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Small superficially ulcerated skin lesions were observed between October 2009 and September 2011 during captive care of two orphaned sea otter pups: one northern (Enhydra lutris kenyoni) in Alaska and one southern (Enhydra lutris nereis) in California. Inclusions consistent with poxviral infection were diagnosed by histopathology in both cases. Virions consistent with poxvirus virions were seen on electron microscopy in the northern sea otter, and the virus was successfully propagated in cell culture. DNA extraction, pan-chordopoxviral PCR amplification, and sequencing of the DNA-dependent DNA polymerase gene revealed that both cases were caused by a novel AT-rich poxvirus. Bayesian and maximum likelihood phylogenetic analyses found that the virus is divergent from other known poxviruses at a level consistent with a novel genus. These cases were self-limiting and did not appear to be associated with systemic illness. To our knowledge, this is the first report of a poxvirus in a mustelid species. The source of this virus, mode of transmission, zoonotic potential, and biological significance are undetermined.

Agreement between the final DSM-5 ASD criteria, Childhood Autism Rating Scale (CARS), and Checklist for Autism Spectrum Disorder (CASD) was assessed in 143 children with ASD and other disorders (e.g., ADHD, intellectual disability, and oppositional defiant disorder). Diagnostic agreement between the CARS and CASD was high (94%), but their agreement with the DSM-5 was lower (84% and 88%). Agreement between the DSM-5 and both the CARS and CASD increased to 94% and diagnostic accuracy increased from 92% to 96% when one less DSM-5 social communication and interaction symptom was required for a diagnosis. Children with ASD not meeting DSM-5 criteria most often did not have criterion A2 (deficits in nonverbal social communication). Total scores on the DSM-5, CASD, and CARS were far higher for children with mild ASD (formerly PDDNOS) than no ASD, indicating that these children are clearly on the autism spectrum and are quite different from children with other disorders. However, only one child with mild ASD was identified by the DSM-5. This study and 11 others show that the DSM-5 under-identifies children with ASD, particularly children at the mild end of the spectrum. This can be rectified by requiring one less social communication and interaction symptom for a diagnosis.

A two and a half year old spayed female Miniature Australian Shepherd presented to a Montana veterinary clinic with acute onset of anorexia, vomiting and depression. Two days prior, the dog was exposed to an algal bloom in a community lake. Within h, the animal became lethargic and anorexic, and progressed to severe depression and vomiting. A complete blood count and serum chemistry panel suggested acute hepatitis, and a severe coagulopathy was noted clinically. Feces from the affected dog were positive for the cyanobacterial biotoxin, microcystin-LA (217 ppb). The dog was hospitalized for eight days. Supportive therapy consisted of fluids, mucosal protectants, vitamins, antibiotics, and nutritional supplements. On day five of hospitalization, a bile acid sequestrant, cholestyramine, was administered orally. Rapid clinical improvement was noted within 48 h of initiating oral cholestyramine therapy. At 17 days post-exposure the dog was clinically normal, and remained clinically normal at re-check, one year post-exposure. To our knowledge, this is the first report of successful treatment of canine cyanobacterial (microcystin) toxicosis. Untreated microcystin intoxication is commonly fatal, and can result in significant liver damage in surviving animals. The clinical success of this case suggests that oral administration of cholestyramine, in combination with supportive therapy, could significantly reduce hospitalization time, cost-of-care and mortality for microcystin-poisoned animals.

The mechanism by which inhaled anesthetics work is not fully understood, although they have been extensively used. Much research has been done showing the likelihood that there is more than one pathway or mechanism of action. A long-term goal of our laboratory is to decipher these mechanisms using Drosophila melanogaster, an excellent model organism for this purpose. In order to do this, we have modified and constructed an apparatus called the inebriometer to quantitatively analyze the response of flies to inhaled anesthetics. While the inebriometer is not new to the fly community, our updated design provides a relatively low-labor, high-throughput means for performing screens in search of genes involved in the anesthetic mechanism. Here we describe our construction of an airtight inebriometer that we have designed for this purpose. We also provide data that validates this apparatus and establishes a procedure for its use.

