Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.

BACKGROUND: Brentuximab vedotin (BV) is a key therapeutic agent for patients with relapsed/refractory classical Hodgkin lymphoma (cHL). The outcomes of patients experiencing disease progression after BV are poorly described. PATIENTS AND METHODS: We reviewed our institutional database to identify patients with cHL treated with BV who were either refractory to treatment or experienced disease relapse. We collected clinicopathologic features, treatment details at progression and outcome. RESULTS: One hundred patients met inclusion criteria, with a median age of 32 years (range 18-84) at progression after BV. The median number of treatments before BV was 3 (range 0-9); 71 had prior autologous stem cell transplant. The overall response rate (ORR) to BV was 57%, and the median duration of BV therapy was 3 months (range 1-25). After disease progression post-BV, the most common treatment strategies were investigational agents (n = 30), gemcitabine (n = 15) and bendamustine (n = 12). The cumulative ORR to therapy was 33% (complete response 15%). After a median follow-up of 25 months (range 1-74), the median progression-free (PFS) and overall survival (OS) were 3.5 and 25.2 months, respectively. In multivariate analysis, no factors analyzed were predictive of PFS; age at progression >45 years and serum albumin <40 g/l at disease progression were associated with increased risk of death. Among patients who achieved response to therapy, allogeneic stem cell transplantation was associated with a non-significant trend toward superior OS (P = 0.11). CONCLUSIONS: Patients with BV-resistant cHL have poor outcomes. These data serve as a reference for newer agents active in BV-resistant disease.

Topographical presentation of dental wear as arches in a French mediaeval population.

UNLABELLED: The diversity of notation systems for recording dental characteristics and the means used to display them makes comparisons and interdisciplinary collaboration difficult. OBJECTIVE: The aim of the present study is to propose the use of a method employed by experts worldwide but which may be new to bioarchaeologists. Since 1971 we have used the International Dental Federation (FDI) system, which provides the location of dental characteristics and the morphotype of each tooth at the same time, thus avoiding the need to specify upper or lower, and right or left to state the tooth position in the dental arch. DESIGN: To demonstrate the use of the FDI system, we applied it to the study of dental wear in a mediaeval Mediterranean skeletal sample from France consisting of 58 paired mandibles and maxillae belonging to 29 female and 29 male adults and divided into two age groups: young or aged 20-30 years, and mature or aged over 30 years. Tooth wear was recorded according to Brabant's index, which consists of four levels and four directions. Data were displayed in the form of curves, according to the FDI and taking age and sex into account. RESULTS: Analysis of the results shows a tooth wear distribution that is significantly different between upper and lower horizontal and oblique directions in females and males, and between upper and lower horizontal and oblique heavy wear in females and males. Moreover, a significantly asymmetrical horizontal and oblique distribution of wear was found in the young adult group. Thus, the use of criteria defined by precise reference points for recording data, and displaying results in the form of curves, makes comparison using superimposition easy and reliable and permits a more objective study of tooth wear. CONCLUSIONS: Furthermore, using a notation system that is employed worldwide helps to build multidisciplinary projects, and offers the possibility of comparing large amounts of data easily, which should provide enhanced data for bioarchaeology in the future.

Frequency of dental caries in four historical populations from the chalcolithic to the middle ages.

The majority of dental carie studies over the course of historical period underline mainly the prevalence evolution, the role of carbohydrates consumption and the impact of access to dietary resources. The purpose of the present investigation was to compare population samples from two archaeological periods the Chacolithic and Middle Age taking into account the geographical and socio economical situation. The study concerned four archaelogical sites in south west France and population samples an inlander for the Chalcolithic Age, an inlander, an costal and urban for the Middle Age. The materials studied included a total of 127 maxillaries, 103 mandibles and 3316 teeth. Data recorded allowed us to display that the Chalcolithic population sample had the lowest carie percentage and the rural inlander population samples of Middle Age the highest; in all cases molars were teeth most often affected. These ones differences could be explained according to time period, carious lesions were usually less recorded in the Chalcolithic Age than the Middle because of a lesser cultivation of cereals like in les Treilles Chacolithic population sample. In the Middle Age population samples, the rural inland sample Marsan showed the highest frequency of caries and ate more cereal than the coastal Vilarnau and the poor urban St Michel population samples, the first one ate fish and Mediterranean vegetal and fruits and the second one met difficulties to food access, in both cases the consumption of carbohydrates was lesser than Marsan population sample who lived in a geographical land convice to cereals cultivation.

Study of dental caries and periapical lesions in a mediaeval population of the southwest France: differences in visual and radiographic inspections.

Dental caries and periapical lesions have often been studied in archaeological samples. The majority of these studies concern lesions detected clinically and, in some cases, radiography is used to improve the scoring results. The purpose of the present study was to compare and combine the two methods for recording caries and cysts. The studied dental material derived from a mediaeval sample from the south of France. The study included sixty mandibles (788 teeth). Each tooth was observed clinically and radiographically. Absence of teeth was noted and unerupted teeth, which could be viewed on radiographs were also noted. The location and degree of development of each lesion were recorded. Occlusal lesions of degree 1 were mostly detected clinically (5.1% vs.1.4% detected radiographically). Radiographic detection increased the score of approximal lesions of degree 2 (1.4% vs. 0.7%) and the detection of intraosseous lesions. This research has shown that the combination of radiographic and clinical examinations improves the caries detection and thus, increases the caries score in a studied dental sample.

mtDNA variation in the Buryat population of the Barguzin Valley: New insights into the micro-evolutionary history of the Baikal area.

BACKGROUND: Southern Siberian populations, including the Buryat, have been of great interest in investigating the exchanges between Eastern and Western Eurasia and understanding the peopling of Siberia and the New World. AIM: Previous studies mainly employed a phylogenetic approach, and thus used pooled samples to detect a maximum of variability. As different sampling strategies may result in different pictures of a population's evolutionary history, we proposed in this study to focus on a local Buryat population selected on the basis of geographical, archaeological and ethno-historical data. SUBJECTS AND METHODS: This study investigated a local population from the Barguzin Valley, on the north-western shores of Lake Baikal identified as the most likely place of Buryat origin. We analysed mitochondrial DNA (mtDNA) RFLPs markers, HVS-I and HVS-II sequences to discuss the genetic variability of this population, and to compare our local sample with pooled Buryat samples and neighbouring Siberian populations. RESULTS: The Barguzin Buryat sample shows depressed neutrality scores compared to the pooled Buryat sample, and different genetic affinities with the Mongol and Turco-Evenk populations. CONCLUSION: These results underline the need to use local samples, in addition to pooled samples, to investigate the history of human populations at the micro-evolutionary level.

Dental caries, tooth wear and diet in an adult medieval (12th-14th century) population from mediterranean France.

OBJECTIVES: The aims of the present work were to determine the frequency and distribution of caries and tooth wear on paired maxillae of a mediaeval sample from southwest France in which the sex of the remains had been established, and to make a relation with the diet of this population. MATERIALS AND METHODS: The sample analysed consisted of the dental remains of 58 adult individuals (29 men and 29 women) excavated from the mediaeval cemetery of the archaeological site of Vilarnau d'Amont (southwest France). A total of 1395 teeth were examined. RESULTS: The frequency of ante-mortem tooth loss for the sample was 8.7% and the frequency of caries was 17.5%. The frequencies of carious lesions in adult men and women's dentition were 21.9% and 14.0%. The most frequent were occlusal (49.7% and 34.3%) and approximal caries (26.5% and 37.4%). Concerning tooth wear, all 58 individuals were affected by attrition (100%) and more than 90% of the teeth were concerned. Most of them showed the presence of dentin clusters. There was no significant difference between men and women for caries and tooth wear. DISCUSSION: These findings are similar to those of other studies on European populations of the same socio-economic status and confirm the predominance of tooth wear over carious lesions during this period. Both caries and tooth wear may be related to the regional diet of this rural population.

[Study of dental attrition in a medieval adult population from Southwest France]. / Etude de l'attrition dentaire au sein d'une population médiévale adulte du Sud-Ouest de la France.

INTRODUCTION: The aim of the authors was to study dental attrition in a medieval sample of paired mandibles and maxillas from the Southwest France (IX to XV century). MATERIALS AND METHODS: We selected 58 adult individuals with maxillas and mandibles in good state of conservation, 29 women and 29 men from the medieval collection of Vilarnau-d'Amont (Western Pyrenees, France). Attrition was graded according to the Brabant index. RESULTS: We found a high prevalence of attrition in this sample. The first molars (M1) were the maxillary and mandibular teeth most concerned by attrition. The most frequent attrition level was level 2, with dentin exposure. We did not find any significant difference of tooth wear between maxillary and mandibular teeth, even if maxillary teeth seemed to be more worn. There was symmetry of attrition between the left and right side. There was no significant difference between men and women. DISCUSSION: Working on paired mandibles and maxillas showed that attrition in the middle age was a global phenomenon, intermaxillary and symmetric. It was much more severe than today, rapidly evolving and generalized because of the abrasive quality of food, cooking, chewing habits, and intensity of chewing pressure.

[Study of the prevalence and distribution of dental caries in a medieval population in Southwest France]. / Etude de la prévalence et de la distribution carieuse dans une population médiévale du Sud-Ouest de la France.

INTRODUCTION: Teeth are an interesting material for the study of ancient populations. The aim of our study was to determine the prevalence and distribution of caries in a medieval sample of paired maxillas in a rural population in Southwest France and to compare men and women. MATERIALS AND METHODS: Our sample included 58 adults, 29 men and 29 women, with dentate maxillas in good state of conservation, for a total of 1,395 teeth out of a possible 1,846 (75%). The number of caries and their localization were noted. RESULTS: The frequency of antemortem missing teeth was 8.67%. The prevalence of caries was 17.46% and the most frequent caries were occlusal and proximal. Second and third molars were the most frequently affected maxillary and mandibular teeth. Caries on maxillary teeth were statistically more frequent than on mandibular teeth (p<0.05). There was no significant difference between men and women (p>0.05). DISCUSSION: Our study showed that the frequency and the distribution of dental caries in this medieval population from southwest France were comparable to those of other European populations from the same period. The low level of caries was probably due to attrition and noncariogenic food. Differences between men and women were not significant, even though our results suggest that men were much more concerned by caries than women, especially for posterior teeth. A different diet may be the reason for this difference.

Effects of polyphenols on skin damage due to ultraviolet A rays: an experimental study on rats.

BACKGROUND: Ultraviolet (UV) radiation causes many acute and chronic conditions such as oedema of the skin, sunburn, immunosuppression, photo-ageing and skin cancer. The use of antioxidants has become of paramount importance in prevention of the damage caused by ultraviolet radiation. Epigallocatechin-3-gallate (EGCG), one of the main components of green tea, has been reported to have anti-inflammatory, antioxidant and anticarcinogenic properties. AIM: The aim of this experimental study was to investigate to what extent EGCG prevented acute skin damage caused by UVA. MATERIAL AND METHOD: The sample contained 2% EGCG, which was prepared in hydrophilic ointment (USP XXIV) as the vehicle. Twenty-four 12-week-old Wistar albino rats are included in the study and divided into four groups, each containing six rats. Group I was formed to be the control group, which was not applied any topical medication or exposed to UV radiation. Group II was formed to observe acute effects of UVA on the skin, Group III was formed to observe effectiveness of topical EGCG on the skin applied 30 min after exposure to UVA, and Group IV was formed to observe topical EGCG applied 30 min before exposure to UVA. All groups were examined for sunburn cells, leucocyte infiltration, dermo-epidermal activity, collagen changes and elastic fibre pathologies on 24 and 72 h. Statistical analysis was performed using spss 11.5, and chi-squared test was used for the evaluation of parameters. RESULTS: Group IV showed a statistically significant decrease in sunburn cells and dermo-epidermal activation compared with Group II. Group II showed significant increase in all parameters compared with Group I, showing the effects of UV exposure alone, and no difference was detected in Group II and III. CONCLUSION: These results show a protective effect of EGCG when applied topically before UVA exposure. No benefit was detected when EGCG was applied after UV exposure.

Study of GM immunoglobulin allotypic system in Berbers and Arabs from Morocco.

The GM immunoglobulin allotype polymorphism was investigated in four Moroccan populations: three Berber groups from Khenifra (Middle Atlas), Amizmiz (High Atlas), and Bouhria (Beni Snassen) and one Arabic-speaking sample from the Doukkala area (Abda, Chaouia, Doukkali, and Tadla districts in south-central Morocco). In order to characterize the genetic relationships between the populations, our results were compared with those obtained for other North African groups (from Morocco, Algeria, Tunisia, and Niger) and for Middle-East Africans, sub-Saharans, and Southwest Europeans. Based on GM haplotype frequencies, Factorial Correspondence Analyses, F(ST) significance testing, and hierarchical analyses of variance were performed. Our results reveal that Moroccan populations have heterogeneous GM profiles with high frequencies of GM haplotypes in Europeans (from 76% for Doukkala to 88% for Bouhria) and relatively high frequencies of GM haplotypes in sub-Saharans (from 11% for Bouhria to 23% for Amizmiz). The genetic diversity observed among Moroccans is not significantly correlated with either geographic or linguistic differentiation. In spite of their cultural and historical differentiation, we did not discover any significant genetic differences between Berbers and Arabic-speakers from Morocco. However, when large geographical areas are considered, our population samples are integrated in the North African GM variation, significantly distant from sub-Saharan groups but with a close relationship with Southwest European populations.

De-aromatizing phosphole.

Quantum-chemical DFT calculations using the B3LYP functionals have been carried out for 1-R-substitued phospholes and some 1-R-substitued 3,4-dimethylphospholes where R = H, Me, Ph, CN, OH, OMe, F, Cl, and Br. The aromaticity of the phospholyl rings is interpreted as a function of geometric, magnetic, and energetic indexes. It is shown, in agreement with previous experimental results, that phosphole aromaticity does not correlate with pyramidality at phosphorus. Variation of hyperconjugative and, to a lesser extent, conjugative effects is responsible for the change in cyclic delocalization for the phospholes studied here.

Effect of therapeutic immunization with HIV type 1 recombinant glycoprotein 160 ImmunoAG vaccine in HIV-infected individuals with CD4+ T cell counts of >or=500 and 200-400/mm3 (AIDS Clinical Trials Group Study 246/946).

AIDS Clinical Trials Group (ACTG) 246/946 was a double-blinded, randomized, controlled trial of HIV-1 MN rgp160 ImmunoAG vaccine in HIV-infected patients with CD4(+) T cell counts >or=500 and 200-400/mm(3). The main objectives were to study the safety and immunogenicity of this vaccine and to study the persistence of the immune responses after vaccination over a longer period of time. Fifteen patients with CD4(+) T cell counts of >or=500/mm(3) were enrolled in the ACTG 246 study. ACTG 246 patients received a monthly injection of vaccine or control for 6 months and then injections every 2 months. After completion of this study, seven new patients with CD4(+) T cell counts of 200-400/mm(3) entered into the ACTG 946 study. These study patients received highly active antiretroviral therapy (HAART) (ritonavir, didanosine, and stavudine) for 9 weeks to stabilize their viral load and then each patient received a monthly injection of vaccine or control substance for 6 months with HAART. The study of these two relatively small populations showed that the vaccine was safe without any adverse effect both in the patients with CD4(+) T cell counts of >or=500 and 200-400/mm(3). The vaccine was also immunogenic in patients with CD4(+) T cell counts of >or=500/mm(3) as measured by gp160-specific lymphocyte proliferative responses, and it persisted after they had received more than six vaccine injections, for a longer period of time.

Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy.

Cytotoxic T lymphocytes (CTLs) are an important defense against human immunodeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppressing replication, the evolution of T cell phenotypes and HIV-specific CD8+ lymphocytes was prospectively investigated in 41 patients initiating combination therapy. Suppression of viremia to <200 copies/mL was associated with increases in naive cells (CD45RA+62L+) and declines in activated T cells (CD95+ cell counts and CD38+ HLA-DR+). HIV-specific tetramer-staining CD8+ T cells were detected in 6 of 10 HLA-A*0201-positive persons, which declined in 5 with treatment. CTL precursor frequencies were markedly consistent before and after treatment. Eight (72%) of 11 recognized > or =1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8+ T cells, including those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capable of differentiating into effectors remains stable, and the recognition of new epitopes may occur.

On the potential catalytic role of electron capture in gas-phase condensation reactions: a theoretical exploratory study of the CH2O2 and CH3ON systems.

The potential activation by electron capture of H2+CO2 or CO+H2O reactions, leading to HCOOH (formic acid), and of CO+NH3, HCN+H2O and HNC+H2O reactions, leading to HC(O)NH2 (formamide), have been studied theoretically. Ab initio calculations at the DFT, CCSD, CCSD(T) and QCISD(T) levels have been performed with the 6-311G(3df,2p) and 6-311+G(3df,2p) basis sets, whose performances are compared in the evaluation of the negative electron affinities of HCN and HNC. A routine method, CCSD/6-311+G(3df,2p)//B3LYP/6-311G(3df,2p), was then used for a survey of the potential energy surfaces of the above reactions. It has been shown that a promising reaction pathway was found in the catalytic anionic activation of HNC+H2O condensation, at an energy ≤2 eV for the incident electron.

Methods for investigation of the relationship between drug-susceptibility phenotype and human immunodeficiency virus type 1 genotype with applications to AIDS clinical trials group 333.

Use of human immunodeficiency virus (HIV) drug-resistance testing in therapeutic decision making may be aided by understanding the relationship between results of genotypic and drug-susceptibility phenotypic assays. We investigated this relationship by applying 3 different statistical methods-cluster analysis, recursive partitioning, and linear discriminant analysis-to results for 72 patients followed in the Adult AIDS Clinical Trials Group (ACTG) protocol 333. ACTG 333 was a multicenter, randomized trial comparing 2 formulations of saquinavir (SQV) to indinavir (IDV) in patients with extensive hard-gel SQV experience. Data include protease amino acid sequences and 50% inhibitory concentrations for SQV and IDV at baseline. The 3 methods give similar results showing the association of mutations at codons 10, 63, 71, and 90 with in vitro resistance to IDV and SQV. Recursive partitioning is especially useful because it can identify interactions among mutations at different codons and accommodates many types of data as well as missing observations.

Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team.

The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Reduced mobilization of CD34+ stem cells in advanced human immunodeficiency virus type 1 disease.

Granulocyte colony-stimulating factor (r-met Hu G-CSF; filgrastim; 10 microgram/kg/day for 7 days) was used to mobilize CD34+stem cells into the peripheral blood of human immunodeficiency virus type 1 (HIV-1)-infected individuals and a group of HIV-1-uninfected donors as a measure of immunologic reserve in HIV-1-infected people. G-CSF mobilized CD34+ cells of HIV-1-infected individuals with cell counts >500 CD4+ cells/mm3, as well as in HIV-1-uninfected donors. In contrast, CD34 cell mobilization was significantly blunted in HIV-1-infected individuals with cell counts <500 CD4+ cells/mm3 (<200 cell days vs. >650 cell days, P<.0005, compared with the >500 CD4+ cell cohort). At least 1.75x10(7) CD34 cells were harvested by leukapheresis from patients in each study cohort. CD34+ cell viability and the ability to differentiate precursor cells into myeloid and erythroid progenitor cells were not affected by HIV-1 infection.

Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response.

The effects of 1 year of zidovudine, lamivudine, and ritonavir treatment on immune reconstitution were evaluated in 34 human immunodeficiency virus (HIV)-infected individuals. After 48 weeks of therapy, 20 (59%) subjects had <100 copies HIV RNA/mL. CD4+ T cells increased from a median of 192/mm3 at baseline to 362/mm3 at week 48. Lymphocyte proliferative responses to Candida normalized within 12 weeks, but responses to HIV and tetanus remained depressed throughout therapy. Alloantigen responses increased within 12 weeks and then declined to baseline levels. Recovery of delayed-type hypersensitivity responses occurred after 12 weeks for Candida and after 48 weeks for mumps. The magnitude of virologic suppression was correlated with numeric increases in CD4+ T cells, but not with measures of functional immune reconstitution. Plasma virus suppression <100 copies/mL was not significantly correlated with increases in CD4+ T cells or functional immune reconstitution.

GM and KM immunoglobulin allotypes in a Spanish Pyrenean population: Val d'Aran.

Four hundred and thirteen unrelated individuals (202 autochthonous and 211 non-autochthonous) of Val d'Aran (Catalan Pyrenees) have been analysed for the GM and KM immunoglobulin genetic system using the inhibition haemagglutination method. This population was defined by eight GM haplotypes (GM*3 23 5*, GM*3 5*, GM*1,17 21,28, GM*1,2,17 21,28, GM*1,17 5*, GM*1,17 5,6,11,24, GM*1,17 10,11,13,15 and GM*1,17 10,11,13,15,16) inferred from the 17 observed phenotypes. The Val d'Aran population frequencies conform to Hardy-Weinberg expectations. The frequencies of phenotypes and haplotypes show a definite homogeneity between the autochthonous and non-autochthonous people of Val d'Aran and 11 other Pyrenean populations (Mauléon, Macaye, St. Jean Pied de Port, Vallée de L'Ouzom, Gavarnie, Barèges, Luz St. Sauveur, Esparros, Camurac, Capcir and Pays de Sault) that have already been studied for the same allotypes. A factorial correspondence analysis was performed for the 12 autochthonous Pyrenean populations, showing a high frequency of the GM*3 23 5* haplotype in the three Pyrenean regions (Western, Central and Eastern), while the GM*1,17 21,28 haplotype is mainly found in the Central region, GM*3 5* in the Eastern and Western zones, and the GM*1,2,17 21,28 is mainly present in the Central and Eastern populations. The results show a relative regional homogeneity, so there is no evidence of a frequency gradient in the Pyrenean populations for the GM and KM genetic systems. It may, however, be noticed that the Central Pyrenean populations form a group, with one population (Vallée de l'Ouzom) isolated from the rest, probably because of its particular model of inheritance by which the heritage is passed to the first born without sex consideration. It has been possible to point out some differences in the genetic structure of the autochthonous and non-autochthonous Val d'Aran population and to place the autochthonous Aranese group among its Pyrenean neighbours.