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Objectives: To implement and evaluate a rehabilitation-inclusive service delivery model at a tertiary cancer hospital. Methods: The “Rehab-Toolkit”, a structured assessment tool comprising validated functional measures, was introduced in an inpatient cancer service. Consecutive inpatients were enrolled, and a Reach, Effectiveness, Adoption, Implementation, and Maintenance framework guided the analysis of barriers and facilitators for subacute care at clinic and system levels. Results: The implementation of the Rehab-Toolkit was incorporated into routine inpatient care. Major pre-implementation barriers included: absence of routine standardized functional assessment tools, limited coordination amongst acute and subacute care providers, low awareness of rehabilitation medicine amongst patients and professionals, and insufficient engagement of subacute care with interdisciplinary stakeholders in clinical decision-making. Following the intervention, there was a notable increase in awareness and the contributory role of subacute rehabilitation services, rehabilitation “needs” assessment, and referral pathways. Recommendations for process change included: development of clinical pathways, establishment of subacute referral systems and discharge coordinator roles, inclusion of subacute rehabilitation services in acute interdisciplinary team meetings, enhanced staff education and knowledge. Conclusion: Integration of rehabilitation services into cancer care can proactively manage functional morbidity. While the implementation process proved feasible and effective, robust process evalu-ation and longer term follow-up are necessary for sustained success.

BackgroundIn response to the widespread transmission of COVID-19 in Australia, healthcare facilities implemented stringent infection control measures, and mandatory and manual screening procedures were introduced to ensure the safety of patients and healthcare staff. However, these necessary measures resulted in imbalances within the healthcare system, a shortage of front-line workers and impacts on patient experience and wait times. The prioritization of infection control measures shifted resources away from routine care, causing delays in accessing necessary healthcare services.Methods and FindingsTo address these challenges, we developed and implemented an Internet of Things (IoT) Smart Screening eGate solution in partnership with a large metropolitan children’s hospital in Australia. This solution integrated a contactless health self-service web app, thermal camera, and physical barrier to automate the COVID-19 health screening and data recording process. During the 3-month pilot period, we deployed the eGate at multiple entrances to the hospital, and monitored the number of users of the system in different periods. We also used a framework of formative evaluation to classify user design challenges within limited resources and improved the design of the eGate to enhance its effectiveness. Our findings show that the IoT eGate solution improved the efficiency of the screening process and reduced the workload and exposure risks of front-line staff and anyone who required access to the hospital. By automating the screening process, we reduced the need for manual screening and minimized contact between individuals, thus reducing the risk of potentially infected.ConclusionIn conclusion, our pilot study demonstrated the potential of IoT technologies in improving the efficiency and safety of medical facilities during pandemics and provided a series of recommendations for the translation of IoT technologies for medical facilities, including the importance of co-design and collaboration with stakeholders, user-centered design, and ongoing monitoring and evaluation.

Introduction Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely.Methods and analysis This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint.Ethics and dissemination This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145).

Introduction Cancer-related cognitive impairment is common among people diagnosed with and treated for cancer. This can be a distressing and disabling side effect for impacted individuals. Interventions to mitigate cognitive dysfunction are available, but, to date, most have been trialled in samples that are largely or exclusively composed of people with solid tumours. Intervention strategies to support cognitive functioning are needed, but there is a paucity of research in this area. The main aim of this study is to test the feasibility and acceptability of methods and procedures intended for use in a definitive trial of a web-based cognitive rehabilitation programme, Responding to Cognitive Concerns (eReCog), in people who have received chemotherapy for aggressive lymphoma.Methods and analysis The proposed study is a single-site, parallel-group, pilot randomised controlled trial, with one baseline and one follow-up (or postintervention) assessment. 38 people from the target population with low perceived cognitive function based on the Cognitive Change Screen will be recruited from a specialist cancer centre between July 2023 and June 2024. After baseline assessment, participants will be randomised one-to-one to receive usual care only (a factsheet about changes in memory and thinking for people with cancer) or eReCog plus usual care. The 4-week eReCog intervention consists of four online modules offering psychoeducation on cognitive impairment associated with cancer and its treatment, skills training for improving memory, and attention and relaxation training. Study outcomes will include the feasibility of recruitment and retention at follow-up assessment (primary outcomes), as well as adherence to, usability of and intrinsic motivation to engage with eReCog, and compliance with study measures. The potential efficacy of eReCog will also be evaluated.Ethics and dissemination Ethical approval was granted by the Peter MacCallum Cancer Centre Human Research Ethics Committee in Victoria, Australia (HREC/97384/PMCC). Study findings will be disseminated via peer-reviewed publications and conference presentations.Trial registration number Australian New Zealand Clinical Trials Registry, ACTRN12623000705684.

Abstract Eltrombopag has been previously shown to be effective in reversing azacitidine‐mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate‐ to high‐risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort were associated with treatment outcomes. Based on the available data, we observed no imbalance in the mutational profiles between treatment arms or a clear association between identified somatic mutations and clinical outcomes.

Follicular Lymphoma (FL) treatment initiation is largely determined by tumor burden and symptoms. In the pre-rituximab era, the Group d’Etude des Lymphomes Folliculaires (GELF) developed widely adopted criteria to identify high tumor burden FL patients to harmonize clinical trial populations. The utilization of GELF criteria (GELFc) in routine therapeutic decision-making is poorly described. This multicenter retrospective study evaluated patterns of GELFc at presentation and GELFc utilization in therapeutic decision-making in newly diagnosed, advanced stage rituximab-era FL. Associations between GELFc, treatment given, and patient survival were analyzed in 300 eligible cases identified between 2002-2019. 163 (54%) had ≥1 GELFc at diagnosis. The presence or cumulative number of GELFc did not predict PFS in patients undergoing watch-and-wait (WW) or those receiving systemic treatment. Of interest, in patients with ≥1 GELFc, 16/163 (10%) underwent initial watch-and-wait (comprising 22% of the watchand- wait cohort). In those receiving systemic therapy +/- radiotherapy, 74/215 (34%) met no GELFc. Our data suggest clinicians are using adjunctive measures to make decisions regarding treatment initiation in a significant proportion of patients. By restricting FL clinical trial eligibility only to those meeting GELFc, reported outcomes may not be applicable to a significant proportion of patients treated in routine care settings.

Abstract Electronic medication management (eMM) systems are designed to improve safety, but there is little evidence of their effectiveness in paediatrics. This study assesses the short-term (first 70 days of eMM use) and long-term (one-year) effectiveness of an eMM system to reduce prescribing errors, and their potential and actual harm. We use a stepped-wedge cluster randomised controlled trial (SWCRCT) at a paediatric referral hospital, with eight clusters randomised for eMM implementation. We assess long-term effects from an additional random sample of medication orders one-year post-eMM. In the SWCRCT, errors that are potential adverse drug events (ADEs) are assessed for actual harm. The study comprises 35,260 medication orders for 4821 patients. Results show no significant change in overall prescribing error rates in the first 70 days of eMM use (incident rate ratio [IRR] 1.05 [95%CI 0.92–1.21], but a 62% increase (IRR 1.62 [95%CI 1.28–2.04]) in potential ADEs suggesting immediate risks to safety. One-year post-eMM, errors decline by 36% (IRR 0.64 [95%CI 0.56–0.72]) and high-risk medication errors decrease by 33% (IRR 0.67 [95%CI 0.51–0.88]) compared to pre-eMM. In all periods, dose error rates are more than double that of other error types. Few errors are associated with actual harm, but 71% [95%CI 50–86%] of patients with harm experienced a dose error. In the short-term, eMM implementation shows no improvement in error rates, and an increase in some errors. A year after eMM error rates significantly decline suggesting long-term benefits. eMM optimisation should focus on reducing dose errors due to their high frequency and capacity to cause harm.

IntroductionPulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Until now, no prospective biomarker to predict new onset of SSc-ILD or SSc-PAH in patients with SSc has reached clinical application. In homeostasis, the receptor for advanced glycation end products (RAGE) is expressed in lung tissue and involved in cell-matrix adhesion, proliferation and migration of alveolar epithelial cells, and remodeling of the pulmonary vasculature. Several studies have shown that sRAGE levels in serum and pulmonary tissue vary according to the type of lung-related complication. Therefore, we investigated levels of soluble RAGE (sRAGE) and its ligand high mobility group box 1 (HMGB1) in SSc and their abilities to predict SSc-related pulmonary complications.MethodsOne hundred eighty-eight SSc patients were followed retrospectively for the development of ILD, PAH, and mortality for 8 years. Levels of sRAGE and HMGB1 were measured in serum by ELISA. Kaplan-Meier survival curves were performed to predict lung events and mortality and event rates were compared with a log-rank test. Multiple linear regression analysis was performed to examine the association between sRAGE and important clinical determinants.ResultsAt baseline, levels of sRAGE were significantly higher in SSc-PAH-patients (median 4099.0 pg/ml [936.3-6365.3], p = 0.011) and lower in SSc-ILD-patients (735.0 pg/ml [IQR 525.5-1988.5], p = 0.001) compared to SSc patients without pulmonary involvement (1444.5 pg/ml [966.8-2276.0]). Levels of HMGB1 were not different between groups. After adjusting for age, gender, ILD, chronic obstructive pulmonary disease, anti-centromere antibodies, the presence of puffy fingers or sclerodactyly, use of immunosuppression, antifibrotic therapy, or glucocorticoids, and use of vasodilators, higher sRAGE levels remained independently associated with PAH. After a median follow-up of 50 months (25-81) of patients without pulmonary involvement, baseline sRAGE levels in the highest quartile were predictive of development of PAH (log-rank p = 0.01) and of PAH-related mortality (p = 0.001).ConclusionsHigh systemic sRAGE at baseline might be used as a prospective biomarker for patients with SSc at high risk to develop new onset of PAH. Moreover, high sRAGE levels could predict lower survival rates due to PAH in patients with SSc.

Objective: To assess the long-term functional, psychosocial and participation outcomes in an Australian cohort of non-Hodgkin lymphoma (NHL) survivors. Methods: A cross-sectional sample of adult NHL survivors at the Peter MacCallum Cancer Centre (between 2015 and 2020), participated by completing validated questionnaires. A series of analyses described their current level of function, psychosocial well-being, and participation. Results: Of 129 participants (mean (M) ± standard deviation (SD) age: 62.5 ± 8.8 years), the majority (58%) had aggressive NHL and grade III–IV (72%), with time since diagnosis of 4.6 ± 1.2 years. Participants reported ongoing issues after completion of treatment: fatigue (63%), bladder dysfunction (61%), cognitive impairment (53%), and NHL-related pain (46%). Most made good functional recovery (M ± SD) (Functional Independent Measure-Motor: 79.5 ± 8.2), reported minimal change in their negative emotional states, and NHL-specific quality of life (QoL) (Functional Assessment of Cancer Therapy–Lymphoma: 133.5 ± 22.1). Participants were “well” adjusted to community living (Community Integration Measure: 42.2 ± 7.4) and satisfied with their current life (Satisfaction with Life Scale: 26.3 ± 6.0). Factors significantly associated with the poorer current level of function were: age at diagnosis < 60 years, time since NHL diagnosis > 4.5 years, and aggressive NHL type. Conclusion: Despite good functional recovery and adjustment in the community, NHL survivors report the presence of ongoing residual impairments and cognitive issues, which requires long-term rehabilitation-inclusive management. LAY ABSTRACT This cross-sectional study evaluated functional and psychosocial outcomes in non-Hodgkin lymphoma (NHL) survivors. Most patients made a good functional recovery and reported minimal change in their negative emotional states and quality of life after they were discharged. Patients reported satisfaction with their current life and were “well” adjusted to community living after NHL treatment. However, many reported ongoing issues, specifically fatigue, bladder dysfunction, cognitive impairment, and NHL-related pain. Those below 60 years of age when diagnosed, with time since NHL of over 4.5 years, and with aggressive and advanced NHL grades were associated with a poorer current level of function. These findings suggest that, despite patients’ potential adjustment to disability over time (response-shift phenomenon), many patients with NHL need long-term rehabilitation-inclusive management of ongoing disability and psychosocial issues in the community post-discharge.