Isotopic analysis of serially sampled vibrissae (whiskers) is a powerful method to investigate changes in an individual’s resource and habitat use over time, which is difficult or impossible to accomplish using traditional dietary proxies such as observation or scat analysis. A vibrissae-based isotopic approach is limited by knowledge of vibrissae growth rates, which are required to determine the time period represented by each subsampled segment. Likewise, determining the magnitude of, and variation in, isotopic differences between a consumer and its diet, commonly referred to as trophic discrimination factors (TDFs), is a crucial step in quantifying diet composition using stable isotopes. TDF estimates are available only for a few mammalian taxa. We measured vibrissae growth rates and d 13 C and d 15 N TDFs in captive southern sea otters (Enhydra lutris nereis). Sea otters were administered 15 N-enriched glycine intravenously and vibrissae were collected periodically and serially sampled for carbon (d 13 C) and nitrogen (d 15 N) isotope analysis. Growth of adult sea otter vibrissae was linear with a mean (6SD) rate of 7.7 (6 1.2) cm/year. Mean (6SD) whole diet–vibrissae TDFs were 2.8% (60.2%) for d 13 C and 5.5% (60.2%) for d 15 N. Mean (6SD) lipid-extracted diet–vibrissae TDFs were 2.4% (60.2%) for d 13 C and 4.9% (60.3%) for d 15 N. d 13 C TDFs were similar to previously reported values for mammalian carnivores, but d 15 N TDFs were higher than expected. These results will increase the accuracy of isotopic diet analyses of mustelids and other carnivores for which there are few estimates of TDFs and no estimates of vibrissae growth rates.

Objective: The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women. Methods: A multicenter, randomized, double-blind, placebo-controlled 24-month trial was conducted to assess the effect of 80 or 120 mg of daily aglycone hypocotyl soy isoflavone supplementation on quality of life in 403 postmenopausal women using a validated Menopause-Specific Quality of Life questionnaire. Results: Menopause-Specific Quality of Life domain scores at 1 year and 2 years were similar to baseline. There were no differences in domain scores among treatment groups. Conclusions: Soy isoflavone supplementation offers no benefit to quality of life in postmenopausal women.

A retrospective study of the pathologic findings in weedy ( Phyllopteryx taeniolatus) and leafy ( Phycodurus eques) seadragons was performed on specimens submitted to 2 reference laboratories from 1994 to 2012 to determine the range and occurrence of diseases affecting aquarium-held populations. One hundred two and 94 total diagnoses were recorded in weedy and leafy seadragons, respectively. Two of the more common etiologic diagnoses in both species were mycobacteriosis and scuticociliatosis, whereas myxozoanosis was common in weedy seadragons. Metazoan parasite infections were less common etiologic diagnoses. There were no correlations between mycobacteriosis and ciliate protozoan infections in either species. Myxozoanosis was usually found in combination with other diseases and, except for 1 case, was restricted to weedy seadragons. Phaeohyphomycosis, nonmycobacterial bacterial infections, and trauma were also important but less frequent diagnoses. Intestinal coccidiosis was found in weedy but not leafy seadragons. Mineralization of the swim bladder was detected in 26 of 197 leafy seadragons and only 2 of 257 weedy seadragons. Although weedy and leafy seadragons share certain diseases of significance to exhibit populations, there are diseases unique to each species about which the veterinary pathologist, clinician, or diagnostician should be aware.

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient."A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided.Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions.The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

The purposes of this study are to define the pattern of injuries sustained by dismounted troops exposed to improvised explosive devices blasts treated at a Role 3 combat support hospital and to assess injury patterns and mortality associated with the mechanism. Our hypothesis was that mortality is associated with pelvic fracture, massive transfusion, high Injury Severity Score (ISS), multiple limb amputations, and transfer from a Role 2 facility.Retrospective study of 457 patients. Analysis performed on trauma registry data and systematic review of radiographs.99.9% were men with a median age of 23 years and median ISS 10. 141 patients (30.9%) required massive blood transfusion. Limb amputations were frequently observed injuries, 109 of 172 amputees (63.4%) had a double amputation. 34 subjects (7.4%) had pelvic fractures; majority of pelvic fractures (88%) were unstable (Tile B or C). Risk factors associated with the overall mortality rate of 1.8% were an ISS greater than 15 (odds ratio: 11.5; 95% confidence interval: 1.38, 533; p = 0.009), need for massive transfusion (p0.0001), and the presence of a pelvic fracture (odds ratio: 7.63; 95% confidence interval: 1.13, 41.3; p = 0.018).Dismounted improvised explosive devices blast injuries result in devastating multiple limb amputations and unstable pelvic fractures, which are associated with mortality after initial trauma resuscitation at a Role 3 hospital.

