Grazing herbivores reduce herbaceous biomass and fire activity across African savannas.

Fire and herbivory interact to alter ecosystems and carbon cycling. In savannas, herbivores can reduce fire activity by removing grass biomass, but the size of these effects and what regulates them remain uncertain. To examine grazing effects on fuels and fire regimes across African savannas, we combined data from herbivore exclosure experiments with remotely sensed data on fire activity and herbivore density. We show that, broadly across African savannas, grazing herbivores substantially reduce both herbaceous biomass and fire activity. The size of these effects was strongly associated with grazing herbivore densities, and surprisingly, was mostly consistent across different environments. A one-zebra increase in herbivore biomass density (~100 kg/km2 of metabolic biomass) resulted in a ~53 kg/ha reduction in standing herbaceous biomass and a ~0.43 percentage point reduction in burned area. Our results indicate that fire models can be improved by incorporating grazing effects on grass biomass.

Revolutions in Lipid Isomer Resolution: Application of Ultrahigh-Resolution Ion Mobility to Reveal Lipid Diversity.

Many families of lipid isomers remain unresolved by contemporary liquid chromatography-mass spectrometry approaches, leading to a significant underestimation of the structural diversity within the lipidome. While ion mobility coupled to mass spectrometry has provided an additional dimension of lipid isomer resolution, some isomers require a resolving power beyond the capabilities of conventional platforms. Here, we present the application of high-resolution traveling-wave ion mobility for the separation of lipid isomers that differ in (i) the location of a single carbon-carbon double bond, (ii) the stereochemistry of the double bond (cis or trans), or, for glycerolipids, (iii) the relative substitution of acyl chains on the glycerol backbone (sn-position). Collisional activation following mobility separation allowed identification of the carbon-carbon double-bond position and sn-position, enabling confident interpretation of variations in mobility peak abundance. To demonstrate the applicability of this method, double-bond and sn-position isomers of an abundant phosphatidylcholine composition were resolved in extracts from a prostate cancer cell line and identified by comparison to pure isomer reference standards, revealing the presence of up to six isomers. These findings suggest that ultrahigh-resolution ion mobility has broad potential for isomer-resolved lipidomics and is attractive to consider for future integration with other modes of ion activation, thereby bringing together advanced orthogonal separations and structure elucidation to provide a more complete picture of the lipidome.

Single Cell Metabolite Detection Using Inertial Microfluidics-Assisted Ion Mobility Mass Spectrometry.

Single-cell metabolite measurement remains highly challenging due to difficulties related to single cell isolation, metabolite detection, and identification of low levels of metabolites. Here, as a first step of the technological development, we propose a novel strategy integrating spiral inertial microfluidics and ion mobility mass spectrometry (IM-MS) for single-cell metabolite detection and identification. Cells in methanol suspension are inertially focused into a single stream in the spiral microchannel. This stream of separated cells is delivered to the nanoelectrospray needle to be lysed and ionized and subsequently analyzed in real time by IM-MS. This analytical system enables six to eight single-cell metabolic fingerprints to be collected per minute, including gas-phase collisional cross section (CCS) measurements as an additional molecular descriptor, giving increased confidence in metabolite identification. As a proof of concept, the metabolic profiles of three types of cancer cells (U2OS, HepG2, and HepG2.215) were successfully screened, and 19 distinct lipids species were identified with CCS value filtering. Furthermore, principal component analysis (PCA) showed differentiation of the three cancer cell lines, mainly due to cellular surface phospholipids. Taken together, our technology platform offers a simple and efficient method for single-cell lipid profiling, with additional ion mobility separation of lipids significantly improving the confidence toward identification of metabolites.

Failing to meet the goals of periodontal recall programs. What next?

Supportive periodontal care is a crucial aspect of the management of chronic periodontitis and peri-implantitis and is inevitably a long-term commitment for both the clinician and the patient. The principal goals of supportive care are to achieve a high standard of plaque control, minimize bleeding and maintain pockets at less than 6 mm. Gain of attachment around natural teeth during supportive periodontal care has been reported, although gain of attachment and of bone during supportive care may be a more pragmatic and aspirational aim in the longer term. Furthermore, we occasionally see patients for whom, despite excellent home and professional care (surgical or nonsurgical), including the management of risk factors, supportive periodontal care appears to be failing and therefore for such patients the clinician needs to consider further management options. This review considers, in particular, the options of using local or systemically delivered antimicrobials to eradicate periodontal and peri-implant disease progression and discusses the extent to which culture and sensitivity testing before the prescription of systemically delivered antimicrobials may be a cost-effective alternative to prescribing 'blind'.

