Origin and structure of Devensian depressions at Letton, Herefordshire

Groups of circular to oval enclosed depressions in soft sediments of Pleistocene age are relatively common in north-west Europe. These features are normally interpreted as being either glacial or periglacial in origin. Where these features are developed in glacial sediments, a glacial (and specifically ‘kettle hole’) genesis is considered most likely. Some groups of features, however, have been re-interpreted as being periglacial in origin and are thought to be the remains of cryogenic mounds (former pingos or palsas/lithalsas). The problem at many sites, of course, is correct identification and previously this was often resolved through extensive trenching of the sediments. The use of geophysics in the form of electrical resistivity tomography and ground probing radar, however, can aid investigation and interpretation and is less invasive. A group of enclosed depressions in the Letton area of Herefordshire within the Last Glacial Maximum ice limit (Late Devensian) have been investigated in this way. The morphology and internal structure of the features and their existence in glaciolacustrine sediments of Late Devensian age strongly suggests that these depressions are kettle holes resulting from ice block discharge into a shallow lakes or lakes, and hence a glacial origin is supported. The lack of any ramparts surrounding the depressions (at the surface or any evidence of these at depth) and the fact that they do not overlap (‘mutually interfere’) indicates that they are not the remains of cryogenic mounds.

Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: a tutorial

The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a trial. Predictive probabilities are then updated and so become more accurate as the trial progresses. Suitable priors can act as pseudo samples, which make small sample clinical trials more informative. Thus patients have better chances to receive better treatments. The goal of this paper is to provide a tutorial for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, real data from three clinical trials are presented as examples to illustrate how to conduct a Bayesian approach for phase II single-arm clinical trials with binary outcomes.

Mechanisms and function of flower and inflorescence reversion

Flower and inflorescence reversion involve a switch from floral development back to vegetative development, thus rendering flowering a phase in an ongoing growth pattern rather than a terminal act of the meristem. Although it can be considered an unusual event, reversion raises questions about the nature and function of flowering. It is linked to environmental conditions and is most often a response to conditions opposite to those that induce flowering. Research on molecular genetic mechanisms underlying plant development over the last 15 years has pinpointed some of the key genes involved in the transition to flowering and flower development. Such investigations have also uncovered mutations which reduce floral maintenance or alter the balance between vegetative and floral features of the plant. How this information contributes to an understanding of floral reversion is assessed here. One issue that arises is whether floral commitment (defined as the ability to continue flowering when inductive conditions no longer exist) is a developmental switch affecting the whole plant or is a mechanism which assigns autonomy to individual meristems. A related question is whether floral or vegetative development is the underlying default pathway of the plant. This review begins by considering how studies of flowering in Arabidopsis thaliana have aided understanding of mechanisms of floral maintenance. Arabidopsis has not been found to revert to leaf production in any of the conditions or genetic backgrounds analysed to date. A clear-cut reversion to leaf production has, however, been described in Impatiens balsamina. It is proposed that a single gene controls whether Impatiens reverts or can maintain flowering when inductive conditions are removed, and it is inferred that this gene functions to control the synthesis or transport of a leaf-generated signal. But it is also argued that the susceptibility of Impatiens to reversion is a consequence of the meristem-based mechanisms controlling development of the flower in this species. Thus, in Impatiens, a leaf-derived signal is critical for completion of flowering and can be considered to be the basis of a plant-wide floral commitment that is achieved without accompanying meristem autonomy. The evidence, derived from in vitro and other studies, that similar mechanisms operate in other species is assessed. It is concluded that most species (including Arabidopsis) are less prone to reversion because signals from the leaf are less ephemeral, and the pathways driving flower development have a high level of redundancy that generates meristem autonomy even when leaf-derived signals are weak. This gives stability to the flowering process, even where its initiation is dependent on environmental cues. On this interpretation, Impatiens reversion appears as an anomaly resulting from an unusual combination of leaf signalling and meristem regulation. Nevertheless, it is shown that the ability to revert can serve a function in the life history strategy (perenniality) or reproductive habit (pseudovivipary) of many plants. In these instances reversion has been assimilated into regular plant development and plays a crucial role there.

Design and analysis of climate model experiments for the efficient estimation of anthropogenic signals

