Safety and feasibility of triage and rapid discharge of patients with chest pain from emergency room: A pragmatic, randomized noninferiority control trial of the European Society of Cardiology (ESC) 0 to 1 hour pathway vs conventional 0 to 3 hour accelerated diagnostic protocol.

Patients presenting with chest pain represent a significant proportion of Emergency Department (ED) attendances but only a minority, typically 10%, have a final diagnosis of myocardial infarction (MI). Prompt discharge of patients without MI will alleviate ED overcrowding as well as improve patient satisfaction and reduce exposure to risk of hospital acquired infections such as Covid 19. The measurement of cardiac troponin (cTn) by a high sensitivity method is recommended by the National Institute for health and Care Excellence (NICE) for rapid categorization of patients presenting with chest pain. Strategies proposed include measurement on admission and 1 hour from admission (ESC 0-1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and 3 hours from admission (0-3-hour pathway, which is conventional and widely adopted). The primary objective of this study is twofold: firstly, to assess the safety, feasibility, and impact of implementing the ESC (European Society of Cardiology) 0 to 1-hour pathway in clinical practice by reference to the more established ESC 0 to 3-hour protocol. The principal outcome measure will be the safety of the ESC 0 to 1-hour protocol. However, there are concerns that the time from sample draw to result availability (typically around 60 minutes) will impact on the feasibility of the ESC 0 to 1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyzer (point of care testing, POCT), which will produce results in 15 minutes is a feasible alternative to laboratory testing. We will compare the results produced by POCT with the laboratory results in the context of the ESC 0 to 1 hour and 0 to 3-hour pathway, as a nested controlled study in the context of a randomized controlled trial. (clinicaltrials.gov: NCT05322395).

Starvation differentially affects gene expression, immunity and pathogen susceptibility across symbiotic states in a model cnidarian.

Mutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with food limitation to influence gene expression and stress response programming in the sea anemone Exaiptasia pallida (Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB correlated with increased immunity only in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under food scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and non-symbiotic anemone, 'defence' responses were similarly regulated in Aiptasia and the facultative coral, but not in the non-symbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways-including NF-κB-does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.

Symbiosis modulates gene expression of symbionts, but not coral hosts, under thermal challenge.

Increasing ocean temperatures are causing dysbiosis between coral hosts and their symbionts. Previous work suggests that coral host gene expression responds more strongly to environmental stress compared to their intracellular symbionts; however, the causes and consequences of this phenomenon remain untested. We hypothesized that symbionts are less responsive because hosts modulate symbiont environments to buffer stress. To test this hypothesis, we leveraged the facultative symbiosis between the scleractinian coral Oculina arbuscula and its symbiont Breviolum psygmophilum to characterize gene expression responses of both symbiotic partners in and ex hospite under thermal challenges. To characterize host and in hospite symbiont responses, symbiotic and aposymbiotic O. arbuscula were exposed to three treatments: (1) control (18°C), (2) heat (32°C), and (3) cold (6°C). This experiment was replicated with B. psygmophilum cultured from O. arbuscula to characterize ex hospite symbiont responses. Both thermal challenges elicited classic environmental stress responses (ESRs) in O. arbuscula regardless of symbiotic state, with hosts responding more strongly to cold challenge. Hosts also exhibited stronger responses than in hospite symbionts. In and ex hospite B. psygmophilum both down-regulated gene ontology pathways associated with photosynthesis under thermal challenge; however, ex hospite symbionts exhibited greater gene expression plasticity and differential expression of genes associated with ESRs. Taken together, these findings suggest that O. arbuscula hosts may buffer environments of B. psygmophilum symbionts; however, we outline the future work needed to confirm this hypothesis.

Rebuild the Academy: Supporting academic mothers during COVID-19 and beyond.

The issues facing academic mothers have been discussed for decades. Coronavirus Disease 2019 (COVID-19) is further exposing these inequalities as womxn scientists who are parenting while also engaging in a combination of academic related duties are falling behind. These inequities can be solved by investing strategically in solutions. Here we describe strategies that would ensure a more equitable academy for working mothers now and in the future. While the data are clear that mothers are being disproportionately impacted by COVID-19, many groups could benefit from these strategies. Rather than rebuilding what we once knew, let us be the architects of a new world.

Promoting inclusive metrics of success and impact to dismantle a discriminatory reward system in science.

Success and impact metrics in science are based on a system that perpetuates sexist and racist "rewards" by prioritizing citations and impact factors. These metrics are flawed and biased against already marginalized groups and fail to accurately capture the breadth of individuals' meaningful scientific impacts. We advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion. We outline pathways for a paradigm shift in scientific values based on multidimensional mentorship and promoting mentee well-being. These actions will require collective efforts supported by academic leaders and administrators to drive essential systemic change.

Conserving ecosystem integrity: Ecological theory as a guide for marine protected area monitoring.

Global policies increasingly focus on the importance of maintaining or improving the integrity of ecosystems, but defining, assessing, and monitoring integrity in marine protected areas (MPAs) remains a challenge. In this paper, we conceptualized ecological integrity along dimensions of heterogeneity and stability containing seven components: physical structure, diversity, function, persistence, resistance, resilience, and natural variability. Through a structured literature search, we identified indicators and metrics used for quantifying ecosystem status components in the marine environment, then reviewed MPA management plans worldwide for inclusion of these components. We evaluated 202 papers applying 83 ecological indicators built from 72 metrics. Ecosystem components were most comprehensively addressed by metrics of taxa presence, organisms count, and area occupied by benthic organisms, and community structure, biomass, and percent cover indicators. Of the 557 MPA management plans we reviewed globally, 93% used at least one ecosystem status term or its synonym in an ecologically relevant context, but 39% did not address any components of stability. In particular, resistance was mentioned in only 1% of management plans, but in some cases it may be inferred from indicators and metrics used to track the best addressed component in management plans, diversity. Plans for MPAs with both an ecological/biological purpose and a research and education purpose contained ecosystem status terms more frequently than other plans, suggesting that engagement with the scientific community may have improved the application of these terms. An improved understanding of how to operationalize and measure ecological integrity can help MPA monitoring and management.

The impact of jejunostomy feeding on nutritional outcomes after oesophagectomy.

BACKGROUND: Nutritional status is compromised long-term following oesophagectomy. Controversy surrounds the optimal route for nutrition support postoperatively and there is wide variation in the use of feeding jejunostomy tubes. METHODS: A retrospective service evaluation was conducted for all consecutive adults who underwent oesophagectomy for a cancer diagnosis within a specialist centre between April 2016 and July 2019 (n = 165). Nutritional and clinical outcomes were compared for patients who received jejunostomy feeding (n = 24), versus those who did not (n = 141). RESULTS: Patients with feeding jejunostomy lost significantly less weight at both 6 and 12 months postoperatively compared to those without jejunostomy (p ≤ 0.001 and p = 0.001, respectively). This remained statistically significant in multiple regression, controlling for age, gender, preoperative tumour staging and adjuvant treatment (p ≤ 0.001 and p = 0.03, respectively). Median length of home enteral feeding was 10 weeks after discharge in the jejunostomy group. We observed minor jejunostomy tube-related complications in four patients (16.7%). Of those readmitted within 90 days of surgery in the non-jejunostomy group, nutritional failure was a factor in 43.2% of these readmissions. "Rescue tube feeding" was required by 8.5% of the non-jejunostomy group within the first postoperative year, including 6.4% within 90 days of surgery. CONCLUSIONS: Use of short-term supplementary jejunal feeding in addition to oral intake after hospital discharge is beneficial for maintaining weight after oesophagectomy. We suggest a future randomised-controlled trial to confirm these findings.

Pilot Study of Intensive Trismus Intervention Using Restorabite™ During Unilateral Adjuvant Radiation for Head and Neck Cancer.

