Sequence analysis and genomic organization of Aphid lethal paralysis virus: a new member of the family Dicistroviridae

The complete nucleotide sequence of the genomic RNA of an aphid-infecting virus, Aphid lethal paralysis virus (ALPV), has been determined. The genome is 9812 nt in length and contains two long open reading frames (ORFs), which are separated by an intergenic region of 163 nt. The first ORF (5' ORF) is preceded by an untranslated leader sequence of 506 nt, while an untranslated region of 571 nt follows the second ORF (3' ORF). The deduced amino acid sequences of the 5' ORF and 3' ORF products respectively showed similarity to the non-structural and structural proteins of members of the newly recognized genus Cripavirus (family Dicistroviridae). On the basis of the observed sequence similarities and identical genome organization, it is proposed that ALPV belongs to this genus. Phylogenetic analysis showed that ALPV is most closely related to Rhopalosiphum padi virus, and groups in a cluster with Drosophila C virus and Cricket paralysis virus, while the other members of this genus are more distantly related. Infectivity experiments showed that ALPV can not only infect aphid species but is also able to infect the whitefly Trialeurodes vaporariorum, extending its host range to another family of the order Hemipter

The supersymmetric Ward identities on the lattice

Supersymmetric (SUSY) Ward identities are considered for the N=1 SU(2) SUSY Yang Mills theory discretized on the lattice with Wilson fermions (gluinos). They are used in order to compute non-perturbatively a subtracted gluino mass and the mixing coefficient of the SUSY current. The computations were performed at gauge coupling $\beta$=2.3 and hopping parameter $\kappa$=0.1925, 0.194, 0.1955 using the two-step multi-bosonic dynamical-fermion algorithm. Our results are consistent with a scenario where the Ward identities are satisfied up to O(a) effects. The vanishing of the gluino mass occurs at a value of the hopping parameter which is not fully consistent with the estimate based on the chiral phase transition. This suggests that, although SUSY restoration appears to occur close to the continuum limit of the lattice theory, the results are still affected by significant systematic effects.Comment: 34 pages, 7 figures. Typo corrected, last sentence reformulated, reference added. To appear in Eur. Phys. J.

Universality of Mixed Action Extrapolation Formulae

Mixed action theories with chirally symmetric valence fermions exhibit very desirable features both at the level of the lattice calculations as well as in the construction and implementation of the low energy mixed action effective field theory. In this work we show that when such a mixed action effective field theory is projected onto the valence sector, both the Lagrangian and the extrapolation formulae become universal in form through next to leading order, for all variants of discretization methods used for the sea fermions. Our conclusion relies on the chiral nature of the valence quarks. The result implies that for all sea quark methods which are in the same universality class as QCD, the numerical values of the physical coefficients in the various mixed action chiral Lagrangians will be the same up to lattice spacing dependent corrections. This allows us to construct a prescription to determine the mixed action extrapolation formulae for a large class of hadronic correlation functions computed in partially quenched chiral perturbation theory at the one-loop level. For specific examples, we apply this prescription to the nucleon twist--2 matrix elements and the nucleon--nucleon system. In addition, we determine the mixed action extrapolation formula for the neutron EDM as this provides a nice example of a theta-dependent observable; these observables are exceptions to our prescription.Comment: 36 pages, appendix on twisted mass sea fermions added, expanded discussion of NLO operators, version published in JHEP; typographical errors corrected in Eqs. (68) and (69

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Centre symmetric 3d effective actions for thermal SU(N) Yang-Mills from strong coupling series

We derive three-dimensional, Z(N)-symmetric effective actions in terms of Polyakov loops by means of strong coupling expansions, starting from thermal SU(N) Yang-Mills theory in four dimensions on the lattice. An earlier action in the literature, corresponding to the (spatial) strong coupling limit, is thus extended by several higher orders, as well as by additional interaction terms. We provide analytic mappings between the couplings of the effective theory and the parameters $N_\tau,\beta$ of the original thermal lattice theory, which can be systematically improved. We then investigate the deconfinement transition for the cases SU(2) and SU(3) by means of Monte Carlo simulations of the effective theory. Our effective models correctly reproduce second order 3d Ising and first order phase transitions, respectively. Furthermore, we calculate the critical couplings $\beta_c(N_\tau)$ and find agreement with results from simulations of the 4d theory at the few percent level for $N_\tau=4-16$.Comment: 27 pages, 21 figures; final version published in JHEP; attached the corresponding Erratum (ref. JHEP 1107:014,2011, DOI 10.1007/JHEP07(2011)014) for ease of consultatio

Supporting older patients in making healthcare decisions:The effectiveness of decision aids; A systematic review and meta-analysis

Objective: To systematically review randomized controlled trials and clinical controlled trials evaluating the effectiveness of Decision Aids (DAs) compared to usual care or alternative interventions for older patients facing treatment, screening, or care decisions.Methods: A systematic search of several databases was conducted. Eligible studies included patients ≥ 65 years or reported a mean of ≥ 70 years. Primary outcomes were attributes of the choice made and decision making process, user experience and ways in which DAs were tailored to older patients. Meta-analysis was conducted, if possible, or outcomes were synthesized descriptively.Results: Overall, 15 studies were included. Using DAs were effective in increasing knowledge (SMD 0.90; 95% CI [0.48, 1.32]), decreasing decisional conflict (SMD −0.15; 95% CI [−0.29, −0.01]), improving patient-provider communication (RR 1.67; 95% CI [1.21, 2.29]), and preparing patients to make an individualized decision (MD 35.7%; 95% CI [26.8, 44.6]). Nine studies provided details on how the DA was tailored to older patients.Conclusion: This review shows a number of favourable results for the effectiveness of DAs in decision making with older patients.Practice implications: Current DAs can be used to support shared decision making with older patients when faced with treatment, screening or care decisions.</p

A Grounded Theory of Interdisciplinary Communication and Collaboration in the Outpatient Setting of the Hospital for Patients with Multiple Long-Term Conditions

Interdisciplinary communication and collaboration are crucial in the care of people with multiple long-term conditions (MLTCs) yet are often experienced as insufficient. Through the lens of complexity science, this study aims to explain how healthcare professionals (HCPs) adapt to emerging situations in the care of patients with MLTC by examining interdisciplinary communication and collaboration in the outpatient hospital setting. We used the constant comparative method to analyze transcribed data from seven focus groups with twenty-one HCPs to generate a constructivist grounded theory of ‘interdisciplinary communication and collaboration in the outpatient setting of the hospital for patients with multiple long-term conditions’. Our theory elucidates the various pathways of communication and collaboration. Why, when, and how team members choose to collaborate influences if and to what degree tailored care is achieved. There is great variability and unpredictability to this process due to internalized rules, such as beliefs on the appropriateness to deviate from guidelines, and the presence of an interprofessional identity. We identified organizational structures that influence the dynamics of the care team such as the availability of time and financial compensation for collaboration. As we strive for tailored care for patients with MLTC, our theory provides promising avenues for future endeavors.</p

A Grounded Theory of Interdisciplinary Communication and Collaboration in the Outpatient Setting of the Hospital for Patients with Multiple Long-Term Conditions

Interdisciplinary communication and collaboration are crucial in the care of people with multiple long-term conditions (MLTCs) yet are often experienced as insufficient. Through the lens of complexity science, this study aims to explain how healthcare professionals (HCPs) adapt to emerging situations in the care of patients with MLTC by examining interdisciplinary communication and collaboration in the outpatient hospital setting. We used the constant comparative method to analyze transcribed data from seven focus groups with twenty-one HCPs to generate a constructivist grounded theory of ‘interdisciplinary communication and collaboration in the outpatient setting of the hospital for patients with multiple long-term conditions’. Our theory elucidates the various pathways of communication and collaboration. Why, when, and how team members choose to collaborate influences if and to what degree tailored care is achieved. There is great variability and unpredictability to this process due to internalized rules, such as beliefs on the appropriateness to deviate from guidelines, and the presence of an interprofessional identity. We identified organizational structures that influence the dynamics of the care team such as the availability of time and financial compensation for collaboration. As we strive for tailored care for patients with MLTC, our theory provides promising avenues for future endeavors.</p