Use of the Analytic Hierarchy Process for Medication Decision-Making in Type 2 Diabetes

AimTo investigate the feasibility and utility of the Analytic Hierarchy Process (AHP) for medication decision-making in type 2 diabetes.MethodsWe conducted an AHP with nine diabetes experts using structured interviews to rank add-on therapies (to metformin) for type 2 diabetes. During the AHP, participants compared treatment alternatives relative to eight outcomes (hemoglobin A1c-lowering and seven potential harms) and the relative importance of the different outcomes. The AHP model and instrument were pre-tested and pilot-tested prior to use. Results were discussed and an evaluation of the AHP was conducted during a group session. We conducted the quantitative analysis using Expert Choice software with the ideal mode to determine the priority of treatment alternatives.ResultsParticipants judged exenatide to be the best add-on therapy followed by sitagliptin, sulfonylureas, and then pioglitazone. Maximizing benefit was judged 21% more important than minimizing harm. Minimizing severe hypoglycemia was judged to be the most important harm to avoid. Exenatide was the best overall alternative if the importance of minimizing harms was prioritized completely over maximizing benefits. Participants reported that the AHP improved transparency, consistency, and an understanding of others’ perspectives and agreed that the results reflected the views of the group.ConclusionsThe AHP is feasible and useful to make decisions about diabetes medications. Future studies which incorporate stakeholder preferences should evaluate other decision contexts, objectives, and treatments.     

Ecological Risk Assessment for Irgarol 1051 and Its Major Metabolite in United States Surface Waters

The objective of this study was to determine the ecological risk of the antifoulant Irgarol 1051 and its major metabolite (GS26575) in United States surface waters by using a probabilistic approach. Distributions of environmental exposure data were compared with the distribution of species response data from laboratory studies to quantify the likelihood and significance of ecological risk. Water monitoring data from both the Chesapeake Bay (2001) and southeast Florida (1999–2001) were used to characterize exposure. Toxicity testing has demonstrated that plants are much more sensitive to Irgarol and GS26575 than animals; therefore, the conservative effects benchmark used to characterize risk was the plant 10th centile for both Irgarol (251 ng/L) and GS26575 (12,500 ng/L). Ecological risk from Irgarol exposure in Chesapeake Bay marinas, a river, and a mainstem area was generally low with the possible exception of the Port Annapolis marina in Annapolis, Maryland. This enclosed marina has a high density of boats, a low flushing rate, and has historically been reported as a “worst case scenario” for other antifoulants such as tributyltin. Ecological risk from GS26575 exposure at Chesapeake Bay sites was judged to be very low as all environmental concentrations were an order of magnitude below the effects threshold for plants. Ecological risk from Irgarol exposure in southeast Florida surface waters was found to be low at various marina, port, river, bay/embayment, channel, and ocean areas. Even the highest Irgarol concentration reported in southeast Florida waters (182 ng/L) was less than the conservative Irgarol effects benchmark of 251 ng/L (plant 10th centile). Ecological risk from GS26575 exposure in southeast Florida waters was also very low.     

Cancer mortality risk among workers at the Mayak nuclear complex

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.     

Brief communication: Why sleep in a nest? empirical testing of the function of simple shelters made by wild chimpanzees

All great apes build nightly a structure ("nest" or "bed") that is assumed to function primarily as a sleeping-platform. However, several other nest function hypotheses have been proposed: antipredation, antipathogen, and thermoregulation. I tested these simple shelter functions of chimpanzee nests in an experiment for which I was the subject in Fongoli, Senegal. I slept 11 nights in chimpanzee nests and on the bare ground to test for differences in sleep quality, potential exposure to disease through bites from possible vectors, and insulation. No difference was found in the total amount of sleep nor in sleep quality; however, sleep was more disturbed on the ground. Differences in sleep disturbance between arboreal and ground conditions seemed primarily due to causes of anxiety and alertness, e.g., vocalizations of terrestrial mammals. Arboreal nest-sleeping seems to reduce risk of bites from possible disease vectors and provide insulation in cold conditions. This preliminary, but direct, test of chimpanzee nest function has implications for the evolutionary transition from limb-roosting to nest-reclining sleep in the hominoids, and from tree-to-ground sleep in the genus Homo.     

Assessing intervention efficacy on high‐risk drinkers using generalized linear mixed models with a new class of link functions

Unhealthy alcohol use is one of the leading causes of morbidity and mortality in the United States. Brief interventions with high‐risk drinkers during an emergency department (ED) visit are of great interest due to their possible efficacy and low cost. In a collaborative study with patients recruited at 14 academic ED across the United States, we examined the self‐reported number of drinks per week by each patient following the exposure to a brief intervention. Count data with overdispersion have been mostly analyzed with generalized linear mixed models (GLMMs), of which only a limited number of link functions are available. Different choices of link function provide different fit and predictive power for a particular dataset. We propose a class of link functions from an alternative way to incorporate random effects in a GLMM, which encompasses many existing link functions as special cases. The methodology is naturally implemented in a Bayesian framework, with competing links selected with Bayesian model selection criteria such as the conditional predictive ordinate (CPO). In application to the ED intervention study, all models suggest that the intervention was effective in reducing the number of drinks, but some new models are found to significantly outperform the traditional model as measured by CPO. The validity of CPO in link selection is confirmed in a simulation study that shared the same characteristics as the count data from high‐risk drinkers. The dataset and the source code for the best fitting model are available in Supporting Information.     

Individual variation in behavioural plasticity: direct and indirect effects of boldness,exploration and sociability on habituation to predators in lizards

Little is known about the factors causing variation in behavioural plasticity and the interplay between personality and plasticity. Habituation to predators is a special case of behavioural plasticity. We investigated the direct and indirect effects of boldness, exploration and sociability traits on the habituation ability of Iberian wall lizards, considering exposure and sex effects. Individual boldness was consistent across several non-habituation contexts, but it did not significantly affect habituation. Exploration had a strong direct effect on habituation, with more exploratory individuals being able to habituate faster than less exploratory ones, probably because of their ability to assess risk better. Individual variation in habituation was also affected by sociability, but this was an indirect effect mediated by exposure to the predator. Less social individuals avoided refuges with conspecific cues, increasing exposure to the predator and eventually habituation. Finally, the direct effects of sex (females habituated faster than males) were opposite to its indirect effects through exposure. We conclude that risk assessment, instead of the proactivity–reactivity gradient usually considered in the literature, can affect behavioural plasticity through complex interactions between direct and indirect effects, including exploratory behaviour, degree of exposure to the predator and sex, which represent novel mechanisms generating inter-individual variation in plasticity.     

Risk Assessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Equivalents in Tissue Samples from Three Species in the Denver Metropolitan Area

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are possible contaminants of concern in areas with a history of organochlorine pesticide production or various other industrial chlo-rination processes. The Rocky Mountain Arsenal (RMA), a Superfund site near Denver, CO, has a history of various industrial processes that may have led to the release of these compounds and subsequent exposure and risk to surrounding biota. PCDDs, and PCDFs, and non- and mono-ortho-substituted PCBs cause a common set of toxic effects that are mediated through the aryl-hydrocarbon receptor (AhR). The total AhR-medi-ated activity of tissue samples collected from the RMA and surrounding reference areas was determined by both instrumental and bioanalytical techniques. Concentrations of dioxin equivalents were measured in carp eggs, great horned owl livers, and American kestrel eggs collected from the RMA and from off-post reference sites. Detected concentrations of dioxin equivalents were used to assess risk to exposed wildlife through the use of Toxicity Reference Values (TRVs) and Hazard Quotients (HQs). Carp and kestrel egg samples had small HQ values, while some great horned owls had relatively large HQ values, indicating exposure to and possible risks from dioxins or dioxin-like chemicals.     

A method for assessing alternative effects functions that uses simulation with EMDEX data

A method for evaluating a variety of alternative biologically plausible effects functions through the use of simulation studies conducted on personal-monitor exposure data is described. Using magnetic field time series collected with EMDEX instruments, we demonstrate how the method can be used to explore (1) how the outputs from various effects functions simulations compare to the results obtained by assuming that effects are proportional to time average field strength; (2) how the results of epidemiological studies might be used to assess the relative likelihood that each of the alternative effects functions describes biological reality; and (3) how the results might be used to assess possible health risks. Although the available data are sufficient to demonstrate the general method, they are not yet sufficient to support actual discrimination among possible alternatives. The arguments on the use of the method are for illustrative purposes only. © 1995 Wiley-Liss, Inc.     

Effects function analysis of ELF magnetic field exposure in the electric utility work environment

The incomplete understanding of the relation between power-frequency fields and biological responses raises problems in defining an appropriate metric for exposure assessment and epidemiological studies. Based on evidence from biological experiments, one can define alternative metrics or effects functions that embody the relationship between field exposure patterns and hypothetical health effects. In this paper, we explore the application of the “effects function” approach to occupational exposure data. Our analysis provides examples of exposure assessments based on a range of plausible effects functions. An EMDEX time series data set of ELF frequency (40–800 Hz) magnetic field exposure measurements for electric utility workers was analyzed with several statistical measures and effects functions: average field strength, combination of threshold and exposure duration, and field strength changes. Results were compared for eight job categories: electrician, substation operator, machinist, welder, plant operator, lineman/splicer, meter reader, and clerical. Average field strength yields a different ranking for these job categories than the ranks obtained using other biologically plausible effects functions. Whereas the group of electricians has the highest exposure by average field strength, the group of substation operators has the highest ranking for most of the other effects functions. Plant operators rank highest in the total number of field strength changes greater than 1 μT per hour. The clerical group remains at the lowest end for all of these effects functions. Our analysis suggests that, although average field strength could be used as a surrogate of field exposure for simply classifying exposure into “low” and “high,” this summary measure may be misleading in the relative ranking of job categories in which workers are in “high” fields. These results indicate the relevance of metrics other than average field strength in occupational exposure assessment and in the design and analysis of epidemiological studies. Bioelectromagnetics 18:365–375, 1997. © 1997 Wiley-Liss, Inc.     

Intracultural Variation in Folk Medical Knowledge: A Comparison Between Curers and Noncurers

This paper investigates variation in folk medical beliefs in a Tarascan community in west-central Mexico. The data are from a structured interview completed with ten traditional curers and a like-sized comparison group of noncurers. Three possible patterns of interinformant agreement are described and tested using the quadratic assignment program. The results suggest that although curers and noncurers do differ, the differences are not so great that they represent two variant systems of medical beliefs. Rather, there is a single system of beliefs common to both groups, but with curers showing higher agreement among themselves in expressing this system than noncurers. This finding, and a related one showing higher agreement among older informants, are explained in terms of culture learning. Curers and older people share more knowledge about illness because of their greater experience in both dealing with and communicating about illness. A model of folk medical knowledge is then presented and systematic variation from this model examined.     

Evaluating alternative exposure indices in epidemiologic studies on extremely low-frequency magnetic fields

Choosing the right exposure index for epidemiological studies on 50–60 Hz magnetic fields is difficult due to the lack of knowledge about critical exposure parameters for the biological effects of magnetic fields. This paper uses data from a previously published epidemiological investigation on early pregnancy loss (EPL) to study the methods of evaluating the exposure-response relationship of 50 Hz magnetic fields. Two approaches were used. The first approach was to apply generalized additive modeling to suggest the functional form of the relationship between EPL and magnetic field strength. The second approach evaluated the goodness of fit of the EPL data with eight alternative exposure indices: the 24 h average of magnetic field strength, three indices measuring the proportion of time above specified thresholds, and four indices measuring the proportion of time within specified intensity windows. Because the original exposure data included only spot measurements, estimates for the selected exposure indices were calculated indirectly from the spot measurements using empirical nonlinear equations derived from 24 h recordings in 60 residences. The results did not support intensity windows, and a threshold-type dependence on field strength appeared to be more plausible than a linear relationship. In addition, the study produced data suggesting that spot measurements may be used as surrogates for other exposure indices besides the time average field strength. No final conclusions should be drawn from this study alone, but we hope that this exercise stimulates evaluation of alternative exposure indices in other planned and ongoing epidemiological studies. © 1996 Wiley-Liss, Inc.     

Contrast and range effects for category, magnitude and labeled magnitude scales in judgements of sweetness intensity

The labeled magnitude scale (LMS) is a verbally anchored quasi-logarithmically spaced response scale with properties similar to magnitude estimation. Three experiments examined whether the LMS showed context effects similar to those found with magnitude estimation and category scales. Two versions of the LMS were used, one anchored at the high end to the strongest imaginable sweetness and the other to the strongest imaginable oral sensation. In a simple contrast experiment, subjects judged the sweetness of a 10% sucrose fruit beverage in the context of a less sweet (5%) beverage or a more sweet (20%) beverage. Consistent with previous literature, the sweetness was judged more intense in the low context and less intense in the high context, for all scaling methods. In a second experiment, this effect persisted (although was smaller) when the contextual item preceded the to-be-rated item, a so-called 'reversed-pair' design. Once again, the effect was highly significant for all scaling methods. In a third experiment, a range effect was examined using wide and narrow ranges of concentration. Psychophysical functions were flatter in a wide context and steeper in a narrow context, consistent with previous observations on range-mapping bias. This result was obtained for all scales. In three common contextual effects, the labeled magnitude scale behaved similarly to other scaling procedures. Its application to comparisons across individuals may be limited if those individuals have different experiential contexts within which they make their judgements.     

The prognosis of hyperlysinemia: an interim report.

Ten patients with familial hyperlysinemia with lysine-ketoglutarate reductase deficiency, identified through newborn screening programs or family surveys, were selected for review. Ages ranged from 2 to 24 years when last examined. A low-protein diet had been administered to two patients, which reduced the plasma lysine levels from 20 mg per dl or more to about 12 mg per dl. The rest were untreated. Mental development was judged normal or above average in nine. Mildly subnormal performance in three was considered appropriate to family and social background. No adverse mental or physical effects could be attributed to the hyperlysinemia. A normal child has been born to a mother with hyperlysinemia, indicating that the fetus may develop normally despite exposure to high lysine levels.     

Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three consecutive studies

Certain epidemiological and experimental studies raised concerns about the safety of radiofrequency (RF) electromagnetic fields because of a possible increased risk of leukemia and lymphoma. In this study, an RF field used in mobile telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats as a model for human breast cancer. Three experiments were carried out under strictly standardized conditions and were started on the same day of three consecutive years. The field consisted of a GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively low power flux density (100 microW/cm(2) +/- 3 dB) and was applied continuously throughout each experiment to freely moving animals. The specific absorption rates averaged over the whole body were 17.5-70 mW/kg. The highest values in young animals were at or around the exposure limit permissible for the general public (i.e. 80 mW/kg). The animals were palpated weekly for the presence of mammary tumors and were killed humanely when tumors reached a diameter of 1-2 cm to allow a reliable histopathological classification and a distinction between malignant and benign subtypes. The overall results of the three studies are that there was no statistically significant effect of RF-field exposure on tumor latency and that the cumulative tumor incidence at the end of the experiment was unaffected as well. The risk ratios were 1.08 (95% CI: 0.91-1.29) and 0.96 (95% CI: 0.85-1.07) for benign and malignant tumors, respectively. These observations are in agreement with other published findings. In the first experiment, however, the median latency for the development of the first malignant tumor in each animal was statistically significantly extended for RF-field-exposed animals compared to controls (278 days compared to 145 days, P = 0.009). No such differences were detected in the two subsequent experiments. These results show that low-level RF radiation does not appear to possess carcinogenic or cancer-promoting effects on DMBA-induced mammary tumors. To explain the mechanisms underlying the different results obtained in the three experiments, a hypothesis is presented which is based upon the neuroendocrine control mechanisms involved in the promotion of DMBA-induced mammary tumors. Despite the apparent absence of stimulatory effects of low-level RF-field exposure on the development and growth of solid tumors, it will be necessary to verify these results for leukemias and lymphomas, which may have completely different biological control mechanisms.     

Methodologies for predicting the expected combined stochastic radiobiological effects of different ionizing radiations and some applications

A methodology for predicting the expected combined stochastic radiobiological effects of sequential exposure to different ionizing radiations is used to arrive at a methodology for predicting the radiobiological effects of simultaneous exposure. Both methodologies require developing additive-damage dose-effect models. Additive-damage dose-effect models are derived assuming (a) each radiation comprised by the combined exposure produces initial damage called critical damage that could lead to the radiobiological effect of interest; (b) doses of different radiations that lead to the same level of radiobiological effect (or risk) can be viewed as producing the same amount of critical damage and being indistinguishable as far as the effects of subsequently administered radiation. Derived dose-effect functions that describe the risk per individual, conditional on radiation dose, are called risk functions. The methodologies allow the use of known radiation-specific risk functions to derive risk functions for combined effects of different radiations. The risk functions for combined exposure to different radiations are called global risk functions. For sequential exposures to different ionizing radiations, the global risk functions derived depend on how individual radiation doses are ordered. Global risk functions can also differ for sequential and simultaneous exposure. The methodologies are used to account for some previously unexplained radiobiological effects of combined exposure to high and low linear-energy-transfer radiations.     

