Connectivity at the Large Carnivore Scale: The Kafue-Zambezi Interface

The growth and expansion of human populations and resource demands is driving large scale fragmentation and loss of wildlife habitat, isolating wildlife populations and pushing many species towards extinction at local to global scales. Attempts to promote connectivity between wildlife managed areas at transboundary scales has been proposed as a solution to negative effects associated with population isolation. Such approaches commonly require the maintenance of wildlife populations throughout human-dominated landscapes subject to various degrees of effective protection.The aims of this study are to (1) assess the status of the large carnivore guild throughout ten wildlife managed areas comprising the Zambian component of Kavango-Zambezi Transfrontier Conservation Area between Kafue National Park and the Simalaha Wildlife Recovery Sanctuary on the Zambezi River; (2) model habitat suitability and connectivity in this landscape for Lion, Leopard and Spotted hyena; and (3) develop a site-specific map of human footprint pressure for the landscape and test if it can be used a proxy for determining the occurrence of these three species. And further, explore if there are thresholds in human footprint pressure beyond which species are likely extirpated from wildlife managed areas.Methods included library studies to determine historical status of the large carnivore guild and twenty-six common prey species, spoor tracking in conjunction with qualitative surveys and supplemental data analysis to ascertain species current distribution, remote sensing with ground-truthing to build landcover maps, Maximum Entropy and Current Flow models, and extensive use of Geographic Information Systems.The findings conclude that there have been large scale losses in species assemblages throughout majority of southern wildlife managed areas, including the Simalaha Wildlife Recovery Sanctuary. However, no detectable changes were evident in Kafue National Park and surrounding Game Management Areas. Human activities are limiting habitat suitability and scope for occurrence in central southern areas of the landscape, with the likelihood of a connectivity bottleneck occurring. There is significant overlap in habitat requirements and scope for species movement. Human footprint pressure models appear to demonstrate utility as a proxy measure for occurrence of our large carnivore subset, though require some refinements and supplemental data layers to increase predictive power. Human footprint pressure at the wildlife managed area scale indicates threshold levels at which target species occur or are locally extirpated.Analyses have identified important additions to the existing wildlife managed area network in Open communal land that could provide valuable habitat and connectivity for target species given effective management and finance, including containment of negative human disturbance variables modelled (agro-pastoralist activities and infrastructure development). The effects of poaching are also hypothesized to be a significant driver limiting species persistence.Continued expansion of human population, settlement and agro-pastoralist activities will limit scope for expansion of large carnivores and their principle prey throughout the Kafue-Zambezi interface, effectively severing connectivity and isolating the Greater Kafue System from adjacent wildlife managed areas in the Kavango-Zambezi Transfrontier Conservation Area.Narratives surrounding the development of wildlife-based land uses and species-level connectivity benefit from the application of conservation science and generation of empirical data to guide management

Reciprocal hydrodynamic response estimation in a random spreading sea

Direct estimation of the hydrodynamic response of an offshore structure in a random spreading sea can lead to large computational costs. In this paper the actual spreading sea is replaced by an idealised diffuse wave field and the diffuse field reciprocity (DFR) relationship is derived analytically and verified against diffraction analysis for offshore application. The DFR approach provides an analytical expression for the estimation of the wave loading spectrum in a spreading sea. It is very efficient because only the added damping coefficients are required. Furthermore, if normalised to the peak amplitude of a spreading sea, an upper bound response can be obtained using the reciprocal approach. And this is demonstrated using a spar type floating wind turbine. Given that the hydrodynamic coefficients are routine outputs for offshore structural design, engineers would obtain the upper bound response without additional computational cost using this new approach

Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfection

AbstractThe identification of mechanisms that prevent infection with human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) would facilitate the development of an effective AIDS vaccine. In time-course experiments, protection against detectable superinfection with homologous wild-type SIV was achieved within 21 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral immunity. Partial protection against superinfection was achieved within 10 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral and cellular immunity. Furthermore, co-inoculation of live attenuated SIV with wild-type SIV resulted in a significant reduction in peak virus loads compared to controls that received wild-type SIV alone. These findings imply that innate immunity or non-immune mechanisms are a significant component of early protection against superinfection conferred by inoculation with live attenuated SIV

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

Status of terrestrial mammals at the Kafue-Zambezi Interface: Implications for transboundary connectivity

The Kavango–Zambezi Transfrontier Conservation Area Programme promotes landscape-level connectivity between clusters of wildlife management areas in five neighbouring countries. However, declining regional biodiversity can undermine efforts to maintain, expand and link wildlife populations. Narratives promoting species connectivity should thus be founded on studies of system and state changes in key resources. By integrating and augmenting multiple data sources throughout eight wildlife management areas, covering 1.7 million ha, we report changes during 1978–2015 in the occurrence and distribution of 31 mammal species throughout a landscape linking the Greater Kafue System to adjacent wildlife management areas in Namibia and Botswana. Results indicate species diversity is largely unchanged in Kafue National Park and Mulobezi and Sichifulo Game Management Areas. However, 100% of large carnivore and 64% of prey diversity have been lost in the Simalaha areas, and there is no evidence of migrational behaviour or species recolonization from adjacent wildlife areas. Although temporal sampling scales influence the definition of species occupancy and distribution, and data cannot elucidate population size or trends, our findings indicate an emerging connectivity bottleneck within Simalaha. Evidence suggests that at current disturbance levels the Greater Kafue System, Zambia's majority component in the Kavango–Zambezi Transfrontier Conservation Area, is becoming increasingly isolated at the trophic scale of large mammals. Further investigations of the site-specific, interacting drivers influencing wildlife distribution and occurrence are required to inform appropriate conservation interventions for wildlife recovery in key areas identified to promote transboundary connectivity in the Kavango–Zambezi Transfrontier Conservation Area

Benefits of wildlife-based land uses on private lands in Namibia and limitations affecting their development

Legislative changes during the 1960s–1970s granted user rights over wildlife to landowners in southern Africa, resulting in a shift from livestock farming to wildlifebased land uses. Few comprehensive assessments of such land uses on private land in southern Africa have been conducted and the associated benefits are not always acknowledged by politicians. Nonetheless, wildlife-based land uses are growing in prevalence on private land. In Namibia wildlife-based land use occurs over c. 287,000 km2. Employment is positively related to income from ecotourism and negatively related to income from livestock. While 87% of meat from livestock is exported $95% of venison from wildlife-based land uses remains within the country, contributing to food security. Wildlife populations are increasing with expansion of wildlife-based land uses, and private farms contain 21–33 times more wildlife than in protected areas. Because of the popularity of wildlife-based land uses among younger farmers, increasing tourist arrivals and projected impacts of climate change on livestock production, the economic output of wildlife-based land uses will probably soon exceed that of livestock. However, existing policies favour livestock production and are prejudiced against wildlife-based land uses by prohibiting reintroductions of buffalo Syncerus caffer, a key species for tourism and safari hunting, and through subsidies that artificially inflate the profitability of livestock production. Returns from wildlife-based land uses are also limited by the failure to reintroduce other charismatic species, failure to develop fully-integrated conservancies and to integrate black farmers sufficiently.TRAFFIC East/Southern Africa and Tom Milliken for instigating this project and the German Federal Ministry for Economic Cooperation and Development and African Wildlife Conservation Fund.http://journals.cambridge.orgam201

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society