Is It Always Unethical to Use a Placebo in a Clinical Trial?

Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the efficacy and safety of many treatments.     

When Is Hub Gene Selection Better than Standard Meta-Analysis?

Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when) hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data). Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis) and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility) in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA) in three comprehensive and unbiased empirical studies: (1) Finding genes predictive of lung cancer survival, (2) finding methylation markers related to age, and (3) finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1). However, standard meta-analysis methods perform as good as (if not better than) a consensus network approach in terms of validation success (criterion 2). The article also reports a comparison of meta-analysis techniques applied to gene expression data and presents novel R functions for carrying out consensus network analysis, network based screening, and meta analysis.     

Is it Good to Make Happy People?

Would it be good, other things being equal, for additional people to exist whose lives would be worth living? I examine and reject several arguments for the answer that it would not be good; then I offer opposing arguments that I believe are more successful. Thus, I agree with utilitarians who say that it is better for there to be more happy people. Next I argue for the stronger claim that the happiness of potential people is as important as that of adults. Potential quality of life, then, matters in a host of bioethical issues: abortion, commercial surrogacy, the treatment of defective newborns, and so on. What is the practical upshot of all this? I reject the idea that we must do whatever is necessary to prolong life worth living. But I also reject the view that the side-effects of overpopulation always outweigh the value of realizing potential happiness. So I advocate a middle position, which I do not identify precisely. Even from this middle position, however, potential happiness is more important than is commonly assumed in bioethics.     

Of What Use Is Sex to Bacteria?

Though bacteria are predominantly asexual, the genetic information in their genomes can be expanded and modified through mechanisms that introduce DNA from outside sources. Bacterial sex differs from that of eukaryotes in that it is unidirectional and does not involve gamete fusion or reproduction. The input of DNA during bacterial sex generates diversity in two ways--through the alteration of existing genes by recombination and through the introduction of novel sequences--and each of these processes has been shown to aid in the survival and diversification of lineages.     

Does It Make Sense to Restore Wildland Fire in Changing Climate?

Forest restoration guided by historical reference conditions of fire regime, forest structure, and composition has been increasingly and successfully applied in fire‐adapted forests of western North America. But because climate change is expected to alter vegetation distributions and foster severe disturbances, does it make sense to restore the ecological role of wildland fire through management burning and related activities such as tree thinning? I suggest that some site‐ and date‐specific historical conditions may be less relevant, but reference conditions in the broad sense are still useful. Reference conditions encompass not only the recent past but also evolutionary history, reflecting the role of fire as a selective force over millennia. Taking a long‐term functional view of historical reference conditions as the result of evolutionary processes can provide insights into past forest adaptations and migrations under various climates. As future climates change, historical reference data from lower, southerly, and drier sites may be useful in places that are higher, northerly, and currently wetter. Almost all models suggest that the future will have substantial increases in wildfire occurrence, but prior to recent human‐caused fire exclusion, fire‐adapted pine forests of western North America were among the most frequently burned in the world. Restoration of patterns of burning and fuels/forest structure that reasonably emulate historical conditions prior to fire exclusion is consistent with reducing the susceptibility of these ecosystems to catastrophic loss. Priorities may include fire and thinning treatments of upper elevation ecotones to facilitate forest migration, whereas vulnerable low‐elevation forests may merit less management investment.     

Is there more to GABA than synaptic inhibition?

In the mature brain, GABA (gamma-aminobutyric acid) functions primarily as an inhibitory neurotransmitter. But it can also act as a trophic factor during nervous system development to influence events such as proliferation, migration, differentiation, synapse maturation and cell death. GABA mediates these processes by the activation of traditional ionotropic and metabotropic receptors, and probably by both synaptic and non-synaptic mechanisms. However, the functional properties of GABA receptor signalling in the immature brain are significantly different from, and in some ways opposite to, those found in the adult brain. The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal.     

Peak Waste: When Is It Likely to Occur?

