A technique for pediatric total skin electron irradiation

<p>Abstract</p> <p>Background</p> <p>Total skin electron irradiation (TSEI) is a special radiotherapy technique which has generally been used for treating adult patients with mycosis fungoides. Recently, two infants presented with leukemia cutis isolated to the skin requiring TSEI. This work discusses the commissioning and quality assurance (QA) methods for implementing a modified Stanford technique using a rotating harness system to position sedated pediatric patients treated with electrons to the total skin.</p> <p>Methods and Results</p> <p>Commissioning of pediatric TSEI consisted of absolute calibration, measurement of dosimetric parameters, and subsequent verification in a pediatric patient sized cylindrical phantom using radiographic film and optically stimulated luminance (OSL) dosimeters. The depth of dose penetration under TSEI treatment condition was evaluated using radiographic film sandwiched in the phantom and demonstrated a 2 cm penetration depth with the maximum dose located at the phantom surface. Dosimetry measurements on the cylindrical phantom and in-vivo measurements from the patients suggested that, the factor relating the skin and calibration point doses (i.e., the <it>B</it>-factor) was larger for the pediatric TSEI treatments as compared to adult TSEI treatments. Custom made equipment, including a rotating plate and harness, was fabricated and added to a standard total body irradiation stand and tested to facilitate patient setup under sedated condition. A pediatric TSEI QA program, consisting of daily output, energy, flatness, and symmetry measurements as well as in-vivo dosimetry verification for the first cycle was developed. With a long interval between pediatric TSEI cases, absolute dosimetry was also repeated as part of the QA program. In-vivo dosimetry for the first two infants showed that a dose of ± 10% of the prescription dose can be achieved over the entire patient body.</p> <p>Conclusion</p> <p>Though pediatric leukemia cutis and the subsequent need for TSEI are rare, the ability to commission the technique on a modified TBI stand is appealing for clinical implementation and has been successfully used for the treatment of two pediatric patients at our institution.</p

Computational Prediction and Molecular Characterization of an Oomycete Effector and the Cognate Arabidopsis Resistance Gene

Hyaloperonospora arabidopsidis (Hpa) is an obligate biotroph oomycete pathogen of the model plant Arabidopsis thaliana and contains a large set of effector proteins that are translocated to the host to exert virulence functions or trigger immune responses. These effectors are characterized by conserved amino-terminal translocation sequences and highly divergent carboxyl-terminal functional domains. The availability of the Hpa genome sequence allowed the computational prediction of effectors and the development of effector delivery systems enabled validation of the predicted effectors in Arabidopsis. In this study, we identified a novel effector ATR39-1 by computational methods, which was found to trigger a resistance response in the Arabidopsis ecotype Weiningen (Wei-0). The allelic variant of this effector, ATR39-2, is not recognized, and two amino acid residues were identified and shown to be critical for this loss of recognition. The resistance protein responsible for recognition of the ATR39-1 effector in Arabidopsis is RPP39 and was identified by map-based cloning. RPP39 is a member of the CC-NBS-LRR family of resistance proteins and requires the signaling gene NDR1 for full activity. Recognition of ATR39-1 in Wei-0 does not inhibit growth of Hpa strains expressing the effector, suggesting complex mechanisms of pathogen evasion of recognition, and is similar to what has been shown in several other cases of plant-oomycete interactions. Identification of this resistance gene/effector pair adds to our knowledge of plant resistance mechanisms and provides the basis for further functional analyses

Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase

Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we describe a mutant of Arabidopsis thaliana that is impaired in BABA-induced disease immunity (ibi1) but is hypersensitive to BABA-induced growth repression. IBI1 encodes an aspartyl-tRNA synthetase. Enantiomer-specific binding of the R enantiomer of BABA to IBI1 primed the protein for noncanonical defense signaling in the cytoplasm after pathogen attack. This priming was associated with aspartic acid accumulation and tRNA-induced phosphorylation of translation initiation factor eIF2α. However, mutation of eIF2α-phosphorylating GCN2 kinase did not affect BABA-induced immunity but relieved BABA-induced growth repression. Hence, BABA-activated IBI1 controls plant immunity and growth via separate pathways. Our results open new opportunities to separate broad-spectrum disease resistance from the associated costs on plant growth

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Self or other: Directors’ attitudes towards policy initiatives for external board evaluation

Recurrent crises in corporate governance have board practice and created policy pressure to assess the effectiveness of boards. Since the 1990s boards have faced calls to undertake regular, formal evaluation. Since 2010, the UK Corporate Governance Code has urged large corporations to engage outside parties to conduct them at least every three years, a move that other jurisdictions have copied. Despite this policy importance, little research has been conducted into processes or outcomes of board evaluation. This study explores the attitudes of directors on evaluation, whether self-administered or facilitated by others. We find acceptance of the principle but reservations about the value and even honesty in questionnaire-based approaches. We find scepticism about, but also acknowledgement of, the benefits of using outside facilitators, especially for their objectivity and because their interviewing elicits insights into board dynamics. As this practice expands beyond listed companies to non-listed ones, charities, and even governance branches of government, our findings point to a need to professionalise outside facilitation

Working with Adult Survivor of Childhood Sexual Abuse: Creating a Safe Place, Building Strengths

Experiencing sexual abuse often creates a feeling of powerlessness in the child, leaving the child with the perception of having little control over what happens. Physiological effects of childhood sexual abuse have also been found, such as long-term dysregulation of physiological stress response systems. With the varied and unique experiences of each person, adult survivors of child sexual abuse are not a homogeneous group. There is little agreement in the literature on the best therapeutic approach for adult survivors of child sexual abuse. Individual, group and family counselling and cognitive-behavioural interventions have been found to be effective with some clients. Phase-based treatment has also been suggested, in which the initial phase focuses on establishing therapeutic alliance and stabilizing and preparing the client, before moving into more in-depth work in later phase. This chapter describes appropriate assessment and intervention with an adult survivor of childhood sexual abuse