Agrobacterium tumefaciens gene transfer to Casuarina glauca : a tropical nitrogen-fixing tree

Transgenic calli of the tropical tree #Casuarina glauca were produced using #Agrobacterium tumefaciens-mediated gene transfer. Hypocotyls, cotyledons and epicotyls were excised from 30-60-day old #Casuarina seedlings and cocultivated with #Agrobacterium strain C58C1(pGV2260) containing the binary vector BIN19GUSINT. Transformed calli were selected on nutrient medium supplemented with 0,5 microM NAA, 2,5 microM BA and 50 mg/l kanamycin. Some of the factors influencing T-DNA transfer to #C. glauca$ explants were studied. Optimal transformation rates were obtained when explants from 45-day old seedlings were cocultivated for 3 days in the presence of 25 microM acetosyringone. Transgenic buds differentiated on 10% of the calli grown on transformed epicotyls. Evidence for genetic transformation was obtained by beta-glucuronidase assay, PCR and Southern hybridization. (Résumé d'auteur

t(5;9)(q32;p24) KANK1/PDGFRB

Review on t(5;9)(q32;p24) KANK1/PDGFRB, with data on clinics, and the genes involved

Fear of reprisal and change agency in the public health and social service system: Protocol for a sequential mixed methods study

Abract Background:   Since they are key witnesses to the systemic difficulties and social inequities experienced by vulnerable patients, health and social service (HSS) professionals and clinical managers must act as change agents. Using their expertise to achieve greater social justice, change agents employ a wide range of actions that span a continuum from the clinical (microsystem) to the societal (macrosystem) sphere and involve actors inside and outside the HSS system. Typically, however, clinical professionals and managers act in a circumscribed manner, that is, within the clinical sphere and with patients and colleagues. Among the hypotheses explaining this reduced scope of action is the fear of reprisal. Little is known about the prevalence of this fear and its complex dynamics. Objective:   The overall aim is to gain a better understanding of the complex dynamic process leading to clinical professionals’ and managers’ fear of reprisal in their change agent actions and senior administrators’ and managers’ determination of wrongdoing. The objectives are (1) to estimate the prevalence of fear of reprisal among clinical professionals and managers; (2) to identify the factors involved in (a) the emergence of this fear among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; (3) to describe the process of emergence of (a) the fear of reprisal among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; and (4) to document the legal and ethical issues associated with the factors identified (objective 2) and the processes described (objective 3). Methods:   Based on the Exit, Voice, Loyalty, Neglect model, a 3-part sequential mixed methods design will include (1) a web-based survey (objective 1), (2) a qualitative grounded theory design (objectives 2 and 3), and (3) legal and ethical analysis (objective 4). Survey: 77,794 clinical professionals or clinical managers working in the Québec public HSS system will be contacted via email. Data will be analyzed using descriptive statistics. Grounded theory design: for each of the 3 types of participants (clinical professionals, clinical managers, and senior administrators and managers), a theoretical sample of 15 to 30 people will be selected via various strategies. Data will be independently analyzed using constant comparison process. Legal and ethical analysis: situations described by participants will be analyzed using, respectively, applicable legislation and jurisprudence and 2 ethical models. Results:   This ongoing study began in June 2022 and is scheduled for completion by March 2027. Conclusions:   Instead of acting, fear of reprisal could induce clinical professionals to tolerate situations that run counter to their social justice values. To ensure they use their capacities for serving a population that is or could become vulnerable, it is important to know the prevalence of the fear of reprisal and gain a better understanding of its complex dynamics. International Registered Report Identifier (IRRID): PRR1-10.2196/4840

Can a pharmacy intervention improve the metabolic risks of mental health patients? Evaluation of a novel collaborative service

Background: The pressure on healthcare services worldwide has driven the incorporation of disease state management services within community pharmacies in developed countries. Pharmacists are recognised as the most accessible healthcare professionals, and the incorporation of these services facilitates patient care. In Australia, the opportunity to manage pharmacy patients with mental illness has been underutilised, despite the existence of service models for other chronic conditions. This paper is an independent evaluation of a novel service developed by a community pharmacy in Perth, Western Australia. The service represents collaboration between a nurse practitioner and community pharmacy staff in the management of mental health patients with metabolic risks. Methods: We applied practice service standards for Australian community pharmacies to develop an evaluation framework for this novel service. This was followed by semi -structured interviews with staff members at the study pharmacy to explore service processes and procedures. Descriptive analysis of interviews was supplemented with analysis of patients’ biometric data. All data were evaluated against the developed framework. Results: The evaluation framework comprised 13 process, 5 out comes, and 11 quality indicators. Interview data from eight staff members and biometric data from 20 community-dwelling mental health patients taking antipsychotics were evaluated against the framework. Predominantly, patients were managed by the pharmacy’s nurse practitioner, with medication management provided by pharmacists. Patients’ biometric measurements comprised weight, blood pressure, blood glucose levels, lipid profiles and management of obesity, smoking, hypertension and diabetes. Positive outcomes observed in the patient data included weight loss, smoking cessation, and improved blood pressure, blood glucose and lipid levels. Conclusions: The developed framework allowed effective evaluation of the service, and may be applicable to other pharmacy services. The metabolic clinic met key process, quality and outcomes indicators. The positive patient outcomes may assist in securing further funding

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR 12]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I\u2013III invasive early BC at age 6440 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60\u20130.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94\u20132.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients\u2019 counseling on treatment, prevention, and surveillance strategies

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)

Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis

ETV6 mutations in early immature human T cell leukemias

A substantial proportion of adult T-ALL samples display gene expression and mutation characteristics of both T cell and acute myeloid leukemias; mutations in ETV6 are found exclusively within this new molecular subgroup of adult T-ALL patients

Design, pointing control, and on-sky performance of the mid-infrared vortex coronagraph for the VLT/NEAR experiment

Vortex coronagraphs have been shown to be a promising avenue for high- contrast imaging in the close-in environment of stars at thermal infrared (IR) wavelengths. They are included in the baseline design of the mid-infrared extremely large telescope imager and spectrograph. To ensure good performance of these coronagraphs, a precise control of the centering of the star image in real time is needed. We previously developed and validated the quadrant analysis of coronagraphic images for tip-tilt sensing estimator (QACITS) pointing estimator to address this issue. While this approach is not wavelength-dependent in theory, it was never implemented for mid-IR observations, which leads to specific challenges and limitations. Here, we present the design of the mid-IR vortex coronagraph for the "new Earths in the α Cen Region (NEAR) experiment with the Very Large Telescope (VLT)/Very Large Telescope imager and spectrometer for the mid-infrared (VISIR) instrument and assess the performance of the QACITS estimator for the centering control of the star image onto the vortex coronagraph. We use simulated data and on-sky data obtained with VLT/VISIR, which was recently upgraded for observations assisted by adaptive optics in the context of the NEAR experiment. We demonstrate that the QACITS-based correction loop is able to control the centering of the star image onto the NEAR vortex coronagraph with a stability down to 0.015 λ / D rms over 4 h in good conditions. These results show that QACITS is a robust approach for precisely controlling in real time the centering of vortex coronagraphs for mid-IR observations.Peer reviewe