The effects of subcurative praziquantel treatment on life-history traits and trade-offs in drug-resistant Schistosoma mansoni

Natural selection acts on all organisms, including parasites, to maximize reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian state-space models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma mansoni may be limited by life-history costs not present in susceptible counterparts. S. mansoni parasites from a praziquantel-susceptible (S), a praziquantel-resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by praziquantel treatment in the R line, could limit the spread of R parasites under praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life-history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond

Understanding the social in a digital age

Datafication, algorithms, social media and their various assemblages enable massive connective processes, enriching personal interaction and amplifying the scope and scale of public networks. At the same time, surveillance capitalists and the social quantification sector are committed to monetizing every aspect of human communication, all of which threaten ideal social qualities, such as togetherness and connection. This Special Issue brings together a range of voices and provocations around ‘the social’, all of which aim to critically interrogate mediated human connection and their contingent socialities. Conventional methods may no longer be adequate, and we must rethink not only the fabric of the social but the very tools we use to make sense of our changing social formations. This Special Issue raises shared concerns with what the social means today, unpicking and rethinking the seams between digitization and social life that characterize today’s digital age

Tracing ‘21st Century Literacies’ in College and Career Ready State Standards: A Multi-State Scalar Analysis

This paper brings together resources of sociocultural literacy studies (Heath, 1983; Street, 1984; Barton, Hamilton, & Ivanic, 1999) and policy attribute analysis (Porter, Floden, Freeman, Schmidt, & Schwille, 1988) to examine how the meaning of “21st century skills/literacies” - as emphasized in recent college and career-readiness (CCR) standards - is framed and negotiated across state and district scales

Technical note: a simple procedure for removing temporal discontinuities in ERA-Interim upper stratospheric temperatures for use in nudged chemistry-climate model simulations

This note describes a simple procedure for removing unphysical temporal discontinuities in ERA-Interim upper stratospheric global mean temperatures in March 1985 and August 1998 that have arisen due to changes in satellite radiance data used in the assimilation. The derived temperature adjustments (offsets) are suitable for use in stratosphere-resolving chemistry-climate models that are nudged (relaxed) to ERA-Interim winds and temperatures. Simulations using a nudged version of the Canadian Middle Atmosphere Model (CMAM) show that the inclusion of the temperature adjustments produces temperature time series that are devoid of the large jumps in 1985 and 1998. Due to its strong temperature dependence, the simulated upper stratospheric ozone is also shown to vary smoothly in time, unlike in a nudged simulation without the adjustments where abrupt changes in ozone occur at the times of the temperature jumps. While the adjustments to the ERA-Interim temperatures remove significant artefacts in the nudged CMAM simulation, spurious transient effects that arise due to water vapour and persist for about 5 yr after the 1979 switch to ERA-Interim data are identified, underlining the need for caution when analysing trends in runs nudged to reanalyses

Capturing Hiproofs in HOL Light

Hierarchical proof trees (hiproofs for short) add structure to ordinary proof trees, by allowing portions of trees to be hierarchically nested. The additional structure can be used to abstract away from details, or to label particular portions to explain their purpose. In this paper we present two complementary methods for capturing hiproofs in HOL Light, along with a tool to produce web-based visualisations. The first method uses tactic recording, by modifying tactics to record their arguments and construct a hierarchical tree; this allows a tactic proof script to be modified. The second method uses proof recording, which extends the HOL Light kernel to record hierachical proof trees alongside theorems. This method is less invasive, but requires care to manage the size of the recorded objects. We have implemented both methods, resulting in two systems: Tactician and HipCam

Year 1 State Report: Kentucky

This report examines how the state of Kentucky approached college- and career-ready standards implementation during a time of transition. As their state legislature mandates a review of the standards and accountability system every six years, the Kentucky Department of Education (KDE) is in the midst of drafting potential revisions for public review and official implementation by summer 2017. For the purposes of this report and in keeping with C-SAIL’s focus, the authors concentrate on implementation of Kentucky’s English language arts (ELA) and math standards

Synthesis of chelating bidentate and tridentate cyano ligands and their complexes with Group VII metal carbonyls

Two new bidentate cyano ligands, DiCN-3 (2) and DEN-4 (3) (a,w-bis(2-cyanophenoxy)propane and -butane, respectively), have been prepared. These ligands and the ethane analogue DEN-2 (1) react with Mn(C0)5Br to afford complexes of the composition Mr~(cO)~(DicN-n)Br (n= 2, 9; n = 3, 10; n = 4, 11). Complexes 9 and 10 appear to be mononuclear and contain 13- and 14-membered chelate rings, respectively. Ligand 3 in 11 might be either chelated or bridged. IR studies of the reaction between 1-3 and Mn2(C0)6(CH&N)2(p-Br)2 show that, under identical conditions, more nitrile groups of 1 than of 2 and 3 are bound to the Mn(C0)3Br unit; this results suggests that DiCN-2 is a better chelating ligand than DiCN-3 or DiCN-4. A novel tricyano ligand, TriCN (1,3,5-tris(2-cyanophenyl)benzene (8)) has been synthesized from 2methylacetophenone. TriCN functions either as a bidentate ligand, as in M(CO)3(TriCN)Br (M = Mn, 12; M = Re, 14), or as a tridentate ligand, as in [M(CO),(TriCN)]PF6 (M = Mn, 13; M = Re, IS). Complexes 13 and 15 of TriCN are the first examples in which a tridentate cyano ligand chelates to a single metal center through its nitrogen lone pairs

Year 1 State Report: Ohio

This report examines how the state of Ohio approached college- and career-ready standards implementation during a time of transition, as they revised the Ohio Learning Standards in 2015–2016. The approval process will take place in 2016–2017, with new materials and revised standards ready for the 2017–2018 school year. For the purposes of this report and in keeping with C-SAIL’s focus, the authors concentrate on implementation of Ohio’s English language arts (ELA) and math standards

Year 1 State Report: Massachusetts

This report examines how the state of Massachusetts approached college- and career-ready standards implementation during a time of transition, as it develops the Next-Generation Massachusetts Comprehensive Assessment System, or the “Next-Gen MCAS,” in 2015–2016. The transition will take place in 2016–2017, with full implementation of the next-generation assessment by the spring of 2017. For the purposes of this report and in keeping with C-SAIL’s focus, the authors concentrate on implementation of Massachusetts’ English language arts (ELA) and math standards