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Group living can lead to kleptoparasitism, the theft of resources by competitors. Under such conditions, foragers may alter their behavior to minimize competition. However, it is unclear how such behavioral changes impact foraging performance. Archerfish (Toxotes spp.) are a good model for investigating the behavioral responses to kleptoparasitism, as their hunting method (shooting waterjets at insects perched above the water) leaves them vulnerable to theft. They must hit the target prey with sufficient force to dislodge it; thus, the prey may land some distance away from the shooter. Kleptoparasitism rates increase with group size in archerfish, and individuals alter their behavior around conspecifics. We investigated whether group size affected shooting success, using 7-spot archerfish T. chatareus. We considered a fish's shot to be successful if it knocked a fly, placed on a transparent platform above the tank, into the water. The probability of shooting success was modeled as a function of group size, aiming duration, nearest neighbor distance and position, and trial number. We found no effect of group size, aiming duration, or nearest neighbor distance or position on shooting success. Shooting success increased as trials progressed, likely due to the fish becoming more familiar with the task. We also found no change in the kleptoparasitism rate between group sizes. Instead, the likelihood of the shooter consuming the prey depended on the types of competition present at the time of shooting. We suggest that archerfish shooting behavior can be influenced by the presence of conspecifics in ways not previously considered.
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Good site characterization is essential for the selection of remediation alternatives for impacted soils. The value of site characterization is critically dependent on the quality and quantity of the data collected. Current methods for characterizing impacted soils rely on expensive manual sample collection and off-site analysis. However, recent advances in terrestrial robotics and artificial intelligence offer a potentially revolutionary set of tools and methods that will help to autonomously explore natural environments, select sample locations with the highest value of information, extract samples, and analyze the data in real-time without exposing humans to potentially hazardous conditions. A fundamental challenge to realizing this potential is determining how to design an autonomous system for a given investigation with many, and often conflicting design criteria. This work presents a novel design methodology to navigate these criteria. Specifically, this methodology breaks the system into four components - sensing, sampling, mobility, and autonomy - and connects design variables to the investigation objectives and constraints. These connections are established for each component through a survey of existing technology, discussion of key technical challenges, and highlighting conditions where generality can promote multi-application deployment. An illustrative example of this design process is presented for the development and deployment of a robotic platform characterizing salt-impacted oil & gas reserve pits. After calibration, the relationship between the in situ robot chloride measurements and laboratory-based chloride measurements had a good linear relationship (R2-value = 0.861) and statistical significance (p-value = 0.003).
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Robótica , Suelo , Suelo/química , Monitoreo del Ambiente/métodos , Inteligencia ArtificialRESUMEN
Objectives: Studies in the USA, Canada and France have reported higher surgical site infection (SSI) risk in patients with a penicillin allergy label (PAL). Here, we investigate the association between PALs and SSI in the UK, a country with distinct epidemiology of infecting pathogens and range of antimicrobial regimens in routine use. Methods: Electronic health records and national SSI surveillance data were collated for a retrospective cohort of gastrointestinal surgery patients at Cambridge University Hospitals NHS Foundation Trust from 1 January 2015 to 31 December 2021. Univariable and multivariable logistic regression were used to examine the effects of PALs and the use of non-ß-lactam-based prophylaxis on likelihood of SSI, 30â day post-operative mortality, 7â day post-operative acute kidney injury and 60â day post-operative infection/colonization with antimicrobial-resistant bacteria or Clostridioides difficile. Results: Our data comprised 3644 patients and 4085 operations; 461 were undertaken in the presence of PALs (11.3%). SSI was detected after 435/4085 (10.7%) operations. Neither the presence of PALs, nor the use of non-ß-lactam-based prophylaxis were found to be associated with SSI: adjusted OR (aOR) 0.90 (95% CI 0.65-1.25) and 1.20 (0.88-1.62), respectively. PALs were independently associated with increased odds of newly identified MRSA infection/colonization in the 60â days after surgery: aOR 2.71 (95% CI 1.13-6.49). Negative association was observed for newly identified infection/colonization with third-generation cephalosporin-resistant Gram-negative bacteria: aOR 0.38 (95% CI 0.16-0.89). Conclusions: No evidence was found for an association between PALs and the likelihood of SSI in this large UK cohort, suggesting significant international variation in the impact of PALs on surgical patients.
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OBJECTIVE: To describe the presentation and management of lumbar bone stress injuries (LBSI), recurrent LBSI, and lumbar nonunited defects in elite Australian male and female cricket players. DESIGN: Retrospective case series. SETTING: Professional domestic and international cricket teams over 13 seasons. PARTICIPANTS: Elite Australian cricket players. INDEPENDENT VARIABLES: Symptomatic LBSI requiring time off cricket and lumbar nonunited defects, both confirmed by imaging. MAIN OUTCOME MEASURES: Incidence, presentation, history, healing, and management. RESULTS: 211 LBSI were identified at an average incidence of 5.4 per 100 players per season. LBSI were most common in male pace bowlers younger than 20 years of age (58.1 per 100 players per season), however, were also observed in older players, females, and non-pace bowlers. Recurrent LBSI accounted for 33% (27%-40%) of all LBSI. Median days to return to match availability was 182 (128-251) days for all LBSI, with a shorter time frame observed for new and less severe injuries, and male spin bowlers. Healing was demonstrated in 87% (81%-91%) of all LBSI cases. 29 nonunited defects were identified and predisposed subsequent pain, LBSI, and spondylolisthesis. CONCLUSIONS: LBSI are experienced by approximately 5.4 in every 100 elite Australian cricket players per season, with a high time cost of approximately 4 to 8 months. Nonunited defects also have a high time cost with associated subsequent lumbar spine issues. The findings of this study reinforce the importance of early detection and conservative management of LBSI, particularly for younger male pace bowlers and players with recurrent LBSI, which may be supported by MRI.
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Traumatismos en Atletas , Traumatismos de la Espalda , Críquet , Humanos , Masculino , Femenino , Anciano , Traumatismos en Atletas/diagnóstico por imagen , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/terapia , Estudios Retrospectivos , Australia/epidemiologíaRESUMEN
BACKGROUND: Shigella sonnei is a pathogen of growing global importance as a cause of diarrhoeal illness in childhood, particularly in transitional low-middle income countries (LMICs). Here, we sought to determine the incidence of childhood exposure to S. sonnei infection in a contemporary transitional LMIC population, where it represents the dominant Shigella species. METHODS: Participants were enrolled between the age of 12-36 months between June and December 2014. Baseline characteristics were obtained through standardized electronic questionnaires, and serum samples were collected at 6-month intervals over two years of follow-up. IgG antibody against S. sonnei O-antigen (anti-O) was measured using an enzyme-linked immunosorbent assay (ELISA). A four-fold increase in ELISA units (EU) with convalescent IgG titre >10.3 EU was taken as evidence of seroconversion between timepoints. RESULTS: A total of 3,498 serum samples were collected from 748 participants; 3,170 from the 634 participants that completed follow-up. Measures of anti-O IgG varied significantly by calendar month (p = 0.03). Estimated S. sonnei seroincidence was 21,451 infections per 100,000 population per year (95% CI 19,307-23,834), with peak incidence occurring at 12-18 months of age. Three baseline factors were independently associated with the likelihood of seroconversion; ever having breastfed (aOR 2.54, CI 1.22-5.26), history of prior hospital admission (aOR 0.57, CI 0.34-0.95), and use of a toilet spray-wash in the household (aOR 0.42, CI 0.20-0.89). CONCLUSIONS: Incidence of S. sonnei exposure in Ho Chi Minh City is substantial, with significant reduction in the likelihood of exposure as age increases beyond 2 years.
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Disentería Bacilar , Shigella , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Shigella sonnei , Vietnam/epidemiología , Antígenos O , Inmunoglobulina G , Disentería Bacilar/epidemiologíaRESUMEN
Prominent ears (PEs) are the most frequent congenital external ear deformity, occurring in â¼5% of the population. Although the deformity does not usually cause functional difficulties, it can significantly affect the patient's psychological and social health. The authors aim to present the Welsh experience of pinnaplasty, reviewing our outcomes and complications. A retrospective cross-sectional study was performed of all patients undergoing pinnaplasty in Morriston Hospital, Swansea, Wales. We represent the tertiary plastic surgery referral unit across Wales. We included all patients undergoing pinnaplasty between 2015 and 2022 inclusive. We excluded patients undergoing revision procedures or those who had no follow-up. Over the 7-year period, 236 pinnaplasties were performed and 203 were included in the analysis. Ninety-six percent of cases were performed using a cartilage-sparing approach, which represents the mainstay in our unit. The mean follow-up length for our cases was 12 months. Revision procedures were required in 4% of cases. Three hematomas (1.5%) and one (0.5%) wound dehiscence due to infection were recorded and required a return to the operating room. Suture extrusion was noted in 5% of cases (10 patients); 4.5% (9) cases were affected by either hypertrophic or keloid scarring. Across the United Kingdom, cosmetic procedures have come under scrutiny, namely, because of a difficult economic climate. In the era of tight fiscal control in health care, it is pertinent to analyze the outcomes and performance metrics of our operations regularly, thus aiding in the development of an established evidence base to advocate for our respective patients.
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We report a novel Globicatella species causing extensive soft tissue infection in a man bitten by a stray domestic cat in the United Kingdom. We identified this bacterium by 16S rRNA gene sequencing, whole-genome sequencing, and biochemical profiling and determined antimicrobial drug susceptibility.
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Aerococcaceae , Infecciones por Bacterias Grampositivas , Infecciones de los Tejidos Blandos , Animales , Gatos , Infecciones por Bacterias Grampositivas/microbiología , ARN Ribosómico 16S/genética , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Aerococcaceae/genética , Bacterias/genéticaRESUMEN
Although studies on fish cognition are increasing, consideration of how methodological details influence the ability to detect and measure performance is lagging. Here, in two separate experiments the authors compared latency to leave the start position, latency to make a decision, levels of participation and success rates (whether fish entered the rewarded chamber as first choice) across different physical designs. Experiments compared fish performance across (a) two sizes of T-mazes, large and standard, and a plus-maze, and (b) open choice arenas with either two or four doors. Fish in T-mazes with longer arms took longer to leave the start chamber and were less likely to participate in a trial than fish in T-mazes with shorter arms. The number of options, or complexity, in a maze significantly impacted success but did not necessarily impact behavioural measures, and did not impact the number of fish that reached a chamber. Fish in the plus-maze had similar latencies to leave the start box and time to reach any chamber as fish in the same-sized T-maze but exhibited lower overall success. Similarly, in an open choice arena, increasing the number of options - doors to potential reward chambers - resulted in lower probability of success. There was an influence of reward position in the choice arena, with rewarded chambers closest to the sides of the arena resulting in lower latencies to enter and higher probability of decision success. Together the results allow the authors to offer practical suggestions towards optimal maze design for studies of fish cognition.
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Cognición , Peces , Animales , Aprendizaje por LaberintoRESUMEN
The bulk-boundary correspondence relates topologically protected edge modes to bulk topological invariants and is well understood for short-range free-fermion chains. Although case studies have considered long-range Hamiltonians whose couplings decay with a power-law exponent α, there has been no systematic study for a free-fermion symmetry class. We introduce a technique for solving gapped, translationally invariant models in the 1D BDI and AIII symmetry classes with α>1, linking together the quantized winding invariant, bulk topological string-order parameters, and a complete solution of the edge modes. The physics of these chains is elucidated by studying a complex function determined by the couplings of the Hamiltonian: in contrast to the short-range case where edge modes are associated to roots of this function, we find that they are now associated to singularities. A remarkable consequence is that the finite-size splitting of the edge modes depends on the topological winding number, which can be used as a probe of the latter. We furthermore generalize these results by (i) identifying a family of BDI chains with α<1 where our results still hold and (ii) showing that gapless symmetry-protected topological chains can have topological invariants and edge modes when α-1 exceeds the dynamical critical exponent.
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BACKGROUND: Antibiotic allergy labels are important barriers to treatment and antimicrobial stewardship, but their prevalence in UK hospitals is poorly described. OBJECTIVE: To ascertain the prevalence and characteristics of antibiotic allergy labels in a large UK hospital setting and estimate the proportion of penicillin allergy labels for which point-of-care (POC) delabeling assessment would be appropriate. METHODS: Electronic health records data were analyzed from all patients treated at Cambridge University Hospitals NHS Foundation Trust in 2019. Validated POC delabeling risk stratification criteria were retrospectively applied to penicillin allergy labels. RESULTS: Recorded reactions to antibiotics were present in 11.8% of all patients (32,148 of 273,216), 16.3% of inpatients (13,874 of 85,230), and 9.7% of outpatients (18,274 of 187,986). Penicillins were the commonest reaction precipitant described (9.0% of patients; 24,646 of 273,216), followed by sulfonamides/trimethoprim (1.4%; 3869 of 273,216) and macrolides/lincosamides (1.3%; 3644 of 273,216). A total of 3.9% of inpatients had recorded reactions to >1 antibiotic class (3348 of 85,230). Cutaneous manifestations were the most commonly described reaction features (40.7% of labels; 15,821 of 38,902). Of 15,949 labels describing probable or possible penicillin "allergy" with sufficient detail to allow for the retrospective assessment of POC delabeling suitability, 1702 were deemed suitable for removal or downgrading of the label to "intolerance" without further investigation (10.7%), 11,887 were appropriate for POC assessment using an oral penicillin challenge (OPC) or OPC with prior bedside skin testing (74.5%), and 2360 were identified as unsuitable for any form of POC assessment (14.8%). CONCLUSIONS: Antibiotic allergy labels are highly prevalent in a UK hospital setting. A large proportion of penicillin allergy labels may be suitable for POC delabeling assessment.
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Programas de Optimización del Uso de los Antimicrobianos , Hipersensibilidad a las Drogas , Humanos , Estudios Retrospectivos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Antibacterianos/efectos adversos , Penicilinas/efectos adversos , Hospitales , Reino Unido/epidemiologíaRESUMEN
Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.
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Mitocondrias , Organogénesis , Animales , Femenino , Humanos , Ratones , Embarazo , Linaje de la Célula , ADN Mitocondrial/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales , Especificidad de Órganos , Desarrollo Embrionario , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismoRESUMEN
In September 2022, the European Commission published its new regulation on recycled plastic materials for food contact. It allows newly developed, non-authorized technologies and approaches, or so-called novel technologies, to be deployed in the field to generate the data needed for establishing regulatory and/or fit for purpose processes. The data shall be generated by using suitable methods, but the regulation does not give a more detailed description on those. In this study, commercially purchased buckets made of post-consumer recycled polypropylene were screened, using a number of different analytical approaches. Sample preparation methods, analysis techniques, and the data and information generated were compared. The results clearly demonstrate the need for a detailed characterization of such materials and the advantages and disadvantages of the analysis using conventional gas chromatography with flame ionization detection and mass spectrometery as well as two-dimensional comprehensive gas chromatography with time of flight mass spectrometry.
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The expansion of mitochondrial DNA molecules with deletions has been associated with aging, particularly in skeletal muscle fibers; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage (RA) to mitochondrial DNA containing deletion mutations, but there is also evidence that cells can selectively remove defective mitochondrial DNA. Here we present a spatial model that, without an RA, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data. A standard model based on RA yields waves that are too fast. We provide a formula that predicts that wave speed drops with copy number, consonant with experimental data. Crucially, our model yields traveling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that mutant loads observed in single-cell experiments can be produced by de novo mutation rates that are drastically lower than previously thought for neutral models. Given this exemplar of how spatial structure (multiple linked mtDNA populations), noise, and density affect muscle cell aging, we introduce the mechanism of stochastic survival of the densest (SSD), an alternative to RA, that may underpin other evolutionary phenomena.
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ADN Mitocondrial , Mitocondrias , ADN Mitocondrial/genética , Senescencia Celular/genética , Fibras Musculares EsqueléticasRESUMEN
OBJECTIVES: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). METHODS: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. RESULTS: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms. CONCLUSIONS: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/epidemiología , Personal de Salud , Hospitales de Enseñanza , Humanos , Estudios Prospectivos , Factores de Riesgo , Estudios Seroepidemiológicos , Reino Unido/epidemiologíaRESUMEN
Background: Healthcare-associated (HCA) SARS-CoV-2 infection is a significant contributor to the spread of the 2020 pandemic. Timely review of HCA cases is essential to identify learning to inform infection prevention and control (IPC) policies and organisational response. Aim: To identify key areas for improvement through rapid investigation of HCA SARS-CoV-2 cases and to implement change. Methods: Cases were identified based on date of first positive SARS-CoV-2 PCR sample in relation to date of hospital admission. Cases were reviewed using a structured gap analysis tool to identify key learning points. These were discussed in weekly multidisciplinary meetings to gain consensus on learning outcomes, level of harm incurred by the patient and required actions. Learning was then promptly fed back to individual teams and the organisation. Findings: Of the 489 SARS-CoV-2 cases admitted between 10th March and 23rd June 2020, 114 suspected HCA cases (23.3%) were reviewed; 58/489 (11.8%) were ultimately deemed to be HCA. Five themes were identified: individual patient vulnerability, communication, IPC implementation, policy issues and organisational response. Adaptations to policies based on these reviews were completed within the course of the initial phase of the pandemic. Conclusion: This approach enabled timely learning and implementation of control measures and policy development.
