Case Report: Concomitant Diagnosis of Plasma Cell Leukemia in Patient With JAK2 Positive Myeloproliferative Neoplasm.

Plasma cell dyscrasias and myeloproliferative neoplasms (MPN) are hematologic malignancies arising from two distinct hematopoietic cell lineages. They rarely occur concomitantly. Here, we report a case of a patient with a recent diagnosis of a JAK2 V617F positive MPN who presented with a new diagnosis of plasma cell leukemia. The patient had presented to the hospital with a leukocytosis predominantly comprised of plasma cells, followed by work-up involving peripheral blood flow cytometry, FISH analysis, and bone-marrow biopsy. FISH analysis was suggestive of a common progenitor cell for these distinct hematologic malignancies. To our knowledge, this case represents the second reported instance of a concomitant JAK2 positive MPN with primary plasma cell leukemia

A Note on the Real Federal Deficit

Two alternative ways of extracting a measure of the real federal deficit from a measure of the nominal federal debt are discussed. One equates the real federal deficit to the real value of the change in the nominal debt. Aspects of the issues of crowding out, the use of the deficit as an indicator of fiscal policy, and the feasibility of permanent deficits are taken up to show that both measures are important and neither is merely the wrong way to calculate the other.

Megathrust Splay Faults at the Focus of the Prince William Sound Asperity, Alaska

[1] High-resolution sparker and crustal-scale air gun seismic reflection data, coupled with repeat bathymetric surveys, document a region of repeated coseismic uplift on the portion of the Alaska subduction zone that ruptured in 1964. This area defines the western limit of Prince William Sound. Differencing of vintage and modern bathymetric surveys shows that the region of greatest uplift related to the 1964 Great Alaska earthquake was focused along a series of subparallel faults beneath Prince William Sound and the adjacent Gulf of Alaska shelf. Bathymetric differencing indicates that 12 m of coseismic uplift occurred along two faults that reached the seafloor as submarine terraces on the Cape Cleare bank southwest of Montague Island. Sparker seismic reflection data provide cumulative Holocene slip estimates as high as 9 mm/yr along a series of splay thrust faults within both the inner wedge and transition zone of the accretionary prism. Crustal seismic data show that these megathrust splay faults root separately into the subduction zone décollement. Splay fault divergence from this megathrust correlates with changes in midcrustal seismic velocity and magnetic susceptibility values, best explained by duplexing of the subducted Yakutat terrane rocks above Pacific plate rocks along the trailing edge of the Yakutat terrane. Although each splay fault is capable of independent motion, we conclude that the identified splay faults rupture in a similar pattern during successive megathrust earthquakes and that the region of greatest seismic coupling has remained consistent throughout the Holocene

Prospectus, March 12, 2003

https://spark.parkland.edu/prospectus_2003/1007/thumbnail.jp

ERK/MAPK Signaling Drives Overexpression of the Rac-GEF, PREX1, in BRAF- and NRAS-Mutant Melanoma

Recently we identified that PREX1 overexpression is critical for metastatic but not tumorigenic growth in a mouse model of NRAS-driven melanoma. In addition, a PREX1 gene signature correlated with and was dependent on ERK mitogen-activated protein kinase (MAPK) activation in human melanoma cell lines. In the current study, the underlying mechanism of PREX1 overexpression in human melanoma was assessed. PREX1 protein levels were increased in melanoma tumor tissues and cell lines compared with benign nevi and normal melanocytes, respectively. Suppression of PREX1 by siRNA impaired invasion but not proliferation in vitro. PREX1-dependent invasion was attributable to PREX1-mediated activation of the small GTPase RAC1 but not the related small GTPase CDC42. Pharmacologic inhibition of ERK signaling reduced PREX1 gene transcription and additionally regulated PREX1 protein stability. This ERK-dependent upregulation of PREX1 in melanoma, due to both increased gene transcription and protein stability, contrasts with the mechanisms identified in breast and prostate cancers, where PREX1 overexpression was driven by gene amplification and HDAC-mediated gene transcription, respectively. Thus, although PREX1 expression is aberrantly upregulated and regulates RAC1 activity and invasion in these three different tumor types, the mechanisms of its upregulation are distinct and context-dependent

