Panic attacks, sudden episodes of intense fear accompanied by physical and psychological symptoms, affect approximately 23% of the population. Panic disorder, diagnosed in 2 to 4%, involves recurrent attacks followed by persistent worry about further attacks, leading to functional impairment and avoidance behaviours. We conducted genome-wide association meta-analyses of panic attacks and panic disorder (61,746 and 29,775 cases, respectively, and 105,814 controls), identifying the first genome-wide significant variants for both traits (16 for panic attacks; 7 for panic disorder). Geneset analysis using single-cell RNA sequencing data implicated afferent neurons from the eye, heart, and lung in panic attacks, suggesting a critical role for sensory processing and interoceptive awareness. Further analyses suggested that these associations generalize to other psychiatric disorders. These findings offer novel insights into the biological mechanisms underlying panic, the role of afferent neurons, and may inform the development of more targeted and effective interventions. ### Competing Interest Statement Prof Breen has received honoraria, research or conference grants and consulting fees from Illumina, Otsuka, and COMPASS Pathfinder Ltd. Prof McIntosh has received research support from Eli Lilly, Janssen, and the Sackler Foundation, and has also received speaker fees from Illumina and Janssen. Prof Walters has received grant funding from Takeda. Professor Hickie has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca, Janssen Cilag) projects focused on the identification and better management of anxiety and depression. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies. All other authors declare no conflicts of interest. ### Funding Statement AGDS/QSkin The Australian Genetics of Depression Study was funded by grant 108663 from the Australian National Health and Medical Research Council (NHMRC) This work was supported by NHMRC Investigator Grants to BLM (2017176) NRW (1173790) NGM (1172990) and IBH (2016346) The QSkin Study is supported by an NHMRC Clinical Trials and Cohort Grant [APP1185416] DCW is supported by a NHMRC Investigator Grant [APP1155413] EMB received funding from the University of Queensland Health Research Accelerator Program GLAD+ We thank the NIHR Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and Kings College London for funding This study represents independent research supported by the NIHR Biomedical Research Centre BioResource at South London and Maudsley NHS Foundation Trust and Kings College London We gratefully acknowledge capital equipment funding from the Maudsley Charity (Grant Ref 980) and Guys and St Thomass Charity (Grant Ref STR130505) Lifelines Cohort Study The Lifelines Biobank initiative has been made possible by funding from the Dutch Ministry of Health Welfare and Sport the Dutch Ministry of Economic Affairs the University Medical Center Groningen (UMCG the Netherlands) University of Groningen and the Northern Provinces of the Netherlands The generation and management of GWAS genotype data for the Lifelines Cohort Study is supported by the UMCG Genetics Lifelines Initiative (UGLI) UGLI is partly supported by a Spinoza Grant from NWO awarded to Cisca Wijmenga The authors wish to acknowledge the services of the Lifelines Cohort Study the contributing research centers delivering data to Lifelines and all the study participants QIMR GBP We thank the participants for giving their time and support for this project We acknowledge and thank M Steffens for her generous donations in loving memory of J Banks Data collection was funded and data analysis was supported by the Australian National Health and Medical Research Council (No APP1138514) to SEM SEM is supported by a National Health and Medical Research Council Investigator Grant (No APP2025674) TEDS We gratefully acknowledge the ongoing contribution of the Twins Early Development Study (TEDS) participants and their families TEDS is funded by a UK Medical Research Council (MRC) programme grant (MR/V012878/1) to TC Eley (previously MR/M021475/1 to R Plomin) UK Biobank This research has been conducted using the UK Biobank Resource under Application Number 82087 This work uses data provided by patients and collected by the NHS as part of their care and support Additional The authors acknowledge the use of the Kings College London research computing facility CREATE (https://doi.org/10.18742/rnvf-m076) NS received funding from a UKRI Future Leaders Fellowship [grant number MR/T04327X/1] and the UK Dementia Research Institute award number UK DRI-5008 through UK DRI Ltd ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: QIMR Berghofer Medical Research Institute Human Research Ethics Committee in Brisbane Australia; University Medical Center Groningen medical ethical committee; Ethical approval for the GLAD Study and NBR COPING study was obtained from the London-Fulham Research Ethics Committee (REC reference 18/LO/1218 and 20/SW/0078 respectively. COPING project no. 282754); TEDS has been granted ethical approval by the Kings College London ethics committee (References: PNM/09/10-104 and HR/DP-20/21-22060) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Summary statistics will be made available upon acceptance from a website such as Figshare or the GWAS catalog.