Trismus commonly arises after surgery for head and neck cancer (HNC) and its severity is potentiated by postoperative radiotherapy. While the benefit of trismus rehabilitation after surgery and radiotherapy is well established, the evidence during radiotherapy is less clear. This may be due to poor adherence to trismus exercises secondary to acute mucositis. This study assessed the feasibility of using a novel trismus device during adjuvant radiotherapy for HNC in patients with acute postoperative trismus. Prospective single-arm cohort feasibility study. Eligible patients had undergone surgery with curative intent for HNC, planned for adjuvant radiotherapy, and were suitable for trismus rehabilitation. Participants completed a 10-week exercise program using a novel jaw stretching device. Study outcomes were adherence, maximal incisal opening (MIO), and trismus-related function and quality of life scores, assessed at baseline, 10 weeks, and 6 months after commencing exercises. Nine patients diagnosed with trismus after primary surgery were recruited. The mean increase in MIO at 10 weeks was 7.8 mm (range -4 to 15 mm, p = 0.03), and at 6 months was 10.6 mm (range 1-26 mm, p = 0.03). Significant improvements were observed in trismus-related quality of life (Gothenburg Trismus Questionnaire; p = 0.04). Adherence to the exercises was 100% in week 1-2, 67% in weeks 3-6, and 100% at 10 weeks (1 month post radiation). This study demonstrates the feasibility of using a novel jaw stretching device during adjuvant radiotherapy. Further evaluation is warranted to assess the effectiveness of early intervention and prevention of trismus during HNC radiotherapy.Level of Evidence: IV.

Work engagement, psychological empowerment and relational coordination in long-term care: A mixed-method examination of nurses' perceptions and experiences.

Nurse engagement, empowerment and strong relationships among staff, residents and families, are essential to attract and retain a suitably qualified and skilled nursing workforce for safe, quality care. There is, however, limited research that explores engagement, empowerment and relational coordination in long-term care (LTC). Nurses from an older persons' mental health and dementia LTC unit in Australia participated in this study. Forty-one nurses completed a survey measuring psychological empowerment, work engagement and relational coordination. Twenty-nine nurses participated in individual interviews to further explore these concepts. Although nurses reported high psychological empowerment and work engagement, their relationships with key stakeholders varied. Our findings suggest that nurses in LTC require both supports and opportunities to contribute as active members of the multiprofessional care team that includes tailored education, professional development and positive interactions within the care team. Regular support is needed to enable nurses to feel empowered, foster relationships and communication, and facilitate work engagement. Based on these findings, we suggest that it is important to find ways to ensure that all who provide care perceive that they are part of the whole care team and able to contribute to the care and well-being of people in LTC.

Fostering collaborative practice through interprofessional simulation for occupational therapy, physiotherapy, dietetics, and nursing students.

Literature regarding simulation for learning interprofessional collaborative practice (IPCP) indicates a need to include a range of health professions and to focus on students' development of team communication and conflict resolution skills in day-to-day healthcare delivery. This study evaluated the impact of interprofessional simulation for occupational therapy, physiotherapy, dietetics, and nursing students on interprofessional collaboration competencies, specifically collaborative communication and conflict resolution during day-to-day interactions, and their intention for IPCP during placement. A series of simulations featuring the potential for interprofessional conflict and involving explicit coaching on communication and conflict resolution were conducted. A single cohort pre-test post-test design included the Students' Perceptions of Interprofessional Clinical Education Revised (SPICE-R), the Interprofessional Collaborative Competencies Attainment Survey (ICCAS), and an open response survey question on future intended practice. A total of 237 students participated in the simulation experience. Overall scores and scores on all IPCP competencies in the ICASS (n = 193) and SPICE-R (n = 226) improved for all professions post-simulation. The mean score of the ICCAS increased for 98% of the respondents and similarly the mean score of the SPICE-R increased for 71% of the respondents. Open-ended responses indicated students' intentions to pursue self-leadership in IPCP. Students who participated in an interprofessional simulation reported perceived improvements in IPCP competencies and were encouraged to initiate IPCP when on placement in the practice setting.

Rampant asexual reproduction and limited dispersal in a mangrove population of the coral Porites divaricata.

