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Early detection of sepsis is challenging to achieve with current diagnostic methods, leading to expenditures of $27 billion annually in the United States with significant associated mortality. Various scoring systems have been proposed such as the sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria for identification of sepsis, but their sensitivities range from 60% to 70% when used in the emergency department triage. Other methods for the recognition of sepsis may rely on laboratory work, in addition to vitals monitoring, and are often outpaced by the development of sepsis. Automated alerts have not shown any reduction in mortality thus far. New technology may fill a critical gap in the early detection of sepsis. The ideal bedside screening device for would demonstrate rapid time to result, high portability, and high sensitivity to not miss cases, but also reasonable specificity to prevent provider fatigue from excessive false alerts. Non-invasive end-organ perfusion devices analyzing lactate and capillary refill time (CRT) tend to perform well in speed and portability, but may be less sensitive. Biomarker devices demonstrate a wider array of performance metrics. Those analyzing a single biomarker tend to be more sensitive but are less specific to the diagnosis of sepsis than technologies that assess multiple biomarkers, which in turn have lower sensitivity. Additionally, biomarker devices are generally invasive requiring blood samples, which may or may not be feasible in all patients especially when serial draws are needed. Sepsis is a complex disease process and most likely will require a combination of improved technology in addition to vital signs and high-risk patient history for better recognition. This review examines recent advances in the device-based early detection of sepsis between 2017 and 2020 with emphasis on bedside diagnostics, divided into markers of perfusion and biomarkers commonly implicated in sepsis. [ABSTRACT FROM AUTHOR]

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3. [ABSTRACT FROM AUTHOR]

Although other disciplines have explored sound as more than oral language, music, or noise, educational scholarship exploring everyday soundscapes still has room to grow. In this article, a team of transdisciplinary scholars from education, writing and rhetoric, and ethnomusicology explore new possibilities for sound in research and teaching by examining a cross-course assignment grounded in the sonic experiences of a residential, living-learning college community. Through examining student-produced compositions, we introduce a number of relevant insights into the relationships between space, community, and a pedagogy of aurality. [ABSTRACT FROM AUTHOR]

Objective: Bupropion is often categorized as a newer generation antidepressant and assessed with serotonin reuptake inhibitors as a lower risk than older tricyclic antidepressants (TCAs). The objective of this study was to compare outcomes in adolescent suicide from ingestions between bupropion and TCA medications. Study design: An analysis of the National Poison Data System for exposures coded “suspected suicide” in adolescents (age: 13-19) was undertaken for the years 2013-2016 and included TCAs or bupropion. We compared clinical effects, therapies and medical outcomes. Results: Over the four-year period there were 2253 bupropion and 1496 TCA adolescent suspected suicide calls. There was a significant linear increase in bupropion ingestions over the four years. Across all years, there were on average 189.2 (95% CI: 58.1-320.4; p = .01) more ingestions of bupropion than TCA. When comparing bupropion to a TCA, ingestions of bupropion were significantly more likely to be accompanied by seizure (30.7% vs 3.9%; p < .01), to be admitted (74.8% vs 61.6%; p < .01) and medical outcomes to be coded as a major outcome (19.3% vs 10.0%; p < .01). The number of cases with death or major clinical outcome for both increased over the four-year period. Ingestions of bupropion were less likely to have hypotension (2.7% vs 8.0%; p < .01) and less likely to be intubated (5.6% vs 16.4%; p < .01) as compared to ingestions of TCA. Conclusions: Adolescents who overdose on a single medication in a suicide attempt with bupropion have a statistically significant higher incidence of major outcomes and seizures. The risks of bupropion as a potential means of suicidal gesture by overdose must be considered, and weighed against its benefits and side effect profile when choosing an appropriate agent for the treatment of depression in adolescents. [ABSTRACT FROM AUTHOR]

Background: Migraine headaches are a common reason for pediatric emergency department (ED) visits. Small studies suggest the potential efficacy of sub-anesthetic doses of propofol for migraine with a favorable side effect profile and potentially decreased length of stay (LOS).Objective: The objective of this study was to compare the efficacy of low-dose propofol (LDP) to standard therapy (ST) in pediatric migraine treatment.Methods: We conducted a prospective, pragmatic randomized controlled trial from April 2014 through June 2016 in the ED at two pediatric hospitals. Patients aged 7-19 years were eligible if they were diagnosed with migraine by the emergency physician and had a presenting visual analog pain score (VAS) of 6-10. Primary outcome was the percent of pain reduction. Secondary outcomes were ED LOS, 24-h rebound headache, return visits to the ED, and adverse reactions.Results: Seventy-four patients were enrolled, but 8 were excluded, leaving 66 patients in the final analysis (36 ST, 30 LDP). Pain reduction was 59% for ST and 51% for LDP (p = 0.34) with 72.2% vs. 73.3% achieving a VAS ≤ 4 with initial therapy (p = 0.92). There was a nonsignificant trend toward shorter median LOS from drug administration to final disposition favoring propofol (79 min vs. 111 min; p = 0.09). Rebound headache was significantly more common in the ST vs. LDP group (66.7% vs. 25.0%; p = 0.01).Conclusions: LDP did not achieve better pain reduction than ST, however, LDP was associated with significantly fewer rebound headaches and a nonsignificant trend toward shorter median LOS from drug administration to disposition. [ABSTRACT FROM AUTHOR]

The authors convey their thoughts on social workers offering innovative care to children in acute psychiatric crisis. Topics mentioned include the prevalence of pediatric mental health disorders in the U.S., therapeutic alliance as a factor in predicting successful outcomes, and Child and Adolescent Psychiatry Consultation-Liaison Service at Oregon Health & Science University.

Blood and blood-component therapy triggers immunological reactions in recipients. Transfusion-related immunomodulation [TRIM] is an important complex biological immune reaction to transfusion culminating in immunosuppression. The mechanisms underlying TRIM include the presence of residual leukocytes and apoptotic cells, the transfusion of immunosuppressive cytokines either present in donor components or generated during blood processing, the transfer of metabolically active growth factor-loaded microparticles and extracellular vesicles and the presence of free hemoglobin or extracellular vesicle-bound hemoglobin. TRIM variables include donor-specific factors as well as processing variables. TRIM may explain, at least in part, the controversial negative clinical outcomes observed in cancer patients receiving transfusion in the context of curative-intent surgeries. The use of novel technologies including metabolomics and proteomics on stored blood may pave the way for a deeper understanding of TRIM in general and its impact on cancer progression. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus ( HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle ( LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. Methods LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 n m sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi- LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi- LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C ( ATAHC) and Hepatitis C Incidence and Transmission Study in prison ( HITS-p) cohorts. Results Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi- LVP level was independently associated with spontaneous HCV clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level. Conclusions Maxi- LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi- LVP level is an independent predictor of spontaneous clearance of acute HCV. [ABSTRACT FROM AUTHOR]

Background: Opioid abuse is a public health epidemic in the United States. Much literature has focused on the prescribing practices of physicians and opioid misuse by adults. However, there are limited data on the effect of opioid prescriptions on adolescent recreational ingestion of these medications.Objectives: The objective of this study was to assess for a relationship between opioid prescribing practices across the United States and adolescent opioid ingestion calls to poison centers.Methods: This was an observational study using the National Poison Data System. The study population consisted of poison center calls regarding adolescents between 2005 and 2010 in the database with a coding of "intentional abuse" and an opioid ingestion. National opioid prescription estimates were generated using nationally representative outpatient and inpatient databases.Results: There were 4186 adolescent opioid ingestion calls during the study period. There was a general increase between 2005 and 2010 in both teen opioid abuse calls (617 in 2005 to 782 in 2010) and national opioid prescriptions (approximately 78 million in 2005 to 108 million in 2010). For each opioid prescription increase per 100 persons per year, the annual teen opioid abuse calls increased by 1.8% (95% confidence interval 0.9-2.8%), equivalent to an absolute increase of about 0.04 to 0.05 calls per 100,000 teens annually.Conclusions: There appears to be an association between opioid prescriptions nationally and poison center calls for adolescent opioid ingestions. This is particularly important in this patient population because of impulsivity and early exposure to substance abuse. Providers should be aware of the nonmedical use of opioids by adolescents and educate patients accordingly. [ABSTRACT FROM AUTHOR]

This article examines two multimodal compositions produced with the support of a multiliteracy center. Each case involves multiple people, technologies, and resources. Distribution and emergence —two concepts borrowed from complex systems theory—help us understand the distinctive nature of the composing practices exemplified by these two cases. More specifically, the composing practices described here can be understood as examples of Pea's (1993) “distributed intelligence” and Lindquist, Hart-Davidson, and Grabill's (2010) “distributed invention.” These two examples prompt me to hypothesize about the way multiliteracy centers can maximize their potential to facilitate distributed and emergent composing practices. I suggest that multiliteracy centers should consider adopting policies, structures, and designs that facilitate connections, support long visits, attend to affective dimensions of relationships, and encourage play. [ABSTRACT FROM AUTHOR]

Background: Headaches are common in the pediatric population, and increase in prevalence with age. The abortive medications currently used have a number of potential side effects. Sodium valproate (VPA) has been shown to be effective for acute treatment in the adult population, but no data exist in the pediatric population.Objective: The objective of this study was to evaluate the effectiveness of VPA for acute pediatric headache in the emergency department.Methods: This was a retrospective case series of all patients <19 years of age treated in the pediatric emergency department (PED) at two tertiary care pediatric hospitals and with a final diagnosis of migraine or headache who received parenteral VPA. Data collected included patient demographics, pain reduction, length of stay, and final disposition.Results: From July 2010 to February 2014, there were 16 patients who received VPA for acute headache in the PED; 4 were excluded. Eighty-three percent were discharged home. Mean length of stay in the PED before VPA was 395 min, and 120 min after VPA administration. Patients achieved a 17% mean pain score reduction before VPA and approximately an additional 40% mean pain reduction after VPA infusion.Conclusions: VPA appears to be an effective agent for acute pediatric headache in this small series. Patients responded well to VPA in a relatively short amount of time. Further studies are needed to evaluate its effectiveness in combination with other first-line medications or as a single agent. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus (HCV) associates with lipoproteins to form “lipoviral particles” (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance. Methods HCV RNA, LVP ( d <1.07 g/ml) and non-LVP ( d >1.07 g/ml) fractions, were quantified in patients with HCV-G3 (n = 39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP + non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n = 51). Results In HCV-G3 LVP load correlated inversely with HDL-C (r = −0.421; p = 0.008), and apoE (r = −0.428; p = 0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R 2 = 16.2%; p = 0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 ( p <0.001). PCSK9 did not correlate with LDL-C in HCV-G3 or G1. Conclusions The inverse correlation of LVP with apoE in HCV-G3, compared to the reverse in HCV-G1 suggests HCV genotype-specific differences in apoE mediated viral entry. Lower PCSK9 and LDL concentrations imply upregulated LDLR activity in HCV-G3. [ABSTRACT FROM AUTHOR]

Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants ( n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression. [ABSTRACT FROM AUTHOR]

Where have all the emergency paediatric mental health patients gone during COVID-19? Abbreviation ED emergency department INTRODUCTION The novel coronavirus that results in COVID-19 has significantly impacted the global healthcare system and economy since first reported in December 2019.1 Many countries and states have enacted stay-at-home orders and implemented social distancing guidelines to mitigate disease transmission. B, paediatric mental health census gl DISCUSSION Emergency departments increasingly provide urgent mental health care for youth.3 This study demonstrates a dramatic decrease in utilisation of a paediatric ED for paediatric mental health following a COVID-19 stay-at-home order. [Extracted from the article]

Background & Aims Hepatitis C virus ( HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n-3) polyunsaturated fatty acids ( PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol® 40-80 mg) and n-3 PUFA (Omacor®1 g and 2-4 g) on HCV- RNA and lipoviral particles ( LVP) in difficult to treat prior non-responders. Methods Patients ( n = 60) were randomly allocated in a factorial design to: no active drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA + fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for 12 weeks and followed up to week 24. Comparison was made between fluvastatin ( n = 24) vs no fluvastatin ( n = 26) and n-3 PUFA high-dose ( n = 17) vs low-dose ( n = 17) vs none ( n = 16). The primary outcomes were change in total HCV- RNA, LVP and ALT at week 12 compared with baseline. Secondary outcome was change in interferon-gamma-inducible protein-10 ( IP10) as a measure of interferon activation. Results 35% had compensated cirrhosis and 45% were prior null responders. There was no significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased median IP10 concentration by −39 pg/ml (−111, 7.0 pg/ml Q1-Q3). Conclusions Fluvastatin and n-3 PUFAs have no effect on plasma HCV- RNA or LVP. The effect of low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a supplemental therapy to enhance interferon sensitivity. [ABSTRACT FROM AUTHOR]

Studies suggest that headache accounts for approximately 1% of pediatric emergency department ( ED) visits. ED physicians must distinguish between primary headaches, such as a tension or migraine, and secondary headaches caused by systemic disease including neoplasm, infection, or intracranial hemorrhage. A recent study found that 40% of children presenting to the ED with headache were diagnosed with a primary headache, and 75% of these were migraine. Once the diagnosis of migraine has been made, the ED physician is faced with the challenge of determining appropriate abortive treatment. This review summarizes the most recent literature on pediatric migraine with an emphasis on diagnosis and abortive treatment in the ED. [ABSTRACT FROM AUTHOR]

We present GoldMine, a methodology for generating assertions automatically in hardware. Our method involves a combination of data mining and static analysis of the register transfer level (RTL) design. The RTL design is first simulated to generate data about the design's dynamic behavior. The generated data is then mined for “candidate assertions” that are likely to be invariants. The data mining algorithm is a decision-tree-based supervised learning algorithm. These candidate assertions are then passed through a formal verification engine to filter out the spurious candidates. The assertions that are attested as true by the formal engine are system invariants. These are then evaluated by a process of designer ranking that is provided as feedback to the data mining engine. We demonstrate the scalability of GoldMine by showing assertion generation of the RTL of Sun's OpenSparc T2 many-threaded processor. Our results show that GoldMine can generate complex, high coverage assertions for sequential as well as combinational designs in RTL, thereby minimizing human effort in this process. GoldMine assertions distill the random input stimulus space and can be used for calibrating directed tests. They can be used in a regression test suite of an evolving RTL. They are also useful in providing differing perspectives from the designer, as well as hints to designers for manually writing assertions. [ABSTRACT FROM PUBLISHER]

Abstract: Context: Persistent pain after treatment for breast cancer (PPBCT) is a common side effect of breast cancer treatment, with prevalence as high as 50%. It is predominantly a neuropathic condition. Objectives: The aim of this cross-sectional, questionnaire-based study was to examine the emotional characteristics of patients with PPBCT in long-term breast cancer patients. A secondary objective was to characterize the risk factors and severity of that pain. Methods: From March 1, 2010 to April 9, 2010, long-term follow-up patients were invited to complete a questionnaire. This recorded their surgical and demographic data and ascertained whether they had PPBCT. If the patient had pain, she completed a range of validated self-report questionnaires and questions about the nature of the pain, including a visual analogue scale. Results: One hundred eleven patients completed the questionnaire; 33 (29.7%) patients reported chronic pain at a median time of 64 months postoperatively (interquartile range 54.25). Patients with persistent pain were not significantly more anxious (t105 =−0.369, P =0.713) or depressed (t105 =0.713, P =0.507) than patients without pain. Patients with constant pain compared with intermittent pain were significantly more anxious (t25 =−3.460, P =0.002). Preoperative pain conferred a fivefold increased risk of PPBCT (odds ratio [OR]=5.17, 95% confidence interval [CI]=1.79–14.97, P =0.002); chemotherapy conferred a threefold increased risk (OR=3.004, 95% CI=1.22–7.40, P =0.017). Conclusion: We have shown significant numbers of patients suffer from PPBCT. At a median time of 64.5 months, women with pain are not significantly more anxious or depressed than women without pain. Preoperative pain and chemotherapy have been highlighted as risk factors. [Copyright &y& Elsevier]

Background & Aims: Hepatitis C virus (HCV) interacts with apolipoproteins B (apoB) and E (apoE) to form infectious lipoviral particles (LVP). Response to peginterferon is influenced by interferon-stimulated genes (ISGs) and IL28B genotype. LDL cholesterol (LDL-C) also predicts interferon response, therefore we hypothesised that LVP may also be associated with interferon sensitivity. Methods: LVP (HCV RNA density ⩽1.07g/ml) and ‘non-LVP’ (d >1.07g/ml) were measured in 72 fasted HCV-G1 patients by iodixanol density gradient ultracentrifugation and the LVP ratio (LVP/LVP+non-LVP) was calculated. Fasting lipid profiles and apolipoproteins B and E were measured. Interferon-gamma-inducible protein 10kDa (IP10), a marker of ISGs, was measured by ELISA. Results: Complete early virological response (EVR) was associated with lower apoE (23.9±7.7 vs. 36.1±15.3mg/L, p =0.013), higher LDL-C (p =0.039) and lower LVP ratios (p =0.022) compared to null responders. In multivariate linear regression analysis, apoE was independently associated with LVP (R2 19.5%, p =0.003) and LVP ratio (p =0.042), and negatively with LDL-C (p <0.001). IP10 was significantly associated with ApoB (p =0.001) and liver stiffness (p =0.032). IL28B rs12979860 CC was associated with complete EVR (p =0.044), low apoE (CC 28±11 vs. CT/TT 35±13mg/L, p =0.048) and higher non-LVP (p =0.008). Logistic regression analysis indicated that patients with high LVP ratios were less likely to have EVR (odds ratio 0.01, p =0.018). Conclusions: In HCV-G1, interferon sensitivity is characterised by low LVP ratios and low apoE levels in addition to higher LDL-C and IL28B rs12979860 CC. Null-response is associated with increased LVP ratio. The association of apoE and LVP with peginterferon treatment response suggests that lipid modulation is a potential target to modify interferon sensitivity. [Copyright &y& Elsevier]

Atherosclerosis has been described as a liver disease of the heart . The liver is the central regulatory organ of lipid pathways but since dyslipidaemias are major contributors to cardiovascular disease and type 2 diabetes rather than liver disease, research in this area has not been a major focus for hepatologists. Virus–host interaction is a continuous co-evolutionary process involving the host immune system and viral escape mechanisms . One of the strategies HCV has adopted to escape immune clearance and establish persistent infection is to make use of hepatic lipid pathways. This review aims to: [•] update the hepatologist on lipid metabolism [•] review the evidence that HCV exploits hepatic lipid pathways to its advantage [•] discuss approaches to targeting host lipid pathways as adjunctive therapy. [ABSTRACT FROM AUTHOR]

Abstract: An array of new technologies has made it much easier for non-specialists to fabricate three-dimensional products ranging from clothes to plastic prototypes. This article explores the implications of these new developments for composition and rhetoric using a heuristic derived from earlier discussions of visual and multimodal rhetoric. Analysis of these discussions suggests that at least four kinds of arguments are made for new rhetorical modes: arguments from infrastructural accessibility, from rhetorical effectiveness, from cultural status, and from (de)specialization. Applying this schema to three-dimensional fabricated rhetoric reveals that three-dimensional rhetoric is increasingly available as an option to ordinary citizens, offers distinctive rhetorical opportunities, is valued by the broader culture outside the academy, and can be usefully understood through analytical frameworks regularly used by the field of composition and rhetoric. This article concludes that when placed in the hands of ordinary rhetors, three-dimensional rhetoric is potentially transformative and offers important cultural and political opportunities. By appropriating the rhetoric of fabricated objects, we can more effectively achieve the goals of equality and social justice. [ABSTRACT FROM AUTHOR]

Optimal timing for elective repair of total anomalous pulmonary venous return (TAPVR) in the case of an unobstructed anomalous pathway is unclear. All infants with a diagnosis of TAPVR as an isolated lesion who underwent surgical repair at Children's Hospital of Wisconsin from 1991 to 2007 were reviewed to assess location of drainage, presence of obstruction, age at presentation, age at surgery, death, need for extracorporeal membrane oxygenation (ECMO), length of hospital stay, length of mechanical ventilation (MV), and late pulmonary venous obstruction. A total of 65 patients were identified: 38 (59%) with supracardiac drainage, 10 (15%) with cardiac drainage, 11 (17%) with infracardiac drainage, and 6 (9%) with mixed drainage. For 39 (60%) of the 65 patients, obstruction was identified preoperatively. Three early and five late deaths occurred after surgery (12%), all involving patients with preoperative obstruction. Most of the late deaths (80%) involved patients who experienced recurrent obstruction. Of the 65 patients, 26 (40%) had no obstruction preoperatively, and none died, required ECMO support, or experienced late obstruction. For the 26 patients without obstruction, the timing of surgery was elective at the discretion of the supervising cardiologist. Among these 26 patients, 15 had surgery less than 10 days after presentation (median age, 18 days), and 53% of these 15 patients (8/15) had MV less than 5 days. In contrast, all 11 patients who had elective surgery more than 10 days after presentation (median age, 56 days) required MV for more than 5 days ( p = 0.007). Isolated TAPVR appears to be at the highest risk for death and late postoperative obstruction when obstruction is present preoperatively. Patients with unobstructive TAPVR do very well, but potential morbidity related to prolonged MV appears to be significantly reduced by early elective surgery. [ABSTRACT FROM AUTHOR]

Abstract: This article focuses on Ink, a Multiplayer Online Game (MOG) being developed at Michigan State University. The design of Ink reflects the developers’ understanding of writing pedagogy and rhetorical theory. Ink allows players to enter into complex rhetorical situations that include exigencies, audiences, and rhetorical purposes. The developers of Ink hope that placing players in these rhetorical situations will facilitate literacy learning while simultaneously providing a satisfying game experience. Players will hopefully learn while having fun. In order to test the effectiveness of Ink as a game and learning environment, the authors designed a small-scale preliminary study with a focus group of student playtesters. The study was designed to answer three fundamental questions: Will players write? Will players have fun? Will players learn? The study generated some evidence that the answer to all three questions is “yes.” [Copyright &y& Elsevier]

Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium. CMR was performed in nine persons affected with IDC/FDC. Healthy controls came from the general population (n = 6) or were unaffected family members of FDC patients (n = 3) without signs or symptoms of IDC/FDC or any structural cardiac abnormalities. The myocardial partition coefficient for gadolinium contrast (λGd) was determined by T1 measurements. LV shape and function and MBF were assessed by standard CMR methods. λGd was elevated in LDC/FDC patients vs. healthy controls (λGd = 0.56 ± 0.15 vs. 0.41 ± 0.06; P = 0.002), and correlated with LV enlargement (r = 0.61 for λGd vs. end-diastolic volume indexed by height; P < 0.01) and with ejection fraction (r = -0.80; P < 0.001). The extracellular volume fraction was higher in IDC patients than in healthy controls (0.31 ± 0.05 vs. 0.24 ± 0.03; P = 0.002). Resting MBF was lower in IDC patients (0.64 ± 0.13 vs. 0.91 ± 0.22; P = 0.01) than unaffected controls and correlated with both the partition coefficient (r = -0.57; P = 0.012) and the extracellular volume fraction (r = -0.56; P = 0.019). The expansion of the extracellular space correlated with reduced MBF and ventricular dilation. Expansion of the extracellular matrix may be a key contributor to contractile dysfunction in IDC patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effects of intravenous magnesium on converting acute onset atrial fibrillation to sinus rhythm, reducing ventricular response and risk of bradycardia. Design and data sources: Randomised controlled trials evaluating intravenous magnesium to treat acute onset atrial fibrillation from MEDLINE (1966 to 2006), EMBASE (1990 to 2006) and Cochrane Controlled Trials Register without language restrictions. Review methods: Two researchers independently performed the literature search and data extraction. Results: 10 randomised controlled trials, including a total of 515 patients with acute onset atrial fibrillation, were considered. Intravenous magnesium was not effective in converting acute onset atrial fibrillation to sinus rhythm when compared to placebo or an alternative antiarrhythmic drug. When compared to placebo, adding intravenous magnesium to digoxin increased the proportion of patients with a ventricular response <100 beats/min (58.8% vs 32.6%; OR 3.2, 95% CI 1.93 to 5.42; p<0.001). When compared to calcium antagonists or amiodarone, intravenous magnesium was less effective in reducing the ventricular response (21.4% vs 58.5%; OR 0.19, 95% CI 0.09 to 0.44; p<0.001) but also less likely to induce significant bradycardia or atrioventricular block (0% vs 9.2%; OR 0.13, 95% CI 0.02 to 0.76; p=0.02). The use of intravenous magnesium was associated with transient minor symptoms of flushing, tingling and dizziness in about 17% of the patients (OR 14.5, 95% CI 3.7 to 56.7; p<0.001). Conclusions: Adding intravenous magnesium to digoxin reduces fast ventricular response in acute onset atrial fibrillation. The effect of intravenous magnesium on the ventricular rate and its cardiovascular side effects are less significant than other calcium antagonists or amiodarone. Intravenous magnesium can be considered as a safe adjunct to digoxin in controlling the ventricular response in atrial fibrillation. [ABSTRACT FROM AUTHOR]

We have defined regions of the skeletal muscle ryanodine receptor (RyR1) essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and for the organization of DHPR into tetrad arrays by expressing RyR1-RyR3 chimerae in dyspedic myotubes. RyR1-RyR3 constructs bearing RyR1 residues 1-1681 restored wild-type DHPR tetrad arrays and, in part, skeletal-type excitation-contraction (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca2+ currents (retrograde signaling) to WI RyR1 levels. Within this region, the D2 domain (amino acids 1272-1455), although ineffective on its own, dramatically enhanced the formation of tetrads and EC coupling rescue by constructs that otherwise are only partially effective. These findings suggest that the orthograde signal and DHPR tetrad formation require the contributions of numerous RyR regions. Surprisingly, we found that RyR3, although incapable of supporting EC coupling or tetrad formation, restored a significant level of Ca2+ current, revealing a functional interaction with the skeletal muscle DHPR. Thus, our data support the hypotheses that (i) the structural/functional link between RyR1 and the skeletal muscle DHPR requires multiple interacting regions, (ii) the D2 domain of RyR1 plays a key role in stabilizing this interaction, and (iii) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein- protein interactions. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the potential beneficial and adverse effects of frusemide to prevent or treat acute renal failure in adults. Design Meta-analysis of randomised controlled trials. Data sources Cochrane controlled trials register (2005 issue 4), Embase, and Medline (1966 to 1 February 2006), without language restrictions. Review methods Two reviewers checked the quality of the studies and independently extracted data. Results Nine randomised controlled trials totalling 849 patients with or at risk of acute renal failure were included. Outcome measures not significantly different after frusemide treatment were in-hospital mortality (relative risk 1.11, 95% confidence interval 0.92 to 1.33), risk for requiring renal replacement therapy or dialysis (0.99, 0.80 to 1.22), number of dialysis sessions required (weight mean difference -0.48 sessions, -1.45 to 0.50), and proportion of patients with persistent oliguria (urine output <500 ml/day: 0.54, 0.18 to 1.61). Stratifying studies that used frusemide to prevent or treat acute renal failure did not change die results on mortality (relative risk ratio 2.10, 95% confidence interval 0.67 to 6.63) and die risk for requiring dialysis (4.12, 0.46 to 37.2). Evidence suggested an increased risk of temporary deafness and tinnitus in patients treated with high doses of frusemide (relative risk 3.97, 95% confidence interval 1.00 to 15.78). Conclusions Frusemide is not associated with any significant clinical benefits in die prevention and treatment of acute renal failure in adults. High doses may be associated with an increased risk of ototoxicity [ABSTRACT FROM AUTHOR]

Presents information on the characterization of high-voltage 4H-Silicon carbide (SiC) Schottky diodes under high gamma irradiation. Critical electric field strength of SiC; Schematic cross section of the irradiated diodes; Typical forward characteristics of the difference Schottky diodes before and after each radiation dose.

Provides insights into the overgrazed and undermanaged arid regions of the U.S. Impact of desertification on the ability of the arid land to support life; Symptoms which are manifested by an arid area suffering from diversification; Factors that contribute to the diversification of the Navajo Indian reservation.

Part II. Examines the economic and environmental effects of water use in arid lands of the western United States. Wellton-Mohawk Irrigation District in southwestern Arizona; Santa Cruz Basin in southcentral Arizona; San Joaquin Basin in California. INSET: FEDERAL DISASTER RELIEF.

Focuses on the development of the arid region of western United States. Agricultural output of the arid West in 1977; Factors that contributed to the region's development; Solution to the land's aridity.

Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1–2 months later, suggesting a public health opportunity for intervention. This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges. [ABSTRACT FROM AUTHOR]

Summary: Background: Seladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory and anti‐pruritic effects. Aims: To evaluate the long‐term safety and efficacy of seladelpar in patients with PBC. Methods: In an open‐label, international, long‐term extension study, patients with PBC completing seladelpar lead‐in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non‐alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. Results: There were no serious treatment‐related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. Conclusions: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16. [ABSTRACT FROM AUTHOR]

Background: The assessment of capillary refill time (CRT) is a common physical examination technique. However, despite its importance and its widespread use, there is little standardization, which can lead to inaccurate assessments.Objective: In this article, we assessed how different physicians estimate CRT. We hypothesized that when different physicians are presented with the same recordings of CRT, clinicians will, on average, provide different CRT estimates.Methods: Using recordings of different fingertip compressions, physicians assessed and documented when capillary refill had returned to normal. Videos were recorded of the fingertips only, with no other identifying markers or subject characteristics provided. Videos were shown at one-quarter speed to allow time for recognition and response to the capillary refill. The primary outcome was physician estimates of CRT for each video recording.Results: An analysis of variance regression revealed significant differences in physician estimates of CRT when examining the same CRT videos from 34 subjects. Further regression analyses reveal the importance of controlling for the physician that is examining the patient when predicting a patient's CRT.Conclusions: Results indicate that some physicians gave, on average, slower CRT estimates, whereas others gave, on average, faster CRT estimates. Objective approaches and innovations in assessment of capillary refill have the potential to increase the diagnostic accuracy of this important clinical examination finding. [ABSTRACT FROM AUTHOR]

