What is clinical effectiveness?

Clinical trials and other forms of evaluation of medical treatment are held to give an objective assessment of the ‘clinical effectiveness’ of the medical treatments under evaluation. This kind of evaluation is central to the evidence-based medicine movement, as it provides a basis for the rational selection of treatment. The ethical status of randomised clinical trials is widely agreed to depend crucially upon the state of equipoise regarding which of two (or more) treatments is more (or most) effective in a defined population. However, the meaning and nature of ‘clinical effectiveness’ are unclear. in this paper, I discuss the proposals to define clinical effectiveness as a relational property and as an intrinsic property, and the way effectiveness may supervene upon more fundamental physical properties of treatments. I discuss whether effectiveness is a single property or a family of properties; the types of outcome which can be explained by effectiveness properties; and the relationship between ‘objective’ and ‘preference’ outcomes. This paper suggests that while it may be possible to put clinical effectiveness on a proper metaphysical footing, in practice the language of clinical effectiveness is more properly a topic of the human sciences than of the natural sciences.     

What are definitions of life good for? Transdisciplinary and other definitions in astrobiology

The attempt to define life has gained new momentum in the wake of novel fields such as synthetic biology, astrobiology, and artificial life. In a series of articles, Cleland, Chyba, and Machery claim that definitions of life seek to provide necessary and sufficient conditions for applying the concept of life—something that such definitions cannot, and should not do. We argue that this criticism is largely unwarranted. Cleland, Chyba, and Machery approach definitions of life as classifying devices, thereby neglecting their other epistemic roles. We identify within the discussions of the nature and origin of life three other types of definitions: theoretical, transdisciplinary, and diagnostic definitions. The primary aim of these definitions is not to distinguish life from nonlife, although they can also be used for classificatory purposes. We focus on the definitions of life within the budding field of astrobiology, paying particular attention to transdisciplinary definitions, and diagnostic definitions in the search for biosignatures from other planets.     

Backtranslating clinical knowledge for use in cheminformatics—What is the potential?

'From bench to bedside' is seeing a very strong focus in current Drug Discovery. However, often overlooked are the advantages that turn out if data is used 'from bedside to bench', the fact one can also make beneficial use of clinical information in early Drug Discovery. By leveraging the wealth of clinical data carried by each marketed drug, down to the level of a single person, one can gain a deep insight that can be leveraged in conjunction with chemical structure information and therefore within all kinds of cheminformatics analyses. This supports the design of drugs that better fit the requirements of a well-defined subpopulation. Within this contribution I am going to focus on the realm of cheminformatics applications and how this data can thereby used to better impact the decisions of medicinal chemists.     

What can the residents of malaria endemic countries do to protect themselves against malaria?

The incidence of malaria may vary substantially between adjacent communities and within an individual community, even in areas of high malaria transmission. Analysis of the factors responsible for these local variations in the incidence of malaria may identify potential control measures. Factors shown to be associated with local protection against malaria in some situations include house position, house design, the use of insect repellents and mechanical barriers such as bednets and curtains. The efficacy of insecticide treated nets and curtains in preventing mortality and morbidity from malaria, at least in the short-term, has been demonstrated convincingly. However, other measures of personal protection have not been evaluated in large trials which have clinical malaria as their endpoint. Such trials are needed to see if new malaria control tools can be identified that will assist current international efforts to improve malaria control, especially in Africa. The millions of non-immune travellers who visit malaria endemic areas each year need to protect themselves against malaria and the ways in which they can do this most effectively have been studied extensively. However, less attention has been paid to the local population of malaria endemic areas. What steps can they adopt to provide personal protection against malaria and how effective are these measures? Clues to which measures might be effective can come from study of the reasons for local variations in the incidence of malaria.     

What is an adequate length of baseline in research and clinical practice with chronic headache?

We examined the representativeness of baseline headache diary recording periods of 1, 2, 3, and 4 weeks for three kinds of headache disorder — tension, migraine, and combined migraine and tension. For research purposes at pretreatment, 2 weeks of diary recording are preferable for tension headache, while at least 3 weeks are preferred for migraine and combined headache. At follow-up, 1 week of diary recording appears adequate for all three headache types. Recommendations are also made for clinical practice.This research was supported by grants from NINCDS, NS-23440, and NIMH, MH-41341.     

What is menstruation for? On the projectibility of functional predicates in menstruation research

In 1993, biologist Margie Profet captured the attention of the popular press with the publication of her radical thesis: menstruation has a function. Traditional theories, she claims, typically view menstruation as a functionless by-product of cyclic flux. The details of Profet’s functional account are similarly radical: she argues that menstruation has been naturally selected to defend the female reproductive tract from sperm-borne pathogens. There are a number of weaknesses in Profet’s evolutionary analysis. However, I focus on a set of pragmatic problems that arise prior to any details of her evolutionary account. In arguing for the importance of pragmatic considerations, I draw from the linguistic analyses of Nelson Goodman. I conclude that critical investigation of the evolutionary details of Profet’s pathogen defense account will be more feasible if and when biologists more frequently feature the female system of pathogen defense in their inductive generalisations. The system needs to be better entrenched before its functional components, such as menstruation, can be thoroughly investigated.     

What is cooperative breeding in mammals and birds? Removing definitional barriers for comparative research

Cooperative breeding (i.e. when alloparents care for the offspring of other group members) has been studied for nearly a century. Yet, inconsistent definitions of this breeding system still hamper comparative research. Here, we identify two major inconsistencies, discuss their consequences and propose a way forward. First, some researchers restrict the term ‘cooperative breeding’ to species with non-breeding alloparents. We show that such restrictive definitions lack distinct quantitative criteria to define non-breeding alloparents. This ambiguity, we argue, reflects the reproductive-sharing continuum among cooperatively breeding species. We therefore suggest that cooperative breeding should not be restricted to the few species with extreme reproductive skew and should be defined independent of the reproductive status of alloparents. Second, definitions rarely specify the type, extent and prevalence of alloparental care required to classify species as cooperative breeders. We thus analysed published data to propose qualitative and quantitative criteria for alloparental care. We conclude by proposing the following operational definition: cooperative breeding is a reproductive system where >5% of broods/litters in at least one population receive species-typical parental care and conspecifics provide proactive alloparental care that fulfils >5% of at least one type of the offspring's needs. This operational definition is designed to increase comparability across species and disciplines while allowing to study the intriguing phenomenon of cooperative breeding as a behaviour with multiple dimensions.     

What is driving male mate preference evolution in Jamaican field crickets?

Male mating preferences are often a neglected aspect of studies on sexual selection. Male mating preferences may evolve if they provide males with direct‐fitness benefits such as increased opportunity to fertilize more eggs or indirect‐fitness benefits such as enhanced offspring survival. We tested these ideas using Jamaican field crickets, Gryllus assimilis, previously shown to exhibit male mating preferences. We randomly mated males to either their preferred or non‐preferred potential mates and then asked whether mating treatment influenced egg oviposition or offspring viability. Preferred females were not significantly more fecund and did not produce more viable eggs or offspring than non‐preferred females. Male mate preferences were therefore inconsistent with both the direct‐ and indirect‐fitness benefits hypotheses under the conditions of our experiment. Our null results leave us with an open question about what is driving the evolution of mating preferences in male crickets. Future research should explore the whether the offspring of preferred females are more attractive, have stronger immune systems, and/or experience higher adult longevity.     

Phage display: a useful tool for malaria research?

Defining the molecular intricacies of malaria pathogenesis is a vital area of medical and scientific research. Sophisticated methods have been developed to identify and characterise host-parasite interactions that are important in infection. Phage display involves the combinatorial display of proteins or peptides on the surface of bacteriophage. The technology provides an invaluable tool for screening diverse libraries for polypeptides that have a high affinity for a given target. Phage display in malaria research has proven successful, not only in mapping the protein-protein interactions that are important in Plasmodium biology, but also in the identification of molecules that might be exploited in the design of therapeutic agents or vaccines.     

What is the evidence for the clinical value of SBRT in cancer of the cervix?

AimThe aim of this review is to describe and analyze indications and results of the use of SBRT in uterine cervix cancer, reviewing articles published from January 2010 up to August 2017, for any one of the four indications listed:

• 1Patient refusal or anatomic impediments to interstitial or intracavitary brachytherapy (BCT), i.e. SBRT as an “alternative” for BCT;
• 2Patients with voluminous tumors, or asymmetric tumors where BCT alone would not achieve curative doses, i.e. SBRT as a primary adjunct to BCT;
• 3Pelvic and para aortic adenopathy where SBRT could be used as a boost, i.e. SBRT as a primary adjunct to external beam pelvic radiotherapy;
• 4Small volume recurrences (postoperative or post radiotherapy), i.e. SBRT for salvage.

BackgroundCervix cancer standard treatment involves pelvic irradiation and chemotherapy, recent advances in irradiation techniques might offer new possible approaches.Material and methodsSystematic review of the English language literature about Cervix cancer, SBRT, published from January 2010 to January 2018 identified through a database search of PubMed, and Ovid MEDLINE, using pre-defined search phrases.ResultsThe results in the literature, in general, demonstrate rather weak efficacy of SBRT. In this review, we did not find strong evidence to recommend routine SBRT as a primary treatment for cervico-uterine cancers, i.e. as a replacement for BCT; in highly selected cases it might be considered useful as salvage therapy for relapsed cervix cancer.ConclusionThe existing data to not warrant recommending SBRT for the definitive treatment of cervix cancer, but may have some value in the recurrent/relapsed setting.     

