Uncovering the correlation between neurotransmitter-specific functional connectivity and multidimensional anxiety in a non-clinical cohort.

Research on anxiety faces challenges due to the wide range of symptoms, making it difficult to determine if different aspects of anxiety are linked to distinct neurobiological processes. Both alterations in functional brain connectivity (FC) and monoaminergic neurotransmitter systems are implicated as potential neural bases of anxiety. We aimed to investigate whole-brain FC involving monoaminergic nuclei and its association with anxiety dimensions in 178 non-clinical participants. Nine anxiety-related scales were used, encompassing trait and state anxiety scores, along with measures of cost-probability, hypervigilance, reward-punishment sensitivity, uncertainty, and trait worry. Resting-state functional magnetic resonance imaging data were acquired, focusing on seven brainstem regions representing serotonergic, dopaminergic, and noradrenergic nuclei, with their FC patterns voxel-wise correlated with the scales. All models underwent family-wise-error correction for multiple comparisons. We observed intriguing relationships: trait and state anxiety scores exhibited opposing correlations in FC between the dorsal raphe nucleus and the paracingulate gyrus. Additionally, we identified shared neural correlates, such as a negative correlation between the locus coeruleus and the frontal pole. This connection was significantly associated with scores on measures of probability, hypervigilance, reward sensitivity, and trait worry. These findings underscore the intricate interplay between anxiety dimensions and subcortico-cortical FC patterns, shedding light on the underlying neural mechanisms governing anxiety.

Altered functional connectivity of the subthalamus and the bed nucleus of the stria terminalis in obsessive-compulsive disorder.

BACKGROUND: The assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity. METHODS: Eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses. RESULTS: In comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus. CONCLUSIONS: This study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.

First insight into the Neolithic subsistence economy in the north-east Iberian Peninsula: paleodietary reconstruction through stable isotopes.

OBJECTIVES: The study of subsistence strategies among Neolithic communities in north-east Iberia, late-fifth to early-fourth millennia cal BC, enables a more in-depth study of the activities and behavior of the inhabitants of this region, where paleodiets have been little studied. The objectives of this study are, therefore, to determine the diet and subsistence patterns of those communities and to consider whether any relation existed between their subsistence strategies and environmental, geographic, and/or social factors. MATERIALS AND METHODS: Bone samples from 25 middle Neolithic human individuals at seven archeological sites and comparative faunal samples were analyzed, and compared with contemporary series in Mediterranean Europe. Carbon and nitrogen isotope ratios (δ13 C and δ15 N) of bone collagen were studied to determine the dietary patterns. RESULTS: Dietary habits proved to be similar between communities, apart from some interpopulational variations in subsistence strategies. Their diet was based on C3 terrestrial resources with a major vegetal protein component. DISCUSSION: The reported variations in interpopulational subsistence strategies among the compared Mediterranean societies do not seem to be directly related to the settlement region. Together with archeological data, this indicates the influence of socioeconomic factors in the Neolithic human diet. A general tendency toward a lesser use of aquatic resources is seen in this period in Iberia and the rest of the Mediterranean, as also documented for contemporary communities in the west and north of Europe. The data obtained will be important for further studies of socioeconomic patterns in European Neolithic societies.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study.

BACKGROUND: The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD: A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS: Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS: OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive-compulsive disorder.

Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

Non-metric dental analysis of human interactions around the Pyrenees during the Neolithic and their biological impact.

BACKGROUND: Interactions across the Pyreneans during the Middle-Neolithic (V-IV millennium BCE) have been described for a long time. Nevertheless, except for a few examples and attempts to describe them, the biological impact of these interactions on the human groups' make-up is not yet understood. The present work analyzes the biological affinities of different groups from both sides of these mountains that represent the Populations of the Middle- and Late-Neolithic by means of the dental morphology. METHODS: We present novel dental morphological data of 221 individuals from 11 archaeological sites. These data have been analyzed and compared to those from previously published twenty Iberian sites and one French site. Data were recovered following the ASUDAS protocol, and MMD biological measure was calculated between groups. RESULTS: Our results suggest that there were some differences between the analyzed populations. These differences were observed at each side of the Pyrenees, but also across them. Concretely, the coastal groups across the mountains show more affinities between each other than the inland groups. In addition, the differences between groups decreased by the end of the Neolithic. CONCLUSIONS: Therefore, our results indicate that the intense trade activities registered in the coastal area between both sides of the Pyrenees would have had the greatest biological impacts in the homogenisation of the groups. Although less intense, the across mountain network and coastal to mountain area trade networks to the south of Pyreneans, also influenced the biological make-up of the groups.

Stratigraphic context and direct dating of the Neandertal mandible from Cova del Gegant (Sitges, Barcelona).

Stratigraphic study of the Cova del Gegant's sedimentary fill revealed different cycles of accumulation of typical interior cave and delta facies. A precise chronology for these deposits, the faunal remains and stone tools contained therein was obtained by radiocarbon, U-Th and OSL. Our results indicate that the Upper Pleistocene archaeological sequence dates between 49.3 +/- 1.8 ka BP, the U-Th age of the overlying flowstone, and 60.0 +/- 3.9 ka BP, the OSL age of the basal deposits. We have also directly dated the site's Neandertal mandible to 52.3 +/- 2.3 ka by U-Th.

Growing up in Ancient Sardinia: Infant-toddler dietary changes revealed by the novel use of hydrogen isotopes (δ2H).

Detailed information about the lives and deaths of children in antiquity is often in short supply. Childhood dietary histories are, however, recorded and maintained in the teeth of both juveniles and adults. Primary tooth dentinal collagen does not turn over, preserving a sequential record of dietary changes. The use of nitrogen (δ15N) and carbon (δ13C) isotope values of incrementally sampled dentin are used in the study of breastfeeding practices but evidence for the addition of weaning foods, both in terms of mode and, particularly, duration, has remained analytically inaccessible to date. Here, we demonstrate how the novel use hydrogen isotope (δ2H) values of sequentially micro-sampled dentin collagen, measured from individuals excavated from a Punic cemetery, in Sardinia, Italy, can serve as a proxy for weaning food type and duration in ancient childhood diet. The weaning rate and age, based on the decline in δ15N and δ13C values of permanent first molars and the concomitant increase in δ2H, appears to be broadly similar among six individuals. Hydrogen isotopes vary systematically from a low value soon after birth, rising through early childhood. The early post-birth values can be explained by the influence of 2H-depleted lipids from mother's breastmilk and the later δ2H rise is consistent with, among other things, a substantial portion of boiled foodstuffs, such as the higher δ2H values observed in porridge. Overall δ2H in dentin shows great promise to elucidate infant and childhood feeding practices, and especially the introduction of supplementary foods during the weaning process.

Prehistoric funerary complexity in northern Iberia studied by using dental morphology.

During the Neolithic Age and afterwards, several funerary practices coexisted in the northeast of the Iberian Peninsula from the Mediterranean to the Atlantic. According to archaeological data, there was a coexistence of sepulchral caves and megalithic monuments at the end of the Neolithic, following the dominance of open-air pit burials during the Middle Neolithic. The aim of this work is to analyze the biological relationships between individuals representing those cultures, based on their dental morphology - the first such attempt. This study presents data of 156 individuals from this period, and will allow elucidate the population dynamics including the role of migrations and other factors. The results indicate that there were no significant differences between the groups living in Atlantic and Mediterranean areas. Moreover, pairwise comparisons for each trait only show two significant results. This lack of differences could be related to trade activities between the two basins, which would contribute to individual exchanges between groups. Furthermore, according to biological affinities, trade activities along the Mediterranean Sea had a more marked influence over the Catalan populations than those from the Atlantic basin. There are no biological differences between groups representing the open-air pit culture and the sepulchral caves in each area. Finally, the megalithic groups from the Atlantic basin differ the most from the surrounding populations. This could be indicative of a slightly different biological origin of the people related to this culture.

Brain structural correlates of obsessive-compulsive disorder with and without preceding stressful life events.

Objectives There is growing evidence supporting a role for stressful life events (SLEs) at obsessive-compulsive disorder (OCD) onset, but neurobiological correlates of such effect are not known. We evaluated regional grey matter (GM) changes associated with the presence/absence of SLEs at OCD onset. Methods One hundred and twenty-four OCD patients and 112 healthy controls were recruited. Patients were split into two groups according to the presence (n = 56) or absence (n = 68) of SLEs at disorder's onset. A structural magnetic resonance image was acquired for each participant and pre-processed with Statistical Parametric Mapping software (SPM8) to obtain a volume-modulated GM map. Between-group differences in sociodemographic, clinical and whole-brain regional GM volumes were assessed. Results SLEs were associated with female sex, later age at disorder's onset, more contamination/cleaning and less hoarding symptoms. In comparison with controls, patients without SLEs showed GM volume increases in bilateral dorsal putamen and the central tegmental tract of the brainstem. By contrast, patients with SLEs showed specific GM volume increases in the right anterior cerebellum. Conclusions Our findings support the idea that neuroanatomical alterations of OCD patients partially depend on the presence of SLEs at disorder's onset.

Activation of human lymphomononuclear cells by peptides derived from extracellular matrix proteins.

A series of peptides of 15 amino acids with sequences contained in human extracellular matrix (ECM) proteins (fibronectin, laminin A, laminin B1, tenascin, undulin, alpha 1-chain of type IV and VIII collagen and alpha 2-chain of type VIII collagen) have been synthesized. The selected structures conformed to the following pattern: (i) Pro at position 6, (ii) Leu, Lys, Ile, Val, Ala or Gly at position 2, (iii) Glu or Asp at position 11. Fibronectin and the indicated peptides, when present in cultures of lymphomononuclear cells from healthy donors, promoted stimulation of monocytes manifested by a release of IL-1 alpha, IL-beta, IL-6 and TNF alpha; an increase in the percentage of cells expressing CD14, CD16, CD11b and CD14/CD16; an increase in cytotoxicity against HT-29. Cytotoxicity against K562 and Daudi cells (targets of NK and LAK cells) was also observed together with an increase in the percentage of cells expressing CD56, CD56/CD16 (corresponding to NK cells), and CD56/CD8 (corresponding to NK-like lymphocytes), indicating a stimulation of lymphocytes. Activated monocytes and lymphocytes contained a large number of granules with DNAse activity. These results suggest that at least some of the immunological properties of ECM proteins could be accounted for by motifs fulfilling a characteristic sequence pattern shared by all of them.

Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A.

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether.

Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO.

Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS). Liver-type arginase I mRNA was present in all subsets. Apoptosis was followed by the expression of T cell intracellular antigen (TIA) and the simultaneous detection of DNA stainability by propidium iodine and annexin V binding. Apoptosis was practically absent both in activated CD14(++)CD33(++)DR(++)CD25(++)CD69(++)CD71(++/+) CD16(-) cells, expressing A-II mRNA and having arginase activity, but not iNOS mRNA, and in not fully mature large CD14(++)CD16(+)CD23(+)DR(++) monocytes, expressing simultaneously both mRNAs and having both enzyme activities. However, differentiated small CD14(+/++)CD16(+)CD69(+)CD25(+/-)CD71(++)CD23(+) DR(++) monocytes, expressing high levels of iNOS mRNA, exhibited apoptotic signs. Amounts of NO synthesised by monocytes co-expressing iNOS and arginase changed with the addition of arginine or an iNOS inhibitor; in that case a correlation of NO production and apoptotic features was observed. Data suggest a regulatory role for endogenous NO in apoptosis of stimulated and differentiated monocytes, and also that iNOS and A-II, when simultaneously present, could control the production of NO as a consequence of their competition for arginine.

A case of bilateral macrodontia of mandibular second premolars from a Chalcolithic context in the Iberian Peninsula.

Isolated macrodontia, consisting of the gigantism of a single tooth, is an extremely rare condition. Only 16 cases of isolated macrodontia of mandibular second premolars have been reported to date. Although the aetiology of this phenomenon remains unknown, many authors have related it to the control of the apoptotic process, leading to the patterning and size of dental cusps. There is not a clear genetic inheritance pattern since only two of those 16 cases correspond to close relatives. To our knowledge, there have been no reports of isolated macrodontia of mandibular second premolars in archaeological remains. Cova del Pantà de Foix site is a Chalcolithic sepulchral cave situated in the North-East of the Iberian Peninsula in which the remains of at least 30 individuals were recovered. Most of these individuals show several signs of environmental stressors. The current study presents the first case of isolated bilateral macrodontia of mandibular premolars from an archaeological context, corresponding to a young male individual discovered in this site. This condition could be the last consequence of environmental factors epigenetically affecting apoptosis processes in early tooth development and a possible genetic predisposition to show a shape-deviation in the dentition.

The emergence of mesolithic cemeteries in SW Europe: insights from the El Collado (Oliva, Valencia, Spain) radiocarbon record.

Located on the Iberian Mediterranean coast, El Collado is an open-air site where a rescue excavation was conducted over two seasons in 1987 and 1988. The archaeological work excavated a surface area of 143 m2 where 14 burials were discovered, providing skeletal remains from 15 individuals. We have obtained AMS dates for 10 of the 15 individuals by means of the direct dating of human bones. The ranges of the probability distribution of the calibrated dates suggest that the cemetery was used during a long period of time (781-1020 years at a probability of 95.4%). The new dates consequently set back the chrono-cultural attribution of the cemetery from the initial proposal of Late Mesolithic to an older date in the Early Mesolithic. Therefore, El Collado becomes the oldest known cemetery in the Iberian Peninsula, earlier than the numerous Mesolithic funerary contexts documented on the Atlantic façade such as the Portuguese shell-middens in the Muge and Sado Estuaries or the funerary sites on the northern Iberian coast.

The measurement of transforming growth factor type beta (TGF beta) levels produced by peripheral blood mononuclear cells requires the efficient elimination of contaminating platelets.

