Debate: Subgroup analyses in clinical trials: fun to look at - but don't believe them!

Analysis of subgroup results in a clinical trial is surprisingly unreliable, even in a large trial. This is the result of a combination of reduced statistical power, increased variance and the play of chance. Reliance on such analyses is likely to be more erroneous, and hence harmful, than application of the overall proportional (or relative) result in the whole trial to the estimate of absolute risk in that subgroup. Plausible explanations can usually be found for effects that are, in reality, simply due to the play of chance. When clinicians believe such subgroup analyses, there is a real danger of harm to the individual patient.     

A simple reason for a big difference: wolves do not look back at humans,but dogs do

The present investigations were undertaken to compare interspecific communicative abilities of dogs and wolves, which were socialized to humans at comparable levels. The first study demonstrated that socialized wolves were able to locate the place of hidden food indicated by the touching and, to some extent, pointing cues provided by the familiar human experimenter, but their performance remained inferior to that of dogs. In the second study, we have found that, after undergoing training to solve a simple manipulation task, dogs that are faced with an insoluble version of the same problem look/gaze at the human, while socialized wolves do not. Based on these observations, we suggest that the key difference between dog and wolf behavior is the dogs' ability to look at the human's face. Since looking behavior has an important function in initializing and maintaining communicative interaction in human communication systems, we suppose that by positive feedback processes (both evolutionary and ontogenetically) the readiness of dogs to look at the human face has lead to complex forms of dog-human communication that cannot be achieved in wolves even after extended socialization.     

G protein-coupled receptor dimers: look like their parents,but act like teenagers!

Abstract

G protein-coupled receptors (GPCRs) represent the largest group of cell surface receptors and an important pharmacological target. Though originally thought to act in a one receptor–one effector fashion, it is now known that these receptors are capable of oligomerization and can function as dimers or higher order oligomers in native tissue. They do not only assemble with identical receptors as homodimers, but also associate with different GPCRs to form heterodimers. We discuss here how heterodimeric GPCRs can assemble, traffic and signal in a manner distinct from their individual receptor components or from homodimers. These receptor pairs are also demonstrated to be regulated by different chaperones, Rabs and scaffolding proteins, further emphasizing their potential as unique targets. We believe in the importance of investigating each GPCR heterodimer as an individual signaling complex, as they appear to act differently from each monomer constituting them. Just as teenagers may resemble their parents and share their genetic makeup, they can still act in a manner that is entirely unique!     

Mathematical biophysics of color vision II: Theory of color changes induced by the alternation of colors at various frequencies.

A model previously introduced to account for a number of phenomena of color vision is studied for the conditions in which the alternation of colors is periodic. The case of three primary receptors having no differences in their time constants is considered for the situations such as the temporal alternation of two primaries, a primary and a neighboring binary, a primary and white, a binary and white, etc. Using the same mathematical model which was used to account for the enhancement effect of interrupted illumination, it is found possible to account for observed changes in hue in a qualitative manner. A method is suggested for measuring the color changes quantitatively. This method is readily adapted for demonstration purposes. The model shows that there should be differences between “primaries” and “binaries” with respect to change in hue. In principle, therefore, comparison between theory and experiment should yield information regarding the physiological primaries. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command under contract No. AF 18 (600) 1454.     

Differential facial resemblance of young children to their parents: who do children look like more?

In humans, paternal investment is highly variable and is modulated by paternity uncertainty. Facial phenotypic similarity between a father and a child is one possible paternity indicator. However, whether such paternal-biased traits are expressed in children is unclear, as previous empirical results are contradictory. Therefore, we quantified the facial resemblance between a child and each of his or her parents, from birth to 6 years old. Resemblance was assessed from pictures of the face by nonrelated judges. We found that, at all ages, children resemble both their parents more than would be expected by chance, although there is a differential resemblance toward one or the other parent depending on the age and sex of the child. For newborns, boys and girls resemble their mothers more, this differential resemblance persisting through time for girls. For boys, an inversion occurs and they resemble their fathers more between 2 and 3 years of age. The resemblance ascribed by the parents shows that, at birth, mothers ascribe a resemblance to the father, as previously found, although assessment by external judges revealed the opposite. These results suggest that facial appearance is a cue for kin recognition between a father and a child. Patterns of differential resemblance are discussed within the context of evolutionary theories on parental investment.     

Granulocyte-macrophage colony-stimulating factor （GM-CSF） and T-cell responses： what we do and don＇t know

Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.     