Gingival recession and root caries in the ageing population: a critical evaluation of treatments.

AIM: To review evidence for the treatments of gingival recession and root caries in older populations. MATERIALS & METHODS: A systematic approach was adopted to identify reviews and articles to allow us to evaluate the treatments for gingival recession and root caries. Searches were performed in PubMed, Medline and Embase, the Cochrane trials register and bibliographies of European and World Workshops. OBSERVATIONS: Gingival recession: We identified no articles that focussed specifically on older populations. Conversely, no evidence suggested that Miller class I and II lesions should be managed differently in older patients when compared to younger cohorts. Six systematic reviews included older patients and suggested that connective tissue grafts are the treatment of choice, alone or in combination with enamel matrix derivative. Root caries can be controlled at the population level by daily brushing with fluoride-containing toothpastes, whilst active decay may be inactivated using professional application of fluoride varnishes/solutions or self-applied high-fluoride toothpaste. Active root caries lesions that cannot be cleaned properly by the patient may be restored by minimally invasive techniques. CONCLUSIONS: Gingival recession and root caries will become more prevalent as patients retain their teeth for longer. Whilst surgical (gingival recession) and non-operative approaches (root caries) currently appear to be favoured, more evidence is needed to identify the most appropriate strategies for older people.

Intraspecific trait variation drives functional responses of old-field plant communities to nutrient enrichment.

Environmental changes are expected to shift the distribution of functional trait values in plant communities through a combination of species turnover and intraspecific variation. The strength of these shifts may depend on the availability of individuals with trait values adapted to new environmental conditions, represented by the functional diversity (FD) of existing community residents or dispersal from the regional species pool. We conducted a 3-year nutrient- and seed-addition experiment in old-field plant communities to examine the contributions of species turnover and intraspecific variation to community trait shifts, focusing on four key plant functional traits: vegetative height, leaf area, specific leaf area (SLA), and leaf dry matter content (LDMC). We further examined the influence of initial FD and seed availability on the strength of these shifts. Community mean height, leaf area, and SLA increased in response to fertilization, and these shifts were driven almost entirely by intraspecific variation. The strength of intraspecific shifts in height and leaf area was positively related to initial intraspecific FD in these traits. Intraspecific trait responses to fertilization varied among species, with species of short stature displaying stronger shifts in SLA and LDMC but weaker shifts in leaf area. Trait shifts due to species turnover were generally weak and opposed intraspecific responses. Seed addition altered community taxonomic composition but had little effect on community trait shifts. These results highlight the importance of intraspecific variation for short-term community functional responses and demonstrate that the strength of these responses may be mediated by community FD.

The effect of fire on habitat selection of mammalian herbivores: the role of body size and vegetation characteristics.

Given the role of fire in shaping ecosystems, especially grasslands and savannas, it is important to understand its broader impact on these systems. Post-fire stimulation of plant nutrients is thought to benefit grazing mammals and explain their preference for burned areas. However, fire also reduces vegetation height and increases visibility, thereby potentially reducing predation risk. Consequently, fire may be more beneficial to smaller herbivores, with higher nutritional needs and greater risks of predation. We tested the impacts of burning on different sized herbivores' habitat preference in Serengeti National Park, as mediated by burning's effects on vegetation height, live : dead biomass ratio and leaf nutrients. Burning caused a less than 4 month increase in leaf nitrogen (N), and leaf non-N nutrients [copper (Cu), potassium (K), and magnesium (Mg)] and a decrease in vegetation height and live : dead biomass. During this period, total herbivore counts were higher on burned areas. Generally, smaller herbivores preferred burned areas more strongly than larger herbivores. Unfortunately, it was not possible to determine the vegetation characteristics that explained burned area preference for each of the herbivore species observed. However, total herbivore abundance and impala (Aepyceros melampus) preference for burned areas was due to the increases in non-N nutrients caused by burning. These findings suggest that burned area attractiveness to herbivores is mainly driven by changes to forage quality and not potential decreases in predation risk caused by reductions in vegetation height.

Body size mediated coexistence in swans.

Differences in body sizes may create a trade-off between foraging efficiency (foraging gains/costs) and access to resources. Such a trade-off provides a potential mechanism for ecologically similar species to coexist on one resource. We explored this hypothesis for tundra (Cygnus columbianus) and trumpeter swans (Cygnus buccinator), a federally protected species, feeding solely on sago pondweed (Stuckenia pectinata) tubers during fall staging and wintering in northern Utah. Foraging efficiency was higher for tundra swans because this species experienced lower foraging and metabolic costs relative to foraging gains; however, trumpeter swans (a) had longer necks and therefore had access to exclusive resources buried deep in wetland sediments and (b) were more aggressive and could therefore displace tundra swans from lucrative foraging locations. We conclude that body size differentiation is an important feature of coexistence among ecologically similar species feeding on one resource. In situations where resources are limiting and competition for resources is strong, conservation managers will need to consider the trade-off between foraging efficiency and access to resources to ensure ecologically similar species can coexist on a shared resource.

Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: conformational selection highlights a new concept in allosteric inhibitor design.

The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound "B" and C-subunit-bound "H"-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through "induced fit" alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially "select" inactive conformations of target proteins by satisfying all "binding" constraints alone without inducing conformational changes necessary for activation.

Integrating defense and leaf economic spectrum traits in a tropical savanna plant.

Introduction: Allocation to plant defense traits likely depends on resource supply, herbivory, and other plant functional traits such as the leaf economic spectrum (LES) traits. Yet, attempts to integrate defense and resource acquisitive traits remain elusive. Methods: We assessed intraspecific covariation between different defense and LES traits in a widely distributed tropical savanna herb, Solanum incanum, a unique model species for studying allocations to physical, chemical, and structural defenses to mammalian herbivory. Results: We found that in a multivariate trait space, the structural defenses - lignin and cellulose - were positively related to the resource conservative traits - low SLA and low leaf N. Phenolic content, a chemical defense, was positively associated with resource acquisitive traits - high SLA and high leaf N - while also being associated with an independent third component axis. Both principal components 1 and 3 were not associated with resource supply and herbivory intensity. In contrast, spine density - a physical defense - was orthogonal to the LES axis and positively associated with soil P and herbivory intensity. Discussion: These results suggest a hypothesized "pyramid" of trade-offs in allocation to defense along the LES and herbivory intensity axes. Therefore, future attempts to integrate defense traits with the broader plant functional trait framework, such as the LES, needs a multifaceted approach that accounts for unique influences of resource acquisitive traits and herbivory risk.

A disease-mediated trophic cascade in the Serengeti and its implications for ecosystem C.

Tree cover is a fundamental structural characteristic and driver of ecosystem processes in terrestrial ecosystems, and trees are a major global carbon (C) sink. Fire and herbivores have been hypothesized to play dominant roles in regulating trees in African savannas, but the evidence for this is conflicting. Moving up a trophic scale, the factors that regulate fire occurrence and herbivores, such as disease and predation, are poorly understood for any given ecosystem. We used a Bayesian state-space model to show that the wildebeest population eruption that followed disease (rinderpest) eradication in the Serengeti ecosystem of East Africa led to a widespread reduction in the extent of fire and an ongoing recovery of the tree population. This supports the hypothesis that disease has played a key role in the regulation of this ecosystem. We then link our state-space model with theoretical and empirical results quantifying the effects of grazing and fire on soil carbon to predict that this cascade may have led to important shifts in the size of pools of C stored in soil and biomass. Our results suggest that the dynamics of herbivores and fire are tightly coupled at landscape scales, that fire exerts clear top-down effects on tree density, and that disease outbreaks in dominant herbivores can lead to complex trophic cascades in savanna ecosystems. We propose that the long-term status of the Serengeti and other intensely grazed savannas as sources or sinks for C may be fundamentally linked to the control of disease outbreaks and poaching.

Large herbivores facilitate a dominant grassland forb via multiple indirect effects.

While large herbivores are critically important components of terrestrial ecosystems and can have pronounced top-down effects on plants, our understanding of the underlying mechanisms driving these effects remains incomplete. Large herbivores can alter plant growth, reproduction, and abundance through direct effects (predominantly consumption) and through indirect effects via altered interactions with abiotic factors and other species. We know considerably less about these indirect effects than the direct effects. Here, we integrate medium- and small-scale field experiments to investigate how a large vertebrate herbivore, cattle (Bos taurus), affects the aboveground biomass of a dominant forb species, Artemisia scoparia, via diverse direct and indirect pathways in a temperate grassland in northeast China. Although cattle consumed this forb, its biomass increased significantly in response to grazing, due to multiple indirect positive effects that outweighed the direct negative effects of consumption. Cattle preferentially consumed the competing grass Leymus chinensis, and altered Artemisia microhabitats by reducing total plant cover and litter biomass and by increasing the abundance of co-occurring ant species (e.g., Formica spp. and Lasius spp.). This led to additional indirect positive effects on A. scoparia likely due to (1) increased light availability in understory layers and other limiting resources (e.g., soil nutrients and moisture) caused by removal of competitors and plant litter at the soil surface and (2) the changes in resource availability (e.g., soil nutrients and moisture) associated with ant colonies. Our results show that large herbivores can affect plant growth not only via direct consumption, but also via multiple indirect effects. Focusing on the causes and consequences of herbivore-induced indirect effects will not only help us to better understand the influence of these animals in ecological systems, but will also lead to more effective land management and conservation practices in the regions they inhabit.

Label-free quantitative proteomics analysis of etiolated maize seedling leaves during greening.

To better understand light regulation of C(4) plant maize development, we investigated dynamic proteomic differences between green seedlings (control), etiolated seedlings, and etiolated seedlings illuminated for 6 or 12 h using a label-free quantitative proteomics approach based on nanoscale ultraperformance liquid chromatography-ESI-MS(E). Among more than 400 proteins identified, 73 were significantly altered during etiolated maize seedling greening. Of these 73 proteins, 25 were identified as membrane proteins that seldom had been identified with two-dimensional electrophoresis methods, indicating the power of our label-free method for membrane protein identification; 31 were related to light reactions of chlorophyll biosynthesis, photosynthesis, and photosynthetic carbon assimilation. The expression of photosystem II subunits was highly sensitive to light; most of them were not identified in etiolated maize seedlings but drastically increased upon light exposure, indicating that the complex process of biogenesis of the photosynthetic apparatus correlates with the transition from a dark-grown to a light-grown morphology. However, transcriptional analysis indicated that most transcripts encoding these proteins were not regulated by light. In contrast, the levels of mRNAs and proteins for enzymes involved in carbon assimilation were tightly regulated by light. Additionally phosphoenolpyruvate carboxykinase, the key enzyme of the phosphoenolpyruvate carboxykinase C(4) pathway, was more tightly regulated by light than the key enzymes of the NADP-malic enzyme C(4) pathway. Furthermore phosphoenolpyruvate carboxylase 1C, which was originally reported to be specifically expressed in roots, was also identified in this study; expression of this enzyme was more sensitive to light than its isoforms. Taken together, these results represent a comprehensive dynamic protein profile and light-regulated network of C(4) plants for etiolated seedling greening and provide a basis for further study of the mechanism of gene function and regulation in light-induced development of C(4) plants.

Introduced grazers can restrict potential soil carbon sequestration through impacts on plant community composition.

Grazing occurs over a third of the earth's land surface and may potentially influence the storage of 10(9) Mg year(-1) of greenhouse gases as soil C. Displacement of native herbivores by high densities of livestock has often led to overgrazing and soil C loss. However, it remains unknown whether matching livestock densities to those of native herbivores can yield equivalent soil C sequestration. In the Trans-Himalayas we found that, despite comparable grazing intensities, watersheds converted to pastoralism had 49% lower soil C than watersheds which retain native herbivores. Experimental grazer-exclusion within each watershed type, show that this difference appears to be driven by indirect effects of livestock diet selection, leading to vegetation shifts that lower plant production and reduce likely soil C inputs from vegetation by c. 25 gC m(-2) year(-1). Our results suggest that while accounting for direct impacts (stocking density) is a major step, managing indirect impacts on vegetation composition are equally important in influencing soil C sequestration in grazing ecosystems.

Ciliate diversity and distribution across an environmental and depth gradient in Long Island Sound, USA.

The nature and extent of microbial biodiversity remain controversial with persistent debates over patterns of distributions (i.e. cosmopolitanism versus endemism) and the processes that structure these patterns (neutrality versus selection). We used culture-independent approaches to address these issues focusing on two groups of ciliates, the Oligotrichia (Spirotrichea) and Choreotrichia (Spirotrichea) across an environmental gradient. We assessed SSU rDNA diversity in ciliate communities at six stations in Long Island Sound spanning the frontal region that separates the fresher Connecticut River outflow plume from the open Sound. As in previous studies, we find one abundant cosmopolitan species (Strombidium biarmatum), a few moderately abundant sequences, and a long list of rare sequences. Furthermore, neither ciliate diversity nor species composition showed any clear relationship to measured environmental parameters (temperature, salinity, accessory pigment composition and chorophyll). Overall, we observed that diversity decreased moving from nearshore to offshore. We also conducted analyses to detect clustering among the sampled communities using the software Unifrac. This approach revealed three significant clusters grouping samples from nearshore, surface and deep/well mixed stations. We find no strong fit of our communities to log series, geometric or log normal distributions, though one of the 3 clusters is most consistent with a log series distribution. However, when we remove the abundant cosmopolitan species S. biarmatum, all three clusters fit to a log series distribution. These analyses suggest that, with the exception of one cosmopolitan species, the oligotrich and choreotrich communities at these stations may be distributed in a neutral manner.

Landscape-scale analyses suggest both nutrient and antipredator advantages to Serengeti herbivore hotspots.

Mechanistic explanations of herbivore spatial distribution have focused largely on either resource-related (bottom-up) or predation-related (top-down) factors. We studied direct and indirect influences on the spatial distributions of Serengeti herbivore hotspots, defined as temporally stable areas inhabited by mixed herds of resident grazers. Remote sensing and variation in landscape features were first used to create a map of the spatial distribution of hotspots, which was tested for accuracy against an independent data set of herbivore observations. Subsequently, we applied structural equation modeling to data on soil fertility and plant quality and quantity across a range of sites. We found that hotspots in Serengeti occur in areas that are relatively flat and located away from rivers, sites where ungulates are less susceptible to predation. Further, hotspots tend to occur in areas where hydrology and rainfall create conditions of relatively low-standing plant biomass, which, coupled with grazing, increases forage quality while decreasing predation risk. Low-standing biomass and higher leaf concentrations of N, Na, and Mg were strong direct predictors of hotspot occurrence. Soil fertility had indirect effects on hotspot occurrence by promoting leaf Na and Mg. The results indicate that landscape features contribute in direct and indirect ways to influence the spatial distribution of hotspots and that the best models incorporated both resource- and predation-related factors. Our study highlights the collective and simultaneous role of bottom-up and top-down factors in determining ungulate spatial distributions.

Herbivore effects on above- and belowground plant production and soil nitrogen availability in the Trans-Himalayan shrub-steppes.

Large mammalian herbivores may have positive, neutral, or negative effects on annual net aboveground plant production (NAP) in different ecosystems, depending on their indirect effects on availability of key nutrients such as soil N. In comparison, less is known about the corresponding influence of grazers, and nutrient dynamics, over annual net belowground plant production (NBP). In natural multi-species plant communities, it remains uncertain how grazing influences relative allocation in the above- and belowground compartments in relation to its effects on plant nutrients. We evaluated grazer impacts on NAP, NBP, and relative investment in the above- and belowground compartments, alongside their indirect effects on soil N availability in the multiple-use Trans-Himalayan grazing ecosystem with native grazers and livestock. Data show that a prevailing grazing intensity of 51% increases NAP (+61%), but reduces NBP (-35%). Grazing also reduced C:N ratio in shoots (-16%) and litter (-50%), but not in roots, and these changes coincided with increased plant-available inorganic soil N (+23%). Areas used by livestock and native grazers showed qualitatively similar responses since NAP was promoted, and NBP was reduced, in both cases. The preferential investment in the aboveground fraction, at the expense of the belowground fraction, was correlated positively with grazing intensity and with improvement in litter quality. These results are consistent with hypothesized herbivore-mediated positive feedbacks between soil nutrients and relative investment in above- and belowground compartments. Since potentially overlapping mechanisms, such as N mineralization rate, plant N uptake, compositional turnover, and soil microbial activity, may contribute towards these feedbacks, further studies may be able to discern their respective contributions.

Cost effectiveness of a lidocaine 5% medicated plaster compared with pregabalin for the treatment of postherpetic neuralgia in the UK: a Markov model analysis.

BACKGROUND: Published analyses have demonstrated that the lidocaine (lignocaine) plaster is a cost-effective treatment for postherpetic neuralgia (PHN) relative to gabapentin or pregabalin. However, these analyses have been based on indirect comparisons from placebo-controlled trials, and there is evidence of a discrepancy between the outcomes of direct and indirect analyses. Fortunately, recent publication of the results of a head-to-head trial comparing the lidocaine plaster and pregabalin in patients with PHN or diabetic polyneuropathy allows customization of the existing model to more accurately reflect the relative cost effectiveness of these two products. OBJECTIVE: To assess the cost-effectiveness of the lidocaine 5% medicated plaster compared with pregabalin for the treatment of PHN in the UK primary-care setting. METHODS: A Markov model has been developed to assess the costs and benefits of the lidocaine plaster and pregabalin over a 6-month time horizon for the treatment of patients with PHN who are intolerant to tricyclic antidepressants and in whom analgesics are ineffective or contraindicated. The model structure allows for differences in costs, utilities (derived from published data and from the head-to-head trial) and transition probabilities between the initial 30-day run-in period and maintenance therapy, and also takes account of add-in medication and drugs received by patients discontinuing therapy. The calculation was based on data from the recent head-to-head trial described above. Additional data sources included published literature, discussions with a Delphi panel, official price/tariff lists and national population statistics. The study was conducted from the perspective of the UK National Health Service (NHS). RESULTS: The base-case analysis (1.71 lidocaine plasters per day used in the head-to-head trial for the PHN population) indicated that the total cost of treating PHN patients for 6 months with the lidocaine plaster was pound 980 per patient treated, compared with pound 784 for pregabalin (year of costing 2009). Costs for 1 month without pain and intolerable adverse events (AEs) (modified TWIST analysis) were pound 126 for the lidocaine plaster relative to pregabalin. The average patient treated with the lidocaine plaster experienced 0.321 quality-adjusted life-years (QALYs) over the 6-month period modelled compared with 0.254 QALYs for pregabalin. Quality-of-life benefits were attributed to the favourable AE profile of the lidocaine plaster. Subsequently, the lidocaine plaster cost pound 2925 per QALY gained relative to pregabalin. However, patient level longitudinal data have shown that the actual clinical usage of the lidocaine plaster is 1.1 plasters per day. If this more realistic assumption is used in the model, the total cost for a 6-month treatment period was pound 756 for the lidocaine plaster, which dominated treatment with pregabalin. Scenario analyses and sensitivity analyses had minimal impact on the results, confirming the robustness of the study. The incremental cost-effectiveness ratios for the lidocaine plaster remained well below pound 35,000 per QALY gained in all analyses. CONCLUSION: This analysis showed that the lidocaine 5% medicated plaster is a cost-effective method for obtaining sustained relief of localized neuropathic pain associated with PHN compared with pregabalin in a UK setting, in terms of both the cost per QALY gained and the cost per additional month without symptoms, when used for patients who do not experience sufficient pain relief from standard analgesics.

Episodic herbivory, plant density dependence, and stimulation of aboveground plant production.

Herbivory is a major energy transfer within ecosystems; an open question is under what circumstances it can stimulate aboveground seasonal primary production. Despite multiple field demonstrations, past theory considered herbivory as a continuous process and found stimulation of seasonal production to be unlikely. Here, we report a new theoretical model that explores the consequences of discrete herbivory events, or episodes, separated in time. We discovered that negative density (biomass) dependence of plant growth, such as might be expected from resource limitation of plant growth, favors stimulation of seasonal production by infrequent herbivory events under a wide range of herbivory intensities and maximum plant relative growth rates. Results converge to those of previous models under repeated, short-interval herbivory, which generally reduces seasonal production. Model parameters were estimated with new and previous data from the Serengeti ecosystem. Patterns of observed frequent and large magnitude stimulated production in these data agreed generally with those predicted by the episodic herbivory model. The model thus may provide a new framework for evaluating the sustainability and impact of herbivory.

Cross-boundary human impacts compromise the Serengeti-Mara ecosystem.

Protected areas provide major benefits for humans in the form of ecosystem services, but landscape degradation by human activity at their edges may compromise their ecological functioning. Using multiple lines of evidence from 40 years of research in the Serengeti-Mara ecosystem, we find that such edge degradation has effectively "squeezed" wildlife into the core protected area and has altered the ecosystem's dynamics even within this 40,000-square-kilometer ecosystem. This spatial cascade reduced resilience in the core and was mediated by the movement of grazers, which reduced grass fuel and fires, weakened the capacity of soils to sequester nutrients and carbon, and decreased the responsiveness of primary production to rainfall. Similar effects in other protected ecosystems worldwide may require rethinking of natural resource management outside protected areas.