BACKGROUND:People with severe mental illness (SMI) have a higher risk of premature mortality than the general population. AIMS:To investigate whether the life expectancy gap for people with SMI is widening, by determining time trends in excess life-years lost. METHOD:This population-based study included people with SMI (schizophrenia, bipolar disorder and major depression) alive on 1 January 2000. We ascertained SMI from psychiatric hospital admission records (1981-2019), and deaths via linkage to the national death register (2000-2019). We used the Life Years Lost (LYL) method to estimate LYL by SMI and sex, compared LYL to the Scottish population and assessed trends over 18 3-year rolling periods. RESULTS:We included 28 797 people with schizophrenia, 16 657 with bipolar disorder and 72 504 with major depression. Between 2000 and 2019, life expectancy increased in the Scottish population but the gap widened for people with schizophrenia. For 2000-2002, men and women with schizophrenia lost an excess 9.4 (95% CI 8.5-10.3) and 8.2 (95% CI 7.4-9.0) life-years, respectively, compared with the general population. In 2017-2019, this increased to 11.8 (95% CI 10.9-12.7) and 11.1 (95% CI 10.0-12.1). The life expectancy gap was lower for bipolar disorder and depression and unchanged over time. CONCLUSIONS:The life expectancy gap in people with SMI persisted or widened from 2000 to 2019. Addressing this entrenched disparity requires equitable social, economic and health policies, healthcare re-structure and improved resourcing, and investment in interventions for primary and secondary prevention of SMI and associated comorbidities.

BACKGROUND:Depression is associated with a range of adverse physical health outcomes. We aimed to quantify the association between depression and the subsequent rate of accrual of long-term physical health conditions in middle and older age. METHODS AND FINDINGS:We included 172,556 participants from the UK Biobank (UKB) cohort study, aged 40-71 years old at baseline assessment (2006-2010), who had linked primary care data available. Using self-report, primary care, hospital admission, cancer registry, and death records, we ascertained 69 long-term physical health conditions at both UKB baseline assessment and during a mean follow-up of 6.9 years. We used quasi-Poisson models to estimate associations between history of depression at baseline and subsequent rate of physical condition accrual. Within our cohort, 30,770 (17.8%) had a history of depression. Compared to those without depression, participants with depression had more physical conditions at baseline (mean 2.9 [SD 2.3] versus 2.1 [SD 1.9]) and accrued additional physical conditions at a faster rate (mean 0.20 versus 0.16 additional conditions/year during follow-up). After adjustment for age and sex, participants with depression accrued physical morbidities at a faster rate than those without depression (RR 1.32, 95% confidence interval [CI] [1.31, 1.34]). After adjustment for all sociodemographic characteristics, the rate of condition accrual remained higher in those with versus without depression (RR 1.30, 95% CI [1.28, 1.32]). This association attenuated but remained statistically significant after additional adjustment for baseline condition count and social/lifestyle factors (RR 1.10, 95% CI [1.09, 1.12]). The main limitation of this study is healthy volunteer selection bias, which may limit generalisability of findings to the wider population. CONCLUSIONS:Middle-aged and older adults with a history of depression have more long-term physical health conditions at baseline and accrue additional physical conditions at a faster rate than those without a history of depression. Our findings highlight the importance of integrated approaches to managing both mental and physical health outcomes.

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ABSTRACT The Survey for Distant Solar Twins aims to find stars very similar to the Sun at distances of 1–$4\, {\rm kpc}$, several times more distant than any currently known solar twins and analogues. The goal is to identify the best stars with which to test whether the fine-structure constant, α, varies with dark matter density in our Galaxy. Here, we use epic, our line-by-line differential technique, to measure the stellar parameters – effective temperature Teff, surface gravity log g, and metallicity [Fe/H] – from moderate-resolution (R ≲ 32 000) spectra of 877 solar twin and analogue candidates (547 at 1–$4\, {\rm kpc}$) observed with the High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on the Anglo-Australian Telescope. These are consistent with expectations for Teff and log g from photometry, and for [Fe/H] from the Besançon stellar population model. epic provides small enough uncertainties ($\sim 90\, {\rm K}$, $0.08\, {\rm dex}$, and $0.05\, {\rm dex}$, respectively), even at the low signal-to-noise ratios available (${\rm S/N}\gtrsim$ 25 per pixel), to identify 299 new solar analogues ($\ge 90~{{\ \rm per\ cent}}$ confidence) and 20 solar twins (≥50 per cent confidence), 206 and 12 of which are at 1–$4\, {\rm kpc}$. By extending epic to measure line broadening and lithium abundance from HERMES spectra, and with ages derived from isochrone fitting with our stellar parameters, we identify 174 solar analogues at 1–$4\, {\rm kpc}$ that are relatively inactive, slowly rotating, and with no evidence of spectroscopic binarity. These are the preferred targets for follow-up spectroscopy to measure α.

Electromagnetic interference (EMI) in pulse width modulated converters is exacerbated through carrier based modulation techniques that are associated with sharp spectral peaks around multiples of the switching frequency.As a mitigation measure, spread spectrum techniques are used, that distribute the carrier spectral energy over a certain frequency range to attenuate the EMI spectrum.This paper presents an alternative implementation of spread spectrum modulation through adaptive hysteresis bands, that regulate the moving average of switching frequency in a current controlled permanent magnet synchronous motor drive.Simulation results are presented through a comparison of input EMI and common mode voltage spectra for different modulation techniques.The proposed method demonstrates notable attenuation of spectral peaks when compared to carrier based modulation, while simultaneously overcoming large switching frequency deviations that are otherwise prevalent in classical hysteresis current control.

Background: Providing user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. Objective: The objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. Methods: MoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. Results: The key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed "branching logic"). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. Conclusions: By combining different software tools-Oracle SQL, R, and REDCap-and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure.

Background The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. Methods We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. Results Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. Conclusion Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

ABSTRACT Studies of solar twins have key impacts on the astronomical community, but only ∼100–200 nearby solar twins (<1 kpc) have been reliably identified over the last few decades. The aim of our survey (SDST) is to identify ∼150–200 distant solar twins and analogues (up to ≲4 kpc) closer to the Galactic Centre. We took advantage of the precise Gaia and Skymapper surveys to select Sun-like candidates in a 2-deg field, which were observed with the HERMES spectrograph on the Anglo-Australian Telescope. We successfully built up the required signal-to-noise ratio (25-per-pixel in the HERMES red band) for most targets as faint as Gaia G of 17.4 mag. The stellar photometric/astrometric parameters (e.g. Teff, log g, mass) of our candidates are derived in this paper, while the spectroscopic parameters will be presented in the third paper in this SDST series. The selection success rate – the fraction of targets which belong to solar twins or analogues – was estimated from simulated survey data and the Besançon stellar population model, and compared with the actual success rate of the survey. We find that expected and actual success rates agree well, indicating that the numbers of solar twins and analogues we discover in SDST are consistent with expectations, affirming the survey approach. These distant solar analogues are prime targets for testing for any variation in the strength of electromagnetism in regions of higher dark matter density, and can make additional contributions to our understanding of, e.g. Galactic chemical evolution in the inner Milky Way.

Background: This study explores whether differences in religious/spiritual beliefs and behaviours (RSBB) are associated with dietary patterns in the parental generation of the Avon Longitudinal Study of Parents and Children (ALSPAC).Methods: 13,689 enrolled mothers and their associated partners from a prospective cohort study (ALSPAC) in Southwest England were included in analyses. Dietary patterns were assessed via principal components derived from food frequency questionnaires completed by mothers in pregnancy (32 weeks gestation), and by both mothers and partners 4 years post-partum. Estimated nutrient intakes, and whether participants were following recommended nutrient intake guidelines, were also examined. Belief in God/divine power, religious affiliation, and frequency of attendance at a place of worship were used as RSBB exposures (all measured during pregnancy). We first explored whether RSBB was associated with dietary patterns in unadjusted and confounder-adjusted linear regression models. If associations were found, we examined whether RSBB was associated with differences in nutrient intake (linear regression) and following nutrient intake guidelines (logistic regression). Multiple imputation was used to impute missing data.Results: In pregnant mothers, and adjusting for confounders, RSBBs were associated with higher “traditional” (i.e., ‘meat and two veg’) and lower “vegetarian” dietary pattern scores. Attendance at a place of worship and non-Christian religious affiliation were also associated with higher “health-conscious” dietary pattern scores. Attendance at a place of worship was associated with increased micronutrient intake and following recommended micronutrient intake guidelines, while effects were weaker for belief in God/divine power and religious affiliation. Comparable patterns were observed for mothers and partners 4 years post-partum, although associations between RSBBs and nutrient intakes were weaker for partners.Conclusion: RSBBs are associated with broad dietary patterns and nutrient intake in this cohort. If these reflect causal relationships, differences in diet may be potential mediators on the pathway between RSBB and subsequent health outcomes.

We define two ‘problems of altruism’. The first is the classic problem of altruism, defined as the issue of how a behavior which decreases an individual’s lifetime reproductive success, while helping another individual (or individuals) increase their lifetime reproductive success, can evolve. We also define a ‘second-order problem of altruism’, where different authors have different conceptions of what does, and does not, constitute ‘altruism’, including approaches based on kin selection, multi-level selection theory, short-term altruism and psychological altruism.

Background Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. Methods We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”). Discussion This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. Trial registration ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021

In this article we use Emirbayer and Desmond's institutional reflexivity framework to critically examine the production of racial knowledge in British criminology. Identifying weakness, neglect and marginalization in theorizing race and racism, we focus principally on the disciplinary unconscious element of their three-tier framework, identifying and interrogating aspects of criminology's 'obligatory problematics', 'habits of thought' and 'position-taking' as well as its institutional structure and social relations that combine to render the discipline 'institutionally white'. We also consider, briefly, aspects of criminology's relationship to race, racism and whiteness in the USA. The final part of the article makes the case for British criminology to engage in telling and narrating racisms, urging it to understand the complexities of race in our subject matter, avoid its reduction to class and inequality, and to pay particular attention to reflexivity, history, sociology and language, turning to face race with postcolonial tools and resolve.

S. mitis is an abundant member of the commensal microbiota of the oral cavity and pharynx, which has the potential to promote systemic infections. By analyzing a collection of S. mitis strains isolated from the oral cavity at commensal states or from systemic infections (blood strains), we established that S. mitis ubiquitously express the surface immunodominant protein, PcsB (also called GbpB), required for binding to sucrose-derived exopolysaccharides (EPS). Immuno dot blot assays with anti-PcsB antibodies and RT-qPCR transcription analyses revealed strain-specific profiles of PcsB production associated with diversity in pcsB transcriptional activities. Additionally, blood strains showed significantly higher levels of PcsB expression compared to commensal isolates. Because Streptococcus mutans co-colonizes S. mitis dental biofilms, and secretes glucosyltransferases (GtfB/C/D) for the synthesis of highly insoluble EPS from sucrose, profiles of S. mitis binding to EPS, biofilm formation and evasion of the complement system were assessed in sucrose-containing BHI medium supplemented or not with filter-sterilized S. mutans culture supernatants. These analyses showed significant S. mitis binding to EPS and biofilm formation in the presence of S. mutans supernatants supplemented with sucrose, compared to BHI or BHI-sucrose medium. In addition, these phenotypes were abolished if strains were grown in culture supernatants of a gtfBCD-defective S. mutans mutant. Importantly, GtfB/C/D-associated phenotypes were enhanced in high PcsB-expressing strains, compared to low PcsB producers. Increased PcsB expression was further correlated with increased resistance to deposition of C3b/iC3b of the complement system after exposure to human serum, when strains were previously grown in the presence of S. mutans supernatants. Finally, analyses of PcsB polymorphisms and bioinformatic prediction of epitopes with significant binding to MHC class II alleles revealed that blood isolates harbor PcsB polymorphisms in its functionally conserved CHAP-domain, suggesting antigenic variation. These findings reveal important roles of PcsB in S. mitis-host interactions under commensal and pathogenic states, highlighting the need for studies to elucidate mechanisms regulating PcsB expression in this species.

