Incremental Escalation Research Articles

Tolerability and efficacy of a reduced dose adenosine stress cardiac magnetic resonance protocol under general anesthesia in infants and children.

Intravenous adenosine induces pharmacological stress by causing vasodilatation and thus carries the risk of severe hypotension when combined with vasodilatory effects of anesthetic agents. This study describes our experience with a reduced dose adenosine cardiac magnetic resonance imaging (MRI) protocol in young children under general anesthesia (GA). This is a retrospective report of all patients from birth to 18years who underwent adenosine stress cardiac MRI under GA between August 2018 and November 2022. Based on our anecdotal experience of severe adverse effects in patients receiving adenosine infusion under GA and in discussion with the pediatric anesthesia team, we developed a modified protocol starting at a dose of 110 mcg/kg/min with incremental escalation to a full dose of 140 mcg/kg/min to achieve desired hemodynamic effect. Twenty-two children (mean age 6.5years, mean weight 28kg) satisfied the inclusion criteria. The diagnoses included Kawasaki disease (7), anomalous aortic origin of left coronary artery (3), anomalous aortic origin of right coronary artery (2), coronary fistula (3), repaired d-transposition of great arteries (2), repaired anomalous left coronary artery from pulmonary artery (2), repaired truncus arteriosus with left coronary artery occlusion (1), extracardiac-Fontan with left coronary artery myocardial bridge (1), and post heart transplantation (1). Nine patients needed dose escalation beyond 110 mcg/kg/min. Two patients had transient hypotension during testing (systemic blood pressure drop > 25mmHg). No patient developed significant heart block or bronchospasm. Six patients (repeat study in one) demonstrated inducible perfusion defects (27%) on stress perfusion sequences-5 of whom had confirmed significant coronary abnormalities on angiography or direct surgical inspection. A reduced/incremental dose adenosine stress cardiac MRI protocol under GA in children is safe and feasible. This avoids severe hypotension which is both unsafe and may result in inaccurate data.

Fighting the last war: Is presidential hindsight 20‐20?

Fighting the last war lays out the contours of a theoretical framework that explains U.S. presidential decisions to cut losses or double down on major post-Vietnam military conflicts. The archival sources and principal interviews give readers an insider's look into presidents' conflict decision making. The article explains how the Vietnam War catastrophe shaped Presidents Reagan and Clinton's attempts to avoid a similar quagmire in Lebanon in 1983–1984 and Somalia in 1993, respectively. It then shows how new lessons from 9/11 and beyond shaped Presidents Bush and Obama's decisions to surge troops and employ counterinsurgency strategies in Iraq (2007) and Afghanistan (2009). While Vietnam-era lessons remained important to all these presidents, pre-9/11 they believed entrapment risks from incremental escalation were worse than de-escalation risks. After 9/11, the logic flipped.

The cross-sectional, longitudinal, and transitional associations between perceived support and suicidal ideation and behavior in late adolescence and emerging adulthood: Adjacent-category logit models.

Suicidal ideation (SI) and attempts (SA) are prevalent in late adolescence and emerging adulthood. Prior research has identified perceived support as a correlate of SI and SA. Less is known, though, about the role of perceived support in differentiating among suicidal outcomes and between the incremental escalation of suicidal outcomes from SI to SA to serious suicide attempts (SSA). Using ordinal regression, we used Wave 1 and 2 data from the National Longitudinal Study of Adolescent to Adult Health (N=4500; 53% female; Mage =16.6; 12% Hispanic) to examine cross-sectional, longitudinal, and transitional models of perceived support and suicidality. Cross-sectional results indicated that youths with higher perceived support were less likely to have suicidal ideation. Longitudinal results showed that youths with higher perceived support at Wave 1 were less likely to have suicidal ideation or serious suicide attempts at Wave 2. Transitional model results revealed that higher perceived support at Wave 1 was negatively associated with escalation in suicidal outcomes from Wave 1 to 2. We discuss findings in the context of theories of suicide and discuss implications for suicide risk identification, intervention, and prevention efforts in late adolescence and emerging adulthood.

