternal BMI attenuates the positive association between maternal BMI and infant birthweight (interaction −0.88; 95% confidence interval, −1.49, −0.27). The inclusion of nonlinear maternal BMI terms did not change the conclusions. Conclusions Increases in the mean infant birthweight associated with maternal obesity are attenuated when the father is obese. While maternal BMI contributed more to the mean infant birthweight than paternal BMI, a couple-centered approach to preconception health advice is recommended, given the documented relationships between parental obesity and childhood weight beyond infancy. Further studies in both assisted reproductive technology and general population cohorts assessing the parental BMI interaction on infant birthweight are warranted.

Calibrating network analyzer is still an issue for bended access port devices (devices with access). Bended accesses can give additional errors which are taken into account by using a new design standards of Vector Network Analyzer (VNA) calibration. This Thru-Reflect-Line calibration technique is computed from ABCD parameters that easily allow to remove the bended port effects. This approach is based on the assumption that the Vector Network Analyzer error boxes can be considered as passive system. Furthermore, the method can be applied for de-embedding devices with bended accesses. This calibration and de-embedding technique could be applied, for example, to a coplanar circulator or a power divider measurement which have access lines at 120° from each other.

Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone-fold domain (HFD)-containing proteins forming three histone-fold (HF) pairs, to which the double HFD-containing SUPT3H adds one HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that (i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H, (ii) SUPT3H is not essential for mESC survival, but required for their growth and self-renewal, and (iii) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.

BACKGROUND Background: Only a minority of adult males who experience depression or anxiety receive any formal help from a healthcare professional for these issues. While psychotherapeutic e-mental health interventions may circumvent or reduce many of the barriers males experience when accessing mental health care, the effects of these interventions in male populations have not been evaluated. OBJECTIVE Objectives: (1) Synthesise the characteristics of psychotherapeutic e-mental health interventions for depression or anxiety that have been trialled and evaluated in male populations; (2) synthesise and meta-analyse the effects of these interventions on depression and anxiety outcomes in males, including examining the influence of participant, intervention, and study characteristics. METHODS Methods: Systematic searches (January 2000-October 2020) of six online research databases, manual reference list searching, and citation searches of included articles. Study quality was assessed using the Qualsyst tool, with a minimum total score of 0.55 prespecified for inclusion. Data were narratively synthesised and, where possible, meta-analysed. RESULTS Results: Seven papers comprising 552 male participants were included. A total of 177 studies were excluded because although they met all other inclusion criteria, they did not present analysable data on male participants. With a lowest total score of 0.85, study quality was high and no exclusions were made due to poor quality. Four studies used a single-arm pre-post design and three were randomised controlled trials (all with inactive/care as usual control conditions); five studies were focused on treating existing symptoms, while two focused on prevention. The seven studied interventions varied in content, length, and format. Only one intervention was classified as gender sensitive, having been designed specifically for male needs. All of the studies used non-gendered, self-report symptom measures to measure the effects of their intervention. All three randomised controlled trials detected no post-trial difference in depression symptoms between male intervention and male control participants. All four treatment studies presenting pre-post data reported post-intervention improvements in depression or social anxiety symptoms; this was supported by our meta-analysis of the two pre-post design depression treatment studies, which found a medium-sized, positive effect of treatment interventions on depression symptoms in pre-post data (g=0.64, p CONCLUSIONS Conclusions: Limited data indicate that psychotherapeutic e-mental health treatment interventions resulted in pre- to post-intervention improvements in male depression symptoms; superior outcomes were not seen when compared to inactive/care as usual control conditions. There is urgent need for consideration of gender and sex throughout the development, evaluation, and dissemination of these interventions for males, and for additional information on their effects. CLINICALTRIAL

Time-restricted feeding (TRF) initiated early during the dark phase prevents the metabolic consequences of a high-fat diet in rodent models. However, the metabolic consequences of delaying the initiation of TRF, akin to breakfast skipping in humans, is unclear. We assigned 8-week-old male C57BL/6J mice (n = 192) to chow or high-fat diet ad libitum (AL) for 4 weeks, before randomization to continue AL or 10 h of TRF, initiated at lights off (TRFe) or 4-h after lights off (TRFd) for a further 8 weeks. Oral glucose tolerance tests (1 g/kg), metabolic monitoring and body composition by echoMRI were performed, and tissues were collected at six time points. TRF reduced weight and fat mass vs AL, with a greater reduction in TRFe vs TRFd. TRF improved glucose tolerance and protected mice from high-fat diet-induced hepatosteatosis vs AL, with no difference between TRFe and TRFd. TRF increased the amplitude of Bmal1, Cry1, Per2, Nampt, and Nocturnin mRNA levels in liver. A phase delay in Bmal1, Cry1, Per2, Reverbα, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight benefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the translational potential of this dietary approach in humans.