eMental Health Bridges Project: A Web Site Development Project to Provide Needed Mental and Physical Health Information to People with Serious Mental Illness [English and Spanish versions]

A Spanish translation of this publication is available to download under Additional Files below. The eMental Health Bridges project will promote health literacy by developing, testing, and implementing: 1) eMH4me training modules to provide guidance for individuals with SMI on web-based information searching, judging source and site credibility, and interpreting data; and 2) web site prototypes that will serve as a connection to essential physical health information for individuals living with SMI. eMental Health Bridges will embrace user experience and design accommodations required for individuals with SMI to benefit fully from eHealth resources

Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis (OA) is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor (EGFR) signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus (DMM) to induce OA in two mouse models with reduced EGFR activity, one with genetic modification (Egfr Wa5/+ mice) and the other one with pharmacological inhibition (gefitinib treatment). Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 (MMP13), the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α (HIF2α), a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation

Long-Term Effects of Chronic Intermittent Ethanol Exposure in Adolescent and Adult Rats: Radial-Arm Maze Performance and Operant Food Reinforced Responding

Background: Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats. Methodology/Principal Findings: Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward ntegration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory. Conclusions/Significance: These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future research

Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus

Exposure to Staphylococcus aureus has a variety of outcomes, from asymptomatic colonization to fatal infection. Strong evidence suggests that host genetics play an important role in susceptibility, but the specific host genetic factors involved are not known. The availability of genome-wide single nucleotide polymorphism (SNP) data for inbred Mus musculus strains means that haplotype association mapping can be used to identify candidate susceptibility genes. We applied haplotype association mapping to Perlegen SNP data and kidney bacterial counts from Staphylococcus aureus-infected mice from 13 inbred strains and detected an associated block on chromosome 7. Strong experimental evidence supports the result: a separate study demonstrated the presence of a susceptibility locus on chromosome 7 using consomic mice. The associated block contains no genes, but lies within the gene cluster of the 26-member extended kallikrein gene family, whose members have well-recognized roles in the generation of antimicrobial peptides and the regulation of inflammation. Efficient mixed-model association (EMMA) testing of all SNPs with two alleles and located within the gene cluster boundaries finds two significant associations: one of the three polymorphisms defining the associated block and one in the gene closest to the block, Klk1b11. In addition, we find that 7 of the 26 kallikrein genes are differentially expressed between susceptible and resistant mice, including the Klk1b11 gene. These genes represent a promising set of candidate genes influencing susceptibility to Staphylococcus aureus

Evolution of circular, non-equatorial orbits of Kerr black holes due to gravitational-wave emission: II. Inspiral trajectories and gravitational waveforms

The inspiral of a ``small'' ($\mu \sim 1-100 M_\odot$) compact body into a ``large'' ($M \sim 10^{5-7} M_\odot$) black hole is a key source of gravitational radiation for the space-based gravitational-wave observatory LISA. The waves from such inspirals will probe the extreme strong-field nature of the Kerr metric. In this paper, I investigate the properties of a restricted family of such inspirals (the inspiral of circular, inclined orbits) with an eye toward understanding observable properties of the gravitational waves that they generate. Using results previously presented to calculate the effects of radiation reaction, I assemble the inspiral trajectories (assuming that radiation reacts adiabatically, so that over short timescales the trajectory is approximately geodesic) and calculate the wave generated as the compact body spirals in. I do this analysis for several black hole spins, sampling a range that should be indicative of what spins we will encounter in nature. The spin has a very strong impact on the waveform. In particular, when the hole rotates very rapidly, tidal coupling between the inspiraling body and the event horizon has a very strong influence on the inspiral time scale, which in turn has a big impact on the gravitational wave phasing. The gravitational waves themselves are very usefully described as ``multi-voice chirps'': the wave is a sum of ``voices'', each corresponding to a different harmonic of the fundamental orbital frequencies. Each voice has a rather simple phase evolution. Searching for extreme mass ratio inspirals voice-by-voice may be more effective than searching for the summed waveform all at once.Comment: 15 pages, 11 figures, accepted for publication in PRD. This version incorporates referee's comments, and is much less verbos

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient

A vascularized composite tissue allotransplantation (VCA) was performed at the Children’s Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at “hand areas”, reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip’s somatosensory response

Isotopes in pyrogenic carbon: a review

Pyrogenic carbon (PC; also known as biochar, charcoal, black carbon and soot) derived from natural and anthropogenic burning plays a major, but poorly quantified, role in the global carbon cycle. Isotopes provide a fundamental fingerprint of the source of PC and a powerful tracer of interactions between PC and the environment. Radiocarbon and stable carbon isotope techniques have been widely applied to studies of PC in aerosols, soils, sediments and archaeological sequences, with the use of other isotopes currently less developed. This paper reviews the current state of knowledge regarding (i) techniques for isolating PC for isotope analysis and (ii) processes controlling the carbon (<sup>13</sup>C and <sup>14</sup>C), nitrogen, oxygen, hydrogen and sulfur isotope composition of PC during formation and after deposition. It also reviews the current and potential future applications of isotope based studies to better understand the role of PC in the modern environment and to the development of records of past environmental change

A new conceptual framework for revenge firesetting

Revenge has frequently been acknowledged to account for a relatively large proportion of motives in deliberate firesetting. However, very little is actually known about the aetiology of revenge firesetting. Theoretical approaches to revenge-seeking behaviour are discussed. A brief review of how revenge is accounted for in existing theoretical explanations of deliberate firesetting and the known characteristics of revenge firesetters are provided. On this basis, the authors suggest, as a motive, revenge firesetting has to date been misconceptualised. A new conceptual framework is thus proposed, paying particular attention to the contextual, affective, cognitive, volitional and behavioural factors which may influence and generate a single episode of revenge firesetting. Treatment implications and suggestions for future research are also provided

What Are the Economic Consequences of Unplanned Readmissions After TKA?

BACKGROUND: In 2009, the Center for Medicare & Medicaid Services (CMS) began penalizing hospitals with high rates of 30-day readmissions after hospitalizations for certain conditions. This policy will expand to include TKA in 2015. QUESTIONS/PURPOSES: What are the median profits and contribution margins of: (1) Medicare-reimbursed TKA, (2) 30-day TKA readmission, and (3) entire episode of care for readmitted TKA patients within 30 days compared to nonreadmitted patients? (4) Under new CMS guidelines, what financial penalty will the authors' institution face if its arthroplasty readmission rate exceeds the national average? METHODS: A retrospective review of 3218 primary TKAs performed during 2 years at a large urban academic hospital network was conducted using administrative and financial data. RESULTS: The median profit and contribution margins, respectively, were as follows: TKA episode, USD 5209 and USD 11,726; 30-day readmission, USD 608 and USD 3814; TKA visit with readmission, USD 2855 and USD 13,901; TKA visit without readmission, USD 5300 and USD 11,652. Readmission penalties could reach USD 6.21 million per year for the authors' institution. DISCUSSION: If our results are generalizable, unplanned TKA readmissions lead to diminished total profit. Although associated with a positive contribution margin, this is likely to be a short-term phenomenon as the new CMS policy will result in readmissions coming at a steep cost to referral centers