Increased male investment in sperm competition results in reduced maintenance of gametes.

Male animals often show higher mutation rates than their female conspecifics. A hypothesis for this male bias is that competition over fertilization of female gametes leads to increased male investment into reproduction at the expense of maintenance and repair, resulting in a trade-off between male success in sperm competition and offspring quality. Here, we provide evidence for this hypothesis by harnessing the power of experimental evolution to study effects of sexual selection on the male germline in the seed beetle Callosobruchus maculatus. We first show that 50 generations of evolution under strong sexual selection, coupled with experimental removal of natural selection, resulted in males that are more successful in sperm competition. We then show that these males produce progeny of lower quality if engaging in sociosexual interactions prior to being challenged to surveil and repair experimentally induced damage in their germline and that the presence of male competitors alone can be enough to elicit this response. We identify 18 candidate genes that showed differential expression in response to the induced germline damage, with several of these previously implicated in processes associated with DNA repair and cellular maintenance. These genes also showed significant expression changes across sociosexual treatments of fathers and predicted the reduction in quality of their offspring, with expression of one gene also being strongly correlated to male sperm competition success. Sex differences in expression of the same 18 genes indicate a substantially higher female investment in germline maintenance. While more work is needed to detail the exact molecular underpinnings of our results, our findings provide rare experimental evidence for a trade-off between male success in sperm competition and germline maintenance. This suggests that sex differences in the relative strengths of sexual and natural selection are causally linked to male mutation bias. The tenet advocated here, that the allocation decisions of an individual can affect plasticity of its germline and the resulting genetic quality of subsequent generations, has several interesting implications for mate choice processes.

Developmental bias predicts 60 million years of wing shape evolution.

The degree to which developmental biases affect trait evolution is subject to much debate. Here, we first quantify fluctuating asymmetry as a measure of developmental variability, i.e., the propensity of developmental systems to create some phenotypic variants more often than others, and show that it predicts phenotypic and standing genetic variation as well as deep macroevolutionary divergence in wing shape in sepsid flies. Comparing our data to the findings of a previous study demonstrates that developmental variability in the sepsid fly Sepsis punctum strongly aligns with mutational, standing genetic, and macroevolutionary variation in the Drosophilidae--a group that diverged from the sepsid lineage ca. 64 My ago. We also find that developmental bias in S. punctum wing shape aligns with the effects of allometry, but less so with putatively adaptive thermal plasticity and population differentiation along latitude. Our findings demonstrate that developmental bias in fly wings predicts evolvability and macroevolutionary trajectories on a much greater scale than previously appreciated but also suggest that causal explanations for such alignments may go beyond simple constraint hypotheses.

Environmental complexity mitigates the demographic impact of sexual selection.

Sexual selection and the evolution of costly mating strategies can negatively impact population viability and adaptive potential. While laboratory studies have documented outcomes stemming from these processes, recent observations suggest that the demographic impact of sexual selection is contingent on the environment and therefore may have been overestimated in simple laboratory settings. Here we find support for this claim. We exposed copies of beetle populations, previously evolved with or without sexual selection, to a 10-generation heatwave while maintaining half of them in a simple environment and the other half in a complex environment. Populations with an evolutionary history of sexual selection maintained larger sizes and more stable growth rates in complex (relative to simple) environments, an effect not seen in populations evolved without sexual selection. These results have implications for evolutionary forecasting and suggest that the negative demographic impact of sexually selected mating strategies might be low in natural populations.

Association Between Coronavirus Disease 2019 Vaccination and Mortality After Major Operations.

OBJECTIVE: The objective of this study was to compare postoperative 90-day mortality between (1) fully vaccinated patients with COVID-19-positive and negative diagnosis, and (2) vaccinated and unvaccinated patients with COVID-19 positive diagnosis. BACKGROUND: Societal guidelines recommend postponing elective operations for at least 7 weeks in unvaccinated patients with preoperative coronavirus disease 2019 (COVID-19) infection. The role of vaccination in this infection-operation time risk is unclear. METHODS: We conducted a national US multicenter retrospective, matched cohort study spanning July 2021 to October 2022. Participants were included if they underwent a high-risk general, vascular, orthopedic, neurosurgery, or genitourinary surgery. All-cause mortality occurring within 90 days of the index operation was the primary outcome. Inverse probability treatment weighted propensity scores were used to adjust logistic regression models examining the independent and interactive associations between mortality, exposure status, and infection proximity. RESULTS: Of 3401 fully vaccinated patients in the 8-week preoperative period, 437 (12.9%) were COVID-19-positive. Unadjusted mortality rates were not significantly different between vaccinated patients with COVID-19 (22, 5.0%) and vaccinated patients without COVID-19 (99, 3.3%; P = 0.07). After inverse probability treatment weighted adjustment, mortality risk was not significantly different between vaccinated COVID-19-positive patients compared to vaccinated patients without COVID-19 (adjusted odds ratio = 1.38, 95% CI: 0.70, 2.72). The proximity of COVID-19 diagnosis to the index operation did not confer added mortality risk in either comparison cohort. CONCLUSIONS: Contrary to risks observed among unvaccinated patients, postoperative mortality does not differ between patients with and without COVID-19 when vaccinated against the severe acute respiratory syndrome coronavirus 2 virus and receiving a high-risk operation within 8 weeks of the diagnosis, regardless of operation timing relative to diagnosis.

Coevolution of longevity and female germline maintenance.

An often-overlooked aspect of life-history optimization is the allocation of resources to protect the germline and secure safe transmission of genetic information. While failure to do so renders significant fitness consequences in future generations, germline maintenance comes with substantial costs. Thus, germline allocation should trade off with other life-history decisions and be optimized in accordance with an organism's reproductive schedule. Here, we tested this hypothesis by studying germline maintenance in lines of seed beetle, selected for early (E) or late (L) reproduction for 350 and 240 generations, respectively. Female animals provide maintenance and screening of male gametes in their reproductive tract and oocytes. Here, we reveal the ability of young and aged E- and L-females to provide this form of germline maintenance by mating them to males with ejaculates with artificially elevated levels of protein and DNA damage. We find that germline maintenance in E-females peaks at young age and then declines, while the opposite is true for L-females, in accordance with the age of reproduction in the respective regime. These findings identify the central role of allocation to secure germline integrity in life-history evolution and highlight how females can play a crucial role in mitigating the effects of male germline decisions on mutation rate and offspring quality.

Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Systematic approaches to assessing high-temperature limits to fertility in animals.

Critical thermal limits (CTLs) gauge the physiological impact of temperature on survival or critical biological function, aiding predictions of species range shifts and climatic resilience. Two recent Drosophila species studies, using similar approaches to determine temperatures that induce sterility (thermal fertility limits [TFLs]), reveal that TFLs are often lower than CTLs and that TFLs better predict both current species distributions and extinction probability. Moreover, many studies show fertility is more sensitive at less extreme temperatures than survival (thermal sensitivity of fertility [TSF]). These results present a more pessimistic outlook on the consequences of climate change. However, unlike CTLs, TFL data are limited to Drosophila, and variability in TSF methods poses challenges in predicting species responses to increasing temperature. To address these data and methodological gaps, we propose 3 standardized approaches for assessing thermal impacts on fertility. We focus on adult obligate sexual terrestrial invertebrates but also provide modifications for other animal groups and life-history stages. We first outline a "gold-standard" protocol for determining TFLs, focussing on the effects of short-term heat shocks and simulating more frequent extreme heat events predicted by climate models. As this approach may be difficult to apply to some organisms, we then provide a standardized TSF protocol. Finally, we provide a framework to quantify fertility loss in response to extreme heat events in nature, given the limitations in laboratory approaches. Applying these standardized approaches across many taxa, similar to CTLs, will allow robust tests of the impact of fertility loss on species responses to increasing temperatures.

