Durability for 12 months of antibody response to a booster dose of monovalent BNT162b2 in adults who had initially received 2 doses of inactivated vaccine.

This study examined the strength and durability of antibody responses in 277 adults who received a heterologous third dose of the BNT162b2 vaccine, following two doses of an inactivated vaccine. Neutralizing antibody levels against both the ancestral virus and Omicron BA.2 subvariant decreased from one month to 6 months after the third dose, and were then maintained at 12 months. Participants who received both a fourth dose and reported a SARS-CoV-2 infection had the highest antibody titers at 365 days after the third dose. Individuals with chronic medical conditions had lower antibody levels against the Omicron BA.2 subvariant at 12 months after the third dose. The results suggest that the heterologous third dose provides durable neutralizing antibody responses, which may be influenced by subsequent infection or vaccination and pre-existing medical conditions. These findings may help explain the differences in immune protection between vaccination and natural infection.

SARS-CoV-2-specific CD8+ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years.

Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8+ and CD4+ T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a- and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8+ and CD4+ T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8+ T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID.

Integrating HRMAS-NMR Data and Machine Learning-Assisted Profiling of Metabolite Fluxes to Classify Low- and High-Grade Gliomas.

Diagnosing and classifying central nervous system tumors such as gliomas or glioblastomas pose a significant challenge due to their aggressive and infiltrative nature. However, recent advancements in metabolomics and magnetic resonance spectroscopy (MRS) offer promising avenues for differentiating tumor grades both in vivo and ex vivo. This study aimed to explore tissue-based metabolic signatures to classify/distinguish between low- and high-grade gliomas. Forty-six histologically confirmed, intact solid tumor samples from glioma patients were analyzed using high-resolution magic angle spinning nuclear magnetic resonance (HRMAS-NMR) spectroscopy. By integrating machine learning (ML) algorithms, spectral regions with the most discriminative potential were identified. Validation was performed through univariate and multivariate statistical analyses, along with HRMAS-NMR analyses of 46 paired plasma samples. Amongst the various ML models applied, the logistics regression identified 46 spectral regions capable of sub-classifying gliomas with accuracy 87% (F1-measure 0.87, Precision 0.82, Recall 0.93), whereas the extra-tree classifier identified three spectral regions with predictive accuracy of 91% (F1-measure 0.91, Precision 0.85, Recall 0.97). Wilcoxon test presented 51 spectral regions significantly differentiating low- and high-grade glioma groups (p < 0.05). Based on sensitivity and area under the curve values, 40 spectral regions corresponding to 18 metabolites were considered as potential biomarkers for tissue-based glioma classification and amongst these N-acetyl aspartate, glutamate, and glutamine emerged as the most important markers. These markers were validated in paired plasma samples, and their absolute concentrations were computed. Our results demonstrate that the metabolic markers identified through the HRMAS-NMR-ML analysis framework, and their associated metabolic networks, hold promise for targeted treatment planning and clinical interventions in the future.

Bayesian Inference Using the Proximal Mapping: Uncertainty Quantification Under Varying Dimensionality.

In statistical applications, it is common to encounter parameters supported on a varying or unknown dimensional space. Examples include the fused lasso regression, the matrix recovery under an unknown low rank, etc. Despite the ease of obtaining a point estimate via optimization, it is much more challenging to quantify their uncertainty. In the Bayesian framework, a major difficulty is that if assigning the prior associated with a p -dimensional measure, then there is zero posterior probability on any lower-dimensional subset with dimension d < p . To avoid this caveat, one needs to choose another dimension-selection prior on d , which often involves a highly combinatorial problem. To significantly reduce the modeling burden, we propose a new generative process for the prior: starting from a continuous random variable such as multivariate Gaussian, we transform it into a varying-dimensional space using the proximal mapping. This leads to a large class of new Bayesian models that can directly exploit the popular frequentist regularizations and their algorithms, such as the nuclear norm penalty and the alternating direction method of multipliers, while providing a principled and probabilistic uncertainty estimation. We show that this framework is well justified in the geometric measure theory, and enjoys a convenient posterior computation via the standard Hamiltonian Monte Carlo. We demonstrate its use in the analysis of the dynamic flow network data.

Antibody Fc receptor binding and T cell responses to homologous and heterologous immunization with inactivated or mRNA vaccines against SARS-CoV-2.

Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.

Assessing the Readability, Reliability, and Quality of AI-Modified and Generated Patient Education Materials for Endoscopic Skull Base Surgery.

BACKGROUND: Despite National Institutes of Health and American Medical Association recommendations to publish online patient education materials at or below sixth-grade literacy, those pertaining to endoscopic skull base surgery (ESBS) have lacked readability and quality. ChatGPT is an artificial intelligence (AI) system capable of synthesizing vast internet data to generate responses to user queries but its utility in improving patient education materials has not been explored. OBJECTIVE: To examine the current state of readability and quality of online patient education materials and determined the utility of ChatGPT for improving articles and generating patient education materials. METHODS: An article search was performed utilizing 10 different search terms related to ESBS. The ten least readable existing patient-facing articles were modified with ChatGPT and iterative queries were used to generate an article de novo. The Flesch Reading Ease (FRE) and related metrics measured overall readability and content literacy level, while DISCERN assessed article reliability and quality. RESULTS: Sixty-six articles were located. ChatGPT improved FRE readability of the 10 least readable online articles (19.7 ± 4.4 vs. 56.9 ± 5.9, p < 0.001), from university to 10th grade level. The generated article was more readable than 48.5% of articles (38.9 vs. 39.4 ± 12.4) and higher quality than 94% (51.0 vs. 37.6 ± 6.1). 56.7% of the online articles had "poor" quality. CONCLUSIONS: ChatGPT improves the readability of articles, though most still remain above the recommended literacy level for patient education materials. With iterative queries, ChatGPT can generate more reliable and higher quality patient education materials compared to most existing online articles and can be tailored to match readability of average online articles.

Engineered Skin Substitutes in Dermatologic Surgery: A Systematic Review.

BACKGROUND: Artificial skin substitutes are a flexible alternative to autografting in Mohs micrographic surgery (MMS), but the characteristics and clinical outcomes of skin substitutes are not well defined. OBJECTIVE: Summarize clinical data of skin substitutes in MMS for cutaneous malignancy. METHODS: A MEDLINE/Embase/Web of Science search was conducted. Articles with original data on outcomes after skin substitute use in MMS for cutaneous malignancy were included. Articles not in English or without original data were excluded. Bias was assessed using the Oxford CEBM Levels of Evidence Table. Outcomes were synthesized using weighted averages. This study was prospectively registered in PROSPERO. RESULTS: Of 1,007 articles, 40 met eligibility for inclusion. In total, 898 patients who underwent MMS and received a skin substitute were included. Xenografts were most commonly used ( n = 613). Semi-synthetic grafts (∼$<1/cm 2 ) and xenografts (∼$10/cm 2 ) are most affordable. Overall, outcomes were excellent for all skin substitutes, with a small proportion of patients experiencing correctable complications. CONCLUSION: Skin substitutes are highly effective in MMS, with enormous potential. While the data demonstrate positive outcomes, they predominately draw from small, retrospective studies or case reports. There is also a scarcity of data comparing skin substitutes with each other or controls. Prospective studies are recommended.

Changes on noncontrast magnetic resonance imaging following lymphatic surgery for upper extremity secondary lymphedema.

OBJECTIVE: To assess changes in noncontrast magnetic resonance imaging (MRI)-based biomarkers after upper extremity lymphedema surgery. METHODS: We retrospectively identified secondary upper extremity lymphedema patients who underwent vascularized lymph node transplant (VLNT), debulking lipectomy, or VLNT with a prior debulking (performed separately). All patients with both preoperative and postoperative MRIs were compared. An MRI-based edema scoring system was used: 0 (no edema), 1 (<50% fluid from myofascial to dermis), and 2 (≥50% fluid from myofascial to dermis). Edema scores and subcutaneous thickness (ST) were obtained along four quadrants across the upper and lower third of the arm and forearm each-for a total of 16 anatomical locations-and compared before and after surgery. Net changes in edema scores and ST were then correlated with Lymphoedema Quality-of-Life Questionnaire scores, L-Dex (bioimpedance), and limb volume difference by perometry. RESULTS: Patients who underwent lymphatic surgeries between January 2017 and December 2022 and successfully completed preoperative and postoperative MRI were included, resulting in a total of 33 unilateral secondary upper extremity lymphedema patients m(mean age, 63 ± 14 years; 32 female). The median postoperative follow-up times were 12.5 months (range, 6-19 months) for VLNT, 13.5 months (range, 12-40 months) for debulking, and 12.0 months (range, 12-24 months) for patients who underwent VLNT after debulking surgery. There was a decrease in mean ST in 15 of 16 anatomical segments of the upper extremity after debulking (P < .001), and the edema score increased in 7 of 16 segments (P ≤ .001-.020). Edema stage did not change in patients who underwent VLNT only or VLNT after debulking. ST decreased only along the radial forearm in patients who underwent VLNT after debulking despite an improvement in the Lymphoedema Quality-of-Life Questionnaire score in the former group. There was correlation between a decrease in ST with a decrease in volume within the debulking group (r = 0.79; P < .001). A decrease in ST also correlated with improved lymphedema quality of life questionnaires in the debulking group (r = 0.49; P = .04). CONCLUSIONS: A decrease in ST was demonstrated in most anatomical segments after liposuction debulking, whereas edema stage was increased. Fewer changes were seen with VLNT, possibly a reflection of more gradual changes within this short follow-up period, with the radial forearm potentially revealing the earliest response.

