Maternal characteristics and offspring’s cardiometabolic profile

In the Netherlands, nearly one in five children has overweight or obesity. Children with overweight have an unhealthier cardiometabolic profile and are at increased risk of adult overweight, diabetes and cardiovascular disease compared to children with normal weight. Maternal characteristics, such as maternal prepregnancy body mass index (pBMI), are important predictors of childhood overweight and cardiometabolic profile. This thesis aimed to identify underlying mechanisms, like early pregnancy lipid profile and offspring’s postnatal growth, in the association between maternal pBMI and childhood cardiometabolic profile. The research described in this thesis was conducted within the multi-ethnic prospective Amsterdam Born Children and their Development study (ABCD-study). The research presented in this thesis indicates that maternal characteristics – like high maternal pBMI, an atherogenic early pregnancy lipid profile, both a maternal and paternal family history of diabetes – and postnatal growth are all independently associated with an adverse cardiometabolic profile at age 5-6 years. The association between maternal pBMI and offspring’s cardiometabolic profile is not mediated by maternal early pregnancy lipid profile or postnatal growth, but is modified by postnatal growth, with the most detrimental outcomes found in children of overweight mothers with accelerated postnatal growth. The effects of maternal overweight on faster postnatal growth and an adverse cardiometabolic profile in childhood seem stronger among girls than boys

Static Typing of Complex Presence Constraints in Interfaces

Many functions in libraries and APIs have the notion of optional parameters, which can be mapped onto optional properties of an object representing those parameters. The fact that properties are optional opens up the possibility for APIs and libraries to design a complex "dependency logic" between properties: for example, some properties may be mutually exclusive, some properties may depend on others, etc. Existing type systems are not strong enough to express such dependency logic, which can lead to the creation of invalid objects and accidental usage of absent properties. In this paper we propose TypeScriptIPC: a variant of TypeScript with a novel type system that enables programmers to express complex presence constraints on properties. We prove that it is sound with respect to enforcing complex dependency logic defined by the programmer when an object is created, modified or accessed

Static Typing of Complex Presence Constraints in Interfaces (Artifact)

This artifact is based on TypeScriptIPC, a statically typed programming language with interfaces in which complex presence constraints can be defined. This enables developers to express inter-property constraints on interface properties. The need for these inter-property constraints stems from web APIs, which often impose a complex "dependency logic" between properties. For example, some properties may be mutually exclusive, or the presence of a property may depend on the presence of others, etc. TypeScriptIPC is a variant of TypeScript, in which interfaces are extended to express constraints over multiple properties, using propositional logic. This artifact contains documentation on how to build and run TypeScriptIPC, such that the code snippets from the paper can be run

A Catalogue of Inter-Parameter Dependencies in RESTful Web APIs

Web services often impose dependency constraints that re strict the way in which two or more input parameters can be combined to form valid calls to the service. Unfortunately, current specification languages for web services like the OpenAPI Specification provide no support for the formal description of such dependencies, which makes it hardly possible to automatically discover and interact with services without human intervention. Researchers and practitioners are openly requesting support for modelling and validating dependencies among in put parameters in web APIs, but this is not possible unless we share a deep understanding of how dependencies emerge in practice—the aim of this work. In this paper, we present a thorough study on the presence of dependency constraints among input parameters in web APIs in in dustry. The study is based on a review of more than 2.5K operations from 40 real-world RESTful APIs from multiple application domains. Overall, our findings show that input dependencies are the norm, rather than the exception, with 85% of the reviewed APIs having some kind of dependency among their input parameters. As the main outcome of our study, we present a catalogue of seven types of dependencies consistently found in RESTful web APIsMinisterio de Economía y Competitividad BELI (TIN2015-70560-R)Ministerio de Ciencia, Innovación y Universidades Horatio RTI2018-101204-B-C21Ministerio de Educación, Cultura y Deporte FPU17/0407

Analyzing Flow Cytometry or Targeted Gene Expression Data Influences Clinical Discoveries—Profiling Blood Samples of Pancreatic Ductal Adenocarcinoma Patients

Introduction:Monitoring the therapeutic response of pancreatic ductal adenocarcinoma (PDAC) patients is crucial to determine treatment strategies. Several studies have examined the effectiveness of FOLFIRINOX as a first-line treatment in patients with locally advanced pancreatic cancer, but little attention has been paid to the immunologic alterations in peripheral blood caused by this chemotherapy regimen. Furthermore, the influence of the measurement type (e.g., flow cytometry and targeted gene expression) on the clinical discoveries is unknown. Therefore, we aimed to scrutinize the influence of using flow cytometry or targeted immune gene expression to study the immunological changes in blood samples of PDAC patients who were treated with a single-cycle FOLFIRINOX combined with lipegfilgrastim (FFX-Lipeg). Material and Methods: Whole-blood samples from 44 PDAC patients were collected at two time points: before the first FOLFIRINOX cycle and 14 days after the first cycle. EDTA blood tubes were used for multiplex flow cytometry analyses to quantify 18 immune cell populations and for complete blood count tests as the standard clinical routine. The flow cytometry data were analyzed with FlowJo software. In addition, Tempus blood tubes were used to isolate RNA and measure 1230 immune-related genes using NanoString Technology®. Data quality control, normalization, and analysis were performed using nSolver™ software and the Advanced Analysis module. Results: FFX-Lipeg treatment increased the number of neutrophils and monocytes, as shown by flow cytometry and complete blood count in concordance with elevated gene expression measured via targeted gene expression profiling analysis. Interestingly, flow cytometry analysis showed an increase in the number of B and T cells after treatment, while targeted gene expression analysis showed a decrease in B and T cell-specific gene expression. Conclusions: Targeted gene expression complements flow cytometry analysis to provide a comprehensive understanding of the effects of FFX-Lipeg. Flow cytometry and targeted gene expression showed increases in neutrophils and monocytes after FFX-Lipeg. The number of lymphocytes is increased after treatment; nevertheless, their cell-specific gene expression levels are downregulated. This highlights that different techniques influence clinical discoveries. Therefore, it is important to carefully select the measurement technique used to study the effect of a treatment.</p

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.</p

Quality-of-Life Impact of an Investigational Subunit-Adjuvanted Herpes Zoster Vaccine in Adults ≥50 Years of Age

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Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

The primary cause of morbidity and mortality in patients with multiple myeloma(MM) is an infection. Therefore there is great concern about the susceptibility to the outcome of COVID-19 infected patients with MM. This retrospective study describes the baseline characteristics and outcome data of COVID-19 infection in 650 patients with plasma cell disorders, collected by the International Myeloma Society to understand the initial challenges faced by myeloma patients during COVID-19 pandemic. Analysis were performed for hospitalized MM patients. Among hospitalized patinets, the median age was 69 years, and nearly all patients(96%) had MM. Approximately 36% were recently diagnosed(2019-2020), and 54% of patients were receiving first-line therapy. Thirty-three percent of patients have died, with significant geographic variability, ranging from 27% to 57% of hospitalized patients. Univariate analysis identified age, ISS3, high-risk disease, renal disease, suboptimal myeloma control(active or progressive disease), and one or more comorbidities as risk factors for higher rates of death. Neither history of transplant, including within a year of COVID-19 diagnosis, nor other anti-MM treatments were associated with outcomes. Multivariate analysis found that only age, high-risk MM, renal disease, and suboptimal MM control remained independent predictors of adverse outcome with COVID-19 infection. The management of MM in the era of COVID-19 requires careful consideration of patient and disease-related factors to decrease the risk of acquiring COVID-19 infection, while not compromising disease control through appropriate MM treatment. This study provides initial data to develop recommendations for the management of MM patients with COVID-19 infection