Melanoma and ionizing radiation: is there a causal relationship?

This review was initiated in response to concerns that ionizing radiation could be a cause of melanoma. Studies presenting the relative risks for melanoma after external ionizing radiation exposure were in seven categories: (1) The Canadian Radiation Dose Registry, (2) nuclear industry workers, (3) subjects near nuclear test blasts, (4) survivors of the atomic bombings of Japan, (5) airline pilots and cabin attendants, (6) recipients of medical radiation, and (7) radiological technicians. Relative risks for leukemia in each of the studies were used to confirm the likelihood of exposure to ionizing radiation. When studies within a category were compatible, meta-analytic methods were used to obtain combined estimates of the relative risk, and a meta-regression analysis of melanoma relative risk compared to leukemia relative risk was used to examine consistency across exposure categories. Generally, exposure categories with elevated relative risks of leukemia had proportionately elevated relative risks of melanoma. This suggests that people exposed to ionizing radiation may be at increased risk of developing melanoma, although alternative explanations are possible. Future epidemiological studies of ionizing radiation effects should include melanoma as an outcome of interest.     

Effects of 900 MHz electromagnetic fields exposure on cochlear cells' functionality in rats: evaluation of distortion product otoacoustic emissions

In recent years, the widespread use of mobile phones has been accompanied by public debate about possible adverse consequences on human health. The auditory system is a major target of exposure to electromagnetic fields (EMF) emitted by cellular telephones; the aim of this study was the evaluation of possible effects of cellular phone-like emissions on the functionality of rat's cochlea. Distortion Products OtoAcoustic Emission (DPOAE) amplitude was selected as cochlea's outer hair cells (OHC) status indicator. A number of protocols, including different frequencies (the lower ones in rat's cochlea sensitivity spectrum), intensities and periods of exposure, were used; tests were carried out before, during and after the period of treatment. No significant variation due to exposure to microwaves has been evidenced.     

Prenatal exposure to radiofrequencies: Effects of WiFi signals on thymocyte development and peripheral T cell compartment in an animal model

Wireless local area networks are an increasing alternative to wired data networks in workplaces, homes, and public areas. Concerns about possible health effects of this type of signal, especially when exposure occurs early in life, have been raised. We examined the effects of prenatal (in utero) exposure to wireless fidelity (WiFi) signal‐associated electromagnetic fields (2450 MHz center‐frequency band) on T cell development and function. Pregnant mice were exposed whole body to a specific absorption rate of 4 W/kg, 2 h per day, starting 5 days after mating and ending 1 day before the expected delivery. Sham‐exposed and cage control groups were used as controls. No effects on cell count, phenotype, and proliferation of thymocytes were observed. Also, spleen cell count, CD4/CD8 cell frequencies, T cell proliferation, and cytokine production were not affected by the exposure. These findings were consistently observed in the male and female offspring at early (5 weeks of age) and late (26 weeks of age) time points. Nevertheless, the expected differences associated with aging and/or gender were confirmed. In conclusion, our results do not support the hypothesis that the exposure to WiFi signals during prenatal life results in detrimental effects on the immune T cell compartment. Bioelectromagnetics 33:652–661, 2012. © 2012 Wiley Periodicals, Inc.     

The Role of Social Contexts in Adolescence: Context Protection and Context Risk in the United States and China

A theoretical framework about protective factors (models protection, controls protection, support protection) and risk factors (models risk, opportunity risk, vulnerability risk) was employed to articulate the content of 4 key contexts of adolescent life—family, peers, school, and neighborhood—in a cross-national study of problem behavior among 7th-, 8th-, and 9th-grade adolescents in the United States (n = 1,596) and the People's Republic of China (n = 1,739). Results were very similar in both samples and across genders. Measures of protection and risk in each of the 4 contexts uniquely contributed to the account of problem behavior involvement even when individual-level measures of protection and risk were controlled. Context protection was also shown to moderate individual-level risk and protection in 1 context moderated risk within that context and in other contexts. Controls protection—protection provided by rules, regulations, and expected sanctions for transgression from adults and peers—was the most important measure of context protection in all but 1 context. The family and peer contexts were the most influential in the U.S. sample, and the peer and school contexts were the most influential in the Chinese sample; the neighborhood context was least influential in both samples.