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Infectious diarrhoea is common post-allogeneic haematopoietic stem-cell transplantation (alloHSCT). While the epidemiology of Clostridioides difficile infection (CDI) post-alloHSCT has been described, the impact of other diarrhoeal pathogens is uncertain. We reviewed all alloHSCT between 2017–2022 at a single large transplant centre; 374 patients were identified and included. The 1-year incidence of infectious diarrhoea was 23%, divided into viral (13/374, 3%), CDI (69/374, 18%) and other bacterial infections (16/374, 4%). There was a significant association between infectious diarrhoea within 1-year post-transplant and the occurrence of severe acute gastrointestinal graft-versus-host-disease (GVHD, OR = 4.64, 95%CI 2.57–8.38, p

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4−CD8−) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion:: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

Anchor scour from shipping is increasingly recognised as a global threat to benthic marine biodiversity, yet no replicated ecological assessment exists for any seabed community. Without quantification of impacts to biota, there is substantial uncertainty for maritime stakeholders and managers of the marine estate on how these impacts can be managed or minimised. Our study focuses on a region in SE Australia with a high proportion of mesophotic reef (30 m), where ships anchor while waiting to enter nearby ports. Temperate mesophotic rocky reefs are unique, providing a platform for a diversity of biota, including sponges, ahermatypic corals and other sessile invertebrates. They are rich in biodiversity, provide essential food resources, habitat refugia and ecosystem services for a range of economically, as well as ecologically important taxa. We examined seven representative taxa from four phyla (porifera, cnidaria, bryozoan, hydrozoa) across anchored and 'anchor-free' sites to determine which biota and which of their morphologies were most at risk. Using stereo-imagery, we assessed the richness of animal forest biota, morphology, size, and relative abundance. Our analysis revealed striking impacts to animal forests exposed to anchoring with between three and four-fold declines in morphotype richness and relative abundance. Marked compositional shifts, relative to those reefs that were anchor-free, were also apparent. Six of the seven taxonomic groups, most notably sponge morphotypes, exhibited strong negative responses to anchoring, while one morphotype, soft bryozoans, showed no difference between treatments. Our findings confirm that anchoring on reefs leads to the substantial removal of biota, with marked reductions of biodiversity and requires urgent management. The exclusion of areas of high biological value from anchorages is an important first step towards ameliorating impacts and promoting the recovery of biodiversity.

Chronic Neutrophilic Leukemia (CNL) is a rare BCR-ABL negative myeloproliferative neoplasm that affects approximately 1 in a million individuals. The typical age of onset and disease presentation is in elderly patients with a median age of 63 and a range of 9-84. The oncogenic driver of CSF3R, the G-CSF receptor protein, in CNL has been classified over the last decade and has improved therapies for patients with targeted Tyrosine Kinase Inhibitors, such as Ruxolitinib (a potent JAK1/2 inhibitor). Currently, the only curative option is an allogeneic hemopoietic stem cell transplant with typical median overall survival of 2 years. Because of the low occurrence rate of CNL, there have only been 3 germline cases of CSF3R classified in literature. With these patients, they exhibit a lifelong skewing of the myeloid lineage causing gross neutrophilia. Our patient presented at 13 months with leukocytosis and neutrophilia, resulting in genetic testing revealing the diagnosis of the youngest documented case of CNL. A germline CSF3R T618I constitutive activating mutation was documented in our patient and in her father. Her father had documented lifelong leukocytosis of indeterminate origin and it was not until 33 that genetic testing was done, and he was diagnosed with CNL. He underwent an allogeneic stem cell transplant after being admitted with gross hepatosplenomegaly with a WBC of 322, the highest recorded in a germline CNL patient in literature. Our patient presented to clinic with leukocytosis ranging from 45-98 and hepatosplenomegaly. After a bone marrow aspirate and biopsy was taken to determine disease stage and severity, we immediately began Ruxolitinib therapy. We began 20 mg BID dosing based on platelets and monitored response to therapy while conducting targeted RNA-seq for myelodysplastic and myeloid leukemia genes on the bone marrow, which did not detect any secondary mutations. Ruxolitinib dosing was tapered down in a stepwise fashion, until the patient arrived at the current dose of 7.5 mg BID Ruxolitinib, resulting in stable leukocyte counts around 25. As part of monitoring, we are currently conducting 6-month BM procedures and NGS for AML/MDS genes and Ruxolitinib resistance mutations alongside monthly CBCs. Our patient has been on Ruxolitinib for 9 months and has not developed any secondary contributing mutations and remains sensitive to therapy. We continue to monitor our patient’s response to Ruxolitinib to determine if germline predisposition alters the transformative nature of the disease. Within T618I germline CNL cases, we are investigating the difference in phenotype and disease burden that we observe in our patient’s family compared to literature. Based on current cases, it seems that germline CNL does not transform during childhood and adolescence into AML without the influence of a secondary mutation. Retrospective studies into previous cases of CNL to determine if there is a higher frequency of germline origin could pave the way for potential early-stage therapies and detection of CNL prior to transformation. Citation Format: Kevin Zhang, Matthew Rees, Mahsa Khanlari, Laura Rooms, Raul Ribeiro, Marcin Wlodarski. Pediatric Germline CSF3R T618I mutation gives insight into disease progression and long-term therapy options of Chronic Neutrophilic Leukemia [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A38.

