Sensitivity and specificity of polymerase chain reaction in Giemsa-stained slides for diagnosis of visceral leishmaniasis in children

The aim of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) in the detection of Leishmania DNA in archived Giemsa-stained bone marrow slides for diagnosis of visceral leishmaniasis (VL), and to compare PCR with conventional diagnostic techniques, like direct microscopy and parasite culture. Specimens of archived Giemsa-stained bone marrow slides from 91 patients with VL and from 79 controls with other diseases or conditions were studied. PCR showed the highest sensitivity (92.3%) and had good specificity (97.5%). Direct examination detected 79.1% and culture 59% of positive samples. In addition, PCR was able to detect VL in 16 of 19 patients (84.2%) with negative microscopy. PCR in Giemsa-stained bone marrow slides is a suitable tool for confirming diagnosis in patients with VL and may be useful in the diagnosis of difficult cases. Slide smears are easily stored, do not require special storage conditions such as low temperatures, and can be easily mailed to centers where PCR is available, making it an excellent option for diagnosis in the field.

Magnetic resonance cholangiography features of biliary abnormalities due to cavernous transformation of the portal vein.

BACKGROUND: The aim of this retrospective and monocentric study was to describe the magnetic resonance cholangiography (MRC) features of biliary abnormalities related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From September 2001 to May 2003, MRC was performed in 10 consecutive patients who had a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC in nine patients. It consisted of stenoses, ductal narrowing or irregularities involving the common bile duct for three patients with extrahepatic portal vein thrombosis discovered a mean of 1.5 years ago, or involving both right and left intrahepatic bile ducts and common bile duct for six patients with extrahepatic portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of intrahepatic bile ducts was seen for seven patients, four of them having cholestasis. For three patients with symptomatic cholestasis, direct cholangiography (DC) was performed and showed the same findings as MRC which nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC seems to constitute an accurate tool to investigate noninvasively patients with portal biliopathy.

Effect of the chitin synthesis inhibitor triflumuron on the development, viability and reproduction of Aedes aegypti

The control of Aedes aegypti is impaired due to the development of resistance to chemical insecticides. Insect Growth Regulators (IGR) exhibit distinct mechanisms of action and are considered potential vector control alternatives. Studies regarding the effects of sublethal IGR doses on the viability of resulting adults will contribute to eval-uating their impact in the field. We analyzed several aspects of Ae. aegypti adults surviving exposure to a partially lethal dose of triflumuron, a chitin synthesis inhibitor. A highly significant difference in the proportion of males and females was noted in the triflumuron-exposed group (65.0% males) compared to the controls (50.2% males). Triflumuron affected adult longevity, particularly for females; after 16 days, only 29.2% of males and 13.8% of females were alive, in contrast with 94% survival of the control mosquitoes. The locomotor activity was reduced and the blood-feeding ability of the treated females was also affected (90.4% and 48.4% of the control and triflumuron-exposed females, respectively, successfully ingested blood). Triflumuron-surviving females ingested roughly 30% less blood and laid 25% fewer eggs than the control females. The treated males and females exhibited a diminished ability to copulate, resulting in less viable eggs.

Manufacturing and characterization of a recombinant adeno-associated virus type 8 reference standard material.

Gene therapy approaches using recombinant adeno-associated virus serotype 2 (rAAV2) and serotype 8 (rAAV8) have achieved significant clinical benefits. The generation of rAAV Reference Standard Materials (RSM) is key to providing points of reference for particle titer, vector genome titer, and infectious titer for gene transfer vectors. Following the example of the rAAV2RSM, here we have generated and characterized a novel RSM based on rAAV serotype 8. The rAAV8RSM was produced using transient transfection, and the purification was based on density gradient ultracentrifugation. The rAAV8RSM was distributed for characterization along with standard assay protocols to 16 laboratories worldwide. Mean titers and 95% confidence intervals were determined for capsid particles (mean, 5.50×10(11) pt/ml; CI, 4.26×10(11) to 6.75×10(11) pt/ml), vector genomes (mean, 5.75×10(11) vg/ml; CI, 3.05×10(11) to 1.09×10(12) vg/ml), and infectious units (mean, 1.26×10(9) IU/ml; CI, 6.46×10(8) to 2.51×10(9) IU/ml). Notably, there was a significant degree of variation between institutions for each assay despite the relatively tight correlation of assay results within an institution. This outcome emphasizes the need to use RSMs to calibrate the titers of rAAV vectors in preclinical and clinical studies at a time when the field is maturing rapidly. The rAAV8RSM has been deposited at the American Type Culture Collection (VR-1816) and is available to the scientific community.

