Cost-effectiveness of preoperative localization studies in primary hyperparathyroid disease

OBJECTIVE: To evaluate the effect of preoperative localization studies on the surgical management of patients with primary hyperparathyroid disease (PHPT). SUMMARY BACKGROUND DATA: Reported cure rates of initial surgical exploration for PHPT are close to 95%. Preoperative localization studies are frequently obtained to improve surgical success and decrease operative time. METHODS: Initial cervical exploration was performed in 113 patients with PHPT from 1981 to 1993. Twenty-four patients (21%) had surgery without preoperative localization studies. The remaining 89 patients (79%) had 132 noninvasive preoperative localization studies. Success of the localization studies in tumor localization, pathologic findings, postoperative serum calcium levels, and operative times were compared. Patient costs of the studies were calculated. RESULTS: Disease was identified during operation in 23 of 24 patients (96%) having cervical exploration without preoperative localization studies, and they had normal calcium levels after surgery. Eighty-seven of 89 patients (98%) having preoperative localization studies were surgically cured. The highest sensitivity rate (60%) and highest positive predictive value (79%) of the localization studies were found with thallium-technetium scintiscanning. Average cost of the localization studies was $901 per patient. Combination studies were obtained in 32 patients at an average cost of $1,314 per patient without improving sensitivity. Mean operating time did not differ for localized and nonlocalized patients. CONCLUSIONS: Preoperative localization studies did not improve parathyroid localization or cure rate and did not substantially shorten operating time in initial cervical exploration for PHPT. The economic burden of routine preoperative localization studies in these patients is not justified.     

Chemical inhibitors when timing is critical: a pharmacological concept for the maturation of T cell contacts

Cellular signal transduction proceeds through a complex network of molecular interactions and enzymatic activities. The timing of these molecular events is critical for the propagation of a signal and the generation of a specific cellular response. To define the timing of signalling events, we introduce the combination of high-resolution confocal microscopy with the application of small-molecule inhibitors at various stages of signal transduction in T cells. Inhibitors of Src-family tyrosine kinases and actin dynamics were employed to dissect the role of the lymphocyte-specific tyrosine kinase Lck in the formation and maintenance of T cell receptor/CD3-dependent contacts. Anti-CD3epsilon-coated coverslips served as a highly defined stimulus. The kinetics of the recruitment of the yellow fluorescent protein-tagged signalling protein ZAP-70 were detected by high-resolution confocal microscopy. The analysis revealed that at 5 min after receptor engagement, Lck activity was required for maintenance of contacts. In contrast, after 20 min of receptor engagement, the contacts were Lck-independent. The relevance of the timing of inhibitor application provides a pharmacological concept for the maturation of T cell-substrate contacts.     

Sandwich, double-reference-wave, holographic, phase-shift interferometry

Phase-shift interferometry has provided a straightforward method for converting interferograms to phase maps. Unfortunately, some of the most powerful pulsed holographic interferometry techniquesare generally not compatible with phase-shift interferometry. One solution is to employ two reference waves, one for each of the two object waves to be interfered, that can be phase stepped during reconstruction. Practical aberration and alignment problems render this approach difficult. A simple method that employs a second hologram, sandwiched with the first, which produces the required two reference waves during reconstruction, is presented. The process compensates for both chromatic and geometric aberrations that otherwise render the phase-shift method unusable.     

Thermal and slip mechanism effects in rapid indentation by a flat punch

Summary The rapid indentation of a fully-coupled thermoelastic body by a flat, smooth rigid punch is studied in a 2D dynamic analysis. A semi-infinite punch width is assumed to be a valid short-time model, and a zone of slip mechanisms is assumed to form under the punch edge, and to relax the stresses there. The mathematical problem is reduced by superposition and transform methods to a Wiener-Hopf equation which, despite the dependence of poles and branch points on the time transform parameter, can be solved exactly. Imposition of the stress relaxation property of the zone then removes the singularity in punch edge stresses, thereby giving a relation for the contact region temperature change. Because a thermoelastic characteristic length of 0(10^–4)m is the scale factor, this transform can be inverted for so-called long times without invalidating the short-time nature of the model. The inversion shows that, despite the absence of actual plasticity and contact friction, nominal but not negligible temperature increases can occur in the contact region.     

Decision support aids with anthropomorphic characteristics influence trust and performance in younger and older adults

This study examined the use of deliberately anthropomorphic automation on younger and older adults' trust, dependence and performance on a diabetes decision-making task. Research with anthropomorphic interface agents has shown mixed effects in judgments of preferences but has rarely examined effects on performance. Meanwhile, research in automation has shown some forms of anthropomorphism (e.g. etiquette) have effects on trust and dependence on automation. Participants answered diabetes questions with no-aid, a non-anthropomorphic aid or an anthropomorphised aid. Trust and dependence in the aid was measured. A minimally anthropomorphic aide primarily affected younger adults' trust in the aid. Dependence, however, for both age groups was influenced by the anthropomorphic aid. Automation that deliberately embodies person-like characteristics can influence trust and dependence on reasonably reliable automation. However, further research is necessary to better understand the specific aspects of the aid that affect different age groups. Automation that embodies human-like characteristics may be useful in situations where there is under-utilisation of reasonably reliable aids by enhancing trust and dependence in that aid. Practitioner Summary: The design of decision-support aids on consumer devices (e.g. smartphones) may influence the level of trust that users place in that system and their amount of use. This study is the first step in articulating how the design of aids may influence user's trust and use of such systems.     

MicroRNA Regulation of Breast Cancer Stemness

Recent advances in our understanding of breast cancer have demonstrated that cancer stem-like cells (CSCs, also known as tumor-initiating cell (TICs)) are central for progression and recurrence. CSCs are a small subpopulation of cells present in breast tumors that contribute to growth, metastasis, therapy resistance, and recurrence, leading to poor clinical outcome. Data have shown that cancer cells can gain characteristics of CSCs, or stemness, through alterations in key signaling pathways. The dysregulation of miRNA expression and signaling have been well-documented in cancer, and recent studies have shown that miRNAs are associated with breast cancer initiation, progression, and recurrence through regulating CSC characteristics. More specifically, miRNAs directly target central signaling nodes within pathways that can drive the formation, maintenance, and even inhibition of the CSC population. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as biomarkers and promising clinical therapeutics, and presents a comprehensive summary of currently validated targets involved in CSC-specific signaling pathways in breast cancer.