The Economic Benefits Resulting from the First 8 Years of the Global Programme to Eliminate Lymphatic Filariasis (2000–2007)

Background

Between 2000–2007, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) delivered more than 1.9 billion treatments to nearly 600 million individuals via annual mass drug administration (MDA) of anti-filarial drugs (albendazole, ivermectin, diethylcarbamazine) to all at-risk for 4–6 years. Quantifying the resulting economic benefits of this significant achievement is important not only to justify the resources invested in the GPELF but also to more fully understand the Programme''s overall impact on some of the poorest endemic populations.

Methodology

To calculate the economic benefits, the number of clinical manifestations averted was first quantified and the savings associated with this disease prevention then analyzed in the context of direct treatment costs, indirect costs of lost-labor, and costs to the health system to care for affected individuals. Multiple data sources were reviewed, including published literature and databases from the World Health Organization, International Monetary Fund, and International Labour Organization

Principal Findings

An estimated US$21.8 billion of direct economic benefits will be gained over the lifetime of 31.4 million individuals treated during the first 8 years of the GPELF. Of this total, over US$2.3 billion is realized by the protection of nearly 3 million newborns and other individuals from acquiring lymphatic filariasis as a result of their being born into areas freed of LF transmission. Similarly, more than 28 million individuals already infected with LF benefit from GPELF''s halting the progression of their disease, which results in an associated lifetime economic benefit of approximately US$19.5 billion. In addition to these economic benefits to at-risk individuals, decreased patient services associated with reduced LF morbidity saves the health systems of endemic countries approximately US$2.2 billion.

Conclusions/Significance

MDA for LF offers significant economic benefits. Moreover, with favorable program implementation costs (largely a result of the sustained commitments of donated drugs from the pharmaceutical industry) it is clear that the economic rate of return of the GPELF is extremely high and that this Programme continues to prove itself an excellent investment in global health.     

A black-and-red stick insect from the Philippines – observations on the external anatomy and natural history of a new species of Orthomeria

A new stick insect of the genus Orthomeria Kirby, 1904 (Phasmatodea, Aschiphasmatidae) is described from the Philippines. Orthomeria (Orthomeria) kangi sp. n. is readily distinguished from all other congeners by the distinctive blood red colouration of the costal region of the hind wings. Major features of the external morphology of adults, eggs, and first-instar nymphs are illustrated. Locomotory attachment pads are of the smooth type with irregular microgrooves on the contact surface. An unusual condition of male terminalia is the absence of tergal thorn pads on segment 10. The male clasping organs are represented by an elongated vomer terminating in a prominent spine, and by incurved cerci featuring a bilobed apex equipped with a sharp blade-like ridge. Intraspecific variation in body colouration and hind wing length occurs in females. The new species lives at 400-650 m elevation in the surroundings of the Sablang and Tuba regions, in the Benguet Province of Luzon island. Host plants include Ficus spp. (Moraceae), and Pipturus spp. and Leucosyke spp. (Urticaceae). Observations on the mating and defensive behaviour are presented. Orthomeria (Orthomeria) catadromus (Westwood, 1859) is recognised as a junior synonym of Orthomeria (Orthomeria) pandora (Westwood, 1859), syn. n. A lectotype is designated for both species. Finally, an updated identification key to the species of the subgenus Orthomeria is provided.     

Neurofeedback—The Significance of Reinforcement and the Search for an Appropriate Strategy for the Success of Self-regulation

Nine healthy children took part in five sessions of feedback and instrumental conditioning of slow cortical potentials (SCPs). The feedback conditions (the relation between the feedback signal and amplitude of SCP) were inverted after two sessions. Neither the children nor the therapists were aware of this change. The adjustment of the children to the new feedback setting and the self-regulation strategies employed were investigated. The results were as follows: (a) Healthy children achieved control over cortical negativity within two sessions. (b) The change of feedback conditions worsened the regulation abilities, which then improved again within the following three sessions. (c) After the first two sessions, the participants were able to describe strategies that were successful during different phases of self-regulation. (d) Following the change in the feedback conditions, the children re-evaluated the way they influenced their SCPs. However, they did not alter the cognitive or behavioral strategies. The study demonstrated that positive and negative reinforcement and the knowledge of results are more important for successful self-regulation than the search for effective strategies. The relevance of these findings is discussed.     

Cessation of Mass Drug Administration for Lymphatic Filariasis in Zanzibar in 2006: Was Transmission Interrupted?

BackgroundLymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4–6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.ConclusionsOur findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.     

Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters – A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs

Fatty acid binding proteins (FABPs), in particular FABP5 and FABP7, have recently been identified by us as intracellular transporters for the endocannabinoid anandamide (AEA). Furthermore, animal studies by others have shown that elevated levels of endocannabinoids resulted in beneficial pharmacological effects on stress, pain and inflammation and also ameliorate the effects of drug withdrawal. Based on these observations, we hypothesized that FABP5 and FABP7 would provide excellent pharmacological targets. Thus, we performed a virtual screening of over one million compounds using DOCK and employed a novel footprint similarity scoring function to identify lead compounds with binding profiles similar to oleic acid, a natural FABP substrate. Forty-eight compounds were purchased based on their footprint similarity scores (FPS) and assayed for biological activity against purified human FABP5 employing a fluorescent displacement-binding assay. Four compounds were found to exhibit approximately 50% inhibition or greater at 10 µM, as good as or better inhibitors of FABP5 than BMS309403, a commercially available inhibitor. The most potent inhibitor, γ-truxillic acid 1-naphthyl ester (ChemDiv 8009-2334), was determined to have K_i value of 1.19±0.01 µM. Accordingly a novel α-truxillic acid 1-naphthyl mono-ester (SB-FI-26) was synthesized and assayed for its inhibitory activity against FABP5, wherein SB-FI-26 exhibited strong binding (K_i 0.93±0.08 µM). Additionally, we found SB-FI-26 to act as a potent anti-nociceptive agent with mild anti-inflammatory activity in mice, which strongly supports our hypothesis that the inhibition of FABPs and subsequent elevation of anandamide is a promising new approach to drug discovery. Truxillic acids and their derivatives were also shown by others to have anti-inflammatory and anti-nociceptive effects in mice and to be the active component of Chinese a herbal medicine (Incarvillea sinensis) used to treat rheumatism and pain in humans. Our results provide a likely mechanism by which these compounds exert their effects.     

The Postnatal Development of the Cerebellum— A fMRI and Silver Study

Summary The aim of this study was to evaluate the postnatal development of the cerebella of the pig and to compare this with the activation of the fMRI. The cells in the cerebella were studied by silver technique and the activation of the fMRI in the cerebella was initiated by flexion and extension of the hind paw. Our results showed an increase of the branching of the cells of the cerebellar cortex postnatally, coordinated with registration of fMRI active sites in the cerebella at 6-month postnatal. We concluded that the full maturation of the cerebella was around 6-month postnatal in the pig.     

The Ethical Basis for Sustainable Human Security: A Place for Anthropocentrism?

The deep and lasting changes to human behaviour that are required to address the global environmental crisis necessitate profound shifts in moral foundations. They amount to a change in what individuals and societies conceive of as progress. This imperative raises important questions about the justification, ends, and means of large-scale changes in people’s ethics. In this essay I will focus on the ends—the direction of moral change as prescribed by the goal of sustainable human flourishing. I shall present a meta-ethical critique of anthropocentrism and propose that only an ecocentric ethic can support the sustainable flourishing of humanity. This proposition does not necessarily contradict itself. My claim will be that the values subsumed under the broad concept of anthropocentrism are categorically counterproductive, informing an undesirable concept of “progress”. I support this claim with two lines of argument. On the one hand, the end values of anthropocentrism are shallow and the “flourishing of humanity” is ill-defined. The conceptual constraints of anthropocentrism itself preclude a more concise definition which would take into account the utter dependence of the flourishing of humanity on the health of ecological support structures. On the other hand, pursuing the values that inform the actions of anthropocentrists (which may be identical with the “flourishing of humanity”) leads to unintended and undesirable outcomes, even from the view of the anthropocentrist herself. Those problems are not encountered with an ecocentric ethic, and the conceptual steps necessary to adopt it are not insurmountable.     

Combined Pulse Electroporation – A Novel Strategy for Highly Efficient Transfection of Human and Mouse Cells

The type of a nucleic acid and the type of the cell to be transfected generally affect the efficiency of electroporation, the versatile method of choice for gene regulation studies or for recombinant protein expression. We here present a combined square pulse electroporation strategy to reproducibly and efficiently transfect eukaryotic cells. Cells suspended in a universal buffer system received an initial high voltage pulse that was continuously combined with a subsequent low voltage pulse with independently defined electric parameters of the effective field and the duration of each pulse. At comparable viable cell recoveries and transfection efficiencies of up to 95% of all cells, a wide variety of cells especially profited from this combined pulse strategy by high protein expression levels of individual cells after transfection. Long-term silencing of gene expression by transfected small interfering RNA was most likely due to the uptake of large nucleic acid amounts as shown by direct detection of fluorochromated small interfering RNA. The highly efficient combined pulse electroporation strategy enables for external regulation of the number of naked nucleic acid molecules taken up and can be easily adapted for cells considered difficult to transfect.     

Optimization of the All-D Peptide D3 for Aβ Oligomer Elimination

The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer’s disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized d-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified d-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.     

Development of SCN Connectivity and the Circadian Control of Arousal: A Diminishing Role for Humoral Factors?

The suprachiasmatic nucleus (SCN) is part of a wake-promoting circuit comprising the dorsomedial hypothalamus (DMH) and locus coeruleus (LC). Although widely considered a “master clock,” the SCN of adult rats is also sensitive to feedback regarding an animal''s behavioral state. Interestingly, in rats at postnatal day (P)2, repeated arousing stimulation does not increase neural activation in the SCN, despite doing so in the LC and DMH. Here we show that, by P8, the SCN is activated by arousing stimulation and that selective destruction of LC terminals with DSP-4 blocks this activational effect. We next show that bidirectional projections among the SCN, DMH, and LC are nearly absent at P2 but present at P8. Despite the relative lack of SCN connectivity with downstream structures at P2, day-night differences in sleep-wake activity are observed, suggesting that the SCN modulates behavior at this age via humoral factors. To test this hypothesis, we lesioned the SCN at P1 and recorded sleep-wake behavior at P2: Day-night differences in sleep and wake were eliminated. We next performed precollicular transections at P2 and P8 that isolate the SCN and DMH from the brainstem and found that day-night differences in sleep-wake behavior were retained at P2 but eliminated at P8. Finally, the SCN or DMH was lesioned at P8: When recorded at P21, rats with either lesion exhibited similarly fragmented wake bouts and no evidence of circadian modulation of wakefulness. These results suggest an age-related decline in the SCN''s humoral influence on sleep-wake behavior that coincides with the emergence of bidirectional connectivity among the SCN, DMH, and LC.     

Mozzarella Cheese – A Review of the Structural Development During Processing

From its journey from milk through to its end use, Mozzarella cheese undergoes significant transformations in its makeup of components and their structural arrangement. The typical Mozzarella processing steps each alter the structural configuration of the system. The colloidal dispersion of proteins, fat, lactose and minerals that is milk experiences physical, thermal, chemical, biological and ionic induced changes to its composition and structure throughout the manufacturing process and storage. This review critically evaluates the literature related to the structural changes occurring as a result of each step in Mozzarella cheese production process. Emphasis is placed on the role of each step and the induced transformations at the micro and macro scale in the system. Additionally, the review also looks at the changes that occur as a result of storage. This evolution in structure culminates in the creation of an end product with a bi-continuous gel structure that has a desired functionality in its end use.     

