Neuroendocrine neoplasms of the sinonasal region

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small‐cell and large‐cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high‐grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2259–E2266, 2016     

Untangling the alliance-outcome correlation: exploring the relative importance of therapist and patient variability in the alliance

Although the therapeutic alliance is a consistent predictor of psychotherapy outcomes, research has not distinguished between the roles of patient and therapist variability in the alliance. Multilevel models were used to explore the relative importance of patient and therapist variability in the alliance as they relate to outcome among 331 patients seen by 80 therapists (therapist average caseload was 4.1). Patients rated both the alliance and outcome and all models adjusted for baseline psychological functioning. The results indicated that therapist variability in the alliance predicted outcome, whereas patient variability in the alliance was unrelated to outcome. Reasons why therapist variability as opposed to patient variability predicted outcome are discussed. Clinical implications include therapists monitoring their contribution to the alliance, clinics providing feedback to therapists about their alliances, and therapists receiving training to develop and maintain strong alliances.     

Development and application of an oral challenge mouse model for studying Clostridium perfringens type D infection

Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections.     

Which are the best nations and institutions for revolutionary science 1987–2006? Analysis using a combined metric of Nobel prizes,Fields medals,Lasker awards and Turing awards (NFLT metric)

I have previously suggested that Nobel prizes can be used as a scientometric measurement of 'revolutionary science'; and that for this purpose it would be better if more Nobel prizes were awarded, especially in three new subjects of mathematics, medicine and computing science which have become major sciences over recent decades. In the following analysis of the last 20 years from 1987 to 2006, I use three prestigious prizes in mathematics (Fields medal), medicine (Lasker award for Clinical Medical Research) and computing science (A.M. Turing award) which are plausible surrogates for Nobel prizes. The combined Nobel-Fields-Lasker-Turing (NFLT) metric is strongly dominated by the USA. However the distribution implies that revolutionary science may be somewhat more broadly distributed than the pure Nobel metric suggests. The UK and France seem to be significant nations in some types of revolutionary science (although the UK has declined substantially as a centre of revolutionary science); and Germany, Switzerland, Japan, Russia, Denmark and Norway also feature. The top world institutions for revolutionary science according to NFLT are MIT, Stanford and Princeton - all in the USA - and the USA has 19 institutions with at least three prize-winners. Second is France, with three institutions having three or more winners; the UK and Norway have one each. The NFLT metric confirms previous observations that many public universities in the Western USA have now become a major focus of revolutionary science; and that Harvard has declined from its previous status as the top world centre of revolutionary science to about seventh-place. This analysis confirms the potential value of increasing the number of Nobel prizes as a means of identifying and monitoring centres of excellence in revolutionary science.     

Psychological neoteny and higher education: associations with delayed parenthood

In a recent Medical Hypotheses editorial, I suggested the name psychological neoteny (PN) to refer to the widely-observed phenomenon that adults in modernizing liberal democracies increasingly retain many of the attitudes and behaviors traditionally associated with youth. I further suggested that PN is a useful trait for both individuals and the culture in modernizing societies; because people need to be somewhat child-like in their psychology order to keep learning, developing and adapting to the rapid and accelerating pace of change. Thirdly, I put forward the hypothesis that the major cause of PN in modernizing societies is the prolonged duration of formal education. Here I present a preliminary empirical investigation of this hypothesis of psychological neoteny. Marriage and parenthood are indicative of making a choice to 'settle down' and thereby move on from the more flexible lifestyle of youth; and furthermore these are usually commitments which themselves induce a settling down and maturation of attitudes and behaviors. A sevenfold expansion of participation in UK higher education up to 2001 was reflected in delay in marriage and parenthood. Increasing number of years of education is quantitatively the most important predictor of increasing age of the mother at the time of her first birth: among women college graduates about half are aged 30 or older at the time of their first birth--a rise of 400% in 25 years. Parenthood is associated with a broad range of psychologically 'maturing' and socially-integrating effects in both men and women. However, the economic effect is different in men and women: after parenthood men are more likely to have a job and work more hours while women change in the opposite direction. The conclusion is that psychological neoteny is indeed increasing, and mainly as a consequence of the increasing percentage of school leavers going into higher education. But at present it is unclear whether this trend is overall beneficial or harmful; and the answer may be different for men and women.