Predictors of Acute Liver Failure in Patients With Acute Hepatitis A: An Analysis of the 2016-2018 San Diego County Hepatitis A Outbreak.

Background:Between 2016 and 2018, San Diego County experienced a hepatitis A outbreak with a historically high mortality rate (3.4%) that highlighted the need for early recognition of those at risk of developing acute liver failure (ALF). Methods:A retrospective case series of adult hospitalized patients with acute hepatitis A. Results:One hundred six patients with hepatitis A were studied, of whom 11 (10.4%) developed ALF, of whom 7 (6.6%) died. A history of alcohol abuse, hyperbilirubinemia, hypoalbuminemia, hyponatremia, and anemia were associated with increased odds of developing ALF. Initial Maddrey's and Model of End-Stage Liver Disease Sodium (MELD-Na) scores were also associated with the development of ALF. Multivariable analysis showed that a higher initial MELD-Na score (odds ratio [OR], 1.205; 95% confidence interval [CI], 1.018-1.427) and a lower initial serum albumin concentration (OR, 9.35; 95% CI, 1.15-76.9) were associated with increased odds of developing ALF. Combining serum albumin and MELD-Na (SAM; C-statistic, 0.8878; 95% CI, 0.756-0.988) yielded a model that was not better than either serum albumin (C-statistic, 0.852; 95% CI, 0.675-0.976) or MELD-Na (C-statistic, 0.891; 95% CI, 0.784-0.968; P = .841). Finally, positive blood cultures were more common among patients with ALF compared with those without ALF (63.6% vs 4.3%; P < .00001). Conclusions:Hypoalbuminemia was associated with an increased risk of ALF in patients with acute hepatitis A. Positive blood cultures and septic shock as a cause of death were common among patients with ALF. Providers caring for patients with acute hepatitis A should monitor for early signs of sepsis and consider empiric antibiotics, especially in patients presenting with hypoalbuminemia

Experimental evidence that ovary and oviducal gland extracts influence male agonistic behavior in squids

Author Posting. © Marine Biological Laboratory, 2004. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 206 (2004): 1-3.Recent investigations of sensory and behavioral cues that initiate sexual selection processes in the squid Loligo pealeii have determined that egg capsules deposited on the substrate provide a strong visual and chemotactile stimulus to males, even in the absence of females (1, 2, 3). The visual stimulus of egg capsules attracts males to the eggs, and when the males touch the eggs, they encounter a chemical stimulus that leads to highly aggressive fighting behavior. We have recently demonstrated that egg capsule extracts implanted in artificial egg capsules elicit this aggressive behavior (4). In this communication, we present evidence that the salient chemical factor originates in the ovary and perhaps the oviducal gland of the female reproductive tract

2003 Manifesto on the California Electricity Crisis

The authors, an ad-hocgroup of professionals with experience in regulatory and energy economics, share a common concern with the continuing turmoil facing the electricity industry ("the industry") in California. Most ofthe authorsendorsed the first California Electricity Manifesto issued on January 25, 2001. Almost two years have passed since that first Manifesto. While wholesale electric prices have moderated and California no longer faces the risk of blackouts, in many ways the industry is in worse shape now than it was at the start of 2001. As a result, the group of signatories continues to have a deep concern with the conflicting policy directions being pursued for the industry at both the State and Federal levels of government and the impact the uncertainties associated with these conflicting policies will have, long term, on the economy of California. Theauthorshave once again convened under the auspices of the Institute of Management, Innovation and Organization at the University of California, Berkeley, to put forward ourtheir ideas on a basic set of necessary policies to move the industry forward for the benefit of all Californians and the nation. The authors point out that theydo not pretend to be "representative." They do bring, however, a very diverse range of backgrounds and expertise.Technology and Industry, Regulatory Reform

Tree-mycorrhizal associations detected remotely from canopy spectral properties

A central challenge in global ecology is the identification of key functional processes in ecosystems that scale, but do not require, data for individual species across landscapes. Given that nearly all tree species form symbiotic relationships with one of two types of mycorrhizal fungi – arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) fungi – and that AM- and ECM-dominated forests often have distinct nutrient economies, the detection and mapping of mycorrhizae over large areas could provide valuable insights about fundamental ecosystem processes such as nutrient cycling, species interactions, and overall forest productivity. We explored remotely sensed tree canopy spectral properties to detect underlying mycorrhizal association across a gradient of AM- and ECM-dominated forest plots. Statistical mining of reflectance and reflectance derivatives across moderate/high-resolution Landsat data revealed distinctly unique phenological signals that differentiated AM and ECM associations. This approach was trained and validated against measurements of tree species and mycorrhizal association across ~130 000 trees throughout the temperate United States. We were able to predict 77% of the variation in mycorrhizal association distribution within the forest plots (P \u3c 0.001). The implications for this work move us toward mapping mycorrhizal association globally and advancing our understanding of biogeochemical cycling and other ecosystem processes

Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers

Background: Molecular characterization of tumors has been critical for identifying important genes in cancer biology and for improving tumor classification and diagnosis. Long non-coding RNAs, as a new, relatively unstudied class of transcripts, provide a rich opportunity to identify both functional drivers and cancer-type-specific biomarkers. However, despite the potential importance of long non-coding RNAs to the cancer field, no comprehensive survey of long non-coding RNA expression across various cancers has been reported. Results: We performed a sequencing-based transcriptional survey of both known long non-coding RNAs and novel intergenic transcripts across a panel of 64 archival tumor samples comprising 17 diagnostic subtypes of adenocarcinomas, squamous cell carcinomas and sarcomas. We identified hundreds of transcripts from among the known 1,065 long non-coding RNAs surveyed that showed variability in transcript levels between the tumor types and are therefore potential biomarker candidates. We discovered 1,071 novel intergenic transcribed regions and demonstrate that these show similar patterns of variability between tumor types. We found that many of these differentially expressed cancer transcripts are also expressed in normal tissues. One such novel transcript specifically expressed in breast tissue was further evaluated using RNA in situ hybridization on a panel of breast tumors. It was shown to correlate with low tumor grade and estrogen receptor expression, thereby representing a potentially important new breast cancer biomarker. Conclusions: This study provides the first large survey of long non-coding RNA expression within a panel of solid cancers and also identifies a number of novel transcribed regions differentially expressed across distinct cancer types that represent candidate biomarkers for future research

Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance

Extra-ocular muscle MRI in genetically-defined mitochondrial disease

Conventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease

Cyclophosphamide- metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study

Abstract Introduction Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. Methods We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. Results In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. Conclusions These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500