Is the incidence of malaria decreasing in endemic area of Turkey?

Much international business and tourism travels occur, as well as the deployment of soldiers to other places. The aim of this study was both to determine incidence of malaria in the military hospital, Diyarbakir, southeast region of Turkey, and to point out the incidence of this disease. During the study period (1997-2004), 609 cases were found in a military hospital, which is in an endemic area for vivax malaria. This article review trends in current malaria status as well as possible factors for the decreasing prevalence throughout the study period.     

What is mzXML good for?

mzXML (extensible markup language) is one of the pioneering data formats for mass spectrometry-based proteomics data collection. It is an open data format that has benefited and evolved as a result of the input of many groups, and it continues to evolve. Due to its dynamic history, its structure, purpose and applicability have all changed with time, meaning that groups that have looked at the standard at different points during its evolution have differing impressions of the usefulness of mzXML. In discussing mzXML, it is important to understand what mzXML is not. First, mzXML does not capture the raw data. Second, mzXML is not sufficient for regulatory submission. Third, mzXML is not optimized for computation and, finally, mzXML does not capture the experiment design. In general, it is the authors’ opinion that XML is not a panacea for bioinformatics or a substitute for good data representation, and groups that want to use mzXML (or other XML-based representations) directly for data storage or computation will encounter performance and scalability problems. With these limitations in mind, the authors conclude that mzXML is, nonetheless, an indispensable data exchange format for proteomics.     

What is mzXML good for?

mzXML (extensible markup language) is one of the pioneering data formats for mass spectrometry-based proteomics data collection. It is an open data format that has benefited and evolved as a result of the input of many groups, and it continues to evolve. Due to its dynamic history, its structure, purpose and applicability have all changed with time, meaning that groups that have looked at the standard at different points during its evolution have differing impressions of the usefulness of mzXML. In discussing mzXML, it is important to understand what mzXML is not. First, mzXML does not capture the raw data. Second, mzXML is not sufficient for regulatory submission. Third, mzXML is not optimized for computation and, finally, mzXML does not capture the experiment design. In general, it is the authors' opinion that XML is not a panacea for bioinformatics or a substitute for good data representation, and groups that want to use mzXML (or other XML-based representations) directly for data storage or computation will encounter performance and scalability problems. With these limitations in mind, the authors conclude that mzXML is, nonetheless, an indispensable data exchange format for proteomics.     

Gene-knockout mice in malaria research: useful or misleading?

Gene-knockout mice have been extensively used in the study of several malaria-induced pathologies. Some investigators believe that the deficient, infected mice mimic disease aspects produced in the absence of the target gene, but others believe that the deficient mice models mainly explain the effects of compensatory, related molecules. Comparison of some of the most relevant knockout mouse studies for understanding cerebral malaria and parasitemia and their related human reports shows that gene-knockout mice are useful tools that support conclusions from human genetic studies. These mice have helped to indicate new resistance genes against human malaria and have provided valuable information about mechanisms of malaria resistance in mice.     

What is the time scale of magnetic field interaction in biological systems?

An experimental test constraining the intrinsic time scale of a primary physical mechanism that detects extremely-low-frequency (ELF) magnetic fields in biological systems is proposed. The suggested test postulates that a transductive mechanism operating on time scales much shorter than the period of an applied magnetic field cannot obtain any information about the exposure conditions other than the absolute magnitude of the field. By generating field exposures that differ in their vector properties but are equivalent in their time-varying absolute amplitude, it is possible to differentiate between two broad classes of mechanisms: 1) those with intrinsic time scales comparable with or longer than those of the external influence, and 2) those that are much faster than the period of the applied field. The hypothesis assumes an experimental model proven to respond to magnetic fields and sensitive to a change of about a factor of two in one of the field parameters (AC, DC amplitude or frequency). The case of general linearly polarized fields is discussed, and an analytical solution for the case of perpendicular AC/DC fields is given. Bioelectromagnetics 18:244–249, 1997 © 1997 Wiley-Liss, Inc.     

What is a plant nutrient? Changing definitions to advance science and innovation in plant nutrition

Plant and Soil - Current definitions of essential or beneficial elements for plant growth rely on narrowly defined criteria that do not fully represent a new vision for plant nutrition and...     

What is the function of MSP-I on the malaria merozoite?

In the absence o f any clear enzymatic activity, attempts to define the role of merozoite surface protein-I have focused mainly on analysis of its structure, on its interaction with the immune system and on binding assays. But how does our knowledge of the structure o f this protein contribute to functional studies? Are there data to suggest a role in the evasion of effective host immune responses? Binding studies have used the intact protein or various fragments and peptides, but do such approaches provide a reliable indicator of function? In this article, Tony Holder and Mike Blackman review these areas.