Background: Pediatric emergency department (PED) visits among children and adolescents with acute mental health needs have increased over the past decade with long wait times in the PED awaiting disposition.Objective: The objective of this study was to evaluate the effect of a new pediatric mental health liaison program with the hypothesis that this model reduces length of stay (LOS) and hospitalization rates among pediatric mental health patients.Methods: This was a pre- and postintervention retrospective study of the year prior to (June 2012-June 2013) and the year after (October 2013-October 2014) implementation of a new PED psychiatric team. All patients aged 1-18 years with a mental health International Classification of Diseases-9(th) Revision code were included. Patients who did not receive a Psychiatry consult in the PED were excluded.Results: There were 83 encounters in the year prior to and 129 encounters in the year after the implementation of the liaison program. There was an increase in the suicidality of mental health patients during this time. There was a significant decrease in mean PED LOS of 27% (95% confidence interval [CI] 0-46%; p = 0.05) from pre- to postintervention period. The decrease in the proportion of patients admitted/transferred to an inpatient psychiatric facility in the postintervention year was statistically significant (odds ratio 0.35; 95% CI 0.17-0.71; p < 0.01).Conclusions: The use of a dedicated child psychiatrist and mental health social worker to the PED results in significantly decreased LOS and need for admission without any change in return visit rate. Larger, multicenter studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6–9, 10–12, 13–15, and 16–18. Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population. [ABSTRACT FROM AUTHOR]

A new cell topology named the dodecagonal (a polygon with twelve sides, short for Dod) cell is proposed to optimize the gate-to-drain capacitance ( C gd ) and reduce the specific ON-resistance ( R on , sp ) of 4H-SiC planar power MOSFETs. The Dod and the octagonal (Oct) cells are used in the layout design of the 650 V SiC MOSFETs in this work. The experimental results confirm that the Dod-cell MOSFET achieves a 2.2× lower R on , sp , 2.1× smaller high-frequency figure of merit (HF-FOM), higher turn on/off dv/dt, and 29% less switching loss than the fabricated Oct-cell MOSFET. The results demonstrate that the Dod cell is an attractive candidate for high-frequency power applications. [ABSTRACT FROM AUTHOR]

Background: Monitoring of capillary refill time (CRT) is a common bedside assessment used to ascertain peripheral perfusion in a patient for a vast array of conditions. The literature has shown that a change in CRT can be used to recognize life-threatening conditions that cause decreased perfusion, such as sepsis, and aid in resuscitation. The current practice for calculating CRT invites subjectivity and produces a highly variable result. Innovative technology may be able to standardize this process and provide a reliable and accurate value for use in diagnostics and treatment. This study aimed to assess a new technology (DCR by ProMedix Inc.) for rapid, bedside, and noninvasive detection of CRT. Methods: This was a secondary analysis of a prospective observational study evaluating the accuracy of new technology towards CRT-guided diagnosis of sepsis. It was carried out in the adult emergency departments (ED) of an academic tertiary care medical center. Patients seeking care in the ED were determined eligible if they were > 18 years in age and exhibited chief complaints suggestive of possible sepsis. The CRT produced by the technology was compared to the gold standard manual waveform assessment. Results: 218 consecutive subject enrollments were included and multiple measurements were made on each patient. Data with irregular waveforms were excluded. A total of 692 waveforms were evaluated for CRT values by a pair of trained PhD biomedical engineers. The average age of the cohort was 50.62 and 51.4% female. Results showed a Pearson correlation coefficient of 0.91 for the device CRT compared to the CRT gold standard. The Pearson correlation coefficient for the two independent engineering review of the waveform data was 0.98. This device produces accurate, consistent results and eliminates the subjectivity of CRT measurements that is in practice currently. [ABSTRACT FROM AUTHOR]

We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk of disease progression (alkaline phosphatase [ALP] ≥1.67xupper limit of normal [ULN]) who were receiving or intolerant to ursodeoxycholic acid. In this 52-week, phase II, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5 mg/day (n = 53) or 10 mg/day (n = 55) or assigned to 2 mg/day (n = 11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10 mg/day. The primary efficacy endpoint was ALP change from baseline to Week 8. Mean baseline ALP was 300, 345, and 295 U/L in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean ± standard error ALP reductions from baseline were 26 ± 2.8%, 33 ± 2.6%, and 41 ± 1.8% in the 2 mg (n = 11), 5 mg (n = 49), and 10 mg (n = 52) cohorts (all p ≤0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, composite response (ALP <1.67xULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events, and 4 patients discontinued due to adverse events. Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus. NCT02955602 2016-002996-91 Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10 mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores. [Display omitted] • Seladelpar (2, 5, 10 mg) was assessed in patients with primary biliary cholangitis. • ALP was dose-dependently reduced by 23% to 43% at Week 12. • ALP was normalized in 33% of patients in the 10 mg cohort at Week 52. • Up to 67% of patients met the composite ALP and bilirubin endpoint at Week 52. • Seladelpar was safe, with no treatment-related serious adverse events or deaths. [ABSTRACT FROM AUTHOR]