In recent years there has been an increasing interest in measuring the levels of TGF beta produced by peripheral blood mononuclear cells (PBMC), since its abnormal regulation seems to be involved in several pathological states. Platelet-contamination, a common feature in PBMC populations isolated by the standard Ficoll-Paque method, would theoretically disturb the measurement of the levels of TGF beta produced by mononuclear cells, since platelets represent an important source of this cytokine. In this study, supernatants of PBMC cultures from healthy subjects, either platelet-contaminated or uncontaminated, were assayed for TGF beta activity in three different bioassays. We report that the presence of platelets led in most cases to an important overestimation of the TGF beta levels produced by MNC in the Swiss-3T3 bioassay and in a PBMC proliferation assay. In contrast, in the Mv1Lu bioassay these levels were significantly underestimated, an effect which we attribute to the presence of other platelet-derived growth factors. These results suggest that the elimination of platelets from PBMC cultures is essential if TGF beta production by mononuclear cells is to be studied.

Simultaneous evaluation of phagocytosis and Fc gamma R-mediated oxidative burst in human monocytes by a simple flow cytometry method.

In this study we describe a fast, simple, and objective flow cytometry method to quantify simultaneously phagocytosis and Fc gamma R-mediated oxidative burst in human monocytes. Peripheral blood monocytes isolated by elutriation were sequentially incubated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and sheep erythrocytes opsonized with rabbit IgG (SRBC-IgG), and then analysed by flow cytometry. Two parameters were studied simultaneously in the same cell population: forward scatter modifications (grade of phagocytosis) and fluorescence intensity of DCFH oxidation (index of oxidative burst). We found a statistically significant correlation (r = 0.96274) between the forward scatter increase and the amount of phagocytosis as determined by light microscopy. We also found a significant correlation between the oxidative burst and phagocytosis studied both microscopically (r = 0.7714) and by flow cytometry (r = 0.78056). As the presence of DCFH did not impair monocyte phagocytosis, we conclude that this simple method could be a useful tool in functional studies of monocytes.

Allogeneic stem cell transplantation with reduced-intensity conditioning is potentially feasible as an outpatient procedure.

Allogeneic stem cell transplantation (allo-SCT) after a reduced-intensity conditioning (RIC) protocol is associated with decreased short-term toxicity. This suggests that the procedure could be performed on an outpatient basis. We analysed the incidence and risk factors of grade >or=2 conditioning-related toxicities (CRTs) as a hallmark for hospital admission, in 41 consecutive patients allografted from an HLA identical sibling after RIC. The RIC regimen consisted of fludarabine plus melphalan for lymphoid malignancies, and fludarabine plus busulphan for myeloid malignancies. In all, 11 patients (27%) did not experience any toxicity. The more frequent CRTs observed were neutropenic fever and gastrointestinal toxicity. The median duration of hospitalisation was 27 (range, 17-50) days. If allo-SCT had been planned as an outpatient procedure and admission indicated only in the case of >or=2 CRTs, the inpatient period would have decreased to 9 (range, 0-33) days (P<0.001). No risk factors for CRTs were identified. Allo-SCT after an RIC regimen is a well-tolerated procedure. Our results warrant a prospective pilot trial of nonmyeloablative allo-SCT performed in the outpatient setting.

Comparison of the classic Glucksberg criteria and the IBMTR Severity Index for grading acute graft-versus-host disease following HLA-identical sibling stem cell transplantation. International Bone Marrow Transplant Registry.

Acute graft-versus-host disease (AGVHD) severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC). Recently, the International Bone Marrow Transplant Registry (IBMTR) developed a new Severity Index by regrouping the patterns of organ involvement into five Indexes (0-D) that appeared more predictive of transplant-related mortality (TRM) and transplant failure (TF, relapse or TRM). We studied the predictive value of both grading systems of TRM, TF and GVHD-related mortality (GTRM) in a series of 114 consecutive patients > or = 12 years old allografted from a histocompatible sibling at our institution, 100 of whom were evaluable for AGVHD. The IBMTR Severity Index showed better incremental prediction of TRM (relative risks (RR) of 1, 1.5, 1.4, 2 and 2.5 for Indexes 0, A, B, C and D), TF (RRs of 1, 1.6, 1.6, 2 and 2.3, respectively) and GTRM (RRs of 1, 2.2 and 4.8 for Indexes B, C and D) than the GSC. With the GSC different outcomes for TRM and TF were found only from grade 0 to I-II and 0 to IV or I-III to IV, but not from I-II to III. The GSC also appeared less predictive of GTRM (RRs of 1, 0.4 and 2.9 for grades II, III and IV). In our relatively small patient sample, the new IBMTR Severity Index appeared more predictive of transplant outcome than the GSC, especially between no AGVHD, early Indexes (A-B) and advanced Indexes (C-D).