Sports are important activities for youth, with millions of children and adolescents participating in organized sports and recreational activities every year. Sports participation has many benefits but can also cause injuries, accounting for two-thirds of all injuries in Canadian adolescents and resulting in hundreds of thousands of medical visits annually. Despite the frequency of sports-related injuries in youth, many practising pediatricians are not comfortable managing these issues, citing a lack of teaching and clinical exposure during training. Many studies have found deficits in musculoskeletal (MSK) and sport and exercise medicine (SEM) training in residency programs in North America, including Canadian pediatric residency programs. To address this learning gap, Canadian pediatric residency programs should incorporate more MSK/SEM training and clinical exposure to these issues. A standardized national curriculum in MSK/SEM will help ensure that community pediatricians practicing in Canada are adequately prepared to care for active youth.

Ventricular septal rupture (VSR) following myocardial infarction is rare in the reperfusion era. The decrease in patients presenting with myocardial infarction during the coronavirus-2019 (COVID-19) pandemic could result in more frequent VSR. This report describes two patients with VSR presenting late after myocardial infarction and treated at a single institution. (Level of Difficulty: Beginner.)

Objective: To evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation interventions in patients with lymphoma. Data sources: A comprehensive literature search was conducted using medical/health science databases up to 1 October 2020. Bibliographies of pertinent articles, journals and grey literature were searched. Data extraction and synthesis: Two reviewers independently selected and reviewed potential reviews for methodological quality and graded the quality of evidence for outcomes using validated tools. Any discrepancies were resolved by final group consensus. Results: Twelve systematic reviews (n = 101 studies, 87,132 patients with lymphoma) evaluated 3 broad categories of rehabilitation interventions (physical modalities, nutrition and complementary medicine). Most reviews were of moderate-to-low methodological quality. The findings suggest: moderate-quality evidence for exercise programmes for improved fatigue and sleep disturbance; low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and an inverse association between sunlight/ultraviolet radiation exposure and incidence of non-Hodgkin’s lymphoma; and very low-quality evidence for beneficial effects of yoga for sleep disturbances. Association between physical activity and lymphoma risk is indistinct. Conclusion: Despite a range of rehabilitation modalities used for patients with lymphoma, high-quality evidence for many is sparse. Beneficial effects of exercise programmes were noted for fatigue, psychological symptoms and quality of life. More research with robust study design is required to determine the effective rehabilitation approaches.

Sydney Children’s Hospitals Network (SCHN) is the largest network of hospitals and services for children in Australia. It is a public service of NSW (New South Wales) Health, part of the NSW Government. The NSW geographic area serviced is 800,628 square km, with a population of 7,861,100 people, but children come from across Australia for the expert care SCHN provides. SCHN cares for 151,000 children every year, with over 50,000 inpatient admissions and over 1.1m outpatient encounters. More than 65% of these presentations consist of patients who have an established relationship with SCHN due to the complex/chronic nature of their diagnosis(s). SCHN wanted to connect with their outpatients, to inform/support changing care needs, to improve patients’ understanding of their conditions and to connect information across providers. All patients have providers locally outside the network, so SCHN wanted to support the patient as the conduit of their information, ultimately improving the care experience and health outcomes. SCHN had a vision of giving patients a digital record they could interact with meaningfully, centered around them. This digital vision would address several care delivery challenges: inefficient communication missed appointments managing changing conditions and medications lack of a shared record The digital vision became a co-design project with SCHN’s consumers, named the “Memory” project. The vision became reality in May 2017 with the successful trial of the “My Health Memory” (MHM) smartphone application. The first iteration of MHM allowed patients and carers to: Efficiently manage appointments and minimise care delays: receive new and updated appointments (including telehealth links straight to device) automatically from the EHR to their app request reschedules from their app receive appointment reminders, ensuring they come to appointments, are ready for care, and can find their way with digital wayfinding instructions staff can asynchronously review and reschedule requests via a request list and rebook Exchange clinical data to support care: access discharge summaries, care plans and reconciled medication lists from their app. push education to the app Communicate securely: clinical staff can securely message patients/carers from their workflow, and patients/carers can respond from their app. communications are automatically saved as a progress note in the EHR, eliminating manual documentation trial group implementation was a success resulting in a hospital wide implementation March 2018. Metrics achieved include: 80% of eligible patients registered (from trial group) Outpatient clinic No Show rates decreased by 74%. 8,748 messages sent between MHM and the EHR resulting in 30% fewer outpatient calls to nursing staff Reduction in secondary sources of truth for patient communication, reducing iatrogenic risk. 94.9% of app users have rated MHM as being useful in the care of their child. over 7,000 EHR documents shared to the app Over 6,000 activated users (October 2018) The 6 month MHM app roadmap includes; patient/carer uploaded documents and document sharing. Surveys with EHR integration & integration to Australia’s My Health Record. Sydney University have commenced a study On the MHM app titled Leveraging e-Applications for Patients (and families)

Waste biomass from the palm oil industry is currently burned as a means of disposal and solutions are required to reduce the environmental impact. Whilst some waste biomass can be recycled to provide green energy such as biogas, this investigation aimed to optimise experimental conditions for recycling palm waste into substrate for insects, farmed as a sustainable high-protein animal feed. NMR spectroscopy and LC-HRMS were used to analyse the composition of palm empty fruit bunches (EFB) under experimental conditions optimised to produce nutritious substrate rather than biogas. Statistical pattern recognition techniques were used to investigate differences in composition for various combinations of pre-processing and anaerobic digestion (AD) methods. Pre-processing methods included steaming, pressure cooking, composting, microwaving, and breaking down the EFB using ionic liquids. AD conditions which were modified in combination with pre-processing methods were ratios of EFB:digestate and pH. Results show that the selection of pre-processing method affects the breakdown of the palm waste and subsequently the substrate composition and biogas production. Although large-scale insect feeding trials will be required to determine nutritional content, we found that conditions can be optimised to recycle palm waste for the production of substrate for insect rearing. Pre-processing EFB using ionic liquid before AD at pH6 with a 2:1 digestate:EFB ratio were found to be the best combination of experimental conditions.

Nuclear magnetic resonance (NMR) spectroscopy profiling was used to provide an unbiased assessment of changes to the metabolite composition of seeds and to define genetic variation for a range of pea seed metabolites. Mature seeds from recombinant inbred lines, derived from three mapping populations for which there is substantial genetic marker linkage information, were grown in two environments/years and analyzed by non-targeted NMR. Adaptive binning of the NMR metabolite data, followed by analysis of quantitative variation among lines for individual bins, identified the main genomic regions determining this metabolic variability and the variability for selected compounds was investigated. Analysis by t-tests identified a set of bins with highly significant associations to genetic map regions, based on probability (p) values that were appreciably lower than those determined for randomized data. The correlation between bins showing high mean absolute deviation and those showing low p-values for marker association provided an indication of the extent to which the genetics of bin variation might be explained by one or a few loci. Variation in compounds related to aromatic amino acids, branched-chain amino acids, sucrose-derived metabolites, secondary metabolites and some unidentified compounds was associated with one or more genetic loci. The combined analysis shows that there are multiple loci throughout the genome that together impact on the abundance of many compounds through a network of interactions, where individual loci may affect more than one compound and vice versa. This work therefore provides a framework for the genetic analysis of the seed metabolome, and the use of genetic marker data in the breeding and selection of seeds for specific seed quality traits and compounds that have high commercial value.

Natural decision-making often involves extended decision sequences in response to variable stimuli with complex structure. As an example, many animals follow odor plumes to locate food sources or mates, but turbulence breaks up the advected odor signal into intermittent filaments and puffs. This scenario provides an opportunity to ask how animals use sparse, instantaneous, and stochastic signal encounters to generate goal-oriented behavioral sequences. Here we examined the trajectories of flying fruit flies (Drosophila melanogaster) and mosquitoes (Aedes aegypti) navigating in controlled plumes of attractive odorants. While it is known that mean odor-triggered flight responses are dominated by upwind turns, individual responses are highly variable. We asked whether deviations from mean responses depended on specific features of odor encounters, and found that odor-triggered turns were slightly but significantly modulated by two features of odor encounters. First, encounters with higher concentrations triggered stronger upwind turns. Second, encounters occurring later in a sequence triggered weaker upwind turns. To contextualize the latter history dependence theoretically, we examined trajectories simulated from three normative tracking strategies. We found that neither a purely reactive strategy nor a strategy in which the tracker learned the plume centerline over time captured the observed history dependence. In contrast, "infotaxis", in which flight decisions maximized expected information gain about source location, exhibited a history dependence aligned in sign with the data, though much larger in magnitude. These findings suggest that while true plume tracking is dominated by a reactive odor response it might also involve a history-dependent modulation of responses consistent with the accumulation of information about a source over multi-encounter timescales. This suggests that short-term memory processes modulating decision sequences may play a role in natural plume tracking.

MOTIVATION:Modern analytical techniques such as LC-MS, GC-MS and NMR are increasingly being used to study the underlying dynamics of biological systems by tracking changes in metabolite levels over time. Such techniques are capable of providing information on large numbers of metabolites simultaneously, a feature that is exploited in non-targeted studies. However, since the dynamics of specific metabolites are unlikely to be known a priori this presents an initial subjective challenge as to where the focus of the investigation should be. Whilst a number of feed-forward software tools are available for manipulation of metabolomic data, no tool centralizes on clustering and focus is typically directed by a workflow that is chosen in advance. RESULTS:We present an interactive approach to time-course analyses and a complementary implementation in a software package, MetaboClust. This is presented through the analysis of two LC-MS time-course case studies on plants (Medicago truncatula and Alopecurus myosuroides). We demonstrate a dynamic, user-centric workflow to clustering with intrinsic visual feedback at all stages of analysis. The software is used to apply data correction, generate the time-profiles, perform exploratory statistical analysis and assign tentative metabolite identifications. Clustering is used to group metabolites in an unbiased manner, allowing pathway analysis to score metabolic pathways, based on their overlap with clusters showing interesting trends.

The drought–stress response in plant involves the cross-talk between abscisic acid (ABA) and other phytohormones, such as jasmonates and ethylene. The auxin indole-3-acetic acid (IAA) plays an integral part in plant adaptation to drought stress. Investigation was made to see how the main auxin IAA interacted with other plant hormones under water stress, applied through two different growth conditions (solid and hydroponic). Medicago sativa plants nodulated by the Ensifer meliloti wild type 1021 (Ms-1021) and its IAA-overproducing RD64 derivative strains (Ms-RD64) were subjected to drought stress, comparing their response. When the expression of nifH gene and the activity of the nitrogenase enzyme were measured after stress treatments, Ms-RD64 plants recorded a significantly weaker damage. These results were correlated with a lower biomass reduction, and a higher Rubisco protein level measured for the Ms-RD64-stressed plants as compared to the Ms-1021-stressed ones. It has been verified that the stress response observed for Ms-RD64-stressed plants was related to the production of greater amount of low-molecular-weight osmolytes, such as proline and pinitol, measured in these plants. For the Ms-RD64 plants the immunoblotting analysis of thylakoid membrane proteins showed that some of the photosystem proteins increased after the stress. An increased non-photochemical quenching after the stress was also observed for these plants. The reduced wilting signs observed for these plants were also connected to the significant down-regulation of the MtAA03 gene involved in the ABA biosynthesis, and with the unchanged expression of the two genes (Mt-2g006330 and Mt-8g095330) of ABA signaling. When the expression level of the ethylene-signaling genes was evaluated by qPCR analysis no significant alteration of the key positive regulators was recorded for Ms-RD64-stressed plants. Coherently, these plants accumulated 40% less ethylene as compared to Ms-1021-stressed ones. The results presented herein indicate that the variations in endogenous IAA levels, triggered by the overproduction of rhizobial IAA inside root nodules, positively affected drought stress response in nodulated alfalfa plants.

Plants suffer multiple, simultaneous assaults from above and below ground. In the laboratory, pests and/or pathogen attack are commonly studied on an individual basis. The molecular response of the plant to attack from multiple organisms and the interaction of different defense pathways is unclear. The inducible systemic responses of the potato (Solanum tuberosum L.) host plant were analyzed to characterize the plant-mediated indirect interactions between a sedentary, endoparasitic nematode (Globodera pallida), and a phloem-sucking herbivore (Myzus persicae). The reproductive success of M. persicae was greater on potato plants pre-infected with G. pallida compared to control plants. Salicylic acid (SA) increased systemically in the leaves of potato plants following nematode and aphid infection singly with a corresponding increase in expression of SA-mediated marker genes. An increase in jasmonic acid associated with aphid infection was suppressed when plants were co-infected with nematodes. Our data suggests a positive, asymmetric interaction between a sedentary endoparasitic nematode and a sap-sucking insect. The systemic response of the potato plant following infection with G. pallida indirectly influences the performance of M. persicae. This work reveals additional secondary benefits of controlling individual crop pests.

Histone deacetylase inhibitors (HDACi) can induce hyperacetylation of both histone and non-histone target resulting in epigenetic reprogramming and altered activity, stability and localisation of non-histone proteins to ultimately mediate diverse biological effects on cancer cells and their microenvironment. Clinical trials have demonstrated single agent HDACi to have activity in hematological malignancies, in particular T-cell lymphoma and Hodgkin lymphoma. Combination strategies with standard therapies based on pre-clinical data are being employed with significant success due to their excellent side effect profile. Correlative studies will provide valuable information on the sub-groups of patients more likely to respond or be resistant to HDACi therapy, while long-term monitoring for toxicities is also needed.

Purpose - The aim of this paper is to investigate how a client's cooperative procurement procedures influence subcontractor involvement, value creation, and innovation in the construction of complex facilities. Design/methodology/approach - Empirical data were collected through interviews, surveys and participation in workshops during a longitudinal action research case study. The case project was located in Sweden and concerned the construction of plant facilities for manufacturing of pharmaceutical products. Findings - The case study findings reveal that the client's procurement procedures affect the level of subcontractor involvement and integration, but that this does not necessarily result in increased subcontractor value creation and innovation in the construction process. Research limitations/implications - Since the empirical results are based on data collected from only one case project, the possibilities for generalisations are limited. Practical implications - Clients' procurement procedures heavily affect subcontractor involvement, but in order to increase subcontractor contributions to innovation and value creation the actors should adopt a long-term perspective and actively work to establish an innovation-friendly climate. Originality/value - This paper focuses on the often-neglected importance of subcontractors and their contributions to innovation and value creation. [ABSTRACT FROM AUTHOR]