Depression is the leading cause of disability worldwide(1). The microbiota-gut-brain axis may play a role in the aetiology of depression, and probiotics show promise for improving mood and depressive state(2). Further evidence is required to support mechanisms and in high-risk populations, such as those with sub-threshold depression (which may be 2-3 times more prevalent than diagnosed depression)(3). The aims were to assess the efficacy of a probiotic compared with placebo in reducing the severity of depressive symptoms in participants with subthreshold depression, and to investigate potential mechanistic markers of inflammatory, antioxidant status and stress response. A double-blind, randomised, placebo-controlled trial was conducted in participants meeting diagnosis of subthreshold depression (DSM-5); aged 18-65 years; ≥18.5 kg/m2 body mass index; not taking antidepressants, centrally acting medications, probiotics nor antibiotics for at least 6 weeks. The probiotic (4 × 109 AFU/CFU, 2.5 g freeze-dried powder containing Lactobacillus fermentum LF16 (DSM26956), L. rhamnosus LR06 (DSM21981), L. plantarum LP01 (LMG P-21021), Bifidobacterium longum BL04 (DSM 23233)) or placebo was taken daily for 3-months. Data was collected at 3 study visits (pre-, mid- (6 weeks), post-intervention). Self-reported questionnaires measured psychological symptoms (Beck Depression Inventory, BDI; Hospital Anxiety Depression Scale, HADS) and quality of life. Blood and salivary samples were collected for biomarkers including cortisol awakening response (CAR). General linear models examined within-group and between-group differences across all time points. Thirty-nine participants completed the study (n = 19 probiotic; n = 20 placebo) using intention-to-treat analysis. The probiotic group decreased in BDI score by −6.5 (95% CI −12.3; −0.7) and −7.6 (95% CI −13.4; −1.8) at 6 and 12 weeks, respectively. The HADS-A score decreased in the probiotic group by −2.8 (95% CI −5.2; −0.4) and −2.7 (95% CI −5.1; −0.3) at 6 and 12, respectively. The HADS-D score decreased in the probiotic group by −3.0 (95% CI −5.4; −0.7) and −2.5 (−4.9; −0.2) at 6 and 12 weeks of intervention, respectively. No between group differences were found. There were no changes in perceived stress or quality of life scores. The probiotic group had reduced hs-CRP levels (7286.2 ± 1205.8 ng/dL vs. 5976.4 ± 1408.3; P = 0.003) and increased total glutathione (14.2 ± 8.9 ng/dL vs. 9.3 ± 4.7; P = 0.049) compared to placebo, post intervention. Lower levels of CAR were found in the probiotic compared to placebo (−0.04 ± 0.17 μg/dL vs. 0.16 ± 0.25; P = 0.009). A significant reduction in depressive symptoms and anxiety was observed within the probiotic group only. These results were supported by improvements observed in biomarkers, suggesting probiotics may improve psychological wellbeing in adults experiencing sub-threshold depression, by potential pathways involved in central nervous system homeostasis and inflammation. Future analyses are required to understand changes within the intestinal microbiota and to clarify how their metabolites facilitate emotional processing.

Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many “omics” factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All five msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study’s success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the lack of agreement regarding the definition of aerosol-generating procedures and potential risk to healthcare personnel. We convened a group of Massachusetts healthcare epidemiologists to develop consensus through expert opinion in an area where broader guidance was lacking at the time.

Hospitals are increasingly consolidating into health systems. Some systems have appointed healthcare epidemiologists to lead system-level infection prevention programs. Ideal program infrastructure and support resources have not been described. We informally surveyed 7 healthcare epidemiologists with recent experience building and leading system-level infection prevention programs. Key facilitators and barriers for program structure and implementation are described.

While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts $z > 6$ , their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared $K_{\rm s}$ -band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately $1200\ \mathrm{deg}^2$ . Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at $z=5.55$ , with another source potentially at $z \sim 8$ . We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep $K_{\rm s}$ -band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions $K_{\rm s}$ -band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at $z \gtrsim 6.5$ .

This is the first article in a two-part series describing subject and family perspectives from the central thalamic deep brain stimulation for the treatment of traumatic brain injury using the Medtronic PC + S first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury, with subjects who were deemed capable of providing voluntary informed consent. In this article, we report on interviews conducted prior to surgery wherein we asked participants about their experiences recovering from brain injury and their perspectives on study enrollment and participation. We asked how risks and benefits were weighed, what their expectations and fears were, and how decisions were reached about trial participation. We found that informed consent and enrollment decisions are fraught. Subjects and families were often split, with subjects more focused on putative benefits and families concerned about incremental risk. Both subjects and families viewed brain injury as disruptive to personal identity and relationships. As decisions were made about study enrollment, families struggled with recognizing the re-emergent agency of subjects and ceding decision-making authority to subjects who had previously been dependent upon them for protection and guidance. Subjects and family members reported a hope for the relief of cognitive disabilities, improved quality of life, normalization of interpersonal interactions, and a return to work or school as reasons for study participation, along with altruism and a desire to advance science. Despite these aspirations, both subjects and families appreciated the risks of the intervention and did not suffer from a therapeutic misconception. A second essay to be published in the next issue of Cambridge Quarterly of Healthcare Ethics—Clinical Neuroethics will describe interviews conducted after surgery, the effects of cognitive restoration for subjects, families, and challenges presented to the social structures they will call upon to support them through recovery. This subsequent article will be available online prior to its formal publication in October 2023.

This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).

The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.

The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.