Accounts of debates in the House of Commons, March– April 1731, supplementary to the diary of the first earl of Egmont

John Perceval (1685–1748), 1st Viscount Perceval and (from 1733) 1st Earl of Egmont, was an assiduous recorder of his own life and times. His diaries, published by the Historical Manuscripts Commission from manuscripts in the British Library, are the best source for parliamentary debates at Westminster in the 1730s. For the years 1730-1733, when Perceval sat in the Commons (as an Irish peer) they are remarkably full. His practice seems to have been to prepare two versions (presumably on the basis of notes taken in the House), the first attributing speeches to individuals, and the second, entered up in the diary, which listed speakers and summarized all arguments on each side. His letterbooks for 1731 contain accounts of five debates that embody his first editing process, with speeches attributed to individuals. They were sent to an Irish correspondent, Marmaduke Coghill, and largely omitted from the diary because Perceval had already transcribed them elsewhere. They are new to historians and cast light on two main issues: the unsuccessful attempts by Perceval and the ‘Irish lobby’ to persuade the British parliament to settle the Irish woollen trade, a question bedevilling Anglo-Irish relations in this period; and an attempt by the opposition to stir up anger against perceived Spanish aggression against Gibraltar. One of the most interesting features is the insight afforded into the Commons performances of Sir Robert Walpole: his management of debates, his own style of speaking, and his sharp exchanges with opponents like William Pulteney.

Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor

FFA2 is a G protein-coupled receptor that responds to short chain fatty acids (SCFAs) and has generated interest as a therapeutic target for metabolic and inflammatory conditions. However, definition of its functions has been slowed by a dearth of selective ligands that can distinguish it from the closely related FFA3. At present, the only selective ligands described for FFA2 suffer from either poor potency, altered signaling due to allosteric modes of action, or a lack of function at non-human orthologs of the receptor. To address the need for novel selective ligands, we synthesized two compounds potentially having FFA2 activity and examined the molecular basis of their function. These compounds were confirmed to be potent and selective FFA2 agonists that interact with the orthosteric binding site. A combination of ligand structure-activity relationship, pharmacological analysis, homology modeling, species ortholog comparisons and mutagenesis studies were then employed to define the molecular basis of selectivity and function of these ligands. From this, we identified key residues within both extracellular loop 2 (ECL2) and the transmembrane domain (TM) regions of FFA2 critical for ligand function. One of these ligands was active with reasonable potency at rodent orthologs of FFA2 and demonstrated the role of FFA2 in the regulation of lipolysis in murine 3T3-L1 adipocytes. Together, these findings describe the first potent and selective FFA2 orthosteric agonists and demonstrate key aspects of ligand interaction within the orthosteric binding site of FFA2 that will be invaluable in future ligand development at this receptor.

Eve and evolution: Christian responses to the first woman question, 1860-1900

Historians of encounters between evolutionary science and Christianity have long been aware of the significance placed upon debates about the applicability of evolution to Adam. It has not been widely noticed, however, that in more conservative circles the creation of Eve was frequently thought to be a more difficult problem to solve. This essay examines how, in distinctive ways, the creation of Eve became a point of contention among three communities of conservative Christian thinkers grappling with the implications of evolutionary theory in the period 1860-1900.

Impact of a play-based curriculum in the first two years of primary school: literacy and numeracy outcomes over seven years

In 2000–2002 an innovative early years curriculum, the Enriched Curriculum (EC), was introduced
into 120 volunteer schools across Northern Ireland, replacing a traditional curriculum similar to
others across the UK at that time. It was intended by the designers to be developmentally appropriate
and play-based with the primary goal of preventing the experience of persistent early failure in
children. The EC was not intended to be a literacy and numeracy intervention, yet it did considerably
alter pedagogy in these domains, particularly the age at which formal reading and mathematics
instruction began. As part of a multi-method evaluation running from 2000–2008, the research
team followed the primary school careers of the first two successive cohorts of EC children, comparing
them with year-ahead controls attending the same 24 schools. Compared to the year-ahead control
group, the findings show that the EC children’s reading and mathematics scores fell behind in
the first two years but the majority of EC children caught up by the end of their fourth year. Thereafter,
the performance of the first EC cohort fell away slightly, while that of the second continued to
match that of controls. Overall, the play-based curriculum had no statistically significant positive
effects on reading and mathematics in the medium term. At best, the EC children’s scores matched
those of controls.

Intercepting the First Pass:Rapid Categorization is Suppressed for Unseen Stimuli

The operations and processes that the human brain employs to achieve fast visual categorization remain a matter of debate. A first issue concerns the timing and place of rapid visual categorization and to what extent it can be performed with an early feed-forward pass of information through the visual system. A second issue involves the categorization of stimuli that do not reach visual awareness. There is disagreement over the degree to which these stimuli activate the same early mechanisms as stimuli that are consciously perceived. We employed continuous flash suppression (CFS), EEG recordings, and machine learning techniques to study visual categorization of seen and unseen stimuli. Our classifiers were able to predict from the EEG recordings the category of stimuli on seen trials but not on unseen trials. Rapid categorization of conscious images could be detected around 100?ms on the occipital electrodes, consistent with a fast, feed-forward mechanism of target detection. For the invisible stimuli, however, CFS eliminated all traces of early processing. Our results support the idea of a fast mechanism of categorization and suggest that this early categorization process plays an important role in later, more subtle categorizations, and perceptual processes.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent. © 2013 John Wiley & Sons Ltd.

Development and validation of the first high performance-lateral flow immunoassay (HP-LFIA) for the rapid screening of domoic acid from shellfish extracts

A lateral flow immunoassay (LFIA) has been developed and fully validated to detect the primary amnesic shellfish poisoning (ASP) toxin, domoic acid (DA). The performance characteristics of two versions of the test were investigated using spiked and naturally contaminated shellfish (mussels, scallops, oysters, clams, and cockles). The tests provide a qualitative result, to indicate the absence or presence of DA in extracts of shellfish tissues, at concentrations that are relevant to regulatory limits. The new rapid assay (LFIA version 2) was designed to overcome the performance limitations identified in the first version of the assay. The improved test uses an electronic reader to remove the subjective nature of the generated results, and the positive cut-off for screening of DA in shellfish was increased from 10 ppm (version 1) to 17.5 ppm (version 2). A simple extraction and test procedure was employed, which required minimal equipment and materials; results were available 15 min after sample preparation. Stability of the aqueous extracts at room temperature (22 C) at four time points (up to 245 min after extraction) and across a range of DA concentrations was 100.3±1.3% and 98.8±2.4% for pre- and post-buffered extracts, respectively. The assay can be used both within laboratory settings and in remote locations. The accuracy of the new assay, to indicate negative results at or below 10 ppm DA, and positive results at or above 17.5 ppm, was 99.5% (n=216 tests). Validation data were obtained from a 2-day, randomised, blind study consisting of multiple LFIA lots (n=3), readers (n=3) and operators (n=3), carrying out multiple extractions of mussel tissue (n=3) at each concentration (0, 10, 17.5, and 20 ppm). No matrix effects were observed on the performance of the assay with different species (mussels, scallops, oysters, clams, and cockles). There was no impact on accuracy or interference from other phycotoxins, glutamic acid or glutamine with various strip incubations (8, 10, and 12 min). The accuracy of the assay, using naturally contaminated samples to indicate negative results at or below 12.5 ppm and positive results at or above 17.5 ppm, was 100%. Variability between three LFIA lots across a range of DA concentrations, expressed as coefficient of variation (% CV), was 1.1±0.4% (n=2 days) based on quantitative readings from the electronic reader. During an 8 week stability study, accuracy of the method with test strips stored at various temperatures (6, 22, 37 and 50 C) was 100%. Validation for both versions included comparisons with results obtained using reference LC-UV methods. © 2013 Elsevier B.V.

Government decisions before and during the First World War and the living standards in Germany during a drastic natural experiment

The First World War hit Germany severely, particularly the agricultural sector, because the outbreak came unexpected and its duration exceeded all expectations. Many resources necessary for agricultural production were required by the war economy and led to shortages and shrinking supplies. Many agricultural laborers were drafted and the blockade imposed by the allies prevented Germany from a great deal of imports. As a consequence, the nutritional situation was devastating, particularly after 1916, and hit all groups of the German society. The period under observation provides one of most drastic natural experiments in the 20th century. This study uses anthropometric data from German soldiers who served in the Second World War to trace living standards between the 1900s and the 1920s. In contrast to other approaches, this paper is able to distinguish between social groups by occupation, religious denominatio\n, regional origin, and city size. The results suggest that although all social strata were hit by famine conditions, the height of farmers, urban citizens, Catholics, and especially individuals born in the highly integrated food-import regions along the coast and the banks of the Rhine declined most.

War, food rationing, and socioeconomic inequality in Germany during the First World War

Germany experienced a devastating period during the First World War due to severely restricted import possibilities and a general shortage of foodstuffs. This study uses the heights of some 4,000 individuals who served during the Second World War to quantify biological living standards from the 1900s to the 1920s, and focuses primarily on socioeconomic inequality during this period. The results suggest that generally the upper social strata, measured by fathers' occupation, exhibited the tallest average height, followed by the middle and lower classes. These socioeconomic differences became more pronounced during the First World War when the rationing system provided a limited food supply. Wealthier individuals were able to purchase additional foodstuffs on black markets. Therefore, children from upper-class families experienced only a small decline in average height compared to their counterparts from the middle and lower social strata.