Relieving pain using dose-extending placebos

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated

Synthesis and Analytics of Rigidified Peptide Architectures: Neuropeptide Y Dipeptide Scan, Ring-Chain-Equilibria of Iminopeptides, Thiazole Amino Acids for Thiopeptide Antibiotics

The architectures (three-dimensional shapes) of peptides determine their respective biological functions. Therefore, the correct alignment of functionalities in a structure by constraining the flexibility is a key process in evolution as well as in medicinal chemistry in order to increase binding affinity and selectivity. The rigidification of a peptide chain can have local effects (incorporation of the amino acid proline) or it can globally restrain flexibility (macrocyclization). Furthermore, the combination of both strategies has given rise to complex antibiotics with highly optimized modes of action. This work approaches these principles in three topics and for different purposes. The first chapter presents a novel scanning strategy which utilizes synthetic local rigidifications for the evaluation of Neuropeptide Y structure and receptor binding patterns. The fundamental process of macrocyclization is topic of the second chapter. For iminopeptides, ring-chain equilibria can be established and controlled, thereby allowing for the thermodynamic analysis of the ring closure. This leads to the identification of structural determinants that influence the inclination of a peptide chain to close the ring. In the third chapter, a sugar-based synthetic pathway leading to highly functionalized thiazole dipeptides is described. This strategy led to the synthesis of core motivs of complex thiopeptide antibiotics, as well as to diastereomers and homologs thereof

Book Review: Domestic Violence and the Politics of Privacy

Review of Domestic Violence and the Politics of Privacy by Kristin A. Kell

"If You Can't Beat them, Join them": A Usability Approach to Interdependent Privacy in Cloud Apps

Cloud storage services, like Dropbox and Google Drive, have growing ecosystems of 3rd party apps that are designed to work with users' cloud files. Such apps often request full access to users' files, including files shared with collaborators. Hence, whenever a user grants access to a new vendor, she is inflicting a privacy loss on herself and on her collaborators too. Based on analyzing a real dataset of 183 Google Drive users and 131 third party apps, we discover that collaborators inflict a privacy loss which is at least 39% higher than what users themselves cause. We take a step toward minimizing this loss by introducing the concept of History-based decisions. Simply put, users are informed at decision time about the vendors which have been previously granted access to their data. Thus, they can reduce their privacy loss by not installing apps from new vendors whenever possible. Next, we realize this concept by introducing a new privacy indicator, which can be integrated within the cloud apps' authorization interface. Via a web experiment with 141 participants recruited from CrowdFlower, we show that our privacy indicator can significantly increase the user's likelihood of choosing the app that minimizes her privacy loss. Finally, we explore the network effect of History-based decisions via a simulation on top of large collaboration networks. We demonstrate that adopting such a decision-making process is capable of reducing the growth of users' privacy loss by 70% in a Google Drive-based network and by 40% in an author collaboration network. This is despite the fact that we neither assume that users cooperate nor that they exhibit altruistic behavior. To our knowledge, our work is the first to provide quantifiable evidence of the privacy risk that collaborators pose in cloud apps. We are also the first to mitigate this problem via a usable privacy approach.Comment: Authors' extended version of the paper published at CODASPY 201

ENHANCING THE VIRTUES OF STUDENTS

Discussions about the permissibility of students using enhancements in education are often framed by the question, “Is a student who uses cognitive-enhancing drugs cheating?” Some argue that students who use these cognitive-enhancing drugs are cheating because these drugs provide an unfair advantage that violates rules of fair competition in education. Others argue that students who use cognitive-enhancing drugs are not cheating because these drugs are merely another progressive educational tool, such as a calculator or computer. While the question of cheating is interesting, it is but only one question concerning the permissibility of enhancement in education. Another interesting question is, “What kinds of students do we want in our academic institutions?” I suggest that one plausible answer to this question concerns the ideals of human excellence or virtues. The students we want in our academic institutions are virtuous or, at least minimally, possess certain virtues.I argue that a virtuous student may choose to use cognitive-enhancing drugs for reasons of self-improvement. That a virtuous student may choose to use cognitive-enhancing drugs for reasons of self-improvement illustrates that under certain conditions motivation can determine the permissibility of using enhancements. Building upon this I suggest a virtues-based institutional rule for governing and guiding students use of cognitive enhancers in an academic institution to be for the right reasons. This ideals of human excellence or virtues approach offers interesting and unique insights for issues of enhancement in education (and for issues of pharmaceutical enhancement in general) because, as it might turn out, that uneasiness many people have about students using cognitive-enhancing drugs has less to do with issues of enhancement and more to do with the motivation and character of students

Repeatability of innervation zone identification in the external anal sphincter muscle

Knowledge of the distribution of the innervation zones (IZs) of the external anal sphincter (EAS) may be useful for preventing anal sphincter incompetence during vaginal delivery. A method proposed for the automatic estimation of the distribution of IZs of EAS from high-density surface electromyography (EMG) was evaluated for repeatability in continent volunteers. Methods: In 13 healthy female subjects (age: 35 11 years) surface EMG signals were acquired using an anal probe with three circumferential electrode arrays (of 16 contacts each) at different depths within the anal canal (15mm distance between the centers of adjacent arrays), during four independent experimental sessions. Three maximal voluntary contractions (MVCs) of 10 sec were performed for each session for a total of 12 contractions per subject. Repeatability of the estimation of the distribution of IZ was tested by evaluating the coefficient of multiple correlations (CMC) between the IZ distributions estimated from the signals recorded from each subject. Results: A high repeatability (CMC > 0.8) was found comparing IZ distributions estimated from signals recorded by each array within the same session. A slightly lower value was obtained considering signals recorded during different sessions (CMC > 0.7), but a higher value (CMC > 0.8) was obtained after aligning the estimated IZ distributions. The realignment compensates for the operator's error in repositioning the probe in the same position during different sessions. Conclusion: This result justifies clinical studies using high-density surface EMG in routine examinations, providing information about IZs of EAS and assessing the possibilities of preventing neuronal trauma during vaginal delivery

Public Health, News Media, and Knowledge Gaps: An investigation into the factors impacting the knowledge gap between West Nile virus and tick borne diseases

The knowledge gap hypothesis, developed in 1970 by Tichenor and colleagues, proposed that socioeconomic status, measured by education, was the prominent cause of knowledge gaps. However, since then many studies have found evidence suggesting factors on many scales from macro-level, such as community conflict to micro-level, such as individual interest and life situation, that impact the knowledge gap despite socioeconomic status. Knowledge gaps pertaining to public health are a threat to the health of both communities and individuals. To investigate a potential public health knowledge gap a convenience sample of an upstate New York population was used to investigate the differences between the knowledge of two different vector transmitted diseases, West Nile virus and tick borne diseases, and how the number of media sources may have influenced that knowledge. A survey was created with several sections pertaining to demographics, media source, and knowledge of the diseases. The results show that there is a statistically significant difference between the scores on the tick borne disease section and West Nile virus section with the higher score being on the tick borne section. There is evidence that suggests that demographic factors such as age, education and income, but not the number of sources, influenced the knowledge gap