Genetic diversity of astroviruses detected in wild aquatic birds in Hong Kong.

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.

Povidone-iodine in vitro antiseptic efficacy as a function of exposure duration, concentration, preparation, and length of storage.

PURPOSE: Although 5% povidone-iodine (PVP-I) is frequently used as an ocular antiseptic agent, there is a lack of consensus regarding the effects of PVP-I concentration, storage after opening, and compounded preparation on PVP-I antisepsis. We performed a series of in-vitro experiments to determine the impact of these factors on PVP-I's inhibition of common causes of post-procedural eye infection. METHODS: Inhibition of microorganism growth was measured in-vitro as a function of active PVP-I exposure time. In control experiments, PVP-I was inactivated before microorganism exposure. Tested PVP-I solutions varied in concentration (0.6%, 5%, or 10%), length of storage after opening (0, 7, or 30 days), and preparation (commercial vs.compounded from stock PI solution). Tested pathogens included S. epidermidis, S. viridans, P. aeruginosa, methicillin-resistant S. aureus, methicillin-sensitive S. aureus, and C. albicans. RESULTS: PVP-I solutions inhibited all bacterial growth by 3 min and fungal growth by 15 s. Compared to 5% PVP-I, the 0.6% PVP-I was less effective in inhibiting S. viridans growth (200 ± 0 colonies vs. 7 ± 8 at 30 s, P = 0.0004; 183 ± 21 vs. 0 ± 0 at 1 min, P = 0.018), but more effective in inhibiting P. aeruginosa (30 ± 20 vs. 200 ± 0 at 15 s, P = 0.019). Compared to commercial and newly-opened PVP-I solutions, compounded preparations and solutions stored for 7 or 30 days after bottle opening either preserved or improved antiseptic efficacy against tested microorganisms. CONCLUSIONS: Concentration of PVP-I solution affects antiseptic efficacy within 1 min of exposure, but all solutions performed equivalently at 3 min. In contrast to results of prior studies investigating dilute PVP-I, the 0.6% PVP-I did not demonstrate a uniformly equivalent or superior anti-septic effect. Compounded preparation and storage length after bottle opening did not decrease PVP-I antiseptic activity.

Returners and explorers dichotomy in the face of natural hazards.

Understanding human mobility patterns amid natural hazards is crucial for enhancing urban emergency responses and rescue operations. Existing research on human mobility has delineated two primary types of individuals: returners, who exhibit a tendency to frequent a limited number of locations, and explorers, characterized by a more diverse range of movement across various places. Yet, whether this mobility dichotomy endures in the context of natural hazards remains underexplored. This study addresses this gap by examining anonymized high-resolution mobile phone location data from Lee County, Florida residents, aiming to unravel the dynamics of these distinct mobility groups throughout different phases of Hurricane Ian. The results indicate that returners and explorers maintained their distinct mobility characteristics even during the hurricane, showing increased separability. Before the hurricane, returners favored shorter trips, while explorers embarked on longer journeys, a trend that continued during the hurricane. However, the hurricane heightened people's inclination to explore, leading to a notable increase in longer-distance travel for both groups, likely influenced by evacuation considerations. Spatially, both groups exhibited an uptick in trips towards the southern regions, away from the hurricane's path, particularly converging on major destinations such as Miami, Fort Lauderdale, Naples, and West Palm Beach during the hurricane.

