The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here  revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses  during breastfeeding are discussed. Very little is known about coronaviruses in human milk and whether breastfeeding is a possible mode of vertical transmission.Limited, weak evidence suggests that some coronaviruses (including SARS‐CoV‐2) may be present in human milk, but these studies do not report methods of sample collection and validation of reverse transcription polymerase chain reaction (RT‐PCR) assays for human milk.Nothing is known about the timing of the antibody response in human milk to SARS‐CoV‐2 infection.Future research should utilize validated methods and focus on both potential risks and protective effects of breastfeeding.1The global pandemic caused by the SARS‐CoV‐2 virus is one of the most compelling and concerning global health crises of our time. Fortunately, this pandemic has rapidly mobilized the full range of expertise represented by researchers, clinicians and public health officials. Although our understanding of the biology, clinical implications and strategies for mitigation continues to evolve, one issue that has received limited attention is the implication of this pandemic for infant feeding practices. This lack of attention has resulted in mixed messages regarding guidance about optimal infant feeding practices  the potential role that breastfeeding could play in vertical transmission of SARS‐CoV‐2 from women to infants via human milk and (2) the potential protective effects of targeted antibodies and other immunoprotective components in human milk against COVID‐19. The goal of this review was to evaluate the published evidence regarding the presence of this and other human coronaviruses in human milk.2We used a variety of databases to identify relevant literature published as of 17 April 2020, and the list of databases and search terms used can be found in Table 2.1This review does not constitute human subject research, and as such, ethical approval was not required.33.1Camelus dromedaries; Conzade et al., The deadliest of the human coronaviruses to date is MERS‐CoV, which emerged in Saudi Arabia in 2012. The disease caused by MERS‐CoV, Middle Eastern respiratory syndrome (MERS), is characterized by severe respiratory illness with symptoms of fever, cough and shortness of breath. MERS‐CoV is a betacoronavirus, and the case fatality rate of MERS is 34% Mahase, . There a3.2A related virus, SARS‐CoV, emerged in 2003 in China, although the disease (severe acute respiratory syndrome [SARS]) quickly spread globally. SARS is clinically manifested by fever, dry cough, headache, muscle aches and difficulty breathing. No treatment exists except supportive care, but there have been no reports of SARS‐CoV transmission since 2004. Like MERS‐CoV, SARS‐CoV is a betacoronavirus, and the case fatality rate of SARS is estimated at 10% Mahase, .Currently, there is one report in which human milk was tested for SARS‐CoV  or Europe . Although this limited geography makes sense given the fact that the initial epicentre of this pandemic was in Asia and this was followed by a large outbreak throughout Italy, studies from other globally representative populations are needed to make definitive conclusions regarding the possible presence and/or role of SARS‐CoV‐2 in human milk. Additionally, the importance of a coordinated, international effort by scientists, clinicians and public health officials to elucidate answers to the many remaining questions related to SARS‐CoV‐2 and breastfeeding cannot be overemphasized.5Human milk is the gold standard for infant feeding. However, confidence as to its safety and best practices around breastfeeding during maternal COVID‐19 infection has been compromised by the lack of rigorous evidence as to whether SARS‐COV‐2 can be vertically transmitted in milk and/or during breastfeeding. As such, there exists an immediate need to rapidly generate rigorous evidence for the role (if any) of human milk and breastfeeding in vertical transmission of COVID‐19 from mothers to infants. To accomplish this, validation of analytical methods for the human milk matrix, viability testing and evaluation of other immune components in milk will all be critical to this effort, especially given the known protective effects of breastfeeding in other infant respiratory infections  in milk produced by infected women, women with infected infants and women who have been exposed to SARS‐CoV‐2; if the virus is identified in milk, its viability must be verified.Multinational population studies documenting (or not documenting) risk of COVID‐19 infections in breastfed versus nonbreastfed infants whose mothers are COVID‐19 positive.Research delineating implications of skin‐to‐skin breastfeeding versus consumption of pumped human milk.To understand the role of human milk and SARS‐CoV‐2 infection, the following points must be rapidly addressed.The authors declare that they have no conflicts of interest.KAL, RMP and JEW performed the literature search. KAL wrote the first draft. All authors read, contributed to and approved the final manuscript.Supporting Information S1Click here for additional data file.


JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano‐adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load‐related strains vary with age and sex. In this study, full‐field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old , male and female C57BL/6J mice with load applied using a noninvasive murine tibial model. Strain maps indicate a nonuniform strain field across the tibial surface, with axial compressive loads resulting in tension on the medial side of the tibia because of its curved shape. The load‐induced surface strain patterns and magnitudes show sexually dimorphic changes with aging. A comparison of the average and peak tensile strains indicates that the magnitude of strain at a given load generally increases during maturation, with tibias in female mice having higher strains than in males. The data further reveal that postmaturation aging is linked to sexually dimorphic changes in average and maximum strains. The strain maps reported here allow for loading male and female C57BL/6J mouse legs in vivo at the observed ages to create similar increases in bone surface average or peak strain to more accurately explore bone mechano‐adaptation differences with age and sex. © 2021 The Authors.  The numerous animal models developed to study mechano‐adaptation have shown that the parameters of the loading regime  dramatically influence the ensuing bone (re)modeling. These studies have found that cyclic compressive loads of 8.7–13 N applied to the tibia of the flexed hind limb in anesthetized mice elicit an osteogenic/antiresorptive response in a spatially restricted manner that correlates with the load magnitude. It is assumed that such adaptation is coordinated in response to a strain‐related stimulus, reliant on magnitude, rate, gradient, fluid velocity caused by strain, or microdamage (from excessive strain).Bone dynamically adapts its architecture in response to the applied loads. This mechano‐adaptation process is central in maintaining bone mass and ensuring sufficient bone strength. Previous clinical studies, in vitro cell culture experiments, and in vivo animal experiments have sought to explore bone's mechano‐adaptive responses.14 The Therefore, calibration is required to ensure that the applied strains are matched during in vivo loading across groups of animals that may have different bone structure and material properties. Thus, most studies have related mechano‐adaptation of bone to the strains measured experimentally using strain gauges, attached to a single location on the exposed cortical bone surface either in vivo, to measure physiologically induced strains, or in representative ex vivo loading, for calibration. Other studies have used finite element (FE) analysis to estimate bone strains, but these analyses require assumptions to be made regarding the geometry, material properties, and loading conditions. It is evident that both methods are limited in providing measurements of the load‐related strain engendered across an entire bone surface.To measure the bone's response to applied loading, most animal models assume that adaptation is engendered in response to a peak strain stimulus.25 The Although applied ex vivo, DIC offers a significant advance over the typical characterization of the bone's mechanical environment. DIC measures strains in inhomogeneous, anisotropic, and nonlinear materials with a complex morphology, like bone. Using ex vivo DIC in combination with an in vivo mouse tibial loading model, we have previously shown that strains engendered on the tibia surface are not homogenous but have focal regions of high strain that become more homogenous after adaptation. We have also used DIC to calibrate load magnitudes to engender a strain‐matched stimulus to tibia in mice with vastly divergent ages. Thus, the location selected for strain calibration is extremely important in experiments exploring how bone responds to loading.Recently, digital image correlation (DIC) has been used to measure high‐resolution, full‐field strains on cortical bone surfaces in the murine tibia–loading model.28 Alt Although comparison of bone adaptation across these studies is challenging because they do not all report changes in the same morphological bone region, they have found that cortical bone in the young murine tibia is very responsive to loading, whereas controversial results have been found in aged bone. Some studies, which have used strain gauges to calibrate the applied load, found that aged bone does not exhibit efficient adaptation at similar strain magnitudes as young bone, interpreting this result as a failure of aged bone to adapt. These data have led to an assertion that bone mechano‐adaptive response is progressively and irreversibly diminished during aging. However, other studies found that the reduced adaptation of aged mice can be reversed by disuse, and recently we found that only two bouts of DIC‐calibrated peak strain‐matched (~0.57%) loading are sufficient to initiate bone adaptation in old female mouse tibia. This is consistent with the notion that high strains have been considered one of the most effective drivers for bone mechano‐adaptation, as observed in previous human and animal studies. Thus, a better understanding of the mechanical stimulus that is needed to restore bone mass in both aged male and female bone, may arise from a comprehensive understanding of the mechanical environment of the bone. In this regard, information on the strain distribution across a bone surface is a key component for a correct bone loading regime at each age and for each sex.The relationship between the mechanical strains on cortical bone and its adaptation has been explored, particularly using the murine tibial–loading model, by comparing regions of bone formation from in vivo μCT, histology, and recently three‐dimensional fluorochrome mapping coupled with FE models of mechanical stimulus.35 AltIn this study, we compare the full‐field strains map of the cortical bone surface in young, adult, and old mice of both sexes in a mouse tibial loading model using DIC. Understanding the difference in the strain map on an entire bone surface under the same loading conditions is important to relate local mechanical stimuli to local biological response in bone tissue during aging and with sex.N = 5/group; Charles River Company), males and females aged 10 weeks old, 22 weeks old, and 20 months old were considered for this study. Mice were sacrificed by cervical dislocation, and left and right tibias were exposed by removing the surrounding muscles. Bones were subsequently covered with a thin layer of matt, water‐based white paint , and speckled with matt, acrylic black ink  using a high‐precision airbrush . Legs were loaded up to 12 N  at 8 N/min load rate, with a preload of 0.2 N, using custom‐built loading cups, which apply an axial load across the knee and ankle joints. During the continuous loading, images of the medial side of the speckled tibia surface