Population and per capita gross domestic product (GDP) projections are used to estimate total global municipal solid waste (MSW) generation over the twenty‐first century. Some projections for global population suggest that it will peak this century. Waste generation rates per capita generally increase with affluence, although in the most affluent countries there is also a trend toward dematerialization. The confluence of these factors means that at some point in the future total global waste generation could possibly peak. To determine when peak waste might occur, we used the shared‐socioeconomic pathway scenarios (used in Intergovernmental Panel on Climate Change [IPCC] studies) combined with estimates of municipal solid waste (MSW) generation rates, extrapolated from our work for the World Bank. Despite the expectation that total MSW generation in Organisation for Economic Co‐operation and Development (OECD) and high‐income countries will peak mid‐century, with current trajectories global peak waste is not expected before 2100. The peak could be moved forward to around 2075 and reduced in intensity by some 30% if a more aggressive sustainability growth scenario were followed, rather than the current business‐as‐usual scenario. Further, the magnitude of peak waste is sensitive to the intensity of waste generation; it could vary from 7.3 to 10.9 megatonnes per day under the sustainability scenario. The timing of peak waste will substantially depend on the development of cities in Sub‐Saharan Africa, where population growth rates are more than double the rest of the world.     

Is there more to enamel matrix proteins than biomineralization?

Enamel proteins are proteins synthesized by ameloblast cells. These proteins are secreted into the enamel extracellular matrix where they nucleate and regulate the growth of hydroxyapatite crystals to form the mineralized enamel covering the crown of the teeth. Although the exact role of these proteins in enamel mineralization is just beginning to be elucidated, new studies suggest that these proteins might have functions outside enamel formation. Furthermore, extracts of enamel proteins are currently being used to regenerate periodontal tissues destroyed by periodontal disease and new studies suggest that they might have chondrogenic and osteogenic properties. These new functions of enamel proteins will be the focus of this review.     

What Is the Good of It—Ethical Controls of Human Subject Health Research?

The term “ethics” covers a multitude of virtues and possibly some sins where ethical perspectives differ. Given the diversity of ethical philosophies there is a question about what common ground can, or should, inform health research ethics. At a minimum it must be consistent with the law. Beyond that, ethics embraces a variety of possible approaches. This raises the question—what criteria are applied in determining the appropriate approach and what standards by way of quality control are applied to its decisional application by ethics committees or other authorities exercising responsibility in this difficult area. The particular issue of ethical perspectives on the use of “big data” in medical research also raises complex issues for consideration.     

Ascertainment Adjustment: Where Does It Take Us?

It is commonly assumed that the parameter estimates of a statistical genetics model that has been adjusted for ascertainment will estimate parameters in the general population from which the ascertained subpopulation was originally drawn. We show that this is true only in certain restricted circumstances. More generally, ascertainment-adjusted parameter estimates reflect parameters in the ascertained subpopulation. In many situations, this shift in perspective is immaterial: the parameters of interest are the same in the ascertained sample and in the population from which it was drawn, and it is therefore irrelevant to which population inferences are presumed to apply. In other circumstances, however, this is not so. This has important implications, particularly for studies investigating the etiology of complex diseases.     

Contrast Enhancement of the Right Ventricle during Coronary CT Angiography – Is It Necessary?

Purpose

It is unclear if prolonged contrast media injection, to improve right ventricular visualization during coronary CT angiography, leads to increased detection of right ventricle pathology. The purpose of this study was to evaluate right ventricle enhancement and subsequent detection of right ventricle disease during coronary CT angiography.

Materials and Methods

472 consecutive patients referred for screening coronary CT angiography were retrospectively evaluated. Every patient underwent multidetector-row CT of the coronary arteries: 128x 0.6mm coll., 100-120kV, rot. time 0.28s, ref. mAs 350 and received an individualized (P3T) contrast bolus injection of iodinated contrast medium (300 mgI/ml). Patient data were analyzed to assess right ventricle enhancement (HU) and right ventricle pathology. Image quality was defined good when right ventricle enhancement >200HU, moderate when 140-200HU and poor when <140HU.

Results

Good image quality was found in 372 patients, moderate in 80 patients and poor in 20 patients. Mean enhancement of the right ventricle cavity was 268HU±102. Patients received an average bolus of 108±24 ml at an average peak flow rate of 6.1±2.2 ml/s. In only three out of 472 patients (0.63%) pathology of the right ventricle was found (dilatation) No other right ventricle pathology was detected.

Conclusion

Right ventricle pathology was detected in three out of 472 patients; the dilatation observed in these three cases may have been picked up even without dedicated enhancement of the right ventricle. Based on our findings, right ventricle enhancement can be omitted during screening coronary CT angiography.     

Is It Feasible to Use Optical Brightener Technology with a Baculovirus Bioinsecticide for Resource-Poor Maize Farmers in Mesoamerica?

Stilbene-derived optical brighteners greatly enhance the infectivity of a number of baculoviruses. This technology has been patented for use with insect pathogenic viruses in the United States and Canada. A baculovirus is currently being tested for its potential as a biological insecticide of Spodoptera frugiperda (Lepidoptera: Noctuidae), the principal insect pest of maize in Mesoamerica. A multiply embedded nucleopolyhedrovirus isolate originally from Nicaragua was bioassayed alone and in the presence of the optical brightener Tinopal LPW (1%), using second instar S. frugiperda larvae. The LC₅₀ value of the virus alone was calculated at 82.1 polyhedral inclusion bodies (PIBs)/mm² of diet compared with 0.71 PIBs/mm² in the presence of Tinopal LPW. In contrast to other studies, the mean time to death of larvae exposed to virus and Tinopal LPW was significantly extended compared to larvae inoculated with virus alone. Analysis of the results of eight independent field trials in Mexico and Honduras revealed a significant positive relationship between log virus dose and percentage mortality observed in S. frugiperda larvae. Virus-induced mortality was approximately 50% at the highest application rate tested: 1000 larval equivalents (LE) of virus/ha. When the impact of parasitism was taken into account, larval mortality increased to 45.0–90.7% in plots treated with virus at 250 LE/ha or more. A cost analysis indicated that approximately 60% pest control can be achieved as a conservative estimate with virus application and the action of parasitoids for the price of a chemical insecticide. Formulating the virus with an optical brightener appears to be an attractive option based on laboratory findings but requires field testing. The use of optical brightener technology will probably be feasible for maize growers in Mesoamerica only if it is highly effective at very low concentrations (<0.1%) or the volume of the virus application can be reduced.     

Is It Possible to Manipulate Scelionidae Wasps’ Preference to a Target Host?

Parasitoid host selection is mainly mediated by chemical cues, which can be adjusted by experience, changing their innate behavior. Therefore, this study evaluated if immature experience (pre-imaginal conditioning) on eggs and volatiles from different host eggs has influence on parasitism and chemotaxic behavior of Telenomus podisi Ashmead and/or Trissolcus basalis Wollaston (Hymenoptera: Scelionidae). Both wasp species were submitted to a multiple-choice parasitism test among Euschistus heros (Fabricius), Piezodorus guildinii (Westwood), and Nezara viridula L. (Hemiptera: Pentatomidae) (Hemiptera: Pentatomidae) egg masses. Eggs from these three stink bugs were equally offered to female parasitoids. After that, adults which emerged from each host were also exposed to parasitism in a multiple-choice test for up to an additional generation. Moreover, in olfactometer “Y,” the behavior of innate and experienced T. podisi females to volatiles from hosts’ egg extracts was tested, to study their learning and memory ability. The original host had influence on T. podisi parasitism; however, T. basalis always parasitized more N. viridula eggs independently of its last rearing host. Innate T. podisi females responded positively to E. heros and P. guildinii egg volatiles, but this behavior was not observed in N. viridula. When T. podisi females were experienced on egg volatiles from a new host, they showed significant learning and memory ability for the specific host volatile for, at least, 24 h. Experienced wasps responded positively to N. viridula and through this result we have evidences about the possibility to manipulate wasp’s preferences to a specific target host.     

The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

Neurochemical Research - Axon regeneration in the CNS is inhibited by many extrinsic and intrinsic factors. Because these act in parallel, no single intervention has been sufficient to enable full...