Originally published: Oxford: Clarendon Press, 1932.

This classic edition presents the correspondence of one of the great thinkers of the 18th century, and offers a rich picture of the man and his age. This first volume contains David Hume's letters from 1727 to 1765. Hume's correspondents include such famous public figures as Jean-Jacques Rousseau, Adam Smith, James Boswell, and Benjamin Franklin.

This classic edition presents the correspondence of one of the great thinkers of the 18th century, and offers a rich picture of the man and his age. This second volume contains David Hume's letters from 1766 to 1776. Hume's correspondents include such famous public figures as Jean-Jacques Rousseau, Adam Smith, James Boswell, and Benjamin Franklin.

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

Lars Porsena Or the Future of Swearing Robert Graves Originally published in 1927 "Not for squeamish readers." Spectator "A deliciously ironical affair." Bystander "Humour and style are beyond criticism." Irish Statesman As relevant now as when it was first published, this volume and its ironic look at the political correctness of society has become a classic of the Today & Tomorrow series. 90pp Breaking Priscian’s Head Or English As She Will Be Spoke and Wrote J Y T Greig Originally (...) published in 1928 "The most vehement attack we have ever read." Morning Post "A rollicking book" Spectator This volume discusses the nature of language, grammar, the influence of America, of slang dialect and many other subjects. 90p **************** Delphos The Future of International Language E Sylvia Pankhurst Originally published in 1927 In this volume, Sylvia Pankhurst argues that an international language would be one of the greatest assets to modern civilization. She surveys past attempts from the sixteenth to the early twentieth centuries and predicts the arrival of the inter-language, its form, its social and cultural utility and its influence for world peace. 90pp Pomona or the Future of English Basil de Sélincourt Originally published in 1926 "Equal to anything yet produced in this brilliant series." Spectator An analysis of the present condition of the English language and the paths along which it is progressing. 88pp. (shrink)

A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients’ perception of material risks, by trained interviewers. Patients’ demographics were obtained. Mann–Whitney U (...) test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education, being employed and younger age group are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea, Drowsiness and Surgical Wound Pain. Patients ranked Heart Attack, Death and Stroke as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist, instead of letting the doctor decide or deciding for themselves. Discussion with the anaesthetist is the preferred medium of communication compared to reading a pamphlet or watching a video. Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship. (shrink)

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and (...) ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062. (shrink)

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary and independent methods (...) that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle. (shrink)

En su artículo de 2000, Hookway pretende argumentar que el principio de justificación inferencial de Fumerton no tiene las consecuencias escépticas que Fumerton observa en él. Nosotros consideramos que Hookway está en lo cierto. Sin embargo, después de hacer algunos comentarios acerca de sus principales consideraciones a favor de esta tesis, desarrollamos una línea argumentativa independiente que refuerce esa misma conclusión.

Using the corpus of JSTOR articles, we investigate the role of gender in collaboration patterns across the scholarly landscape by analyzing gender-based homophily--the tendency for researchers to co-author with individuals of the same gender. For a nuanced analysis of gender homophily, we develop methodology necessitated by the fact that the data comprises heterogeneous sub-disciplines and that not all authorships are exchangeable. In particular, we distinguish three components of gender homophily in collaborations: a structural component that is due to demographics and (...) non-gendered authorship norms of a scholarly community, a compositional component which is driven by varying gender representation across sub-disciplines, and a behavioral component which we define as the remainder of observed homophily after its structural and compositional components have been taken into account. Using minimal modeling assumptions, we measure and test for behavioral homophily. We find that significant behavioral homophily can be detected across the JSTOR corpus and show that this finding is robust to missing gender indicators in our data. In a secondary analysis, we show that the proportion of female representation in a field is positively associated with significant behavioral homophily. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

The statistical properties of a single quantum object and an ensemble of independent such objects are considered in detail for two-level systems. Computer simulations of dynamic zero-point quantum fluctuations for a single quantum object are reported and compared with analytic solutions for the ensemble case.

Introduction While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand. Methods Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed. Results 525 participants completed the informed consent survey (Heng County, China=255, Xinjiang, China=229, Chiang Mai, Thailand=41). Mean age was (...) 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6–10 yrs vs 0–5 yrs: OR=0.27, p=0.03; more than 11 yrs vs 0–5 yrs: OR=0.18, p=0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR=0.07; p=<0.01), not minding (OR=0.26; p=0.03), being bored (OR=0.25; p=0.01) and not finding the questions easy (OR=0.10; p=<0.01). Conclusions Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent. Trial Registration clinicaltrials.gov number NCT00270257. (shrink)

This study investigated the differences between past and future temporal discounting in terms of neural activity in relation to temporal distance. Results show that brain regions are engaged differently in past and future temporal discounting. This is likely because past temporal discounting requires memory reconstruction, whereas future temporal discounting requires the processing of uncertainty about the future. In past temporal discounting, neural activity differed only when preferences were made between rewards received one hour prior and rewards received further in the (...) past. The peak amplitudes of P2 and P3 varied as the temporal distance increased from 2 weeks to 50 years. In future temporal discounting, neural activity differed only when preferences were evaluated between two delayed rewards. The delay conditions and had a significant influence on P2 and N2. Findings indicate the existence of different decision-making systems operating in past and future temporal discounting. (shrink)

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: (...) DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom. (shrink)