were recorded at 1 N intervals using two adjustable charge‐coupled device (CCD) cameras  at a distance of 148 cm to each other and oriented to face the bone surface to provide a field of view of 15 × 12 mm with a resolution of 7.5 × 10.9 μm and a depth of focus of 1.2 mm. The sample was lit by two light‐emitting diode lamps with polarized filters. Calibration was conducted by using a high‐precision 15 mm × 12 mm panel (GOM GmbH). Postprocessing of the images was performed using DIC ARAMIS 5M  System from GOM GmbH with 19 × 19‐pixel square facets, with 15 pixels step facet, resulting in approximately 2500 measurement points on the surface of each tibia. Three images were taken in the undeformed state to allow for the determination of the amount of error (noise) during the experiments, and the surface of each tibia was imaged at least two times to show repeatable strain fields. The analysis of these ex vivo bone images determined linear strain magnitudes and distribution patterns on about 57% of the C57BL6/J mouse tibia surface (centered at 35% of the bone length—corresponding to the visible surface on the tibia bone not hidden by the cups) during aging and with sex. Peak and average strain on the medial surface of the considered region of interest (ROI) of the tibia was calculated at each 1 N load and averaged across the specimens in each group. The average strains were calculated automatically by the software; peak strains were assessed within the ROI without considering the edges that often report noise in the DIC images.Six groups of C57BL/6J mice . Differences in maximum and average strain at the different ages and for the sexes were compared using analysis of variance factorial ANOVA  and post hoc procedures for multiple comparisons. All tests were two tailed and  Figure The spatial strain distribution over the medial side of the considered ROI of the tibia of C57BL/6J mice was measured by the DIC system based on the three components of displacement as previously described.27 Figp < 0.001). At 10 weeks of age, tibias from male and female mice have similar strain patterns, but statistically significant different magnitudes at 12 N . As the mouse ages, the strain at 12 N increases in magnitude and patterns diverge in male and female bones . However, a different behavior was observed between male and females with age: though the averaged strain increased from 10 to 22 weeks old in both male and female mice, the average strain stabilized in females and decreased in males at 20 months old  and material properties that occur with aging. Skeletal maturity in C57BL6/J mice occurs at around 20 weeks of age simultaneously with an increase in bone rigidity, cross‐sectional area, and cortical thickness.49 How with sex‐related geometrical variation already present at 6 years of age, likely caused by differential adaptation to the mechanical loading. During human growth and senescence, hormone differences, disparities in bone adaptation (moment of area) to the dissimilar mechanical environment, and different intracortical porosity microarchitecture contribute to the increased bone fragility experienced in women. Therefore, it is crucial to consider these age‐ and sex‐related differences when planning an exercise or loading regime aimed to restore bone mass in the elderly. In this regard, application of the results of this study as calibration for future studies has potential to increase our knowledge of age‐ and sex‐related differences in bone mechano‐adaptation. This may also allow for improved understanding of bone fragility as it might relate to the different bone mechano‐adaptive responses with age and sex.Analogous changes during aging and sexual dimorphism during growth and maturity are observed in human bones,54 wit Thus, if load is correctly strain‐matched, it is possible to stimulate a cortical mechano‐adaptive response also during aging. For years, loads applied in vivo in animal studies were strain‐matched using a single measure provided by strain gauges, and the lack in response to mechanical loading of aged bones was considered to be caused by either a failure of the osteocytes to sense load or a failure of osteoblasts to lay down new bone. With the use of the DIC strain map calibration, we were able to match the peak‐strain in mature and old bone and show that aged bone is responsive if sufficient load stimulus is applied as a trigger. This further shows the importance of having a full‐field strain map compared with single‐point measures obtained with strain gauges. When comparing the strain map results from our DIC with those obtained using strain gauges, it is clear that the latter significantly underestimate peak strains. Furthermore, inconsistency has been found in the results emerging from previous strain gauge studies, where a peak strain of 0.2%–0.22% was estimated in mature mice either at 8 N (20 weeks old) or at 11.5–12 N . Our results show an average strain of 0.2% at 8 N for female adult bone (22 weeks old), whereas at 12 N the average strain is significantly higher (0.35%) than those estimated by strain gauges. Strain measurement is highly sensitive to measurement location, particularly in irregular, heterogeneous, and anisotropic material like bone. Strain gauge measurements are likely not taken at the exact peak strain site, and gauge location on bone significantly affects strain measurement. The results presented in this study are in agreement with previous full–field bone surface strain measurements taken during tibial loading in C57BL6/J mice. Our studies and others show divergent strains in mouse breeds known to have different material properties at the same age.The DIC data presented here were recorded at 1 N increments up to 12 N. This information can be used to load mouse bones in vivo and accurately match strains to better understand bone mechano‐adaptation and eventually define strain's localized effect on bone architecture. In a previous study, we have used DIC strain maps to calibrate in vivo loading of aged mice tibia  with peak strain‐matched to mature bone  and were able to initiate bone response in aged bone.15 Thu In this study, the relationships between load and average strain on the bone surface of interest are nonlinear. Tibial curvature and irregular geometry, as well as heterogeneity in local mineralization (and stiffness) levels, determine the linear load‐strain relationship at each bone location, for which the slopes may indeed differ. With small loads, the strains on the bone surface are small and thus differences may be less evident, but with increased loads certain bone locations may experience much more strain than others. Thus the relationship between applied load and average strain on the surface of interest will not necessarily be linear. This is an important aspect of the heterogeneity in bone surface strains revealed by DIC that would not be appreciable using strain gauges.Bone is often considered a linear material, in which strain at each single location exhibits a linear relationship with the applied loads. We have shown this is true at discrete points on the surface of the bone.26 In  The data presented here and elsewhere show the importance of evaluating the loads to apply on bone prior to an in vivo load‐adaptation study. They also highlight the likely necessity, in longitudinal studies, for animals to be euthanized at different ages to allow for such calibration. Herein, we generated cortical bone strain maps for tibias of C56BL6/J mice at three ages in both sexes, and five mice per group were sufficient to reveal statistical significant differences. Our previous studies on aging and knock‐out mice detected tibia bone strain differences in groups containing only four bones. However, it is not possible to draw conclusions from these studies on the actual number of mice that will be needed for each bone type and mouse strain examination at different ages. Bone geometry, internal structure, and material properties will always be specimen‐specific, and differences between specimens may become larger with age, even for inbred animals kept under identical conditions. Therefore, future studies using different mouse strains and/or any other condition  will need to include an identical group just to provide accurate strain values for their specific calibration, and to determine the sample number required for this bone strain assessment.Our studies have shown that when aged mice are loaded to match peak strain, adaptation occurs; when they are loaded to match average strain, no adaptation occurs.15 The Using DIC strain maps, we validated a FE model of the bone and correlated the mechanical stimuli to the ensuing spatial changes in osteogenic activity. We found that fluid velocity predicts bone adaptation in adult bone both periosteally and endosteally, whereas strain energy density fails to predict endosteal bone formation. Future studies will further investigate the mechanical stimulus in bone adaptation with age and sex to guide the development of loading protocols to direct bone formation to a specific site in osteopenia.The presented DIC maps can further be used to validate FE models of the tibia loading in C57BL6/J mice, for example, examining the mechanical stimulus for bone adaptation.35 UsiThis study shows that the full‐field strain maps on the cortical tibia bone surface vary in C57BL6/J mice with age and sex. This will make it possible for us to more precisely match strains to the ensuing changes in cellular osteogenic/antiresorptive adaptive activity between the various groups we analyzed. Understanding how mechano‐responsiveness is influenced by aging and sex will help understand changes in mechano‐responsiveness in aged bone.The authors have no conflict of interests.Alessandra Carriero: Conceptualization; formal analysis; funding acquisition; investigation; methodology; project administration; resources; writing‐original draft preparation; writing–review & editing; visualization. Behzad Javaheri: Conceptualization; writing‐review & editing. Neda Bassir Kazeruni: Investigation; methodology; writing‐review & editing. Andrew A. Pitsillides: Conceptualization; funding acquisition; resources; writing‐review & editing. Sandra J. Shefelbine: Conceptualization; funding acquisition; project administration; resources; writing‐review & editing.https://publons.com/publon/10.1002/jbm4.10467.The peer review history for this article is available at


Videogame controller–induced knuckle pads may present in a strikingly unique distribution. Successful paring without recurrence can be achieved when combined with removal of the original insult. Videogame controller–induced knuckle pads may present in a strikingly unique distribution. Successful paring without recurrence can be achieved when combined with removal of the original insult. We present a case of videogame controller–induced knuckle pads on the ulnar and radial surfaces of the digits. Successful treatment without recurrence was achieved when paring was combined with removal of the original insult.A healthy 19‐year‐old male was referred to our clinic with concern for keratoderma given clinical diagnosis of knuckle pads. He presented with firm, nontender, hyperkeratotic papules on the ulnar surface of the proximal interphalangeal joints of the first digits and the radial surface of the second‐fourth digits bilaterally (Figure Knuckle pads are benign, hyperkeratotic papules, nodules, or plaques typically found on the extensor surfaces of the metacarpophalangeal or interphalangeal joints.#15 blade paring of the lesions combined with physician‐directed behavioral modifications—limiting videogame controller use and taking frequent breaks—led to successful treatment Figure . For traNone declared.All authors: made substantial contributions to the preparation of this manuscript and approved the final version for submission.KF: performed literature search, drafted initial version of manuscript, and revised manuscript. SK: contributed significant revisions to the manuscript and acquired images. KP: contributed significant revisions to the manuscript.Patient consent for publication available upon request.