A Strategy to Optimize the Oligo-Probes for Microarray-based Detection of Viruses

DNA microarrays have been acknowledged to represent a promising approach for the detection of viral pathogens. However, the probes designed for current arrays could cover only part of the given viral variants, that could result in false-negative or ambiguous data. If all the variants are to be covered, the requirement for more probes would render much higher spot density and thus higher cost of the arrays. Here we have developed a new strategy for oligonucleotide probe design. Using type I human immunodeficiency virus (HIV-1) tat gene as an example, we designed the array probes and validated the optimized parameters in silico. Results show that the oligo number is significantly reduced comparing with the existing methods, while specificity and hybridization efficiency remain intact. The adoption of this method in reducing the oligo numbers could increase the detection capacity for DNA microarrays, and would significantly lower the manufacturing cost for making array chips.     

A new species of the shrew‐mouse,Archboldomys (Rodentia: Muridae: Murinae), from the Philippines

A new species of murid rodent belonging to the ‘shrew‐mouse’ genus Archboldomys is described from Kalinga Province in northern Luzon Island, Philippines. This is the third known species of this endemic Philippine genus. The new species is distinguished from its congeners by consistent differences in adult body size, limb and tail proportions, coloration and texture of the pelage, and cranial and dental dimensions. Members of this genus are small, diurnal rodents that feed mainly on earthworms and other soil invertebrates, and occur in high elevation montane and mossy forests habitats. The new species may be restricted to the northern portion of the Cordillera Central, whereas its congeners occur in widely separated highland areas in other portions of Luzon. The fact that similar distribution patterns are seen for members of other endemic genera suggests that habitat vicariance may have shaped much of the diversification of murid rodents on Luzon.     

On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis

Parkinson’s disease psychosis (PDP) is a condition that may develop in up to 60 % of Parkinson’s patients, and is a major reason for nursing home placement for those affected. There are no FDA approved drugs for PDP but low doses of atypical anti-psychotic drugs (APDs) are commonly prescribed off-label. Only low-dose clozapine has shown efficacy in randomized controlled trials, but all APDs have black box warnings related to the increased mortality and morbidity when used in elderly demented patients. Using molecular pharmacological profiling of a large collection of marketed drugs, we discovered that potent inverse agonist activity against 5-HT_2A serotonin receptors was a common feature of atypical APDs, especially the atypical APDs used to treat PDP. Since low-dose clozapine therapy selectively blocks this receptor, it was hypothesized that a highly selective 5-HT_2A receptor inverse agonist might provide good symptom control in patients suffering from PDP, with a greatly improved safety and tolerability profile. A high throughput screening and subsequent chemical lead optimization campaign to develop potent, selective 5-HT_2A receptor inverse agonists was launched, eventually resulting in the discovery of pimavanserin. Pimavanserin displays nanomolar potency as a 5-HT_2A receptor inverse agonist, selectivity for 5-HT_2A over 5-HT_2C receptors, and no meaningful activity at any other G-protein coupled receptor. It demonstrated robust activity in preclinical models of schizophrenia and PDP, and did not worsen motoric symptoms, in contrast to the APDs tested. In a Phase III clinical trial, pimavanserin showed highly significant benefits in the primary endpoint, the scale for assessment of positive symptoms-PD, a scale adapted for use in PDP. In addition, improvements in all other efficacy endpoints, including physician’s clinical global impression, caregiver burden, night-time sleep quality and daytime wakefulness, were seen. Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III. An open-label extension study has further demonstrated that pimavanserin is safe and well-tolerated with long-term use. Pimavanserin may therefore offer a viable treatment option for patients suffering from PDP.     

Rapid Assessment Procedure for Loiasis and Mapping Lymphatic Filariasis: Two Perfect Illustrations of “To Be in English or Not to Be”

Interest in filariasis has found a new impetus now that neglected tropical diseases have their own journal. However, some of the advances published in renowned international journals have completely ignored previous publications on the subject, particularly those in languages other than English. The rapid assessment procedure for loiasis and the mapping of lymphatic filariasis provide two perfect illustrations of this. This problem may seem a bit outdated, given that all “good authors” now publish exclusively in English. It certainly is outdated for most areas of medicine. But, surely, this should not be the case for neglected tropical diseases, for which certain long-standing findings are every bit as important as what may be presented as new discoveries. One possibility would be for certain journals, such as PLOS Neglected Tropical Diseases, to include a specific heading permitting the publication in English of older studies that initially appeared in a language other than English. The texts would be English versions respecting the entirety of the original text. Submission should be accompanied by a presentation of the problem, with details and explanatory comments, with submission at the initiative of the authors of the former article in question or their students or sympathizers.Interest in filariasis has found a new impetus now that neglected tropical diseases (NTDs) have their own journal. However, some of the advances published in renowned international journals have completely ignored previous publications on the subject, particularly those in languages other than English. This Viewpoint article is intended to make us ponder the issue of a language gap or discrimination existing in publishing outcomes and reference citations. This is also the question of deleterious effects of the obligation “to be in English or not to be”.The rapid assessment procedure for loiasis (RAPLOA) and the geographical distribution of lymphatic filariasis provide two perfect illustrations of this.The RAPLOA has recently been widely used to determine the regional endemicity of loiasis and to update existing endemicity data for this disease over its global distribution range. This important work has been recently published in PLOS NTDs [1]. The determination, within a population of the prevalence or, preferably, the annual incidence of episodes, of conjunctival migration by adult worms is a simple, non-invasive, relatively sensitive and specific method for evaluating the endemicity of Loa loa. This approach has proved particularly useful in areas in which both loiasis and onchocerciasis are observed: the mass treatment program to control onchocerciasis is based on the use of ivermectin and there is a risk of adverse treatment outcomes in patients carrying large numbers of L. loa worms [2]. In regions of high endemicity, the correlation between the conjunctival migration index and the microfilarial index is strong overall, both for villages and for age groups. Its use as an epidemiological index was clearly proposed in a publication in 1994 [3]. However, as this article was published in French, in Médecine Tropicale (Marseille), it has never been cited, despite being listed in international databases, including PubMed. A poster communication concerning the same issue had no real impact either, despite being presented at an international congress [4]. The origin of this new epidemiological index (RAPLOA) is systematically attributed to two World Health Organization (WHO) publications in 2001 [5] and 2002 [6]. It is true that the studies reported in these publications validated the concept at a large scale and in different endemic foci.The usefulness of specific clinical manifestations (eye worm and Calabar swelling) to assess L. loa had been recommended by different authors as early as 1950 [7]. But the correlation between the microfilarial index and the frequency of ocular migration has not been studied, and even less attention was paid to the notion of an epidemiological index until the epidemiological studies carried out in Congo Republic (former People''s Republic of the Congo) during the 1980s [8]. However, the index as such was clearly defined in 1994 [3]. Here is a direct translation of an excerpt of the French text published in 1994: “For loiasis, the usual parasitological indices (microfilarial index and mean microfilarial density) are the only measures recognized as providing information about the level of endemicity in humans. In addition to requiring blood samples standardized in terms of both volume and sampling time, these indices do not reflect the real level of parasitism, given the high frequency of infected subjects without microfilaria in the blood. Subjects infested with mature, fertile adult worms, as demonstrated by the removal of a subconjunctival female containing microfilaria from a patient with no detectable microfilaria in the blood, are frequently observed. Two symptoms are both specific and frequent in infected subjects both with and without microfilaria in the blood: subconjunctival migration of an adult worm and elusive, migrating edemas of the hands, wrists and lower part of the forearm” [9]. “The index of subconjunctival filarial migration over the preceding year is particularly useful, because it correlates well with the microfilarial index but is more sensitive” (Figure 1). “Its determination involves precise questioning of the patient, which can be facilitated by the use of a demonstration chart, with diagrams and photographs” (see Figure 2).Open in a separate windowFigure 1Index of the subconjunctival migration of Loa loa adult worms and microfilarial index.Reproduced from Medicine Tropicale [3], released under CC BY 2.0 by Medicine Tropicale. IMSC = Indice de Migration Sous-Conjonctivale in French and Index of the SubConjunctival Migration in English. IM = Indice Microfilarien in French and Microfilarial Index in English.Open in a separate windowFigure 2Illustration of the passage of an adult worm (Loa loa) across the eye.This illustration (diagram and photograph) was made for presentation to patients questioned in endemic regions.The conclusion of this article was formulated as follows: “Screening for foci of filarial endemicity could be improved by the use of a simplified method and the validation of simple, inexpensive indices. Once these foci have been identified, a more precise evaluation can be carried out.”What is most astounding about the two WHO publications cited as the origin of this “new epidemiological index” [5], [6] is that the principal authors come from French-speaking African countries and/or work in or with this institution. They would therefore have been able to understand articles written in French. Furthermore, the WHO has a long-standing culture of multilingualism, particularly in English and French.Against this background, the rejection by the Bulletin of the World Health Organization and by other international journals published in English of an opinion article dealing with this issue and using the example of lymphatic filariasis does not seem to be justified, and is another illustration of “to be in English or not to be.”Indeed, filariasis due to Wuchereria bancrofti is systematically described as endemic in Congo and Gabon, two French-speaking countries, in non-specialist works on tropical medicine and in more specialist publications (WHO) despite a total absence of epidemiologic studies and/or confirmed case report over the last 30 years to prove it. What is certain is that no case was found when the last studies were conducted in these countries at the end of the 1970s and during the 1980s but unfortunately published in French. The studies that we carried out in the Congo as part of the National Project on Onchocerciasis and Other Filariases (between 1982 and 1987) confirmed the presence of four types of human filariasis: onchocerciasis, loaiasis, and the filariases caused by Mansonella perstans and M. streptocerca. There was a total absence of confirmed cases of lymphatic filariasis (bancroftosis). In this case, it is not a question of the attribution of merit for a particular “discovery”, but of basic knowledge of the geographic distribution of a scarcely studied disease, lymphatic filiariasis, in French Central Africa. Taking into account only publications in English, even older and poorly structured data, have been, in our opinion, a source of confusion and has led to false conclusions being drawn about the distribution range of this disease. This undoubtedly highlights the need to update knowledge by carrying out prospective studies (which seem to be underway), but these studies do not seem to be considered a matter of priority given the low levels of resources available and current health priorities.This has drawn us to publish this article in a French-language journal, but together with an entire translation into English [10]. Despite the bilingual nature of this publication, the international PubMed database identifies this article as being published in French, effectively ensuring that it will never be consulted, a classic “catch 22” situation! Indeed, this reference has never yet been cited by another author in a journal published in English. It may be that publication of an article in another language than English makes it more likely that it will not be cited, even if the authors of a subsequent article have access to the journal in which it was published and can understand the language used. Here, we begin to encroach on ethical problems and it is probably best not to delve too deeply. However, suffice it to say that the limited dissemination of publications in a language other than English may account for such equivocal attitudes.The problem is not a rivalry between French and English, but the confrontation between English and all other languages of the world. Moreover, the problem is undoubtedly worse for works published in non–Western European languages such as Chinese, Russian, and Japanese, which are arguably even less accessible.All things considered, this problem may seem a bit outdated, given that all “good authors” now publish exclusively in English. It certainly is outdated for most areas of medicine, where everything that is old is assigned to being nothing more than the history of medicine. But, surely, this should not be the case for NTDs, for which certain long-standing findings are every bit as important as what may be presented as new discoveries.One possibility would be for certain journals, such as PLOS NTDs, to include a specific heading permitting the publication of older studies that initially appeared in a language other than English (and are therefore currently little known). The texts included in this heading would essentially be English versions of these articles previously published in other languages, respecting the entirety of the original text.This would concern studies considered of importance because they highlight a point that remains unclear or describe an aspect considered innovative in a review but for which the originality of the article is due more to an incomplete reference list than to a true advance in knowledge. These articles should be judged in light of the knowledge and technical and methodological means available at the time at which they were initially published. Submission should be accompanied by a presentation of the problem, with details and explanatory comments, with submission at the initiative of the authors of the article in question or their students or sympathizers.