Comparative genomic analysis of Fischer F344 rat livers exposed for 90 days to 3-methylfuran or its parental compound furan.

Furan is a naturally forming compound found in heat-processed foods such as coffee, canned meats, and jarred baby food. It is concurrently found with analogues including 2-methylfuran (2-MF) and 3-methylfuran (3-MF), and toxicity studies demonstrate all are potent liver toxins. Toxicity studies found 3-MF is more toxic than either furan, or 2-MF. The present analysis assesses the transcriptional response in liver samples taken from male Fischer (F344) rats exposed to furan or 3-MF from 0 to 2.0 and 0-1.0 mg/kg bw/day, respectively, for 90 days. Transcriptional analyses found decreased liver function and fatty acid metabolism are common responses to both furan and 3-MF exposure. Furan liver injury promotes a ductular reaction through Hippo and TGFB signalling, which combined with increased immune response results in ameliorating perturbed bile acid homeostasis in treated rats. Failure to activate these pathways in 3-MF exposed rats and decreased p53 activity leads to cholestasis, and increased toxicity. Finally, BMD analysis indicate many of the most sensitive pathways affected by furan and 3-MF exposure relate to metabolism - malate dehydrogenase and glucose metabolism with BMDLs of 0.03 and 0.01 mg/kg bw/day for furan and 3-MF exposure, respectively, which agrees with BMDLs previously reported for apical and microarray data.

Impact of shield location on staff and caregiver dose rates for I-131 radiopharmaceutical therapy patients.

The goal of this study is to investigate the effect of the location and width of a single lead shield on the dose rate of staff and caregivers in a hospital room with an I-131 patient. The best orientation of the patient and caregiver relative to the shield was determined based on minimizing staff and caregiver radiation dose rates. Shielded and unshielded dose rates were simulated using a Monte Carlo computer simulation and validated using real-world ionisation chamber measurements. Based on a radiation transport analysis using an adult voxel phantom published by the International Commission on Radiological Protection, placing the shield near the caregiver yielded the lowest dose rates. However, this strategy reduced the dose rate in only a tiny area of the room. Furthermore, positioning the shield near the patient in the caudal direction provided a modest dose rate reduction while shielding a large room area. Finally, increased shield width was associated with decreasing dose rates, but only a four-fold dose-rate reduction was observed for standard width shields. The recommendations of this case study may be considered as potential candidate room configurations where radiation dose rates are minimized, however these findings must be weighed against additional clinical, safety, and comfort considerations.

Systematic Review Examining the Reporting of Race and Ethnicity in Sport-Related Concussion Studies.

OBJECTIVE: Sport-related concussion (SRC) is an evolving public health concern among youth athletes. Despite emerging evidence that race/ethnicity are important factors in determining concussion outcomes, studies examining race/ethnicity are limited. We conducted a systematic review to: 1) determine the prevalence of SRC studies that report race/ethnicity of their participants, 2) describe how race/ethnicity are used within each study, and 3) assess predictive factors for reporting of race/ethnicity. DATA SOURCES: PubMed/Embase/PsycINFO/CINAHL databases. STUDY SELECTION: Study inclusion criteria were: 1) primary/peer-reviewed research 2) related to the diagnosis/treatment/recovery of SRC 3) involving school-aged athletes (ages 5-25) 4) with ≥ 25 participants. The search was performed 03/2021 and included only studies published after 03/2013. DATA EXTRACTION: For each article, we looked at whether race/ethnicity were reported, and if so, which races/ethnicities were mentioned. For each race/ethnicity mentioned, we extracted the corresponding sample size and how they were used as variables in the study. DATA SYNTHESIS: Of 4,583 studies screened, 854 articles met inclusion criteria. Of the included articles, 132 (15.5%) reported race of their sample and 65 (7.6%) reported ethnicity, whereas 721 (84.4%) reported neither. When examining the demographic characteristics of the 132 studies that reported race, 69.8% of athletes were reported to be White. Additionally, 79.5% of these studies solely used race as a demographic descriptor as opposed to as a main exposure or covariate of interest. Studies published more recently were more likely to report race. Further, specific study/journal topics and geographic location of the authors were more likely to report race. CONCLUSIONS: Reporting of race/ethnicity is limited in current SRC literature. Future studies should improve the reporting of race/ethnicity, diversify study samples by focusing on enrolling athletes from underrepresented groups, and consider the potential impact of race/ethnicity as social determinants of health on risk factors, recovery, and long-term sequelae after SRC.

Suicide-Related Stigma and Social Responsibility Moderate the Effects of an Online Suicide Prevention Gatekeeper Training Program.

Aim: Gatekeeper interventions are universal programs designed for use by the general public that provide brief training sessions in responding to suicidal risk. To date, the evidence base for the efficacy of gatekeeper intervention training programs has been mixed. However, little attention has been paid to potential psychological moderators of the efficacy of suicide gatekeeper interventions. We explore the potential moderating effects of suicide-related stigma and social responsibility on the efficacy of a suicide prevention gatekeeper training program.Methods: Participants were 179 college students with a mean age of 19.05 years (SD = 1.82, range 18-31). Participants were 71.5% women, 48.6% Hispanic, and 19.6% non-Hispanic White.Results: Results indicated that higher scores on suicide-related stigma were associated with smaller intervention effects on gatekeeper self-efficacy. In contrast, higher scores on social responsibility were associated with greater intervention effects with regard to gatekeeper preparedness and gatekeeper likelihood.Conclusion: An improved understanding of the factors associated with efficacy of gatekeeper intervention programs may lead to the development of improved gatekeeper interventions. These findings may also contribute to the development of targeted gatekeeper interventions for specific cultural or occupational groups.HighlightsGatekeeper self-efficacy was moderated by levels of suicide-related stigma.Gatekeeper preparedness and likelihood were moderated by personal responsibility.Understanding moderators of gatekeeper efficacy may improve gatekeeper interventions.

High-Dose Aflibercept for Neovascular AMD and DME in Suboptimal Responders to Standard-Dose Aflibercept.

Purpose: To assess the effect of higher dose (HD) aflibercept on visual acuity (VA), optical coherence tomography outcomes, and injection burden in eyes with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) that responded suboptimally to standard-dose aflibercept. Methods: This retrospective analysis included eyes with clinically significant disease activity on monthly therapy (AMT) (injection interval ≤35 days) or clinically significant increased activity on extension (IAE) (injection interval >36 days) that were switched from aflibercept 2 mg to aflibercept HD (3 mg to 4 mg). Outcomes were assessed at baseline, after injections 1 through 4, and at 6, 9, and 12 months. Results: Overall, 318 eyes of 288 adult patients were analyzed (eyes with nAMD: 59 AMT, 147 IAE; eyes with DME: 50 AMT, 62 IAE). Most of the study cohort received aflibercept HD 3 mg (nAMD: 73% AMT and 58% IAE; DME: 49% AMT and 68% IAE); the remainder received 4 mg. The mean best VA improved significantly with AMT and was maintained with IAE. In all groups, the central subfield thickness decreased significantly and the mean injection intervals increased or remained stable. No new safety signals were observed. Conclusions: Aflibercept HD might improve outcomes while decreasing treatment burden for eyes that respond suboptimally to standard dosing.

Emerging challenges of the impacts of pharmaceuticals on aquatic ecosystems: A diatom perspective.

Pharmaceuticals are a ubiquitous group of emerging pollutants of considerable importance due to their biological potency and potential to elicit effects in wildlife and humans. Pharmaceuticals have been quantified in terrestrial, marine, fresh, and transitional waters, as well as the fauna and macro-flora that inhabit them. Pharmaceuticals can enter water ways through different human and veterinary pathways with traditional wastewater treatment, unable to completely remove pharmaceuticals, discharging often unknown quantities to aquatic ecosystems. However, there is a paucity of available information regarding the effects of pharmaceuticals on species at the base of aquatic food webs, especially on phytoplankton, with research typically focussing on fish and aquatic invertebrates. Diatoms are one of the main classes of phytoplankton and are some of the most abundant and important organisms in aquatic systems. As primary producers, diatoms generate ∼40 % of the world's oxygen and are a vital food source for primary consumers. Diatoms can also be used for bioremediation of polluted water bodies but perhaps are best known as bio-indicators for water quality studies. However, this keystone, non-target group is often ignored during ecotoxicological studies to assess the effects of pollutants of concern. Observed effects of pharmaceuticals on diatoms have the potential to be used as an indicator of pharmaceutical-induced impacts on higher trophic level organisms and wider ecosystem effects. The aim of this review is to present a synthesis of research on pharmaceutical exposure to diatoms, considering ecotoxicity, bioremediation and the role of diatoms as bio-indicators. We highlight significant omissions and knowledge gaps which need addressing to realise the potential role of diatoms in future risk assessment approaches and help evaluate the impacts of pharmaceuticals in the aquatic environment at local and global scales.

TMJ Disorders in Athletes.

ABSTRACT: Temporomandibular joint dysfunction is common in both the general population and athletes with a much higher incidence in women than in men. We review current research on temporomandibular joint disorders, discuss relevant risk factors, manifestations of temporomandibular disorders in athletes, and treatment options. Certain sports, particularly contact sports, pose an increased risk for problems with the temporomandibular joint. The stress of athletic performance also may be a contributing factor. Mouthguards should be encouraged for prevention of injury and physical therapy is the most effective treatment.

Extended length of stay and related costs associated with dementia in acute care hospitals in Ireland.

OBJECTIVE: To estimate the additional impact of dementia on in-patient length of stay (LOS) and related costs in Irish acute hospitals. Both principal and secondary diagnosis effects are estimated and valued. METHODS: This is a cross-sectional study based on administrative data collected on all public hospital in-patient discharges in Ireland for people aged 65 years and older in 2019. Coarsened exact matching (CEM) was undertaken to account for observed confounders between dementia and non-dementia groups, while generalised linear modelling (GLM) was used to compare differences in LOS. RESULTS: Patients with a principal diagnosis of dementia spent on average 17.5 (CI: 15.42, 19.56; p < .01) d longer in hospital than similar patients with no principal diagnosis of dementia. LOS was 6.7 (CI: 6.31, 7.14; p < .01) d longer for patients with a secondary diagnosis of dementia compared to similar patients with no secondary diagnosis of dementia. The additional annual cost of care for patients in hospitals with a secondary (principal) diagnosis of dementia was €62.0 million (€13.2 million). CONCLUSIONS: This study highlights the economic impact of extended LOS for patients with dementia in Irish acute hospitals. Addressing specific dementia-related needs of people in hospital is likely to optimise resource use and decrease health care costs in acute care settings.

Hallucinating symmetric protein assemblies.

Deep learning generative approaches provide an opportunity to broadly explore protein structure space beyond the sequences and structures of natural proteins. Here, we use deep network hallucination to generate a wide range of symmetric protein homo-oligomers given only a specification of the number of protomers and the protomer length. Crystal structures of seven designs are very similar to the computational models (median root mean square deviation: 0.6 angstroms), as are three cryo-electron microscopy structures of giant 10-nanometer rings with up to 1550 residues and C33 symmetry; all differ considerably from previously solved structures. Our results highlight the rich diversity of new protein structures that can be generated using deep learning and pave the way for the design of increasingly complex components for nanomachines and biomaterials.

EPIC: an evaluation of the psychological impact of early-phase clinical trials in cancer patients.

