Search

As sustainable development practitioners have worked to “ensure healthy lives and promote well-being for all” and “conserve life on land and below water”, what progress has been made with win–win interventions that reduce human infectious disease burdens while advancing conservation goals? Using a systematic literature review, we identified 46 proposed solutions, which we then investigated individually using targeted literature reviews. The proposed solutions addressed diverse conservation threats and human infectious diseases, and thus, the proposed interventions varied in scale, costs, and impacts. Some potential solutions had medium-quality to high-quality evidence for previous success in achieving proposed impacts in one or both sectors. However, there were notable evidence gaps within and among solutions, highlighting opportunities for further research and adaptive implementation. Stakeholders seeking win–win interventions can explore this Review and an online database to find and tailor a relevant solution or brainstorm new solutions.

The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops. Importantly, ERK1/2 inhibition may have clinical utility in overcoming acquired resistance to RAF and MEK inhibitors, where RAS/MAPK pathway reactivation has occurred, such as relapsed BRAF V600E/K melanoma. We describe our structure-based design approach leading to the discovery of AZD0364, a potent and selective inhibitor of ERK1 and ERK2. AZD0364 exhibits high cellular potency (IC50= 6 nM) as well as excellent physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties and has demonstrated encouraging antitumor activity in preclinical models.

A multidisciplinary approach covering synthetic, physical, and analytical chemistry, high-throughput experimentation and experimental design, process engineering, and solid-state chemistry is used to develop a large-scale (kilomole) Suzuki–Miyaura process. Working against clear criteria and targets, a full process investigation and optimization package is described highlighting how and why key decisions are made in the development of large-scale pharmaceutical processes.

Infectious disease contributed to historical declines and extirpations of bighorn sheep (Ovis canadensis) in North America and continues to impede population restoration and management. Reports of pneumonia outbreaks in free‐ranging bighorn sheep following contact with domestic sheep have been validated by the results of 13 captive commingling experiments. However, ecological and etiological complexities still hinder our understanding and control of respiratory disease in wild sheep. In this paper, we review the literature and summarize recent data to present an overview of the biology and management of pneumonia in bighorn sheep. Many factors contribute to this population‐limiting disease, but a bacterium (Mycoplasma ovipneumoniae) host‐specific to Caprinae and commonly carried by healthy domestic sheep and goats, appears to be a primary agent necessary for initiating epizootics. All‐age epizootics are usually associated with significant population declines, but mortality rates vary widely and factors influencing disease severity are not well understood. Once introduced, M. ovipneumoniaecan persist in bighorn sheep populations for decades. Carrier females may transmit the pathogen to their susceptible lambs, triggering fatal pneumonia outbreaks in nursery groups, which limit recruitment and slow or prevent population recovery. The demographic costs of disease persistence can be equal to or greater than the impacts of the initial epizootic. Strain typing suggests that spillover of M. ovipneumoniaeinto bighorn sheep populations from domestic small ruminants is ongoing and that consequences of spillover are amplified by movements of infected bighorn sheep across populations. Therefore, current disease management strategies focus on reducing risk of spillover from reservoir populations of domestic sheep and goats and on limiting transmission among bighorn sheep. A variety of techniques are employed to prevent contacts that could lead to transmission, including limiting the numbers and distribution of both wild and domestic species. No vaccine or antibiotic treatment has controlled infection in domestic or wild sheep and to date, management actions have been unsuccessful at reducing morbidity, mortality, or disease spread once a bighorn sheep population has been exposed. More effective strategies are needed to prevent pathogen introduction, induce disease fadeout in persistently infected populations, and promote population resilience across the diverse landscapes bighorn sheep inhabit. A comprehensive examination of disease dynamics across populations could help elucidate how disease sometimes fades out naturally and whether population resilience can be increased in the face of infection. Cross‐jurisdictional adaptive management experiments and transdisciplinary collaboration, including partnerships with members of the domestic sheep and goat community, are needed to speed progress toward sustainable solutions to protect and restore bighorn sheep populations. © 2017 The Wildlife Society. Pneumonia contributed to historical declines of bighorn sheep and impedes population restoration. Management priorities include 1) reducing risk of spillover from domestic sheep and goats 2) facilitating pathogen extinction after spillover has occurred, and 3) exploring options for increasing individual and population resilience in the face of infection.

