The NCBI Databases: an Evolutionist’s Perspective

The National Center for Biotechnology Information (NCBI) organizes information resources for life scientists on an evolutionary scheme. This facilitates research about present-day organisms. The recent discovery of a new arenavirus, the LUJO virus, illustrates the utility of adopting evolution as a central architectural principle for life sciences databases: using the NCBI’s resources, clinicians were able to classify the new virus in real time—soon enough to aid in the diagnosis and treatment of a hemorrhagic fever caused by the LUJO virus. Topics fundamental to the study of evolution, often thought of as useless, are indeed vital because they inform how life science information ought to be organized.     

A Statistical Perspective on Prevention Trials: A View from the Women’s Health Initiative

Chronic disease prevention trials test strategies to reduce the risk of a specific health event in generally healthy people. These strategies are often thought to affect other health conditions and their use in the population requires a very favorable safety profile. A prevention trial assessing such a strategy is most valuable when designed to capture the overall public health impact and hence provide more comprehensive, reliable information for policy and practice. This broad agenda, and particularly the assessment of multiple outcomes, creates statistical challenges in the design, monitoring, and reporting of such a trial. In this article these issues are described in the context of the Women’s Health Initiative, a large randomized prevention trial testing three interventions in post-menopausal women: hormone therapy, a low-fat diet and calcium and vitamin D supplementation. Each intervention was hypothesized to influence multiple chronic disease rates including cardiovascular disease, stroke, cancers, and fractures. Here the design, monitoring, and reporting of the WHI trials is reviewed in the context of multiple outcomes and the approach to a global assessment of these interventions is described.     

The Stewart Approach – One Clinician’s Perspective

Peter Stewart added controversy to an already troubled subject when he entered the clinical acid-base arena. His approach puts water dissociation at the centre of the acid-base status of body fluids. It is based on six simultaneous equations, incorporating the Laws of Mass Action, Mass Conservation, and Electrical Neutrality. Together with Gibbs-Donnan equilibria, these equations explain the diagnostically important PaCO₂/pH relationship, and improve understanding of the physiologic basis of traditional acid-base approaches. Spin-offs have included new scanning tools for unmeasured ions, in particular the ‘strong ion gap’ and ‘net unmeasured ions’. The most controversial feature is the designation of pH and bicarbonate concentrations as dependent variables, answerable exclusively to three independent variables. These are the strong ion difference (SID), the total concentration of non-volatile weak acid (A_TOT), and PCO₂. Aspects of this assertion conflict with traditional renal physiology, and with current models of membrane H⁺/base transporters, oxidative phosphorylation, and proton and bicarbonate ionophores. The debate in this area is ongoing. Meanwhile, Stewart-style diagnostic and decision support systems such as the ‘Strong Ion Calculator’ and the web-site www.acidbase.org are now appearing.     

Alzheimer’s Disease and Epilepsy: A Perspective on the Opportunities for Overlapping Therapeutic Innovation

Early-onset Alzheimer’s disease (AD) is associated with variants in amyloid precursor protein (APP) and presenilin (PSEN) 1 and 2. It is increasingly recognized that patients with AD experience undiagnosed focal seizures. These AD patients with reported seizures may have worsened disease trajectory. Seizures in epilepsy can also lead to cognitive deficits, neuroinflammation, and neurodegeneration. Epilepsy is roughly three times more common in individuals aged 65 and older. Due to the numerous available antiseizure drugs (ASDs), treatment of seizures has been proposed to reduce the burden of AD. More work is needed to establish the functional impact of seizures in AD to determine whether ASDs could be a rational therapeutic strategy. The efficacy of ASDs in aged animals is not routinely studied, despite the fact that the elderly represents the fastest growing demographic with epilepsy. This leaves a particular gap in understanding the discrete pathophysiological overlap between hyperexcitability and aging, and AD more specifically. Most of our preclinical knowledge of hyperexcitability in AD has come from mouse models that overexpress APP. While these studies have been invaluable, other drivers underlie AD, e.g. PSEN2. A diversity of animal models should be more frequently integrated into the study of hyperexcitability in AD, which could be particularly beneficial to identify novel therapies. Specifically, AD-associated risk genes, in particular PSENs, altogether represent underexplored contributors to hyperexcitability. This review assesses the available studies of ASDs administration in clinical AD populations and preclinical studies with AD-associated models and offers a perspective on the opportunities for further therapeutic innovation.

     

Questions of Methodology in Aristotle’s Zoology: A Medieval Perspective

During the Middle Ages Aristotle’s treatises were accessible to intellectuals via translations and commentaries. Among his works on natural philosophy, the zoological books received relatively little scholarly attention, though several medieval commentators carefully studied Aristotle’s investigations of the animal kingdom. Averroes completed in 1169 a commentary on an Arabic translation of Aristotle’s Parts of Animals and Generation of Animals. In 1323 Gersonides completed his supercommentary on a Hebrew translation of Averroes’ commentary. This article examines how these two medieval commentators interpret the first book of Aristotle’s Parts of Animals, at the center of which stand methodological questions regarding the study of animals. Aristotle’s discussion of classification is presented by Averroes and Gersonides in light of an epistemological debate concerning the requisite method for scientific inquiries and discoveries. Sense perception is contrasted with rational reasoning, and ultimately a combined method is proposed, sense perception maintaining supremacy. These commentators outline a clear link between the systematic arrangement of animal species as offered by Aristotle, and his subsequent logical demonstrations which, according to them, form the core of biological investigations.     

Taxonomic Practice and Middle Missouri Prehistory: A Perspective on Donald J. Lehmer’s Contributions

Abstract

This paper is an attempt to explicate Donald J. Lehmer’s taxonomic practices. It begins with an examination of his 1954 response to the limitations of the Midwestern Taxonomic System, continues with a discussion of Lehmer and Caldwell’s attempt to introduce the Willey and Phillips Phase-Tradition-Horizon System and ends with an interpretation of the taxonomic modifications Lehmer introduced in his final synthesis of Middle Missouri prehistory. The logical properties of the M.T.S. and the Willey and Phillips System are used throughout as a background against which Lehmer’s accomplishments and mistakes can be brought into sharp focus.     

Willingness to Consult a Veterinarian on Physician’s Advice for Zoonotic Diseases: A Formal Role for Veterinarians in Medicine?

Physicians appear to find zoonotic diseases a challenge and consider that this topic belongs more to the veterinary profession. However, veterinarians have no formal role in clinical medicine. Data were collected as part of the Queensland Social Survey 2014 to determine the willingness of the public, if diagnosed with a zoonotic disease, to consult a veterinarian on the advice of a physician. Self-reported willingness to consult with a veterinarian at the respondent’s own expense was 79.8% (95% CI: 81.96%-77.46%) (976/1223). If the cost was funded by Medicare, the Australian public health insurance scheme, 90.7% (95% CI: 92.18%-88.92%) (1109/1223) would be willing to consult a veterinarian. Therefore, a large majority of Australian residents would be willing to consult with a veterinarian on the advice of their physician if they had a zoonotic disease. Does this indicate a possible new role for veterinarians under Clinical One Health?     

A Spotlight on Preschool: The Influence of Family Factors on Children’s Early Literacy Skills

Rationale

Phonological awareness, letter knowledge, oral language (including sentence recall) and rapid automatised naming are acknowledged within-child predictors of literacy development. Separate research has identified family factors including socio-economic status, parents’ level of education and family history. However, both approaches have left unexplained significant amounts of variance in literacy outcomes. This longitudinal study sought to improve prospective classification accuracy for young children at risk of literacy failure by adding two new family measures (parents’ phonological awareness and parents’ perceived self-efficacy), and then combining the within-child and family factors.

Method

Pre-literacy skills were measured in 102 four year olds (46 girls and 56 boys) at the beginning of Preschool, and then at the beginning and end of Kindergarten, when rapid automatised naming was also measured. Family factors data were collected at the beginning of Preschool, and children’s literacy outcomes were measured at the end of Year 1 (age 6–7 years).

Results

Children from high-risk backgrounds showed poorer literacy outcomes than low-risk students, though three family factors (school socio-economic status, parents’ phonological awareness, and family history) typically accounted for less Year 1 variance than the within-child factors. Combining these family factors with the end of Kindergarten within-child factors provided the most accurate classification (i.e., sensitivity = .85; specificity = .90; overall correct = .88).

Implications

Our approach would identify at-risk children for intervention before they began to fail. Moreover, it would be cost-effective because although few at-risk children would be missed, allocation of unnecessary educational resources would be minimised.     

Pituitary Adenoma: A Clinician’S Perspective

ObjectiveTo review the underlying causes of pituitary lesions, a rational approach to their diagnosis, and therapeutic options.MethodsThe types of pituitary lesions and their clinical manifestations are reviewed, and treatment strategies and long-term follow-up are discussed.ResultsA pituitary adenoma is quite common and poses a challenge to the clinician to determine the clinical significance, the appropriate diagnosis, the need for treatment, and the appropriate therapy or therapies. The treatment of a pituitary adenoma depends on the type of tumor; a prolactinoma is treated medically with a dopamine agonist drug, and other lesions are usually treated by transsphenoidal surgical removal. Replacement of a deficient hormone or hormones is necessary for optimal functioning. Some patients require more than one treatment, including surgical intervention, replacement of a hormone or hormones, medications to lower hormone hypersecretion to normal (for prolactinoma, acromegaly, or Cushing disease), pituitary radiation therapy (optimally with focused irradiation such as the Gamma Knife or LINEAC), and, in the situation of persistent Cushing disease, bilateral adrenalectomy as a last resort. Lifelong monitoring is necessary for all these patients.ConclusionThe goal is to decrease the mass effect of the adenoma, to restore normal pituitary function, and to suppress hormone hypersecretion. Achievement of this goal necessitates the cooperation and interdisciplinary efforts of several medical specialties. (Endocr Pract. 2008;14:757-763)     

Dobzhansky and Montagu’s Debate on Race: The Aftermath

Dobzhansky and Montagu debated the use and validity of the term “race” over a period of decades. They failed to reach an agreement, and the “debate” has continued to the present. The ms contains an account of the debate to the present. This essay is part of a Special Issue, Revisiting Garland Allen’s Views on the History of the Life Sciences in the Twentieth Century.     

From River Management to River Basin Management: A Water Manager’s Perspective

Chironomid larvae were sampled sequentially from small experimental rice fields in southern New South Wales, Australia. Sampling was undertaken during the 1995, 1997, 1998 and 1999 crop establishment periods, starting 10 days after flooding (DAF) and continuing at 5 day intervals until 35 DAF. No agrochemical treatments were applied to the fields at any stage. Seventeen species were identified from 3429 recovered larvae. The most abundant species were Chironomus tepperi Skuse (0–91% of 35 day totals), Procladius paludicola Skuse (7–78%) and Polypedilum nubiferum (Skuse) (2–12%). No other taxon accounted for more than 8% of recovered larvae in any year. C. tepperi colonised fields more rapidly than other taxa and, when present, had only a single generation. The abundance of C. tepperi varied dramatically from year to year: from total absence in 1997 to a peak density exceeding 13 000 larvae m⁻² in 1998. Significant differences between post-flood sampling times (R = 0.407, p= 0.009) and between years (R = 0.495, p = 0.001) were found using ANOSIM2 analysis. C. tepperi had a greater impact on community variability at 10 and 15 DAF (42–58%) than any other species, with P. paludicola exerting the most influence from 20 DAF onwards. Exceptionally high densities of C. tepperi in 1998 led to high levels of turbidity, which apparently prolonged the duration of the single C. tepperi cohort by suppressing water temperatures. Comparison of plant densities in the monitored bays to those in nearby bays receiving effective chemical protection shows that rice plant loss increased in response to higher C. tepperi densities. No plant loss occurred in 1997 when C. tepperi was absent, suggesting the other chironomid species present in the fields are not routinely involved in causing significant crop damage.     

The Neutral—Niche Debate: A Philosophical Perspective

Ecological communities around the world are under threat while a consensus theory of community structure remains elusive. In the last decade ecologists have struggled with two seemingly opposing theories: niche-based theory that explains diversity with species’ differences and the neutral theory of biodiversity that claims that much of the diversity we observe can be explained without explicitly invoking species’ differences. Although ecologists are increasingly attempting to reconcile these two theories, there is still much resistance against the neutral theory of biodiversity. Here we argue that the dispute between the two theories is a classic example of the dichotomy between philosophical perspectives, realism and instrumentalism. Realism is associated with specific, small-scale and detailed explanations, whereas instrumentalism is linked to general, large-scale, but less precise accounts. Recognizing this will help ecologists get both niche-based and neutral theories in perspective as useful tools for understanding biodiversity patterns.