Antihypertensives’ Rock around the Clock

Although homeostasis is a commonly accepted concept, there is incontrovertible evidence that biological processes and functions are variable and that variability occurs in cycles. In order to explain and understand dysregulation, which has not been embraced by homeostatic principles, the allostatic model has emerged as the first serious challenge to homeostasis, going beyond its homeostatic roots. Circadian rhythm is the predominant variation in the body, and it is a pattern according to which many physiological and pathological events occur. As there is strong experimental and clinical evidence that blood pressure fluctuations undergo circadian rhythm, there is equally strong evidence that targeted time therapy for hypertension provides a better outcome of the disease. The research has gone even further throughout the development and approval process for the use of pulsatile drug release systems, which can be considered as an option for an even more convenient dosage regimen of the medicines needed.

THE ROLE OF THE CISG IN CANADIAN CONTRACT PRACTICE: AN EMPIRICAL STUDY

In much of the legal literature, the fact that the United Nations Convention on Contracts for the International Sale of Goods (CISG) has been ratified by so many nations constitutes incontrovertible evidence of its success. This narrative fails to account, however, for the fact that private parties can choose to exclude the CISG from their international sales contracts. This Article draws upon a hand-collected dataset of contracts executed by public companies in Canada to show that these companies overwhelmingly choose to exclude the CISG from their international sales agreements. It also shows that these same companies are frequently unaware that selecting the law of a Canadian province can result in the application of the CISG and that few (if any) of these companies consciously select the CISG by selecting provincial law. While the Article turns up a few tantalizing hints that attorneys practicing in Quebec may be slightly more receptive to the CISG than attorneys practicing in the rest of Canada, the overall portrait that emerges is of a nation where this treaty is excluded by sophisticated actors in almost all cases. This finding raises important questions of whether the CISG is achieving its intended purpose of facilitating international trade.

The moral economy of early intervention

In November 2015, protests erupted in Oxford in response to the decision of the Oxfordshire County Council to cut, among other things, forty-four Children’s Centres and seven Early Intervention Hubs. The debate about whether these centres could be considered as disposable or not did not get to an agreement. I argue that the main cause of this outcome is that the opposing arguments were based on moral positions that were not only incompatible but fundamentally incommensurable. Those in favour of reducing deficit spending argue that cuts to social services (including family and children services) are unavoidable. Parents, however, refuse to accept austerity measures that will undermine the rights of their children to access services that will improve their chances in life. Neither position is based on incontrovertible evidence. On the one hand, the decision to cut a given service always involves the arbitrary evaluation of that service against other services that will not be cut. On the other, the demand to fund those services is based on the hope that early intervention initiatives will benefit children, even if the evidence that early intervention works is unconclusive or thin. On the basis of a thematic analysis of twenty-seven stories written by Oxfordshire parents, I interpret this conflict using the notion of moral economy, and argue that such an approach allows an appreciation of the link between health economics, perinatal mental health, the morality of parenting, and the early intervention discourse.

Toward a Muscular Public Health

This chapter assesses why public health persists in suggesting courses of actions for the entire population, to be taken on a population’s behalf. The answer is simple: public health professionals know best for populations; individuals know best for themselves. After assembling incontrovertible evidence, public health providers try to universalize its application for the good of all. Society entrusts public health to understand what is in the public good and to act on it. Therefore, when public health providers know the healthiest answer, they should be relentless in seeking its implementation. It is up to society to decide if public health should or should not be in a position to flex its muscles. However, when public health providers see the opportunity to improve the public’s health, which derives from the combination of evidence and public agreement, they should act, even in the absence of consensus.

My approach to water-assisted colonoscopy

The goal of diagnostic colonoscopy is to achieve procedural completion while maximising effectiveness, patient acceptance and safety. In recent years, international interest in water-assisted colonoscopy (WAC) has been steadily gathering pace. A plethora of high-quality randomised controlled trials and meta-analyses now offer incontrovertible evidence into the benefits of WAC, both for the endoscopist and the patient. Despite this, uptake of WAC within the UK has been limited, with the lack of educational resources representing a significant barrier. This practical step-by-step guide is aimed at both existing practitioners and trainees, with a view to promoting familiarity with WAC and potentially for incorporation into daily practice which may ultimately have a positive effect on quality of colonoscopy and patient experience.