Evaluation of baked egg oral immunotherapy in French children with hen's egg allergy.

Introduction and gradual incremental escalation of a low dose of baked egg may accelerate the resolution of severe hen's egg (HE) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked egg oral immunotherapy (OIT) in children with HE allergy after a low-dose baked egg oral food challenge (OFC). In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 71 children with HE allergy and high egg-white (EW) and ovomucoid specific IgE levels, who underwent a total of 164 OFC (71 baked egg, then 93 unbaked egg). Mean age at first low-dose baked egg OFC was 6years. Median EW specific IgE was 14.0kUA/L, and median ovomucoid specific IgE was 11.7kUA/L. Most children were treated with baked egg OIT. Our study shows that 78.9% of the children did not react to first low-dose baked egg OFC (702mg of HE protein). 8.7% of children discontinued OIT at home. Finally, desensitization to unbaked HE was achieved in 47 children (66.2% of children allergic to HE). Children with lower EW specific IgE levels had a significantly higher probability of becoming desensitized to HE. We did not report any anaphylactic reactions to baked egg OIT. Most children with HE allergy and high egg-white (EW) and ovomucoïd specific IgE levels tolerate the introduction of baked egg. Baked egg OIT is safe, and anaphylaxis to baked egg OIT has not been observed.

Benefits of baked milk oral immunotherapy in French children with cow's milk allergy.

Introduction and gradual incremental escalation of a low dose of baked milk may accelerate the resolution of severe cow's milk (CM) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked milk oral immunotherapy (OIT) in children with CM allergy after a low-dose baked milk oral food challenge (OFC). In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 64 children with CM allergy and high milk and casein-specific IgE levels, who underwent a total of 171 milk OFC. Mean age at 1st OFC was 4.8years. Mean CM-specific IgE was 47.9 kUA/L, and mean casein-specific IgE was 42.3 kUA/L. Most children were treated with baked milk OIT. Our study shows that 67.2% of the children did not react to 1st low-dose baked milk OFC (168.6mg of CM protein). Eighteen percent of children stopped the OIT at home. Finally, desensitization to fresh milk was achieved in 27 children (42.2% of children allergic to CM). Children with lower CM-specific IgE levels have a significantly higher probability of becoming desensitized to unbaked CM. Most children with CM allergy and high milk and casein-specific IgE levels tolerate the introduction of baked milk. However, the occurrence of anaphylactic reactions during OIT remains possible.

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches.

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.