BACKGROUND: Anxiety and depression in patients with cancer is associated with decreased quality of life and increased morbidity and mortality. However, these are often overlooked and untreated. Early-phase clinical trials (EPCTs) recruit patients with advanced cancers who frequently lack future treatment options, which may lead to increased anxiety and depression. Despite this, EPCTs do not routinely consider psychological screening for patients. PATIENTS AND METHODS: This prospective observational study explored levels of anxiety and depression alongside impact of trial participation in the context of EPCTs. The Hospital Anxiety and Depression Scale and the Brief Illness Perceptions Questionnaire were completed at the point of EPCT consent, the end of screening and at pre-specified time points thereafter. RESULTS: Sixty-four patients (median age 56 years; median Eastern Cooperative Oncology Group performance status 1) were recruited. At consent, 57 patients returned questionnaires; 39% reported clinically relevant levels of anxiety whilst 18% reported clinically relevant levels of depression. Sixty-three percent of patients experiencing psychological distress had never previously reported this. Males were more likely to be depressed (P = 0.037) and females were more likely to be anxious (P = 0.011). Changes in anxiety or depression were observed after trial enrolment on an individual level, but not significant on a population level. CONCLUSIONS: Patients on EPCTs are at an increased risk of anxiety and depression but may not seek relevant support. Sites offering EPCTs should consider including psychological screening to encourage a more holistic approach to cancer care and consider the sex of individuals when tailoring psychological support to meet specific needs.

Genomic analysis of Fisher F344 rat kidneys from a reproductive study following dietary ochratoxin A exposure.

Ochratoxin A (OTA) is a mycotoxin produced by species of Penicillium and Aspergillus, and is found in many commodities including cereal grains, nuts, and coffee. OTA is a renal carcinogen and nephrotoxin at high concentrations, targeting the proximal tubules. This study uses transcriptomics and the previously reported apical data (Bondy et al., 2021) to infer mode-of-action of OTA toxicity in male and female rats exposed to low doses of OTA in utero and throughout development. Our findings support a male-specific activation of the innate and adaptive immune responses in F1 pups to OTA exposure. This was not found in the female F1 pups, and may be due to female-specific increased p38 activity and VDR signaling. Differentially expressed genes related to karyomegaly, MAPK activity, and immune activation appears to develop from in utero exposure to OTA whereas those related to decreased kidney and liver function, and changes to reproductive pathways occur in both rat generations. Together, these transcriptional results confirm that dietary exposure to OTA causes renal toxicity as well as alterations to hepatic and reproductive pathways in rats. In utero exposure of rats to OTA results in sex-specific alterations in immune response pathways, VDR signaling, and p38 activity.

CMYA5 establishes cardiac dyad architecture and positioning.

Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease. Here, we use proximity proteomics in intact, living hearts to identify proteins enriched near dyads. Among these proteins is CMYA5, an under-studied striated muscle protein that co-localizes with Z-lines, junctional sarcoplasmic reticulum proteins, and transverse tubules in mature cardiomyocytes. During cardiac development, CMYA5 positioning adjacent to Z-lines precedes junctional sarcoplasmic reticulum positioning or transverse tubule formation. CMYA5 ablation disrupts dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload. These data provide mechanistic insights into cardiomyopathy pathogenesis by demonstrating that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, establishes dyad architecture, and regulates dyad Ca2+ release.

Overview and Diagnostic Accuracy of Near Infrared Spectroscopy in Carotid Endarterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Carotid endarterectomy is recommended for the prevention of ischaemic stroke due to carotid stenosis. However, the risk of stroke after carotid endarterectomy has been estimated at 2% - 5%. Monitoring intra-operative cerebral oxygenation with near infrared spectroscopy (NIRS) has been assessed as a strategy to reduce intra- and post-operative complications. The aim was to summarise the diagnostic accuracy of NIRS to detect intra-operative ischaemic events, the values associated with ischaemic events, and the relative contribution of external carotid contamination to the NIRS signal in adults undergoing carotid endarterectomy. DATA SOURCES: EMBASE, MEDLINE, Cochrane Centre Register of Controlled Trials, and reference lists through May 2019 were searched. REVIEW METHODS: Non-randomised and randomised studies assessing NIRS as an intra-operative monitoring tool in carotid endarterectomy were included. Studies using NIRS as the reference were excluded. Risk of bias was assessed using the Newcastle Ottawa Scale, RoB-2, and QUADAS-2. RESULTS: Seventy-six studies were included (n = 8 480), under local (n = 1 864) or general (n = 6 582) anaesthesia. Seven studies were eligible for meta-analysis (n = 524). As a tool for identifying intra-operative ischaemia, specificity increased with more stringent NIRS thresholds, while there was unpredictable variation in sensitivity across studies. A Δ20% threshold under local anaesthesia resulted in pooled estimates for sensitivity and specificity of 70.5% (95% confidence interval, CI, 54.1 - 82.9) and 92.4% (95% CI 85.5 - 96.1) compared with awake neurological monitoring. These studies had low or unclear risk of bias. NIRS signal consistently dropped across clamping and recovered to pre-clamp values upon de-clamp in most studies, and larger decreases were observed in patients with ischaemic events. The contribution of extracranial signal to change in signal across clamp varied from 3% to 50%. CONCLUSION: NIRS has low sensitivity and high specificity to identify intra-operative ischaemia compared with awake monitoring. Extracranial signal contribution was highly variable. Ultimately, data from high quality studies are desperately needed to determine the utility of NIRS.

Personalized dosimetry of177Lu-DOTATATE: a comparison of organ- and voxel-level approaches using open-access images.

177Lu-DOTATATE (Lutathera®) enables targeted radionuclide therapy of neuroendocrine tumors expressing somatostatin receptor type 2. Though patient-specific dosimetry estimates may be clinically important for predicting absorbed dose-effect relationships, there are multiple relevant dosimetry paradigms which are distinct in terms of clinical effort, numerical output and added-value. This work compares three different approaches for177Lu-DOTATATE dosimetry, including 1) an organ-level approach based on reference phantom MIRD S-values scaled to patient-specific organ masses (MIRDcalc), 2) an organ-level approach based on Monte Carlo simulation in a patient-specific mesh phantoms (PARaDIM), and 3) a 3D approach based on Monte Carlo simulation in patient-specific voxel phantoms.Method. Serial quantitative SPECT/CT images for two patients receiving177Lu-DOTATATE therapy were obtained from archive in theDeep Bluedatabase. For each patient, the serial CT images were co-registered to the first time point CT using a deformable registration technique aided by virtual landmarks placed in the kidney pelves and the lesion foci. The co-registered SPECT images were integrated voxel-wise to generate time-integrated activity maps. Lesions, kidneys, liver, spleen, lungs, compact bone, spongiosa, and rest of body were segmented at the first imaging time point and overlaid on co-registered integrated activity maps. The resultant segmentation was used for three purposes: 1) to generate patient-specific phantoms, 2) to determine organ-level time-integrated activities, and 3) to generate dose volume histograms from 3D voxel-based calculations.Results. Mean absorbed doses were computed for lesions and 48 tissues with MIRDcalc software. Mean organ absorbed doses and dose volume histograms were obtained for lesions and 6 tissues with the voxel Monte Carlo approach. Lesion- and organ-level absorbed dose estimates agreed within ±26% for the lesions and ±13% for the critical organs, among the different methods tested. Overall good agreement was observed with the dosimetry estimates from the NETTER-1 trial.Conclusions. For personalized177Lu-DOTATATE dosimetry, a combined approach was determined to be valuable, which utilized two dose calculation methods supported by a single image processing workflow. In the absence of quantitative imaging limitations, the voxel Monte Carlo method likely provides valuable information to guide treatment by considering absorbed dose non-uniformity in lesions and organs at risk. The patient-scaled reference phantom method also provides valuable information, including absorbed dose estimates for non-segmented organs, and more accurate dose estimates for complex radiosensitive organs including the active marrow.

Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.

BACKGROUND: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Plasmodium falciparum. METHODS: We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the P. falciparum reticulocyte-binding protein homolog 5 (RH5), formulated in AS01B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145. FINDINGS: The RH5.1/AS01B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 µg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Following primary and secondary CHMI of vaccinees with blood-stage P. falciparum, a significant reduction in parasite growth rate was observed, defining a milestone for the blood-stage malaria vaccine field. We show that growth inhibition activity measured in vitro using purified immunoglobulin G (IgG) antibody strongly correlates with in vivo reduction of the parasite growth rate and also identify other antibody feature sets by systems serology, including the plasma anti-RH5 IgA1 response, that are associated with challenge outcome. CONCLUSIONS: Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease. FUNDING: This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.

Genome Sequences of Akoni, Ashton, and Truong, Podoviridae Bacteriophages Isolated from Microbacterium foliorum.

Cluster EK2 Akoni, Ashton, and Truong are lytic Podoviridae actinobacteriophages that were isolated from soil in Florida using Microbacterium foliorum NRRL B-24224 as the host. The genomes are 54,307 bp, 54,560 bp, and 54,309 bp, respectively, and are 60% GC rich. Each genome contains a novel 13,464-bp gene that encompasses 25% of the genome.

Systemic toxicities of trastuzumab-emtansine predict tumor response in HER2+ metastatic breast cancer.

The mechanism by which trastuzumab-emtansine (T-DM1) causes systemic toxicities apart from trastuzumab alone is currently unknown. We hypothesized that the systemic toxicities from T-DM1 may have been caused by the free and active maytansine released from the lysed HER2+ tumor cells, and if so, they may correlate with the response to treatment and eventually disease-free survival or patient outcome. In a retrospective, observational study, we evaluated 73 patients from three centers in the United States and Canada with advanced HER2+ breast cancer that received at least one dose of T-DM1. Toxicity grades were summed to create a corresponding toxicity sum score (TSS), and its association with clinical outcomes was analyzed. A higher TSS was significantly associated with longer progression-free survival with an HR = 0.66 [95% confidence interval [CI]: 0.47-0.92], P = .014, for each 1-point increase in the TSS score. Adjusted for baseline platelet count, aspartate transaminase and alanine transaminase, higher TSS remains significantly associated with longer progression-free survival with adjusted HR = 0.67 [95% CI: 0.47-0.93], P = .020. The analysis suggests that the systemic toxicities of T-DM1 were significantly correlated with its clinical efficacy. This is the first report to correlate the systemic toxicities of T-DM1 with clinical outcome. Further, this suggests that systemic toxicities of antibody-drug conjugates (ADCs) may serve as a predictive biomarker, particularly if noncleavable linkers are used. If confirmed in larger prospective studies, the present finding is significant because most ADCs do not have a biomarker predictive of clinical outcome other than the presence or absence of the antibody target.

A Rapid Assessment of Disaster Preparedness Needs and Resources during the COVID-19 Pandemic.

Background: This year has seen the emergence of two major crises, a significant increase in the frequency and severity of hurricanes and the COVID-19 pandemic. However, little is known as to how each of these two events have impacted the other. A rapid qualitative assessment was conducted to determine the impact of the pandemic on preparedness and response to natural disasters and the impact of past experiences with natural disasters in responding to the pandemic. Methods: Semi-structured interviews were conducted with 26 representatives of 24 different community-based programs in southern Louisiana. Data were analyzed using procedures embedded in the Rapid Assessment Procedure-Informed Community Ethnography methodology, using techniques of immersion and crystallization and focused thematic analysis. Results: The pandemic has impacted the form and function of disaster preparedness, making it harder to plan for evacuations in the event of a hurricane. Specific concerns included being able to see people in person, providing food and other resources to residents who shelter in place, finding volunteers to assist in food distribution and other forms of disaster response, competing for funds to support disaster-related activities, developing new support infrastructures, and focusing on equity in disaster preparedness. However, several strengths based on disaster preparedness experience and capabilities were identified, including providing a framework for how to respond and adapt to COVID and integration of COVID response with their normal disaster preparedness activities. Conclusions: Although prior experience has enabled community-based organizations to respond to the pandemic, the pandemic is also creating new challenges to preparing for and responding to natural disasters.

Playing God and tampering with nature: popular labels for real concerns in synthetic biology.

Public engagement in science with diverse cross-sections of the community is considered a critical aspect of responsible biotechnological innovation. While the research community shows willingness to engage with both ambivalent and supportive audiences about potentially disruptive technological advances, there is less enthusiasm for engaging with groups who hold deeply opposing views to such advances. 'Playing God' and 'tampering with nature' are popular examples of intrinsic objections often made in opposition to the development or use of novel genetic technologies. Historically appearing in arguments against the pursuit of genetically modified organisms in agriculture and food industries, intrinsic objections have previously been labelled by the science community as inconsistent, non-scientific, and vague. Now found in a range of innovation contexts, the domain of synthetic biology appears to attract such objections consistently. We present the findings from a large Australian study (N = 4593) which suggests 'playing God' objections and their variants can be multilayered and, at times, accompanied by meaningful information about risk perceptions. We use qualitative analysis of open-ended responses from an online survey to show how these objections are articulated in response to selected synthetic biology applications across environmental and health domains. Our research invites a rethink of how the synthetic biology community perceives, and engages with, people who express intrinsic objections. These people may additionally hold extrinsic concerns that may be potentially addressed, or at least reasonably considered, through dialogue. We offer some concluding remarks for engaging with publics who employ these types of arguments to communicate unease with aspects of technology development and use.

Dairy cow trade-off preference for 2 different lying qualities: Lying surface and lying space.

Lying down is an important behavior for cows, contributing to their health and welfare. With dairy cows being housed for increasingly longer periods, if not year-round, it is important to ensure that dairy cow lying comfort is not compromised when they are housed. The aim of this study was to assess cow preference for 2 different qualities of lying area that appear to be important to cows-surface type and an open lying space-to better understand how to optimize lying comfort for cows when housed. Twenty-four Holstein dairy cows were used during the study, which took place in Scotland from July to November 2018. The study consisted of 6 experimental periods, each lasting a total of 21 d. Cows were tested 4 at a time and individually housed in their own test pen. Each pen had 3 lying surfaces: sand, mattress, and straw (2.4 m × 2.4 m each) with a freestall in the middle of each, which could be removed. Cows were given access to one surface at a time (training period) with a freestall for 2 d, and then given a choice of all 3 surfaces for 2 d. When given the choice with freestalls in position, cows spent, on average, the largest amount of their lying time on straw (46.6 ± 7.8%) followed by mattress (44.3 ± 12.4%). Freestalls were then removed and the training and choice phase was repeated on the following day, with cows, on average, spending the most time lying on straw (64.4 ± 7.2%). Finally, a freestall was refitted onto each cow's most preferred surface and the cows were given a choice between lying on their most preferred surface with a freestall (P1 + freestall) or on their second or third preferred surface without a freestall (P2 + open and P3 + open, respectively) for 3 d. During this final trade-off stage, of the 19 cows for which data were available, 14 cows chose to give up the opportunity to lie down on their most preferred surface to have more space on P2 + open and P3 + open, 3 cows chose to lie down on P1 + freestall, and 2 cows made no clear choice. Overall, cows spent the largest amount of their total lying time on their second most preferred surface as an open lying space (65.7 ± 6.9%) compared with their preferred surface with a freestall (20.5 ± 5.9%) and their third preferred surface as an open lying space (13.8 ± 3.7%). The results indicate that when lying down, these dairy cows value an open lying space more than the lying surface.