added all abstracts

1 files changed, 232 insertions, 5 deletions

diff --git a/bussiness_understanding/main.tex b/bussiness_understanding/main.tex
index c64fc0e..f01b002 100644
--- a/bussiness_understanding/main.tex
+++ b/bussiness_understanding/main.tex
@@ -24,9 +24,47 @@ A \gls{model} is a model.
     \item other papers
 \end{itemize}
 
-\section{Influenza mortality papers}
+\section{background}
+
+\cite{GuidanceIndustryClinical2007}
+Influenza viruses are enveloped ribonucleic acid viruses belonging to the family of
+Orthomyxoviridae and are divided into three distinct types on the basis of antigenic differences
+of internal structural proteins (Ref. 2). Two influenza types, Type A and B, are responsible for
+yearly epidemic outbreaks of respiratory illness in humans and are further classified based on the
+structure of two major external glycoproteins, hemagglutinin (HA) and neuraminidase (NA).
+Type B viruses, which are largely restricted to the human host, have a single HA and NA
+subtype. In contrast, numerous HA and NA Type A influenza subtypes have been identified to
+date. Type A strains infect a wide variety of avian and mammalian species.
+Type A and B influenza variant strains emerge as a result of frequent antigenic change,
+principally from mutations in the HA and NA glycoproteins. These variant strains may arise
+through one of two mechanisms: selective point mutations in the viral genome (Refs. 3 and 4) or
+from reassortment between two co-circulating strains (Refs. 5 and 6).
+Since 1977, influenza A virus subtypes H1N1 and H3N2, and influenza B viruses have been in
+global circulation in humans. The current U.S. licensed inactivated trivalent vaccines are
+formulated to prevent influenza illness caused by these influenza viruses. Because of the
+frequent emergence of new influenza variant strains, the antigenic composition of influenza
+vaccines needs to be evaluated yearly, and the trivalent inactivated influenza vaccines are
+reformulated almost every year. The immune response elicited by previous vaccination may not
+be protective against new variants.
+The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on
+Immunization Practices (ACIP) has expanded the recommendations for receipt of influenza
+vaccination to include an increasing scope of at risk populations, currently including pregnant
+women, persons 50 years of age and older, and children 6 to 59 months of age (Refs. 7, 8, and 9).
+
+Increased demand for influenza vaccines, including that resulting from the broader
+recommendations, the withdrawal from the U.S. market by several influenza vaccine
+manufacturers, and intermittent decreases in vaccine production due to manufacturing problems
+have led to shortages or delays in the availability of influenza vaccine over the past several
+seasons. These shortages highlight both the complexity of the production process and the need
+to increase the availability of influenza vaccines from multiple manufacturers. Currently, even
+with full production, manufacturing capacity would not produce enough seasonal influenza
+vaccine to vaccinate all those for whom the vaccine is now recommended. Finally, the
+availability of adequate supplies of licensed seasonal inactivated influenza vaccines from
+multiple manufacturers will be of value in responding to the emergence of a new pandemic
+influenza strain.
+
+\subsection{Influenza mortality papers}
 
-\subsection{US mortality associated influenza abstract}
 \cite{thompsonMortalityAssociatedInfluenza2003}
 Context  Influenza and respiratory syncytial virus (RSV) cause substantial
 morbidity and mortality. Statistical methods used to estimate deaths in the
@@ -95,7 +133,6 @@ deliberations of the Advisory Committee on Immunization Practices (ACIP)
 regarding influenza vaccination recommendations3 guided our choice of age
 groups for these analyses.
 
-\subsection{England influenza mortality}
 \cite{greenMortalityAttributableInfluenza2013}
 Very different influenza seasons have been observed from 2008/09-2011/12 in
 England and Wales, with the reported burden varying overall and by age group.
@@ -126,7 +163,6 @@ preparatory work to establish a routine mortality monitoring system ahead of
 introduction of the UK universal childhood seasonal influenza vaccination
 programme in 2013/14.
 