Modified Thermodilution for Simultaneous Cardiac Output and Recirculation Assessment in Veno-venous Extracorporeal Membrane Oxygenation: A Prospective Diagnostic Accuracy Study.

BACKGROUND: Thermodilution is unreliable in veno-venous extracorporeal membrane oxygenation (VV-ECMO). Systemic oxygenation depends on recirculation fractions and ratios of extracorporeal membrane oxygenation (ECMO) flow to cardiac output. In a prospective in vitro simulation, this study assessed the diagnostic accuracy of a modified thermodilution technique for recirculation and cardiac output. The hypothesis was that this method provided clinically acceptable precision and accuracy for cardiac output and recirculation. METHODS: Two ECMO circuits ran in parallel: one representing a VV-ECMO and the second representing native heart, lung, and circulation. Both circuits shared the right atrium. Extra limbs for recirculation and pulmonary shunt were added. This study simulated ECMO flows from 1 to 2.5 l/min and cardiac outputs from 2.5 to 3.5 l/min with recirculation fractions (0 to 80%) and pulmonary shunts. Thermistors in both ECMO limbs and the pulmonary artery measured the temperature changes induced by cold bolus injections into the arterial ECMO limb. Recirculation fractions were calculated from the ratio of the areas under the temperature curve (AUCs) in the ECMO limbs and from partitioning of the bolus volume (flow based). With known partitioning of bolus volumes between ECMO and pulmonary artery, cardiac output was calculated. High-precision ultrasonic flow probes served as reference for Bland-Altman plots and linear mixed-effect models. RESULTS: Accuracy and precision for both the recirculation fraction based on AUC (bias, -5.4%; limits of agreement, -18.6 to 7.9%) and flow based (bias, -5.9%; limits of agreement, -18.8 to 7.0%) are clinically acceptable. Calculated cardiac output for all recirculation fractions was accurate but imprecise (RecirculationAUC: bias 0.56 l/min; limits of agreement, -2.27 to 3.4 l/min; and RecirculationFLOW: bias 0.48 l/min; limits of agreement, -2.22 to 3.19 l/min). Recirculation fraction increased bias and decreased precision. CONCLUSIONS: Adapted thermodilution for VV-ECMO allows simultaneous measurement of recirculation fraction and cardiac output and may help optimize patient management with severe respiratory failure.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Integral assessment of gas exchange during veno-arterial ECMO: accuracy and precision of a modified Fick principle in a porcine model.

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co2) or oxygen uptake (V̇o2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content V̇o2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired V̇o2 bias 482 [LoA -760 to 1,724 mL/min] for expired V̇co2) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

Immune microenvironment and lymph node yield in colorectal cancer.

BACKGROUND: Lymph node (LN) harvesting is associated with outcomes in colonic cancer. We sought to interrogate whether a distinctive immune milieu of the primary tumour is associated with LN yield. METHODS: A total of 926 treatment-naive patients with colorectal adenocarcinoma with more than 12 LNs (LN-high) were compared with patients with 12 or fewer LNs (LN-low). We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, and BRAF V600E. RESULTS: The LN-high group was comprised of younger patients, longer resections, larger tumours, right-sided location, and tumours with deficient mismatch repair (dMMR). The tumour microenvironment showed higher CD8+ cells infiltration and B2MG expression on tumour cells in the LN-high group compared to the LN-low group. The estimated mean disease-specific survival was higher in the LN-high group than LN-low group. On multivariate analysis for prognosis, LN yield, CD8+ cells, extramural venous invasion, perineural invasion, and AJCC stage were independent prognostic factors. CONCLUSION: Our findings corroborate that higher LN yield is associated with a survival benefit. LN yield is associated with an immune high microenvironment, suggesting that tumour immune milieu influences the LN yield.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Mixed support for an alignment between phenotypic plasticity and genetic differentiation in damselfly wing shape.

