This paper is one of several in this Special Issue of the International Journal of Hyperthermia that discusses the current state of knowledge about the human health risks of hyperthermia. This special issue emanated from a workshop sponsored by the World Health Organization in the Spring of 2002 on this topic. It is anticipated that these papers will help to establish guidelines for human exposure to conditions leading to hyperthermia. This comprehensive review of the literature makes it clear that much more work needs to be done to clarify what the thresholds for thermal damage are in humans. This review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature are provided as well as a detailed discussion about the underlying assumptions that go into these calculations. There are few in vivo papers examining the type and extent of damage that occurs in the lower temperature range for hyperthermic exposures (e.g. 39-42 degrees C). Therefore, it is clear that estimation of thermal dose to effect at these thermal exposures is less precise in that temperature range. In addition, there are virtually no data that directly relate to the thermal sensitivity of human tissues. Thus, establishment of guidelines for human exposure based on the data provided must be done with significant caution. There is detailed review and presentation of thermal thresholds for tissue damage (based on what is detectable in vivo). The data are normalized using thermal dosimetric concepts. Tables are included in an Appendix Database which compile published data for thresholds of thermal damage in a variety of tissues and species. This database is available by request (contact MWD or PJH), but not included in this manuscript for brevity. All of the studies reported are for single acute thermal exposures. Except for brain function and physiology (as detailed in this issue by Sharma et al) one notes the critical lack of publications examining effects of chronic thermal exposures as might be encountered in occupational hazards. This review also does not include information on the embryo, which is covered in detail elsewhere in this volume (see article by Edwards et al.) as well as in a recent review on this subject, which focuses on thermal dose.

Ultrasmall fluorescent silica nanoparticles (SNPs) and core−shell SNPs surface functionalized with polyethylene glycol (PEG), specific surface ligands, and overall SNP size in the regime below 10 nm are of rapidly increasing interest for clinical applications, because of their favorable biodistribution and safety profiles. Here, we present an aqueous synthesis methodology for the preparation of narrowly size-dispersed SNPs and core−shell SNPs with size control below 1 nm, i.e., at the level of a single atomic layer. Different types of fluorophores, including near-infrared (NIR) emitters, can be covalently encapsulated. Brightness can be enhanced via addition of extra silica shells. This methodology further enables synthesis of <10 nm sized fluorescent core and core−shell SNPs with previously unknown compositions. In particular, the addition of an aluminum sol gel precursor leads to fluorescent aluminosilicate nanoparticles (ASNPs) and core−shell ASNPs. Encapsulation efficiency and brightness of highly negatively charged NIR fluorophores is enhanced, relative to the corresponding SNPs without aluminum. Resulting particles show quantum yields of ∼0.8, i.e., starting to approach the theoretical brightness limit. All particles can be PEGylated providing steric stability. Finally, heterobifunctional PEGs can be employed to introduce ligands onto the PEGylated particle surface of fluorescent SNPs, core−shell SNPS, and their aluminum-containing analogues, producing ligand-functionalized <10 nm NIR fluorescent nanoprobes. In order to distinguish these water-based-synthesis-derived materials from the earlier alcohol-based modified Stober process derived fluorescent core−shell SNPs referred to as Cornell dots or C dots, the SNPs and ASNPs described here and synthesized in water will be referred to as Cornell prime dots or C′ dots and AlC′ dots. These organic−inorganic hybrid nanomaterials may find applications in nanomedicine, including cancer diagnostics and therapy (theranostics).

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In this review we have summarized the basic principles that govern the relationships between thermal exposure (Temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. We have also attempted to identify specific thermal dose information (for safety and injury) for a variety of tissues in a variety of species. We address the use, accuracy and difficulty of conversion of an individual time and temperature (thermal doses) to a standardized value (eg equivalent minutes at 43 degrees C) for comparison of thermal treatments. Although, the conversion algorithm appears to work well within a range of moderately elevated temperatures (2-15 deg C) above normal physiologic baseline (37-39 deg C) there is concern that conversion accuracy does not hold up for temperatures which are minimally or significantly above baseline. An extensive review of the literature suggests a comprehensive assessment of the "thermal doesto-tissue effect" has not previously been assembled for most individual tissues and never been viewed in a semi-comprehensive (tissues and species) manner.Finally, we have addressed the relationship of thermal does-to-effect vs. baseline temperature. This issues is important since much of the thermal dose-to-effect information has been accrued in animal models with baseline temperatures 1-2 deg higher than that of humans. INTRODUCTIONThe purpose of this review is to present basic concepts relating thermal dose (time at temperature) to cell killing and tissue damage. © 2003 SPIE HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThis review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature (cumulative minutes at 43° / CEM) are provided as well as some discussion about the underlying assumptions that go into these calculations. There are few in vivo papers, examining the type and extent of damage that occurs in the lower temperature range for hypothermic exposures (e.g. 39-42°C). Although not specifically calculated, the authors believe the CEM analysis for estimating an equivalent thermal does not retain a high degree of accuracy when temperatures above 55°C or so. Therefore it is appears that estimation of thermal dose to effect at low (temperatures a few degree above baseline body temperature) and high temperatures are more difficult to assesses and quantify. It is also apparent from this review that an extremely large variation in the type and the quality of tissue damage endpoint assessment significantly affects the ability to accurately compared study results.The authors have assembled a detailed review of thermal thresholds for tissue damage in the majority of organs (based on what is detectable in vivo). The data are normalized using thermal dosimeter concepts. This database is available by reques...

The risk of psychiatric patient assaults on staff members is increasing yearly, with resultant increases in employee victim suffering, medical expense, and lost productivity. Traditionally considered a clinician responsibility, the management of patient violence also has important administrative implications. This article presents a review of the risk factors associated with violence that includes the characteristics of patients who assault but adds the characteristics of employee victims of such assaults as well as contextual variables. Additional data from a two-year study of a peer-help crisis intervention program for employee victims of patient assaults are included. The mental health administrative implications of this approach are outlined.