Actinomycetes and their products: a look at the future

World Journal of Microbiology and Biotechnology -     

Not all colors are equal: predation and color polytypism in the aposematic poison frog Oophaga pumilio

Aposematic organisms are not predicted to show high levels of warning signal diversity because they are expected to be under stabilizing selection to decrease costs of ‘educating’ predators about their unpalatability. However, systematic changes in warning signals (polytypism) can be expected if they represent adaptations to local predators. The aposematic strawberry poison frog (Oophaga pumilio) is red throughout its mainland distribution in Costa Rica and Panamá, but displays high levels of warning signal diversity in the Bocas del Toro Archipelago of Panamá. Both coloration and spot pattern vary in a polytypic sense. Sexual selection contributes to maintaining the polytypism, but little work has investigated the potential influence of predation. We used unspotted models of O. pumilio to determine if predation might help explain the color polytypism on Isla Colón in the Bocas del Toro Archipelago of Panamá. We tested whether attack rates differed among the red mainland morph, green/yellow Isla Colón morph, and the brown control. We found that frog color significantly predicted being attacked. The local green Isla Colón models were attacked more than foreign red or brown models. No difference in attack rate existed between red and brown control models. Our results suggest that the red mainland morph possesses a more effective warning signal, even when it is not the local morph. Honest signaling of unpalatability, neophobia, and the use of search images by local predators are potential explanations. Similarity of the brown model to other local poison frogs might explain the lower attack rate compared to previous work. The attack rate was lower on Isla Colón compared to mainland Costa Rica, which supports the hypothesis that less overall predation in the Bocas del Toro Archipelago may contribute to the overall warning signal diversity in O. pumilio there by relaxing selection for aposematic traits.     

"Actually, I don't feel that bad": managing diabetes and the clinical encounter

A major issue for persons treating and managing adult-onset diabetes (NIDDM) is the "problem of compliance." I consider the clinical encounter in the overall context of diabetes management as a punctuated experience focused on the cultivation of an ideal self whose "technologies" and "ethics of self-care" mimic a capitalist logic that links self-discipline, productivity, and health. Both clinicians and their patients share and identify with many of the cultural referents and social values that circulate through medical advice and practice. However, using individual examples, I show how this shared logic can produce idiosyncratic regimes of self-care and clinical practice that result in hybrid medical practices incorporating differing objectives and emphases concerned with a tolerable present or an ideal future. Rather than organizing principles for research and medical practice, I suggest that medical compliance and noncompliance should be considered part of the rhetoric to be explained within the regimes of a pursuit of health.     

Enrichment and nonhuman primates: "first, do no harm"

Since the 1998 publication of The Psychological Well-Being of Nonhuman Primates by the National Research Council, and the 1991 implementation of the 1985 Animal Welfare Act Amendment, many formal and informal nonhuman primate enrichment programs have been put into practice. Reports of their successes and failures, however, are few. All programs have at least two things in common: (1) They are best when designed and maintained by teams of individuals with species-specific expertise; (2) the members of those teams, the stakeholders, usually include principal investigators, animal care and use committee members, veterinarians, and animal care staff. Discussions in this article address general principles about enrichment, goals of such programs from the perspective of each of the major stakeholders, and recently published sources of related information. These discussions follow the central premise that enrichment should benefit all involved and "First, do no harm."     

Red blood cells that do and red blood cells that don't: how to resist a persistent parasite

Sixty years ago, Haldane proposed that certain abnormalities in red blood cells could be selected as malaria-resistance genes. Population studies have confirmed that many human polymorphisms confer resistance to severe malaria, although the mechanisms of protection remain unknown. A recent article proposes a new mechanism for explaining the protective effects of hemoglobin C (HbC). HbC-containing red blood cells have modified displays of malaria surface proteins that reduce parasite adhesiveness and could reduce the risk of severe disease.     

The biological basis of a universal constraint on color naming: cone contrasts and the two-way categorization of colors

Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming. Here we report that the two-way categorization along the fault line is correlated with the sign of the L- versus M-cone contrast of a stimulus color. Moreover, we found that the sign of the L-M cone contrast also accounted for the two-way clustering of the spatially distributed neural responses in small regions of the macaque primary visual cortex, visualized with optical imaging. These small regions correspond to the hue maps, where our previous study found a spatially organized representation of stimulus hue. Altogether, these results establish a direct link between a universal constraint on color naming and the cone-specific information that is represented in the primate early visual system.     

Intestinal "bioavailability" of solutes and water: we know how but not why.

Only minimal quantities of ingested and normally secreted solutes and water are excreted in the stool. This near 100% bioavailability means that the diet and kidneys are relatively more important determinants of solute, water and acid-base balance than the intestine. Intestinal bioavailability is based on excess transport capacity under normal conditions and the ability to adapt to altered or abnormal conditions. Indeed, the regulatory system of the intestine is as complex, segmented and multi factorial as in the kidney. Alterations in the rate and intestinal site of absorption reflect this regulation, and the diagnosis and treatment of various clinical abnormalities depend on the integrity of intestinal absorptive processes. However, the basis for this regulation an bioavailability are uncertain. Perhaps they had survival value for mammals, a phylogenic class that faced the twin threats of intestinal pathogens and shortages of solutes and water.