Research on rare diseases:ten years of progress and challenges at IRDiRC

The International Rare Diseases Research Consortium (IRDiRC) is a global collaborative initiative launched in 2011, aimed at tackling rare diseases through research. Here, we summarize IRDiRC’s vision and goals and highlight achievements and prospects after its first decade.</p

Natural and Induced Environment around the International Space Station (ISS) as Observed during On-Orbit Operations of the Robotic External Leak Locator (RELL)

Final Document is attached. The Robotic External Leak Locator (RELL) was deployed to the International Space Station (ISS) with the goal of detecting and locating on-orbit leaks around the ISS. Three activities to investigate and corroborate the background natural and induced environment of ISS were performed with RELL as part of the on-orbit validation and demonstration conducted in November December 2016. The first demonstration activity pointed RELL directly in the ram and wake directions for one orbit each. The ram facing measurements showed high partial pressure for mass-to-charge ratio 16, corresponding to atomic oxygen (AO), as well as the presence of mass-to-charge ratio 17. RELLs view in the wake-facing direction included more ISS structure and several Environmental Control and Life Support System (ECLSS) on-orbit vents were detected, including the Carbon Dioxide Removal Assembly (CDRA), Russian segment ECLSS, and Sabatier vents. The second demonstration activity pointed RELL at three faces of the P1 Truss segment. Effluents from ECLSS and European Space Agency (ESA) Columbus module on-orbit vents were detected by RELL. The partial pressures of mass-to-charge ratios 17 and 18 remained consistent with the first on-orbit activity of characterizing the natural environment. The third demonstration activity involved RELL scanning an Active Thermal Control System (ATCS) radiator. Three locations along the radiator were scanned and the angular position of RELL with respect to the radiator was varied. Mass-to-charge ratios 16 and 17 both had upward shifts in partial pressure when pointing toward the Radiator Beam Valve Modules (RBVMs), likely corresponding to a known, small ammonia leak

International Space Station (ISS) Environmental Control and Life Support System (ECLSS) Vent Flow Reflection and Detection by Robotic External Leak Locator (RELL)

On-orbit Robotic External Leak Locator (RELL) (i.e., mass spectrometer and ion gauge) measurements on the International Space Station (ISS) are presented to show the detection of recurring Environmental Control and Life Support System (ECLSS) vents at multiple ISS locations and RELL pointing directions. The path of ECLSS effluents to the RELL detectors is not entirely obvious at some locations, but the data indicates that diffuse gas-surface reflection or scattering resulting from plume interaction with vehicle surfaces is responsible. RELL was also able to confirm the ISS ECLSS constituents and distinguish them from the ammonia leak based on the ion mass spectra and known venting times during its operation to locate a leak in the ISS port-side External Active Thermal Control System (EATCS) coolant loop

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Natural and Induced Environment Around the International Space Station (ISS) as Observed During On-Orbit Operations of the Robotic External Leak Locator (RELL)

The Robotic External Leak Locator (RELL) was deployed to the International Space Station (ISS) with the goal of detecting and locating on-orbit leaks around the ISS. Three activities to characterize the background natural and induced environment of ISS were performed with RELL as part of the on-orbit validation and demonstration conducted in November and December 2016. The first demonstration activity pointed RELL directly in the ram (+X) and wake (-X) directions for one orbit each. The ram facing measurements showed high partial pressure for mass-to-charge ratio 16, corresponding to atomic oxygen (AO), as well as the presence of mass-to-charge ratio 17. RELL's view in the wake-facing direction included more ISS structure and several Environmental Control and Life Support System (ECLSS) on-orbit vents were detected, including the Carbon Dioxide Removal Assembly (CDRA), Russian segment ECLSS, and Sabatier vents. The second demonstration activity pointed RELL at three faces of the P1 Truss segment. Effluents from ECLSS and European Space Agency (ESA) Columbus module on-orbit vents were detected by RELL. The partial pressures of mass-to-charge ratios 17 and 18 remained consistent with the first on-orbit activity of characterizing the natural environment. The third demonstration activity involved RELL scanning an Active Thermal Control System (ATCS) radiator. Three locations along the radiator were scanned and the angular position of RELL with respect to the radiator was varied. Mass-to-charge ratios 16 and 17 both had upward shifts in partial pressure when pointing toward the Radiator Beam Valve Modules (RBVMs), likely corresponding to a known, small ammonia leak

Reply to "Spinal Cord Atrophy Is a Preclinical Marker of Progressive MS"

No abstract availabl

Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation

Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions

Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment

Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes

Risk factors for mortality among children under 5 years of age with severe diarrhea in low- and middle-income countries: Findings from the WHO-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children under five years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low and middle-income countries. METHODS: Data from the WHO-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children less than five years of age who were hospitalized with diarrhea between 2008-2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis is comprised of 234,781 cases, including 1,219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, OR = 3.54; 95% CI = 2.81-4.50), female sex (OR = 1.18; 95% CI= 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI= 1.01-3.25), no vomiting (OR = 1.13, 95% CI= 0.98-1.30), severe dehydration (OR = 3.79; 95% CI = 3.01-4.83), and being negative for rotavirus on an ELISA test (OR = 2.29; 95% CI= 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO Regions (OR = 130.62 comparing the African Region to the European region; 95% CI= 55.72-422.73), while cases from the European region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections