Objectives
Several single‐tablet regimens (STRs) are now available and are recommended for first‐line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been ...systematically studied. We examined the characteristics associated with initiation of STRs versus multi‐tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV).
Methods
A retrospective cohort study of nPHIV youth aged 13–24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV‐1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year.
Results
Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01–2.58, white (AOR 2.41; 95% CI 1.13–5.13) or Hispanic (AOR 2.38; 95% CI 1.32–4.27) race/ethnicity, and baseline CD4 count 351–500 cells/μL (AOR 1.94; 95% CI 1.18–3.19) and > 500 cells/μL (AOR 1.76; 95% CI 1.0–3.10). STR use was not associated with a shorter time to VS compared with MTR use hazard ratio (HR) 1.07; 95% CI 0.90–1.28.
Conclusions
Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.
Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied ...the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection.
The predictability of virus-host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we ...examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.
OBJECTIVES:Lessons learned from battle have been fundamental to advancing the care of injuries that occur in civilian life. Equally important is the need to further refine these advances in civilian ...practice, so they are available during future conflicts. The Major Extremity Trauma Research Consortium (METRC) was established to address these needs.
METHODS:METRC is a network of 22 core level I civilian trauma centers and 4 core military treatment centers—with the ability to expand patient recruitment to more than 30 additional satellite trauma centers for the purpose of conducting multicenter research studies relevant to the treatment and outcomes of orthopaedic trauma sustained in the military. Early measures of success of the Consortium pertain to building of an infrastructure to support the network, managing the regulatory process, and enrolling and following patients in multiple studies.
RESULTS:METRC has been successful in maintaining the engagement of several leading, high volume, level I trauma centers that form the core of METRC; together they operatively manage 15,432 major fractures annually. METRC is currently funded to conduct 18 prospective studies that address 6 priority areas. The design and implementation of these studies are managed through a single coordinating center. As of December 1, 2015, a total of 4560 participants have been enrolled.
CONCLUSIONS:Success of METRC to date confirms the potential for civilian and military trauma centers to collaborate on critical research issues and leverage the strength that comes from engaging patients and providers from across multiple centers.
The American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and American Association for Thoracic Surgery, along with key specialty and ...subspecialty societies, have completed a 2-part revision of the appropriate use criteria (AUC) for coronary revascularization. In prior coronary revascularization AUC documents, indications for revascularization in acute coronary syndromes and stable ischemic heart disease (SIHD) were combined into 1 document. To address the expanding clinical indications for coronary revascularization, and to align the subject matter with the most current American College of Cardiology/American Heart Association guidelines, the new AUC for coronary artery revascularization were separated into 2 documents addressing SIHD and acute coronary syndromes individually. This document presents the AUC for SIHD.
Clinical scenarios were developed to mimic patient presentations encountered in everyday practice. These scenarios included information on symptom status; risk level as assessed by noninvasive testing; coronary disease burden; and, in some scenarios, fractional flow reserve testing, presence or absence of diabetes, and SYNTAX score. This update provides a reassessment of clinical scenarios that the writing group felt were affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document but employs the recent modifications in the methods for developing AUC, most notably, alterations in the nomenclature for appropriate use categorization.
A separate, independent rating panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate for the clinical scenario presented. Scores of 1 to 3 indicate that revascularization is considered rarely appropriate for the clinical scenario, whereas scores in the mid-range of 4 to 6 indicate that coronary revascularization may be appropriate for the clinical scenario.
As seen with the prior coronary revascularization AUC, revascularization in clinical scenarios with high symptom burden, high-risk features, and high coronary disease burden, as well as in patients receiving antianginal therapy, are deemed appropriate. Additionally, scenarios assessing the appropriateness of revascularization before kidney transplantation or transcatheter valve therapy are now rated. The primary objective of the AUC is to provide a framework for the assessment of practice patterns that will hopefully improve physician decision making.
Global ozone analyses, based on assimilation of stratospheric profile and ozone column measurements, and NOy predictions from the Real‐time Air Quality Modeling System (RAQMS) are used to estimate ...the ozone and NOy budget over the continental United States during the July–August 2004 Intercontinental Chemical Transport Experiment–North America (INTEX‐A). Comparison with aircraft, satellite, surface, and ozonesonde measurements collected during INTEX‐A show that RAQMS captures the main features of the global and continental U.S. distribution of tropospheric ozone, carbon monoxide, and NOy with reasonable fidelity. Assimilation of stratospheric profile and column ozone measurements is shown to have a positive impact on the RAQMS upper tropospheric/lower stratosphere ozone analyses, particularly during the period when SAGE III limb scattering measurements were available. Eulerian ozone and NOy budgets during INTEX‐A show that the majority of the continental U.S. export occurs in the upper troposphere/lower stratosphere poleward of the tropopause break, a consequence of convergence of tropospheric and stratospheric air in this region. Continental U.S. photochemically produced ozone was found to be a minor component of the total ozone export, which was dominated by stratospheric ozone during INTEX‐A. The unusually low photochemical ozone export is attributed to anomalously cold surface temperatures during the latter half of the INTEX‐A mission, which resulted in net ozone loss during the first 2 weeks of August. Eulerian NOy budgets are shown to be very consistent with previously published estimates. The NOy export efficiency was estimated to be 24%, with NOx + PAN accounting for 54% of the total NOy export during INTEX‐A.