Tarnishing Tinseltown: Hollywood’s Responses to Nazi Germany

Tarnishing Tinseltown: Hollywood’s Responses to Nazi Germany Lawrence Baron Thomas Doherty, Hollywood and Hitler 1933–1939. New York: Columbia University Press, 2013. Pp. 448. Cloth $35.00. ISBN 978-0231163927. Ben Urwand, The Collaboration: Hollywood’s Pact with Hitler. Cambridge, MA: Belknap Press, 2013. Pp. 336. Hardcover $26.95. ISBN 978-0674724747. Not since the publication of Daniel Goldhagen’s Hitler’s Willing Executioners has a scholarly monograph generated so much controversy within and outside of academia as Ben Urwand’s The Collaboration. He indignantly indicts Hollywood for colluding with Nazi Germany’s censorship demands to purge Jewish characters and anti-Nazi themes from American movies during the 1930s. Urwand’s sweeping condemnation of Hollywood’s complicity contrasts sharply with Thomas Doherty’s more balanced assessment of how the American film industry responded to Hitler’s incremental escalation of anti-Semitic, expansionist, and repressive policies before the outbreak of World War II. The initial trigger for the debate over the conflicting interpretations proffered by the two authors was the publicity campaign for The Collaboration. Harvard University Press hired Goldberg McDuffie Communications to promote Urwand’s book, scheduled for release in October 2013, seven months after Doherty’s hit the shelves in April. In what appears to have been an attempt to counteract the positive reviews Hollywood and Hitler had begun to receive, the marketing firm provided advance copies of The Collaboration to prospective reviewers in June. The cover letter accompanying the review copies denigrated the depth of Doherty’s research and touted that of Urwand’s: “Whereas Doherty relied on flawed, superficial accounts in domestic trade papers, Urwand discovered a vast array of primary resource materials.”1 While Urwand does not specifically mention Hollywood and Hitler (which he presumably had not read when he was writing The Collaboration) in the text of his book, he curtly dismisses it in a footnote as “a lively account, but one [End Page 59] that is limited to reports that appeared in American trade papers.” (256) To be sure, Urwand delved into the German archives to unearth reports about the hectoring of the film industry by Georg Gyssling, Nazi Germany’s consul in Los Angeles, but Doherty also draws on a “rich repository of archival sources” beyond the trade press, including the files of the Production Code Administration (PCA), the Motion Picture Producers and Distributors of America (MPPDA), and memos from federal officials. (375) Both books reveal how the major studios avoided direct criticism of Hitler and his anti-Semitic policies, abandoned or altered scripts that might antagonize Nazi Germany, and eliminated Jewish characters from their movies in the 1930s. They similarly attribute these concessions to the film industry’s commercial stakes in the German market. A main point of contention between the two scholars is whether this self-censorship constituted “collaboration,” exacted primarily by Germany’s threat to deny distribution licenses to the films of studios that did not abide by the content parameters it established, as Urwand claims, or a continuation of Hollywood’s standard practice of editing films and scripts to gain the approval of the PCA and local and state censorship boards in the United States and to placate domestic interest groups and foreign governments, as Doherty posits. The first reviewers of Urwand’s book seized upon the incendiary charge he leveled at the movie moguls by giving their pieces sensationalist titles such as, “Hollywood’s Creepy Love Affair with Adolf Hitler,” “Scholar Asserts That Hollywood Avidly Aided Nazis,” “When Hollywood Held Hands With Hitler,” and “Hollywood’s Deal with The Devil (Hitler).”2 Yet these titles only slightly exaggerated Urwand’s censure of Hollywood’s kowtowing to Nazi demands. In the prologue to his book, he unambiguously declares, “Over the course of the investigation, one word kept reappearing in both the German and American records: ‘collaboration’ (Zusammenarbeit). And gradually it became clear that this word accurately described the particular arrangement between the Hollywood studios and the German government in the 1930s.”(8) Amplifying his thesis, he argues, “The studio heads, who were mostly immigrant Jews, went to dramatic lengths to hold on to their investment in Germany. Although few remarked on it at the time, these men followed...

Impact of drilling fluid viscosity, velocity and hole inclination on cuttings transport in horizontal and highly deviated wells

Deviation from vertical path makes drill cuttings to accumulate on the lower side of the wellbore that induces the formation of cuttings bed. Subsequently, relative problems occur while drilling. Excessive torque and drag, difficulties in running casing in hole and accomplishing good cementing jobs and mechanical pipe sticking are few of the classical examples of such problems. Therefore, a comprehensive understanding of influential parameters on hole cleaning seems to be essential. This paper indicates the results of an experimental study that was carried out to evaluate cuttings removal efficiency using three types of drilling fluid. The experimental works were conducted using a 17-feet long opaque flow loop of 2-in. diameter as the test section. For each test, the amount of cuttings transport performance (CTP) was determined from weight measurements. Viscosity was investigated together with other two influential parameters, namely fluid velocity and hole inclination under various flow conditions. It is shown that the increase in drilling fluid viscosity has improved CTP by approximately 8 % at all angles provided the flow regime remained turbulent while velocity was kept constant. However, further increase of viscosity as flow regime was turning into transient or laminar flow, has lessened CTP by a total average of 12 %. It was also revealed that an incremental escalation in hole inclination from 60° to 90° has a positive effect on CTP, i.e., it will be improved up to 40 %. Drilling fluid velocity was found to have significant impact on CTP as it could attain maximum percentage of 98 %.

Nuclear energy 2011: A watershed year

2011 was a watershed for nuclear power. In March, all eyes focused on Japan, where the world’s third severe accident at a nuclear plant unfolded. The accident at the Fukushima Daiichi Nuclear Power Station will have a paradigm-changing impact on the global future of nuclear energy, though its scope and direction still remain to be seen. The author reviews reassessments undertaken around the world after the accident in Japan and underlines Europe’s critical role in whether the future of nuclear energy will be global. Japan’s nuclear safety shock was sudden and dramatic. But 2011 also witnessed an incremental escalation of continuing crises in North Korea, Iran, and South Asia in the absence of effective global nuclear governance. The author points to the politicization of the International Atomic Energy Agency, its limited authority, and the inability of major powers to cooperate effectively as reasons that nuclear governance remains ineffective. This breakdown in global nuclear governance will also challenge the Nuclear Suppliers Group, which sets the rules for nuclear commerce. The author reflects on 2011 and highlights what to look out for in 2012.

Constructing Vietnam�.�.�.�

“It should be no cause for surprise that [the Soviets] have chosen Indo-China as an issue which enables them … to drive Britain and the United States into an embarrassing endorsement of a French policy conducted from the beginning on principles widely different from their own,’1 opined The Economist in its edition of February 11, 1950, reflecting on the recognition of the state of Vietnam by the United States and Britain in the wake of Joseph Stalin's and Mao Zedong's decision to recognize the Democratic Republic of Vietnam. As The Economist anticipated, Western recognition of the French puppet regime in Vietnam was merely the first step. In May 1950, the United States offered ten million dollars in direct support of the French military effort and also created the Military Assistance Advisory Group in Saigon. The incremental escalation of American involvement in the Vietnam wars began, culminating in the landing of U.S. combat forces in 1965.

Thomas Schelling's Contributions to Game Theory

Thomas Schelling brings game theory to life, and does so in two senses. First, instead of the abstract and austere beauty of mathematical theorems that we find in most of game theory going back to von Neumann, Morgenstern and Nash, he gives us lively and memorable examples to explain and illustrate his ideas. Schelling’s (1960a, p. 21) pictures of bargaining—“When two dynamite trucks meet on a road wide enough for one, who backs up?”—and of tacit coordination—can two people who are told to meet each other in New York city on a specified day, but are not told the place or time and are unable to contact each other, successfully meet? (1960a, pp. 55–56)—are among the best known. But my personal favorite is Schelling’s (1965, pp. 66–67) example of the strategy of “salami tactics” for defeating threats by incremental escalation:

Explaining War Termination: a Boolean Analysis of Causes

An understanding of why states fight wars requires an understanding of why they end wars. These phenomena form interrelated parts of a larger process of interstate bargaining. Yet, compared to the research on the outbreak of wars, there has been much less attention paid to their termination. These conflicts end when the belligerents reach convergent expectations that they have more to gain or less to lose if they stop fighting than if they continue to do so. This article presents several factors hypothesized to hasten or delay this mutual recognition and, therefore, to shorten or prolong a conflict. Boolean algebra is applied to study the individual and joint effects of these factors on the duration of 23 interstate wars during 1945-92. The results show that short wars stem from different causal combinations, therefore suggesting the inadequacy of any monocausal explanation. Moreover, this analysis points to the importance of context-specific understanding because the same factors can have different effects on shortening war and different factors can have similar effects on this outcome under different circumstances. Contrary to the argument in favor of an incremental escalation of military pressure on an adversary, massive and intense fighting at the outset of a war has been nearly a necessary though insufficient condition for a quick ceasefire. This conclusion supports the view that private information inclines states to fight wars but the revelation of this information in the subsequent fighting puts them in a better position to reach a settlement.