Corals are critical to marine biodiversity. Reproduction and dispersal are key to their resilience, but rarely quantified in nature. Exploiting a unique system-a fully censused, longitudinally characterized, semi-isolated population inhabiting mangroves-we used 2bRAD sequencing to demonstrate that rampant asexual reproduction most likely via parthenogenesis and limited dispersal enable the persistence of a natural population of thin-finger coral (Porites divaricata). Unlike previous studies on coral dispersal, knowledge of colony age and location enabled us to identify plausible parent-offspring relationships within multiple clonal lineages and develop tightly constrained estimates of larval dispersal; the best-fitting model indicates dispersal is largely limited to a few metres from parent colonies. Our results explain why this species is adept at colonizing mangroves but suggest limited genetic diversity in mangrove populations and limited connectivity between mangroves and nearby reefs. As P. divaricata is gonochoristic, and parthenogenesis would be restricted to females (whereas fragmentation, which is presumably common in reef and seagrass habitats, is not), mangrove populations likely exhibit skewed sex ratios. These findings suggest that coral reproductive diversity can lead to distinctly different demographic outcomes in different habitats. Thus, coral conservation will require the protection of the entire coral habitat mosaic, and not just reefs.

Evidence of sweepstakes reproductive success in a broadcast-spawning coral and its implications for coral metapopulation persistence.

Processes governing genetic diversity and adaptive potential in reef-building corals are of interest both for fundamental evolutionary biology and for reef conservation. Here, we investigated the possibility of "sweepstakes reproductive success" (SRS) in a broadcast spawning coral, Acropora hyacinthus, at Yap Island, Micronesia. SRS is an extreme yearly variation in the number of surviving offspring among parents. It is predicted to generate genetically differentiated, low-genetic-diversity recruit cohorts, containing close kin individuals. We have tested these predictions by comparing genetic composition of size classes (adults and juveniles) at several sites on the island of Yap. We did see the genome-wide dip in genetic diversity in juveniles compared to adults at two of the four sites; however, both adults and juveniles varied in genetic diversity across sites, and there was no detectable genetic structure among juveniles, which does not conform to the classical SRS scenario. Yet, we have identified a pair of juvenile siblings at the site where juveniles had the lowest genetic diversity compared to adults, an observation that is hard to explain without invoking SRS. While further support for SRS is needed to fully settle the issue, we show that incorporating SRS into the Indo-West Pacific coral metapopulation adaptation model had surprisingly little effect on mean rates of coral cover decline during warming. Still, SRS notably increases year-to-year variation in coral cover throughout the simulation.

Discovery of a novel pseudo ß-hairpin structure of N-truncated amyloid-ß for use as a vaccine against Alzheimer's disease.

One of the hallmarks of Alzheimer's disease (AD) are deposits of amyloid-beta (Aß) protein in amyloid plaques in the brain. The Aß peptide exists in several forms, including full-length Aß1-42 and Aß1-40 - and the N-truncated species, pyroglutamate Aß3-42 and Aß4-42, which appear to play a major role in neurodegeneration. We previously identified a murine antibody (TAP01), which binds specifically to soluble, non-plaque N-truncated Aß species. By solving crystal structures for TAP01 family antibodies bound to pyroglutamate Aß3-14, we identified a novel pseudo ß-hairpin structure in the N-terminal region of Aß and show that this underpins its unique binding properties. We engineered a stabilised cyclic form of Aß1-14 (N-Truncated Amyloid Peptide AntibodieS; the 'TAPAS' vaccine) and showed that this adopts the same 3-dimensional conformation as the native sequence when bound to TAP01. Active immunisation of two mouse models of AD with the TAPAS vaccine led to a striking reduction in amyloid-plaque formation, a rescue of brain glucose metabolism, a stabilisation in neuron loss, and a rescue of memory deficiencies. Treating both models with the humanised version of the TAP01 antibody had similar positive effects. Here we report the discovery of a unique conformational epitope in the N-terminal region of Aß, which offers new routes for active and passive immunisation against AD.

Heat challenge elicits stronger physiological and gene expression responses than starvation in symbiotic Oculina arbuscula.

Heterotrophy has been shown to mitigate coral-algal dysbiosis (coral bleaching) under heat challenge, but the molecular mechanisms underlying this phenomenon remain largely unexplored. Here, we quantified coral physiology and gene expression of fragments from 13 genotypes of symbiotic Oculina arbuscula after a 28-d feeding experiment under (1) fed, ambient (24 °C); (2) unfed, ambient; (3) fed, heated (ramp to 33 °C); and (4) unfed, heated treatments. We monitored algal photosynthetic efficiency throughout the experiment, and after 28 d, profiled coral and algal carbohydrate and protein reserves, coral gene expression, algal cell densities, and chlorophyll-a and chlorophyll-c2 pigments. Contrary to previous findings, heterotrophy did little to mitigate the impacts of temperature, and we observed few significant differences in physiology between fed and unfed corals under heat challenge. Our results suggest the duration and intensity of starvation and thermal challenge play meaningful roles in coral energetics and stress response; future work exploring these thresholds and how they may impact coral responses under changing climate is urgently needed. Gene expression patterns under heat challenge in fed and unfed corals showed gene ontology enrichment patterns consistent with classic signatures of the environmental stress response. While gene expression differences between fed and unfed corals under heat challenge were subtle: Unfed, heated corals uniquely upregulated genes associated with cell cycle functions, an indication that starvation may induce the previously described, milder "type B" coral stress response. Future studies interested in disentangling the influence of heterotrophy on coral bleaching would benefit from leveraging the facultative species studied here, but using the coral in its symbiotic and aposymbiotic states.

Emergency paediatric medicine consultation-a practical guide to a consultation with refugee and asylum-seeking children within the paediatric emergency department.

There are increasing numbers of refugee and asylum-seeking children entering the UK annually who face significant barriers to accessing healthcare services. Clinicians working in the emergency department should have an awareness of the journeys children may have taken and the barriers they face in accessing care and have a holistic approach to care provision. We conducted a narrative literature review and used experiential knowledge of paediatricians working in the Paediatric Emergency Department to formulate a step-by-step screening tool. We have formulated a step-by-step screening tool, CCHILDS (Communication, Communicable diseases, Health-physical and mental, Immunisation, Look after (safeguarding), Deficiencies, Sexual health) which can be used by healthcare professionals in the emergency department. CONCLUSION: Due to increasing numbers of refugee and asylum-seeking children, it is important that every point of contact with healthcare professionals is an impactful one on their health, well-being and development. Future work would include validation of our tool. WHAT IS KNOWN: •The number of refugees globally are rapidly increasing, leading to an increase in the number of presentations to the PED. These patients are often medically complex and may have unique and sometimes unexpected presentations that could be attributed to by their past. There are a multitude of resources available outlining guidance on the assessment and management of refugee children. WHAT IS NEW: •This review aims to succinctly summarise the guidance surrounding the assessment of refugee children presenting to the PED and ensure that healthcare professionals are aware of the pertinent information regarding this cohort. It introduces the CCHILDS assessment tool which has been formulated through a narrative review of the literature and acts as a mnemonic to aid professionals in their assessment of refugee children in the PED.

Microbial Community Dynamics Provide Evidence for Hypoxia during a Coral Reef Mortality Event.

In July 2016, a severe coral reef invertebrate mortality event occurred approximately 200 km southeast of Galveston, Texas, at the East Flower Garden Bank, wherein ∼82% of corals in a 0.06-km2 area died. Based on surveys of dead corals and other invertebrates shortly after this mortality event, responders hypothesized that localized hypoxia was the most likely direct cause. However, no dissolved oxygen data were available to test this hypothesis, because oxygen is not continuously monitored within the Flower Garden Banks sanctuary. Here, we quantify microbial plankton community diversity based on four cruises over 2 years at the Flower Garden Banks, including a cruise just 5 to 8 days after the mortality event was first observed. In contrast with observations collected during nonmortality conditions, microbial plankton communities in the thermocline were differentially enriched with taxa known to be active and abundant in oxygen minimum zones or that have known adaptations to oxygen limitation shortly after the mortality event (e.g., SAR324, Thioglobaceae, Nitrosopelagicus, and Thermoplasmata MGII). Unexpectedly, these enrichments were not localized to the East Bank but were instead prevalent across the entire study area, suggesting there was a widespread depletion of dissolved oxygen concentrations in the thermocline around the time of the mortality event. Hydrographic analysis revealed the southern East Bank coral reef (where the localized mortality event occurred) was uniquely within the thermocline at this time. Our results demonstrate how temporal monitoring of microbial communities can be a useful tool to address questions related to past environmental events. IMPORTANCE In the northwestern Gulf of Mexico in July 2016, ∼82% of corals in a small area of the East Flower Garden Bank coral reef suddenly died without warning. Oxygen depletion is believed to have been the cause. However, there was considerable uncertainty, as no oxygen data were available from the time of the event. Microbes are sensitive to changes in oxygen and can be used as bioindicators of oxygen loss. In this study, we analyze microbial communities in water samples collected over several years at the Flower Garden Banks, including shortly after the mortality event. Our findings indicate that compared to normal conditions, oxygen depletion was widespread in the deep-water layer during the mortality event. Hydrographic analysis of water masses further revealed some of this low-oxygen water likely upwelled onto the coral reef.

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.

The role of sodium-glucose co-transporter-2 inhibitors in frail older adults with or without type 2 diabetes mellitus.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors offer significant outcome benefits beyond glucose lowering, including reduced risk of cardiovascular death, all-cause mortality, major adverse cardiovascular events, hospitalisations for heart failure and progression of renal disease. Considering these therapeutic effects, minimal incremental risk for hypoglycaemia and simplicity of administration, this drug class appears to be an attractive therapeutic option for older adults, and post hoc analysis of trial data provides support for the use of SGLT2 inhibitors in this population. Nevertheless, despite favourable clinical trial data, there has been some hesitance in clinical practice prescribing these drugs to older frail adults due to the limited therapeutic experience in this population and insufficient long-term safety data. In this review article, we evaluate the risk-benefit profile for the use of SGLT2 inhibitors in this population and suggest that rather than being a treatment to avoid, SGLT2 inhibitors should be considered a valid therapeutic option for older frail adults with or without diabetes.

Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England.

BACKGROUND: The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence. METHODS: All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 µg Hb/g faeces defined a positive test. RESULTS: Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1-9.3%). Negative predictive value was 99.8% (CI 99.5-99.9%). Sensitivity was 84.3% (CI 71.4-93.0%), specificity 85.0% (CI 83.8-86.1%). The area under the ROC curve was 0.92 (CI 0.86-0.96). A threshold of 37 µg Hb/g faeces would identify patients with an individual 3% risk of cancer. CONCLUSIONS: FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.

A framework for understanding gene expression plasticity and its influence on stress tolerance.

Phenotypic plasticity can serve as a stepping stone towards adaptation. Recently, studies have shown that gene expression contributes to emergent stress responses such as thermal tolerance, with tolerant and susceptible populations showing distinct transcriptional profiles. However, given the dynamic nature of gene expression, interpreting transcriptomic results in a way that elucidates the functional connection between gene expression and the observed stress response is challenging. Here, we present a conceptual framework to guide interpretation of gene expression reaction norms in the context of stress tolerance. We consider the evolutionary and adaptive potential of gene expression reaction norms and discuss the influence of sampling timing, transcriptomic resilience, as well as complexities related to life history when interpreting gene expression dynamics and how these patterns relate to host tolerance. We highlight corals as a case study to demonstrate the value of this framework for non-model systems. As species face rapidly changing environmental conditions, modulating gene expression can serve as a mechanistic link from genetic and cellular processes to the physiological responses that allow organisms to thrive under novel conditions. Interpreting how or whether a species can employ gene expression plasticity to ensure short-term survival will be critical for understanding the global impacts of climate change across diverse taxa.