TM for the detection of LAVA  when they are buried within the far‐field ventricular signal, especially in regions of preserved myocardial thickness, such as the left ventricular (LV) septum. The LV substrate and the tachycardia circuit during ventricular tachycardias of a 60‐year‐old man with dilated cardiomyopathy were mapped using an ultra‐high‐density mapping system and then the LumipointTM, analyzing the EGMs of interest, identified the LAVA in the inferoseptal region. This algorithm may be helpful to quickly target the septal substrate avoiding misleading interpretation.We report the use of the new automated tool Lumipoint The Lumipoint tool allows electrophysiologists to quickly identify and target the septal substrate analyzing thousands of electrograms and illuminating signals of interest on the map. EGMelectrogramICDimplantable defibrillatorLAVAlocal abnormal ventricular activitiesLVleft ventricleRAOright anterior oblique viewRFradiofrequencyRVright ventricleVTventricular tachycardias1Local abnormal ventricular activities (LAVA) are defined as sharp high‐frequency ventricular potentials, distinct from far‐field ventricular electrograms (EGM), which can be detected during sinus or paced rhythms.2TM algorithm to rapidly look for EGMs of interestTM search window inside the QRS and asking the software to illuminate fragmented potentials, we saw that LAVA spanned the whole inferoseptal wall from the base to the apex , VT was no longer inducible. After a follow‐up of 7 months, no VT recurrence was reported by the patient or detected by his ICD.A 60‐year‐old man with dilated cardiomyopathy was referred to our laboratory for recurrent episodes of ventricular tachycardias (VTs), which were usually terminated by high‐energy shocks from his dual‐chamber implantable defibrillator (ICD). We mapped both the left ventricular (LV) substrate and the tachycardia circuit during VT using the Orion multipolar basket catheter and the Rhythmia mapping system (Boston Scientific). The substrate map was acquired during RV pacing Figure . At thisx Figure . After h3TM can address the physician to look at signals in a region where a fragmented activity exists. In this case, the fragmented activity was found inside the QRS complex. Normal tissue typically does not show fragmented signals but just a single rapid deflection inside the QRS; therefore, if a fragmented activity is found inside the QRS, which means that in addition to the far field from normal tissue, there are other sharp ventricular potentials and this is exactly the definition of LAVA. So, if a fragmented activity is found by the LumipointTM software inside the QRS in a specific region, this means that the same region harbors LAVA. At this point, by looking at the LAVA signals, the electrophysiologist can differentiate the high‐amplitude far‐field from the lower‐amplitude near‐field LAVA.LAVA may appear at any time during or after the far‐field ventricular signal during sinus or paced rhythm, and their lateness depends on both the local conduction delay and the anatomic location of the arrhythmogenic region.When the area suspected of harboring LAVA is quite extensive, these pacing maneuvers have to be carried out throughout the region of interest, with the risk of unmasking fewer abnormal EGMs than originally thought. Another maneuver used in order to find a poorly coupled near‐field potential is pacing at a fixed rate from the catheter recording the suspected LAVA. When a long stimulus‐to‐QRS (greater than 40 ms) is detected, slow conduction away from the pacing site indicates an abnormal substrate.TM software is a new automated algorithm that is able to illuminate areas of the LV whose EGMs have multiple deflections. This tool is very effective in spotting septal LAVA, as indicated by our case, since it eliminates the subjectivity of the human eye in assessing high‐frequency signals that are buried within, or very close in activation to, far‐field signals. The software analyses thousands of EGMs in a matter of seconds, providing a clear identification of the septal region harboring signals with multiple deflections. The same analysis by the eye of the physician would be much more time‐consuming and would inevitably introduce some subjectivity. Even if the physician applies pacing maneuvers to the signals illuminated by the software, in order to confirm the nature of LAVA, the process depends on the rapid identification of a very likely septal substrate. In addition to this, the LumipointTM software is also a reannotation tool, and it can be used to correctly annotate LAVA instead of far field.The nature of fractionation split and the lateness of septal LAVA are strongly influenced by the activation wavefront. However, despite the introduction of ultra‐high‐density mapping systems, it is still time‐consuming in daily practice to create multiple substrate maps (as through RV and LV pacing). The fractionation tool of the new Lumipoint4TM algorithm was helpful in rapidly identifying septal LAVA, which constituted the critical substrate of the clinical VT.In our case, the new LumipointNo external funding was obtained for this project. Francesco Maddaluno and Maurizio Malacrida are Boston Scientific employees, no other conflicts of interest exist.Video S1Click here for additional data file.Video S2Click here for additional data file.Video S3Click here for additional data file.Supplementary MaterialClick here for additional data file.Supplementary MaterialClick here for additional data file.Supplementary MaterialClick here for additional data file.


Homarus gammarus), the size of claws relative to body size correlates positively with male mating success and is presumably under sexual selection. At the same time, an intensive trap fishery exerts selection against large claws in males. MPAs could therefore be expected to resolve these conflicting selective pressures and preserve males with large claws. We explored this hypothesis by contrasting claw size of males and females in three pairs of MPAs and nearby fished areas in southern Norway. By finding that male lobsters have up to 8% larger claws inside MPAs compared to similarly sized males in fished areas, our study provides evidence that MPAs rescue a secondary sexual trait. Recovery from harvest selection acting on claws is the most likely explanation; however, the higher abundance of lobster inside MPAs does not rule out a plastic response on claw size due to increased competition. Regardless of the underlying cause, our study demonstrates (a) the value of protected areas as a management tool for mitigating fisheries‐induced evolution and (b) that MPAs help maintaining the scope for sexual selection in populations with vulnerable life histories and complex mating system.Marine protected areas (MPAs) are increasingly implemented worldwide to maintain and restore depleted populations. However, despite our knowledge on the myriad of positive responses to protection, there are few empirical studies on the ability to conserve species’ mating patterns and secondary sexual traits. In male European lobsters ( Yet, humans can act as a very strong selective agent sometimes opposing what is favoured by natural selection pressures , individuals harvested near protected areas in Canada had larger average horn size compared to rams shot far from protected areas  decreased with distance from a national park  found that large claws increase male mating success. Specifically, sexual selection seems to be acting more strongly on relative claw size (with respect to body size) than on absolute claw size or body size  claw and a minor incisor‐toothed (cutter) claw. In most species, males grow larger and heavier claws than females and are considered secondary sexual traits  males and females is estimated to be 31 and 54 years, respectively  are large, long‐lived sexually dimorphic crustaceans in temperate waters distributed from the north of Norway to Morocco in North Africa, including the Mediterranean Sea , Kvernskjær in Østfold County  and Bolærne in Vestfold County  was measured to the nearest millimetre as a measure of body size. We measured the width of the major crusher claw as the widest part of the crusher claw  to obtain a measure of claw size  in all three counties. Claw data were collected between 2017 and 2019. Each of the MPAs and the monitored fished areas was sampled simultaneously before the start of the fishing season, between 20 August and 10 September each year, so that shared temporal effects can be accounted for. All lobster were caught using a set of 25 individually marked mackerel‐baited two‐chambered Parlour traps placed at the bottom at depths between 8 and 30 m, with a 24‐hr soak time prior to each haul (yielding 100 hauls in each area per year). The traps were positioned evenly throughout the study areas at preferred lobster habitats, typically rocky and hard bottom substrate. Traps used in the fishery have escape openings to allow undersized lobster to escape. The traps used in the sampling programme, however, have no escape openings to increase the size range of captured animals. Data on location, depth and lobster catch of every trap were recorded. All captured lobster were sexed, and total length (2.3Status), adjusted for body size (TL). Injuries to and loss of appendages are common among decapod crustacean and are exacerbated by fishing methods  was plotted for a visual comparison of population density between reserves and fished areas over the last 13 years. To provide a measure of mean density for the years with claw measures, we averaged the CPUE over the last 3 years . To investigate the effects of protection on claws, we first tested whether the probability of missing one or both claws differed between areas  is the response variable, with the factor County accounting for spatial differences among the three counties  as levels. As a first step, we censored any lobsters that had very small crusher claws, most likely resulting from a regeneration of a lost claw. Claw loss inhibits growth in crustaceans , regenerated claws are typically smaller than intact claws, even after multiple moults  since harvest selection is assumed to only operate on legal‐sized lobster , only 4.6% were caught in the fished areas. Thus, we restricted our models to compare only the overlapping size range between fished areas and MPAs . If harvest selection acts on relative claw size, a significant interaction effect can be expected due to cumulative selective mortality that should lead to increasing difference with age (which is assumed to be closely correlated with body size). The interaction was dropped if nonsignificant (p > .05). The three sampling years were pooled as a preliminary model revealed no year effect on claw width (results not shown). All statistical analyses were performed in R 3.5.1  for legal‐sized lobster. From 2017 to 2019, the same years as claw measurements were taken, and the lobster catches in the MPAs were 5.08 times higher in Aust‐Agder, 3.58 times higher in Vestfold and 2.87 times higher in Østfold than in their respective fished areas  or females . Moreover, females were more likely to miss a claw in the MPAs , but no such difference was evident for males . After removing individuals with missing claws and with incomplete measurement data, 2,560 lobster  had intact crusher claws: 1,707 from the MPAs and 853 from the fished areas  accounted for 4.3% of the total catch, 5.4% in MPAs and 2.2% in fished areas. There was no relation between claw loss and body size in either males . Using Vestfold as an example, the model predicted that the average male entering the fishery (250 mm TL) would have the same crusher claw size in the fished area and the protected area . However, with increasing body size, all claws became progressively larger in the MPAs; claws were an estimated 8% larger in MPA males with a body size of 362 mm TL, which corresponds to the largest male captured in the fished area , their relative claw size also differed between fished and protected areas as the additive effect of Status was significant , bolder individuals are more likely to be attracted to and captured in baited traps because they also grow faster and require more food .The larger claws of lobster in the MPA are most likely a reflection of the high and selective fishing mortality outside MPAs  output from large females  could counter opposing selection pressures in nearby fished areas. Additionally, spillover by males with attractive phenotypes to harvested areas  can strengthen sexual selection through dispersal and gene flow if they are able to reproduce before they are harvested , sex‐changing fishes with dominance hierarchies or nest‐builders with territorial behaviour, many of which are numerous in both temperate and tropical reef ecosystems. A natural next step should be to investigate the responses of other species in the same study system, for example the sexually dimorphic brown crab . The discrepancy in trait expression between protected and fished areas also serves as a strong warning signal about unintended consequences of selective fishing. MPAs with animals not selected by fishing will exchange individuals and genotypes with surrounding areas and can therefore be effective in curbing undesired phenotypic selection from harvesting  and the Norwegian Directorate of Fisheries . The European lobster is categorized as being of Least Concern in the Norwegian Red List for Species after the new revisions in 2015 .Fig S1‐S2Click here for additional data file.