-\subsection{Global mortality paper}
 \cite{iulianoEstimatesGlobalSeasonal2018}
 Background
 Estimates of influenza-associated mortality are important for national and
@@ -172,7 +208,7 @@ than previously reported, suggesting that previous estimates might have
 underestimated disease burden. The contribution of non-respiratory causes of
 death to global influenza-associated mortality should be investigated.
 
-\section{Vaccine success criteria}
+\subsection{Vaccine success criteria}
 \cite{zhouHospitalizationsAssociatedInfluenza2012}
 
 Background. Age-specific comparisons of influenza and respiratory syncytial
@@ -203,6 +239,197 @@ are consistent with those from previous studies focusing either on influenza or
 RSV. Our approach provides robust national comparisons of hospitalizations
 associated with these 2 viral respiratory pathogens by age group and over time.
 
+\cite{GuidanceIndustryClinical2007}
+something about the effectiveness of vaccines.
+
+\cite{dejongHaemagglutinationinhibitingAntibodyInfluenza2003}
+
+The results of the haemagglutination-inhibiting (HI) antibody test for
+influenza virus antibody in human sera closely match those produced by virus
+neutralization assays and are predictive of protection. On the basis of the
+data derived from 12 publications concerning healthy adults, we estimated the
+median HI titre protecting 50\% of the vaccinees against the virus concerned at
+28. This finding supports the current policy requiring vaccines to induce serum
+HI titres of > or = 40 to the vaccine viruses in the majority of the vaccinees.
+Unfortunately similar studies are scanty for the elderly, the group most at
+risk of influenza. There still remain many unsolved technical problems with the
+HI assay and we recommend that these problems be studied and the virus
+neutralization test as a predictor of resistance to influenza be assessed.
+Although the studies on this issue often give conflicting results, they
+generally show that HI antibody responses to influenza vaccination tend to
+diminish with increasing age, when health is often compromized. Advanced age in
+itself seems not to be an independent factor in this process. However, even in
+completely healthy elderly individuals the response to vaccination with an
+antigenically new virus may be strongly reduced compared with younger
+vaccinees.
+
+\subsection{antibody response vaccine}
+\cite{sridharCellularImmuneCorrelates2013}
+The role of T cells in mediating heterosubtypic protection against natural
+influenza illness in humans is uncertain.  The 2009 H1N1 pandemic (pH1N1)
+provided a unique natural experiment to determine whether crossreactive
+cellular immunity limits symptomatic illness in antibody-naive individuals. We
+followed 342 healthy adults through the UK pandemic waves and correlated the
+responses of pre-existing T cells to the pH1N1 virus and conserved core protein
+epitopes with clinical outcomes after incident pH1N1 infection. Higher
+frequencies of pre-existing T cells to conserved CD8 epitopes were found in
+individuals who developed less severe illness, with total symptom score having
+the strongest inverse correlation with the frequency of interferon-g (IFN-g)+
+interleukin-2 (IL-2)− CD8+ T cells (r = −0.6, P = 0.004). Within this
+functional CD8+IFN-g+IL-2− population, cells with the CD45RA+ chemokine (C-C)
+receptor 7 (CCR7)− phenotype inversely correlated with symptom score and had
+lung-homing and cytotoxic potential. In the absence of crossreactive
+neutralizing antibodies, CD8+ T cells specific to conserved viral epitopes
+correlated with crossprotection against symptomatic influenza. This protective
+immune correlate could guide universal influenza vaccine development.
+
+\cite{bentebibelInductionICOSCXCR3}
+The role of T cells in mediating heterosubtypic protection against natural
+influenza illness in humans is uncertain.  The 2009 H1N1 pandemic (pH1N1)
+provided a unique natural experiment to determine whether crossreactive
+cellular immunity limits symptomatic illness in antibody-naive individuals. We
+followed 342 healthy adults through the UK pandemic waves and correlated the
+responses of pre-existing T cells to the pH1N1 virus and conserved core protein
+epitopes with clinical outcomes after incident pH1N1 infection. Higher
+frequencies of pre-existing T cells to conserved CD8 epitopes were found in
+individuals who developed less severe illness, with total symptom score having
+the strongest inverse correlation with the frequency of interferon-g (IFN-g)+
+interleukin-2 (IL-2)− CD8+ T cells (r = −0.6, P = 0.004). Within this
