On the Differences Between Blood and Red Ink: A Second Look at the Policy Arguments for the Abrogation of the Economic Loss Rule in Consumer Litigation

The long-running debate concerning the scope of the economic loss rule\u27 presents issues which are important in themselves and as illustrations of broader questions.2 Litigants and commentators champion the opposing schools of thought through close analysis of precedent;3 the exchange of views as to the nature of tort law and contract law;4 and occasionally, economic analysis

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections

Large-scale discovery of enhancers from human heart tissue.

Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart

The long-term evolution of the spin, pulse shape, and orbit of the accretion-powered millisecond pulsar SAX J1808.4-3658

We present a 7 yr timing study of the 2.5 ms X-ray pulsar SAX J1808.4-3658, an X-ray transient with a recurrence time of ~2 yr, using data from the Rossi X-ray Timing Explorer covering 4 transient outbursts (1998-2005). We verify that the 401 Hz pulsation traces the spin frequency fundamental and not a harmonic. Substantial pulse shape variability, both stochastic and systematic, was observed during each outburst. Analysis of the systematic pulse shape changes suggests that, as an outburst dims, the X-ray "hot spot" on the pulsar surface drifts longitudinally and a second hot spot may appear. The overall pulse shape variability limits the ability to measure spin frequency evolution within a given X-ray outburst (and calls previous nudot measurements of this source into question), with typical upper limits of |nudot| < 2.5x10^{-14} Hz/s (2 sigma). However, combining data from all the outbursts shows with high (6 sigma) significance that the pulsar is undergoing long-term spin down at a rate nudot = (-5.6+/-2.0)x10^{-16} Hz/s, with most of the spin evolution occurring during X-ray quiescence. We discuss the possible contributions of magnetic propeller torques, magnetic dipole radiation, and gravitational radiation to the measured spin down, setting an upper limit of B < 1.5x10^8 G for the pulsar's surface dipole magnetic field and and Q/I < 5x10^{-9} for the fractional mass quadrupole moment. We also measured an orbital period derivative of Pdot = (3.5+/-0.2)x10^{-12} s/s. This surprising large Pdot is reminiscent of the large and quasi-cyclic orbital period variation observed in the so-called "black widow" millisecond radio pulsars, supporting speculation that SAX J1808.4-3658 may turn on as a radio pulsar during quiescence. In an appendix we derive an improved (0.15 arcsec) source position from optical data.Comment: 22 pages, 10 figures; accepted for publication in Ap

Invasive Group A Streptococcal Infection in High School Football Players, New York City, 2003

After being notified that 2 high school football teammates were hospitalized with confirmed or suspected invasive group A streptococcal infections, we conducted an investigation of possible spread among other team members. This investigation highlights a need for guidelines on management of streptococcal and other infectious disease outbreaks in team sport settings

Intensive swift and LCO monitoring of PG 1302–102 : active galactic nucleus disk reverberation mapping of a supermassive black hole binary candidate

This work is supported by the NANOGrav National Science Foundation Physics Frontiers Center award No. 2020265 and NASA grant 80NSSC24K0251. Research at UC Irvine was supported by NSF grant AST-1907290. E.M.C. gratefully acknowledges support from the NSF through grant No. AST-1909199.We present an intensive multiwavelength monitoring campaign of the quasar PG 1302−102 with Swift and the Las Cumbres Observatory network telescopes. At z ∼ 0.3, it tests the limits of the reverberation mapping (RM) technique in probing the accretion disk around a supermassive black hole (SMBH) and extends the parameter space to high masses and high accretion rates. This is also the first time the RM technique has been applied to test disk structures predicted in the SMBH binary model that has been suggested for this source. PG 1302−102 was observed at a ∼daily cadence for ∼9 months in 14 bands spanning from X-ray to UV and optical wavelengths, and it shows moderate to significant levels of variability correlated between wavelengths. We measure the interband time lags, which are consistent with a τ ∝ λ 4/3 relation as expected from standard disk reprocessing, albeit with large uncertainties. The disk size implied by the lag spectrum is consistent with the expected disk size for its black hole mass within uncertainties. While the source resembles other reverberation-mapped active galactic nuclei in many respects, and we do not find evidence supporting the prevalent hypothesis that it hosts an SMBH binary, we demonstrate the feasibility of studying SMBH binaries from this novel angle and suggest possibilities for the LSST Deep Drilling Fields.Peer reviewe

Clinical course, costs and predictive factors for response to treatment in carpal tunnel syndrome: The PALMS study protocol

Background Carpal tunnel syndrome (CTS) is the most common neuropathy of the upper limb and a significant contributor to hand functional impairment and disability. Effective treatment options include conservative and surgical interventions, however it is not possible at present to predict the outcome of treatment. The primary aim of this study is to identify which baseline clinical factors predict a good outcome from conservative treatment (by injection) or surgery in patients diagnosed with carpal tunnel syndrome. Secondary aims are to describe the clinical course and progression of CTS, and to describe and predict the UK cost of CTS to the individual, National Health Service (NHS) and society over a two year period. Methods/Design In this prospective observational cohort study patients presenting with clinical signs and symptoms typical of CTS and in whom the diagnosis is confirmed by nerve conduction studies are invited to participate. Data on putative predictive factors are collected at baseline and follow-up through patient questionnaires and include standardised measures of symptom severity, hand function, psychological and physical health, comorbidity and quality of life. Resource use and cost over the 2 year period such as prescribed medications, NHS and private healthcare contacts are also collected through patient self-report at 6, 12, 18 and 24 months. The primary outcome used to classify treatment success or failures will be a 5-point global assessment of change. Secondary outcomes include changes in clinical symptoms, functioning, psychological health, quality of life and resource use. A multivariable model of factors which predict outcome and cost will be developed. Discussion This prospective cohort study will provide important data on the clinical course and UK costs of CTS over a two-year period and begin to identify predictive factors for treatment success from conservative and surgical interventions

Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability

ABSTRACT Enzymatic conversion of hydrocodone to hydromorphone is catalyzed by cytochrome P450 2D6, which is inactive in about 7% of Caucasians [poor metabolizers (PMs)] and can be inhibited by quinidine pretreatment in the remainder [extensive metabolizers (EMs)]. If hydromorphone, having a substantially higher -receptor affinity than hydrocodone, contributes importantly to the physiological and subjective effects of oral hydrocodone, then PMs should be less responsive to the same doses, and quinidine pretreatment should cause EMs to temporarily respond as PMs. Seventeen EMs and 8 PMs who previously responded positively to hydromorphone s.c. received placebo and hydrocodone (10 mg, 15 mg and 22.5 mg p.o.) and were retested with their favorite dose after placebo or quinidine (100 mg) pretreatment; physiological and subjective measures were collected at base line and four times after drug administration, and urine was collected for 8 hr. EMs and PMs were equally responsive to oral hydrocodone, and quinidine had no consistent effect on their responses, even though quinidine abolished the pre-existing metabolic differences in hydromorphone production, as measured in urine. These data suggest only a small role of hydromorphone in eliciting abuserelated responses to oral hydrocodone. The genetic polymorphism of the drug-metabolizing enzyme CYP2D6 results in phenotypic differences in the pharmacokinetics of many drugs One drug for which there is evidence of phenotypic differences in response is codeine, which is O-demethylated by CYP2D6 to form morphine Hydrocodone differs structurally from codeine in that the C6-position is occupied by a keto-group, and thus the drug does not undergo the extensive conjugation (Ͼ60%) that codeine undergoe

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms