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Expression of the src-family kinase lymphocyte-specific protein tyrosine kinase (Lck) at the plasma membrane is essential for it to fulfill its pivotal role in signal transduction in T lymphocytes. MAL, an integral membrane protein expressed in specific types of lymphoma, has been shown to play an important role in targeting Lck to the plasma membrane. Here we report that MAL interacts with Inverted Formin2 (INF2), a formin with the atypical property of promoting not only actin polymerization but also its depolymerization. In Jurkat T cells, INF2 colocalizes with MAL at the cell periphery and pericentriolar endosomes and along microtubules. Videomicroscopic analysis revealed that the MAL+ vesicles transporting Lck to the plasma membrane move along microtubule tracks. Knockdown of INF2 greatly reduced the formation of MAL+ transport vesicles and the levels of Lck at the plasma membrane and impaired formation of a normal immunologic synapse. The actin polymerization and depolymerization activities of INF2 were both required for efficient Lck targeting. Cdc42 and Rac1, which bind to INF2, regulate Lck transport in both Jurkat and primary human T cells. Thus, INF2 collaborates with MAL in the formation of specific carriers for targeting Lck to the plasma membrane in a process regulated by Cdc42 and Rac1., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

We created a petition for a national inquiry into the Australian system of research ethics and governance, to inform the politicians about the problems with the existing system. We analyzed the reasons that signatories offered for why signing the petition was important to them. A total of 409 comments (by 805 signatories) focused on five major themes: (1) views on previous changes to the system of research ethics and governance; (2) drawbacks of the existing system; (3) suggested changes to the system; (4) anticipated impacts of changing the system; and (5) miscellaneous/other comments. Comments ranged from several words to over 400 words in length, and most often focused on the procedural aspects, and commented on theme 2: drawbacks of the existing system.

The rising rate of preprints and publications, combined with persistent inadequate reporting practices and problems with study design and execution, have strained the traditional peer review system. Automated screening tools could potentially enhance peer review by helping authors, journal editors, and reviewers to identify beneficial practices and common problems in preprints or submitted manuscripts. Tools can screen many papers quickly, and may be particularly helpful in assessing compliance with journal policies and with straightforward items in reporting guidelines. However, existing tools cannot understand or interpret the paper in the context of the scientific literature. Tools cannot yet determine whether the methods used are suitable to answer the research question, or whether the data support the authors’ conclusions. Editors and peer reviewers are essential for assessing journal fit and the overall quality of a paper, including the experimental design, the soundness of the study’s conclusions, potential impact and innovation. Automated screening tools cannot replace peer review, but may aid authors, reviewers, and editors in improving scientific papers. Strategies for responsible use of automated tools in peer review may include setting performance criteria for tools, transparently reporting tool performance and use, and training users to interpret reports.

Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.

Zymogen secretory granules in pancreatic acinar cells express two vesicle-associated membrane proteins (VAMP), VAMP2 and -8, each controlling 50% of stimulated secretion. Analysis of secretion kinetics identified a first phase (0-2 min) mediated by VAMP2 and second (2-10 min) and third phases (10-30 min) mediated by VAMP8. Induction of acinar pancreatitis by supramaximal cholecystokinin (CCK-8) stimulation inhibits VAMP8-mediated mid- and late-phase but not VAMP2-mediated early-phase secretion. Elevation of cAMP during supramaximal CCK-8 mitigates third-phase secretory inhibition and acinar damage caused by the accumulation of prematurely activated trypsin. VAMP8-/- acini are resistant to secretory inhibition by supramaximal CCK-8, and despite a 4.5-fold increase in total cellular trypsinogen levels, are fully protected from intracellular trypsin accumulation and acinar damage. VAMP8-mediated secretion is dependent on expression of the early endosomal proteins Rab5, D52, and EEA1. Supramaximal CCK-8 (60 min) caused a 60% reduction in the expression of D52 followed by Rab5 and EEA1 in isolated acini and in in vivo The loss of D52 occurred as a consequence of its entry into autophagic vacuoles and was blocked by lysosomal cathepsin B and L inhibition. Accordingly, adenoviral overexpression of Rab5 or D52 enhanced secretion in response to supramaximal CCK-8 and prevented accumulation of activated trypsin. These data support that acute inhibition of VAMP8-mediated secretion during pancreatitis triggers intracellular trypsin accumulation and loss of the early endosomal compartment. Maintaining anterograde endosomal trafficking during pancreatitis maintains VAMP8-dependent secretion, thereby preventing accumulation of activated trypsin.

IntroductionPrevention is the most cost-effective approach to promote population health, yet little is known about the delivery of health promotion interventions in the nation's largest Medicaid program, Medi-Cal. The purpose of this study was to inventory health promotion interventions delivered through Medi-Cal Managed Care Plans; identify attributes of the interventions that plans judged to have the greatest impact on their members; and determine the extent to which the plans refer members to community assistance programs and sponsor health-promoting community activities.MethodsThe lead health educator from each managed care plan was asked to complete a 190-item online survey in January 2013; 20 of 21 managed care plans responded. Survey data on the health promotion interventions with the greatest impact were grouped according to intervention attributes and measures of effectiveness; quantitative data were analyzed using descriptive statistics.ResultsHealth promotion interventions judged to have the greatest impact on Medi-Cal members were delivered in various ways; educational materials, one-on-one education, and group classes were delivered most frequently. Behavior change, knowledge gain, and improved disease management were cited most often as measures of effectiveness. Across all interventions, median educational hours were limited (2.4 h), and median Medi-Cal member participation was low (265 members per intervention). Most interventions with greatest impact (120 of 137 [88%]) focused on tertiary prevention. There were mixed results in referring members to community assistance programs and investing in community activities.ConclusionManaged care plans have many opportunities to more effectively deliver health promotion interventions. Establishing measurable, evidence-based, consensus standards for such programs could facilitate improved delivery of these services.

Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. We used a MYC target gene signature that predicts poor neuroblastoma prognosis to identify the histone chaperone FACT (facilitates chromatin transcription) as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small-molecule curaxin compound CBL0137 markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma.

This work was supported by grants (BFU2006-01925, BFU2009-07886, and CONSOLIDER COAT CSD2009-00016) to M.A.A. from the Ministerio de Ciencia e Innovación (MICINN), Spain. R.M. is the holder of a contract from the Ramón y Cajal Program of the MICINN., Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation., Depto. de Genética, Fisiología y Microbiología, Fac. de Ciencias Biológicas, TRUE, pub

Expression of the src-family kinase lymphocyte-specific protein tyrosine kinase (Lck) at the plasma membrane is essential for it to fulfill its pivotal role in signal transduction in T lymphocytes. MAL, an integral membrane protein expressed in specific types of lymphoma, has been shown to play an important role in targeting Lck to the plasma membrane. Here we report that MAL interacts with Inverted Formin2 (INF2), a formin with the atypical property of promoting not only actin polymerization but also its depolymerization. In Jurkat T cells, INF2 colocalizes with MAL at the cell periphery and pericentriolar endosomes and along microtubules. Videomicroscopic analysis revealed that the MAL+ vesicles transporting Lck to the plasma membrane move along microtubule tracks. Knockdown of INF2 greatly reduced the formation of MAL+ transport vesicles and the levels of Lck at the plasma membrane and impaired formation of a normal immunologic synapse. The actin polymerization and depolymerization activities of INF2 were both required for efficient Lck targeting. Cdc42 and Rac1, which bind to INF2, regulate Lck transport in both Jurkat and primary human T cells. Thus, INF2 collaborates with MAL in the formation of specific carriers for targeting Lck to the plasma membrane in a process regulated by Cdc42 and Rac1.

Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation. © 2010 Elsevier Inc.

Background: The MAL2 gene, encoding a four-transmembrane protein of the MAL family, is amplified and overexpressed in breast and other cancers, yet the significance of this is unknown. MAL-like proteins have trafficking functions, but their molecular roles are largely obscure, partly due to a lack of known binding partners. Methods: Yeast two-hybrid screening of a breast carcinoma cDNA expression library was performed using a full-length MAL2 bait, and subsequent deletion mapping experiments were performed. MAL2 interactions were confirmed by co-immunoprecipitation analyses and confocal microscopy was employed to compare protein subcellular distributions. Sucrose density gradient centrifugation of membranes extracted in cold Triton X-100 was employed to compare protein distributions between Triton X-100-soluble and -insoluble fractions. Results: The tumor-associated protein mucin 1 (MUC1) was identified as a potential MAL2 partner, with MAL2/ MUC1 interactions being confirmed in myc-tagged MAL2-expressing MCF-10A cells using coimmunoprecipitation assays. Deletion mapping experiments demonstrated a requirement for the first MAL2 transmembrane domain for MUC1 binding, whereas the MAL2 N-terminal domain was required to bind D52-like proteins. Confocal microscopy identified cytoplasmic co-localisation of MUC1 and MAL2 in breast cell lines, and centrifugation of cell lysates to equilibrium in sucrose density gradients demonstrated that MAL2 and MUC1 proteins were co-distributed between Triton X-100-soluble and -insoluble fractions. However coimmunoprecipitation analyses detected MAL2/MUC1 interactions in Triton X-100-soluble fractions only. Myc- MAL2 expression in MCF-10A cells was associated with both increased MUC1 detection within Triton X-100- soluble and -insoluble fractions, and increased MUC1 detection at the cell surface. Conclusion: These results identify MUC1 as a novel MAL2 partner, and suggest a role for MAL2 in regulating MUC1 expression and/or localisation.

Lynne Parkinson1,2, Pauline Chiarelli3, Jennifer Byrne1, Richard Gibson1, Suzanne McNeill4, Gillian Lloyd5, Wendy Watts6, Julie Byles11Research Centre for Gender, Health and Ageing, Faculty of Health, The University of Newcastle, NSW, Australia; 2Hunter Ageing Research, Faculty of Health, The University of Newcastle, NSW, Australia; 3Faculty of Health, The University of Newcastle, NSW, Australia; 4NC Trauma Orthopedics, John Hunter Hospital, New Lambton Heights, NSW, Australia; 5Hunter New England Health, Wallsend Community Health Centre, Wallsend, NSW, Australia; 6Royal Newcastle Centre, John Hunter Hospital, New Lambton Heights, NSW, AustraliaAbstract: Evidence suggests that bladder control problems develop or worsen as a result of fractured neck of femur (#NOF) and its subsequent management. The primary aim of this study was to reduce the prevalence and severity of post surgery continence problems among patients, aged from 60-years, undergoing surgery for #NOF, using a best practice “case-management model” multifactorial intervention. Eligible consenting patients admitted with #NOF were randomized to intervention or control group. Self-report questionnaires compared pre-surgery, post surgery, and follow-up continence status between groups.This pilot randomized controlled trial, which included 45 eligible patients aged 60 to 93-years, found no evidence that the intervention was effective in reducing prevalence of post-surgery incontinence in this acute setting. Staff surveys highlighted the need for open communication between the research team and hospital staff. Unclear results were attributed to the small sample size.A central outcome was evidence that intervention to improve continence management for older people post-surgery is imperative. Focused assessment and treatment for those most at risk of incontinence after #NOF would be more acceptable to staff and a more efficient use of resources. A simple screening tool would ensure that those

This research explored children’s ideas about micro-organisms across three age groups and employed a survey methodology using multiple methods. The research focussed on exploring children’s ideas across specific conceptual themes pertinent to understanding about micro-organisms. Data were analysed qualitatively and quantitatively and a hierarchy of mental models for each conceptual theme, typical of children’s ideas across all the age groups, was developed as a result of data analysis. What this research has established is that the prevalence of the different models for each conceptual theme alters between different age groups. A typology of these models for each age group has been developed and this has shown how children’s ideas change with age, what levels of progression occur and in which particular conceptual themes progression is greatest. Two important themes emerged from the data; these were anthropocentric ideas and an associated notion that micro-organisms are essentially malevolent. These themes were evident in children’s ideas across all age groups and throughout the conceptual catalogue being investigated. A negative view of micro-organisms dominates many children’s thinking in such diverse concepts such as classification, living, disease and decay. Implications for learning and teaching microbiology at school, for the age groups studied, are discussed and implications for curriculum development are considered.

In the 1990's, the U.S. saw one of the largest periods of migration to its shores in its history. This surge of immigrants can be classified predominantly as Latino or Asian, which will inevitably result in demographic changes within the country. The largest proportion of immigrants claim Mexico as their country of origin, and according to the U.S. Census Bureau, Hispanics now represent the country's largest minority population. Given these facts, it is important to examine a body of literature that warns of the "balkanization" of America and suggests an inability of this new wave of immigrants to assimilate into American society. Previous research on attitudes towards immigrants has found both cultural and economic indicators to be important determinants of public opinion on this issue. I will expand this research by examining how the public perception of the ability of immigrants to assume an "American" identity and assimilate into society will affect attitudes towards immigrants. My primary research questions are: 1) How do different conceptions of national identity affect attitudes towards immigrants? 2) How do perceptions of the ability of immigrant groups to integrate into American society affect restrictionist views on immigration policy? 3) What group and individual-level characteristics determine differing levels of support for the dimensions of American national identity? My findings suggest that the weight attributed to three distinct dimensions of national identity conditions attitudes towards immigrants and their incorporation into American society.

The immediate effect of changing the driving cutaneous input to locations within primary somatosensory cortex (SI) was examined by denervating one or more digits of the rat hindpaw by amputation or local anesthesia. When all or part of a receptive field of a cluster of neurons was denervated, it was found that the cortical location recorded from gained responsiveness to cutaneous stimulation of hindpaw areas bordering the denervated region. In 22 of the 29 animals studied this expansion took place within 5 min of the denervation.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

This report reviews the joint British Society for Proteome Research (BSPR) and European Bioinformatics Institute (EBI) 2007 meeting, ‘Integrative Proteomics: From Molecules to Systems’ which took place at the Wellcome Trust Conference Centre, Hinxton, UK, from 25th to 27th July. The aim of this year's meeting was to explore how the integration of ‘omic’ technologies can lead to a comprehensive understanding of cellular organization, differentiation and signalling. Studies investigating protein–protein interactions and trafficking illustrated how the combination of proteomics and bioinformatics is allowing systems biology to develop as a discipline in its own right.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). Conclusion: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.