+functional CD8+IFN-g+IL-2− population, cells with the CD45RA+ chemokine (C-C)
+receptor 7 (CCR7)− phenotype inversely correlated with symptom score and had
+lung-homing and cytotoxic potential. In the absence of crossreactive
+neutralizing antibodies, CD8+ T cells specific to conserved viral epitopes
+correlated with crossprotection against symptomatic influenza. This protective
+immune correlate could guide universal influenza vaccine development.
+
+\cite{trieuLongtermMaintenanceInfluenzaSpecific2017}
+Background. Annual vaccination for healthcare workers and other high-risk
+groups is the mainstay of the public health strategy to combat influenza.
+Inactivated influenza vaccines confer protection by inducing neutralizing
+antibodies efficiently against homologous and closely matched virus strains. In
+the absence of neutralizing antibodies, cross-reactive T cells have been shown
+to limit disease severity. However, animal studies and a study in
+immunocompromised children suggested that repeated vaccination hampers CD8+ T
+cells. Yet the impact of repeated annual influenza vaccination on both
+cross-reactive CD4+ and CD8+ T cells has not been explored, particularly in
+healthy adults.  Methods. We assembled a unique cohort of healthcare workers
+who received a single AS03-adjuvanted H1N1pdm09 vaccine in 2009 and
+subsequently either repeated annual vaccination or no further vaccination
+during 2010–2013. Blood samples were collected before the influenza season or
+vaccination to assess antibody and T-cell responses.  Results. Antibody titers
+to H1N1pdm09 persisted above the protective level in both the repeated- and
+single-vaccination groups.  The interferon γ+ (IFN-γ+) and multifunctional CD4+
+T-cell responses were maintained in the repeated group but declined
+significantly in the single-vaccination group. The IFN-γ+CD8+ T cells remained
+stable in both groups.  Conclusions. This study provides the immunological
+evidence base for continuing annual influenza vaccination in adults.
+
+\subsection{Machine learning usage}
+
+\cite{furmanApoptosisOtherImmune2013}
+Despite the importance of the immune system in many diseases, there are
+currently no objective benchmarks of immunological health. In an effort to
+identifying such markers, we used influenza vaccination in 30 young (20–30
+years) and 59 older subjects (60 to >89 years) as models for strong and weak
+immune responses, respectively, and assayed their serological responses to
+influenza strains as well as a wide variety of other parameters, including gene
+expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset
+phenotypes and in vitro cytokine stimulation. Using machine learning, we
+identified nine variables that predict the antibody response with 84\% accuracy.
+Two of these variables are involved in apoptosis, which positively associated
+with the response to vaccination and was confirmed to be a contributor to
+vaccine responsiveness in mice. The identification of these biomarkers provides
+new insights into what immune features may be most important for immune health.
+
+\cite{sobolevAdjuvantedInfluenzaH1N1Vaccination2016}
+Adjuvanted vaccines afford invaluable protection against disease, and the
+molecular and cellular changes they induce offer direct insight into human
+immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu
+vaccine, healthy individuals made expansive, complex molecular and cellular
+responses that included overt lymphoid as well as myeloid contributions.
+Unexpectedly, this early response was subtly but significantly different in
+people older than ~35 years. Wide-ranging adverse clinical events can seriously
+confound vaccine adoption, but whether there are immunological correlates of
+these is unknown.  Here we identify a molecular signature of adverse events
+that was commonly associated with an existing B cell phenotype. Thus
+immunophenotypic variation among healthy humans may be manifest in complex
+pathophysiological responses.
+
+\cite{tsangGlobalAnalysesHuman2014}
+A major goal of systems biology is the development of models that accurately
+predict responses to perturbation. Constructing such models requires the
+collection of dense measurements of system states, yet transformation of data
+into predictive constructs remains a challenge. To begin to model human
+immunity, we analyzed immune parameters in depth both at baseline and in
+response to influenza vaccination. Peripheral blood mononuclear cell
+transcriptomes, serum titers, cell subpopulation frequencies, and B cell
+responses were assessed in 63 individuals before and after vaccination and were
