The evolution of multiple mating: Costs and benefits of polyandry to females and of polygyny to males

Polyandry is a paradox: why do females mate multiple times when a single ejaculate often provides enough sperm for lifetime egg production? Gowaty et al. addressed explanations for polyandry in Drosophila pseudoobscura from the perspective of hypotheses based on sex differences in costs of reproduction (CoR). Contrary to CoR, Gowaty et al. showed that (1) a single ejaculate was inadequate for lifetime egg production; (2) polyandry provided fitness benefits to females beyond provision of adequate sperm and (3) fitness benefits of polyandry were not offset by costs. Here, I discuss predictions of the ad hoc hypotheses of CoR and three alternative hypotheses to CoR to facilitate a discussion and further development of a strong inference approach to experiments on the adaptive significance of polyandry for females. Each of the hypotheses makes testable predictions; simultaneous tests of the predictions will provide a strong inference approach to understanding the adaptive significance of multiple mating. I describe a sex-symmetric experiment meant to evaluate variation in fitness among lifelong virgins (V); monogamous females and males with one copulation (MOC); monogamous females and males with multiple copulations (MMC); PAND, polyandrous females; and PGYN, polygynous males. Last, I recommend the study of many different species, while taking care in choice of study species and attention to the assumptions of specific hypotheses. I particularly urge the study of many more Drosophila species both in laboratory and the wild to understand the “nature of flies in nature,” where opportunities and constraints mold evolutionary responses

On the relative expressiveness of higher-order session processes

By integrating constructs from the λ-calculus and the π-calculus, in higher-order process calculi exchanged values may contain processes. This paper studies the relative expressiveness of HOπ, the higher-order π-calculus in which communications are governed by session types. Our main discovery is that HO, a subcalculus of HOπ which lacks name-passing and recursion, can serve as a new core calculus for session-typed higher-order concurrency. By exploring a new bisimulation for HO, we show that HO can encode HOπ fully abstractly (up to typed contextual equivalence) more precisely and efficiently than the first-order session π-calculus (π). Overall, under session types, HOπ, HO, and π are equally expressive; however, HOπ and HO are more tightly related than HOπ and π

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas

Efficacy of FODMAP Elimination and Subsequent Blinded Placebo-Controlled Provocations in a Randomised Controlled Study in Patients with Ulcerative Colitis in Remission and Symptoms of Irritable Bowel Syndrome:A Feasibility Study

Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging

Out-of-Hospital Cardiac Arrest in Patients With Psychiatric Disorders - Characteristics and Outcomes

Aims To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders. Methods We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001–2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression. Results Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32–0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70–0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72–0.83), shockable heart rhythm (0.37 95% CI, 0.33–0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59–0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0–10.0%) in 2006 to 13.9% (CI 12.4–15.4%) in 2015 and from 7.0% (4.3–10.8%) in 2006 to 7.0% (CI 4.5–9.7%) in 2015, respectively. Conclusion Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time