Evidence-based alternative medicine?

The validity of evidence-based medicine (EBM) is the subject of ongoing controversy. The EBM movement has proposed a "hierarchy of evidence," according to which randomized controlled trials (RCTs) and meta-analyses of RCTs provide the most reliable evidence concerning the efficacy of medical interventions. The evaluation of alternative medicine therapies highlights problems with the EBM hierarchy. Alternative medical researchers-like those in mainstream medicine-wish to evaluate their therapies using methods that are rigorous and that are consistent with their philosophies of medicine and healing. These investigators have three ways to relate their work to EBM. They can accept the EBM hierarchy and carry out RCTs when possible; they can accept the EBM standards but argue that the special characteristics of alternative medicine warrant the acceptance of "lower" forms of evidence; or they can challenge the EBM approach and work to develop new research designs and new standards of evidence that reflect their approach to medical care. For several reasons, this last option is preferable. First, it will best meet the needs of alternative medicine practitioners. Moreover, because similar problems beset the evaluation of mainstream medical therapies, reevaluation of standards of evidence will benefit everyone in the medical community--including, most importantly, patients.     

Community assembly: alternative stable states or alternative transient states?

The concept of alternative stable states has long been a dominant framework for studying the influence of historical contingency in community assembly. This concept focuses on stable states, yet many real communities are kept in a transient state by disturbance, and the utility of predictions for stable states in explaining transient states remains unclear. Using a simple model of plant community assembly, we show that the conditions under which historical contingency affects community assembly can differ greatly for stable versus transient states. Differences arise because the contribution of such factors as mortality rate, environmental heterogeneity and plant-soil feedback to historical contingency changes as community assembly proceeds. We also show that transient states can last for a long time relative to immigration rate and generation time. These results argue for a conceptual shift of focus from alternative stable states to alternative transient states for understanding historical contingency in community assembly.     

Tumor microenvironment–associated modifications of alternative splicing

Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors.     

Is alternative splicing of mammalian genes conservative?

The conservation of alternative splicing in orthologous genes from the human and mouse genomes was analyzed. Alternatively spliced mouse genes from the AsMamDB database were used to scan the draft human genome. The mouse protein isoforms were aligned with respect to orthologous human genes, and thus the exon-intron structure of the latter was established. Proteins isoforms that could not be aligned throughout their length were analyzed in detail using the human EST alignment.     

A fluorescent ligand-binding alternative using Tag-lite® technology

G-protein-coupled receptors (GPCRs) are crucial cell surface receptors that transmit signals from a wide range of extracellular ligands. Indeed, 40% to 50% of all marketed drugs are thought to modulate GPCR activity, making them the major class of targets in the drug discovery process. Binding assays are widely used to identify high-affinity, selective, and potent GPCR drugs. In this field, the use of radiolabeled ligands has remained so far the gold-standard method. Here the authors report a less hazardous alternative for high-throughput screening (HTS) applications by the setup of a nonradioactive fluorescence-based technology named Tag-lite(?). Selective binding of various fluorescent ligands, either peptidic or not, covering a large panel of GPCRs from different classes is illustrated, particularly for chemokine (CXCR4), opioid (δ, μ, and κ), and cholecystokinin (CCK1 and CCK2) receptors. Affinity constants of well-known pharmacological agents of numerous GPCRs are in line with values published in the literature. The authors clearly demonstrate that the Tag-lite binding assay format can be successfully and reproducibly applied by using different cellular materials such as transient or stable recombinant cells lines expressing SNAP-tagged GPCR. Such fluorescent-based binding assays can be performed with adherent cells or cells in suspension, in 96- or 384-well plates. Altogether, this new technology offers great advantages in terms of flexibility, rapidity, and user-friendliness; allows easy miniaturization; and makes it completely suitable for HTS applications.     

Male horn dimorphism in the scarab beetle, Onthophagus taurus: do alternative reproductive tactics favour alternative phenotypes?

In a variety of organisms morphological variation is discrete rather than continuous. Discrete variation within a sex has attracted particular interest as it is thought to reflect the existence of alternative adaptations to a heterogeneous selection environment. The beetle Onthophagus taurus shows a dimorphism for male horns: males that exceed a critical body size develop a pair of long, curved horns on their heads, while smaller males remain hornless. In this study we report on the alternative reproductive tactics used by males with these two morphologies, and present experimental and behavioural data suggesting that these alternative tactics selectively favour discretely different male phenotypes. Horned males aggressively defended tunnel entrances containing breeding females. Fights involved the use of horns, and males with longer horns were more likely to win fights. In contrast, hornless males employed nonaggressive sneaking behaviours when faced with competitively superior males. Sneaking behaviours appeared to require high degrees of manoeuvrability inside tunnels to access and mate with females despite the presence of a guarding male. Comparisons of running performances of males with identical body sizes but different horn lengths suggest that the possession of horns reduces male agility inside tunnels. Thus, horn possession confers a clear advantage to males using fighting behaviours to access females, whereas hornlessness may be favoured in males that rely primarily on sneaking behaviours. Combined, the two alternative reproductive tactics used by male O. taurus appear to favour opposite horn phenotypes, which may explain the paucity of intermediate morphologies in natural populations of O. taurus. Copyright 2000 The Association for the Study of Animal Behaviour.     

Cell-death alternative model organisms: why and which?

Classical model organisms have helped greatly in our understanding of cell death but, at the same time, might have constrained it. The use of other, non-classical model organisms from all biological kingdoms could reveal undetected molecular pathways and better-defined morphological types of cell death. Here we discuss what is known and what might be learned from these alternative model systems.     

Obesogens and obesity—An alternative view?

It is accepted that diet is a major contributor to the obesity epidemic, but environmental ‘obesogenic’ chemicals have also been suggested recently as playing a role, based on in vitro, animal and epidemiological studies. Using two such ‘obesogen’ examples (bisphenol A, certain phthalate esters), we argue that their association with obesity and obesity‐related disorders in humans could be circumstantial, and thus non‐causal, because a Western style diet increases exposure to these compounds. This possibility needs to be addressed before further (confounded) epidemiological studies on ‘obesogens’ are undertaken.     

Trails: an alternative to the field demonstration?

For many students, the traditional field demonstration has several disadvantages. The trail is suggested as an alternative technique, which may be appropriate for students who are not biology specialists, and for senior pupils. The advantages of this method include simpler presentation of information and questions, freedom for the tutor to assist weaker or more questioning students, flexibility in the timing of the exercise, and the need for careful preparation. The use of trails in assessment is suggested. Examples from trails used with Landscape Architecture students are given.     

Green Islands — nutrition not predation —an alternative hypothesis

Summary Mountain birch trees are said to survive as green islands around nests of red ants in Finnish Lapland because the ants kill larvae which would defoliate trees during outbreaks of the moth O. autumnata. An alternative hypothesis says that because the ants will concentrate soil nutrients (and possibly ameliorate soil moisture and temperature) in and around their nests, they provide a more favourable site for trees growing nearby. These trees are therefore less stressed and a poorer source of food for defoliators at times of outbreaks. Few if any young O. autumnata larvae survive on the trees which then survive in green islands around ant nests.     

Unemployment rates: an alternative to the Jarman index?

OBJECTIVE--To compare the Jarman index with alternative deprivation measures with regard to its usefulness to district health authorities as an indicator of need at small area level. DESIGN--The Jarman index (UPA (8)), Townsend''s index of material deprivation, the Scottish Development Department''s index, the Department of the Environment''s basic index, and unemployment rates were compared in respect of their correlation with measures of morbidity by electoral ward in a typical English district health authority. Measures of morbidity comprised standardised mortality ratios, admission rates (standardised and non-standardised), and permanent sickness rates. Spearman rank correlation coefficients were calculated for each combination of measures and were then ranked for each of the deprivation indices. SETTING--The 59 electoral wards of the Central Nottinghamshire Health Authority. RESULTS--The Jarman index consistently ranked lower in respect of its correlation with measures of morbidity than did the other deprivation measures. Current unemployment rates correlated well with morbidity measures, in particular with hospital admission rates, with correlations ranging from 0.669 to 0.830 for average and standardised all age admission rates. CONCLUSIONS--The Jarman index seems to be the least appropriate of these indices for health authority use. Unemployment rate merits further consideration as a simple, up to date marker for deprivation and consequent need for health service provision.     

What about the ducks? An alternative vaccination strategy.

Like most emerging disease threats, avian influenza is a zoonotic disease maintained in nature by wildlife. In this case, the reservoir of infection is migratory waterfowl, primarily ducks. Rather than trying to vaccinate most of the world's human population in response to the threat of an avian influenza pandemic, it might be more prudent to vaccinate key reservoir wildlife species from which pandemic strains evolve. This strategy would require a much more intensive research effort to understand the evolution of avian influenza viruses in nature, but it would be far less costly than any of the alternatives. Research priorities for emerging zoonoses, such as new strains of avian influenza viruses, should be re-evaluated with an emphasis on ways to intervene at their source, the natural reservoir hosts from which they originate, rather than focusing up on human-based interventions, which are too often too late.