Despite the introduction of a number of new therapeutic classes including targeted inhibitors, immunotherapy, and antibody-drug conjugates, the ability to achieve long-term disease control in the majority of patients with advanced cancer remains elusive due to the emergence of resistance. While our understanding of resistance mechanisms continues to expand through preclinical and clinical sequencing efforts, comprehensive approaches to map the distribution of potential resistance mechanisms in a given cell line and drug context require the development of novel approaches. Here, we describe the design of a platform for profiling cancer resistance at scale. Beginning with a single sensitive parental cancer cell line, the EGFR-mutant lung cancer line PC9, we optimize pre-existing diversity using a combination of single-cell subcloning and alkylator mutagenesis, and generate 50 independently evolved clones resistant to the EGFR inhibitor osimertinib. Profiling of this library via multiplexed whole genome sequencing (WGS) demonstrates convergent mutations in the MAPK pathway. Taking a similar approach, we profile the NTRK1-fusion-driven KM12 colon cancer cell line, yielding convergent, clinically observed, on-target resistance mutations to the NTRK inhibitor larotrectinib. Taken together, these results provide an initial proof-of-concept for the high-throughput generation of viable drug-resistant cancer clones. Future efforts to increase mutational diversity as well as assess additional drug and disease contexts will broaden the utility of this approach. Citation Format: Arvind Ravi, Sainikhil Sontha, Maisha Chowdhury, Jacob Smigiel, Matthew Rees, Brian Danysh, Jennifer Roth, Laxmi Parida, Eric Lander, Gad Getz. A platform for deep evolutionary profiling of cancer resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 143.

Immune checkpoint blockade is effective for a subset of patients across many cancers, but most patients are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatase PTPN2 is a central regulator of inflammation, and genetic deletion of PTPN2 on either tumour cells or host immune cells promotes anti-tumour immunity. However, inhibitors of PTPN2 with suitable pharmacokinetic properties for oral administration have not been described. Here, we present the characterization of ABBV-CLS-484 (A484), a potent active site inhibitor of PTPN2 and the closely related phosphatase PTPN1. A484 treatment in vitro amplifies the response to interferon gamma, and monotherapy A484 treatment generates robust anti-tumour immunity in several murine cancer models. Through in vivo studies and single cell transcriptional profiling of tumour-infiltrating lymphocytes (TIL) from A484-treated mice, we show that A484 inflames the tumour microenvironment and promotes CD8+ T cell function by enhancing cytokine signaling and decreasing T cell exhaustion and dysfunction. Our results demonstrate that oral administration of small molecule inhibitors of PTPN2/N1 can induce potent anti-tumour immunity in mouse models. PTPN2/N1 inhibitors offer a promising new strategy for cancer immunotherapy and are currently being evaluated clinically in patients with advanced solid tumours (NCT04777994). More broadly, our study shows that small molecule inhibitors of key intracellular immune regulators can achieve efficacy comparable to current antibody-based immune checkpoint blockade in preclinical models. Finally, to our knowledge A484 represents the first active-site phosphatase inhibitor to enter clinical evaluation for cancer immunotherapy and may pave the way for additional therapeutics targeting this important class of enzymes. Citation Format: Hakimeh Ebrahimi-Nik, Arvin Iracheta-Vellve, Kira E. Olander, Thomas R.G. Davis, Sarah Y. Kim, Mitchell D. Yeary, James C. Patti, Tyler M. Balon, Omar Ismail Avila, Cun Lan Chuong, Meng-Ju Wu, Christina K. Baumgartner, Keith M. Hamel, Kathleen A. McGuire, Rebecca Mathew, Carey Backus, Ian C. Kohnle, Zhaoming Xiong, Elliot P. Farney, Jennifer M. Frost, Geoff T. Halvorsen, Matthew Rees, Andrew Boghossian, Melissa Ronan, Jennifer A. Roth, Todd R. Golub, Gabriel K. Griffin, Nabeel El-Bardeesy, Clay C. Beauregard, Philip R. Kym, Kathleen B. Yates, Robert T. Manguso. Small molecule inhibition of PTPN2/1 inflames the tumour microenvironment and unleashes potent CD8+ T cell immunity [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A41.

Background There is great interest in utilizing nanoparticles to improve drug delivery to central nervous system (CNS) tumors, but the biologic features underlying successful delivery at the tumor site are not known. METHODS We developed a pooled screening assay to investigate cellular features predictive of nanoparticle delivery and screened 35 fluorescent nanoparticle formulations against 488 pooled cancer cell lines with DNA barcodes. The nanoparticle library was comprised of nonlethal liposomal or polymeric cores with varied surface functionality, including natural and synthetic polymers. Cells were profiled using fluorescence-activated cell sorting and barcodes sequenced and deconvolved to generate an association score for each nanoparticle-cell line pair. RESULTS Of 488 cancer cell lines, 22 cancer cell lineages (tissues of origin) were included. There were 35 cell lines derived from CNS tumors; of these 22 were classified as astrocytoma or glioblastoma, one as oligodendroglioma, and 2 as medulloblastoma. Of CNS tumor cell lines, 40% were from female patients and average age at cell line derivation was 52 years; TP53 hotspot mutations were detected in 25/35 lines, PTEN hotspot mutations in 15/25 lines. Using unsupervised hierarchical clustering by nanoparticle association profiles, CNS tumor lines did not cluster together by lineage, subtype, or mutation status but rather by baseline expression of genes involved in nanocarrier trafficking. Nanoparticle association profiles were heterogeneous among the CNS tumor lines for most formulations, though CNS tumor lines had high association with polystyrene formulations with respect to other lineages. Select CNS tumor lines had high uptake of liposomes coated with the natural polymers fucoidan, alginate, hyaluronic acid and chondroitin sulfate; these trends were further probed in a non-pooled screen of 5 additional cell lines. Conclusions Uptake of liposomal and polymeric nanoparticles is heterogeneous across CNS tumor lines, but can be predicted using baseline gene expression.

The acidity of the α-proton in peptides has an essential role in numerous biochemical reactions and underpins their stereochemical integrity, which is critical to their biological function. We report a detailed kinetic and computational study of the acidity of the α-proton in two cyclic peptide systems: diketopiperazine (DKP) and triketopiperazine (TKP). The kinetic acidity (protofugality) of the α-protons were determined though hydrogen deuterium exchange studies in aqueous solutions. The acidities of the α-proton in prolyl residues were increased by 3–89 fold relative to other amino acid residues (prolyl > glycyl ≫ alanyl > tyrosyl). Experimental and computational evidence for the stereoelectronic origins of this enhanced prolyl reactivity is presented. TKPs were 106-fold more reactive than their DKP analogues towards deprotonation, which we attribute to the advanced development of aromaticity in the earlier transition state for proton transfer in these cases. A Brønsted linear free energy analysis of the reaction data was conducted to provide estimates of α-proton pKas., Kinetic and computational studies reveal that prolyl residues in cyclic peptides are substantially more acidic than other residues due to a stereoelectronic effect.

Immune checkpoint blockade is effective for a subset of patients across many cancers, but most patients are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatase PTPN2 is a central regulator of inflammation, and genetic deletion of PTPN2 on either tumor cells or host immune cells promotes anti-tumor immunity. However, inhibitors of PTPN2 have not been described. Here, we present the validation of ABBV-CLS-484, a potent catalytic inhibitor of PTPN2 and the closely related phosphatase PTPN1. ABBV-CLS-484 treatment of tumor cells in vitro phenocopies the genetic deletion of PTPN2/N1, causing both amplified transcriptional responses to IFNg and reduced cell viability across human cancer cell lines. Monotherapy ABBV-CLS-484 treatment generates robust anti-tumor immunity in several murine cancer models with efficacy comparable to anti-PD-1 treatment. Through genetic studies, we show that while ABBV-CLS-484 can act on both tumor cells and the host immune system, IFN sensing and PTPN2/N1 expression on tumor cells are not always required for efficacy, suggesting that PTPN2/N1 inhibition on host immune cells may be sufficient for activity of the drug. Through scRNAseq profiling of TILs from both ABBV-CLS-484-treated and anti-PD-1-treated tumors, we show that ABBV-CLS-484 induces unique transcriptional changes to both myeloid and lymphoid populations in the tumor microenvironment which are dominated by enhanced IFN sensing and a shift from suppressive to pro-inflammatory phenotypes. ABBV-CLS-484 treatment enhances the activation and effector functions of CD8+ T cells while decreasing the expression of genes classically associated with T cell exhaustion and dysfunction such as Tox. The efficacy of ABBV-CLS-484 is critically dependent on CD8+ T cells and treatment with ABBV-CLS-484 results in greater levels of T cell infiltration into tumors and a more diverse repertoire of expanded T cell clones relative to anti-PD-1. Thus, the PTPN2/N1 inhibitor ABBV-CLS-484 is a highly effective immunotherapy with monotherapy efficacy across mouse tumor models. Small molecule inhibitors of PTPN2 offer a promising new strategy for cancer immunotherapy by targeting an IFN signaling checkpoint and are currently being evaluated clinically in patients with advanced solid tumors (NCT04777994). Citation Format: Arvin Iracheta-Vellve, Hakimeh Ebrahimi-Nik, Thomas R. Davis, Kira E. Olander, Sarah Y. Kim, Mitchell D. Yeary, James C. Patti, Ian C. Kohnle, Christina K. Baumgartner, Keith M. Hamel, Kathleen A. McGuire, Cun Lan Chuong, Zhaoming Xiong, Elliot P. Farney, Jennifer M. Frost, Matthew Rees, Andrew Boghossian, Melissa Ronan, Jennifer A. Roth, Todd R. Golub, Gabriel K. Griffin, Clay Beauregard, Philip R. Kym, Kathleen B. Yates, Robert T. Manguso. Targeting the immune checkpoint PTPN2 with ABBV-CLS-484 inflames the tumor microenvironment and unleashes potent CD8+ T cell immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 606.

Introduction The requirements for successful completion of Pediatric Residency is clear, but until recently there was very little guidance regarding physician work-life integration. Given the growing awareness of physician burnout and the increased physician suicide rate compared to the general public (American Journal of Psychiatry.2004. 161(12), 2295-2302), our program deemed it necessary to implement a curriculum focused on wellness early in medical training. Methods Our program implemented a Professional Development and Wellness Week (7 days) during intern year. During this week, interns are required to meet with their adviser, shadow an inpatient nurse, and create a “chalk talk”. Otherwise, they are provided a menu of personal and professional activity suggestions. Interns complete a survey at the end of their week documenting the completed activities. Outcomes Thus far, 13 of 24 (54%) Pediatric residents have completed their PDW week and post-completion survey. The most commonly selected activities included: completing outstanding MedHub evaluations (100%), engaging in a favorite hobby (100%), attending a health-related appointment (92%), and organizing email/EMR (76%). Results The most common optional activities that residents completed during protected personal development time include administrative tasks (email and evaluations) and healthcare-related activities. Conclusions When provided unstructured time for personal development, interns may prioritize completing outstanding administrative tasks and health-related appointments. This suggests that a longitudinal administrative “half-day” experience may be beneficial. Future directions also include collecting data related to administrative tasks and burnout.

Background/Aims: We surveyed sickle cell disease (SCD) patients who transitioned from pediatric care at Texas Children’s Hematology Center (TCHC) to adult care to determine the characteristics of patients with an adult SCD provider, continuation rates of pre-transition therapies, and patient perceptions of the transition process. Methods: A cross-sectional study was conducted by telephone survey of 44 young adults with SCD, aged 19–29 years, who transitioned from TCHC to adult care within the last 15 years. Results: Findings of the 23-item questionnaire revealed that transitioned patients with current adult providers (68.2%) were more likely to have seen a provider within 6 months of transition (p = 0.023) and to have been on hydroxyurea and/or monthly blood transfusions pre-transition (p = 0.021) than transitioned patients without a provider; 83% of patients on pre-transition hydroxyurea reported continuing hydroxyurea after transition. Transition challenges included inadequate preparation, difficulty finding knowledgeable adult providers, and lack of healthcare insurance/coverage. Conclusion: Transition to adult providers is predicted by establishing care with an adult SCD provider within 6 months of transition and being on pre-transition disease-modifying therapy. Transition may be improved if pediatric hematology centers assist and verify adult provider contact within 6 months of transition and engage patients of all disease severity during transition.

Michael addition of a proline-derived triketopiperazine (TKP) to β-substituted enones and acrylamides, mediated by a cinchona alkaloid catalyst, delivers products possessing a bicyclo[2.2.2]diazaoctane structure in high yield and enantiomeric ratio (er). Further modification of the amide products toward polycyclic scaffolds resembling members of the prenylated alkaloid family is also demonstrated.

In this study, lead (Pb) bioaccessibility was assessed in peri-urban contaminated soils using a variety of established in vitro assays. Bioaccessibility data was then used to predict Pb relative bioavailability (RBA) using published in vivo-in vitro regression models in order to compare calculated estimates and measured values. Lead bioaccessibility varied depending on the in vitro methodology employed with the relative bioavailability leaching procedure (RBALP) and in vitro gastrointestinal (IVG) assays providing more conservative Pb bioaccessibility values compared to those determined using PBET, UBM and Rel-SBRC-I assays. When Pb RBA was calculated, predicted values using PBET-G and UBM-G data were similar to measured Pb RBA values. However, Pb RBA was over-estimated by 1.6-5.5- and 2.6-6.6-fold when data and regression models from RBALP and IVG-G assays were employed. Refereed/Peer-reviewed

This paper addresses key considerations for the design of the expansion of the Port of Haifa, Israel container terminal in an area of moderately high seismicity for the development of several breakwaters/revetments and quays. Design-level ground motions were associated with a M 7.0 earthquake. The proposed port development is also exposed to waves from the Mediterranean Sea. The soil conditions posed several challenges for both static and seismic deformation potential. Both the reclaimed sand and some of the underlying dune sand were determined to be potentially liquefiable. In addition, a layer of soft clay resulted in the potential for excessive settlements and/or low bearing capacity for gravity-based structures. Furthermore, there was a shortage of available sand for reclamation in the dredging areas within the Port, requiring the sourcing of significant reclamation fill from an offshore borrow pit which contained sand with a relatively high fines content. Finally, the proposed terminal is located in environmentally sensitive Haifa Bay, resulting in strict limitations on dredging operations to protect marine life. In order to address these challenges and optimize the design, both static and seismic analyses, using a displacement limit approach, were carried out for breakwater, revetment and quay structures, and these, along with coastal and construction considerations, were used to: (1) select the most cost effective structure types, and subsequently, and (2) optimize their configurations. Analyses considered the quality of the reclamation fill, compaction using vibrocompaction and/or stone columns, and environmental concerns related to dredging and reclamation.

In this study, lead (Pb) bioaccessibility in contaminated soils was assessed using an in vitro method (SBRC) encompassing gastric (SBRC-G) and intestinal (SBRC-I) phases. Initially, bioaccessibility studies were performed with a Pb reference material (Pb acetate, 1-10 mg L⁻¹) in order to determine the influence of pH on Pb solubility. In the gastric phase (pH 1.5), Pb solubility was 100% (100 ± 2.9%, n = 16) irrespective of the Pb concentration added, however, when the pH of the intestinal phase was increased to near neutral, Pb solubility decreased to 14.3 ± 7.2%. In contaminated soils, Pb bioaccessibility varied from 35.7 to 64.1% and 1.2 to 2.7% for SBRC-G and SBRC-Iphases, respectively.When relative bioaccessibility (Rel-SBRCI) was calculated by adjusting the dissolution of Pb from contaminated soils by the solubility of Pb acetate at pH 6.5(intestinal phase pH), Rel-SBRC-I values ranged from 11.7-26.1%. A stepwise regression model based on Pearson correlation factors was used to determine the suitability of in vitro assays for predicting in vivo(swine assay) relative Pb bioavailability. Rel-SBRC-I provided the best estimate of in vivo relative Pb bioavailability for soils used in this study (in vivo relative Pb bioavailability [%] = Rel-SBRC-I [pH 6.5%] × 0.58 + 1.98, r² = 0.53). The versatility of Rel-SBRC-I was demonstrated by accurately predicting relative Pb bioavailability from otherreported in vivo studies. Refereed/Peer-reviewed

Arsenic (As) bioaccessibility in contaminated soils (n=50) was assessed using the simplified bioaccessibility extraction test (SBET). Soils used in the study were collected from sites where As was used as an herbicide (railway corridor) or pesticide (cattle dip sites), from former gold mines and from highly mineralised locations containing geogenic As sources (gossans). In all but three soils, As bioaccessibility was less than 50% indicating that a significant proportion of the total As concentration may not be available for absorption in the gastrointestinal tract following incidental soil ingestion. When regression models were developed based on soil properties, the descriptive variables best able to describe As bioaccessibility in railway corridor, dip site and mine site soils were total As and total or dithionite-citrate extractable (free) iron (Fe). While As bioaccessibility could be predicted (r(2)=0.955, n=50) in these contaminated soils, As bioaccessibility for gossan soils was a poor fit using linear or multivariate regression analysis.

This paper describes the design and evaluation of AffectCam, a wearable system integrating SenseCam and BodyMedia SenseWear for capturing galvanic skin response as a measure of bodily arousal. AffectCam's algorithms use arousal as a filtering mechanism for selecting the most personally relevant photos captured during people's ordinary daily life, i.e. high arousal photos. We discuss initial findings showing that emotional arousal does improve the quality of memory recall associated with emotionally arousing events. In particular, the high arousal photos support richer recall of episodic memories than low arousal ones, i.e. over 50% improvement. We also consider how various phenomenological characteristics of autobiographical memories such as event, emotions, thoughts, place and time are differently cued by the AffectCam.

Currently, a number of in vitro methods are in use worldwide to assess arsenic (As) bioaccessibility in soils. However, a dearth of research has been undertaken to compare the efficacy of the in vitromethodsfor estimating in vivo relativeAsbioavailability. In this study, As bioaccessibility in contaminated soils (n ) 12) was assessed using four in vitro assays (SBRC, IVG, PBET, DIN). In vitro results were compared to in vivo relative As bioavailabilitydata(swineassay)toascertainwhichmethodologies best correlate with in vivo data. Arsenic bioaccessibility in contaminated soils varied depending on the in vitro method employed. For the SBRC and IVG methods, As bioaccessibility generally decreased when gastric-phase values were compared to the intestinal phase. In contrast, extending the PBET and DIN assays from the gastric to the intestinal phase resulted in an increase in As bioaccessibility for some soils tested. Comparison of in vitro and in vivo results demonstrated that the in vitro assay encompassing the SBRC gastric phase provided the best prediction of in vivo relative As bioavailability (R2) 0.75, Pearson correlation) 0.87). However, relative As bioavailability could also be predicted using gastric or intestinal phases of IVG, PBET, and DIN assays but with varying degrees of confidence (R2) 0.53-0.67, Pearson correlation) 0.73-0.82). Refereed/Peer-reviewed

Considerable information is available in the literature regarding the uptake of arsenic (As) from contaminated soil and irrigation water by vegetables. However, few studies have investigated As speciation in these crops while a dearth of information is available on As bioavailability following their consumption. In this study, the concentration and speciation of As in chard, radish, lettuce and mung beans was determined following hydroponic growth of the vegetables using As-contaminated water. In addition, As bioavailability was assessed using an in vivo swine feeding assay. While As concentrations ranged from 3.0 to 84.2 mg As kg−1 (dry weight), only inorganic As (arsenite and arsenate) was detected in the edible portions of the vegetables. When As bioavailability was assessed through monitoring blood plasma As concentrations following swine consumption of As-contaminated vegetables, between 50% and 100% of the administered As dose was absorbed and entered systemic circulation. Arsenic bioavailability decreased in the order mung beans > radish > lettuce = chard.

Arsenic (As) bioavailability in spiked soils aged for up to 12 months was assessed using in vitro and in vivo methodologies. Ageing (natural attenuation) of spiked soils resulted in a decline in in vivo As bioavailability (swine assay) of over 75% in soil A (Red Ferrosol) but had no significant effect on in vivo As bioavailability even after 12 months of ageing in soil B (Brown Chromosol). Sequential fractionation, however, indicated that there was repartitioning of As within the soil fractions extracted during the time course investigated. In soil A, the As fraction associated with the more weakly bound soil fractions decreased while the residual fraction increased from 12% to 35%. In contrast, little repartitioning of As was observed in soil B indicating that natural attenuation may be only applicable for As in soils containing specific mineralogical properties.

The assessment of arsenic (As) bioavailability from contaminated matrices is a crucial parameter for reducing the uncertainty when estimating exposure for human health risk assessment. In vivo assessment of As utilising swine is considered an appropriate model for human health risk assessment applications as swine are remarkably similar to humans in terms of physiology and As metabolism. While limited in vivo As bioavailability data is available in the literature, few details have been provided regarding technical considerations for performing in vivo assays. This paper describes, with examples, surgical, experimental design and analytical issues associated with performing chronic and acute in vivo swine assays to determine As bioavailability in contaminated soil and food. Refereed/Peer-reviewed

An in vivo swine assay was utilised for the determination of arsenic (As) bioavailability in contaminated soils. Arsenic bioavailability was assessed using pharmacokinetic analysis encompassing area under the blood plasma-As concentration time curve following zero correction and dose normalisation. In contaminated soil studies, As uptake into systemic circulation was compared to an arsenate oral dose and expressed as relative As bioavailability. Arsenic bioavailability ranged from 6.9+/-5.0% to 74.7+/-11.2% in 12 contaminated soils collected from former railway corridors, dip sites, mine sites and naturally elevated gossan soils. Arsenic bioavailability was generally low in the gossan soils and highest in the railway soils, ranging from 12.1+/-8.5% to 16.4+/-9.1% and 11.2+/-4.7% to 74.7+/-11.2%, respectively. Comparison of in vivo and in vitro (Simplified Bioaccessibility Extraction Test [SBET]) data from the 12 contaminated soils and bioavailability data collected from an As spiked soil study demonstrated that As bioavailability and As bioaccessibility were linearly correlated (in vivo As bioavailability (mgkg(-1))=14.19+0.93.SBET As bioaccessibility (mgkg(-1)); r(2)=0.92). The correlation between the two methods indicates that As bioavailability (in vivo) may be estimated using the less expensive, rapid in vitro chemical extraction method (SBET) to predict As exposure in human health risk assessment.

Arsenic contamination of groundwater has been reported in many countries throughout the world, most notably in Southeast Asia. In recent years, much attention has focused on the As calamity in Bangladesh and West Bengal, India, following the highly publicized reports of vast populations being exposed to As-contaminated groundwater. Recently, Chakraborti et al. (2004) reported that As levels in groundwater from 50 districts in Bangladesh (representing ~ 2,000 villages) exceeded the Bangladesh drinking water guidelines for As of 50 μ with As concentrations in some cases > 1,500 μ(Tondel et al. 1999). The issue in Bangladesh has been described as “the largest poisoning of a population in history” (Smith et al. 2000), with an estimated 35–70 million inhabitants being at risk of drinking As-contaminated water (Khan et al. 1997). Chronic exposure to As causes significant human health effects including various cancers (skin, lungs, bladder, and kidneys), skin disorders (hyperkeratosis and pigment changes), vascular disease, and diabetes mellitus (Guha Mazumder et al. 1998; Guo et al. 1997; Lein et al. 2001; Mandal and Suzuki 2002; Rahman et al. 2001). The increased incidence of these health effects have been observed in Bangladesh and West Bengal populations exposed to As (Ahmed et al. 2006; Mukherjee et al. 2006). In addition to drinking water, consumption of As-contaminated food is another major source of As exposure. In Bangladesh, As-contaminated water is also used for irrigating crops, particularly rice (Oryza sativa L.), which represents approximately 83% of the total irrigated area in Bangladesh (Dey et al. 1996). As a consequence of irrigating with As-contaminated water, rice may contain elevated levels of As. Arsenic concentrations ranging from 160 to 580 μ have been reported in rice from the Jessore district in Bangladesh (Alam et al. 2002), whereas Meharg and Rahman (2003) reported As concentrations > 1,830 μg/kg in rice from other regions of Bangladesh. Because rice is a staple food in Bangladesh, providing > 70% of the daily calorific intake (Ninno and Dorosh 2001), consumption of contaminated rice may represent a significant As exposure pathway. In fact, Meharg (2004) estimated that consumption of As-contaminated rice may contribute as much as 60% of the daily Bangladeshi dietary As intake based on conservative As concentrations in rice. In addition, absorption of As-contaminated water during the rice cooking process may significantly increase the amount of As in cooked rice (Ackerman et al. 2005; Bae et al. 2002), which is often overlooked when calculating As daily intake values. A number of studies have reported the presence of As in rice, ranging in concentration from 32 to 1,830 μg As/kg (Abedin et al. 2002a, 2002b; Alam et al. 2002; D’Amato et al. 2004; Heitkemper et al. 2001; Kohlmeyer et al. 2003; Meharg 2004; Meharg and Rahman 2003; Schoof et al. 1998; Williams et al. 2005); however, few studies have determined the proportion of inorganic to organic As in rice. In terms of human health risk assessment, As speciation is important because the toxicity of organic, inorganic, trivalent, and pentavalent As species vary greatly (Petrick et al. 2000; Vahter and Concha 2001). In addition, there is a dearth of information on the bioavailability of As in rice after consumption. Bioavailability, in the context of human health risk assessment, refers to the fraction of an administered dose that reaches the central (blood) compartment from the gastrointestinal tract (Ruby et al. 1999). After consumption of As-contaminated rice, it is unclear what proportion of the rice-bound As is absorbed and whether As speciation influences absorption from the gastrointestinal tract. To reduce the uncertainties in estimating exposure and to provide a more accurate estimate of risk, assessment of As bioavailability is critical. In this study, we investigated the concentration and speciation of As in supermarket-bought rice, in rice grown under greenhouse conditions using As-contaminated irrigation water, and in rice cooked in As-contaminated water. In addition, we assessed the bioavailability of As in rice using an in vivo swine assay—an animal model used to predict As uptake for human health risk assessment. We assessed As bioavailability in two different rice preparations to determine whether the mode of As accumulation in the grain (translocation by the plant vs. absorption during cooking) influenced As uptake in the swine model.