The relationship between genetic differentiation and phenotypic plasticity can provide information on whether plasticity generally facilitates or hinders adaptation to environmental change. Here, we studied wing shape variation in a damselfly (Lestes sponsa) across a latitudinal gradient in Europe that differed in time constraints mediated by photoperiod and temperature. We reared damselflies from northern and southern populations in the laboratory using a reciprocal transplant experiment that simulated time-constrained (i.e. northern) and unconstrained (southern) photoperiods and temperatures. After emergence, adult wing shape was analysed using geometric morphometrics. Wings from individuals in the northern and southern populations differed significantly in shape when animals were reared in their respective native environment. Comparing wing shape across environments, we found evidence for phenotypic plasticity in wing shape, and this response differed across populations (i.e. G × E interactions). This interaction was driven by a stronger plastic response by individuals from the northern population and differences in the direction of plastic wing shape changes among populations. The alignment between genetic and plastic responses depended on the specific combination of population and rearing environment. For example, there was an alignment between plasticity and genetic differentiation under time-constrained, but not under non-time-constrained conditions for forewings. We thus find mixed support for the hypothesis that environmental plasticity and genetic population differentiation are aligned. Furthermore, although our laboratory treatments mimicked the natural climatic conditions at northern and southern latitudes, the effects of population differences on wing shape were two to four times stronger than plastic effects. We discuss our results in terms of time constraints and the possibility that natural and sexual selection is acting differently on fore- and hindwings.

Experimental evolution of dispersal: Unifying theory, experiments and natural systems.

Dispersal is a central life history trait that affects the ecological and evolutionary dynamics of populations and communities. The recent use of experimental evolution for the study of dispersal is a promising avenue for demonstrating valuable proofs of concept, bringing insight into alternative dispersal strategies and trade-offs, and testing the repeatability of evolutionary outcomes. Practical constraints restrict experimental evolution studies of dispersal to a set of typically small, short-lived organisms reared in artificial laboratory conditions. Here, we argue that despite these restrictions, inferences from these studies can reinforce links between theoretical predictions and empirical observations and advance our understanding of the eco-evolutionary consequences of dispersal. We illustrate how applying an integrative framework of theory, experimental evolution and natural systems can improve our understanding of dispersal evolution under more complex and realistic biological scenarios, such as the role of biotic interactions and complex dispersal syndromes.

The Effect of Missing Data on the Measurement of Cardiac Arrest Outcomes According to Race.

INTRODUCTION: High-quality data are important to understanding racial differences in outcome following out of hospital cardiac arrest (OHCA). Previous studies have shown differences in OHCA outcomes according to both race and socioeconomic status. EMS reporting of data on race is often incomplete. We aim to determine the effect of missing data on the determination of racial differences in outcomes for OHCA patients. METHODS: We performed a secondary analysis of a data set developed by probabilistically linking the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) and the Michigan Inpatient Database (MIDB). Adult OHCA patients (age >18) who survived to hospital admission between 2014 and 2017 were included. Both datasets recorded patient race and ethnicity with CARES using a single race/ethnicity variable. Patients were categorized as White, Black, other, or missing and only a single choice was allowed. Due to the small number of Hispanic patients and the combined race/ethnicity variable, these patients were excluded. The outcomes of interest were survival to hospital discharge and survival to discharge with Cerebral Performance Category 1 or 2 (good outcome). Outcomes were stratified according to EMS- or hospital-documented race. RESULTS: We included 3,756 matched patients, after excluding 34 Hispanic patients from analysis. Documentation of patient race was missing in 892 (22.1%) of CARES and 212 (5.6%) of MIDB patients. When both datasets documented Black or White race, agreement in race documentation was excellent (κ=0.83). White patients were more likely to have good outcomes than Black in both the CARES (27.3% vs 14.8%) and MIDB (26.9% vs 16.1%) databases (both p < 0.001), but were not more likely to survive (30.8% vs 27.3% p = 0.22; 30.3% vs 28.1%, p = 0.07). Moreover, we found no significant difference in outcome measures based on race documentation for White vs Black patients (good outcome [27.3 vs 26.9% (MIDB)] and [16.1% vs 14.8% (CARES)] respectively and survival [30.8% vs 30.3% (MIDB)] and [27.3 vs 28.1% (CARES)] respectively). CONCLUSION: Despite higher rates of missing EMS documentation, we identified statistically similar rates in OHCA outcome measures between databases. Further work is needed to determine the true effect of missing documentation of race on OHCA outcome measures.