Bat flies on phyllostomid hosts in the Cerrado region: component community, prevalence and intensity of parasitism

Streblidae flies are specialised parasites of bat hosts, mainly phyllostomids. There is a high richness of streblids in the savannah-like Cerrado region; however, there is little quantitative data available in parasitological indices. Here, we describe the component community, prevalence and intensity of a streblid infestation on a phyllostomid bat assemblage in Serra da Bodoquena, a Cerrado region in Southwest Brazil. We conducted surveys by capturing and inspecting bat hosts during the seven-month period between October 2004-December 2005. All the ectoparasites found on the bats were collected in the field and then counted and identified in the laboratory. We captured 327 bats belonging to 13 species, of which eight species were parasitized by 17 species of streblids. Carollia perspicillata and Glossophaga soricina were infested with seven streblid species, whereas the other bat species were infested with four or fewer streblid species. Megistopoda proxima and Aspidoptera falcata flies were found on Sturnira lilium, and Trichobius joblingi was the most prevalent fly on C. perspicillata. Megistopoda aranea and Aspidoptera phyllostomatis were highly prevalent and had a high intensity of infestation on Artibeus planirostris. Overall comparisons of the available data suggest that the component communities of streblids vary more between the Cerrado and Atlantic Forest phytogeographical regions than between localities within the same phytogeographical region.

Analysis of GPCR properties of Frizzled receptors and establishment of the "in vitro" platform for screening of Frizzled agonists/antagonists as potential therapeutic agents

Morphogens of the Wnt protein family are the secreted lipoglycoprotein ligands which initiate several pathways heavily involved in the coordination of various developmental stages of organisms in the majority of animal species. Deregulation of these pathways in the adult leads to formation and sustaining of multiple types of cancer. The latter notion is reinforced by the fact that the very discovery of the first Wnt ligand was due to its role as the causative factor of carcinogenic transformation (Nusse and Varmus, 1982). Nowadays our knowledge on Wnt signaling has "moved with the times" and these pathways were identified to be often crucial for tumor formation, its interactions with the microenvironment, and promotion of the metastases (Huang and Du, 2008; Zerlin et al., 2008; Jessen, 2009). Thus the relevance of the pathway as the target for drug development has further increased in the light of modern paradigms of the complex cancer treatments which target also spreading and growth- promoting factors of tumors by specific and highly efficient substances (Pavet et al., 2010). Presently the field of the Wnt-targeting drug research is almost solely dominated by assays based on transcriptional activation induced by the signaling. This approach resulted in development of a number of promising substances (Lee et al., 2011). Despite its effectiveness, the method nevertheless suffers from several drawbacks. Among the major ones is the fact that this approach is prone to identify compounds targeting rather downstream effectors of the pathway, which are indiscriminately used by all the subtypes of the Wnt signaling. Additionally, proteins which are involved in several signaling cascades and not just the Wnt pathway turn out as targets of the new compounds. These issues increase risks of side effects due to off-target interactions and blockade of the pathway in healthy cells. In the present work we put forward a novel biochemical approach for drug development on the Wnt pathway. It targets Frizzleds (Fzs) - a family of 7-transmbembrane proteins which serve as receptors for Wnt ligands. They offer unique properties for the development of highly specific and effective drugs as they control all branches of the Wnt signaling. Recent advances in the understanding of the roles of heterotrimeric G proteins downstream from Fzs (Katanaev et al., 2005; Liu et al., 2005; Jernigan et al., 2010) suggest application of enzymatic properties of these effectors to monitor the receptor-mediated events. We have applied this knowledge in practice and established a specific and efficient method based on utilization of a novel high-throughput format of the GTP-binding assay to follow the activation of Fzs. This type of assay is a robust and well-established technology for the research and screenings on the GPCRs (Harrison and Traynor, 2003). The conventional method of detection involves the radioactively labeled non-hydrolysable GTP analog [35S]GTPyS. Its application in the large-scale screenings is however problematic which promoted development of the novel non-radioactive GTP analog GTP-Eu. The new molecule employs phenomenon of the time-resolved fluorescence to provide sensitivity comparable to the conventional radioactive substance. Initially GTP-Eu was tested only in one of many possible types of GTP-binding assays (Frang et al., 2003). In the present work we expand these limits by demonstrating the general comparability of the novel label with the radioactive method in various types of assays. We provide a biochemical characterization of GTP-Eu interactions with heterotrimeric and small GTPases and a comparative analysis of the behavior of the new label in the assays involving heterotrimeric G protein effectors. These developments in the GTP-binding assay were then applied to monitor G protein activation by the Fz receptors. The data obtained in mammalian cultured cell lines provides for the first time an unambiguous biochemical proof for direct coupling of Fzs with G proteins. The specificity of this interaction has been confirmed by the experiments with the antagonists of Fz and by the pertussis toxin-mediated deactivation. Additionally we have identified the specificity of Wnt3a towards several members of the Fz family and analyzed the properties of human Fz-1 which was found to be the receptor coupled to the Gi/o family of G proteins. Another process playing significant role in the functioning of every GPCR is endocytosis. This phenomenon can also be employed for drug screenings on GPCRs (Bickle, 2010). In the present work we have demonstrated that Drosophila Fz receptors are involved in an unusual for many GPCRs manifestation of the receptor-mediated internalization. Through combination of biochemical approaches and studies on Drosophila as the model organism we have shown that direct interactions of the Fzs and the α-subunit of the heterotrimeric G protein Go with the small GTPase Rab5 regulate internalization of the receptor in early endosomes. We provide data uncovering the decisive role of this self-promoted endocytosis in formation of a proper signaling output in the canonical as well as planar cell polarity (PCP) pathways regulated by Fz. The results of this work thus establish a platform for the high-throughput screening to identify substances active in the cancer-related Wnt pathways. This methodology has been adjusted and applied to provide the important insights in Fz functioning and will be instrumental for further investigations on the Wnt-mediated pathways.

Sphenoid sinus metastasis as the presenting manifestation of a prostatic adenocarcinoma: case report and overview of the literature.

Although a metastatic presentation of an occult prostatic adenocarcinoma is not uncommon, the majority of these patients present with bone metastasis affecting the axial skeleton. Cranial metastases to the paranasal sinuses are extremely rare. A 56-year-old man presented with loss of vision and numbness of the right side of the face. Computed tomography (CT) scan and cranial magnetic resonance imaging (MRI) revealed a mass invading the sphenoid sinus. The patient underwent surgery to remove the lesion, and the histopathological examination suggested metastasis of an adenocarcinoma, with positive staining to prostatic specific antigen (PSA). However, serum PSA was 4 ng/mL, and the patient did not report any lower urinary tract symptoms or bone pain. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinomas with a Gleason score of 8 [4 + 4]. The subsequent treatment consisted of radiotherapy and androgen deprivation, followed by first- and second-line chemotherapy (docetaxel and cabazitaxel) when the disease progressed. The patient achieved a good response with the last cycle of cabazitaxel and after a 5-year followup is currently alive. Cranial metastases of prostate adenocarcinoma are rare, and there is currently no standard treatment for these patients. Whenever possible, surgery combined with radiotherapy and hormonotherapy is the recommended option.

Emergence and characterisation of vanB vancomycin-resistant Enterococcus faecalis in Rio de Janeiro, Brazil

Here we describe the detection and characterisation of three isolates of vancomycin-resistant VanB-type Enterococcus faecalis. Sequence analysis suggested that these isolates harboured the vanB1 gene. The isolates were susceptible to the majority of antimicrobial agents tested, with the exception of chloramphenicol, erythromycin and vancomycin, and showed distinct profiles of high-level resistance to aminoglycosides. Analysis of the clonal relatedness of the vanB E. faecalis isolates showed similar pulsed-field gel electrophoresis profiles. To our knowledge, this is the first report of the occurrence of enterococcal strains carrying vanB genes in Brazil.

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

Surface-sampling and analysis of TATP by swabbing and gas chromatography/mass spectrometry

The method of sample recovery for trace detection and identification of explosives plays a critical role in several criminal investigations. After bombing, there can be difficulties in sending big objects to a laboratory for analysis. Traces can also be searched for on large surfaces, on hands of suspects or on surfaces where the explosive was placed during preparatory phases (e.g. places where an IED was assembled, vehicles used for transportation, etc.). In this work, triacetone triperoxide (TATP) was synthesized from commercial precursors following reported methods. Several portions of about 6 mg of TATP were then spread on different surfaces (e.g. floors, tables, etc.) or used in handling tests. Three different swabbing systems were used: a commercial swab, pre-wetted with propan-2-ol (isopropanol) and water (7:3), dry paper swabs, and cotton swabs wetted with propan-2-ol. Paper and commercial swabs were also used to sample a metal plate, where a small charge of about 4 g of TATP was detonated. Swabs were sealed in small glass jars with screw caps and Parafilm® M and sent to the laboratory for analysis. Swabs were extracted and analysed several weeks later by gas chromatography/mass spectrometry. All the three systems gave positive results, but wetted swabs collected higher amounts of TATP. The developed procedure showed its suitability for use in real cases, allowing TATP detection in several simulations, including a situation in which people wash their hands after handling the explosive.

Is the effect of inguinal field block with 0.5 % bupivacaine on postoperative pain after hernia repair enhanced by addition of ketorolac or S(+) ketamine ?

Résumé Malgré l'apparition de nouvelles techniques chirurgicales dites « sans tension », l'antalgie post-opératoire après cure de hernie inguinale reste un défi pour les anesthésiologistes. Récemment on a suggéré que l'addition de ketamine ou d'un anti-inflammatoire non-stéroïdien (AINS) à un anesthésique local pourrait améliorer et prolonger l'analgésie postopératoire. Le but de cette étude, à laquelle ont participé 36 patients ASA I-II, était d'évaluer si la coadministration de S(+) ketamine ou de ketorolac renforcerait les effets analgésiques de la bupivacaïne après cure ambulatoire de hernie inguinale sous anesthésie générale. L'analgésie a consisté en une infiltration de la plaie associé à un bloc inguinal avec soit 30 ml de bupivacaïne 0,5 % (n=12), soit 27 ml de bupivacaïne 0,5 % + 3 ml de S(+) ketamine (75 mg) (n=12), soit 28 ml de bupivacaïne 0,5 % + 2 ml de ketorolac (60 mg) (n=12). La prise orale d'antalgique en phase postopératoire était standardisée. L'intensité des douleurs a été évaluée au moyen d'une échelle visuelle analogique (EVA), d'un score verbal d'estimation et par algométrie de pression respectivement 2, 4, 6, 24 et 48 heures après l'intervention. Les trois groupes de patients ont présenté le score de douleur évalué par EVA le plus élevé à 24 heures, score significativement différent de ceux mesurés à 6 et 48 heures (P <0.05). A part une sensation de douleurs significativement moindre (score verbal d'estimation) dans le groupe ketorolac à 24 et 48 heures et seulement à 48 heures dans le groupe ketamine, il n'y avait aucune autre différence entre les groupes pour la durée de l'étude (48 heures) en ce qui concerne les scores de douleur, les seuils de douleur à la pression ou la prise postopératoire d'antalgiques « de secours ». En conclusion, l'addition de S(+) ketamine ou de ketorolac, n'améliore que marginalement l'effet analgésique de la bupivacaïne. Ceci peut-être mis en relation avec la technique de cure de hernie « sans tension » induisant un bas niveau de douleur postopératoire. Abstract Objective: The aim of the study was to assess whether coadministration of S(±) ketamine or ketorolac would enhance or prolong local analgesic effect of bupivacaine after inguinal hernia repair. Design: Prospective double-blind randomized study evaluating pain intensity after surgery under general anesthesia. Setting: Outpatient facilities of the University Hospital of Lausanne. Patient: Thirty-six ASA I-II outpatients scheduled for elective day-case inguinal herniorraphy. Intervention: Analgesia strategy consisted of a wound infiltration and an inguinal field block either with 30 mL bupivacairie (0.5%) or with the same volume of a mixture of 27 mL bupivacaine (0.5%) + 3 mL S(+) ketamine (75 mg) or a 28 mL bupivacaine (0.5%) + 2 ML ketorolac (60 mg). Postoperative analgesic regimen was standardized. Outcome Measures: Pain intensity was assessed with a Visual Analog Seale, a verbal rating score, and by pressure algometry 2, 4, 6, 24, and 48 hours after surgery. Results: The 3 groups of patients experienced the highest Visual Analog Scale pain score at 24 hours, which was different from those at 6 and 48 hours (P < 0.05). Apart from a significantly lower pain sensation (verbal rating score) in the ketorolac group at 24 and 48 hours and only at 48 hours with ketamine, there were no other differences in pain scores, pain pressure thresholds, or rescue analgesic consumption between groups throughout the 48-hour study period. Conclusion: The addition of S (+)-ketamine or ketorolac only minimally improves the analgesic effect of bupivacaine. This may be related to the tension-free hernia repair technique associated with low postoperative pain.

CYR61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma.

Radiotherapy is widely used to treat human cancer. Patients locally recurring after radiotherapy, however, have increased risk of metastatic progression and poor prognosis. The clinical management of postradiation recurrences remains an unresolved issue. Tumors growing in preirradiated tissues have an increased fraction of hypoxic cells and are more metastatic, a condition known as tumor bed effect. The transcription factor hypoxia inducible factor (HIF)-1 promotes invasion and metastasis of hypoxic tumors, but its role in the tumor bed effect has not been reported. Here, we show that tumor cells derived from SCCVII and HCT116 tumors growing in a preirradiated bed, or selected in vitro through repeated cycles of severe hypoxia, retain invasive and metastatic capacities when returned to normoxia. HIF activity, although facilitating metastatic spreading of tumors growing in a preirradiated bed, is not essential. Through gene expression profiling and gain- and loss-of-function experiments, we identified the matricellular protein CYR61 and alphaVbeta5 integrin as proteins cooperating to mediate these effects. The anti-alphaV integrin monoclonal antibody 17E6 and the small molecular alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 suppressed invasion and metastasis induced by CYR61 and attenuated metastasis of tumors growing within a preirradiated field. These results represent a conceptual advance to the understanding of the tumor bed effect and identify CYR61 and alphaVbeta5 integrin as proteins that cooperate to mediate metastasis. They also identify alphaV integrin inhibition as a potential therapeutic approach for preventing metastasis in patients at risk for postradiation recurrences.

