Patients' understanding of risk associated with medication use: impact of European Commission guidelines and other risk scales

Patients want and need comprehensive and accurate information about their medicines so that they can participate in decisions about their healthcare: In particular, they require information about the likely risks and benefits that are associated with the different treatment options. However, to provide this information in a form that people can readily understand and use is a considerable challenge to healthcare professionals. One recent attempt to standardise the Language of risk has been to produce sets of verbal descriptors that correspond to specific probability ranges, such as those outlined in the European Commission (EC) Pharmaceutical Committee guidelines in 1998 for describing the incidence of adverse effects. This paper provides an overview of a number of studies involving members of the general public, patients, and hospital doctors, that evaluated the utility of the EC guideline descriptors (very common, common, uncommon, rare, very rare). In all studies it was found that people significantly over-estimated the likelihood of adverse effects occurring, given specific verbal descriptors. This in turn resulted in significantly higher ratings of their perceived risks to health and significantly lower ratings of their likelihood of taking the medicine. Such problems of interpretation are not restricted to the EC guideline descriptors. Similar levels of misinterpretation have also been demonstrated with two other recently advocated risk scales (Caiman's verbal descriptor scale and Barclay, Costigan and Davies' lottery scale). In conclusion, the challenge for risk communicators and for future research will be to produce a language of risk that is sufficiently flexible to take into account different perspectives, as well as changing circumstances and contexts of illness and its treatments. In the meantime, we urge the EC and other legislative bodies to stop recommending the use of specific verbal labels or phrases until there is a stronger evidence base to support their use.

Interpretation of recommended risk terms: differences between doctors and lay people

Objectives: To examine doctors' (Experiment 1) and doctors' and lay people's (Experiment 2) interpretations of two sets of recommended verbal labels for conveying information about side effects incidence rates. Method: Both studies used a controlled empirical methodology in which participants were presented with a hypothetical, but realistic, scenario involving a prescribed medication that was said to be associated with either mild or severe side effects. The probability of each side effect was described using one of the five descriptors advocated by the European Union (Experiment 1) or one of the six descriptors advocated in Calman's risk scale (Experiment 2), and study participants were required to estimate (numerically) the probability of each side effect occurring. Key findings: Experiment 1 showed that the doctors significantly overestimated the risk of side effects occurring when interpreting the five EU descriptors, compared with the assigned probability ranges. Experiment 2 showed that both groups significantly overestimated risk when given the six Calman descriptors, although the degree of overestimation was not as great for the doctors as for the lay people. Conclusion: On the basis of our findings, we argue that we are still a long way from achieving a standardised language of risk for use by both professionals and the general public, although there might be more potential for use of standardised terms among professionals. In the meantime, the EU and other regulatory bodies and health professionals should be very cautious about advocating the use of particular verbal labels for describing medication side effects.

Mid-late Holocene environmental change and human activities in the northern Apennines, Italy

Radiocarbon-dated palaeoecological records from the upland zone of the northern Apennines spanning the Mid-Late Holocene (last 7000 years) have been evaluated using established criteria for detecting anthropogenic impact on the landscape and environment. The integrated palaeoecological records across the study area collectively indicate human interference with natural vegetation succession and landscape modification from at least the Middle Neolithic. These activities resulted in the progressive decline of Abies, Ulmus, Fraxinus and Tilia, and the spread of Fagus, from ∼7000 cal BP, accompanied at various times by evidence for biomass burning, soil erosion, the expansion of shrubland and herbaceous taxa, and the possible cultivation of Olea, Juglans and Castanea. Comparison of these data with the archaeological scheme for the region, and the climate history of the central-western Mediterranean, has revealed that the palaeoecological records broadly support the archaeological evidence, but suggest that several key vegetation changes also coincide with important periods of climate change, especially at ∼7800–5000 cal BP.

The timing and causes of the Neolithic elm decline: new evidence from the Lower Thames Valley (London, UK)

Two new multi-proxy records of environmental change are provided from Horton Kirby Paper Mill and Old Seager Distillery in the Lower Thames Valley. Each site has evidence for a decline in elm woodland, which at Horton Kirby Paper Mill is recorded earlier than any other published record from the British Isles: sometime between 7320 and 7240 cal BP. Scolytus scolytus/S. multistriatus (the vectors for Dutch elm disease) are recorded after the decline in both sequences, adding to the number of sites with such evidence in the British Isles. Evidence of paludification and human activity are also recorded at the time of the elm decline reinforcing the multi-causal hypothesis. Integration of these results with 21 palaeoenvironmental records has produced a large number of well-dated, multiproxy records of the elm decline in this part of the UK. On the basis of this dataset, a classification system for categorising the relationships between the causal factors of the elm decline is proposed and recommended for future studies.

Holocene alluvial environments at Barking, Lower Thames Valley (London, UK)

Deposit modelling based on archived borehole logs supplemented by a small number of dedicated boreholes is used to reconstruct the main boundary surfaces and the thickness of the main sediment units within the succession of Holocene alluvial deposits underlying the floodplain in the Barking Reach of the Lower Thames Valley. The basis of the modelling exercise is discussed and the models are used to assess the significance of floodplain relief in determining patterns of sedimentation. This evidence is combined with the results of biostratigraphical and geochronological investigations to reconstruct the environmental conditions associated with each successive stage of floodplain aggradation. The two main factors affecting the history and spatial pattern of Holocene sedimentation are shown to be the regional behaviour of relative sea level and the pattern of relief on the surface of the sub-alluvial, Late Devensian Shepperton Gravel. As is generally the case in the Lower Thames Valley, three main stratigraphic units are recognised, the Lower Alluvium, a peat bed broadly equivalent to the Tilbury III peat of Devoy (1979) and an Upper Alluvium. There is no evidence to suggest that the floodplain was substantially re-shaped by erosion during the Holocene. Instead, the relief inherited from the Shepperton Gravel surface was gradually buried either by the accumulation of peat or by deposition of fine-grained sediment from suspension in standing or slow-moving water. The palaeoenvironmental record from Barking confirms important details of the Holocene record observed elsewhere in the Lower Thames Valley, including the presence of Taxus in the valley-floor fen carr woodland between about 5000 and 4000 cal BP, and the subsequent growth of Ulmus on the peat surface.

New models of North West European Holocene palaeogeography and inundation

This paper presents new 500 year interval palaeogeographic models for Britain, Ireland and the North West French coast from 11000 cal. BP to present. These models are used to calculate the varying rates of inundation for different geographical zones over the study period. This allows for consideration of the differential impact that Holocene sea-level rise had across space and time, and on past societies. In turn, consideration of the limitations of the models helps to foreground profitable areas for future research.

Evidence of resilience to past climate change in Southwest Asia: early farming communities and the 9.2 and 8.2 ka events

Climate change is often cited as a major factor in social change. The so-called 8.2 ka event was one of the most pronounced and abrupt Holocene cold and arid events. The 9.2 ka event was similar, albeit of a smaller magnitude. Both events affected the Northern Hemisphere climate and caused cooling and aridification in Southwest Asia. Yet, the impacts of the 8.2 and 9.2 ka events on early farming communities in this region are not well understood. Current hypotheses for an effect of the 8.2 ka event vary from large-scale site abandonment and migration (including the Neolithisation of Europe) to continuation of occupation and local adaptation, while impacts of the 9.2 ka have not previously been systematically studied. In this paper, we present a thorough assessment of available, quality-checked radiocarbon (14C) dates for sites from Southwest Asia covering the time interval between 9500 and 7500 cal BP, which we interpret in combination with archaeological evidence. In this way, the synchronicity between changes observed in the archaeological record and the rapid climate events is tested. It is shown that there is no evidence for a simultaneous and widespread collapse, large-scale site abandonment, or migration at the time of the events. However, there are indications for local adaptation. We conclude that early farming communities were resilient to the abrupt, severe climate changes at 9250 and 8200 cal BP.

Vegetation history, human impact and climate change during prehistory: an island perspective of the isles of Tiree, Coll and north-west Mull

Results of extensive site reconnaissance on the Isles of Tiree, Coll and north-west Mull, Inner Hebrides are presented. Pollen-stratigraphic records were compiled from a profile from Glen Aros, north-west Mull and from two profiles on Coll located at Loch an t-Sagairt and Caolas an Eilean. Quantification of microscopic charcoal provided records that were used to facilitate a preliminary evaluation of the causal driving mechanisms of vegetation change. Bayesian modelling of radiocarbon dates was used to construct preliminary chronological frameworks for these records. Basal sedimentary deposits at Glen Aros contain pollen records that correspond with vegetation succession typical of the early Holocene dating to c. 11,370 cal BP. Woodland development is a key feature of the pollen records dating to the early Holocene, while records from Loch an t-Sagairt show that blanket mire communities were widespread in north-west Coll by c. 9800 cal BP. The Corylus-rise is dated to c. 10,710 cal BP at Glen Aros and c. 9905 cal BP at Loch an t-Sagairt, with records indicating extensive cover of hazel woodland with birch. All of the major arboreal taxa were recorded, though Quercus and Ulmus were nowhere widespread. Analysis of wood charcoal remains from a Mesolithic site at Fiskary Bay, Coll indicate that Salix and Populus are likely to be under-represented in the pollen records. Reconstructed isopoll maps appear to underplay the importance of alder in western Scotland during the mid-Holocene. Alder-rise expansions in microscopic charcoal dating to c. 7300 cal BP at Glen Aros and c. 6510 to 5830 cal BP on Coll provide records of significance to the issue of human-induced burning related to the expansion of alder in Britain. Increasing frequencies in microscopic charcoal are correlated with mid-Holocene records of increasing aridity in western Scotland after c. 7490 cal BP at Glen Aros, 6760 cal BP at Loch an t-Sagairt and 6590 cal BP at Caolas an Eilean, while several phases of increasing bog surface wetness were detected in the Loch an t-Sagairt archive during the Holocene. At least five phases of small-scale woodland disturbance during the Mesolithic period were identified in the Glen Aros profile dating to c. 11,650 cal BP, 9300 cal BP, 7840 cal BP, 7040 cal BP and 6100 cal BP. The timing of the third phase is coincident with evidence of Mesolithic settlement at Creit Dhu, north-west Mull. Three phases of small-scale woodland disturbance were detected at Loch an t-Sagairt dating to c. 9270 cal BP, 8770 cal BP and 8270 cal BP, all of which overlap chronologically with evidence of Mesolithic activity at Fiskary Bay, Coll. A number of these episodes are aligned chronologically with phases of Holocene climate variability such as the 8.2 K event.

The environmental setting of Epipalaeolithic aggregation site Kharaneh IV

The archaeological site of Kharaneh IV in Jordan's Azraq Basin, and its relatively near neighbour Jilat 6 show evidence of sustained occupation of substantial size through the Early to Middle Epipalaeolithic (c. 24,000 - 15,000 cal BP). Here we review the geomorphological evidence for the environmental setting in which Kharaneh IV was established. The on-site stratigraphy is clearly differentiated from surrounding sediments, marked visually as well as by higher magnetic susceptibility values. Dating and analysis of off-site sediments show that a significant wetland existed at the site prior to and during early site occupation (~ 23,000 - 19,000 BP). This may explain why such a substantial site existed at this location. This wetland dating to the Last Glacial Maximum also provides important information on the palaeoenvironments and potential palaeoclimatic scenarios for today's eastern Jordanian desert, from where such evidence is scarce.

Dating WF16: exploring the chronology of a Pre-Pottery Neolithic A settlement in the Southern Levant

A pre-requisite for understanding the transition to the Neolithic in the Levant is the establishment of a robust chronology, most notably for the late Epi-Palaeolithic and Pre-Pottery Neolithic A (PPNA) periods. In this contribution we undertake a dating analysis of the Pre-Pottery Neolithic site of WF16, southern Jordan, drawing on a sample of 46 AMS 14C dates. We utilise Bayesian methods to quantify an old wood effect to provide an offset that we factor into chronological models for a number of individual structures at WF16 and for the settlement as a whole. In doing so we address the influence of slope variations in the calibration curve and expose the significance of sediment and sample redeposition within sites of this nature. We conclude that for the excavated deposits at WF16 human activity is likely to have started by c. 11.84 ka cal bp and lasted for at least c. 1590 years, ceasing by c. 10.24 ka cal bp. This is marked by a particularly intensive period of activity lasting for c. 350 years centred on 11.25 ka cal bp followed by less intensive activity lasting a further c. 880 years. The study reveals the potential of WF16 as a laboratory to explore methodological issues concerning 14C dating of early Neolithic sites in arid, erosional environments.

Examining the relationships between Holocene climate change, hydrology, and human society in Ireland

This thesis explores human-environment interactions during the Mid-Late Holocene in raised bogs in central Ireland. The raised bogs of central Ireland are widely-recognised for their considerable palaeoenvironmental and archaeological resources: research over the past few decades has established the potential for such sites to preserve sensitive records of Holocene climatic variability expressed as changes in bog surface wetness (BSW); meanwhile archaeological investigations over the past century have uncovered hundreds of peatland archaeological features dating from the Neolithic through to the Post-Medieval period including wooden trackways, platforms, and deposits of high-status metalwork. Previous studies have attempted to explore the relationship between records of past environmental change and the occurrence of peatland archaeological sites reaching varying conclusions. More recently, environmentally-deterministic models of human-environment interaction in Irish raised bogs at the regional scale have been explicitly tested leading to the conclusion that there is no relationship between BSW and past human activity. These relationships are examined in more detail on a site-by-site basis in this thesis. To that end, testate amoebae-derived BSW records from nine milled former raised bogs in central Ireland were produced from sites with known and dated archaeological records. Relationships between BSW records and environmental conditions within the study area were explored through both the development of a new central Ireland testate amoebae transfer function and through comparisons between recent BSW records and instrumental weather data. Compilation of BSW records from the nine fossil study sites show evidence both for climate forcing, particularly during 3200-2400 cal BP, as well as considerable inter-site variability. Considerable inter-site variability was also evident in the archaeological records of the same sites. Whilst comparisons between BSW and archaeological records do not show a consistent linear relationship, examination of records on a site-by-site basis were shown to reveal interpretatively important contingent relationships. It is concluded therefore, that future research on human-environment interactions should focus on individual sites and should utilise theoretical approaches from the humanities in order to avoid the twin pitfalls of masking important local patterns of change, and of environmental determinism.

A diatom record of late Holocene climate variation in the northern range of Yellowstone National Park, USA

The changes in diatom species composition in a sediment core from Crevice Lake, Yellowstone National Park, spanning the past 2550 yr, were used to reconstruct long-term limnological and ecological conditions that may be related to late Holocene climate variability. Planktic forms dominate the fossil diatom assemblages throughout this record, but changes in species dominance indicate varying nutrient levels over time, particularly phosphorus. The changes in the nutrient concentrations in the lake were probably driven by changes in temperature and wind strength that affected the duration of watercolumn mixing and thus the extent of nutrient recycling from deep waters. Prior to 2100 cal before present (BP), Stephanodiscus minutulus and Synedra tenera dominated, suggesting long cool springs with extensive regeneration of phosphorus from the hypolimnion that resulted from isothermal mixing. From 2100 to 800 cal BP, these species were replaced by Cyclotella michiganiana and Cyclotella bodanica. These species are characteristic of lower nutrient concentrations and are interpreted here to reflect warm summers with long periods of thermal stratification. From 800 to 50 cal BP, S. minutulus dominated the diatom assemblage, suggesting a return to lengthy mixing during spring. The most dramatic late Holocene changes in the fossil diatom assemblages occurred during the transition from the Medieval Period to the Little Ice Age, approximately 800 cal BP.

Mid- to late-Holocene paleoceanographic changes on the southeastern Brazilian shelf based on grain size records

; High-resolution grain size analyses of three AMS (14)C-dated cores from the Southeastern Brazilian shelf provide a detailed record of mid- to late-Holocene environmental changes in the Southwestern Atlantic Margin. The cores exhibit millennial variability that we associate with the previously described southward shift of the Inter Tropical Convergence Zone (ITCZ) average latitudinal position over the South American continent during the Holocene climatic maximum. This generated changes in the wind-driven current system of the SW Atlantic margin and modified the grain size characteristics of the sediments deposited there. Centennial variations in the grain size are associated with a previously described late-Holocene enhancement of the El Nino-Southern Oscillation (ENSO) amplitude, which led to stronger NNE trade winds off eastern Brazil, favouring SW transport of sediments from the Paraiba do Sul River. This is recorded in a core from off Cabo Frio as a coarsening trend from 3000 cal. BP onwards. The ENSO enhancement also caused changes in precipitation and wind pattern in southern Brazil, allowing high discharge events and northward extensions of the low-saline water plume from Rio de la Plata. We propose that this resulted in a net increase in northward alongshore transport of fine sediments, seen as a prominent fine-shift at 2000 cal. BP in a core from similar to 24 degrees S on the Brazilian shelf. Wavelet-and spectral analysis of the sortable silt records show a significant similar to 1000-yr periodicity, which we attribute to solar forcing. If correct, this is one of the first indications of solar forcing of this timescale on the Southwestern Atlantic margin.

Paleoproductivity changes during the Holocene in the inner shelf of Cabo Frio, southeastern Brazilian continental margin: Benthic foraminifera and sedimentological proxies

Sedimentological and benthic foraminifera analyses carried out on a core (length 4.15 in, collected at 22 degrees 56`31 `` S and 41 degrees 58`48 `` W, at a water depth of 43 in) sampled from the inner shelf of Cabo Frio, southeastern Brazilian continental margin, allowed identification of different hydrodynamic and productivity regimes related to sea-level fluctuations and/or climatic changes, during the last 9.4 ka cal BP. Prior to 7.0 ka cal BP, a less intense hydrodynamic and lower productivity regime occurred at lower sea levels and under drier climatic conditions. Between 7.0 and 5.0 ka cal BP, relatively stronger local oceanic circulation and relatively high productivity were observed, in a scenario of rising sea levels and more humid conditions. From 5.0 to 3.0 ka cal BP, bottom currents weakened and input of nutrients increased, with productivity levels similar to the previous phase at lower sea level and in a drier climate. From 3.0 ka cal BP up to the present, stronger hydrodynamic conditions and a higher productivity regime are linked to the establishment of the upwelling process in Cabo Frio. From 2.5 ka cal BP to the present, upwelling enhancement has been recognized, resulting from the combined action of NE winds and the intensification of the meandering pattern of the Brazil Current (BC). (C) 2008 Elsevier Ltd and INQUA. All rights reserved.

Rock Art at the Pleistocene/Holocene Boundary in Eastern South America

Background: Most investigations regarding the First Americans have primarily focused on four themes: when the New World was settled by humans; where they came from; how many migrations or colonization pulses from elsewhere were involved in the process; and what kinds of subsistence patterns and material culture they developed during the first millennia of colonization. Little is known, however, about the symbolic world of the first humans who settled the New World, because artistic manifestations either as rock-art, ornaments, and portable art objects dated to the Pleistocene/Holocene transition are exceedingly rare in the Americas. Methodology/Principal Findings: Here we report a pecked anthropomorphic figure engraved in the bedrock of Lapa do Santo, an archaeological site located in Central Brazil. The horizontal projection of the radiocarbon ages obtained at the north profile suggests a minimum age of 9,370640 BP, (cal BP 10,700 to 10,500) for the petroglyph that is further supported by optically stimulated luminescence (OSL) dates from sediment in the same stratigraphic unit, located between two ages from 11.7 +/- 0.8 ka BP to 9.9 +/- 0.7 ka BP. Conclusions: These data allow us to suggest that the anthropomorphic figure is the oldest reliably dated figurative petroglyph ever found in the New World, indicating that cultural variability during the Pleistocene/Holocene boundary in South America was not restricted to stone tools and subsistence, but also encompassed the symbolic dimension.