+used to develop a systematic framework to dissect inter- and intra-individual
+variation and build predictive models of postvaccination antibody responses.
+Strikingly, independent of age and pre-existing antibody titers, accurate
+models could be constructed using pre-perturbation cell populations alone,
+which were validated using independent baseline time points. Most of the
+parameters contributing to prediction delineated temporally stable baseline
+differences across individuals, raising the prospect of immune monitoring
+before intervention.
+
+\subsection{Problems of previous studies}
+\cite{chattopadhyaySinglecellTechnologiesMonitoring2014}
+The complex heterogeneity of cells, and their interconnectedness with each
+other, are major challenges to identifying clinically relevant measurements
+that reflect the state and capability of the immune system. Highly multiplexed,
+single-cell technologies may be critical for identifying correlates of disease
+or immunological interventions as well as for elucidating the underlying
+mechanisms of immunity. Here we review limitations of bulk measurements and
+explore advances in single-cell technologies that overcome these problems by
+expanding the depth and breadth of functional and phenotypic analysis in space
+and time. The geometric increases in complexity of data make formidable hurdles
+for exploring, analyzing and presenting results. We summarize recent approaches
+to making such computations tractable and discuss challenges for integrating
+heterogeneous data obtained using these single-cell technologies.
+
+\cite{galliEndOmicsHigh2019}
+High-dimensional single-cell (HDcyto) technologies, such as mass cytometry
+(CyTOF) and flow cytometry, are the key techniques that hold a great promise
+for deciphering complex biological processes. During the last decade, we
+witnessed an exponential increase of novel HDcyto technologies that are able to
+deliver an in-depth profiling in different settings, such as various autoimmune
+diseases and cancer. The concurrent advance of custom data-mining algorithms
+has provided a rich substrate for the development of novel tools in
+translational medicine research. HDcyto technologies have been successfully
+used to investigate cellular cues driving pathophysiological conditions, and to
+identify disease-specific signatures that may serve as diagnostic biomarkers or
+therapeutic targets. These technologies now also offer the possibility to
+describe a complete cellular environment, providing unanticipated insights into
+human biology. In this review, we present an update on the current cutting-edge
+HDcyto technologies and their applications, which are going to be fundamental
+in providing further insights into human immunology and pathophysiology of
+various diseases. Importantly, we further provide an overview of the main
+algorithms currently available for data mining, together with the conceptual
+workflow for high-dimensional cytometric data handling and analysis. Overall,
+this review aims to be a handy overview for immunologists on how to design,
+develop and read HDcyto data.
+
+\cite{simoniMassCytometryPowerful2018}
+Advancement in methodologies for single cell analysis has historically been a
+major driver of progress in immunology. Currently, high dimensional flow
+cytometry, mass cytometry and various forms of single cell sequencing-based
+analysis methods are being widely adopted to expose the staggering
+heterogeneity of immune cells in many contexts. Here, we focus on mass
+cytometry, a form of flow cytometry that allows for simultaneous interrogation
+of more than 40 different marker molecules, including cytokines and
+transcription factors, without the need for spectral compensation. We argue
+that mass cytometry occupies an important niche within the landscape of
+single-cell analysis platforms that enables the efficient and in-depth study of
+diverse immune cell subsets with an ability to zoom-in on myeloid and lymphoid
+compartments in various tissues in health and disease. We further discuss the
+unique features of mass cytometry that are favorable for combining multiplex
+peptide-MHC multimer technology and phenotypic characterization of antigen
+specific T cells. By referring to recent studies revealing the complexities of
+tumor immune infiltrates, we highlight the particular importance of this
+technology for studying cancer in the context of cancer immunotherapy. Finally,
+we provide thoughts on current technical limitations and how we imagine these
+being overcome.
 
 \bibliographystyle{unsrt}
 \bibliography{../references.bib}