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Investigations of origami tessellations as effective media reveal the ability to program the components of their elasticity tensor, and thus control the mechanical behavior of thin sheets. However, existing efforts focus on crease patterns that are composed of parallelogram faces where the parallel lines constrain the quasi-static elastic response. In this work, crease patterns composed of more general trapezoid faces are considered and their low-energy linear response is explored. Deformations of such origami tessellations are modeled as linear isometries that do not stretch individual panels at the small scale yet map to non-isometric changes of coarse-grained fundamental forms that quantify how the effective medium strains and curves at the large scale. Two distinct mode shapes, a rigid breathing mode and a nonrigid shearing mode, are identified in the continuum model. A specific example, which we refer to as Arc-Morph origami, is presented with analytical expressions for its deformations in both the discrete and continuous models. A developable specimen is fabricated and tested to validate the analytical predictions. This work advances the continuum modeling of origami tessellations as effective media with the incorporation of more generic faces and ground states, thereby enabling the investigation of novel designs and applications. The authors investigate the mechanical behavior of origami tessellations composed of trapezoid faces, which are more general but less studied compared to parallelogram faces. They develop analytical expressions for the deformation modes and test the model’s validity through laboratory scale experiments.

PurposeSuccessful oral peptide delivery faces two major hurdles: low enzymatic stability in the gastro-intestinal lumen and poor intestinal membrane permeability. While lipid-based formulations (LBF) have the potential to overcome these barriers, effective formulation of peptides remains challenging. Lipophilic salt (LS) technology can increase the apparent lipophilicity of peptides, making them more suitable for LBF.MethodsAs a model therapeutic peptide, octreotide (OCT) was converted to the docusate LS (OCT.DoS2), and compared to the commercial acetate salt (OCT.OAc2) in oral absorption studies and related in vitro studies, including parallel artificial membrane permeability assay (PAMPA), Caco-2, in situ intestine perfusion, and simulated digestion in vitro models. The in vivo oral absorption of OCT.DoS2 and OCT.OAc2 formulated in self-emulsifying drug delivery systems (SEDDS) was studied in rats.ResultsLS formulation improved the solubility and loading of OCT in LBF excipients and OCT.DoS2 in combination with SEDDS showed higher OCT absorption than the acetate comparator in the in vivo studies in rats. The Caco-2 and in situ intestine perfusion models indicated no increases in permeability for OCT.DoS2. However, the in vitro digestion studies showed reduced enzymatic degradation of OCT.DoS2 when formulated in the SEDDS formulations. Further in vitro dissociation and release studies suggest that the enhanced bioavailability of OCT from SEDDS-incorporating OCT.DoS2 is likely a result of higher partitioning into and prolonged retention within lipid colloid structures.ConclusionThe combination of LS and LBF enhanced the in vivo oral absorption of OCT primarily via the protective effect of LBF sheltering the peptide from gastrointestinal degradation.

Pathogens that are transmitted between wildlife, livestock and humans present major challenges for the protection of human and animal health, the economic sustainability of agriculture, and the conservation of wildlife. Mycobacterium bovis , the aetiological agent of bovine tuberculosis (TB), is one such pathogen. The incidence of TB in cattle has increased substantially in parts of Great Britain in the past two decades, adversely affecting the livelihoods of cattle farmers and potentially increasing the risks of human exposure. The control of bovine TB in Great Britain is complicated by the involvement of wildlife, particularly badgers ( Meles meles ), which appear to sustain endemic infection and can transmit TB to cattle 1 . Between 1975 and 1997 over 20,000 badgers were culled as part of British TB control policy, generating conflict between conservation and farming interest groups 2 . Here we present results from a large-scale field trial 3 , 4 , 5 that indicate that localized badger culling not only fails to control but also seems to increase TB incidence in cattle.

1. The incidence of bovine tuberculosis (TB) in British cattle has risen markedly over the last two decades. Failure to control the disease in cattle has been linked to the persistence of a reservoir of infection in European badgers Meles meles, a nationally protected species. Although badger culling has formed a component of British TB control policy for many years, a recent large-scale randomized field experiment found that TB incidence in cattle was no lower in areas subject to localized badger culling than in nearby areas where no experimental culls occurred. Indeed, analyses indicated that cattle incidence was higher in culled areas. 2. One hypothesis advanced to explain this pattern is that localized culling disrupted badgers' territorial behaviour, potentially increasing the rate of contact between cattle and infected badgers. This study evaluated this hypothesis by investigating badger activity and spatial organization in 13 study areas subjected to different levels of culling. Badger home ranges were mapped by feeding colour-marked baits at badger dens and measuring the geographical area in which colour-marked faeces were retrieved. 3. Badger home ranges were consistently larger in culling areas. Moreover, in areas not subjected to culling, home range sizes increased with proximity to the culling area boundary. Patterns of overlap between home ranges were also influenced by culling. 4. Synthesis and applications. This study demonstrates that culling badgers profoundly alters their spatial organization as well as their population density. These changes have the potential to influence contact rates between cattle and badgers, both where culls occur and on adjoining land. These results may help to explain why localized badger culling appears to have failed to control cattle TB, and should be taken into account in determining what role, if any, badger culling should play in future control strategies.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers ( Meles meles ) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis , the causative agent of bovine tuberculosis (TB), to cattle 1 . Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced 2 , 3 or increased 4 , 5 incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies 2 , 3 , 4 , 5 but will present challenges for policy development.

As an aid to the study of bovine tuberculosis (TB), a simple model has been developed of an epidemic involving two species, cattle and badgers. Each species may infect the other. The proportion of animals affected is assumed relatively small so that the usual nonlinear aspects of epidemic theory are avoided. The model is used to study the long-run and transient effect on cattle of culling badgers and the effect of a period without routine testing for TB, such as occurred during the 2001 epidemic of foot-and-mouth disease in Great Britain. Finally, by examining the changes in cattle TB over the last 15 years, and with some other working assumptions, it is estimated that the net reproduction number of the epidemic is approximately equal to 1.1. The implications for controlling the disease are discussed.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.

The authors provide evidence of important spillover effects of comprehensive health care reform on workers’ compensation (WC) that are likely to reduce WC costs. Using data on more than 20 million emergency room (ER) discharges in Massachusetts and three comparison states, they find that Massachusetts health care reform caused a 6.2 to 8.2% decrease in the per capita number of ER discharges billed to WC. The authors document heterogeneity in the impacts of the reform, shedding light on the mechanisms generating the overall decline in ER discharges billed to WC. Results indicate a larger decrease in WC claiming for weekday admissions than for weekend admissions and for harder-to-verify musculoskeletal discharges than for wounds. The decline in WC discharges is driven both by injured workers increasingly seeking care outside of the ER and by changes in the propensity to bill WC for a given ER discharge.

The Triassic/Jurassic boundary, 208 million years ago, is associated with widespread extinctions in both the marine and terrestrial biota. The cause of these extinctions has been widely attributed to the eruption of flood basalts of the Central Atlantic Magmatic Province 1 , 2 , 3 , 4 . This volcanic event is thought to have released significant amounts of CO 2 into the atmosphere, which could have led to catastrophic greenhouse warming 5 , 6 , 7 , but the evidence for CO 2 -induced extinction remains equivocal. Here we present the carbon isotope compositions of pedogenic calcite from palaeosol formations, spanning a 20-Myr period across the Triassic/Jurassic boundary. Using a standard diffusion model 8 , 9 , we interpret these isotopic data to represent a rise in atmospheric CO 2 concentrations of about 250 p.p.m. across the boundary, as compared with previous estimates of a 2,000–4,000 p.p.m. increase 4 , 5 . The relative stability of atmospheric CO 2 across this boundary suggests that environmental degradation and extinctions during the Early Jurassic were not caused by volcanic outgassing of CO 2 . Other volcanic effects—such as the release of atmospheric aerosols or tectonically driven sea-level change—may have been responsible for this event.

The Randomized Badger Culling Trial (RBCT) began in 1998 to determine the impact of badger culling in controlling bovine tuberculosis in cattle. A total of 1166 badgers (14% of total) proactively culled during the RBCT were found to be tuberculous, offering a unique opportunity to study the pathology caused by Mycobacterium bovis in a large sample of badgers. Of these, 39% of adults (~6% of all adults culled) had visible lesions (detectable at necropsy) of bovine tuberculosis; cubs had a lower prevalence of infection (9%) but a higher percentage of tuberculous cubs (55·5%) had visible lesions. Only ~1% of adult badgers had extensive, severe pathology. Tuberculous badgers with recorded bite wounds (~5%) had a higher prevalence of visible lesions and a different distribution of lesions, suggesting transmission via bite wounds. However, the predominance of lesions in the respiratory tract indicates that most transmission occurs by the respiratory route.