Sustained predation pressure may prevent the loss of anti-predator traits from havened populations.

Conservation havens free of invasive predators are increasingly relied upon for fauna conservation, although havened populations can lose anti-predator traits, likely making them less suitable for life 'beyond the fence'. Sustaining low levels of mammalian predator pressure inside havens may prevent the loss of anti-predator traits from havened populations. We opportunistically compared behavioural and morphological anti-predator traits between four woylie (Bettongia penicillata ogilbyi) populations- one haven isolated from all mammalian predators, one haven containing a native mammalian predator (chuditch; Dasyurus geoffroii), and their respective non-havened counterparts (each containing both chuditch and invasive predators). Havened woylies existing without mammalian predators were smaller (shorter hindfeet, smaller body weight) and less reactive (consumed more food from fox-treated and control feeding stations, less agitated during human handling) than a non-havened reference population. However, in the haven containing chuditch, we found no difference in behaviour or morphology compared to the adjacent non-havened population. Across populations, anti-predator responses tended to appear stronger at sites with higher predator activity, suggestive of an adaptive response across a gradient of predation pressure. Our findings suggest that maintaining mammalian predation pressure in conservation havens could be effective for preventing or slowing the loss of anti-predator traits from these populations.

Prospective validity of a clinical prediction rule for response to non-surgical multidisciplinary management of knee osteoarthritis in tertiary care: a multisite prospective longitudinal study.

OBJECTIVES: We tested a previously developed clinical prediction tool-a nomogram consisting of four patient measures (lower patient-expected benefit, lower patient-reported knee function, greater knee varus angle and severe medial knee radiological degeneration) that were related to poor response to non-surgical management of knee osteoarthritis. This study sought to prospectively evaluate the predictive validity of this nomogram to identify patients most likely to respond poorly to non-surgical management of knee osteoarthritis. DESIGN: Multisite prospective longitudinal study. SETTING: Advanced practice physiotherapist-led multidisciplinary service across six tertiary hospitals. PARTICIPANTS: Participants with knee osteoarthritis deemed appropriate for trial of non-surgical management following an initial assessment from an advanced practice physiotherapist were eligible for inclusion. INTERVENTIONS: Baseline clinical nomogram scores were collected before a trial of individualised non-surgical management commenced. PRIMARY OUTCOME MEASURE: Clinical outcome (Global Rating of Change) was collected 6 months following commencement of non-surgical management and dichotomised to responder (a little better to a very great deal better) or poor responder (almost the same to a very great deal worse). Clinical nomogram accuracy was evaluated from receiver operating characteristics curve analysis and area under the curve, and sensitivity/specificity and positive/negative likelihood ratios were calculated. RESULTS: A total of 242 participants enrolled. Follow-up scores were obtained from 210 participants (87% response rate). The clinical nomogram demonstrated an area under the curve of 0.70 (p<0.001), with greatest combined sensitivity 0.65 and specificity 0.64. The positive likelihood ratio was 1.81 (95% CI 1.32 to 2.36) and negative likelihood ratio 0.55 (95% CI 0.41 to 0.75). CONCLUSIONS: The knee osteoarthritis clinical nomogram prediction tool may have capacity to identify patients at risk of poor response to non-surgical management. Further work is required to determine the implications for service delivery, feasibility and impact of implementing the nomogram in clinical practice.

Evolutionary predictions for a parasite metapopulation: Modelling salmon louse resistance to pest controls in aquaculture.