Presented herein is an experimental design that allows the effects of several radiative forcing factors on climate to be estimated as precisely as possible from a limited suite of atmosphere-only general circulation model (GCM) integrations. The forcings include the combined effect of observed changes in sea surface temperatures, sea ice extent, stratospheric (volcanic) aerosols, and solar output, plus the individual effects of several anthropogenic forcings. A single linear statistical model is used to estimate the forcing effects, each of which is represented by its global mean radiative forcing. The strong colinearity in time between the various anthropogenic forcings provides a technical problem that is overcome through the design of the experiment. This design uses every combination of anthropogenic forcing rather than having a few highly replicated ensembles, which is more commonly used in climate studies. Not only is this design highly efficient for a given number of integrations, but it also allows the estimation of (nonadditive) interactions between pairs of anthropogenic forcings. The simulated land surface air temperature changes since 1871 have been analyzed. The changes in natural and oceanic forcing, which itself contains some forcing from anthropogenic and natural influences, have the most influence. For the global mean, increasing greenhouse gases and the indirect aerosol effect had the largest anthropogenic effects. It was also found that an interaction between these two anthropogenic effects in the atmosphere-only GCM exists. This interaction is similar in magnitude to the individual effects of changing tropospheric and stratospheric ozone concentrations or to the direct (sulfate) aerosol effect. Various diagnostics are used to evaluate the fit of the statistical model. For the global mean, this shows that the land temperature response is proportional to the global mean radiative forcing, reinforcing the use of radiative forcing as a measure of climate change. The diagnostic tests also show that the linear model was suitable for analyses of land surface air temperature at each GCM grid point. Therefore, the linear model provides precise estimates of the space time signals for all forcing factors under consideration. For simulated 50-hPa temperatures, results show that tropospheric ozone increases have contributed to stratospheric cooling over the twentieth century almost as much as changes in well-mixed greenhouse gases.

How does the brain mediate interpretation of incongruent auditory emotions? The neural response to prosody in the presence of conflicting lexico-semantic cues

We frequently encounter conflicting emotion cues. This study examined how the neural response to emotional prosody differed in the presence of congruent and incongruent lexico-semantic cues. Two hypotheses were assessed: (i) decoding emotional prosody with conflicting lexico-semantic cues would activate brain regions associated with cognitive conflict (anterior cingulate and dorsolateral prefrontal cortex) or (ii) the increased attentional load of incongruent cues would modulate the activity of regions that decode emotional prosody (right lateral temporal cortex). While the participants indicated the emotion conveyed by prosody, functional magnetic resonance imaging data were acquired on a 3T scanner using blood oxygenation level-dependent contrast. Using SPM5, the response to congruent cues was contrasted with that to emotional prosody alone, as was the response to incongruent lexico-semantic cues (for the 'cognitive conflict' hypothesis). The right lateral temporal lobe region of interest analyses examined modulation of activity in this brain region between these two contrasts (for the 'prosody cortex' hypothesis). Dorsolateral prefrontal and anterior cingulate cortex activity was not observed, and neither was attentional modulation of activity in right lateral temporal cortex activity. However, decoding emotional prosody with incongruent lexico-semantic cues was strongly associated with left inferior frontal gyrus activity. This specialist form of conflict is therefore not processed by the brain using the same neural resources as non-affective cognitive conflict and neither can it be handled by associated sensory cortex alone. The recruitment of inferior frontal cortex may indicate increased semantic processing demands but other contributory functions of this region should be explored.

Multimodal semantic-associative collateral labelling and indexing of still images

A novel framework for multimodal semantic-associative collateral image labelling, aiming at associating image regions with textual keywords, is described. Both the primary image and collateral textual modalities are exploited in a cooperative and complementary fashion. The collateral content and context based knowledge is used to bias the mapping from the low-level region-based visual primitives to the high-level visual concepts defined in a visual vocabulary. We introduce the notion of collateral context, which is represented as a co-occurrence matrix, of the visual keywords, A collaborative mapping scheme is devised using statistical methods like Gaussian distribution or Euclidean distance together with collateral content and context-driven inference mechanism. Finally, we use Self Organising Maps to examine the classification and retrieval effectiveness of the proposed high-level image feature vector model which is constructed based on the image labelling results.

Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Thalassaemia: its diagnosis and interpretation in past skeletal populations

The diagnosis of thalassaemia in archaeological populations has long been hindered by a lack of pathogonomic features, and the non-specific nature of cribra orbitalia and porotic hyperostosis. In fact, clinical research has highlighted more specific diagnostic criteria for thalassaemia major and intermedia based on changes to the thorax (‘rib-within-a-rib’ and costal osteomas). A recent re-examination of 364 child skeletons from Romano-British Poundbury Camp, Dorset revealed children with general ‘wasting’ of the bones and three children who demonstrated a variety of severe lesions (e.g. zygomatic bone and rib hypertrophy, porotic hyperostosis, rib lesions, osteopenia and pitted diaphyseal shafts) that are inconsistent with dietary deficiency alone, and more consistent with a diagnosis of genetic anaemia. Two of these children displayed rib lesions typical of those seen in modern cases of thalassaemia. The children of Poundbury Camp represent the first cases of genetic anaemia identified in a British archaeological population. As thalassaemia is a condition strongly linked to Mediterranean communities, the presence of this condition in a child from England, found within a mausoleum, suggests that they were born to wealthy immigrant parents living in this small Roman settlement in Dorset. This paper explores the diagnostic criteria for genetic anaemia in the archaeological literature and what its presence in ancient populations can contribute to our knowledge of past human migration.