Reasons for failing to confirm a diagnosis in samples of sheep origin,submitted for laboratory examinations

In Great Britain changes in the proportion of samples submitted to diagnostic laboratories, for which no diagnosis is confirmed, are monitored as a possible indicator of new or emerging diseases. Herewith, perceived reasons for failing to reach a diagnosis were provided for the year 2008. No diagnosis could be confirmed in 39% of these; however, if those subjected to limited testing were excluded, then that proportion was 20%. Most frequently recorded reasons that no diagnosis was confirmed were “incomplete sample range submitted” (8% of total samples submitted), “full diagnostic package not requested” (6%), “post-mortem material required but unavailable” (4%) and “inconclusive test results” (2%). No reason could be identified in 8% of samples submitted. Selection of these samples for further analysis may enhance surveillance for emerging/re-emerging diseases.     

Reproduction humaine: le point de vue du philosophe

This article discusses and essential aspect of the link between ethics and life, as expressed in the concept of bioethics. It discusses the various issues related to human reproduction from “the philosopher’s point of view”. This discussion is limited to the principles of this field. The author starts by justifying a philosophical approach to ethical problems in the context of medicine in general and reproduction in particular, a field which specialists, theoreticians or practitioners of medicine and legal medicine in particular, appear to have ignored. This leads to a discussion of the human aspects of reproduction, from questions concerning the nature of living beings (individuals and species) to the relationship between nature and culture (symbol and freedom). Although man “reproduces” and “procreates”, he is also technically able to “produce himself”. This shift from biological reproduction to procreation must take into account problems related to technological science in medicine (technical control of living material and so-called “neutrality” of the technique). The main bioethical issues involving an ethics of decision-making in the field of human reproduction (contraception, abortion, status of the embryo, medically-assisted procreation, desire to master the “form” of the “reproduced” human, or even the “product”, cloning) are then discussed. Finally, the author proposes elements of a “philosophy of point of view”, requiring responsibility for each decision in the context of an “ethics of discussion”.     

Theory of aggregation in solution. I. General equations and application to the stacking of bases,nucleosides, etc.

Earlier theoretical work on aggregation in imperfect gases and in solutions of protein molecules is reformulated here in such a way as to be applicable to a number of aggregation systems in solution. The theory is most easily developed for an “osmotic” solution. It is exact, in principle, and in particular does not treat the aggregates as an ideal mixture as is usually done. If osmotic virial coefficients are diffcult to measure in a particular case, it is then necessary to relate these coefficients to properties of the more conventional “constant pressure” solution. An important special case is used as an example in the last three sections: The stacking of bases, nucleosides, etc., is represented by a statistical mecchanical model in which the aggregates resemble vertical stacks of checkers.     

The cost of being “real”: black authenticity,colourism, and Billboard Rap Chart rankings

Research on black authenticity identifies “oppressive othering” and “white standards of beauty”, particularly lighter skin tone, as key components. Few studies disentangle which of these two theoretical components matter the most for a particular outcome. Rap music, whose lyrics are often categorized as authentic expressions of blackness, offers an intriguing case to compare the effects of “oppressive othering” (as alcohol and drug lyrics) and “white standards of beauty” (as the rap artist’s skin tone) on national music charts. Analysing artists’ skin tone and lyrical content of songs ranked on Billboard Rap Year-End Charts from 2007 to 2011, results show that lighter skin tone is significantly and positively related to higher chart rankings. Alcohol and drug lyrics, however, had a non-significant effect. Implications are discussed in relation to the effects of the commodified imagery of “authentic” blackness in the new digital era of music.     

The molecular structure of the receptor-ionophore complex at the neuromuscular junction.

A general theory of the molecular structure of receptors for transmitters based only on protein has been presented elsewhere (Smythies, 1974a,b). The acetylcholine receptor at the neuromuscular junction is postulated in particular to be based on a Kusnetsov-Ghokov grid with four sequencestwo “primary” chains A-x-B-cys-A-x-B where A = arg or lys and B = glu or phosphoser and two “secondary” chains of sequence -gly-x-gly-pro-x-ile-cys-asp-x- forming a symmetrical receptor cup of rectangular form. The present paper extends the model to include the gate over the adjacent ionophore (or “ion conductance modulator”: ICM) and the linking mechanism from receptor to gate. These are postulated to consist of a second Kusnetsov-Ghokov grid generated by a third “primary” chain along the side that covers the orifice to the ion conducting channel. The action of ACh is postulated to be to displace an hydrated Ca⁺⁺ ion from the receptor cup and to disrupt the AB rungs in the receptor grid. The middle primary chain then slides 14 Å and the AB links reform. This replaces a bulky amino acid pair normally blocking the ion channel by a less bulky amino acid pair and so hydrated ions can be transmitted. It is further postulated that snake neurotoxins (ACh blockers) in a specified conformation bind mainly to the ionophore grid and prevent the sliding filament mechanism from opening; whereas the snake “cardiotoxins” (ACh agonists)—in a specified conformation—bind to the same sliding filament mechanism in its “open” ionophore gate and prevent it being closed: and histrionicotoxin binds to the same open “gate” but blocks it physically. The hypothesis may rigorously be tested by experiment as it makes detailed predictions on the X-ray structure of the snake neurotoxins and cardiotoxins.     

