Several categories of human X-Y homologous DNA sequences have been recognized. We report that a locus (DXYS77) approximately 14 kb distal to the pseudoautosomal boundary (PAB) is 93% identical in ...nucleotide sequence to a locus (DYS148) on the long arm of the Y chromosome (Yq). Within this segment of pseudoautosomal/Yq homology we identified a member of a family of repeats that are concentrated in Xp22.3 and in the euchromatic portion of the Y chromosome. The repeat sequence structure--a dimer bounded by short terminal repeats--is reminiscent of retroposons derived from RNA polymerase III transcripts.
EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive ...or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.
•Patients with Myc-driven DLBCL had less favorable outcomes after EPOCH, and vorinostat had no impact on HIV or chemotherapy's efficacy.•Permitting 1 cycle of systemic treatment before EPOCH-based chemotherapy facilitated protocol enrollment without worsening outcomes.
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This book contains the proceedings of the third international workshop on "From Parity Violation to Hadronic Structure and more ..." which was held from May 16 to May 20, 2006, at the George ...Eliopoulos conference center on the Greek island of Milos. It is part of a series that started in Mainz in 2002 and was followed by a second workshop in Grenoble in 2004. While originally initiated by the extraction of the strangeness contribution to the electromagnetic form factors of the nucleon, the workshop series has continuously broadened the focus to the application of Parity Violation using hadronic probes and to Parity Violation experiments in atomic physics. Meanwhile there have been many exciting new proposals for using Parity Violation in other areas like in the search for new physics beyond the standard model or in exploring hadron structure. There are also close connections to the open question on the size of the two photon exchange amplitude. Fifty years after the 1956 proposal of Lee and Yang to test the hypothesis of violation of parity symmetry in the weak interaction, the many applications of parity violation in very different experiments are way beyond the scope of what Lee and Yang could have imagined. For the physics topics discussed during this workshop, the application of parity violation has become a standard work horse that allows to extract many physics topics in different experiments.
In West Africa, new management practices such as conservation agriculture with crop residue mulching can improve crop yields for individual farmers. However, in a context of complex social ...interactions between farmers, the introduction of such practices can also lead to conflicts between private interests and communal use of resources, for example the free grazing of crop residues. The objective of this paper was to assess ex-ante the impacts of the practice of crop residue mulching on crop productivity in a village of central Burkina Faso using an agent-based model, AMBAWA, that simulates the flows of biomass and nutrients between crop and livestock systems at the village scale. The model considers the interactions between four types of farmers that were identified in the study site: subsistence-oriented crop farmers, market-oriented crop farmers, agro-pastoralists and pastoralists. The model simulated increased cattle migration outside the village due to increased crop residue scarcity during the dry season with increased proportions of cropland under the practice of conservation agriculture, decreasing the manure availability at village scale. Consequently, the assumed direct yield increases due to soil moisture conservation as a result of mulching did not compensate for the yield losses resulting from lesser amounts of manure available. This effect was felt most strongly by farmers who own relatively large numbers of cattle (agro-pastoralists and pastoralists). The total maize production at village level depended more on the proportion of cropping land that was available for grazing by cattle, and thus not mulched, than on a possible direct effect of mulching on yield per se. The AMBAWA model can support discussion among stakeholders (farmers, traditional and administrative authorities) who are involved in the private and communal management of crop residues and other biomass resources, in order to co-design effective arrangements and practices for their sustainable use.
•AMBAWA is an agent-based model that simulates biomass and nutrients flows.•Biomass flows (manure, crop residue) were considered between four types of farmers.•AMBAWA was used to assess the effect of crop residue mulching on crop productivity.•Mulching decreased yields at village scale due to livestock migration (manure loss).•Agent based models allows co-designing innovative practices in agro-pastoral areas.
Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to ...assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central’s Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols—PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.
Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically ...confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.
Background: Parents are a key source of support for children exposed to single-incident/acute traumas and can thereby play a potentially significant role in children's post-trauma psychological ...adjustment. However, the evidence base examining parental responses to child trauma and child posttraumatic stress symptoms (PTSS) has yielded mixed findings.
Objective: We conducted a systematic review examining domains of parental responding in relation to child PTSS outcomes.
Method: Studies were included if they (1) assessed children (6-19 years) exposed to a potentially traumatic event, (2) assessed parental responses to a child's trauma, and (3) quantitatively assessed the relationship between parental responses and child PTSS outcomes. A systematic search of three databases (APAPsycNet, PTSDpubs, and Web of Science) yielded 27 manuscripts.
Results: Parental overprotection, trauma communication, avoidance of trauma discussion and of trauma reminders, and distraction were consistently related to child PTSS. There was more limited evidence of a role for trauma-related appraisals, harsh parenting, and positive parenting in influencing child outcomes. Significant limitations to the evidence base were identified, including limited longitudinal evidence, single informant bias and small effect sizes.
Conclusion: We conclude that key domains of parental responses could be potential intervention targets, but further research must validate the relationship between these parental responses and child PTSS outcomes.
Child post-traumatic stress symptoms following acute trauma are consistently related to post-trauma parental overprotection, avoidance of trauma discussion and of trauma reminders, and promotion of distraction from trauma-related thoughts and stimuli.
The findings from this review provide a potential rationale for targeting these parental domains in clinical interventions addressing children's post-traumatic stress symptoms.
Future research is needed to validate the longitudinal relationship between parental response domains following children's traumatic exposure and child post-traumatic stress symptoms.
OBJECTIVE:Brentuximab vedotin is a Food and Drug Administration approved anti-CD30 antibody drug conjugate potently active in Hodgkin lymphoma. Trials of brentuximab vedotin with doxorubicin, ...vinblastine, and dacarbazine (AVD-BV) excluded patients with HIV. We studied the safety of AVD-BV in newly diagnosed HIV-associated classical Hodgkin lymphoma .
DESIGN AND METHODS:Patients diagnosed with stage II–IV HIV-associated classical Hodgkin lymphoma received AVD-BV on days 1 and 15 every 28 days for six cycles. Anti-HIV medications with strong CYP3A4 inhibition were excluded. This phase 1 trial followed a 3+3 dose de-escalation design started with brentuximab vedotin at 1.2 mg/kg with standard dosing of AVD. Dose-limiting toxicities were defined in cycle one.
RESULTS:Seven patients were enrolled with six being evaluablefive of six stage III/IV, three with an international prognostic score at least 4. With no dose-limiting toxicities identified, all six were treated at the 1.2 mg/kg dose. Only five grade (G) three nonhematological adverse events were noted in three patientspulmonary infection, diarrhea, and peripheral neuropathy. No G4/5 adverse events occurred. PET/computer tomography was negative in five of six after cycle 2 and six of six post therapy. Progression-free survival was 100% at 25 months with all patients in remission. One patient was deemed ineligible for taking ritonavir, a strong CYP3A4 inhibitor, but developed G3/4 adverse events including febrile neutropenia, and pancreatitis and though consented was excluded from all evaluation.
CONCLUSION:AVD-BV was well tolerated at recommended phase 2 dose of 1.2 mg/kg. Concurrent strong CYP3A4 inhibitors should be avoided. A phase 2 study of AVD-BV is currently enrolling (NCT01771107).
Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who ...strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, “Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it.” We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what “causation” means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called “causative.”
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