Gene-Culture Coevolution

This chapter examines the evidence that our cultural activities have influenced our biological evolution, by drawing on a cocktail of theoretical and empirical findings. It begins by relating findings from theoretical studies, which show through mathematical modeling that gene–culture coevolution is, at least in principle, highly plausible. Then the anthropological evidence for gene–culture coevolution is surveyed. Here, compelling and well-researched case studies provide incontrovertible evidence that gene–culture coevolution is a biological fact. Finally, some genetic data are presented—specifically, studies that have identified human genes subject to recent natural selection, including genes expressed in the brain. Many such genes (strictly, “alleles,” or gene variants) have increased extremely rapidly in frequency over a few thousand years, and this unusually swift spread, known as a “selective sweep,” is taken as a sign of their having being favored by natural selection. The relevance of such studies stems from the fact that the geneticists who carried them out have concluded that the sweeps are almost certainly a response to human cultural activities. Collectively, these three bodies of evidence make a compelling case that culture is not just a product, but also a codirector, of human evolution.

Clovis and the American Mastodon at Big Bone Lick, Kentucky

Contemporaneity of people and the American mastodon (Mammut americanum) at Big Bone Lick, Kentucky, has been extensively debated for more than two hundred years. Newly interpreted stratigraphic excavations and direct AMS ¹⁴C measurements on mastodon bones from Big Bone Lick, Kentucky, indicate that the megafauna are a palimpsest of fossils spanning at least 1,200 calendar years (11,020 ± 30 to 12,210 ± 35 RC yr B.P.). The radiocarbon evidence indicates that mastodons and Clovis people overlapped in time; however, other than one fossil with a possible cut mark and Clovis artifacts that are physically associated with but dispersed within the bone-bearing deposits, there is no incontrovertible evidence that humans hunted Mammut americanum at the site.

‘Saved by the reflexive’

This paper argues for the existence of a dynamic interaction between constructional polysemy and coercion in shaping lower-level configurations of the subjective-transitive construction in English and Spanish. In particular, a fine-grained analysis is provided of those configurations featuring coercion via a reflexive pronoun in the object slot. The corpus-based analysis provided here shows that the verbs in question, regardless of their inherent lexical semantics, are construed in this construction as expressing a personal assessment by the subject/speaker about himself/herself, thus providing incontrovertible evidence for a constructionist analysis of the type invoked here. Moreover, the coercion effects examined here lend further credence to the construction-specific and also language-specific nature of constructions, especially in the light of instances of the reflexive subjective-transitive construction after saber (‘know’) in Spanish. This paper also suggests that the explanatory power of the anatomy of a given construction can be further maximized if the morphosyntactic properties of the XPCOMP are mapped onto their inherent meaning properties.

Chagas’ Disease and the Autoimmunity Hypothesis

SUMMARY The notion that the pathology of Chagas’ disease has an autoimmune component was initially based on the finding of circulating antibodies binding heart tissue antigens in patients and mice chronically infected with Trypanosoma cruzi. Later, T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic mice and patients, extending the concept to include cell-mediated immunity. However, there is disagreement about whether the observed immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host tissue antigens by virtue of molecular mimicry or are elicited by host antigens exposed to lymphocytes after tissue damage caused by the parasite. There is also disagreement about the relevance of immunologic autoreactivities to the pathogenesis of Chagas’ disease because of the lack of reproducibility of some key reports supporting the autoimmunity hypothesis, conflicting data from independent laboratories, conclusions invalidated by advances in our understanding of the immunologic mechanisms underlying cell lysis, and, last but not least, a lack of direct, incontrovertible evidence that cross-reacting antibodies or autoreactive cells mediate the typical pathologic changes associated with human Chagas’ disease. The data and views backing and questioning the autoimmunity hypothesis for Chagas’ disease are summarized in this review.