The Carbon Cycle Kate Rawles ISBN: 978-1906120634 Two Ravens Press, www.tworavenspress.com 300pp; 11.99 £ In June 2006, Kate Rawles set out to cycle over 4,500 miles from El Paso, Texas, [...]

Environmental politics is becoming more popular within the United Kingdom and even though it has supporters from every walk of life, it is difficult to achieve anything within the country's current democratic process. It is a common belief that the major political parties do not represent public opinion and that for any real progress to be made, a major democratic renewal exercise has to occur first.

Trypanosoma cruzi, causative agent of Chagas disease, co-infects its triatomine vector with its sister species Trypanosoma rangeli, which shares 60% of its antigens with T. cruzi. Additionally, T. rangeli has been observed to be pathogenic in some of its vector species. Although T. cruzi-T. rangeli co-infections are common, their effect on the vector has rarely been investigated. Therefore, we measured the fitness (survival and reproduction) of triatomine species Rhodnius prolixus infected with just T. cruzi, just T. rangeli, or both T. cruzi and T. rangeli. We found that survival (as estimated by survival probability and hazard ratios) was significantly different between treatments, with the T. cruzi treatment group having lower survival than the co-infected treatment. Reproduction and total fitness estimates in the T. cruzi and T. rangeli treatments were significantly lower than in the co-infected and control groups. The T. cruzi and T. rangeli treatment group fitness estimates were not significantly different from each other. Additionally, co-infected insects appeared to tolerate higher doses of parasites than insects with single-species infections. Our results suggest that T. cruzi-T. rangeli co-infection could ameliorate negative effects of single infections of either parasite on R. prolixus and potentially help it to tolerate higher parasite doses. [ABSTRACT FROM AUTHOR]

In this paper we derive from first principles the expected body sizes of the parasite communities that can coexist in a mammal of given body size. We use a mixture of mathematical models and known allometric relationships to examine whether host and parasite life histories constrain the diversity of parasite species that can coexist in the population of any host species. The model consists of one differential equation for each parasite species and a single density-dependent nonlinear equation for the affected host under the assumption of exploitation competition. We derive threshold conditions for the coexistence and competitive exclusion of parasite species using invasion criteria and stability analysis of the resulting equilibria. These results are then used to evaluate the range of parasites species that can invade and establish in a target host and identify the ‘optimal’ size of a parasite species for a host of a given body size; ‘optimal’ is defined as the body size of a parasite species that cannot be outcompeted by any other parasite species. The expected distributions of parasites body sizes in hosts of different sizes are then compared with those observed in empirical studies. Our analysis predicts the relative abundance of parasites of different size that establish in the host and suggests that increasing the ratio of parasite body size to host body size above a minimum threshold increases the persistence of the parasite population. [ABSTRACT FROM AUTHOR]

TO EFFECTIVELY DEVELOP PHYSICAL PARAMETERS, TRAINING INTENSITIES SHOULD BE INDIVIDUALIZED TO SUIT AN ATHLETE'S CURRENT FITNESS LEVEL, FOR EXAMPLE, PERCENTAGE OF 1 REPETITION MAXIMUM IN STRENGTH AND POWER DEVELOPMENT. REGARDING ANAEROBIC OR AEROBIC CONDITIONING, A VELOCITY PRESCRIPTION CAN BE BOTH ACCURATE AND EFFECTIVE IN INDIVIDUALIZING ENERGY SYSTEM DEVELOPMENT. HOWEVER, THERE IS A SPARSITY OF RESEARCH AVAILABLE COMPARING THE RANGE OF TESTS CAPABLE OF DETERMINING AN APPROPRIATE VELOCITY. THE FOLLOWING REVIEW DISCUSSES THE OPTIMUM WAY TO DETERMINE AN INDIVIDUAL'S DESIRED TRAINING VELOCITY THROUGH FIELD-BASED TESTING.

New accounting and auditing requirements for charities under both the Scottish and English/Welsh Acts have just been issued. These new requirements pertain mostly to the obligation of charities to keep records and to the format and audit of these organizations' annual accounts and reports. Scottish charities can look for guidelines regarding these requirements in the Charities Accounts (Scotland) Regulations 1992 (Statutory Instrument 1992 no. 2165 s.216). Among the requirements contained in the Scottish Regulations are the keeping of books of accounts and the preparation of an annual statement of accounts. Scottish charities are also required to make such documents available to the public. Like regulations for charities in England and Wales are expected to be issued in the latter part of 1993.

Almost unnoticed last month, the government paved the way for one of the biggest civil engineering projects of recent times: the widening of a 50-mile stretch of the M6 from [...]

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

The seasonal risk to humans of picking up Ixodes ricinusticks in different habitats at 3 recreational sites in the UK was assessed. A comprehensive range of vegetation types was sampled at 3-weekly intervals for 2 years, using standard blanket-dragging complemented by woollen leggings and square ‘heel flags’. Ticks were found in all vegetation types sampled, including short grass close to car parks, but highest densities were consistently found in plots with trees present. Blankets picked up the greatest number of ticks, but heel flags provided important complementary counts of the immature stages in bracken plots; they showed clearly that the decline in tick numbers on blankets in early summer was due to the seasonal growth of vegetation that lifted the blanket clear of the typical questing height, but in reality ticks remained abundant through the summer. Leggings picked up only 11% of the total nymphs and 22% of total adults counted, but this still represented a significant hazard to humans. These results should prompt a greater awareness of the fine-scale distribution of this species in relation to human activities that determines the most likely zones of contact between humans and ticks. Risk communication may then be designed accordingly.

The article looks at the impact of infectious diseases in wolves at the Yellowstone National Park on wolf population dynamics since a huge decline in pup numbers were recorded in 2005 including the history of canine distemper virus outbreaks in 1999, 2005 and 2008.

The optimal harvesting strategies for unstable populations are explored using first discrete time models and second a continuous time model specifically applied to the destabilising effects of the caecal nematode Trichostrongylus tenuison the dynamics of red grouse Lagopus lagopus scoticus.In discrete time models, with overcompensation generating either cyclic or chaotic fluctuations in abundance harvesting can act as both a stabilising and a destabilising process. Maximum yields occur at the harvesting rate that coincides with the point where the harvesting stabilises the overcompensation. Optimal harvesting rates increase with the degree of overcompensation although these are more vulnerable to overharvesting. Harvesting in the continuous time model provides similar results, although observed hunting records do not appear to be stabilised by harvesting. Empirical data on the mortality caused by other natural enemies of red grouse, the hen harrier Circus cyaenusand the louping ill virus, show that these mortalities do stabilise grouse dynamics. One explanation is that both hen harriers and louping ill virus cause significant mortality to chicks before the infective stages of T. tenuisare laid down on the ground, whereas shooting takes place after the infective stages are laid down and thus do not stabilise the populations.

Studies of disease in relation to animal mating systems have focused on sexual selection and the evolution of sexual reproduction. Relatively little work has examined other aspects of ecological and evolutionary relationships between host social and sexual behaviour, and dynamics and prevalence of infectious diseases; this is particularly evident with respect to sexually transmitted diseases (STDs). Here, we use a simulation approach to investigate rates of STD spread in host mating systems ranging from permanent monogamy to serial polygyny or polyandry and complete promiscuity. The model assumes that one sex (female) is differentially attracted to the other, such that groups of varying size are formed within which mating and disease transmission occur. The results show that equilibrium disease levels are generally higher in females than males and are a function of variance in male mating success and the likelihood of a female switching groups between mating seasons. Moreover, initial rates of disease spread (determining whether an STD establishes in a population) depend on patterns of host movement between groups, variance in male mating success and host life history (e.g. mortality rates). Male reproductive success can be reduced substantially by a sterilizing STD and this reduction is greater in males that are more ‘attractive’ to females. In contrast, females that associate with more attractive males have lower absolute fitness than females associating with less attractive males. Thus, the potential for STDs to act as a constraint on directional selection processes leading to polygyny (or polyandry) is likely to depend on the details of mate choice and group dynamics.

Sustainable Cities and Sustainable Development Sustainable Cities. G. Haughton & C. Hunter, 1994, Jessica Kingsley/Regional Studies Association, LondonSustainable Cities in Europe. P. Nijkamp & A. Perrels, 1994, Earthscan, London ISBN 185383, £12.95Toward Sustainable Development Concepts, Methods and Policy. J. C. J. M. van den Bergh & J. van der Straaten, 1994, Island Press, Washington, DC, ISBN 1 55963 3492, £30.00Just Environments: intergenerational, international and interspecies issues. David E. Cooper & Joy A. Palmer (Eds), 1995, London, Routledge, ISBN 0 415-10336-3, pp. 199, index, £11.99First Steps: Local Agenda 21 in practice. Stella Whittaker (Ed.), 1995, London, HMSO, 251 pp. ISBN 0 11 701871 6, £29.95Beyond the Car: essays on the auto culture. Sue Zielinski & Gordon Laird (Eds), 1995, Toronto, Steel Rail Publishing/Transportation Options, 191 pp. ISBN 0 88791 042 4, pbk, C$ 19.95, US$15.95

The End of Nature by Bill McKibben. Harmondsworth: Penguin, 1990. Pp.xi + 212; index. £4.99 (paperback). ISBN 0 14 012306 7The Idea of Wilderness by Max Oelschlaeger. New Haven, CT and London: Yale University Press, 1991. Pp. xii + 477; index. £19.95 (hardback). ISBN 0 300 04851 3The Ecological Self by Freya Mathews. London: Routledge, 1991. Pp. x + 192; index. £35 (hardback). ISBN 0 415 05252 1A Morally Deep World: An Essay on Moral Significance and Environmental Ethics by Lawrence E. Johnson. Cambridge: Cambridge University Press, 1991. Pp.ix + 301; index. £25 (hardback). ISBN 0 521 39310 8

Coevolution with parasites is thought to maintain genetic diversity in host populations. However, while there are sound theoretical reasons to expect heterozygosity and parasite resistance to be related, this pattern has generally been shown only in inbred laboratory and island populations. This leaves doubt as to whether parasite-mediated selection for genetic diversity is in fact a general process. Here we show that haematozoan parasite load is linked to two complementary measures of microsatellite variability, in an outbred population of mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) for which we know that parasites reduce fitness. Moreover, each of the genetic measures predicts a subtly different aspect of parasitism. Microsatellite heterozygosity is related to an individual's risk of parasitism, and mean d2(a broader, more long-term measure of parental relatedness) to the severity of infection among parasitized individuals.

The article reflects on the potential of novel strains of bacteria and viruses to jump from one host species to another in order to cause a disease outbreak such as spread of an H7N9 strain of influenza virus in China. It informs about the a study published in the periodical PLOS Biology in 2013 which states that Mycoplasma gallisepticum which affects the eyes of finches and found in the U.S. has rapidly and repeatedly evolved to become both more and less harmful to its songbird hosts.

The article discusses the issues concerning the healthcare system in Australia in relation to the viewpoint of Nicola Roxon, the Minister for Health and Ageing. It stresses that Roxon should be clear about her agenda regarding healthcare and should give strong emphasis on medical research and effective public health campaigns. Moreover, Nicola Roxon must put health back on the national agenda and should address Australia's single greatest health policy failure.

Flight dispersal of the triatomine bug species Rhodnius pallescens Barber, the principal vector of Chagas disease in Panama, is an important mechanism for spreading Trypanosoma cruzi, causative agent of Chagas disease. This study measures R. pallescens flight performance using a tethered flight mill both when uninfected, and when infected with T. cruzi or Trypanosoma rangeli. Forty-four out of the 48 (91.7%) insects initiated flight across all treatments, and trypanosome infection did not significantly impact flight initiation. Insects from all treatments flew a cumulative distance ranging from 0.5 to 5 km before fatiguing. The median cumulative distance flown before insect fatigue was higher in T. cruzi- and T. rangeli-infected insects than in control insects; however, this difference was not statistically significant. There was a positive relationship between parasite load ingested and time until flight initiation in T. rangeli-infected bugs, and T. rangeli- and T. cruzi-infected females flew significantly faster than males at different time points. These novel findings allow for a better understanding of R. pallescens dispersal ability and peridomestic management strategies for the prevention of Chagas disease in Panama.

Abstract: The basic reproductive ratio, R 0, is a central quantity in the investigation and management of infectious pathogens. The standard model for describing stochastic epidemics is the continuous time epidemic birth-and-death process. The incidence data used to fit this model tend to be collected in discrete units (days, weeks, etc.), which makes model fitting, and estimation of R 0 difficult. Discrete time epidemic models better match the time scale of data collection but make simplistic assumptions about the stochastic epidemic process. By investigating the nature of the assumptions of a discrete time epidemic model, we derive a bias corrected maximum likelihood estimate of R 0 based on the chain binomial model. The resulting ‘removal’ estimators provide estimates of R 0 and the initial susceptible population size from time series of infectious case counts. We illustrate the performance of the estimators on both simulated data and real epidemics. Lastly, we discuss methods to address data collected with observation error. [Copyright &y& Elsevier]