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The present research is focused on the use and evaluation of hydrogen, as a more sustainable alternative to helium, within the context of fast flow modulation comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. In such a respect, a comparison was made between the two mobile phases in terms of speed and overall chromatography performance. All experiments were carried out by using the following column set: low polarity with dimensions 10 m × 0.25 mm ID × 0.25 µm df and medium polarity with dimensions 2 m × 0.10 mm ID × 0.10 µm df. Fundamental gas chromatography parameters (efficiency, resolution) were measured under different experimental conditions, using the two carrier gases. Efficiency was measured in both the first and second dimensions, using a probe compound under isothermal conditions; after defining the optimum carrier gas conditions, a mixture containing 20 pesticides was analyzed to measure resolution, again in the first and second dimensions, using a temperature program. It was found (as expected) that a similar chromatography performance could be attained when using hydrogen, albeit with a circa 25% reduction in analysis time. Signal-to-noise ratios of the pesticides were calculated, using both carrier gases, with such values generally reduced (on average by 14%) when using hydrogen. Finally, a comparison was made between mass spectral profiles obtained analyzing the pesticides and fatty acid methyl esters using the two mobile phases. Even though mass spectral differences were observed, the ion profiles could be considered generally similar.
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Helio , Plaguicidas , Ácidos Grasos , Cromatografía de Gases y Espectrometría de Masas/métodos , Hidrógeno , Espectrometría de Masas/métodosRESUMEN
Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.
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COVID-19 , SARS-CoV-2 , Hospitales , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2/genéticaRESUMEN
Ballistic predation is a rare foraging adaptation: in fishes, most attention has focused on a single genus, the archerfish, known to manipulate water to shoot down prey above the water surface. However, several gourami species also exhibit apparently similar 'shooting' behaviour, spitting water up to 5â cm above the surface. In a series of experiments, we explored the shooting behaviour and aspects of its significance as a foraging ability in the dwarf gourami (Trichogaster lalius). We investigated sex differences in shooting abilities to determine whether gourami shooting is related to the sex-specific bubble nest manufacture where males mix air and water at the surface to form bubbles. We found that, actually, both sexes were equally able to shoot and could learn to shoot a novel target. In a second experiment, we presented untrained gouramis with opportunities to shoot at live prey and found they successfully shot down both fruit flies and crickets. Finally, we explored the effect of target height on shooting performance to establish potential constraints of shooting as a foraging ability. The frequency of attempted shots and success of hitting targets decreased with height, whereas latency to shoot increased. We also observed that repeatable individual differences account for variation in these measures of shooting performance. Together, our results provide evidence that gourami shooting has a foraging function analogous to that of archerfish. Gourami shooting may serve as an example of convergent evolution and provide opportunities for comparative studies into the, as yet unexplored, ecology and evolution of shooting in fishes.
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Perciformes , Agua , Animales , Ecología , Femenino , Peces , Masculino , Conducta PredatoriaRESUMEN
Heteroplasmic mitochondrial DNA (mtDNA) mutations are a common cause of inherited disease, but a few recurrent mutations account for the vast majority of new families. The reasons for this are not known. We studied heteroplasmic mice transmitting m.5024C>T corresponding to a human pathogenic mutation. Analyzing 1167 mother-pup pairs, we show that m.5024C>T is preferentially transmitted from low to higher levels but does not reach homoplasmy. Single-cell analysis of the developing mouse oocytes showed the preferential increase in mutant over wild-type mtDNA in the absence of cell division. A similar inheritance pattern is seen in human pedigrees transmitting several pathogenic mtDNA mutations. In m.5024C>T mice, this can be explained by the preferential propagation of mtDNA during oocyte maturation, counterbalanced by purifying selection against high heteroplasmy levels. This could explain how a disadvantageous mutation in a carrier increases to levels that cause disease but fails to fixate, causing multigenerational heteroplasmic mtDNA disorders.