Michael Servetus (1511-1553) did not discover the lesser circulation

In the April issue of this Journal, C. van Tellingen presented a rather global survey of the historical development of ideas on the movement of the blood.1 We would like to briefly comment on Van Tellingen’s views on Michael Servetus and the latter’s non-existing historical relation to William Harvey’s true discovery of the circulation of the blood.     

The Lenoir thesis revisited: Blumenbach and Kant

Timothy Lenoir launched the historical study of German life science at the end of the 18th century with the claim that J. F. Blumenbach’s approach was shaped by his reception of the philosophy of Immanuel Kant: a ‘teleomechanism’ that adopted a strictly ‘regulative’ approach to the character of organisms. It now appears that Lenoir was wrong about Blumenbach’s understanding of Kant, for Blumenbach’s Bildungstrieb entailed an actual empirical claim. Moreover, he had worked out the decisive contours of his theory and he had exerted his maximal influence on the so-called ‘Göttingen School’ before 1795, when Lenoir posits the main influence of Kant’s thought took hold. This has crucial significance for the historical reconstruction of the German life sciences in the period. The Lenoir thesis can no longer serve as the point of departure for that reconstruction.     

The tribunal of philosophy and its norms: history and philosophy in Georges Canguilhem’s historical epistemology

In this article I assess Georges Canguilhem’s historical epistemology with both theoretical and historical questions in mind. From a theoretical point of view, I am concerned with the relation between history and philosophy, and in particular with the philosophical assumptions and external norms that are involved in history writing. Moreover, I am concerned with the role that history can play in the understanding and evaluation of philosophical concepts. From a historical point of view, I regard historical epistemology, as developed by Gaston Bachelard and Georges Canguilhem, as a conception and practice which came out of the project, elaborated in France from the 1920s to the 1940s, of combining history of science and philosophy. I analyse in particular Canguilhem’s epistemology in his theory and practice of history of science. What he called ‘normative history’ is the focus of my analysis. I evaluate the question of the nature and provenience of the norm employed in normative history, and I compare it with the norm as discussed by Canguilhem in Le normal et le pathologique. While I am critical of Canguilhem’s treatment of history, I conclude that his philosophical suggestion to analyse the formation of scientific concepts ‘from below’ represents a useful model for history and philosophy of science, and that it can be very profitably extended to philosophical concepts.     

The phylogeny fallacy and the ontogeny fallacy

In 1990 Robert Lickliter and Thomas Berry identified the phylogeny fallacy, an empirically untenable dichotomy between proximate and evolutionary causation, which locates proximate causes in the decoding of ‘genetic programs’, and evolutionary causes in the historical events that shaped these programs. More recently, Lickliter and Hunter Honeycutt (Psychol Bull 129:819–835, 2003a) argued that Evolutionary Psychologists commit this fallacy, and they proposed an alternative research program for evolutionary psychology. For these authors the phylogeny fallacy is the proximate/evolutionary distinction itself, which they argue constitutes a misunderstanding of development, and its role in the evolutionary process. In this article I argue that the phylogeny fallacy should be relocated to an error of reasoning that this causal framework sustains: the conflation of proximate and evolutionary explanation. Having identified this empirically neutral form of the phylogeny fallacy, I identify its mirror image, the ontogeny fallacy. Through the lens of these fallacies I attempt to solve several outstanding problems in the debate that ensued from Lickliter and Honeycutt’s provocative article.     

Prostate-specific antigen screening of workers under the age of 40 in Japan

Background: There is no agreement on the usefulness of the prostate-specific antigen (PSA) test for prostate cancer screening in young men in Japan. We believe that medical check-up departments in hospitals conduct prostate cancer screening in subjects under 40 years of age undergoing intensive health check-up for commercial reasons, and speculate that some medical doctors provide tacit consent for this action. To understand the prevalence of PSA testing in young men, the authors examined the age distribution of workers who underwent the PSA test. Methods: The authors used the 2009 intensive health check-up data of male workers aged 30–65 years (n = 298) in a car-manufacturing company to investigate the status of prostate-cancer screening in young men. Multiple comparison was conducted by Tukey's method when the analysis of variance revealed significant difference. Results: According to the frequency distribution of age, 15.8% of the subjects were under 40 years of age. The mean PSA value increased with age, ranging from 1.0 ng/mL in subjects in their 30s’, to 2.0 ng/mL in subjects in their 60s’. The mean PSA level in subjects in their 60s’ was significantly higher than that in subjects in their 30s’ and 40s’. The percentage of subjects with serum PSA levels of 4 ng/mL or higher in subjects in their 30s’, 40s’, 50s’ and 60s’ were 2.1% (1/47), 1.6% (2/125), 4.4% (5/114) and 8.3% (1/12), respectively. Conclusions: One-sixth of male workers attending the health check-up program were under 40 years of age. According to the criteria of the Japanese Urological Association, this examination program included younger subjects who were not candidates for PSA screening.     

Notes on Costeño cultural politics

The article fundamentally endorses Schroeder’s findings that Augusto Sandino failed to develop a significant base among the peoples of the Atlantic Coast. This article also places Schroeder’s argument in a comparative perspective, as it discusses the early 1930s rural mobilization in El Salvador, outlining how the Salvadoran left’s social egalitarian appeals compensated for a degree of cultural insensitivity and lack of knowledge regarding the indigenous peoples of the western part of the country. The article also questions the placement of the mining area as outside of the Atlantic Coast region. It suggests the historical connections of Miskitu Indians and the mining communities and in so doing modifies, to a degree, Schroeder’s argument about the desencuentro between Sandino and the indigenous people.     

Experimental history and Herman Boerhaave’s chemistry of plants

In the early eighteenth century, chemistry became the main academic locus where, in Francis Bacon’s words, Experimenta lucifera were performed alongside Experimenta fructifera and where natural philosophy was coupled with natural history and ‘experimental history’ in the Baconian and Boyleian sense of an inventory and exploration of the extant operations of the arts and crafts. The Dutch social and political system and the institutional setting of the university of Leiden endorsed this empiricist, utilitarian orientation toward the sciences, which was forcefully propagated by one of the university’s most famous representatives in the first half of the eighteenth century, the professor of medicine, botany and chemistry Herman Boerhaave. Recent historical investigations on Boerhaave’s chemistry have provided important insights into Boerhaave’s religious background, his theoretical and philosophical goals, and his pedagogical agenda. But comparatively little attention has been paid to the chemical experiments presented in Boerhaave’s famous chemical textbook, the Elementa chemiae, and to the question of how these experiments relate not only to experimental philosophy but also to experimental history and natural history, and to contemporary utilitarianism. I argue in this essay that Boerhaave shared a strong commitment to Baconian utilitarianism and empiricism with many other European chemists around the middle of the eighteenth century, in particular to what Bacon designated ‘experimental history’ and I will provide evidence for this claim through a careful analysis of Boerhaave’s plant-chemical experiments presented in the Elementa chemiae.     

Alien or endangered? Historical development of Chara connivens in the Baltic coastal waters and its implication for the species management

The occurrence of Chara connivens (Charophyta, Characeae) and its status in the Baltic Sea may raise controversies regarding its origin and historical dispersal pathways in the area. This study critically revises the protection status of C. connivens in the countries around the Baltic Sea, as well as its status on the red lists of endangered plant species (including the HELCOM Red List). The first reports on the presence of C. connivens in the Baltic Sea area were published in the aftermath of Carl Baenitz’s talks given in the early 1870s. Already then, the scientific community was well aware of the fact that C. connivens had been introduced as a ballast plant to the known Baltic areas of occurrence – the first known record of the species is from 1829. Since Poland is the only country where C. connivens is protected, the historical and contemporary distribution of this charophyte in the Polish coastal waters is presented against the background of the available historical and recent records of the species in the Baltic Sea. Recent reports from the second half of the 20th century and the beginning of the 21st century have confirmed a fairly common occurrence of C. connivens in Estonia, Sweden and Poland. This species still occurs on the German coast and has also been reported from Finland (the Åland archipelago). In recent decades, however, the species was considered rare in the Baltic Sea area. In Poland, C. connivens was even classified as extinct, despite earlier data on its occurrence in the Vistula Lagoon in the 1970s, where it was rediscovered in 2011. It was also found in the Szczecin Lagoon a year later. Both localities well suit Luther’s pattern of C. connivens occurrence in areas with intensive shipping and ballast discharge operations in historical times. Based on this in-depth revision of historical and current distribution, it is postulated that C. connivens, as non-indigenous, should not be red-listed in the Baltic Sea area, following the example of Finland. Moreover, its legal status in Poland of a strictly protected species should be reconsidered.     

Mysteries of attraction: Giovanni Pico della Mirandola,astrology and desire

Although in his later years Giovanni Pico della Mirandola (1463–1494) vehemently rejected astrology, he earlier used it in a variety of ways, but primarily to provide further evidence for positions to which he had arrived by other means. One such early use appears in his commentary on his friend Girolamo Benivieni’s love poetry, the Canzone d’amore, of 1486–1487. In the passages discussed here, Pico presents an intensive Platonic natural philosophical analysis based on a deep astrologically informed understanding of human nature as he attempts to explain a perennial question, namely, why one person is attracted to a certain person (or people), and another to others. I will place this discussion of the mysteries of attraction and desire in historical perspective by tracing Pico’s changing relationship to astrology during the course of his short but passionate life, and in historiographic perspective by revising Frances Yates’s still influential views concerning Pico’s contribution to Renaissance thought and his relationship with Marsilio Ficino.     

Complexity,adaptive complexity and the Creative View of natural selection

In this paper, I respond to arguments proposed by Brunnander in this journal issue concerning my position regarding the Creative View of natural selection (Razeto-Barry & Frick, 2011). Brunnander argues that (i) the Creative View we defend does not serve to answer William Paley’s question because (ii) Paley’s question is “why there are complex things rather than simple ones” and (iii) natural selection cannot answer this question. Brunnander’s arguments for (iii) defend a Non-creative View of natural selection (sensu Razeto-Barry & Frick, 2011). Here I claim that Brunnander’s arguments for (iii) are mistaken and I also argue that even accepting (iii) we do not have to accept (i), given that statement (ii) is historically and conceptually flawed. Thus here I analyze Paley’s question from a historical point of view and from a contemporary perspective in a quest for the potential conceptual relevance of Paley’s question today. In this vein I argue that from a contemporary point of view statement (iii) may be correct but for different reasons than those adduced by Brunnander.     

The Role of Historical Persian Gardens on the Health Status of Contemporary Urban Residents

The inherent economic and social challenges in major cities have been known to foster stress among the urban population. Frequent stress over long periods may well have serious damaging outcomes, resulting in ailments such as burnout syndrome, sleeplessness and exhaustion, depression, feelings of panic, among others. Therefore, providing access to resources that may enable people to cope with the stress of urban life has become a crucial phenomenon in the twentieth century. Increasing empirical evidence indicates that the presence of natural areas can contribute to enhancing the quality of life in many ways. This study examines two historical Persian gardens from the residents’ perspective in well-known, historic cities of Iran: Isfahan and Kerman. The data were collected through questionnaires (n = 252), semi-structured interviews (n = 20), and visual observation techniques. The findings demonstrate that nature, diversity and the gardens’ historical background, and coherence motivate the residents’ frequent visits to the gardens, which help to address their social, psychological, and physical needs. In addition, the residents’ involvements and the variety of experiences that occur in the gardens lead to the creation of deeper meanings and values associated with the gardens. Subsequently, these construct functional and emotional attachment that evokes a sense of place and identity and may contribute to society’s health and well-being.     

Implementation fidelity trajectories of a health promotion program in multidisciplinary settings: managing tensions in rehabilitation care

Background

Although the importance of evaluating implementation fidelity is acknowledged, little is known about heterogeneity in fidelity over time. This study aims to generate insight into the heterogeneity in implementation fidelity trajectories of a health promotion program in multidisciplinary settings and the relationship with changes in patients’ health behavior.

Methods

This study used longitudinal data from the nationwide implementation of an evidence-informed physical activity promotion program in Dutch rehabilitation care. Fidelity scores were calculated based on annual surveys filled in by involved professionals (n?=?±?70). Higher fidelity scores indicate a more complete implementation of the program’s core components. A hierarchical cluster analysis was conducted on the implementation fidelity scores of 17 organizations at three different time points. Quantitative and qualitative data were used to explore organizational and professional differences between identified trajectories. Regression analyses were conducted to determine differences in patient outcomes.

Results

Three trajectories were identified as the following: ‘stable high fidelity’ (n?=?9), ‘moderate and improving fidelity’ (n?=?6), and ‘unstable fidelity’ (n?=?2). The stable high fidelity organizations were generally smaller, started earlier, and implemented the program in a more structured way compared to moderate and improving fidelity organizations. At the implementation period’s start and end, support from physicians and physiotherapists, professionals’ appreciation, and program compatibility were rated more positively by professionals working in stable high fidelity organizations as compared to the moderate and improving fidelity organizations (p?<?.05). Qualitative data showed that the stable high fidelity organizations had often an explicit vision and strategy about the implementation of the program. Intriguingly, the trajectories were not associated with patients’ self-reported physical activity outcomes (adjusted model β?=???651.6, t(613)?=???1032, p?=?.303).

Conclusions

Differences in organizational-level implementation fidelity trajectories did not result in outcome differences at patient-level. This suggests that an effective implementation fidelity trajectory is contingent on the local organization’s conditions. More specifically, achieving stable high implementation fidelity required the management of tensions: realizing a localized change vision, while safeguarding the program’s standardized core components and engaging the scarce physicians throughout the process. When scaling up evidence-informed health promotion programs, we propose to tailor the management of implementation tensions to local organizations’ starting position, size, and circumstances.

Trial registration

The Netherlands National Trial Register NTR3961. Registered 18 April 2013.

     

Development of a novel NURR1/NOT agonist from hit to lead and candidate for the potential treatment of Parkinson's disease

In the course of a programme aimed at identifying Nurr1/NOT agonists for potential treatment of Parkinson’s disease, a few hits from high throughput screening were identified and characterized. A combined optimization pointed to a very narrow and stringent structure activity relationship. A comprehensive program of optimization led to a potent and safe candidate drug displaying neuroprotective and anti-inflammatory activity in several in vitro and in vivo models.     

Biotic and abiotic factors affecting the genetic structure and diversity of butternut in the southern Appalachian Mountains,USA

The abundance of butternut (Juglans cinerea L.) trees has severely declined rangewide over the past 50 years. An important factor in the decline is butternut canker, a disease caused by the fungus Ophiognomonia clavigigenti-juglandacearum, which has left the remaining butternuts isolated and sparsely distributed. To manage the remaining populations effectively, information regarding how butternut’s population genetic structure is affected by environmental and historical factors is needed. In this study, we assessed genetic structure and diversity of 161 butternut trees from 19 adjacent watersheds in the southern portion of butternut’s range using 12 microsatellite markers. We assessed the genetic diversity and genetic differentiation among trees grouped at various spatial scales. Our goal was to use historical abundance and land use data for these watersheds, which are now all a part of the Great Smoky Mountains National Park (GSMNP), to understand the ecological and evolutionary forces that challenge the conservation and management of butternut. In general, butternuts within the 19 neighboring watersheds were all part of one continuous population, with gene flow throughout. Significant genetic differentiation was detected between some groups of trees, but the differentiation was quite small and may not represent an ecologically significant distinction. The mean heterozygosity in all watersheds remained high, despite extensive mortality. Overall, genetic diversity and rare alleles were evenly distributed across all watersheds, with some variability in subpopulations containing butternut-Japanese walnut hybrids (Juglans x bixbyi or buarts). These results indicate that management of this species should focus on protection from future hybridization with Japanese walnut, promotion of regeneration, and persistence of all remaining butternut trees, which still retain high levels of genetic diversity.     

A review of major Crohn’s disease susceptibility genes and their role in disease pathogenesis

Crohn’s disease (CD) is a chronic inflammatory bowel disease whose relevance is increasing in industrialized society. Recent genome wide association studies revealed over seventy one loci associated with disease penetrance. Several variants that increase disease risk encode for altered proteins that diminish bacterial host defense. NOD2 alters intracellular bacterial sensing while ATG16L1 is thought to diminish bacterial clearance by impairing autophagy. Additionally, changes in the IBD5 locus are thought to diminish barrier function. Alternatively, recent data indicate a gain of function genetic variant of IL23R is protective amongst European CD patients. These recent genetic discoveries contradict historical theories that Crohn’s disease results from overactive auto-aggressive responses. Rather, new genetic data suggest disease-associated variants encode for dysfunctional proteins that diminish essential innate immune responses against commensal organisms. This review provides an overview of these critical discoveries and places them in their biological context.     