Genomic epidemiology of global carbapenemase-producing Escherichia coli, 2015–2017

We describe the global molecular epidemiology of 229 carbapenemase-producing Escherichia coli in 36 countries during 2015–2017. Common carbapenemases were oxacillinase (OXA) 181 (23%), New Delhi metallo-β-lactamase (NDM) 5 (20%), OXA-48 (17%), Klebsiella pneumoniae carbapenemase 2 (15%), and NDM-1 (10%). We identified 5 dominant sequence types (STs); 4 were global (ST410, ST131, ST167, and ST405), and 1 (ST1284) was limited to Turkey. OXA-181 was frequent in Jordan (because of the ST410-B4/H24RxC subclade) and Turkey (because of ST1284). We found nearly identical IncX3-blaOXA-181 plasmids among 11 STs from 12 countries. NDM-5 was frequent in Egypt, Thailand (linked with ST410-B4/H24RxC and ST167-B subclades), and Vietnam (because of ST448). OXA-48 was common in Turkey (linked with ST11260). Global K. pneumoniae carbapenemases were linked with ST131 C1/H30 subclade and NDM-1 with various STs. The global carbapenemase E. coli population is dominated by diverse STs with different characteristics and varied geographic distributions, requiring ongoing genomic surveillance.The Joint Programming Initiative on Antimicrobial Resistance–Canadian Institute Health Research program and the US National Institutes of Health.http://wwwnc.cdc.gov/eidam2023Medical Microbiolog

EEG microstate quantifiers and state space descriptors during anaesthesia in patients with postoperative delirium: a descriptive analysis.

Postoperative delirium is a serious sequela of surgery and surgery-related anaesthesia. One recommended method to prevent postoperative delirium is using bi-frontal EEG recording. The single, processed index of depth of anaesthesia allows the anaesthetist to avoid episodes of suppression EEG and excessively deep anaesthesia. The study data presented here were based on multichannel (19 channels) EEG recordings during anaesthesia. This enabled the analysis of various parameters of global electrical brain activity. These parameters were used to compare microstate topographies under anaesthesia with those in healthy volunteers and to analyse changes in microstate quantifiers and EEG global state space descriptors with increasing exposure to anaesthesia. Seventy-three patients from the Surgery Depth of Anaesthesia and Cognitive Outcome study (SRCTN 36437985) received intraoperative multichannel EEG recordings. Altogether, 720 min of artefact-free EEG data, including 210 min (29.2%) of suppression EEG, were analysed. EEG microstate topographies, microstate quantifiers (duration, frequency of occurrence and global field power) and the state space descriptors sigma (overall EEG power), phi (generalized frequency) and omega (number of uncorrelated brain processes) were evaluated as a function of duration of exposure to anaesthesia, suppression EEG and subsequent development of postoperative delirium. The major analyses involved covariate-adjusted linear mixed-effects models. The older (71 ± 7 years), predominantly male (60%) patients received a median exposure of 210 (range: 75-675) min of anaesthesia. During seven postoperative days, 21 patients (29%) developed postoperative delirium. Microstate topographies under anaesthesia resembled topographies from healthy and much younger awake persons. With increasing duration of exposure to anaesthesia, single microstate quantifiers progressed differently in suppression or non-suppression EEG and in patients with or without subsequent postoperative delirium. The most pronounced changes occurred during enduring suppression EEG in patients with subsequent postoperative delirium: duration and frequency of occurrence of microstates C and D progressed in opposite directions, and the state space descriptors showed a pattern of declining uncorrelated brain processes (omega) combined with increasing EEG variance (sigma). With increasing exposure to general anaesthesia, multiple changes in the dynamics of microstates and global EEG parameters occurred. These changes varied partly between suppression and non-suppression EEG and between patients with or without subsequent postoperative delirium. Ongoing suppression EEG in patients with subsequent postoperative delirium was associated with reduced network complexity in combination with increased overall EEG power. Additionally, marked changes in quantifiers in microstate C and in microstate D occurred. These putatively adverse intraoperative trajectories in global electrical brain activity may be seen as preceding and ultimately predicting postoperative delirium

Examining the impact of audience response systems on student performance in anatomy education: a randomized controlled trial

Background and Aims: Electronic audience response systems (ARSs) offer the potential to enhance learning and improve performance. However, objective research investigating the use of ARSs in undergraduate education has so far produced mixed, inconclusive results. We investigated the impact of ARSs on short- and long-term test performance, as well as student perceptions of the educational experience, when integrated into undergraduate anatomy teaching. Methods and Results: A cohort of 70 undergraduate medical students were randomly allocated to one of two groups. Both groups received the same anatomy lecture, but one group experienced the addition of ARSs. Multiple-choice tests were conducted before, immediately after the lecture and again 10 weeks later. Self-perceived post-lecture subject knowledge, confidence and enjoyment ratings did not differ between groups. Test performance immediately following the lecture improved when compared against baseline and was modestly but significantly superior in the group taught with ARSs (mean test score of 17.3/20 versus 15.6/20 in the control group, p = 0.01). Tests conducted 10 weeks after the lecture showed no difference between groups (p = 0.61) although overall a small improvement from the baseline test was maintained (p = 0.02). Conclusions: Whilst ARSs offer opportunities to deliver novel education experiences to students, an initial superiority over standard methods does not necessarily translate into longer-term gains in student performance when employed in the context of anatomy education. Key words: medical education; education methodology; education technology; audience response systems; anatomy

Focused Exhumation Along Megathrust Splay Faults in Prince William Sound, Alaska

Megathrust splay faults are a common feature of accretionary prisms and can be important for generating tsunamis during some subduction zone earthquakes. Here we provide new evidence from Alaska that megathrust splay faults have been conduits for focused exhumation in the last 5 Ma. In most of central Prince William Sound, published and new low-temperature thermochronology data indicate little to no permanent rock uplift over tens of thousands of earthquake cycles. However, in southern Prince William Sound on Montague Island, apatite (U–Th)/He ages are as young as 1.1 Ma indicating focused and rapid rock uplift. Montague Island lies in the hanging wall of the Patton Bay megathrust splay fault system, which ruptured during the 1964 M9.2 earthquake and produced ∼9 m of vertical uplift. Recent geochronology and thermochronology studies show rapid exhumation within the last 5 Ma in a pattern similar to the coseismic uplift in the 1964 earthquake, demonstrating that splay fault slip is a long term (3–5 my) phenomena. The region of slower exhumation correlates with rocks that are older and metamorphosed and constitute a mechanically strong backstop. The region of rapid exhumation consists of much younger and weakly metamorphosed rocks, which we infer are mechanically weak. The region of rapid exhumation is separated from the region of slow exhumation by the newly identified Montague Strait Fault. New sparker high-resolution bathymetry, seismic reflection profiles, and a 2012 Mw4.8 earthquake show this feature as a 75-km-long high-angle active normal fault. There are numerous smaller active normal(?) faults in the region between the Montague Strait Fault and the splay faults. We interpret this hanging wall extension as developing between the rapidly uplifting sliver of younger and weaker rocks on Montague Island from the essentially fixed region to the north. Deep seismic reflection profiles show the splay faults root into the subduction megathrust where there is probable underplating. Thus the exhumation and extension in the hanging wall are likely driven by underplating along the megathrust décollement, thickening in the overriding plate and a change in rheology at the Montague Strait Fault to form a structural backstop. A comparison with other megathrust splay faults around the world shows they have significant variability in their characteristics, and the conditions for their formation are not particularly unique