Pests often evolve resistance to pest controls used in agriculture and aquaculture. The rate of pest adaptation is influenced by the type of control, the selective pressure it imposes, and the gene flow between farms. By understanding how these factors influence evolution at the metapopulation level, pest management strategies that prevent resistance from evolving can be developed. We developed a model for the metapopulation and evolutionary dynamics of the salmon louse (Lepeophtheirus salmonis), which is a major parasite affecting salmon aquaculture. Different management scenarios were simulated across a network of salmon farms covering half of Norway, and their effects on louse epidemiology and evolution were investigated. We compared louse controls that differed in how they were deployed through time (discrete vs. continuous), how they impacted the louse life cycle, and in their overall efficacy. We adjusted the strength of selection imposed by treatments, the dominance effect of the resistant allele, and the geographic location at which resistance originated. Continuously acting strategies (e.g., louse-resistant salmon) were generally more effective than discrete strategies at controlling lice, especially when they increased louse mortality during early developmental stages. However, effective strategies also risked imposing frequent and/or strong selection on lice, thus driving rapid adaptation. Resistant alleles were more likely to be lost through genetic drift when they were recessive, had a low-fitness advantage, or originated in low-farm-density areas. The north-flowing current along the Norwegian coastline dispersed resistant genes from south to north, and limited gene flow in the opposite direction. We demonstrate how evolutionary models can produce quantitative predictions over large spatial and temporal scales and for a range of pest control scenarios. Quantitative outputs can be translated into practical management decisions applied at a regional level to minimise the risk of resistance developing.

Identification of Plasma Biomarkers from Rheumatoid Arthritis Patients Using an Optimized Sequential Window Acquisition of All THeoretical Mass Spectra (SWATH) Proteomics Workflow.

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Plasma biomarkers are critical for understanding disease mechanisms, treatment effects, and diagnosis. Mass spectrometry-based proteomics is a powerful tool for unbiased biomarker discovery. However, plasma proteomics is significantly hampered by signal interference from high-abundance proteins, low overall protein coverage, and high levels of missing data from data-dependent acquisition (DDA). To achieve quantitative proteomics analysis for plasma samples with a balance of throughput, performance, and cost, we developed a workflow incorporating plate-based high abundance protein depletion and sample preparation, comprehensive peptide spectral library building, and data-independent acquisition (DIA) SWATH mass spectrometry-based methodology. In this study, we analyzed plasma samples from both RA patients and healthy donors. The results showed that the new workflow performance exceeded that of the current state-of-the-art depletion-based plasma proteomic platforms in terms of both data quality and proteome coverage. Proteins from biological processes related to the activation of systemic inflammation, suppression of platelet function, and loss of muscle mass were enriched and differentially expressed in RA. Some plasma proteins, particularly acute-phase reactant proteins, showed great power to distinguish between RA patients and healthy donors. Moreover, protein isoforms in the plasma were also analyzed, providing even deeper proteome coverage. This workflow can serve as a basis for further application in discovering plasma biomarkers of other diseases.

Colony-level aggression escalates with the value of food resources.

BACKGROUND: Theory predicts that the level of escalation in animal contests is associated with the value of the contested resource. This fundamental prediction has been empirically confirmed by studies of dyadic contests but has not been tested experimentally in the collective context of group-living animals. Here, we used the Australian meat ant Iridomyrmex purpureus as a model and employed a novel field experimental manipulation of the value of food that removes the potentially confounding effects of nutritional status of the competing individual workers. We draw on insights from the Geometric Framework for nutrition to investigate whether group contests between neighbouring colonies escalate according to the value to the colony of a contested food resource. RESULTS: First, we show that colonies of I. purpureus value protein according to their past nutritional intake, deploying more foragers to collect protein if their previous diet had been supplemented with carbohydrate rather than with protein. Using this insight, we show that colonies contesting more highly valued food escalated the contest, by deploying more workers and engaging in lethal 'grappling' behaviour. CONCLUSION: Our data confirm that a key prediction of contest theory, initially intended for dyadic contests, is similarly applicable to group contests. Specifically, we demonstrate, through a novel experimental procedure, that the contest behaviour of individual workers reflects the nutritional requirements of the colony, rather than that of individual workers.

Katnip is needed to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes.

The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the amoeba Dictyostelium discoideum, we find that cells lacking Katnip (Katanin interacting protein) have a general defect in lysosomal delivery and although they make autophagosomes and phagosomes correctly, cells are then unable to digest them. Katnip is largely unstudied yet highly conserved across evolution. Previously studies found that Katnip mutations in animals cause defects in cilia structure. Here we show that Katnip plays a more general role in maintaining microtubule function. We find that loss of Katnip has no overall effect on microtubule dynamics or organization, but is important for the transport and degradation of endocytic cargos. Strikingly, Katnip mutants become highly sensitive to GFP-tubulin expression, which leads to microtubule tangles, defective anaphase extension, and slow cell growth. Our findings establish a general role for Katnip in regulating microtubule function, beyond the roles previously described in cilia. We speculate this is via a key function in microtubule repair, needed to maintain endosomal trafficking and lysosomal degradation.