Beyond chest pain: Incremental value of other variables to identify patients for an early ECG.

BACKGROUND: Chest pain (CP) is the hallmark symptom for acute coronary syndrome (ACS) but is not reported in 20-30% of patients, especially women, elderly, non-white patients, presenting to the emergency department (ED) with an ST-segment elevation myocardial infarction (STEMI). METHODS: We used a retrospective 5-year adult ED sample of 279,132 patients to explore using CP alone to predict ACS, then we incrementally added other ACS chief complaints, age, and sex in a series of multivariable logistic regression models. We evaluated each model's identification of ACS and STEMI. RESULTS: Using CP alone would recommend ECGs for 8% of patients (sensitivity, 61%; specificity, 92%) but missed 28.4% of STEMIs. The model with all variables identified ECGs for 22% of patients (sensitivity, 82%; specificity, 78%) but missed 14.7% of STEMIs. The model with CP and other ACS chief complaints had the highest sensitivity (93%) and specificity (55%), identified 45.1% of patients for ECG, and only missed 4.4% of STEMIs. CONCLUSION: CP alone had highest specificity but lacked sensitivity. Adding other ACS chief complaints increased sensitivity but identified 2.2-fold more patients for ECGs. Achieving an ECG in 10 min for patients with ACS to identify all STEMIs will be challenging without introducing more complex risk calculation into clinical care.

Weak sex-specific evolution of locomotor activity of Sepsis punctum (Diptera: Sepsidae) thermal experimental evolution lines.

Elevated temperatures are expected to rise beyond what the physiology of many organisms can tolerate. Behavioural responses facilitating microhabitat shifts may mitigate some of this increased thermal selection on physiology, but behaviours are themselves mediated by physiology, and any behavioural response may trade-off against other fitness-related activities. We investigated whether experimental evolution in different thermal regimes (Cold: 15 °C; Hot: 31 °C; Intergenerational fluctuation 15/31 °C; Control: 23 °C) resulted in genetic differentiation of standard locomotor activity in the dung fly Sepsis punctum. We assessed individual locomotor performance, an integral part of most behavioral repertoires, across eight warm temperatures from 24 °C to 45 °C using an automated device. We found no evidence for generalist-specialist trade-offs (i.e. changes in the breadth of the performance curve) for this trait. Instead, at the warmest assay temperatures hot-selected flies showed somewhat higher maximal performance than all other, especially cold-selected flies, overall more so in males than females. Yet, the flies' temperature optimum was not higher than that of the cold-selected flies, as expected under the 'hotter-is-better' hypothesis. Maximal locomotor performance merely weakly increased with body size. These results suggest that thermal performance curves are unlikely to evolve as an entity according to theory, and that locomotor activity is a trait of limited use in revealing thermal adaptation.

Behaviour and stability of thermodilution signals in a closed extracorporeal circuit: a bench study.

Thermodilution is the gold standard for cardiac output measurement in critically ill patients. Its application in extracorporeal therapy is limited, as a portion of the thermal indicator is drawn into the extracorporeal circuit. The behaviour of thermodilution signals in extracorporeal circuits is unknown. We investigated thermodilution curves within a closed-circuit and assessed the impact of injection volume, flow and distance on the behaviour of the thermodilution signals and catheter constants. We injected 3, 5, 7 and 10 ml of thermal indicator into a heated closed circuit. Thermistors at distances of 40, 60, 80, and 100 cm from the injection port recorded the thermodilution signals (at flow settings of 0.5, 1, 1.5, and 2 L/min). Area under the curve (AUC), rise time, exponential decay and catheter constants were analysed. Linear mixed-effects models were used to evaluate the impact of circuit flow, distance and injection volume. Catheter positioning did not influence AUC (78 injections). Catheter constants were independent of flow, injection volume or distance to the injection port. The distance to the injection port increased peak temperature and rise time and decreased exponential time constant significantly. The distance to the injection port did not influence catheter constants, but the properties of the thermodilution signal itself. This may influence measurements that depend on the exponential decay of the thermodilution signal such as right ventricular ejection fraction.

Growth rate mediates hidden developmental plasticity of female yellow dung fly reproductive morphology in response to environmental stressors.

Understanding how environmental variation influences even cryptic traits is important to clarify the roles of selection and developmental constraints in past evolutionary divergence and to predict future adaptation under environmental change. Female yellow dung flies (Scathophaga stercoraria) typically have three sperm storage compartments (3S), but occasionally four (4S). More spermathecae are thought to be a female adaptation facilitating sperm sorting after mating, but the phenotype is very rare in nature. We manipulated the flies' developmental environment by food restriction, pesticides, and hot temperatures to investigate the nature and extent of developmental plasticity of this trait, and whether spermatheca expression correlates with measures of performance and developmental stability, as would be expected if 4S expression is a developmental aberration. The spermathecal polymorphism of yellow dung fly females is heritable, but also highly developmentally plastic, varying strongly with rearing conditions. 4S expression is tightly linked to growth rate, and weakly positively correlated with fluctuating asymmetry of wings and legs, suggesting that the production of a fourth spermatheca could be a nonadaptive developmental aberration. However, spermathecal plasticity is opposite in the closely related and ecologically similar Scathophaga suilla, demonstrating that overexpression of spermathecae under developmental stress is not universal. At the same time, we found overall mortality costs as well as benefits of 4S pheno- and genotypes (also affecting male siblings), suggesting that a life history trade-off may potentially moderate 4S expression. We conclude that the release of cryptic genetic variation in spermatheca number in the face of strong environmental variation may expose hidden traits (here reproductive morphology) to natural selection (here under climate warming or food augmentation). Once exposed, hidden traits can potentially undergo rapid genetic assimilation, even in cases when trait changes are first triggered by random errors that destabilize developmental processes.

Timing of a Major Operative Intervention After a Positive COVID-19 Test Affects Postoperative Mortality: Results From a Nationwide, Procedure-matched Analysis.

BACKGROUND: Studies indicate that coronavirus disease 2019 (COVID-19) infection before or soon after operations increases mortality, but they do not comment on the appropriate timing for interventions after diagnosis. OBJECTIVE: We sought to determine what the safest time would be for COVID-19 diagnosed patients to undergo major operative interventions. METHODS: High-risk operations, between January 2020 and May 2021, were identified from the Veterans Affairs COVID-19 Shared Data Resource. Current Procedural Terminology (CPT) codes were used to exact match COVID-19 positive cases (n=938) to negative controls (n=7235). Time effects were calculated as a continuous variable and then grouped into 2-week intervals. The primary outcome was 90-day, all-cause postoperative mortality. RESULTS: Ninety-day mortality in cases and controls was similar when the operation was performed within 9 weeks or longer after a positive test; but significantly higher in cases versus controls when the operation was performed within 7 to 8 weeks (12.3% vs 4.9%), 5 to 6 weeks (10.3% vs 3.3%), 3 to 4 weeks (19.6% vs 6.7%), and 1 to 2 weeks (24.7% vs 7.4%) from diagnosis. Among patients who underwent surgery within 8 weeks from diagnosis, 90-day mortality was 16.6% for cases versus 5.8% for the controls ( P <0.001). In this cohort, we assessed interaction between case status and any symptom ( P =0.93), and case status and either respiratory symptoms or fever ( P =0.29), neither of which were significant statistically. CONCLUSIONS: Patients undergoing major operations within 8 weeks after a positive test have substantially higher postoperative 90-day mortality than CPT-matched controls without a COVID-19 diagnosis, regardless of presenting symptoms.