Data analyses were performed using Cochrane Collaboration RevMan 5.0. Nine studies were identified from the literature review. Of these studies, three studies compared the results of bone–patellar tendon–bone (BPTB) and ligament augmentation and reconstruction system (LARS), while six studies compared the results of four‐strand hamstring tendon graft (4SHG) and LARS. The comparative study showed no difference in Lysholm score and failure risk between autografts and synthetics. The combined results of the meta‐analysis indicated that there was a significantly lower rate of side‐to‐side difference > 3 mm , overall IKDC , complications , and Tegner score  in the synthetics group than in the autografts group. This systematic review comparing long‐term outcomes after cruciate ligament reconstruction with either autograft or synthetics suggests no significant differences in failure risk. Autografts were inferior to synthetics with respect to restoring knee joint stability and patient‐reported outcome scores, and were also associated with more postoperative complications.To describe the outcomes of autografts and synthetics in anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction with respect to instrumented laxity measurements, patient‐reported outcome scores, complications, and graft failure risk. We searched PubMed, Cochrane Library, and EMBASE for published randomized controlled trials (RCT) and case controlled trials (CCTs) to compare the outcomes of the autografts  Arthroscopically assisted anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) reconstruction has been widely used for patients with cruciate ligament lesions, and advances in arthroscopic surgery have yielded good clinical results. However, controversy continues over the choice of graft tissue, including autografts, allografts, and synthetic ligaments. Two of the most common autografts used are bone–patellar tendon–bone (BPTB) and four‐strand hamstring tendon 4SHT)SHT4. Howversus bone–patellar tendon–bone graftsThere have been numerous systematic reviews comparing the results of autograft hamstring et al.P < 0.001), which did not account for the effect of irradiation on the allograft tissue. Christopher et al.et al.There have also been many studies comparing autograft with allograftThe purpose of this systematic review was to conduct a meta‐analysis to compare the effectiveness of cruciate ligament reconstruction using either autografts or synthetics. We hypothesize that autografts or synthetics show no difference in: (i) instrumented laxity measurements; (ii) patient‐reported outcome scores; (iii) complications; or (iv) graft failure risk after cruciate ligament reconstruction.The PRISMA  guidelines were followed from the inception of the study. A review of the literature was performed by two authors (L Li and XM Cao) using PubMed, Cochrane Library, and EMBASE from inception through January 2018. Key search terms included  and [. No language limitations were imposed. The reference lists of the selected articles were reviewed to identify additional studies not found in the original search.Two researchers reviewed the generated list of unique articles for studies that met the following inclusion criteria: (i) Participants: the autografts and synthetics in the treatment of cruciate ligament lesions and minimum 2‐year follow‐up; (ii) Interventions and comparisons: at least two study groups in ACL or PCL reconstruction with either autograft or synthetics, the type of graft fixation was not limited; (iii) Outcome measure: the outcome assessments included instrumented laxity measurements, patient‐reported outcome scores, complications, and graft failure risk; (iv) Study design: CCTs, both randomized controlled trial (RCTs) and case controlled trials (CCTs). The following studies were excluded: (i) case‐based reports or reviews without original data; (ii) studies with imprecise experimental design; and (iii) studies with incomplete data or incorrect data.Two investigators independently extracted data that met our inclusion and exclusion criteria. Disagreement between two reviewers was resolved by discussion or consultation with a third reviewer when necessary. The following information was extracted: details on study designs; patient demographic characteristics; length of clinical follow‐up, percentage lost to follow‐up, description of surgical technique, and clinical variables including follow‐up time, complications, knee laxity measurements with KT‐1000/KT‐2000 arthrometer, patient‐reported quantitative outcome measures . If a study did not specifically state whether it was retrospective or prospective in nature, it was assumed to be retrospective. Failure was defined either as complete or partial rupture of the ligament or as a documented “failure” as defined by each included study. The methodological quality of RCTs was evaluated independently by two of the authors (K Li and L Guo) using the tool for assessing risk of bias described in Chapter 8 of the Cochrane Handbook Systematic Reviews of Interventions (Version 5.1.0). This tool is comprised of a description and judgment for each entry in a “risk of bias” table, where each entry addresses a specific feature of the study. The judgment for each entry involves answering a question, with answers “Yes” indicating low risk of bias, “No” indicating high risk of bias, and “Unclear” indicating either lack of information or uncertainty over the potential for a bias. Quality assessment of non‐RCTs was performed according to the Methodological Index for Non‐Randomized studies (MINORs)OR) and the mean difference (MD) was used for continuous outcomes, both 95% confidence intervals (CI). A χ2 test was used to assess heterogeneity between different studies, inter‐study heterogeneity was assumed in cases in which I2 > 50% or P value <0.1ORs were pooled according to random‐effects models. Alternatively, fixed‐effects models were used. A P value less than 0.05 was considered statistically significant. A sensitivity analysis was conducted by excluding one study in each round and investigating the influence of a single study on the overall meta‐analysis estimate.Data analysis was performed using RevMan 5.3 software. Two authors (JG Lu and ZZ Duan) checked the data during entry to ensure that there were no errors. Dichotomous outcomes were expressed in odds ratio  in the allograft group and 48 months  in the synthetics group. The allograft group contained 79.4% male and 20.6% female patients, and the synthetics group contained 76.5% male and 23.5% female patients. Of the nine studies included in this review, there were three randomized controlled trial, the other six studies were relatively high‐quality retrospective study  in the autografts group and 4.9%  in the synthetics group    , indicating that complications of synthetics were less than autografts.Table et al.et al.Graft rupture was labeled as failure, with other reasons for reoperation categorized as “complications.” Nau A substantial body of literature has examined the factors influencing outcome after ACL reconstruction, including comparisons of tunnel placement, fixation technique, and graft choice. Although many studies argue in favor of one form of autograft over another, confounding variables of such a complex surgery are often difficult to control, and may influence resultsAdmittedly, autograft cruciate reconstruction is the gold standard, providing reliable long‐term results, while this method somewhat reminds us of robbing “Peter to pay Paul.” Logically, an off‐the‐shelf graft without self‐tissue sacrifice would be an ideal choice. Shorter surgical and anesthesia time, fewer postoperative complications, reduced morbidity at the harvest site, faster postoperative recovery and lower incidence of postoperative arthrofibrosis, and less postoperative pain are considered to be the main advantages of allograft usage for ACL replacementet al. also indicated a significant progress from preoperative to short‐term postoperative result in reducing anterior translation and anterolateral rotational instability of the tibia relative to the femur in patients who had undergone ACL reconstruction with a synthetic LARS graftOur meta‐analysis included nine studies. The pooled ORs of these studies indicated that autografts were inferior to synthetics for restoring knee joint stability, patient‐reported outcome scores and were associated with more postoperative complications, but there was no significant difference between two groups with regard to graft failure in any of the studies. Another drawback of autografts is that graft strength decreases during the long period of revascularization. This may lead to graft laxity or rupture during early rehabilitationet al. wrote systematic review was to assess the safety and efficacy of different synthetic devices in cruciate ligament surgery, a limitation of this review is the paucity of well‐conducted clinical trials included and the exclusion of no‐English‐language studies (n = 8)The strengths of this review are its well‐conducted clinical trials and relatively long‐term follow‐up of the papers included in the analysis. To our knowledge, no previously published systematic review of the influence of autograft choice on outcome after cruciate ligament reconstruction surgery has had such rigid inclusion and exclusion criteria. The included studies are all high‐level data with at least two‐year minimum follow‐up and thus provide a high level evidence for clinical decisions. A review by Newman and Atkinson indicated the support of the current literature for the use of LARS in the short to medium term in patients who have undergone ACL reconstruction. However, the authors highlighted the need for high‐quality studies with long‐term follow‐up to determine whether the use of LARS is preferable to autologous graftsBe that as it may, there are several limitations in this study. Firstly, although nine studies were added in this study since the latest systematic review, just three of them were RCT, the other six studies were relatively high‐quality retrospective studies, and thus usually has more potential sources of bias and confounding factors. This might weaken the strength of the findings, and more high‐quality randomized controlled trials with long‐term follow‐up are necessary to make a firm conclusion. Secondly, all the articles included ACL and PCL reconstruction. Thirdly, the majority of studies were limited in their statistical power by small sample size. Further standardization of rehabilitation, utilization of a blinded clinical examiner, and use of additional validated patient‐reported outcome measure would improve the strength of conclusions and meta‐analysis.Our study is the first meta‐analysis to compare the results of the autografts and synthetic ligaments. The combined results of this meta‐analysis indicate a statistical difference between autografts and synthetics in terms of negative outcomes of instrumented laxity, IKDC scores, patient‐reported Lysholm scores, and Tegner activity scores. Thus, our study concludes that cruciate ligament reconstruction with LARS achieved better postoperative effects in terms of restoring knee joint function and stability than autografts and was associated with less postoperative complications. The main advantages of the use of a synthetic ligament in ACL reconstruction are: the immediate recovery of stability and the timely rehabilitation and avoidance of sacrifice of autologous structures. We consider LARS artificial ligament to be an alternative graft for cruciate ligament reconstruction, especially (i) when early rehabilitation is imperative, (ii) in the presence of multiple ligament injuries, and (iii) in revision surgeries in which the availability of autologous tissue for reconstruction is limited.


Biodiversity is under threat worldwide. Over the past decade, the field of population genomics has developed across nonmodel organisms, and the results of this research have begun to be applied in conservation and management of wildlife species. Genomics tools can provide precise estimates of basic features of wildlife populations, such as effective population size, inbreeding, demographic history and population structure, that are critical for conservation efforts. Moreover, population genomics studies can identify particular genetic loci and variants responsible for inbreeding depression or adaptation to changing environments, allowing for conservation efforts to estimate the capacity of populations to evolve and adapt in response to environmental change and to manage for adaptive variation. While connections from basic research to applied wildlife conservation have been slow to develop, these connections are increasingly strengthening. Here we review the primary areas in which population genomics approaches can be applied to wildlife conservation and management, highlight examples of how they have been used, and provide recommendations for building on the progress that has been made in this field. These threats are pervasive and global, so that an estimated 1 million species of plants and animals are at risk of extinction within the next few decades IPBES, . ThreatsSeveral years ago, spurred by technological advances in high‐throughput sequencing, a set of reviews and perspective articles assessed the potential for the field of conservation genomics  – chromosomal regions that have few or no heterozygous nucleotide sites because both chromosome copies derive from a single copy in a relatively recent common ancestor  individuals from Robinson et al. (Felis concolor) individuals. Size classes of ROH correspond to the expected number of generations since the individual’s maternal and paternal lineages shared a common ancestor for that chromosomal region , and it can also provide a backbone for creating a reference genome assembly for the focal species. The growing number of reference genome assemblies is facilitated by large collaborative initiatives focused on taxonomic groups, such as Australian mammals , birds  or all eukaryotes  from water or other environmental samples. Although some genomics techniques such as WGS require DNA samples of relatively high concentration or molecular weight, a growing range of techniques can be applied to low‐quality DNA samples , defined as the size of an ideal, panmictic population that would experience the same loss of genetic variation, through genetic drift, as the observed population. eN is usually smaller than the observed “census” population size (cN), due to a number of factors common in natural populations, particularly wildlife taxa, including fluctuating population size, variance in reproductive success and overlapping generations, although there is wide variation in the eN/cN ratio  and the site frequency spectrum (SFS). They found that RADseq data are effective for precisely estimating eN and for detecting declines in eN over contemporary timescales (20 generations), and that LD‐based methods are superior, provided a sufficient sample size of individuals. If a reference genome assembly with data on recombination rate is available, methods to estimate Ne based on LD among linked loci may be even more effective  in Switzerland and found markedly reduced LD‐based estimates of eN in reintroduced populations compared to the source population or the closely related Iberian ibex (C. pyrenaica)  data from two salamander species  agreed with population size changes inferred from mark–recapture data; because this study included ddRAD sequencing on samples collected decades ago, temporal trends in eN could be estimated for these two species using both mark–recapture and ddRAD. Jensen et al. (Chelonoidis duncanensis) samples from a single island in the Galápagos Island from before and after a bottleneck that reduced eN to just 150–200 in the mid‐20th century. They found that the extent and distribution of genetic variation in the historical and contemporary samples was very similar, which they attributed to a successful ex situ head‐start and release programme.Population genomics approaches can be used to estimate ) Figure . Nunziat) Figure  also foun et al.  comparedNe are also affected by historical population structure and migration  uncovered a long‐term decline of the population from an eN of 10,000 well before the last glaciation to <500 after this period, indicating that this population has been declining for thousands of years. Two subspecies of gorilla also provide an illustrative contrast: in Graur's gorilla (Gorilla beringei graueri), population declines have led to loss of genetic diversity and increased inbreeding, while the mountain gorilla (G. beringei beringei) population has remained small but genetically stable over the past century  that are predicted to result in energy deficit, muscle weakness, skeletal and cranial anomalies, and reduced aggressiveness. Arguably the strongest evidence for inbreeding depression comes from studies that show a negative correlation between fitness and inbreeding coefficients. Huisman et al. (Cervus elaphus) by examining the relationship between several different fitness metrics and inbreeding coefficients estimated using SNPs. In contrast, inbreeding coefficients calculated from a deep and fairly complete pedigree in the same population found evidence for inbreeding depression for fewer traits  across populations. Given that gene flow infuses new genetic variation into populations, there is also a strong interest in wildlife and conservation biology in understanding the amount of gene flow among populations, particularly those isolated in fragmented landscapes  in eastern Washington state using WGS of representative individuals, which has important implications for conservation of this imperiled species . In another example, mitogenomic  among island populations, which suggests recent human movement of foxes. In these examples, genetic and genomic data confirmed the expected delineation of populations by geography, but also quantified the differentiation among them.The first step in inferring population structure using genetic or genomic data is to delineate populations. What constitutes a population is not always obvious for natural populations, and it is important to distinguish demographic and genetic connectivity  populations in southern California, and the barrier effect of major highway corridors can be seen in the genetic separation of wildlife populations  in the Rocky Mountains of Glacier National Park, Montana, USA. Their analyses supported divergence with gene flow among three genetic clusters since the end of the Pleistocene , which they interpreted as the result of south‐to‐north recession of ice sheets.In other cases, geographical delineation of populations is not as clear. Landscape genetics combines population genetics, landscape ecology and spatial statistics to understand the effects of landscape and environmental heterogeneity on gene flow, genetic variation and microevolutionary processes, and to identify barriers between populations , Jones et al.  allele that has swept to high frequency in parts of the snowshoe hare range with milder winter climates. Adaptive introgression into this species may have allowed it to expand its range following Pleistocene glaciation  and the widely introduced rainbow trout (O. mykiss) in western North America reduces fitness of the native species  is listed as endangered under the U.S. Endangered Species Act (ESA), but recent hybridization with coyotes (Canis latrans) as well as historical hybridization with coyotes and other wolf taxa has resulted in substantial controversy. Nonetheless, Waples et al. (Canis lycaon), also has a complex history including recent hybridization. Heppenheimer et al. . Assuming a heritability of migration timing of 0.5, they predict that adult migration timing will advance by ~10 days in response to a 2°C increase in temperature and that quasi‐extinction risk will only be 17% of that faced by populations with no evolutionary potential. Many wildlife species that are the focus of long‐term studies have pedigree data that can be used to estimate heritability of phenotypic traits  is the ability of a population to evolve genetically based changes in traits in response to changing environmental conditions , an endangered New Zealand passerine  by analysing ddRAD data with GEA. Incorporating this climate‐adaptive potential into forecasts of range changes under climate change reduced projected range reductions, highlighting the importance of taking adaptive potential into consideration in climate change vulnerability predictions. The Figure shows this conceptual framework, reprinted from Razgour et al. (Setophaga petechia). They found that populations that will require the greatest shifts in allele frequencies at these adaptive loci to keep pace with climate change have already experienced the most severe population declines, suggesting that inability to adapt to a changing climate may already be causing declines.Another approach for assessing adaptive potential, particularly in the face of climate change, is to examine patterns of local adaptation to climate conditions across the current species range, and then project future climatic changes and species’ responses  – by applying RADseq to samples collected both before and after the disease appeared in three independent populations that were the focus of long‐term field studies. Signatures of selection in this case are shifts in allele frequency and LD at specific genomic locations, and concordant signatures across populations are evidence for an adaptive response. Similarly, Bi et al. (Tamias spp.) spanning a century and identified significant shifts in allele frequencies. Neither of these studies specifically included phenotypic data on potential adaptive traits; nonetheless, both identified specific candidate genes with known function that may affect fitness under changing selection regimes in natural populations.Within populations, adaptive variation and genomic signatures of selection can be detected if samples are available over multiple generations Gompert, . This isi et al.  applied A complementary approach to determine the genetic basis of adaptative variation in natural populations is genome‐wide association studies (GWAS)  comprise a small, isolated population in Italy. Benazzo et al. , such as evolutionarily significant units (ESUs) and management units (MUs). We define an ESU as a classification of populations that have substantial reproductive isolation and adaptive differences so that the population represents a significant evolutionary component of the species  listed under the U.S. ESA did not actually merit listing as a discrete population, while a second  harboured previously unknown genetic differentiation. Genomics studies have more power than previous microsatellite studies to quantify overall (genome‐wide) population differentiation; for instance, McCartney‐Melstad et al. (Rana boylii) and found five extremely differentiated clades that can serve as management units for this species of conservation concern. Barbosa et al. (Microtus cabrerae): ESUs on the basis of overall differentiation, MUs on the basis of differentiation at neutral loci and adaptive units (AUs) on the basis of outlier loci  and steelhead (O. mykiss). Thompson et al. , and hands‐on training in population genomic analysis, including the ConGen workshop at the University of Montana's Flathead Lake Biological station (http://www.umt.edu/sell/cps/congen2019/), the Genomics of Disease in Wildlife workshop at Colorado State University (https://gdwworkshop.colostate.edu/), and a variety of workshops given across Europe by the G‐BIKE (Genomic Biodiversity Knowledge for Resilient Ecosystems) programme (https://sites.google.com/fmach.it/g‐bike‐genetics‐eu/home).Another recommendation for improving the translation of population genomics into improved wildlife conservation and management is training for both aspiring population genomics students and conservation practitioners, ideally together to foster direct interaction between these groups. Population genomics workshops, for example, not only provide technical training in the ever‐expanding field of genomics; they can also provide opportunities for conservation practitioners to gain exposure to the field to give them a better appreciation of the capacity of population genomics, the steps involved, and how to apply it to the species they manage and the questions they face. Fortunately, several genomics workshops now provide venues to discuss the latest developments in population and conservation genomics, such as the annual Population and Conservation Genomics workshop at the International Plant and Animal Genomes Conference  since genomic data have been applied to population genetic questions in nonmodel organisms, population genomics has already helped answer a wide variety of questions in the biology of wildlife species. There has been a relatively slow uptake of population genomics results in influencing policy decisions and wildlife management actions (Shafer et al., Population genomics research is by nature intensive and focused on one or a few species. It has, therefore, been applied to wildlife species that are high‐profile or of significant economic interest, such as captive populations or salmonid fish (Waples et al., A future need in conservation is to understand how population genomics tools can be applied more broadly beyond single focal species, for instance at the ecosystem level (Breed et al., The field of population genomics continues to change rapidly, with technological and analytical advances expanding the tools that are available in wildlife biology at the same time as the need for conservation knowledge and action becomes more urgent. While it may be very difficult to keep up to date with all of the changes, it is critical for both researchers and wildlife professionals to maintain a broad understanding of the population genomics tools that are available and to foster communication between wildlife scientists and practitioners.All authors contributed to writing the manuscript.


Polymers are widely used as dielectric components and electrical insulations in modern electronic devices and power systems in the industrial sector, transportation, and large appliances, among others, where electrical damage of the materials is one of the major factors threatening the reliability and service lifetime. Self‐healing dielectric polymers, an emerging category of materials capable of recovering dielectric and insulating properties after electrical damage, are of promise to address this issue. This paper aims at summarizing the recent progress in the design and synthesis of self‐healing dielectric polymers. The current understanding to the process of electrical degradation and damage in dielectric polymers is first introduced and the critical requirements in the self‐healing of electrical damage are proposed. Then the feasibility of using self‐healing strategies designed for repairing mechanical damage in the healing of electrical damage is evaluated, based on which the challenges and bottleneck issues are pointed out. The emerging self‐healing methods specifically designed for healing electrical damage are highlighted and some useful mechanisms for developing novel self‐healing dielectric polymers are proposed. It is concluded by providing a brief outlook and some potential directions in the future development toward practical applications in electronics and the electric power industry. Recent advancements in self‐healing dielectric polymers are reviewed. The complex mechanisms and characteristics of electrical damage in polymers bring various challenges of applying conventional self‐healing approaches to repair electrical damages in polymers. Besides several emerging approaches to restore insulating properties upon electrical damages, future directions in developing self‐healing insulation devices and systems in practical applications are discussed. This is because the mechanism and damaging process of electrical degradation are fundamentally different from the mechanical damage. A typical electrical damaging event of dielectric polymers is sophisticated, and it involves the electrical treeing process accompanied with electrochemical, photochemical and thermochemical degradation, followed by the catastrophic breakdown. The electrical treeing phenomenon gives rise to the formation of dendric hollow cracks of few micrometers in the tube diameter, which usually fall into the gap between the damaging scales that intrinsic  and extrinsic (larger than tens of micrometers) approaches can heal  or employ reversible chemical bonds (intrinsic approaches) to rebuild the damaged regions and hence gain extended service lifetime. Although various self‐healing materials have been designed to repair mechanical damage ,36 dir graphene‐based, microcapsule‐based and vascular networks, dynamic chemical bonding) and potential application area . However, none of them discussed about self‐healing of electrical damage in polymers. On the other hand, in the field of dielectric polymers, most of the existing studies have focused on improving breakdown strength and thermal stability, modulating dielectric constant, reducing dielectric loss  and exploring other functionalities. Research on electrical tree damage has been limited to improving the tree inception voltage and restraining the tree propagation by adding voltage stabilizers, degradation inhibitors, nano‐/micro‐scale fillers, etc., rather than healing the damage or recovering the insulating property. After a long period of time's exploration and development, recently, self‐healing of electrical tree damage and complete restoration of insulating properties in bulk dielectric polymers were attained. We believe this is the right time to implement a review of the achievement by far in this emerging field, which would serve to inspire future work in self‐healing dielectric polymers.Self‐healing materials designed for repairing mechanical damage have been previously reviewed from different perspectives such as material classification  will accelerate the tree formation process initiated from the defect regions. Above the inception field, electrical tree propagation is driven by partial discharge events in the tree channels, with the initiation voltage depending on the material type and the shape of electrode asperities. After the inception stage, the treeing process usually features decelerated propagation and shows intermittent, stepwise bursts of growth. Then it goes into a relatively slow propagation period (or inactive period) accompanied with tip splitting. The formation of branch channels weakens the local electric field at the tree tips and may lead to the cessation of tree growth. For continued propagation, the tree shows accelerated growth as the forefront branches approach the opposite electrode. Finally, in the runaway stage the accelerated growth turns into catastrophic breakdown, and a micro‐ to millimeter scale through hole is formed.Electrical treeing is initiated by the defect regions, as illustrated in Figure 66 Und as shown in Figure Taking into account the competition between the electrical damage and healing process, i.e., the formation and propagation process of electrical treeing versus the healing rate of the existing self‐healing methods, two periods in the electrical treeing can be utilized to heal the damage: the inception stage and the slow propagation stage. In the inception stage, nano‐scale damage  is involved and the healing methods capable of dealing with molecular‐ to nano‐level cracks would be effective. In the propagation stage when dendric hollow tree channels are formed with diameter of few micrometers and length of hundreds of micrometers or longer, the self‐healing approaches employed should be able to mend micrometer‐ to millimeter‐scale damage. Actually, the electrical tree is a multiscale damage containing microscale cracks and nanoscale voids at tree branch ends,75 as The self‐healing dielectric polymers should possess dielectric properties comparable to the conventional polymer insulations, including breakdown strength, dielectric loss, electrical resistivity, etc.The self‐healing systems should be sensitive to multiple length scale of defects.The healing process must be quicker than the damaging process, e.g., the propagation rate of electrical trees.Considering the special working conditions of dielectric materials and the unpredictable occurrence of electrical damage, ideal self‐healing dielectric polymers should satisfy the basic requirements as follows:33.1In this section, existing self‐healing strategies originally designed for repairing mechanical damage are briefly reviewed, and previous tentative research applying those strategies to the healing of electrical damage in bulk dielectric polymers are discussed. According to the healing mechanism, the existing self‐healing strategies can be roughly divided into two categories: 1) extrinsic self‐healing via embedded healing agent carried by microcapsules, hollow fibers, microvascular, etc., and 2) intrinsic self‐healing without additional healing agent, such as non‐covalent interactions, reversible covalent bonds, and irreversible covalent bonds.3.1.1 Lesaint et al. tried to utilize conventional Grubbs’ catalyst‐based microcapsule self‐healing method to heal electrical trees in epoxy, as shown in Figure  and increase the probability of electrical tree inception. Various single‐component extrinsic self‐healing systems without catalysts have been developed utilizing the healing agents that can cure under external stimulations or upon contacting other reactants, providing opportunities for developing catalyst‐free self‐healing dielectric polymers. But whether or not the healing kinetics can surpass that of the electrical damage process needs to be evaluated.For extrinsic self‐healing approaches, liquid healing agents embedded in the polymer matrix are released into the damaged regions by capillary effect when the carriers are ruptured by the damage, which then polymerize upon contacting the metal‐containing catalysts doped in the matrix.76 Les cable termination and bushing , suggesting that repeated healing is possible if new capsule structures are designed to enable multiple release of healing agents. Another issue associated with the extrinsic self‐healing methods is that incorporation of encapsulated healing agents is repulsive to the manufacturing process of thin films, extruded insulations and other finely structured dielectric components.In many electrical insulation applications requiring high mechanical performance such as fiber‐reinforced composite insulators,84 cabg Figure ,c,‐ethyl‐triazine (2MZ‐AZINE) for ring‐opening polymerization of epoxy at 120–150 °C, 2‐ethyl‐4‐methylimidazole (24‐EMI) that is usually used at 140 °C, and CuBr2(2‐MeIm)4 (the complex of CuBr2 and 2‐methylimidazole) which can be activated at 130–180 °C.The self‐healing approach using in situ electroluminescence requires that the dielectric polymers to be healed are transparent to the UV light, but thermoset insulations in practical applications can be opaque to the UV light because of the embedded additives. To address this issue, Xie et al.63 desOne of the major problems faced by extrinsic self‐healing methods is the instability of the healing agent in long term storage. Conventional unsaturated healing agents or monomers are prone to self‐polymerize in long‐term storage, especially at high temperature conditions. In the anionic polymerization‐based approach, the bisphenol A epoxy resin possessing high thermal stability is adopted as the healing agent. Accelerated thermal aging experiments demonstrate the long‐term effectiveness of the healing agent and EMI‐modified epoxy, which allows for long‐running and high‐temperature insulation applications. However, for all the extrinsic self‐healing methods, the adverse impact of liquid healing agent on dielectric properties still brings up challenges in long‐term electrical insulation. Moreover, gaseous byproducts generated by electrical degradation during the treeing process will accumulate and form voids inside the microcapsules or vascular fibers, and act as insulating defects. In general, although these new designs have overcome some bottleneck issues of self‐healing dielectric polymers, various problems remain to be resolved.4.42 around the breakdown site rather than forming permanent short‐circuit. In this case, the dielectric polymers themselves are not healable and the electrical breakdown sites are still permanent damage thus the “self‐healing” behavior is more often referred to as self‐clearing. As the “real” self‐healing dielectrics, various ultrathin monolayers (few nanometers in thickness)   that the ionic parts are able to flow into the hole and heal the materials at elevated temperature. A dielectric elastomer was reported to be capable of healing electrical breakdown holes in 510 µm thick films by the intermolecular electrostatic interaction between the methyl thioglycolate‐modified butadiene block and the styrene block. As shown in Figure “Self‐healing” film capacitor dielectrics possess the ability to tolerate electrical breakdown by evaporating the metal electrodes of typically a few mm‐circuit.37 In −1, much lower than the commonly used dielectric polymers, e.g., biaxially oriented PP (>700 kV mm−1), LDPE (>350 kV mm−1), and poly(ether imide) . Electrical breakdown in bulk dielectric polymers of high breakdown strength usually results in large‐area ablation and carbonization through the breakdown pathway, and produces a large amount of semi‐conductive degradation byproducts on the surface of the breakdown hole, bringing difficulties to the healing of the damaged region.Among all the studies on the self‐healing of catastrophic breakdown utilizing dynamic bonding chemistries, the maximum electrical breakdown strength of the self‐healing dielectric polymers is around 50 kV mmkV mm−1).123 El5) of dielectric polymers and various concomitant phenomena during electrical degradation provide opportunities for future development. This section proposes some mechanisms and methods, although none of them has been used to heal electrical damage in polymers that are potentially viable for developing new self‐healing dielectric polymers.Despite the aforementioned challenges in the design of self‐healing dielectric polymers, the special working conditions  o5.12 and H2O) in electrical tree channels. As illustrated in Figure  Hydrolysis of CO2 can be catalyzed by amino groups and produce bicarbonate at room temperature. For direct stable sequestration of CO2, zwitter‐ion reaction can be activated at high temperature that is comparable to the working condition of dielectrics in high‐temperature applications. In addition, the organic amine functionalized mesoporous silica nanoparticles MCM‐41‐polyethylenimine can greatly improve the electrical insulating properties including electrical breakdown strength, resistivity and threshold field of space charge injection, which is crucial for extruded DC power cable and many other high‐field insulating applications.The low‐molecular‐weight degradation byproducts generated in the electrically damaged region would accelerate the aging process and impede healing of the materials. Yang et al. developed the degradation inhibitors capable of absorbing gaseous electrical degradation byproducts  produced by ablation and carbonization around the wall of electrical tree channels and breakdown holes, it is difficult to be cleared through chemical reaction. A possible approach is to employ physical penetration paths to deliver active healing agents and cover the surface of damaged regions, which will be discussed in the next section.5.2 Self‐healing using the thermoset‐thermoplastic composites include highly miscible systems  and phase‐separated systems  with the reported healing efficiencies up to 77% and 100%, respectively. In the IPN systems, it is reported that diffusion of linear polymer into the crack interface could heal the crack upon heating. Although the diffusion of linear polymer is limited to micrometer scale and is unable to heal large open cracks, this approach may be utilized to heal the initial trees and to clear the carbonized inert surface of the tree channel walls created by severe partial discharges. As demonstrated by Soxhlet extraction, the linear polymer phase is mobile within the IPN and enables chain interdiffusion and entanglement that brings about temperature‐ and time‐dependent enrichment of the surface. This surface enrichment (or cleaning) process may assist the intrinsic self‐healing approaches against electrical degradation and improve the healing efficiency.Interpenetrating polymer networks (IPNs) are generally thermoset‐thermoplastic composites with certain percentages of the linear polymer phase interpenetrated into the cross‐linked polymer phase.159 Se As illustrated in Figure  This new self‐healing mechanism is promoted by nanoscale design of molecular movement and phase separation, eliminating chemical and physical alterations  and the dependence of self‐healing functionalities on specific chemical components, which possesses potential for healing electrical damage in dielectric polymers.Interdiffusion and entanglement of thermoplastic chains in the healing process of IPNs are driven by Brownian motion and intermolecular van der Waals interaction, which are highly related to the conformation and topology of polymer chains. Urban et al. reported similar self‐healing behaviors in poly(methyl methacrylate)/n‐butyl acrylate [p(MMA/nBA)] and their derivatives in response to mechanical damage.162 As5.3 Generally, the shape memory polymers (SMPs) show at least two separated phases with the higher thermal transition phase standing for the permanent shape below Tperm and the lower thermal transition phase working for the fixation of temporary shape below the switching temperature Ttrans. By heating up the material above Ttrans but below Tperm, the temporary shape will be destroyed, and the permanent shape could be recovered. SMPs would introduce shape memory effect into many easy shaping, light‐weight, and flexible transition temperature areas, and shape memory assisted self‐healing (SMASH) has been attracting more attention. Rodriguez et al. reported a SMASH system that is able to close and bond cracks simultaneously with thermal trigger. This strategy is realized by a blend system consisting of cross‐linked poly(ε‐caprolactone) (n‐PCL) network and linear poly(ε‐caprolactone) (1‐PCL), which combines the shape memory property of the network and the self‐healing function of the linear component together. With the assistance of the shape memory epoxy matrix, they also developed the SMASH coating containing electro‐spun PCL fibers capable of flowing into and rebuilding the crack regions upon heating. Similar works were reported by Zhao et al. Besides the thermally triggered SMPs, some other excitations such as optical, electrical, magnetic, and chemical  ones were used to develop the SMASH materials. Multi‐responsive SMPs provide a variety of damage‐induced or stimuli‐responsive functionalities that could potentially assist the self‐healing of electrical tree and breakdown damage.Lendlein et al. synthesized an AB‐polymer network with shape memory properties.164 Ge Two self‐healing mechanisms are identified depending on the molecular weight of the polymer networks. Viscoelastic shape memory driven by conformational entropic energy stored during mechanical damage enables sufficient molecular mobility for self‐healing while maintaining high strength and stiffness through precise material design. For low molecular weight polymers, surface energy/tension can drive the reduction of newly generated surface areas created upon damage by shallowing and widening wounds until healed. These two autonomous self‐healing mechanisms result from the viscoelastic behavior of polymers irrelevant to the chemical components, and they could potentially serve as general approaches possessing robust healing ability upon chemical degradation in electrical damage.Other driving mechanisms that can be utilized to achieve automatic crack closure include conformational entropy and interfacial energy. Hornat and Urban developed entropy and interfacial energy driven self‐healable polymers capable of repairing without intervention.182 Tw5.4 Other studies referred these constructive bond‐forming reactions as activated remodeling via mechanochemistry (ARM) and used it to produce new chemistry, force accelerated and selective transformations, self‐strengthening or self‐healing polymers, etc. Ramirez et al. demonstrated that mechanochemical reactions can be used to strengthen a polymer subjected to the same shear forces responsible for destructive processes s supercapacitors.For the tree channels and breakdown holes, mechanochemical self‐growing reactions provide the opportunities to make up for the material loss after electrical degradation by self‐growing. Recently, Matsuda et al. proposed a biological metabolism‐inspired strategy to develop self‐growing materials in response to mechanical stress through a mechanochemical transduction.189 As5.5 gel materials have attracted extensive research interest. Some polymer gels can cause bending motion and swelling‐deswelling changes in response to external stimuli including temperature change, light irradiation, electric field, magnetic field, etc. Many smart materials based on the stimuli‐responsive polymer gels have been developed for applications such as artificial muscles, drug delivery systems and biosensors. These smart materials can be divided into three categories: mechanical motion, mass transport, conversion and transmission of information, which could potentially assist the self‐healing of electrical damage by automatic closure of tree channels, storage/release of healing agents and detection of micro‐damage respectively, as illustrated in Figure After Tanaka discovered the “volume phase transition” phenomena ,192 ge on the inner wall of the capsule shell, the microcapsule shells could act as electrically driven actuators and release healing agent/reinforcer to the damaged region where the electric field is enhanced. Like the drug delivery systems, these smart microcapsules are expected to be more sensitive to the initial damage comparing with the conventional microcapsules and the release of healing agent is controlled by the degree of electrical degradation. In addition to self‐healing, the multi‐stress coupled stimuli‐responsive strategies may be used to trigger the intelligent insulating composite systems to implement damage reporting, adaptive strengthen and other functionalities, which provide opportunities to design smart dielectric polymers for electronics and energy applications.In this conceptual design, stimuli‐responsive polymers may be utilized as the shell material to compose smart microcapsule systems. The smart microcapsules may respond to the electric field distortion, magnetic field and ultra‐violet radiation of partial discharge and then proactively release the embedded healing agent/reinforcer to repair/strengthen the damaged region. For example, using electrokinetic molecular assembly reaction of surfactant molecules 196 on6 military , auto industry (scratch‐resistant coating), and so forth. However, few self‐healing strategies have been introduced to the electronics and electric power industry. Witnessing the fast growth of demand in electric energy and electronic devices, we expect that self‐healing electrical insulating systems will play significant roles and possess wide application prospects.Self‐healing is becoming one of the integral functionalities of materials in many technical fields including construction industry ,205 mi conventional fabrication methods of dielectric polymers need to be modified to accommodate the incorporation process of microcapsules, and the long‐term storage of healing agent is also challenging. Regarding intrinsic self‐healing systems, chemical degradation of the dielectrics during electrical aging may destroy the healing functionalities and impede necessary intimate contact of fracture surfaces. Thus clearing of degradation byproducts, enrichment/cleaning of carbonized damage surface and automatic closure of electrical tree channels or breakdown holes should be considered as auxiliary functionalities in self‐healing dielectric systems. Possible solutions include employing degradation product absorbent, interpenetrating self‐healing networks, conformational entropy and surface energy mechanisms in self‐healing dielectric polymers. As the thermoplastic extruded insulation cables are getting more and more popular, the entropy‐driven defect‐targeted superparamagnetic heating approach  shows promise in self‐healing power transmission systems. Stimuli‐responsive polymer gels provide various opportunities in designing smart dielectric systems capable of automatic closure of tree channels, storage/release of healing agents and micro‐damage detection under the multi‐stress‐coupled electrical aging conditions. Mechanochemical self‐strengthening and self‐growing mechanisms provide opportunities for assisting the self‐healing process in competition with the damaging process and achieving ultimate self‐healing ability making up for the material loss in catastrophically damaged regions.The multi‐scale characteristic of electrical damage, complex electrical aging process, and harsh operating conditions bring great challenges in designing self‐healing dielectric polymers. Conventional self‐healing strategies using embedded healing agent will introduce inhomogeneity and insulation defects into the matrix, which may cause local stress enhancement under electric field and increase the probability of electrical damaging. Although improved microcapsule self‐healing epoxy composites using electroluminescence and anionic polymerization have been developed,63 conSelf‐healing of electrical damage in dielectric polymers is an emerging frontier area that is of major difference to the conventional research regarding dielectric and insulation materials, and that significantly broadens the self‐healing concept from repairing mechanical fracture to electrical damage in polymers. The ability to completely restore the dielectric strength and electrical properties of dielectric polymers from electrical tree degradation and catastrophic breakdown offers unprecedented opportunities for the development of smart polymers with greatly increased lifetime, safety and sustainability for electronics and energy applications, which may lead to revolutionary progress in the electronics and electric power industry. The success in this challenging yet promising research field will need interdisciplinary collaboration that brings conceptual advance in dealing with the stringent set of requirements in developing self‐healing dielectric polymers.The authors declare no conflict of interest.


Nevertheless, accumulating evidence from several different laboratories has demonstrated that a subset of CCs display spontaneous activity and CA release in the absence of acetylcholine stimulation. These observations have been reported in both isolated CCs and tissue slices using intracellular or extracellular recording, thus excluding a possible experimental artefact. Biophysical characterization of CC plasma membrane conductances identified a large complement of voltage‐gated Na+, Ca2+ and K+ channels perfectly suited for the generation of spontaneous electrical activity with neuron‐like action potentials (APs)  of the adrenal medulla are neuroendocrine cells that secrete catecholamines (CAs) into the blood in response to stress. Canonically, it has been considered that CAs release is controlled though a cascade of events initiated by sympathetic nervous system. Upon splanchnic nerve activation, acetylcholine is released from the nerve terminals in the proximity of CCs, which activates the nicotinic acetylcholine receptors (nAChRs), leading to plasma membrane depolarization. The membrane depolarization activates the voltage‐gated CaThe Journal of Physiology, proposes a new molecular mechanism responsible for the dynamic switch between CCs’ tonic and burst firing modes  the authors reveal that this background current is not conducted by very obvious candidates like voltage‐gated Na+ or K+ ion channels (NaV KV) or by the Na+/K+‐ATPase pump, but instead it represents a hitherto unidentified CC Na+ conductance. In situ hybridization analysis showed that the Na+ leak channel NALCN is expressed in CCs, suggesting that its conductance is responsible for a more depolarized CC resting membrane potential.A very elegant and thorough biophysical study coming from Nathalie Guerineau's laboratory, published in this issue of et al. V, CaV, KV ion channel complement. The only difference is the Na+ background current (e.g. NALCN expression) which sets the resting membrane potential deciding the firing mode. It is tantalising to speculate that CCs of the adrenal medulla are not a uniform population, with some cells having a higher NALCN expression and therefore being more prone to burst firing or even working as pace‐maker cells that initiate the electrical activity that afterwards can spread through gap junctions to neighbouring cells. Single cell RNA‐seq has provided ample evidence of heterogeneous cell populations in many cell types  and it is only a matter of time till the same questions will be asked in CCs.The study is very timely and has high physiological relevance because the CCs’ electrical activity pattern dramatically affects the amount of CA release. Previously it has been shown that during burst firing mode the CA release is ∼3.5 times higher compared to the amount released during single APs (reviewed in Lingle This inspiring study shows once again that a well‐established neuroendocrine model system like CCs, which has delivered so much information on vesicle exocytosis and cell excitability during the past few decades, still holds many exciting secrets ready to be uncovered.The author declares no conflict of interest.Sole author.This work was not supported by any funding agency.


Given unprecedented rates of biodiversity loss, there is an urgency to better understand the ecological consequences of interactions among organisms that may lost or altered. Positive interactions among organisms of the same or different species that directly or indirectly improve performance of at least one participant can structure populations and communities and control ecosystem process. However, we are still in need of synthetic approaches to better understand how positive interactions scale spatio‐temporally across a range of taxa and ecosystems. Here, we synthesize two complementary approaches to more rigorously describe positive interactions and their consequences among organisms, across taxa, and over spatio‐temporal scales. In the first approach, which we call the mechanistic approach, we make a distinction between two principal mechanisms of facilitation—habitat modification and resource modification. Considering the differences in these two mechanisms is critical because it delineates the potential spatio‐temporal bounds over which a positive interaction can occur. We offer guidance on improved sampling regimes for quantification of these mechanistic interactions and their consequences. Second, we present a trait‐based approach in which traits of facilitators or traits of beneficiaries can modulate their magnitude of effect or how they respond to either of the positive interaction mechanisms, respectively. Therefore, both approaches can be integrated together by quantifying the degree to which a focal facilitator's or beneficiary's traits explain the magnitude of a positive effect in space and time. Furthermore, we demonstrate how field measurements and analytical techniques can be used to collect and analyze data to test the predictions presented herein. We conclude by discussing how these approaches can be applied to contemporary challenges in ecology, such as conservation and restoration and suggest avenues for future research. Given current and predicted future levels of global change and biodiversity loss, there is an urgent need to better understand the consequences of organism interactions that might be lost or altered. This urgency is especially pertinent for positive interactions (facilitation) that influence an organism's environmental tolerance and expand its niche space. In this paper, we address the improved integration of spatio‐temporal dynamics into positive interactions across taxa and ecosystems with two approaches, accompanying hypotheses and analytical techniques. HippopoFor both of these examples, our foundational hypothesis is that the spatio‐temporal extent of positive interactions depends on whether the underlying mechanism is habitat or resource modification. We can argue, for example, that the relative rate of decline in the response surface over the time axis is quicker for resource augmentation than it is for habitat modification. Under the assumptions for the example response surfaces described above, the relative rate of linear decline along the time axis is −2 per unit time for the NH4+ from hippopotamus waste, whereas its only −0.025 per unit time for flow refuge from structural decay of the caddisfly retreat. Although these representative examples from field and laboratory studies are just two of many, they accurately represent how different mechanisms of positive interaction can have orders of magnitude differences in the temporal rates of decay in the response surfaces. Nevertheless, our hypothesis leads to a number of predictions that can be tested to investigate how these two mechanisms of positive interactions will differentially operate in nature. We predict that response surfaces may differ greatly among the (a) response metrics being studied , (b) mechanism of facilitation operating ; Visualization (lead); Writing‐original draft (lead); Writing‐review & editing (lead). Leonardo Calle: Conceptualization (lead); Visualization (lead); Writing‐original draft (supporting); Writing‐review & editing (supporting). Heidi Anderson: Conceptualization ; Visualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). Michelle Briggs: Conceptualization ; Visualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). Sam Carlson: Conceptualization ; Visualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). Michael MacDonald: Conceptualization ; Visualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). J. Holden Reinert: Conceptualization ; Visualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). Lindsey K. Albertson: Conceptualization (lead); Funding acquisition (lead); Visualization (lead); Writing‐original draft (lead); Writing‐review & editing (lead).This article has been awarded Open Data, Open Materials, Preregistered Research Designs Badges. All materials and data are publicly accessible via the Open Science Framework.