The Karyotypes of Angelica dahurica and Their Taxonomical Significance (Umbelliferae)

The present paper deals mainly with the karyotype analysis of five materials in Angelica dahurica collected in Yanbian of Jilin, Anguo of Hebei, Yuxian of Henan, Hangzhou of Zhejiang and Suining of Sichuan. They are under the names “Dongbeidahuo”, “Qibaizhi”, “Yubaizhi”, ”Hangbaizhi” and “Chuanbaizhi” respectively. Among then “Dongbeidahuo” is a wild plant, which occurs in northeastern China, and the others are cultivated as important crude drugs in some provinces. “Qi-Baizhi” and “Yubaizhi” have been identified as conspecific with the wild Baizhi-“Do-Ngbeidahuo” (A. dahurica) according to the external morphological features, whereas the other cultivated ones, “Hangbaizhi” and “Chuanbaizhi”, treated as a variety (A. dahurica var. formosana). The results of karyotype analysis are shown in Plate 1, 2, with the formula 2n=22 =12 m+2 m^SAT+4sm+4st. The karyotypes described here are constantly characterized by satellites attached to the fourth pair of metacentric chromosomes and differ from the published reports on the other species of the genus. It is reasonable to say that the five materials collectively named “Baizhi” are taxonomically closely related to each other and could be regarded as conspecific. Since the second chromosome pair is submetacentric in “Dongbeidahuo”, it may be justifiable to separate the wild plant from the cultivated ones and treat them as two separate varieties.     

Tropicality and abjection: What do we really mean by “Neglected Tropical Diseases”?

Neglected tropical diseases are defined operationally as diseases that prevail in “tropical” regions and are under‐researched, under‐funded, and under‐treated compared with their disease burden. By analysing the adjectives “tropical” and “neglected,” I expose and interrogate the discourses within which the term “neglected tropical disease” derives its meaning. First, I argue that the term “tropical” conjures the notion of “tropicality,” a form of Othering which erroneously explains the disease‐prevalence of “tropical” regions by reference to environmental determinism, rather than colonialism and neocolonialism. Second, I examine the way in which this Othering enables the abjection of tropical regions and their peoples, leading to neglect. I recommend that the term “neglected tropical diseases” be more carefully contextualised within health scholarship, education, and policy.     

Evening typology and morning tiredness associates with low leisure time physical activity and high sitting

Circadian typology is a latent trait that is usually assessed with scoring on a series of questions thought to represent the construct. But, in the classification, most people fall into the intermediate type, i.e. neither a definite morning nor an evening type, but still showing stronger preference towards either end of the continuum. Our aim was to operationalize chronotype using latent class analysis (LCA) for a 6-item scale derived from the original Horne–Östberg Morningness–Eveningness Questionnaire to compare and understand characteristics of chronotype in a population-based sample of adults in Finland. A total of 4904 men and women aged 25–74 years were included. We also analyzed the associations of chronotypes with physical activity (PA) and sitting. We found five latent chronotype groups including “rested more-evening type” (28%), “rested more-morning type” (24%), “morning type” (23%), “tired more-evening type” (17%) and “evening type” (8%) groups. Operationalization of chronotype by LCA suggests that morning alertness is an important feature differentiating chronotypes. Further, the “evening type” and the “tired, more-evening type” had higher odds for none to very low as well as low PA, as compared to “morning type”. In addition, “evening type” was associated with higher odds for more time spent sitting, as compared to “morning type”. Our findings indicate that it is important to assess sleep schedules and morning tiredness, which then could be targeted as a potential mediating factor for health behaviors, in particular, PA and health status.     

Sustainability indicator development—Science or political negotiation?

The efforts to develop sustainability indicators have strongly increased since the beginning of the 1990s, often led by intergovernmental processes. More recently, a number of sustainability indicator development processes have been initiated within large research projects that aim to design tools for sustainability assessments, funded by the European Union. The development of sustainability indicators provides a particular challenge to scientists, given the essentially normative dimension of the concept of “sustainability”. Thus, we argue, the development of sustainability indicators is a process of both scientific “knowledge production” and of political “norm creation”, and both components need to be properly acknowledged. Based on a respective theoretical framework and comparing five cases of sustainability indicator development processes (three science-led and two led by intergovernmental processes), we find that the political norm creation dimension is not fully and explicitly recognized in science-led processes. The paper concludes by discussing a number of implications for the design of sustainability indicator development processes, in particular with regard to participation and representation as well as adjustment of indicators over time.     

Bursting synchronization dynamics of pancreatic β-cells with electrical and chemical coupling

Based on bifurcation analysis, the synchronization behaviors of two identical pancreatic β-cells connected by electrical and chemical coupling are investigated, respectively. Various firing patterns are produced in coupled cells when a single cell exhibits tonic spiking or square-wave bursting individually, irrespectively of what the cells are connected by electrical or chemical coupling. On the one hand, cells can burst synchronously for both weak electrical and chemical coupling when an isolated cell exhibits tonic spiking itself. In particular, for electrically coupled cells, under the variation of the coupling strength there exist complex transition processes of synchronous firing patterns such as “fold/limit cycle” type of bursting, then anti-phase continuous spiking, followed by the “fold/torus” type of bursting, and finally in-phase tonic spiking. On the other hand, it is shown that when the individual cell exhibits square-wave bursting, suitable coupling strength can make the electrically coupled system generate “fold/Hopf” bursting via “fold/fold” hysteresis loop; whereas, the chemically coupled cells generate “fold/subHopf” bursting. Especially, chemically coupled bursters can exhibit inverse period-adding bursting sequence. Fast–slow dynamics analysis is applied to explore the generation mechanism of these bursting oscillations. The above analysis of bursting types and the transition may provide us with better insight into understanding the role of coupling in the dynamic behaviors of pancreatic β-cells.     

Randomness and multilevel interactions in biology

The dynamic instability of living systems and the “superposition” of different forms of randomness are viewed, in this paper, as components of the contingently changing, or even increasing, organization of life through ontogenesis or evolution. To this purpose, we first survey how classical and quantum physics define randomness differently. We then discuss why this requires, in our view, an enriched understanding of the effects of their concurrent presence in biological systems’ dynamics. Biological randomness is then presented not only as an essential component of the heterogeneous determination and intrinsic unpredictability proper to life phenomena, due to the nesting of, and interaction between many levels of organization, but also as a key component of its structural stability. We will note as well that increasing organization, while increasing “order”, induces growing disorder, not only by energy dispersal effects, but also by increasing variability and differentiation. Finally, we discuss the cooperation between diverse components in biological networks; this cooperation implies the presence of constraints due to the particular nature of bio-entanglement and bio-resonance, two notions to be reviewed and defined in the paper.     

Appropriateness in allergic respiratory diseases health care in Italy: definitions and organizational aspects

In a historical period in which sustainability of the National Health Service is mandatory because of the international economical situation, the limited available resources at national level and the tendency of passing from a “population medicine” model towards the concept of “individualized medicine”, the debate on appropriateness of medical and surgical procedures is of central importance. The choosing wisely campaign, started in United States in 2012 and then spread all over the world, tries to summarize which are the most inappropriate procedures for each medical and surgical speciality; as far as allergic respiratory diseases, the most relevant Italian societies and the American Academy defined the allergological procedures with the highest probability of inappropriateness. In Italy, a recent decree of the Ministry of Health defined a list of more than 200 procedures that will be considered as inappropriate in certain conditions; many of these procedures concern allergology, including allergic respiratory diseases. In this commentary we discuss the above mentioned decree and the concept of appropriateness in the field of allergic respiratory diseases, trying to figure out some practical considerations based on the current health resources available in the field of allergology in Italy.     

Follow the money: international donors,external homelands and their effect on Romani media and advocacy

ABSTRACT

While Roma are both Europe’s largest minority, there is no “homeland” state that claims to guard their interest. The lack of “an external national homeland” [Brubaker, R. 1996. Nationalism Reframed: Nationhood and the National Question in the New Europe. Cambridge: Cambridge University Press] to watchdog and safeguard their rights has a particular effect on how Roma engage as political actors and subjects. International donors/foundations have assumed the role of “external homeland”. This article explores the effect that donors’ funding priorities have on Romani advocacy – specifically Romani journalism. Drawing upon multi-sited fieldwork in five countries, extensive document analysis, and interviews, Idemonstrate that the change in Romani media content over the past two decades reflects the shift in funders’ priorities, particularly in relation to the European project. “The Roma” become a tool for donors and European institutions to build a “European” identity while Romani-led advocacy becomes increasingly marganilized.     

What is a cladogram and what is not?

The origins and meanings of “cladogram” are reviewed. Traditionally, “cladogram” has been defined as a graphical representation of an empirical hypothesis of relationships among taxa, based on evidence from synapomorphies alone. Disturbingly, numerous recent authors treat “cladogram” as synonymous with “dendrogram” and do not appreciate the particular methodological connotations of the former term. This is lamented.     

网络药理学和分子对接技术研究桑黄类真菌对疾病的潜在作用机制

桑黄类真菌是一类极具研究价值的药用真菌。近年来,对于桑黄类真菌的研究,多集中于对某一个物种的成分及药理活性的研究,系统比较桑黄类真菌中成分及药理活性的研究较少。本研究利用网络药理学和分子对接技术从理论上初步探讨了5种桑黄类真菌中化合物与疾病之间的分子作用机制。研究结果表明5种桑黄类真菌(栎木桑黄Sanghuangporus quercicola、鲍姆桑黄Sanghuangporus baumii、粗毛纤孔菌Inonotus hispidus、裂蹄木层孔菌Tropicorus linteus、黑盖木层孔菌Phellinus nigrians)中的39种有效成分,对应潜在靶点588个。KEGG通路富集筛选得到165条通路,分析结果发现这39种化合物的靶点主要分布在与炎症、糖尿病、肝癌、阿尔茨海默病和衰老相关的信号通路上。筛选出桑黄类真菌中抗病的潜在靶点共486个,构建抗病靶点的蛋白互作(PPI)网络,并筛选出LCK、STAT3、PTPN11、STAT1、STAT5B、MAPK1、JAK1、MAPK3、JAK3和JAK2作为关键靶点,构建5种桑黄类真菌-化合物-关键靶点-5种疾病的网络互作图,并进行分子对接验证。筛选出的桑黄类真菌中的12个有效成分均可与这些关键靶点产生相互作用,其中酚类化合物居多,此外二萜类化合物异海松酸与MAPK1结合能力最强。因此,5种桑黄类真菌可以通过多种化合物、多种靶点和多种途径起到抗病的作用,本研究为探索桑黄类真菌治疗和预防疾病潜在机制提供了理论基础。     

MicroRNAs and extracellular vesicles in cholangiopathies

Cholangiopathies encompass a heterogeneous group of disorders affecting biliary epithelial cells (i.e. cholangiocytes). Early diagnosis, prognosis and treatment still remain clinically challenging for most of these diseases and are critical for adequate patient care. In the past decade, extensive research has emphasized microRNAs (miRs) as potential non-invasive biomarkers and tools to accurately identify, predict and treat cholangiopathies. MiRs can be released extracellularly conjugated with lipoproteins or encapsulated in extracellular vesicles (EVs). Research on EVs is also gaining attention since they are present in multiple biological fluids and may represent a relevant source of novel non-invasive biomarkers and be vehicles for new therapeutic approaches. This review highlights the most promising candidate miRs and EV-related biomarkers in cholangiopathies, as well as their relevant roles in biliary pathophysiology. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

TRP channels in disease

“Transient receptor potential” cation channels (TRP channels) play a unique role as cell sensors, are involved in a plethora of Ca²⁺-mediated cell functions, and play a role as “gate-keepers” in many homeostatic processes such as Ca²⁺ and Mg²⁺ reabsorption. The variety of functions to which TRP channels contribute and the polymodal character of their activation predict that failures in correct channel gating or permeation will likely contribute to complex pathophysiological mechanisms. Dysfunctions of TRPs cause human diseases but are also involved in a complex manner to contribute and determine the progress of several diseases. Contributions to this special issue discuss channelopathias for which mutations in TRP channels that induce “loss-“ or “gain-of-function” of the channel and can be considered “disease-causing” have been identified. The role of TRPs will be further elucidated in complex diseases of the intestinal, renal, urogenital, respiratory, and cardiovascular systems. Finally, the role of TRPs will be discussed in neuronal diseases and neurodegenerative disorders.     

Selection explanations of token traits

The “negative view” is the claim that natural selection cannot explain why a particular individual has one trait, rather than another. Here, I modify an example from Lewens (2001) to show that this claim is sometimes false. I then advance a variation on the negative view. It is the claim that selection at the organism level within a lineage cannot explain why a particular individual in that lineage has one allele, rather than another. This formulation better describes the explanatory role of selection.