Reel-lay is a fast and cost-effective means for the installation of subsea flowlines and Pipe-In-Pipe systems with outer diameters up to 18”. Pipelines installed by the reel lay method are plastically deformed during installation. The most critical step in the installation of a reeled pipeline occurs at the spool base, when the assembled pipeline is spooled on to the hub of the reel. The nominal level of deformation is dictated by the vessel equipment geometry, applied back tension, and pipe dimensions. Localised increases in deformation are caused by mismatches in bending stiffness between adjacent pipes. The mismatch potential is dictated by the natural variation of yield strength and by dimensional variation that is inherent to linepipe manufacturing processes. Reliability based assessments are commonly applied in the assessment of minimum acceptable wall thickness for reeling. These assessments enable the minimum acceptable wall thickness to be determined with a defined target reliability level, assessing mismatches based upon distributions of wall thickness and yield strength. The mismatch parameter calculation method and the definition of appropriate acceptance criteria are the two most important factors in reeling assessments. Neither of these two factors has been specified in a pipeline design code or a recommended practice available in the public domain. However, there is an increasing level of familiarity in industry; mismatch calculation methods and strain or ovality based acceptance criteria, defined by installation contractors are gaining widespread acceptance. This paper presents a review of the application of reliability based methods currently under use, focusing on mismatch calculation methods, acceptance criteria, and probability of failure calculation methods. Minimisation of costs is of particular importance in the current oil and gas industry climate. Because of this, the ability to specify an optimum wall thickness enables installation contractors to provide more cost effective reeled rigid pipeline solutions. After reviewing the subject matter and existing body of work this paper looks in detail at the deformation responses and failure modes for a range of sizes of reeled pipelines with mismatches. The assessment of deformation responses demonstrates a significant level of conservatism in recently proposed acceptance criteria that is based upon averaged axial strain levels. This conservatism is quantified by probability of failure calculations and provides a strong justification for further optimisation of the minimum wall thickness for reeling. Finally, the beneficial effect of increased reeling tension is quantified in terms of its effect upon probability of failure.

We develop a theoretical framework to elucidate the mechanistic basis of thermal niche partitioning in ectotherms. Using a food web module of two consumers competing for a biotic resource, we investigate how temperature effects on species’ attack and mortality rates scale up to population-level outcomes of coexistence and exclusion. We find that differences between species in their competitive effects ultimately arise from asymmetries generated by the nonlinear nature of the temperature response of mortality: cold-adapted species and thermal specialists limit themselves more strongly than they limit their warm-adapted and generalist competitors. These asymmetries become greater as seasonal temperature fluctuations increase, generating latitudinal variation in coexistence patterns and priority effects. Characterizing species’ thermal niches in terms of mechanistic descriptions of trait responses to temperature allows us to make testable predictions about the population-level outcomes of competition based solely on three fundamental—and easily measurable—quantities: attack rate optima, response breadths, and temperature sensitivity of mortality. We validate our framework by testing its predictions with data from an insect host-parasitoid community. Simply by quantifying the three basic quantities, we predict that priority effects cannot occur in this system, which is borne out by population-level experiments showing that the outcome of competition does not depend on initial conditions. More broadly, our framework can predict the conditions under which exotic invasive species can exclude or coexist with native biota as well as the effects of climate warming on competitive communities across latitudinal gradients.

Collagen hybridizing peptides (CHPs) have a great potential for use in targeted drug delivery, diagnostics, and regenerative medicine due to their ability to specifically bind to denatured collagens associated with many pathologic conditions. Since peptides generally suffer from poor enzymatic stability, resulting in rapid degradation and elimination in vivo, CHP's serum stability is a critical parameter that may dictate its pharmacokinetic behavior. Here, we report the serum stability of a series of monomeric CHP derivatives and establish how peptide length, amino acid composition, terminal modification, and linker chemistry influence their availability in serum. We show that monomeric CHPs comprised of the collagen-like Gly-Pro-Hyp motif are resistant to common serum proteinases and that their stability can be further increased by simple N-terminal labeling which negates CHP's susceptibility to proline-specific exopeptidases. When fluorescent dyes are conjugated to a CHP via maleimide-thiol reaction, the dye can transfer from CHP onto serum proteins (e.g., albumin), resulting in an unexpected drop in signal during serum stability assays and off-target accumulation during in vivo tests. This work is the crucial first step toward understanding the pharmacokinetic behavior of CHPs, which can facilitate the development of CHP-based theranostics.