Reproducibility and validity of a food frequency questionnaire in European and polynesian New Zealanders

The reproducibility and validity of a self‐administered 142‐item food‐frequency questionnaire (FFQ) was assessed in a population comprising 124 European and 52 Polynesian (17 Maori and 35 Pacific Island) New Zealanders aged 40–65 years. Reproducibility correlation coefficients, determined by administration of the same questionnaire on two occasions 3 years apart, were higher in European than Maori and Pacific Island. participants, ranging from 0.47 to 0.87 in Europeans (median 0.66) and from 0.41 to 0.79 in Maori and Pacific Island people (median 0.44). In general, there were no significant differences in mean nutrient intakes calculated from the two FFQs by Europeans or Maori and Pacific Island participants despite their cultural and language differences. When the FFQ was compared with a 3‐day food diary in a sub sample of 101 Europeans, 15 Maori and 22 Pacific Islanders, the validity was good for most nutrients, with overestimation of a few nutrients in each ethnic group. Correlation coefficients between the 3‐day food diary and FFQ ranged from 0.41 to 0.81 in Europeans (median 0.48) and from 0.36 to 0.56 in Maori and Pacific Island people (median 0.55). Ratios of energy intake to resting metabolic rate suggested that Maori and Pacific Island people were more likely to underestimate their habitual energy intake by the 3‐day diet diary method compared to Europeans, but that Europeans were more likely to underestimate total energy intake by the food frequency method and Pacific Island participants to overestimate it. Obese Europeans and Maori were more likely to under‐report dietary intakes by the 3‐day diary method. We conclude that our FFQ performed better in European than Maori and Pacific Island participants.     

Evaluation of an Alaskan streptococcal control program: Importance of the program''s intensity and duration

Prospective follow-up information from the throat culturing results of 1,653 Eskimo children in 12 Alaskan villages was used to evaluate the effect of duration and intensity of a streptococcal control program begun in 1971 while controlling for several other risk factors related to streptococcal colonization. Relative risks of colonization for each of the subsequent study years relative to the first year indicate that the risk of colonization decreased over the duration of the study by 42% in Year 2 to 55% in Year 4 (P less than 0.0001). Cost-cutting measures such as lengthening the time interval between routine throat cultures led to a 37% increase in the risk of colonization (P = 0.0002). A comparison of the number of cases of acute rheumatic fever during the 5-year period before the streptococcal control program with the number of cases during the 5-year program period showed that cases in villages with the program decreased from 11 to 0. In a similar group of comparison villages without the program, the number of cases decreased from 7 to 4. A benefit-cost study of the program indicates that benefit exceeds cost. These findings and the changes in the carriage of streptococcal organisms during the control program underscore the importance of such long-term programs with regularly scheduled culturing in high-risk populations of children.     

Conceptual crises and the addictions: A philosophy of science perspective

This article examines the field of addictions and suggests that it is in the midst of a conceptual crisis. As a result of its immaturity, the addiction's field evidences energy, naivete, curiosity, intensely conflicting and polarized explanations of its identity and purpose, anomalous research findings, and few “facts”. From a philosophy of science perspective, these characteristics are considered as indicators of the developmental stages that are associated with the evolotion of scientific disciplines. A philosophy of science perspective is applied to the history of the substance abuse field and the consequent implications examined. A discussion of normal science, language, the role of paradigms, and scientific reductionism is included.     

MK-2206 Causes Growth Suppression and Reduces Neuroendocrine Tumor Marker Production in Medullary Thyroid Cancer Through Akt Inhibition

Background

Development of targeted therapies for medullary thyroid cancer (MTC) has focused on inhibition of the rearranged during transfection (RET) proto-oncogene. Akt has been demonstrated to be a downstream target of RET via the key mediator phosphoinositide-3-kinase. MK-2206 is an orally administered allosteric Akt inhibitor that has exhibited minimal toxicity in phase I trials. We explored the antitumor effects of this compound in MTC.

Methods

Human MTC-TT cells were treated with MK-2206 (0–20 μM) for 8 days. Assays for cell viability were performed at multiple time points with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The mechanism of action, mechanism of growth inhibition, and production of neuroendocrine tumor markers were assessed with Western blot analysis.

Results

MK-2206 suppressed MTC cell proliferation in a dose-dependent manner (p ≤ 0.001). Levels of Akt phosphorylated at serine 473 declined with increasing doses of MK-2206, indicating successful Akt inhibition. The apoptotic proteins cleaved poly (ADP-ribose) polymerase and cleaved caspase-3 increased in a dose-dependent manner with MK-2206, while the apoptosis inhibitor survivin was markedly reduced. Importantly, the antitumor effects of MK-2206 were independent of RET inhibition, as the levels of RET protein were not blocked.

Conclusions

MK-2206 significantly suppresses MTC proliferation without RET inhibition. Given its high oral bioavailability and low toxicity profile, phase II studies with this drug alone or in combination with RET inhibitors are warranted.