Spatial and temporal contrasts in the distribution of crops and pastures across Amazonia: A new agricultural land use data set from census data since 1950.

Amazonia holds the largest continuous area of tropical forests with intense land use change dynamics inducing water, carbon, and energy feedbacks with regional and global impacts. Much of our knowledge of land use change in Amazonia comes from studies of the Brazilian Amazon, which accounts for two thirds of the region. Amazonia outside of Brazil has received less attention because of the difficulty of acquiring consistent data across countries. We present here an agricultural statistics database of the entire Amazonia region, with a harmonized description of crops and pastures in geospatial format, based on administrative boundary data at the municipality level. The spatial coverage includes countries within Amazonia and spans censuses and surveys from 1950 to 2012. Harmonized crop and pasture types are explored by grouping annual and perennial cropping systems, C3 and C4 photosynthetic pathways, planted and natural pastures, and main crops. Our analysis examined the spatial pattern of ratios between classes of the groups and their correlation with the agricultural extent of crops and pastures within administrative units of the Amazon, by country, and census/survey dates. Significant correlations were found between all ratios and the fraction of agricultural lands of each administrative unit, with the exception of planted to natural pastures ratio and pasture lands extent. Brazil and Peru in most cases have significant correlations for all ratios analyzed even for specific census and survey dates. Results suggested improvements, and potential applications of the database for carbon, water, climate, and land use change studies are discussed. The database presented here provides an Amazon-wide improved data set on agricultural dynamics with expanded temporal and spatial coverage. KEY POINTS: Agricultural census database covers Amazon basin municipalities from 1950 to 2012Harmonized database groups crops and pastures by cropping system, C3/C4, and main cropsWe explored correlations between groups and the extent of agricultural lands.

Management of children and adolescents with primary immune thrombocytopenia: controversies and solutions.

The management including diagnostic procedures, prophylaxis, treatment and follow-up of patients with primary immune thrombocytopenia (ITP) in childhood is controversial due to limited clinical data, difficulties in the estimation of individual bleeding risk and heterogeneity of pathophysiology potentially causing various treatment responses. Advances in the management of children include increased international collaborations, improved quality of diagnosis and treatment, increased clinical data, refinement of consensus statements where clinical evidence is absent, new drugs and last but not least establishment of watch-and-wait strategies. The Intercontinental Cooperative ITP Study Group promotes international collaboration since more than 10 years based on a worldwide network and experience in registries. Future considerations include concentration of available resources, strengthening international collaboration, focusing on most important scientific and clinical questions, such as identification of the subgroup of patients that benefits most from prophylactic platelet-enhancing treatments and investigation of treatment endpoints other than concepts solely based on the platelet count, including bleeding symptoms, health-related quality of life and economical aspects of treatments.

Intravenous immunoglobulins induce potentially synergistic immunomodulations in autoimmune disorders.

The increase in platelets in patients with immune thrombocytopenia (ITP) by intravenous administration of human immunoglobulin concentrates (IVIG) reflects a therapeutic immunomodulatory intervention targeted at the disturbed immune response in many inflammatory and autoimmune disorders. These immunoglobulin concentrates contain large numbers of antibodies as well as trace levels of various other immunologically active molecules. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T- and B- lymphocyte effects, macrophage effects, mediated by distinct Fc-gamma receptors. In addition, effects on complement components and apoptosis have also been observed. Synergism between the different elements of the immune response characterizes the beneficial effects of IVIG in inflammatory and autoimmune disorders. They have immunopathogeneses and clinical manifestations which are difficult to define and therefore IVIG treatment indications remain heterogeneous. Dose finding studies are missing for most of the indications of the drug. In future research, defining the appropriate subgroups of patients should be undertaken. This may be accomplished by prospective registries collecting data on large numbers of patients with long-term follow-up. Controlled clinical and laboratory studies may follow based on new, validated patient selection criteria and focused on mechanisms of action, leading to more evidence-based indications.

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.

[Idiopathic thrombocytopenic purpura in children]. / Idiopathische thrombozytopenische Purpura beim Kind.

In children the rate of acute, transient ITP is much higher than the chronic form of ITP. Often acute childhood ITP is a para- or postinfectious event. Pathophysiologically bleeding symptoms mainly depend on the ratio between normal or increased platelet production and early destruction of platelets. The management of ITP has to be focused on the individual bleeding symptoms rather than to the platelet count (see staging system). Today's treatments are directed against the disturbed immune response. As recent guidelines and surveys demonstrate opinion based recommendations have to be challenged by evidence based clinical research in ITP (see www.unibas.ch/itpbasel).

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

[Improved treatment results in children with AML: Results of study AML-BFM 93]. / Verbesserung der Prognose bei Kindern mit AML: Ergebnisse der Studie AML-BFM 931.

