Improving multi-site benefit functions via Bayesian model averaging: A new approach to benefit transfer

A benefit function transfer obtains estimates of willingness-to-pay (WTP) for the evaluation of a given policy at a site by combining existing information from different study sites. This has the advantage that more efficient estimates are obtained, but it relies on the assumption that the heterogeneity between sites is appropriately captured in the benefit transfer model. A more expensive alternative to estimate WTP is to analyze only data from the policy site in question while ignoring information from other sites. We make use of the fact that these two choices can be viewed as a model selection problem and extend the set of models to allow for the hypothesis that the benefit function is only applicable to a subset of sites. We show how Bayesian model averaging (BMA) techniques can be used to optimally combine information from all models. The Bayesian algorithm searches for the set of sites that can form the basis for estimating a benefit function and reveals whether such information can be transferred to new sites for which only a small data set is available. We illustrate the method with a sample of 42 forests from U.K. and Ireland. We find that BMA benefit function transfer produces reliable estimates and can increase about 8 times the information content of a small sample when the forest is 'poolable'. © 2008 Elsevier Inc. All rights reserved.

A field study assessing the impact of on-site wastewater treatment systems on surface water quality in a Co. Monaghan catchment

Poorly functioning on-site wastewater treatment systems (OSWTS) can be among the many sources of pollution to groundwater and surface water, which are of critical concern owing to potential human and ecological health risks. An investigation into the effects of on-site wastewater treatment systems (OSWTS) on surface water quality has been undertaken at several sites within a catchment in Co. Monaghan. The study sites were located in areas of 'low’ permeability, suggesting that run-off usually dominates over infiltration. Poor treatment performance of OSWTS within the catchment were found to be the result of several factors, including location in areas with unsuitable soil and site characteristics, incorrect installation, poor maintenance and inappropriate operation by the home owner.

Doonloughan: a seasonal settlement site on the Connemara coast

A series of shell middens and miscellaneous habitation sites, located in a dune
system in west County Galway, have been exposed and are slowly disappearing
through wind, wave and surface erosion. In 1992 a project was initiated to
record, sample and date some of these sites and the radiocarbon results
demonstrated that activity in the area spanned the Early Bronze Age through to
the Iron Age and into the early and post medieval periods. This preliminary
fieldwork was succeeded by the excavation of three of the better-preserved sites; a Bronze Age midden in 1994 and two early medieval sites (the subject of this paper), in 1997. The medieval sites dated to the late-seventh to ninth century adand were represented by a sub-circular stone hut with a hearth and the charred remains of a more ephemeral wooden tent-like structure. The discovery of a bronze penannular brooch of ninth/tenth century date at the latter site wouldsuggest that the settlements are not the remains of transient, impoverishedpeoples of the lower classes of society, eking out a living along the coast. The calcareous sands ensured good preservation of organic remains*fish and mammal bones, charred cereal grains, seeds and seaweed, and marine molluscs. Analyses of these indicated exploitation of marine resources but, otherwise, were comparable with the diet and economy represented by assemblages from established contemporary site types of the period. Unlike raths, cranno´gs and monastic settlements, however, the volume of material represented at the Galway sites was slight, despite the excellent preservation conditions. A range of seasonal indicators also suggested temporary habitation: probable latespring/summer occupation of the stone hut site and autumnal occupancy of the second, less substantial site. It is suggested that the machair plain, beside which the dunes are located, was most probably the attraction for settlers to the area and was exploited as an alternative pasture for the seasonal grazing of livestock.
*

Missing Links, Cultural Modernity and the Dead: Anatomically Modern Humans in the Great Cave of Niah (Sarawak, Borneo)

The Great Cave of Niah in Sarawak (northern Borneo) came into the gaze of Western Science through the work of Alfred Russell Wallace, who came to Sarawak in the 1850s to search for ‘missing links’ in his pioneering studies of evolution and the natural history of Island Southeast Asia and Australasia. The work of Tom and Barbara Harrisson in the 1950s and 1960s placed the Great Cave, and particularly their key find, the ‘Deep Skull’, at the nexus of the evolving archaeological framework for the region: for decades the skull, dated in 1958 by adjacent charcoal to c.40,000 BP, was the oldest fossil of an anatomically modern human anywhere in the world and thus critical to ideas about human evolution and dispersal. Although several authorities later questioned the provenance and antiquity of the Deep Skull, renewed investigations of the Harrisson excavations since 2000 have shown that it can be attributed securely to a specific location in the Pleistocene stratigraphy, with direct U-series dating on a piece of the skull indicating an age for it of c.37,500 BP and the first evidence for associated human activity at the site going back to c.50,000 BP. The new work also indicates that the skull is part of a cultural deposit, perhaps a precursor to the long tradition in Borneo of processing of the dead and secondary burial. These indicators of cultural complexity chime with the complexity of the subsistence behaviour of the early users of the caves discussed by Philip Piper and Ryan Rabett in chapter ten of this volume.

Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation

Alport syndrome (AS) is a clinically and genetically heterogeneous renal disorder, predominantly affecting the type IV collagen alpha 3/alpha 4/alpha 5 network of the glomerular basement membrane (GBM). AS can be caused by mutations in any of the three genes encoding these type IV collagen chains. The majority of AS families (85%) are X-linked (XL-AS) involving mutations in the COL4A5 gene. Mutations in the COL4A3 and COL4A4 genes cause autosomal recessive AS (AR-AS), accounting for approximately 14% of the cases. Recently, autosomal dominant AS (AD-AS) was linked to the COL4A3/COL4A4 locus in a large family.

Optimization of an ether series of mGluR5 positive allosteric modulators: Molecular determinants of MPEP site interaction crossover

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) pos. allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topol. similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.

Discovery and SAR of a novel series of non-MPEP site mGlu(5) PAMs based on an aryl glycine sulfonammide scaffold

Herein we report the discovery and SAR of a novel series of non-MPEP site metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on an aryl glycine sulfonamide scaffold. This series represents a rare non-MPEP site mGlu(5) PAM chemotype.

The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum:importance of active site metal ions in the binding of substrates and inhibitors

The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development. This enzyme represents a target at which new antimalarials could be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo. A study on the metal ion binding characteristics of recombinant P. falciparum M17 leucine aminopeptidase (rPfLAP) shows that the active site of this exopeptidase contains two metal-binding sites, a readily exchangeable site (site 1) and a tight binding site (site 2). The enzyme retains activity when the metal ion is removed from site 1, while removal of metal ions from both sites results in an inactive apoenzyme that cannot be reactivated by the addition of divalent metal cations. The metal ion at site 1 is readily exchangeable with several divalent metal ions and displays a preference in the order of preference Zn(2+) > Mn(2+) > Co(2+) > Mg(2+). While it is likely that native PfLAP contains a Zn(2+) in site 2, the metal ion located in site 1 may be dependent on the type and concentration of metal ions in the cytosolic compartment of the parasite. Importantly, the type of metal ion present at site 1 influences not only the catalytic efficiency of the enzyme for peptide substrates but also the mode of binding by bestatin, a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity.