Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination.

Under the ever-present threat of a pandemic influenza strain, the evolution of a broadly reactive, neutralizing, functional, humoral immune response may hold the key to protection against both circulating and emerging influenza strains. We apply a systems approach to profile hemagglutinin- and neuraminidase-specific humoral signatures that track with the evolution of broad immunity in a cohort of vaccinated individuals and validate these findings in a second longitudinal cohort. Multivariate analysis reveals the presence of a unique pre-existing Fcγ-receptor-binding antibody profile in individuals that evolved broadly reactive hemagglutination inhibition activity (HAI), marked by the presence of elevated levels of pre-existing FCGR2B-binding antibodies. Moreover, vaccination with FCGR2B-binding antibody-opsonized influenza results in enhanced antibody titers and HAI activity in a murine model. Together, these data suggest that pre-existing FCGR2B binding antibodies are a key correlate of the evolution of broadly protective influenza-specific antibodies, providing insight for the design of next-generation influenza vaccines.

Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques.

An effective vaccine to prevent HIV transmission has not yet been achieved. Modulation of the microbiome via probiotic therapy has been suggested to result in enhanced mucosal immunity. Here, we evaluated whether probiotic therapy could improve the immunogenicity and protective efficacy of SIV/HIV vaccination. Rhesus macaques were co-immunized with an SIV/HIV DNA vaccine via particle-mediated epidermal delivery and an HIV protein vaccine administered intramuscularly with Adjuplex™ adjuvant, while receiving daily oral Visbiome® probiotics. Probiotic therapy alone led to reduced frequencies of colonic CCR5+ and CCR6+ CD4+ T cells. Probiotics with SIV/HIV vaccination led to similar reductions in colonic CCR5+ CD4+ T cell frequencies. SIV/HIV-specific T cell and antibody responses were readily detected in the periphery of vaccinated animals but were not enhanced with probiotic treatment. Combination probiotics and vaccination did not impact rectal SIV/HIV target populations or reduce the rate of heterologous SHIV acquisition during the intrarectal challenge. Finally, post-infection viral kinetics were similar between all groups. Thus, although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.

Robust monitoring of hypovolemia in intensive care patients using photoplethysmogram signals.

The paper presents a fingertip photoplethysmography based technique to assess patient fluid status that is robust to waveform artifacts and health variability in the underlying patient population. The technique is intended for use in intensive care units, where patients are at risk for hypovolemia, and signal artifacts and inter-patient variations in health are common. Input signals are preprocessed to remove artifact, then a parameter-invariant statistic is calculated to remove effects of patient-specific physiology. Patient data from the Physionet MIMICII database was used to evaluate the performance of this technique. The proposed method was able to detect hypovolemia within 24 hours of onset in all hypovolemic patients tested, while producing minimal false alarms over non-hypovolemic patients.

Prediction of significant vasospasm in aneurysmal subarachnoid hemorrhage using automated data.

BACKGROUND: When vasospasm is detected after aneurysmal subarachnoid hemorrhage (aSAH), it is treated with hypertensive or endovascular therapy. Current classification methods are resource-intensive, relying on specialty-trained professionals (nursing exams, transcranial dopplers, and perfusion imaging). More passively obtained variables such as cerebrospinal fluid drainage volumes, sodium, glucose, blood pressure, intracranial pressure, and heart rate, have not been used to predict vasospasm. We hypothesize that these features may yield as much information as resource-intensive features to classify vasospasm. METHODS: We studied data from 81 aSAH patients presenting within two days of onset. Vasospasm class (VSP) was defined by angiographic vasospasm warranting endovascular treatment. Naïve Bayes (NB) and logistic regression (LR) classifiers were trained on selected variable feature sets from the first three days of illness. Performance of trained classifiers was evaluated using area under the receiver operator characteristic curve (AUC classifier) and F-measure (F classifier). Ablation analysis determined incremental utility of each variable and subsets. RESULTS: 43.2 % developed VSP. During feature selection, the only passively collected variable that did not yield a statistically significant summary statistic was CSF drainage volume. NB classifier trained on all passively obtained features (AUC NB 0.708 and F NB 0.636) outperformed NB classifier trained on resource-intensive features (AUC NB 0.501 and F NB 0.349). CONCLUSIONS: Data-driven analysis of passively obtained clinical data predicted VSP better than current targeted resource-intensive monitoring techniques after aSAH. Automated classification of VSP may be possible.

Limitations of threshold-based brain oxygen monitoring for seizure detection.

BACKGROUND: Brain tissue oxygen (PbtO(2)) monitors are utilized in a threshold-based fashion, triggering actions based on the presumption of tissue compromise when PbtO(2) is less than 20 mmHg. Some early published practice guidelines suggest that seizure is a potential culprit when PbtO(2) crosses this threshold; evidence for this is not well defined. METHODS: Data were collected manually as part of a prospective observational database. PbtO(2) monitors and continuous electroencephalogram (cEEG) were placed by clinical protocol in aneurysmal subarachnoid hemorrhage (aSAH) or traumatic brain injury (TBI) patients with a Glasgow Coma Scale (GCS) ≤ 8. Eight patients with discrete seizures during an overlapping monitored period were identified. Probability of seizure when PbtO(2) value was <20 mmHg (and the inverse) were calculated. RESULTS: There were 343 distinct seizure episodes and 1797 PbtO(2) measurements. 8.9% of seizures were followed by a PbtO(2) value below 20 mmHg. Of all observed low PbtO(2) values, 3.8% were associated with seizure. Seizure length did not influence PbtO(2). Two patients with the highest number of seizures developed low PbtO(2) values post-seizure. CONCLUSIONS: Seizures were neither associated with a PbtO(2) value of <20 mmHg nor associated with a drop in PbtO(2) value across a clinically significant threshold. However, we cannot rule out the existence of any relationship between PbtO(2) and seizure with this limited data set. Prospective research using electronically recorded data is required to more effectively examine the relationship between PbtO(2) and seizure.