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"Gould, Harry D"
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The legacy of punishment in international law
\"The Legacy of Punishment in International Law illustrates how 17th and 18th century rationales for the use of force in support of piracy and colonialism have been transformed into progressive features of contemporary International Law. The classic practice of international punishment was a part of the jus ad bellum, and was the fig leaf for intra-European violence, and for the European conquest of the Americas. It has been transformed, however, into the basis for the assertion of a set of unconditionally, universally binding rules of international law, and for universal jurisdiction over perpetrators of crimes against humanity and war crimes\"-- Provided by publisher.
Book
International criminal bodies
One of the insights of Constructivism is that our world is, in part, made by what we say about it. We make things what they are by saying what they are. One way is through the use of metaphor; by asserting that one thing is another thing. Does our saying that a state is a person make it a person? A way to intervene in this discussion is by addressing it not in the abstract, but guided by a cognate question: Can states commit crimes, a uniquely human act? If states can commit and be liable for crimes, they must be able to form intents. If they are indeed persons in the relevant sense, this is no problem; if their personality is trope, however, attribution of criminal responsibility becomes tenuous. To analyse the issue, I trace the development of the trope of speaking of a group as if it were an individual from Roman Law, through to Hobbes, corporate law and IR Theory. Much hinges on Hobbes' elision of ‘body’ and ‘person’. I conclude that it is too much to expect of a metaphor that it act, that it have reasons, beliefs, and desires, and that these sum to intentions.
Journal Article
Cicero's Ghost
The crime of piracy and the principle of universal jurisdiction in international law have long been closely intertwined. The problem is that much of the account of their relationship is badly garbled, full of mistakes too-often repeated. This is not to say that piracy was not the first crime jure gentium, or that subsequent crimes jure gentium were not built upon an analogy with piracy. Rather the problem lies in the erroneous assertion of a classical basis for the universal proscription of piracy, the misuse of the concept of the hostis humani generis and misunderstanding of its association with piracy, and the overly simple way that this concept has been treated as fundamental to the development of the principle of universal jurisdiction.
Book Chapter
Understanding pain
An estimated 50 million Americans suffer from chronic pain, and an additional 25 million experience acute pain as a result of surgery or injury.Many people assume they must live with pain, but this is simply untrue.
eBook
Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing
Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).
From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.
Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2).
Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.
Journal Article
Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations
Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the \"as-needed\" use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain.
Journal Article
Cyclic-nucleotide signalling in protozoa
Abstract
Compared with the impressive progress in understanding signal transduction pathways and mechanisms in mammalian systems, advances in protozoan signalling processes, including cyclic nucleotide metabolism, have been very slow. This is in large part connected to the fact that the components of these pathways are very different in the protozoan parasites, as confirmed by the recently completed genome. For instance, kinetoplastids have no equivalents to the mammalian Class I adenylyl cyclases (ACs) in their genomes nor any of the subunits of the associated G-proteins. The cyclases in kinetoplastid parasites contain a single transmembrane domain, a conserved intracellular catalytic domain and a highly variable extracellular domain – consistent with the expression of multiple receptor-activated cyclases – but no receptor ligands, agonists or antagonists have been identified. Apicomplexan AC and guanylyl cyclase (GC) are even more unusual, potentially being bifunctional, harbouring either a putative ion channel (AC) or a P-type ATPase-like domain (GC) alongside the catalytic region. Phosphodiesterases (PDEs) and cyclic-nucleotide-activated protein kinases are essentially conserved in protozoa, although mostly insensitive to inhibitors of the mammalian proteins. Some of the PDEs have now been validated as promising drug targets. In the following manuscript, we will summarize the existing literature on cAMP and cGMP in protozoa: cyclases, PDEs and cyclic-nucleotide-dependent kinases.
Journal Article