Can the extinction of Melitaea britomartis in NW Italy be explained by unfavourable weather? An analysis by Optimal Interpolation

We investigated possible correlations between climate-related factors and butterfly range restrictions by selecting a study case represented by four populations of Melitaea britomartis, which become ‘simultaneously’ extinct in NW Italy in 1976–1977 without any observable habitat change. To overcome difficulties related to the analysis of past extinctions and hypothesise causal factors, we applied the Optimal Interpolation method, a statistical method used to create a gridded climatological analysis of temperature and precipitation data, to a historical dataset containing all available information on the Italian butterfly fauna. We tested two different hypotheses: (1) the role of climate change, expressed as a general trend in temperature and precipitation data; (2) the role of extreme weather events, expressed as anomalous conditions during the years of extinctions. Our results show that long-term temperature and precipitation data do not present any clear trend at our study site, suggesting that they cannot be involved in the species’ extinction. On the opposite, 1976 and 1977 were climatologically critical for the study area. In particular, 1977 was characterized by the coldest summer in the entire historical dataset (1958–1977), with strong negative temperature anomalies. Moreover, both years experienced unusually many rainy days during spring and summer. The year 1977 in particular, was the wettest within the entire historical dataset. The years of M. britomartis populations’ extinction were characterised by many more cold and rainy days than usual during the species’ flight period. These results allow us to hypothesize a strong component of unfavourable weather in driving populations’ extinction.     

On the cause and mechanism of phenoptosis

Based upon evolvability theory, phenotypes like aging that offer no apparent individual benefit may evolve nonetheless. Pursuant to that concept, the evolution of a hypothetical, genome-based aging program called phenoptosis was proposed. However, while aging may facilitate evolvability, it need not result from a program specifically selected for that purpose. Instead, it is possible that the potential for aging is conserved within the genome as a part of a beneficial program that orchestrates and integrates developmental transformation of the soma from conception to maturation. Because somatic remodeling is inherently unstable, its continued non-programmatic expression beyond young adulthood (developmental inertia) erodes internal order, initiating and exacerbating aging. Thus, aging may result paradoxically from post-maturational expression of the same programmatic function for somatic transformation that previously provided individual benefit. It did so by ensuring acquisition of reproductive competence, post-reproductive development of parents to nurture offspring and thereby, to guarantee species survival. In an attempt to identify genes capable of controlling developmental inertia, we sequenced DNA from a series of subjects displaying extreme neoteny, i.e. retention of youthful characteristics during adulthood. We hoped to identify mutations associated with delayed development and to compare each subject’s biological and chronological ages. De novo mutations of coding-genes were found in all the subjects, but they could not be definitively identified as a cause of developmental delay. Nonetheless, genetic and epigenetic studies of neotenic subject’s DNA are on-going. We are attempting to determine if phenoptosis specifically evolved to cause aging, or rather if it exists as a cryptic component of the developmental program that expresses its lethal potential serendipitously and only after individual benefit is realized.     

N-Methylanilide and N-methylbenzamide derivatives as phosphodiesterase 10A (PDE10A) inhibitors

PDE10A is a recently identified phosphodiesterase with a quite remarkable localization since the protein is abundant only in brain tissue. Based on this unique localization, research has focused extensively on using PDE10A modulators as a novel therapeutic approach for dysfunction in the basal ganglia circuit including Parkinson’s disease, Huntington’s disease, schizophrenia, addiction and obsessive compulsive disorder. Medicinal chemistry efforts identified the N-methyl-N-[4-(quinolin-2-ylmethoxy)-phenyl]-isonicotinamide (8) as a nanomolar PDE10A inhibitor. A subsequent Lead-optimization program identified analogous N-methylanilides and their corresponding N-methylbenzamides (29) as potent PDE10A inhibitors, concurrently some interesting and unexpected binding modes were identified.