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Persistence of HIV through integration into host DNA in CD4(+) T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8(+) T cells are triggered to kill infected CD4(+) T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial'' HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A*02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8(+) T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4(+) T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.

Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing—termed kick and kill regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. Methods: This phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18–60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART + V + V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4+ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074. Findings: Between June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART + V + V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 copies HIV DNA per 106 CD4+ T-cells in ART + V + V group, with no statistically significant difference between the two groups (mean difference of 0·04 log10 copies HIV DNA per 106 CD4+ T-cells [95% CI −0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events. Interpretation: This kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.

Primary malignant tumors of the aorta are rare, only a handful of isolated cases having been described in the literature. Preoperative diagnosis of these tumors is more the exception than the rule. Diagnosis of aortic tumors is difficult as they can mimic many diverse conditions including atherosclerosis. We report a patient who presented with lower extremity claudication, renal infarction, and diffuse atherosclerosis and who was found to have tumor fragments in blood clots but no evidence of a primary tumor. Immunohistochemistry narrowed the differential diagnosis to a type of sarcoma. Six months later, he developed right flank pain due to a malignant fibrous histiocytoma that involved the abdominal aorta and that had initially manifested as tumor emboli.

Development of a practical, low cost high voltage electrolyte to enable lithium ion battery (LIB) operation above 4.5V will enable high energy density cells for vehicle applications. Towards that end, Dow Energy Materials is investing in programs to develop safe, cost-effective, high voltage electrolyte solutions. This effort leverages core capabilities of Dow’s large R&amp, D organization, such as fundamental modeling, low cost synthesis methods, and combinatorial formulation development. A practical solution to a high voltage electrolyte formulation requires all of these elements for success. This multi-faceted approach was utilized by Dow to determine the viability of ethylmethoxyethyl sulfone (EMES) as a high voltage electrolyte in full lithium ion cells.

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A method of quantifying the integrity of the brain stem auditory evoked responses (BAERs) is applied to specific cases in both the ICU and OR to demonstrate its usefulness as an adjunct to peak latency evaluation. This measure is particularly valuable when peak identification is difficult as a result of poor waveform coherence. Examples are included to demonstrate that this method can also give independent information from peak latency.

The brain stem auditory evoked response (BAER) was monitored intraoperatively in 11 patients with tumors of the posterior fossa. A technique for the objective quantitative assessment of the BAER based on the variance of the phase angle between small group averages is described. The resulting component synchrony measure corroborated standard peak latency and amplitude changes of the BAER during operative manipulation. A discussion of the replication and use of the objective measure is presented.