Conventional clinical signs and symptoms are poor predictors of postoperative cerebrospinal fluid leak: A single-centre cohort perspective.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak remains a concerning complication of the endoscopic endonasal approach (EEA) for skull base pathology. Signs and symptoms suggesting CSF leak often trigger additional workup during the postoperative course. We systematically evaluate associations between subjectively reported clinical signs/symptoms noted during the immediate postoperative period and incidence of postoperative CSF leaks. METHODS: Retrospective chart review was conducted at a tertiary academic medical centre including 137 consecutive patients with intraoperative CSF leak during EEA with primary repair between July 2018 and August 2022. Postoperative CSF leak associations with clinical signs and symptoms were evaluated using positive (PPV) and negative predictive values (NPV), sensitivity, specificity and odds ratio (OR) via univariate logistic regression. RESULTS: Seventy-nine patients (57.7%) had high-flow leaks repaired and 5 (3.6%) developed CSF leaks postoperatively. Of reported symptoms, rhinorrhea was most common (n = 52, 38.0%; PPV [95% CI] = 7.6% [4.8%, 11.9%]), followed by severe headache (n = 47, 34.3%; 6.3% [3.1%, 12.5%]), dizziness (n = 43, 31.4%; 2.3% [0.4%, 12.1%]), salty or metallic taste (n = 20, 14.6%; 9.9% [3.3%, 25.8%]), and throat drainage (n = 10, 7.3%; 9.9% [1.7%, 41.4%]). Nausea or vomiting constituted the most reported sign concerning for CSF leak (n = 73, 53.3%; PPV [95% CI] = 4.1% [2.0%, 8.1%]). On univariate regression, no sign or symptom, including rhinorrhea (OR [95% CI] = 7.00 [0.76-64.44]), throat drainage (3.42 [0.35-33.86]), salty/metallic taste (4.22 [0.66-27.04]), severe headache (3.00 [0.48-18.62]), dizziness (0.54 [0.06-4.94]), fever (3.16 [0.50-19.99]), and nausea/vomiting (1.33 [0.22-8.21]), associated with postoperative CSF leak. CONCLUSIONS: A range of subjectively reported symptoms and signs failed to predict postoperative CSF leak. Further investigation is warranted to inform appropriate attention and response.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Seasonal antigenic prediction of influenza A H3N2 using machine learning.

Antigenic characterization of circulating influenza A virus (IAV) isolates is routinely assessed by using the hemagglutination inhibition (HI) assays for surveillance purposes. It is also used to determine the need for annual influenza vaccine updates as well as for pandemic preparedness. Performing antigenic characterization of IAV on a global scale is confronted with high costs, animal availability, and other practical challenges. Here we present a machine learning model that accurately predicts (normalized) outputs of HI assays involving circulating human IAV H3N2 viruses, using their hemagglutinin subunit 1 (HA1) sequences and associated metadata. Each season, the model learns an updated nonlinear mapping of genetic to antigenic changes using data from past seasons only. The model accurately distinguishes antigenic variants from non-variants and adaptively characterizes seasonal dynamics of HA1 sites having the strongest influence on antigenic change. Antigenic predictions produced by the model can aid influenza surveillance, public health management, and vaccine strain selection activities.

Diagnostic performance of chest CT average intensity projection (AIP) reconstruction for the assessment of pleuro-parenchymal abnormalities.

AIM: The comparison between chest x-ray (CXR) and computed tomography (CT) images is commonly required in clinical practice to assess the evolution of chest pathological manifestations. Intrinsic differences between the two techniques, however, limit reader confidence in such a comparison. CT average intensity projection (AIP) reconstruction allows obtaining "synthetic" CXR (s-CXR) images, which are thought to have the potential to increase the accuracy of comparison between CXR and CT imaging. We aim at assessing the diagnostic performance of s-CXR imaging in detecting common pleuro-parenchymal abnormalities. MATERIALS AND METHODS: 142 patients who underwent chest CT examination and CXR within 24 hours were enrolled. CT was the standard of reference. Both conventional CXR (c-CXR) and s-CXR images were retrospectively reviewed for the presence of consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion by 3 readers in two separate sessions. Sensitivity, specificity, accuracy and their 95% confidence interval were calculated for each reader and setting and tested by McNemar test. Inter-observer agreement was tested by Cohen's K test and its 95%CI. RESULTS: Overall, s-CXR sensitivity ranged 45-67% for consolidation, 12-28% for nodule/mass, 17-33% for linear opacities, 2-61% for reticular opacities, and 33-58% for pleural effusion; specificity 65-83%, 83-94%, 94-98%, 93-100% and 79-86%; accuracy 66-68%, 74-79%, 89-91%, 61-65% and 68-72%, respectively. K values ranged 0.38-0.50, 0.05-0.25, -0.05-0.11, -0.01-0.15, and 0.40-0.66 for consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion, respectively. CONCLUSION: S-CXR images, reconstructed with AIP technique, can be compared with conventional images in clinical practice and for educational purposes.

Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children.

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.