Annals of the New York Academy of Sciences
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This paper presents commentaries on reflux-induced injury of human esophageal epithelium; inflammation in human reflux esophagitis; motor consequences of reflux-induced inflammation in esophageal epithelium; the microscopic morphology of esophageal squamous epithelium; intraluminal impedance in the evaluation of the esophageal mucosa; endoscopic tissue morphology of esophageal squamous epithelium; and the developmental biology of esophageal squamous epithelium.
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Ann. N. Y. Acad. Sci. · Sep 2013
ReviewSacred values in the Israeli-Palestinian conflict: resistance to social influence, temporal discounting, and exit strategies.
Conflicts over sacred values may be particularly difficult to resolve. Because sacred values are nonfungible with material values, standard attempts to negotiate, such as offering material incentives to compromise, often backfire, increasing moral outrage and support for violent action. ⋯ We show that devoted actors (1) were less amenable to social influence, (2) perceived conflict-related events in the past as well as expected events in the future to be temporally closer, and (3) were blind to individual opportunities to escape the conflict. These results suggest that sacred values may affect decision making in a number of ways, which, when combined, contribute to common defense and continuation of conflict.
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Ann. N. Y. Acad. Sci. · Jul 2013
ReviewDevelopment of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma.
The immunotherapeutic agent ipilimumab has helped address a significant unmet need in the treatment of advanced melanoma. Ipilimumab is a fully human monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), thereby augmenting antitumor immune responses. After decades in which a number of clinical trials were conducted, ipilimumab was the first therapy to improve overall survival in a randomized, controlled phase III trial of patients with advanced melanoma. ⋯ These immune-related adverse events were mostly reversible when effective treatment guidelines were followed. Importantly, long-term follow-up of patients who received ipilimumab in a phase III trial showed that 24% survived at least two years, and in phase II studies, a proportion of patients survived at least five years. Evaluation of ipilimumab is ongoing in the adjuvant setting for melanoma, and for advanced disease in nonsmall cell lung, small cell lung, prostate, ovarian, and gastric cancers.
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The human experience of pain is multidimensional and comprises sensory, affective, and cognitive dimensions. Preclinical assessment of pain has been largely focused on the sensory features that contribute to nociception. The affective (aversive) qualities of pain are clinically significant but have received relatively less mechanistic investigation in preclinical models. ⋯ An important advance of such operant behaviors is that these approaches may allow the detection and mechanistic investigation of spontaneous neuropathic or ongoing inflammatory/nociceptive (i.e., nonevoked) pain that is otherwise difficult to assess in nonverbal animals. Operant measures may allow the identification of mechanisms that contribute differentially to reflexive hypersensitivity or to pain affect and may inform the decision to progress novel mechanisms to clinical trials for pain therapy. Additionally, operant behaviors may allow investigation of the poorly understood mechanisms and neural circuits underlying motivational aspects of pain and the reward of pain relief.
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Ann. N. Y. Acad. Sci. · Apr 2013
ReviewManaging obesity in primary care practice: a narrative review.
This narrative review examines randomized controlled trials of the management of obesity in primary care practice, in light of the Centers for Medicare and Medicaid Services' decision to support intensive behavioral weight loss counseling provided by physicians and related health professionals. Mean weight losses of 0.1-2.3 kg were observed with brief (10- to 15-min) behavioral counseling delivered by primary care providers (PCPs) at monthly to quarterly visits. Losses increased to 1.7-7.5 kg when brief PCP counseling was combined with weight loss medication. ⋯ Remotely delivered, intensive (>monthly contact) behavioral counseling, as offered by telephone, yielded losses of 0.4-5.1 kg over the same period. Further study is needed of the frequency and duration of visits required to produce clinically meaningful weight loss (>5%) in primary care patients. In addition, trials are needed that examine the cost-effectiveness of PCP-delivered counseling, compared with that potentially provided by registered dietitians or well-studied commercial programs.