BACKGROUND: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with cytarabine and etoposide. After induction all patients were stratified to the standard or high risk group. To improve outcome in high risk patients high dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the efficacy and toxicity accordingly. PATIENTS AND METHODS: 471 children with de novo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk). RESULTS: Overall, 387 of 471 (82 %) patients achieved remission, 5-year survival, event free survival (EFS), and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 % blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19 % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction reduction after induction occurred in 6 % patients in both arms. In the total group of patients probabilities of five years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin. However, in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome in high risk patients was superior in study 93 compared to study 87 (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %, p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Compared to study AML-BFM 87 treatment results in study AML 93 improved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.

Polymorphisms in inflammatory cytokines and Fcgamma receptors in childhood chronic immune thrombocytopenic purpura: a pilot study.

Inflammatory cytokines and low-affinity Fcgamma receptor (FcgammaR) polymorphisms were investigated in 37 children with chronic immune thrombocytopenic purpura (cITP) and 218 controls. Genotype analysis included common variants in the regulatory regions of cytokines, TNF, LTA, IL1RN, IL1A, IL1B, IL4, IL6 and IL10, and structural variants of the low affinity FcgammaRs, FCGR2A, FCGR3A and FCGR3B. Associations were observed for TNF (P = 0.0032), LTA (P = 0.019), FCGR3A (P = 0.038) and FCGR3B (P = 0.0034). Two combinations of genotypes (TNF and FCGR3A; P = 0.0003, and LTA and FCGR3B; P = 0.011) were significantly associated with cITP. These results provide preliminary evidence that variant genotypes of FcgammaRs and cytokines contribute to cITP pathogenesis.

A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

We describe the identification and in vitro characterization of a series of 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the 20S proteasome. Our initial SAR data demonstrate that the 2-aminobenzylstatine core structure can effectively serve as the basis for designing potent, selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

Modeling of the binding mode of a non-covalent inhibitor of the 20S proteasome. Application to structure-based analogue design.

The 2-aminobenzvlstatine derivative I is a 20S proteasome inhibitor of a novel chemical type identified by high throughput screening. The compound specifically inhibits the chymotrypsin-like catalytic activity of the human proteasome with an IC50 value in the micromolar range. Using the crystal structure of the yeast proteasome, we modeled the structure of the human proteasome in complex with 1. As one of the first applications of the model in our oncology programme targeting the proteasome, we designed an analogue of the inhibitor having enhanced stacking/hydrophobic interactions with the enzyme. One order of magnitude in inhibitory potency was gained.

Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study.

BACKGROUND: Diagnosis and management of idiopathic thrombocytopenic purpura (ITP) have been based primarily on expert opinion and practice guidelines rather than on evidence. We have used a registry to prospectively survey the presenting features and the diagnostic evaluation and management practices used for children with ITP worldwide. METHODS: We used the Intercontinental Childhood ITP Registry which had been widely advertised. 209 physicians from 136 institutions in 38 countries participated by submitting data for each of their newly diagnosed patients. Data from 2031 children with ITP was registered between June, 1997, and May, 2000, and we analysed 6-month follow-up data from 1496 children. FINDINGS: There was a peak in occurrence of childhood ITP during spring and a nadir in the autumn. Mean initial platelet count was 15.4x10(9)/L (SD 19.7). 1447 (73%) of 1976 children were admitted to hospital. Initial management consisted of no drug treatment in 612 (31%), intravenous immunoglobulin in 576 (29%), corticosteroids in 651 (33%), or both in 137 (7%) patients. Intracranial haemorrhage was reported in two patients. INTERPRETATION: The variable approaches to management of childhood ITP demonstrate the need for prospective clinical trials, which should be feasible within such a study group.

Ethnicity and environment may affect the phenotype of immune thrombocytopenic purpura in children.

Little is known about the influence of environmental and ethnic factors on the epidemiology of immune thrombocytopenic purpura (ITP). Therefore we compared the initial presentation and condition after 6 mo in 90 Vietnamese and 89 German and Swiss children with newly diagnosed ITP. Data from the two cohorts were collected within the same time period. No differences in age and sex were observed between the Asian and European cohorts, but significant differences between initial platelet count, the occurrence of dry versus wet bleeding symptoms, and infection preceding the onset of ITP were found. Children who had chronic ITP also differed with respect to platelet count and postinfectious state, but not initial bleeding type. In addition, chronic ITP occurred more often than expected with a male to female ratio of 1.2 in Vietnam and 2 in Germany and Switzerland. The data support the potential influence of environmental or ethnic factors on the different aspects of ITP, and point to the need for further epidemiologic investigations.

Structure-based design of potent CDK1 inhibitors derived from olomoucine.

Cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of the cell cycle, constitutes a possible target in the search for new antitumor agents. Starting from the purine derivative olomoucine and following a structure-based approach, potent inhibitors of this enzyme were rapidly identified. The molecular modeling aspects of this work are described.