A synergistic extraction mixture containing chlorinated cobalt dicarbollide (CCD), carbamoylmethyl phosphine oxide (CMPO), and polyethylene glycol (PEG) has been investigated for the simultaneous ...recovery of cesium, strontium, lanthanides, and actinides from highly acidic media. The extraction properties of this mixture depend on the concentration ratio of the components. For recovery of all major radionuclides, the optimal ratio of CCD:PEG: CMPO = 5:1:1 should be used. The use of diphenyl-N,N-dibutylcarbamoylmethyl phosphine oxide and PEG-400 provides the most efficient recovery of cesium, strontium, lanthanides, and actinides. The possibility of using polyfluorinated ethers, esters, ketones, and sulfones as diluents was examined. Phenyltrifluoromethyl sulfone was the most suitable diluent tested. The use of this diluent allows good extraction properties, chemical and radiation stability, excellent explosion/fire-safety properties, and favorable hydrodynamic characteristics. The extraction of radionuclides from HNO
3
media by mixtures of CCD:PEG:CMPO in phenyltrifluoromethyl sulfone and the subsequent stripping behavior were evaluated.
Ovarian atypical proliferative (borderline) mucinous tumors of gastrointestinal and seromucinous types are considered subtypes within the mucinous tumor category despite the presence of distinctive ...clinicopathologic features that seromucinous tumors share with pure serous tumors. Immunophenotypic differences have not been extensively investigated. Immunohistochemical studies were performed to compare the expression patterns of cytokeratins 7 and 20 (CK7, CK 20), estrogen and progesterone receptors (ER, PR), CA-125, mesothelin, and WT-1 in 28 tumors of gastrointestinal type and 12 tumors of seromucinous type. Both gastrointestinal and seromucinous type tumors had a high frequency of CK7 expression (93% and 100%, respectively). The gastrointestinal type tumors were characterized by frequent expression of CK20 (86%) and CDX2 (39%), infrequent expression of CA-125 (11%) and mesothelin (7%), and lack of expression of ER, PR, and WT-1. In contrast, the seromucinous type tumors were characterized by frequent expression of ER (100%), PR (67%), CA-125 (92%), and mesothelin (83%), infrequent expression of WT-1 (8%), and lack of expression of CK20 and CDX2. The gastrointestinal and seromucinous types of atypical proliferative mucinous tumors are immunophenotypically distinctive tumors. The former are characterized by expression of markers of gastrointestinal-type differentiation (CK20 and CDX2), whereas the latter are characterized by expression of "müllerian-type" markers (ER, PR, CA-125, and mesothelin). Expression of the latter markers in the seromucinous tumors, which also are expressed in pure serous tumors, and lack of expression of gastrointestinal-type markers, combined with the clinicopathologic features these tumors share with pure serous tumors, support the concept that this subtype is more closely related to serous than gastrointestinal type mucinous tumors and justify the designation "seromucinous."
A major objective of the 2006 Second Texas Air Quality Study (TexAQS II) focused on understanding the effects of regional processes on Houston and Dallas ozone nonattainment areas. Here we quantify ...the contributions of background (continental scale) ozone production on Houston and Dallas air quality during TexAQS II using ensemble Lagrangian trajectories to identify remote source regions that impact Houston and Dallas background ozone distributions. Global‐scale chemical analyses, constrained with composition measurements from instruments on the NASA Aura satellite, are used to provide estimates of background composition along ensemble back trajectories. Lagrangian averaged O3 net photochemical production (production minus loss, P‐L) rates along the back trajectories are used as a metric to classify back trajectories. Results show that the majority (6 out of 9 or 66%) of the periods of high ozone in Houston were associated with periods of enhanced background ozone production. Slightly less than 50% (7 out of 15) of the days with high ozone in the Dallas Metropolitan Statistical Area (MSA) show enhanced background ozone production. Source apportionment studies show that 5‐day Lagrangian averaged O3 P‐L in excess of 15 ppbv/d can occur during continental‐scale transport to Houston owing to NOy enhancements from emissions within the Southern Great Lakes as well as recirculation of the Houston emissions. Dallas background O3 P‐L is associated with NOy enhancements from emissions within Chicago and Houston.
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