Treatment switch to nonacog beta pegol factor IX in hemophilia B: A Canadian cost-consequence analysis based on real-world factor IX consumption and clinical outcomes.

Background: The Canadian Bleeding Disorders Registry (CBDR) is a source of real-world data for Canadian patients with hemophilia B. Nonacog beta pegol (N9-GP), an extended half-life (EHL) recombinant factor IX (FIX) concentrate, was awarded a Canadian Blood Services contract in 2018 and subsequently made available across Canada (except Québec) to adult patients. For most patients already on another EHL FIX treatment, a switch to N9-GP occurred.

Complex motion of Greenland Ice Sheet outlet glaciers with basal temperate ice.

Uncertainty associated with ice sheet motion plagues sea level rise predictions. Much of this uncertainty arises from imperfect representations of physical processes including basal slip and internal ice deformation, with ice sheet models largely incapable of reproducing borehole-based observations. Here, we model isolated three-dimensional domains from fast-moving (Sermeq Kujalleq/Store Glacier) and slow-moving (Isunnguata Sermia) ice sheet settings in Greenland.

Rapid basal melting of the Greenland Ice Sheet from surface meltwater drainage.

Subglacial hydrologic systems regulate ice sheet flow, causing acceleration or deceleration, depending on hydraulic efficiency and the rate at which surface meltwater is delivered to the bed. Because these systems are rarely observed, ice sheet basal drainage represents a poorly integrated and uncertain component of models used to predict sea level changes. Here, we report radar-derived basal melt rates and unexpectedly warm subglacial conditions beneath a large Greenlandic outlet glacier.

Thermodynamics of a fast-moving Greenlandic outlet glacier revealed by fiber-optic distributed temperature sensing.

Measurements of ice temperature provide crucial constraints on ice viscosity and the thermodynamic processes occurring within a glacier. However, such measurements are presently limited by a small number of relatively coarse-spatial-resolution borehole records, especially for ice sheets. Here, we advance our understanding of glacier thermodynamics with an exceptionally high-vertical-resolution (~0.

Supraglacial lake drainage at a fast-flowing Greenlandic outlet glacier.

Supraglacial lake drainage events influence Greenland Ice Sheet dynamics on hourly to interannual timescales. However, direct observations are rare, and, to date, no in situ studies exist from fast-flowing sectors of the ice sheet. Here, we present observations of a rapid lake drainage event at Store Glacier, west Greenland, in 2018.

Physical Conditions of Fast Glacier Flow: 3. Seasonally-Evolving Ice Deformation on Store Glacier, West Greenland.

Temporal variations in ice sheet flow directly impact the internal structure within ice sheets through englacial deformation. Large-scale changes in the vertical stratigraphy within ice sheets have been previously conducted on centennial to millennial timescales; however, intra-annual changes in the morphology of internal layers have yet to be explored. Over a period of 2 years, we use autonomous phase-sensitive radio-echo sounding to track the daily displacement of internal layers on Store Glacier, West Greenland, to millimeter accuracy.

Linear response of east Greenland's tidewater glaciers to ocean/atmosphere warming.

Predicting the retreat of tidewater outlet glaciers forms a major obstacle to forecasting the rate of mass loss from the Greenland Ice Sheet. This reflects the challenges of modeling the highly dynamic, topographically complex, and data-poor environment of the glacier-fjord systems that link the ice sheet to the ocean. To avoid these difficulties, we investigate the extent to which tidewater glacier retreat can be explained by simple variables: air temperature, meltwater runoff, ocean temperature, and two simple parameterizations of "ocean/atmosphere" forcing based on the combined influence of runoff and ocean temperature.

Cascading lake drainage on the Greenland Ice Sheet triggered by tensile shock and fracture.

Supraglacial lakes on the Greenland Ice Sheet are expanding inland, but the impact on ice flow is equivocal because interior surface conditions may preclude the transfer of surface water to the bed. Here we use a well-constrained 3D model to demonstrate that supraglacial lakes in Greenland drain when tensile-stress perturbations propagate fractures in areas where fractures are normally absent or closed. These melt-induced perturbations escalate when lakes as far as 80 km apart form expansive networks and drain in rapid succession.

Seismic evidence for complex sedimentary control of Greenland Ice Sheet flow.

The land-terminating margin of the Greenland Ice Sheet has slowed down in recent decades, although the causes and implications for future ice flow are unclear. Explained originally by a self-regulating mechanism where basal slip reduces as drainage evolves from low to high efficiency, recent numerical modeling invokes a sedimentary control of ice sheet flow as an alternative hypothesis. Although both hypotheses can explain the recent slowdown, their respective forecasts of a long-term deceleration versus an acceleration of ice flow are contradictory.

An Observational Study to Assess Brain MRI Change and Disease Progression in Multiple Sclerosis Clinical Practice-The MS-MRIUS Study.

Background & Purpose: To describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS-MRIUS).

Material & Methods: The MS-MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States.

Reliability and validity of the Danish version of the Schema Mode Inventory (SMI).

Schema modes are conceptualized as different parts of oneself, related to specific emotions, cognitions, and behaviors. They are a central concept in schema therapy for personality pathology and other chronic psychiatric disorders. Prior research confirms the factorial validity of the Schema Mode Inventory (SMI), an instrument to assess schema modes.

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration.

Sensitive response of the Greenland Ice Sheet to surface melt drainage over a soft bed.

The dynamic response of the Greenland Ice Sheet (GrIS) depends on feedbacks between surface meltwater delivery to the subglacial environment and ice flow. Recent work has highlighted an important role of hydrological processes in regulating the ice flow, but models have so far overlooked the mechanical effect of soft basal sediment. Here we use a three-dimensional model to investigate hydrological controls on a GrIS soft-bedded region.

Analysis of the microbial community and geochemistry of a sediment core from Great Slave Lake, Canada.

Sediment cores taken from Great Slave Lake, Canada, were analysed to investigate their metabolically active microbial populations and geochemistry. The amplification of cDNA detected metabolically active bacterial (50 separate bands) and archaeal (49 separate band) communities. The bacterial communities were further resolved indicating active actinobacterial and γ-proteobacterial communities (36 and 43 individual bands respectively).

Final results of a long-term, clinical follow-up in fatty liver patients.

Objective: There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk factors at the time of index liver biopsy important for survival and the development of cirrhosis and to describe the causes of death.

Material And Methods: Patients were linked through their personal identification number to the Danish National Registry of Patients and the Register of Causes of Death.

Histological characteristics and prognosis in patients with fatty liver.

Objective: The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis.

Long term prognosis of fatty liver: risk of chronic liver disease and death.

Background And Aims: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation.

Serum YKL-40 is increased in patients with hepatic fibrosis.

Background/aims: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis.

Distribution of liver haemosiderin iron in 187 patients with various types of hepatic diseases.

The purpose of this study was to evaluate the distribution of haemosiderin iron in various regions of the liver (central, intermediary and peripheral hepatocytes, Kupffer cells, portal macrophages and bile duct epithelial cells) in 174 patients with different hepatic diseases (alcoholic cirrhosis (n = 49), alcoholic steatosis (n = 60), non-alcoholic cirrhosis (n = 16), acute hepatitis (n = 20), clinically overt untreated hereditary haemochromatosis (n = 3), miscellaneous disorders (n = 26)), and in 13 subjects with a normal liver biopsy. Furthermore, the relationship between liver haemosiderin iron, biochemical iron status markers and biochemical liver tests was investigated. In haemochromatosis iron was consistently present in all examined regions of the liver, and in 43% of patients with alcoholic liver disease haemosiderin was present in at least one region of the liver lobule.

Six billion neurons lost in AIDS. A stereological study of the neocortex.

Human immunodeficiency virus type 1 (HIV1) is neurotropic. One of the morphological changes that is seen in patients with acquired immunodeficiency syndrome (AIDS) is cerebral atrophy affecting various structures including the neocortex. The cause of atrophy is not known.

Relationships among serum iron status markers, chemical and histochemical liver iron content in 117 patients with alcoholic and non-alcoholic hepatic disease.

Histochemical and chemical liver iron and iron status markers (serum (S-) ferritin, transferrin saturation) were determined in 109 patients with various types of liver disease (71 alcoholic, 38 non-alcoholic disease) and 8 normal subjects. In the series as a whole there was a significant correlation between histochemical hepatocyte iron and chemical iron (rho = 0.48, p = 0.

Quantification of liver fat using magnetic resonance spectroscopy.

Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.

Deposition of C3, the terminal complement complex and vitronectin in primary biliary cirrhosis and primary sclerosing cholangitis.

Characteristics of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are bile duct destruction and portal inflammation. Increased levels of circulating complement activation products are also present. This raises the possibility of involvement of complement-dependent cytotoxic mechanisms in the pathogenesis.