Real-time growth rate for general stochastic SIR epidemics on unclustered networks

Networks have become an important tool for infectious disease epidemiology. Most previous theoretical studies of transmission network models have either considered simple Markovian dynamics at the individual level, or have focused on the invasion threshold and final outcome of the epidemic. Here, we provide a general theory for early real-time behaviour of epidemics on large configuration model networks (i.e. static and locally unclustered), in particular focusing on the computation of the Malthusian parameter that describes the early exponential epidemic growth. Analytical, numerical and Monte-Carlo methods under a wide variety of Markovian and non-Markovian assumptions about the infectivity profile are presented. Numerous examples provide explicit quantification of the impact of the network structure on the temporal dynamics of the spread of infection and provide a benchmark for validating results of large scale simulations.Comment: 45 pages, 8 figures, submitted to Mathematical Biosciences on 29/11/2014; Version 2: resubmitted on 15/04/2015; accepted on 17/04/2015. Changes: better explanations in introduction; restructured section 3.3 (3.3.3 added); section 6.3.1 added; more precise terminology; typos correcte

It takes a village to break up a match: a systemic analysis of formal youth mentoring relationship endings

BACKGROUND Although early closure of formal youth mentoring relationships has recently begun to receive some attention, more information about factors that contribute to premature endings, and how those factors interact, is needed so that empirically-based program practices can be developed and disseminated to prevent such endings and to ensure that youth reap the benefits mentoring can provide. OBJECTIVE This qualitative interview study applies a systemic model of youth mentoring relationships (Keller in J Prim Prev 26:169–188, 2005a) to the study of mentoring relationship endings in community-based mentoring matches to understand why these matches ended. METHOD Mentors, parents/guardians and program staff associated with 36 mentoring matches that had ended were interviewed about their experiences of these relationships and their understanding of why they had ended. Thematic analysis of the interview transcripts and mentoring program case notes for each match followed by systemic modeling of the relationships yielded three major findings. RESULTS A strong mentor–youth relationship is necessary but not sufficient for match longevity. The mentor–youth relationship, even when relatively strong, is unlikely to withstand disruptions in other relationships in the system. Agency contextual factors, such as program practices and policies and staffing patterns, have a critical role to play in sustaining mentoring matches, as they directly influence all of the relationships in the mentoring system. CONCLUSION These findings highlight the importance of considering not just the mentoring dyad but also the parent/guardian and program context when trying to prevent match closures. They also point to several program practices that may support longer mentoring relationships.Accepted manuscrip

Trophoblast biology: Forum introduction

In mammals, a carefully orchestrated dialogue between the mother and conceptus (embryo/fetus and associate extraembryonic membranes) is initiated during the peri-implantation period of pregnancy as the trophoblast develops, functions to signal pregnancy recognition, and initiates implantation. The purpose of this Forum is to highlight comparative aspects of trophoblast morphogenesis and function in mammals

Conceptus signals for establishment and maintenance of pregnancy

Establishment and maintenance of pregnancy results from signaling by the conceptus (embryo/fetus and associated extraembryonic membranes) and requires progesterone produced by the corpus luteum (CL). In most mammals, hormones produced by the trophoblast maintain progesterone production by acting directly or indirectly to maintain the CL. In domestic animals (ruminants and pigs), hormones from the trophoblast are antiluteolytic in that they act on the endometrium to prevent uterine release of luteolytic prostaglandin F2 alpha (PGF). In cyclic and pregnant sheep, progesterone negatively autoregulates expression of the progesterone receptor (PR) gene in the endometrial luminal (LE) and superficial glandular epithelium (GE). Available evidence in cyclic sheep indicates that loss of the PR is closely followed by increases in epithelial estrogen receptors (ER) and then oxytocin receptors (OTR), allowing oxytocin to induce uterine release of luteolytic PGF pulses. In pregnant sheep, the conceptus trophoblast produces interferon tau (IFN tau) that acts on the endometrium to inhibit transcription of the ER alpha gene directly and the OTR gene indirectly to abrogate development of the endometrial luteolytic mechanism. Subsequently, sequential, overlapping actions of progesterone, IFN tau, placental lactogen (PL) and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function to maintain pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that alters the direction of PGF secretion from an endocrine to exocrine direction, thereby sequestering luteolytic PGF within the uterine lumen. Conceptus estrogen also increases expression of fibroblast growth factor 7 (FGF-7) in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the FGF-7 receptor. Strategic manipulation of these physiological mechanisms can offer therapeutic schemes to improve uterine capacity, conceptus survival and reproductive health

Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

iDNA from terrestrial haematophagous leeches as a wildlife surveying and monitoring tool - prospects, pitfalls and avenues to be developed

Invertebrate-derived DNA (iDNA) from terrestrial haematophagous leeches has recently been proposed as a powerful non-invasive tool with which to detect vertebrate species and thus to survey their populations. However, to date little attention has been given to whether and how this, or indeed any other iDNA-derived data, can be combined with state-of-the-art analytical tools to estimate wildlife abundances, population dynamics and distributions. In this review, we discuss the challenges that face the application of existing analytical methods such as site-occupancy and spatial capture-recapture (SCR) models to terrestrial leech iDNA, in particular, possible violations of key assumptions arising from factors intrinsic to invertebrate parasite biology. Specifically, we review the advantages and disadvantages of terrestrial leeches as a source of iDNA and summarize the utility of leeches for presence, occupancy, and spatial capture-recapture models. The main source of uncertainty that attends species detections derived from leech gut contents is attributable to uncertainty about the spatio-temporal sampling frame, since leeches retain host-blood for months and can move after feeding. Subsequently, we briefly address how the analytical challenges associated with leeches may apply to other sources of iDNA. Our review highlights that despite the considerable potential of leech (and indeed any) iDNA as a new survey tool, further pilot studies are needed to assess how analytical methods can overcome or not the potential biases and assumption violations of the new field of iDNA. Specifically we argue that studies to compare iDNA sampling with standard survey methods such as camera trapping, and those to improve our knowledge on leech (and other invertebrate parasite) physiology, taxonomy, and ecology will be of immense future value

Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle

In cattle, conceptus-maternal interactions are critical for the establishment and maintenance of pregnancy. A major component of this early interaction involves the transport of nutrients and secretion of key molecules by uterine epithelial cells to help support conceptus development during the peri-implantation period of pregnancy. Objectives were to: 1) analyze temporal changes in the amino acid (AA) content of uterine luminal fluid (ULF) during the bovine estrous cycle; 2) understand conceptus-induced alterations in AA content; 3) determine expression of AA transporters in the endometrium and conceptus; and 4) determine how these transporters are modulated by (Progesterone) P4. Concentrations of aspartic acid, arginine, glutamine, histidine, lysine, isoleucine, leucine, phenylalanine and tyrosine decreased on Day 16 of the estrous cycle but increased on Day 19 in pregnant heifers (P < 0.05). Glutamic acid only increased in pregnant heifers on Day 19 (P,0.001). Asparagine concentrations were greater in ULF of cyclic compared to pregnant heifers on Day 7 (P < 0.05) while valine concentrations were higher in pregnant heifers on Day 16 (P < 0.05). Temporal changes in expression of the cationic AA transporters SLC7A1 SLC7A4 and SLC7A6 occurred in the endometrium during the estrous cycle/early pregnancy coordinate with changes in conceptus expression of SLC7A4, SLC7A2 and SLC7A1 (P < 0.05). Only one acidic AA transporter (SLC1A5) increased in the endometrium while conceptus expression of SLC1A4 increased (P < 0.05). The neutral AA transporters SLC38A2 and SLC7A5 increased in the endometrium in a temporal manner while conceptus expression of SLC38A7, SLC43A2, SLC38A11 and SLC7A8 also increased (P < 0.05). P4 modified the expression of SLC1A1, -1A4, -1A5, -38A2 , -38A4, -38A7, -43A2, -6A14, -7A1, -7A5 and -7A7 in the endometrium. Results demonstrate that temporal changes in AA in the ULF reflect changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle, some of which are modified by P4. © 2014 Forde et al