Applying genetic technologies to combat infectious diseases in aquaculture.

Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies-sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.

Population genomics of a predatory mammal reveals patterns of decline and impacts of exposure to toxic toads.

Mammal declines across northern Australia are one of the major biodiversity loss events occurring globally. There has been no regional assessment of the implications of these species declines for genomic diversity. To address this, we conducted a species-wide assessment of genomic diversity in the northern quoll (Dasyurus hallucatus), an Endangered marsupial carnivore. We used next generation sequencing methods to genotype 10,191 single nucleotide polymorphisms (SNPs) in 352 individuals from across a 3220-km length of the continent, investigating patterns of population genomic structure and diversity, and identifying loci showing signals of putative selection. We found strong heterogeneity in the distribution of genomic diversity across the continent, characterized by (i) biogeographical barriers driving hierarchical population structure through long-term isolation, and (ii) severe reductions in diversity resulting from population declines, exacerbated by the spread of introduced toxic cane toads (Rhinella marina). These results warn of a large ongoing loss of genomic diversity and associated adaptive capacity as mammals decline across northern Australia. Encouragingly, populations of the northern quoll established on toad-free islands by translocations appear to have maintained most of the initial genomic diversity after 16 years. By mapping patterns of genomic diversity within and among populations, and investigating these patterns in the context of population declines, we can provide conservation managers with data critical to informed decision-making. This includes the identification of populations that are candidates for genetic management, the importance of remnant island and insurance/translocated populations for the conservation of genetic diversity, and the characterization of putative evolutionarily significant units.

Shared intentionality and the representation of groups; or, how to build a socially adept robot.

Pietraszewski provides a compelling case that representations of certain interaction-types are the "cognitive primitives" that allow all tokens of group-in-conflict to be represented within the mind. Here, I argue that the folk concept GROUP encodes shared intentions and goals as more central than these interaction-types, and that providing a computational theory of social groups will be more difficult than Pietraszewski envisages.

Slow and steady wins the race: Spatial and stochastic processes and the failure of suppression gene drives.

Gene drives that skew sex ratios offer a new management tool to suppress or eradicate pest populations. Early models and empirical work suggest that these suppression drives can completely eradicate well-mixed populations, but models that incorporate stochasticity and space (i.e. drift and recolonization events) often result in loss or failure of the drive. We developed a stochastic model to examine these processes in a simple one-dimensional space. This simple space allows us to map the events and outcomes that emerged and examine how properties of the drive's wave of invasion affect outcomes. Our simulations, across a biologically realistic section of parameter space, suggest that drive failure might be a common outcome in spatially explicit, stochastic systems, and that properties of the drive wave appear to mediate outcomes. Surprisingly, the drives that would be considered fittest in an aspatial model were strongly associated with failure in the spatial setting. The fittest drives cause relatively fast moving, and narrow waves that have a high chance of being penetrated by wild-types (WTs) leading to WT recolonization, leading to failure. Our results also show that high rates of dispersal reduce the chance of failure because drive waves get disproportionately wider than WT waves as dispersal rates increase. Overall, wide, slow-moving drive waves were much less prone to failure. Our results point to the complexity inherent in using a genetic system to effect demographic outcomes and speak to a clear need for ecological and evolutionary modelling to inform the drive design process.

Evolutionary balance between foldability and functionality of a glucose transporter.

Despite advances in resolving the structures of multi-pass membrane proteins, little is known about the native folding pathways of these complex structures. Using single-molecule magnetic tweezers, we here report a folding pathway of purified human glucose transporter 3 (GLUT3) reconstituted within synthetic lipid bilayers. The N-terminal major facilitator superfamily (MFS) fold strictly forms first, serving as a structural template for its C-terminal counterpart. We found polar residues comprising the conduit for glucose molecules present major folding challenges. The endoplasmic reticulum membrane protein complex facilitates insertion of these hydrophilic transmembrane helices, thrusting GLUT3's microstate sampling toward folded structures. Final assembly between the N- and C-terminal MFS folds depends on specific lipids that ease desolvation of the lipid shells surrounding the domain interfaces. Sequence analysis suggests that this asymmetric folding propensity across the N- and C-terminal MFS folds prevails for metazoan sugar porters, revealing evolutionary conflicts between foldability and functionality faced by many multi-pass membrane proteins.

"They're Not True Humans:" Beliefs about Moral Character Drive Denials of Humanity.

A puzzling feature of paradigmatic cases of dehumanization is that the perpetrators often attribute uniquely human traits to their victims. This has become known as the "paradox of dehumanization." I address the paradox by arguing that the perpetrators think about their victims as human in one sense, while denying that they are human in another sense. I do so by providing evidence that people harbor a dual character concept of humanity. Research has found that dual character concepts have two independent sets of criteria for their application, one of which is descriptive and one of which is normative. Four experiments provided evidence that people deploy a descriptive criterion according to which being human is a matter of being a Homo sapiens; as well as a normative criterion according to which being human is a matter of possessing a deep-seated commitment to do the morally right thing. Importantly, I found that people are willing to affirm that someone is human in the descriptive sense, while denying that they are human in the normative sense, and vice versa. In addition to providing a solution to the paradox of dehumanization, these findings suggest that perceptions of moral character have a central role to play in driving dehumanization.

Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii.

The global spread of multidrug-resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the F1Fo-adenosine 5'-triphosphate (ATP) synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F1 subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded Fo complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next-generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.

Parasite management in aquaculture exerts selection on salmon louse behaviour.

The evolution of pest resistance to management strategies is a major challenge for farmed systems. Mitigating the effects of pest adaptation requires identifying the selective pressures imposed by these strategies. In Atlantic salmon (Salmo salar) aquaculture, barriers are used to prevent salmon louse (Lepeophtheirus salmonis) larvae (copepodids) from entering salmon cages. These barriers are effective against shallow-swimming copepodids, but those swimming deeper can pass underneath and infest salmon. Laboratory experiments suggest that depth regulation in copepodids is a variable behavioural trait with a genetic basis. We used biological-hydrodynamic dispersal models to assess how this trait variation alters the dispersion of lice through the ocean environment and into farms. The dispersal of copepodids with 3 behavioural phenotypes (deep, mean or shallow) was modelled over winter-spring and spring-summer periods in a Norwegian fjord system with intensive aquaculture. The infestation pressure of each phenotype on barrier cages was estimated from their modelled depth distributions: copepodids deeper than 10 m were predicted to successfully pass underneath barriers. The deep phenotype was the most abundant below 10 m and reached infestation pressures 3 times higher than that of the mean phenotype. In contrast, the shallow phenotype infestation pressure reached less than half that of the mean phenotype. These differences in relative fitness indicate that barriers can impose strong directional selection on the swimming behaviour of copepodids. The strength of this selection varied seasonally and geographically, with selection for the deep phenotype stronger in winter-spring and at coastal locations than in spring-summer and within fjords. These findings can be applied across farms to slow louse adaptation, by limiting barriers during situations of strong selection, although this must be balanced against trade-offs to short-term efficacy. More broadly, our study highlights new ways in which dispersal models can address evolutionary questions crucial for sustainable parasite management in aquaculture.

Structural basis of TRAPPIII-mediated Rab1 activation.

The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo-EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α-helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.

Membrane protein folding and quality control.

Membrane proteins account for a quarter of cellular proteins, and most are synthesised at the endoplasmic reticulum (ER). Insertion and folding of polypeptides in the membrane environment is prone to error, necessitating diverse quality control systems. Recent discoveries have demonstrated how forces act on the nascent chain during insertion, and revealed new translocon components and accessories that facilitate the correct biogenesis of substrates. Our understanding of one of the best studied quality control systems-ER-associated degradation-has been advanced through new structural and functional studies of the core Hrd1 complex, and through the discovery of a new branch of this degradative pathway. New data also reveal how cells resolve clogged translocons, which would otherwise be unable to function. Finally, new work elucidates how mitochondrial tail-anchored proteins that have been mistargeted to the ER are identified and destroyed. Overall, we describe an emerging picture of an increasingly complex quality control network.

Trophic cascade driven by behavioral fine-tuning as naïve prey rapidly adjust to a novel predator.

The arrival of novel predators can trigger trophic cascades driven by shifts in prey numbers. Predators also elicit behavioral change in prey populations, via phenotypic plasticity and/or rapid evolution, and such changes may also contribute to trophic cascades. Here, we document rapid demographic and behavioral changes in populations of a prey species (grassland melomys Melomys burtoni, a granivorous rodent) following the introduction of a novel marsupial predator (northern quoll Dasyurus hallucatus). Within months of quolls appearing, populations of melomys exhibited reduced survival and population declines relative to control populations. Quoll-invaded populations were also significantly shyer than nearby, quoll-free populations of conspecifics. This rapid but generalized response to a novel threat was replaced over the following 2 yr with more threat-specific antipredator behaviors (i.e., predator-scent aversion). Predator-exposed populations, however, remained more neophobic than predator-free populations throughout the study. These behavioral responses manifested rapidly in changed rates of seed predation by melomys across treatments. Quoll-invaded melomys populations exhibited lower per-capita seed take rates, and rapidly developed an avoidance of seeds associated with quoll scent, with discrimination playing out over a spatial scale of tens of meters. Presumably the significant and novel predation pressure induced by quolls drove melomys populations to fine-tune behavioral responses to be more predator specific through time. These behavioral shifts could reflect individual plasticity (phenotypic flexibility) in behavior or may be adaptive shifts from natural selection imposed by quoll predation. Our study provides a rare insight into the rapid ecological and behavioral shifts enacted by prey to mitigate the impacts of a novel predator and shows that trophic cascades can be strongly influenced by behavioral as well as numerical responses.

Effects of learning and adaptation on population viability.

Cultural adaptation is one means by which conservationists may help populations adapt to threats. A learned behavior may protect an individual from a threat, and the behavior can be transmitted horizontally (within generations) and vertically (between generations), rapidly conferring population-level protection. Although possible in theory, it remains unclear whether such manipulations work in a conservation setting; what conditions are required for them to work; and how they might affect the evolutionary process. We examined models in which a population can adapt through both genetic and cultural mechanisms. Our work was motivated by the invasion of highly toxic cane toads (Rhinella marina) across northern Australia and the resultant declines of endangered northern quolls (Dasyurus hallucatus), which attack and are fatally poisoned by the toxic toads. We examined whether a novel management strategy in which wild quolls are trained to avoid toads can reduce extinction probability. We used a simulation model tailored to quoll life history. Within simulations, individuals were trained and a continuous evolving trait determined innate tendency to attack toads. We applied this model in a population viability setting. The strategy reduced extinction probability only when heritability of innate aversion was low (<20%) and when trained mothers trained >70% of their young to avoid toads. When these conditions were met, genetic adaptation was slower, but rapid cultural adaptation kept the population extant while genetic adaptation was completed. To gain insight into the evolutionary dynamics (in which we saw a transitory peak in cultural adaptation over time), we also developed a simple analytical model of evolutionary dynamics. This model showed that the strength of natural selection declined as the cultural transmission rate increased and that adaptation proceeded only when the rate of cultural transmission was below a critical value determined by the relative levels of protection conferred by genetic versus cultural mechanisms. Together, our models showed that cultural adaptation can play a powerful role in preventing extinction, but that rates of cultural transmission need to be high for this to occur.

La adaptación cultural es un medio mediante el cual los conservacionistas pueden ayudar a las poblaciones a adaptarse a las amenazas. Un comportamiento aprendido puede proteger a un individuo de las amenazas y este comportamiento puede transmitirse horizontalmente (dentro de las generaciones) y verticalmente (entre generaciones), lo que otorga rápidamente una protección a nivel poblacional. Aunque esto es posible en teoría, aún no está claro si dichas manipulaciones funcionan dentro de un escenario de conservación; cuáles son las condiciones requeridas para que funcionen las manipulaciones; y cómo pueden afectar el proceso evolutivo. Examinamos modelos en los cuales una población puede adaptarse tanto con mecanismos genéticos como culturales. Nuestro trabajo estuvo motivado por la invasión de sapos altamente tóxicos (Rhinella marina) en todo el norte de Australia y las declinaciones resultantes de cuoles norteños (Dasyurus hallucatus), los cuales atacan y mueren envenenados por los sapos tóxicos. Analizamos si una estrategia de manejo novedoso en la cual los cuoles silvestres son entrenados para evitar a los sapos puede reducir la probabilidad de extinción. Usamos un modelo de simulación diseñado alrededor de la historia de vida de los cuoles. Dentro de las simulaciones, se entrenó a cuoles individuales y una característica en continua evolución determinó la tendencia innata para atacar a los sapos. Aplicamos este modelo en un escenario de viabilidad poblacional. La estrategia redujo la probabilidad de extinción sólo cuando la heredabilidad de la aversión innata fue baja (<20%) y cuando las madres entrenadas entrenaron a más del 70% de sus crías para evitar a los sapos. Cuando ambas condiciones fueron cumplidas, la adaptación genética fue más lenta pero la adaptación cultural rápida mantuvo a la población vigente mientras se completaba la adaptación genética. Para ganar conocimiento sobre las dinámicas evolutivas (en las cuales vimos un pico transitorio en la adaptación cultural a lo largo del tiempo) también desarrollamos un modelo analítico simple de las dinámicas evolutivas. Este modelo mostró que la fuerza de la selección natural declinó conforme incrementó la tasa de transmisión cultural y que la adaptación procedió solamente cuando la tasa de transmisión cultural estuvo por debajo de un valor crítico determinado por los niveles relativos de protección otorgados por los mecanismos genéticos contra los mecanismos evolutivos. En conjunto, nuestros modelos mostraron que la adaptación cultural puede jugar un papel importante en la prevención de la extinción, pero las tasas de transmisión cultural necesitan ser altas para que esto ocurra.

Partial Breast Reconstruction with Lateral Chest Wall Perforator Flap to Facilitate Breast Conservation in Breast Cancer: First 100 Cases with Cancer Outcomes at 8 Years Follow-Up and the Lessons Learned.

BACKGROUND: This is a prospective cohort study of partial breast reconstruction (PBR) with a lateral chest wall perforator flap (LCWPF) to facilitate breast conservation surgery (BCS) for women undergoing surgery for breast cancer. The study was undertaken to study the clinical and cancer outcomes. METHODS: Patients diagnosed with ductal carcinoma in situ (DCIS) or breast cancer who consented to undergo BCS with PBR with LCWPF were included in the study. A prospective database has been maintained to collect information on clinico-pathological features, complications, and follow-up. Patients were asked to complete an anonymised PROM questionnaire over the years. The hospital electronic records were interrogated for women who have completed 5 years follow-up to assess for development of recurrence/events. RESULTS: A total of 105 patients underwent PBR with LCWPFs between 2011 and 2018. Of these, 74% underwent cancer resection and PBR as one operation whilst 26% underwent PBR as a two-stage approach. The median tumor size on pre-op imaging was 30 mm for the one-stage approach and 39.5 mm for the two-stage approach (p-value=0.003). The complication rates were low and the re-operation rate for close margins was 10%, with 4% eventually requiring mastectomy. Good-to-excellent esthetic outcomes were reported in more than 80% of cases by patients and clinicians. The local recurrence rate (LR) was 2%, distant recurrence rate 10.5%, disease free survival (DFS) 86%, distant disease-free survival (DDFS) 89% and overall survival (OS) 94.8% at 4.5 years median follow-up. This procedure provides an effective oncological approach, avoiding mastectomy with a good-to-excellent cosmetic outcome. The follow-up data establishes the safety of this approach. DISCUSSION: This is the first published series of recurrence and survival data in patients undergoing PBR. We intend to continue with data collection to assess long-term outcomes beyond 10 years. The authors would recommend consideration of this technique to facilitate BCS and avoid mastectomy. REGISTRATION: Not applicable.