Natal-host environmental effects on juvenile size, transmission success, and operational sex ratio in the entomopathogenic nematode Steinernema carpocapsae

Trans-host effects can alter the ecological and evolutionary dynamics of parasite and host populations. Here, we examine whether resource limitation within a parasite's natal host affects propagule size and influences parasite fitness in a new host. To alter resource competition, we infected caterpillars with 3 doses of the nematode Steinernema carpocapsae and harvested transmission-stage juveniles either early or late in the infection. We measured the size of these juveniles, and then we examined their ability to colonize and their sex ratio upon maturity in a new host. We found a trade-off between the cumulative number and size of nematodes emerging from a host. Emerging nematode size declined significantly over the time course of the infection, but dose had no significant effects. Larger, early emerging nematodes had greater success in colonizing a new host than smaller, later emerging nematodes, independently of whether they needed to locate the host. Furthermore, although early emerging nematodes resulted in an equal sex ratio in the new host, late emerging nematodes resulted in female-biased populations. These transmission and sex-ratio effects demonstrate that conditions in the natal host can affect parasite fitness, and they suggest that trans-host effects need to be more fully integrated into our studies of parasite populations

Does interspecific competition affect offspring provisioning?

Offspring size is one of the most well-studied life-history traits, yet it is remarkable that few field studies have examined the manner in which the relationship between offspring size and performance (and thus, optimal offspring size) is affected by the local environment. Furthermore, while offspring size appears to be plastic in a range of organisms, few studies have linked changes in offspring size to changes in the relationship between offspring size and performance in the field. Interspecific competition is a major ecological force in both terrestrial and marine environments, but we have little understanding of its role in shaping selection on offspring size. Here we examine the effect of interspecific competition on the relationship between offspring size and performance in the field for the marine bryozoan Watersipora subtorquata along the south coast of Australia. Both interspecific competition and offspring size had strong effects on the post-metamorphic performance of offspring in the field, but importantly, they acted independently. While interspecific competition did not affect the offspring size-performance relationship, mothers experiencing competition still produced larger offspring than mothers that did not experience competition. Because larger offspring are more dispersive in this species, increasing offspring size may represent a maternal strategy whereby mothers produce more dispersive offspring when they experience high competition themselves. This study shows that, while offspring size is plastic in this species, post-metamorphic factors alone may not determine the size of offspring that mothers produce

Correction: The European Society for Blood and Marrow Transplantation (EBMT) consensus guidelines for the detection and treatment of donor-specific anti-HLA antibodies (DSA) in haploidentical hematopoietic cell transplantation

The original version of this Article contained a typographical error in the spelling of the author Marcelo Fernandez-Vina, which was incorrectly given as Marcelo Fernadez-Vina. This has now been corrected in the PDF and HTML versions of the Article

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Sex-specific local life-history adaptation in surface- and cave-dwelling Atlantic mollies (Poecilia mexicana)

Cavefishes have long been used as model organisms showcasing adaptive diversification, but does adaptation to caves also facilitate the evolution of reproductive isolation from surface ancestors? We raised offspring of wild-caught surface- and cave-dwelling ecotypes of the neotropical fish Poecilia mexicana to sexual maturity in a 12-month common garden experiment. Fish were raised under one of two food regimes (high vs. low), and this was crossed with differences in lighting conditions (permanent darkness vs. 12:12 h light:dark cycle) in a 2 × 2 factorial design, allowing us to elucidate potential patterns of local adaptation in life histories. Our results reveal a pattern of sex-specific local life-history adaptation: Surface molly females had the highest fitness in the treatment best resembling their habitat of origin (high food and a light:dark cycle), and suffered from almost complete reproductive failure in darkness, while cave molly females were not similarly affected in any treatment. Males of both ecotypes, on the other hand, showed only weak evidence for local adaptation. Nonetheless, local life-history adaptation in females likely contributes to ecological diversification in this system and other cave animals, further supporting the role of local adaptation due to strong divergent selection as a major force in ecological speciation

The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation

The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms

Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice

Evolutionary consequences of feedbacks between within-host competition and disease control

Lay Summary: Competition often occurs among diverse parasites within a single host, but control efforts could change its strength. We examined how the interplay between competition and control could shape the evolution of parasite traits like drug resistance and disease severity