The evolution and distribution of phage ST160 within Salmonella enterica serotype Typhimurium

Salmonellosis is an internationally important disease of mammals and birds. Unique epidemics in New Zealand in the recent past include two Salmonella serovars: Salmonella enterica subsp. enterica serovar Typhimurium definitive type (DT) 160 (S. Typhimurium DT160) and S. Brandenburg. Although not a major threat internationally, in New Zealand S. Typhimurium DT160 has been the most common serovar isolated from humans, and continues to cause significant losses in wildlife. We have identified DNA differences between the first New Zealand isolate of S. Typhimurium DT160 and the genome-sequenced strain, S. Typhimurium LT2. All the differences could be accounted for in one cryptic phage ST64B, and one novel P22-like phage, ST160. The majority of the ST160 genome is almost identical to phage SE1 but has two regions not found in SE1 which are identical to the P22-like phage ST64T, suggesting that ST160 evolved from SE1 via two recombination events with ST64T. All of the New Zealand isolates of DT160 were identical indicating the clonal spread of this particular Salmonella. Some overseas isolates of S. Typhimurium DT160 differed from the New Zealand strain and contained SE1 phage rather than ST160. ST160 was also identified in New Zealand isolates of S. Typhimurium DT74 and S. Typhimurium RDNC-April06 and in S. Typhimurium DT160 isolates from the USA. The emergence of S. Typhimurium DT160 as a significant pathogen in New Zealand is postulated to have occurred due to the sensitivity of the Salmonella strains to the ST160 phage when S. Typhimurium DT160 first arrived. © 2010 Cambridge University Press

The effect of rotational disorder on the microwave transmission of checkerboard metal square arrays

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThe effect of rotational disorder on the microwave transmission through thin metallic checkerboard arrays has been experimentally studied. Broad resonant features below the onset of diffraction, attributed to electromagnetic radiation coupling through the structure via the evanescent fields of bound surface waves, are found to be strongly dependent on the electrical connectivity of the surface. By applying rotational disorder to the elements comprising the arrays, with the lattice constant and element size unchanged, the electrical connectivity of the structure can be controlled whilst maintaining periodicity. The results show that rotational disorder can significantly affect transmission only when it changes the structure's connectivity. When the initial structure is just above the connectivity threshold (where the metallic occupancy is 50%), increasing disorder causes the resonant features in transmission to invert as the structure switches from a predominantly connected array to a disconnected array. When approximately half of the connections are broken, the resonant features are suppressed, with scattering loss shown to dramatically increase to as much as 40% of the incident power over a broad frequency range. The result is a thin, highly effective scatterer of microwaves.The authors acknowledge the financial support of DSTL. APH and JRS also acknowledge the support of EPSRC through the QUEST programme grant

A Microcosting Approach for Planning and Implementing Community-Based Mental Health Prevention Program: What Does It Cost?

BACKGROUND: Estimating program costs when planning community-based mental health programs can be burdensome. Our aim was to retrospectively document the cost for the first year of planning and implementing Healthy Minds Healthy Communities (HMHC), a mental health promotion and prevention multi-level intervention initiative. This Program is among the first to use the Community Initiated Care (CIC) model in the US and is aimed at building community resilience and the capacity for communities to provide mental health support, particularly among those disproportionately impacted by COVID-19. Our objective is to share our methods for costing a program targeting 10 zip codes that are ethnically and linguistically diverse and provide an example for estimating the cost of a mental health prevention and promotion programs consisting of multiple evidence-based interventions. METHODS: We used a semi-structured interview process to collect cost data through the first year of program planning, start-up and initial implementation from key staff. We calculated costs for each activity, grouped them by major project categories, and identified the cost drivers of each category. We further validated cost estimates through extensive literature review. The cost analysis was done from the provider\u27s perspective, which included the implementing agency and its community partners. We delineated costs that were in-kind contributions to the program by other agency, and community partners. Sensitivity analyses were conducted to estimate uncertainty around parameters. RESULTS: For the first year of the development and implementation of the program, (funded through program and in-kind) is estimated at $1,382,669 (2022 US$). The costs for the three main activity domains for this project are: project management $135,822, community engagement$364,216 and design and execution $756,934. Overall, the cost drivers for the first year of this intervention were: hiring and onboarding staff, in-person community building/learning sessions, communications and marketing, and intervention delivery. CONCLUSION: Implementation of community-based mental health promotion and prevention programs, when utilizing a participatory approach, requires a significant amount of upfront investment in program planning and development. A large proportion of this investment tends to be human capital input. Developing partnerships is a successful strategy for defraying costs

Probing the dynamics of an optically trapped particle by phase sensitive back focal plane interferometry

The dynamics of an optically trapped particle are often determined by measuring intensity shifts of the back-scattered light from the particle using position sensitive detectors. We present a technique which measures the phase of the back-scattered light using balanced detection in an external Mach-Zender interferometer scheme where we separate out and beat the scattered light from the bead and that from the top surface of our trapping chamber. The technique has improved axial motion resolution over intensity-based detection, and can also be used to measure lateral motion of the trapped particle. In addition, we are able to track the Brownian motion of trapped 1 and 3 $\mu$m diameter beads from the phase jitter and show that, similar to intensity-based measurements, phase measurements can also be used to simultaneously determine displacements of the trapped bead as well as the spring constant of the trap. For lateral displacements, we have matched our experimental results with a simulation of the overall phase contour of the back-scattered light for lateral displacements by using plane wave decomposition in conjunction with Mie scattering theory. The position resolution is limited by path drifts of the interferometer which we have presently reduced to obtain a displacement resolution of around 2 nm for 1.1 $\mu$m diameter probes by locking the interferometer to a frequency stabilized diode laser.Comment: 10 pages, 7 figure

Climate effects and stature since 1800

During the last 30 years, economic and social historians have collected and analysed large amounts of anthropometric data in order to explore key aspects of the human past. Attention has also been devoted to the examination of factors that can exert an influence on stature. This article outlines the different ways in which climate might influence stature, either directly or indirectly. It then uses Geographical Information System (GIS) software to explore the relationship between variations in temperature and precipitation and the average heights of men in France, India, Mexico, Spain and the United States (US) over the last two centuries. It is possible to observe an influence of climate on stature in some countries, especially during the nineteenth century, but the relationship weakens across time and largely disappears in recent decades. The attenuation of this relationship is attributed to a process of “technophysio evolution” as countries modernised and developed economically

Sirt1 inhibits resistin expression in aortic stenosis

The development of human calcified aortic stenosis (AS) includes age-dependent processes that have been involved in atherosclerosis, such as infiltration of macrophages in aortic valves, which then promote production of many proinflammatory cytokines, including resistin. However, the molecular mechanisms contributing to these processes are not established. Since Sirt1 has been shown to modulate macrophage biology and inflammation, we examined its levels in human AS and tested its impact on resistin expression. Sirt1 mRNA (p = 0.01) and protein (p,0.05) levels were reduced in explanted valves from AS patients (n = 51) compared to those from control (n = 11) patients. Sirt1 mRNA levels were negatively associated with resistin mRNA levels quantified in AS valves (p = 0.02). Stimulation of Sirt1 by resveratrol or virusdriven overexpression robustly diminished resistin mRNA and protein expression in macrophages, whereas down-regulation of Sirt1 triggered a large increase in resistin expression. These effects were direct, as chromatin immunoprecipitation assays showed that Sirt1 physically interacted with the resistin promoter region at an AP-1 response element. Moreover, Sirt1 blocked c-jun-induced resistin transactivation in gene reporter assays. These findings demonstrate that, in calcified AS, levels of Sirt1 are reduced whereas those of resistin are increased within aortic valve leaflets. Our results also suggest that this loss of Sirt1 expression alleviates its inhibition of resistin transcription in macrophages. Although the overall contribution of this process to the underlying mechanisms for AS disease development remains unresolved, these observations suggest that modification of Sirt1 expression and/or activity could represent a novel approach against inflammation in AS

Tau Signals of R-parity breaking at LEP 200

The detectability at LEP 200 of explicit $R$-parity breaking by tau-number $(L_\tau)$ violating operators is considered. The assumption of $L_\tau$-violation is motivated by the relative lack of constraints on such couplings but similar considerations apply to explicit $L_e$- or $L_\mu$-violation. The $LSP$, now unstable, and not necessarily neutral, decays via $L_\tau$-violating modes. Only signals from the production and decays of $LSP$ pairs are considered, thereby avoiding any dependence on the sparticle mass spectrum. Rather spectacular signals are predicted: spherical events with $m$ leptons (usually containing at least one $\tau$) and $n$ jets $(m,n \leq 4)$, the most characteristic of which are like-sign $\tau\tau$ events. These signals are enumerated for each $LSP$ candidate and quantitative estimates are provided for the favoured case when the $LSP$ is a neutralino. Other new physics signals, which can mimic these signatures, are also briefly discussed.Comment: 27 pages in PHYZZX, six figures (not included, available on request). TIFR/TH/92-29,UH-511-751-92,CERN-TH.6613/9

Enhancing Science Impact in the Coastal Zone through Adaptive Learning

The impact of science to support coastal management may be reduced through social and institutional barriers. Some of these barriers include ineffective community engagement, lack of interaction between scientists and decision makers, and institutional decision-making tradition related to hierarchical mandates. A three-year project has commenced to examine the role of adaptive learning in overcoming some of these barriers to maximize pathways for science and improve decisions made in the coastal zone. Adaptive learning is one of five project areas targeted to enhance science impact, being undertaken by a consortium of nine Australian universities funded through the CSIRO Collaboration Fund. Two of the strategies being explored to maximize adaptive learning to improve science impact include: (i) development of an on-line toolkit for embedding adaptive learning within coastal organizations; and (ii) development and testing of monitoring and evaluation frameworks to improve adaptive learning interventions. While focused on an Australian context, the project addresses broad issues of social and institutional barriers that have relevance for many coastal scientists and decision makers around the globe

A model for anomalous moisture diffusion through a polymer-clay nanocomposite

Experimental data are reported on moisture diffusion and the elastoplastic response of an intercalated nanocomposite with vinyl ester resin matrix and montmorillonite clay filler at room temperature. Observations in diffusion tests show that water transport in the neat resin is Fickian, whereas it becomes anomalous (non-Fickian) with the growth of the clay content. This transition is attributed to immobilization of penetrant molecules on the surfaces of hydrophilic clay layers. Observations in uniaxial tensile tests demonstrate that the response of vinyl ester resin is strongly elastoplastic, whereas an increase in the clay content results in a severe decrease of plastic strains observed as a noticeable reduction of curvatures of the stress--strain diagrams. This is explained by slowing down of molecular mobility in the host matrix driven by confinement of chains in galleries between platelets. Constitutive equations are developed for the anomalous moisture diffusion through and the elastoplastic behavior of a nanocomposite. Adjustable parameters in these relations are found by fitting the experimental data. Fair agreement is demonstrated between the observations and the results of numerical simulation. A striking similarity is revealed between changes in diffusivity, ultimate water uptake and the rate of plastic flow with an increase in the clay content.Comment: 29 pages, 17 figure

Long-term maintenance of certolizumab pegol safety and efficacy, in combination with methotrexate and as monotherapy, in rheumatoid arthritis patients

Introduction The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs). Methods Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared. Results Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations. Conclusions The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients