Salt effect on physiological, biochemical and anatomical structures of two Origanum majorana varieties (Tunisian and Canadian)

In this study, we evaluated the salt concentration effect on plant growth, mineral composition, antioxidant responses and anatomical structure of two varieties of Origanum majorana after exposure to NaCl treatment. Our results show an inclusive behaviour of the two varieties, since the majority of sodium was exported and accumulated in their aerial parts. The Canadian variety (CV) appeared relatively more tolerant to salt than the Tunisian one (TV). Transversal section of leaves showed a thickening of dorsal and ventral cuticle, more importantly in CV than in TV, in the presence and in absence of salt. This was accompanied by an increase in the length of palisade cells, and the width of spongy collenchyma lacuna. The stem had a subquadrangular shape in TV and quadrangular in the Canadian variety. At mature stage, the stem pit was reabsorbed in the TV and replaced by a large cavity, whereas it remained unchanged in CV. The relative salt tolerance of the CV was related to: (1) a good selectivity in favour of K+: (2) a strong peroxidase activity and (3) an increase in the lengthening of palisade cell accompanied with an increase of lacunae in spongy parenchyma in CV.Key words: Origanum majorana, salinity, growth, mineral nutrition, leaves, stems, anatomical, antioxidant

Strategic partner evaluation criteria for logistics service provider networks

Purpose: The purpose of this paper is to establish criteria for evaluating strategic partners in a network of logistics service providers (LSPs) to show how analytical network process (ANP) can be used to identify the weights of these criteria on a case-specific basis, and to investigate whether the ANP model can be used as a starting point to evaluate strategic partners for other LSP networks. Design/methodology/approach: Based on a literature review of vertical cooperation, the authors develop an overview of criteria for the evaluation of partners in a network of LSPs. The authors then apply ANP at LSP1 to validate the criteria, identify weights for these criteria and to validate model outcomes. Furthermore, the authors investigate whether the ANP model developed for LSP1 can be applied to another LSP with similar characteristics (LSP2). In-depth interviews are used to draw conclusions on the modeling approach and the model outcomes. Findings: The research shows that evaluation criteria for partners in vertical partnerships between shippers and LSPs are applicable to LSP partners in horizontal partnership networks. The ANP model with criteria weights provides a good starting point for LSPs to customize the evaluation framework according to their specific needs or operating environments. Originality/value: Limited research is available on evaluating LSP partners in horizontal partnerships. To the best of the authors’ knowledge, this paper is the first to bring forward horizontal LSP partner evaluation criteria to develop an ANP model for LSP partner evaluation and to apply this to two cases, and to provide a starting point for evaluating partners in similar horizontal LSP networks

The potentially morally injurious nature of encountering children during military deployments: A call for research

Armed forces personnel are a population at risk for exposure to potentially traumatic and morally injurious events because of the high-risk nature of military operations. One potentially morally injurious event (PMIE) could be when military personnel encounter children during deployment. These encounters may lead to acute and chronic psychological, behavioural, and social consequences, culminating in moral injury and other adverse mental health problems. According to anecdotal evidence, military personnel reported feeling torn, morally and ethically, in their decisionmaking when they encounter children in the line of duty. The decision to engage or kill a child may be difficult to reconcile with one’s moral and ethical code, and decisions may have deadly consequences for oneself and others. To date, however, no reliable data exist as to the impact that encountering children during deployment may have on psychosocial and spiritual well-being. In this article, additional research into this domain is encouraged by providing a rationale for studying encounters with children during deployment through the lens of a PMIE, as well as r

RNAi dynamics in juvenile Fasciola spp. liver flukes reveals the persistence of gene silencing in vitro

Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a σ-class glutathione transferase (FheσGST).Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200-320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively.In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to infection

In silico characterisation of the complete Ly6 protein family in Fasciola gigantica supported through transcriptomics of the newly-excysted juveniles

Fasciola gigantica is one of the aetiological trematodes associated with fascioliasis, which heavily impacts food-production systems and human and animal welfare on a global scale. In the absence of a vaccine, fascioliasis control and treatment is restricted to pasture management, such as clean grazing, and a limited array of chemotherapies, to which signs of resistance are beginning to appear. Research into novel control strategies is therefore urgently required and the advent of ‘omics technologies presents considerable opportunity for novel drug and vaccine target discovery. Here, interrogation of the first available F. gigantica newly excysted juvenile (NEJ) transcriptome revealed several protein families of current interest to parasitic flatworm vaccine research, including orthologues of mammalian complement regulator CD59 of the Ly6 family. Ly6 proteins have previously been identified on the tegument of Schistosoma mansoni and induced protective immunity in vaccination trials. Incorporating the recently available F. gigantica genome, the current work revealed 20 novel Ly6 family members in F. gigantica and, in parallel, significantly extended the F. hepatica complement from 3 to 18 members. Phylogenetic analysis revealed several distinct clades within the family, some of which are unique to Fasciola spp. trematodes. Analysis of available proteomic databases also revealed three of the newly discovered FhLy6s were present in extracellular vesicles, which have previously been prioritised in studying the host-parasite interface. The presentation of this new transcriptomic resource, in addition to the Ly6 family proteins here identified, represents a wealth of opportunity for future vaccine research

The Aethera Trial: An Ongoing Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at High Risk of Residual Hodgkin Lymphoma Following Autologous Stem Cell Transplant

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Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse

Abstract Introduction The AETHERA trial is a phase 3, randomized, placebo-controlled trial (ClinicalTrials.gov #NCT01100502), which evaluated whether post-ASCT consolidation treatment with brentuximab vedotin (BV) could prevent disease progression in Hodgkin lymphoma (HL) patients at high risk for relapse. The study met its primary endpoint: significant improvement in progression-free survival (PFS) per independent review with BV versus placebo (hazard ratio [HR]=0.57, P=0.001) (Moskowitz, 2015). The 2 most common adverse events (AEs) in the BV- treatment group were peripheral sensory neuropathy (56%) and neutropenia (35%). We are presenting updated efficacy and safety data after approximately 1 additional year of follow-up after the primary analysis. Methods Patients were randomized to receive BV 1.8 mg/kg q3wk or placebo for 16 cycles (approximately 12 months), 30-45 days after transplantation. Randomization was stratified by response to frontline therapy and by best clinical response to pre-ASCT salvage therapy. Patients whose disease had progressed after salvage treatment were not eligible. Patients received CT scans quarterly for the first year and then at 18 and 24 months during long-term follow-up (LTFU). Clinical lymphoma assessments were performed at each cycle of treatment, quarterly during the first year of LTFU, and every 6 months thereafter. AEs were collected for 30 days after the end of treatment, except for peripheral neuropathies and secondary malignancies, which were followed throughout LTFU. Clinical responses to subsequent BV treatment received after progression were also recorded. Results A total of 329 patients were randomized to the BV- (n=165) or placebo- (n=164) treatment arms. Median PFS per investigator assessment was not reached (95% CI not estimable [NE]-NE) in the BV arm and was 15.8 months (95% CI 8.5-44.0) in the placebo arm (HR=0.52, 95% CI 0.37-0.71). A sustained plateau with substantial separation is evident between both treatment groups, with improved PFS at 3-years post-randomization with BV consolidation versus placebo (Figure). The 3-year PFS rate was 61% (95% CI 52-68) for the BV arm and 43% (95% CI 36-51) for the placebo arm. Six PFS events (2 progressions and 4 deaths) were recorded after the 24-month evaluation period in the BV arm and 3 in the placebo arm (2 progressions and 1 death). The HR for PFS per independent review was 0.58 (95% CI 0.41-0.82). No new secondary malignancies have been observed since the primary analysis. The number of cases were comparable between the 2 treatment arms (n=4 BV, n=2 placebo). Malignancies on the BV arm included bladder cancer, lung cancer, pancreatic cancer, and myelodysplastic syndrome (n=1 each). In the placebo arm, secondary malignancies included mantle cell lymphoma and myelodysplastic syndrome (n=1 each). Among the 112 patients on the BV arm who experienced treatment-emergent peripheral neuropathy based on a Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) analysis, 99 patients (88%) experienced some improvement (23%) or complete resolution (65%) of neuropathy symptoms at the time of analysis. Discontinuation of treatment due to an AE occurred in 54 patients (33%) on the BV arm, most commonly due to peripheral sensory and motor neuropathies (14% and 7%, respectively). Patients who discontinued treatment as a result of an AE received a median of 9.5 cycles (range, 1 to 15) on the BV arm. The 2-year PFS rate in these patients was 69% (95% CI 54-79) versus 82% (95% CI 71-89) for patients who completed all 16 treatment cycles. Conclusions Consolidation treatment with BV in HL patients at high risk of relapse after ASCT showed an improvement in PFS versus placebo, approximately 3 years since the last patient was randomized. Kaplan-Meier analysis of PFS per investigator assessment showed a continued benefit of BV consolidation. No additional secondary malignancies have been observed in either treatment arm and most patients experienced resolution of peripheral neuropathy symptoms. We are currently analyzing clinical responses to BV treatment after disease progression. Figure 1. Progression-Free Survival per Investigator Assessment Figure 1. Progression-Free Survival per Investigator Assessment Disclosures Sweetenham: Seattle Genetics Inc.: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. This study investigates the use of brentuximab vedotin for consolidation therapy soon after ASCT. . Walewski:Mundipharma; Roche; Takeda: Honoraria, Other: Travel expenses; Amgen; Boehringer Ingelheim; Celgene; Janssen-Cilag; Mundipharma; Roche; Takeda; Teva: Consultancy; Bayer (Inst); Bayer/Onyx (Inst); Boehringer Ingelheim (Inst); Celgene (Inst); Celltrion (Inst); Gilead Sciences (Inst); GlaxoSmithKline (Inst); GlaxoSmithKline (Inst); Mundipharma (Inst); Pfizer (Inst); Roche (Inst); Roche/Genentech (Inst); Seattle Geneti: Research Funding. Nademanee:Celgene: Consultancy; Seattle Genetics Inc.: Research Funding; Spectrum: Research Funding; Gilead: Consultancy. Masszi:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Agura:Seattle Genetics Inc.: Research Funding. Holowiecki:Seattle Genetics Inc.: Research Funding; Takeda: Other: Travel expenses. Abidi:Seattle Genetics Inc.: Research Funding. Chen:Gilead: Consultancy, Other: Advisory Board; Janssen: Consultancy, Other: Advisory Board; Seattle Genetics: Consultancy, Other: Advisory Board; Genentech, Inc.: Consultancy, Other: Advisory Board. Stiff:Seattle Genetics Inc.: Consultancy, Honoraria, Research Funding. Viviani:Italfarmaco SpA: Consultancy; Teva Italia SpA: Consultancy; Takeda Italia SpA: Consultancy; Takeda International: Consultancy. Carella:Seattle Genetics Inc.: Research Funding. Osmanov:Seattle Genetics Inc.: Research Funding. Bachanova:Seattle Genetics Inc.: Consultancy, Research Funding. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau. Huebner:Takeda Pharmaceuticals International Co.: Employment, Equity Ownership. Larsen:Seattle Genetics Inc.: Employment, Equity Ownership. Hunder:Seattle Genetics Inc.: Employment, Equity Ownership

Alpha thalassaemia-mental retardation, X linked

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s