A new neuropsychological instrument measuring effects of age and drugs on fitness to drive: development, reliability, and validity of MedDrive

Background: Current guidelines underline the limitations of existing instruments to assess fitness to drive and the poor adaptability of batteries of neuropsychological tests in primary care settings. Aims: To provide a free, reliable, transparent computer based instrument capable of detecting effects of age or drugs on visual processing and cognitive functions. Methods: Relying on systematic reviews of neuropsychological tests and driving performances, we conceived four new computed tasks measuring: visual processing (Task1), movement attention shift (Task2), executive response, alerting and orientation gain (Task3), and spatial memory (Task4). We then planned five studies to test MedDrive's reliability and validity. Study-1 defined instructions and learning functions collecting data from 105 senior drivers attending an automobile club course. Study-2 assessed concurrent validity for detecting minor cognitive impairment (MCI) against useful field of view (UFOV) on 120 new senior drivers. Study-3 collected data from 200 healthy drivers aged 20-90 to model age related normal cognitive decline. Study-4 measured MedDrive's reliability having 21 healthy volunteers repeat tests five times. Study-5 tested MedDrive's responsiveness to alcohol in a randomised, double-blinded, placebo, crossover, dose-response validation trial including 20 young healthy volunteers. Results: Instructions were well understood and accepted by all senior drivers. Measures of visual processing (Task1) showed better performances than the UFOV in detecting MCI (ROC 0.770 vs. 0.620; p=0.048). MedDrive was capable of explaining 43.4% of changes occurring with natural cognitive decline. In young healthy drivers, learning effects became negligible from the third session onwards for all tasks except for dual tasking (ICC=0.769). All measures except alerting and orientation gain were affected by blood alcohol concentrations. Finally, MedDrive was able to explain 29.3% of potential causes of swerving on the driving simulator. Discussion and conclusions: MedDrive reveals improved performances compared to existing computed neuropsychological tasks. It shows promising results both for clinical and research purposes.

Spanish multicenter study of the epidemiology and mechanisms of amoxicillin-clavulanate resistance in Escherichia coli.

We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.

Biogeochemical weathering in sedimentary chronosequences of the Rhône and Oberaar Glaciers (Swiss Alps): rates and mechanisms of biotite weathering

We analysed the composition of phyllosilicate minerals in sediments deposited by the Rhone and Oberaar glaciers (Swiss Alps), in order to identify processes and rates of biogeochemical weathering in relation to glacial erosion. The investigated sediments are part of chronosequences consisting of (A) suspended, "fresh" sediment in melt water; (B) terminal moraines from the Little Ice Age (LIA; approximately 1560-1850); and (C) tilts of the Younger Dryas interval (YD; approximately 11'500y BP). Secondary weathering products associated with the suspended sediment have not been observed: we therefore exclude intermittent subglacial storage and weathering of this material and assume that the suspended sediment is directly derived from mechanically abraded bedrock. This implies that biogeochemical weathering processes started once the glacially-derived sediment was deposited in the proglacial area. The combination of a developing vegetation cover, the generally high permeability allowing the percolation of precipitation, and the chemical reactivity related to the dominance of fine-grained material (<63 pm) drives the weathering process and the initial Umbrepts present in LIA profiles undergo podzolisation and lead to the formation of Humods observed in YD profiles. Systematic XRD analyses of these chronosequences show a progressive decrease in biotite contents and a concomitant increase in pedogenically formed vermiculite with increasing sediment age. Biotite contents decrease by 25-50% in the upper 30 cm of the moraines after 145-275 yr in the proglacial environment. Biotite weathering rates are calculated using the difference in the biotite content between unweathered and weathered glacial sediments within the investigated profiles. The reactive mineral surface area is estimated geometrically, both with regards to the total relative surface (WRT) as well as to the relative edge surface (WRE). WRT Biotite weathering rates are estimated as 10(-13)-10-(15) mol(biotite) m(biotite)(-2) s(-1). WRE Biotite weathering rates are on the order of 10(-13)-10(-14) mol(biotite) m(biotite)(-2) s(-1). Biotite weathering rates obtained by this study are in the order of one magnitude higher in comparison to other published field-based weathering rates. Using biotite as an indicator, we therefore suggest that glacially-derived material in the area of the Oberaar and Rhone glaciers is generally subjected to enhanced biogeochemical weathering, starting immediately after deposition in the proglacial zone and subsequently continuing for thousands of years after glacier retreat.