Transitions between mesenchymal and epithelial cells are underpinned by changes in motility, adhesion, and polarity. Netrins and their receptors can control each of these cellular properties, and are emerging as important regulators of epithelial mesenchymal plasticity (EMP). Netrins were first identified in the worm Caenorhabditis elegans as secreted chemoattractants/repellents that could guide migrating mesodermal cells and axonal growth cones. Orthologues were subsequently found to play conserved roles in vertebrates and in the vinegar fly Drosophila. In the years that have followed it has become clear that, in addition to chemotaxis, netrin pathways have a number of other biological roles, many of which are directly relevant to the processes of EMP. Netrins and their receptors regulate morphogenesis of epithelial branched structures in the lung, mammary gland, pancreas, and vasculature, and can also promote the loss of epithelial structure. More recently they have been shown to drive apicobasal cell polarization events in vertebrates, flies, and worms. Given these many and varied roles in regulating epithelial morphogenetic events, together with their well-established roles in cell motility, netrins are likely to remain an important future avenue for EMP research.

The 1989 Exxon Valdez oil spill resulted in the death of 3,000–6,000 sea otters (Enhydra lutris) from exposure to Alaska North Slope crude oil, and the cleaning and rehabilitation of hundreds. The washing and care methods developed during that experience provided standard protocols for treatment of oiled sea otters, largely still in use 20 years later. From 2004 to 2008 at the Marine Wildlife Veterinary Care and Research Center (Santa Cruz, CA, USA), we experimentally manipulated water type (salt–fresh) and temperature, and we monitored otter physiology, behavior, and thermal properties to evaluate recovery from washing in the absence of oil. We also dipped otters in canola oil, and were able to wash one otter naturally oiled with Monterey formation crude oil, using the same methods. Providing soft freshwater in recovery pools reduced recovery time substantially. Warming the freshwater appeared to offer additional benefits in some cases. Infrared thermography and subcutaneous temperature-sensitive passive integrated transponder tags were 2 new technologies that enhanced this research. The improved washing and care methods developed have the potential to reduce the time required for recovery of water repellency of sea otter pelage. © 2012 The Wildlife Society.

A twenty-one-year-old male sandbar shark (Carcharhinus plumbeus) demonstrated signs of chronic weight loss even though its appetite remained unchanged. In addition, the gradual development of a red, circular lesion on its ventral body was noted. After months without any significant changes, a ventral fistula appeared revealing the tip of a wire exposed within its center. The shark was immobilized via intramuscular remote injection through dartgun with etomidate; removed from its exhibit tank; and clinically examined with radiographic imaging, a cell blood count/serum chemistry evaluation, and the use of a metal detector along the body wall. A metallic hook was identified in the coelom about 10 cm cranial to the external fistula. The shark was transferred to an isolation pool for 1 mo. A second immobilization via immersion in eugenol was conducted in order to perform a celiotomy. The hook was located in a liver lobe and was surgically removed. After a prolonged recovery from anesthesia, the shark was released into its primary tank and recovered uneventfully, although some of the skin sutures sloughed prematurely.

The authors of the Childhood Autism Rating Scale (CARS) state in the manual that the best cutoff score for distinguishing low functioning autism (LFA) from intellectual disability is 30 for children and 28 for adolescents and adults. This study determined that a cutoff score of 25.5 was most accurate in differentiating between high functioning autism or Asperger syndrome (HFA; n = 197) and ADHD ( n = 74) in a sample of 1- to 16-year-olds with IQs of 80 or higher. Classification accuracy was 96% using clinician scores and 72% using parent scores. Children with LFA ( n = 193) had significantly higher clinician and parent scores than children with HFA, and scores were negatively correlated with IQ. None of the typical children ( n = 64) earned parent scores greater than 21.

Bacterial infections are an important cause of sea otter (Enhydra lutris) mortality, and some of these infections may originate from terrestrial and anthropogenic sources. Antimicrobials are an important therapeutic tool for management of bacterial infections in stranded sea otters and for prevention of infection following invasive procedures in free-ranging otters. In this study, susceptibility to commonly used antimicrobials was determined for 126 isolates of 15 bacterial species or groups from necropsied, live-stranded injured or sick, and apparently healthy wild sea otters examined between 1998 and 2005. These isolates included both gram-positive and gram- negative strains of primary pathogens, opportunistic pathogens, and environmental flora, including bacterial species with proven zoonotic potential. Minimal evidence of antimicrobial resistance and no strains with unusual or clinically significant multiple-drug resistance patterns were identified. Collectively, these findings will help optimize selection of appropriate antimicrobials for treatment of bacterial diseases in sea otters and other marine species.

Individual dietary preferences and difficulty with animal training create challenges and nutritional concerns when evaluating a captive sea otter (Enhydra lutris) diet. The importance of vitamin A within the body reflects the necessity that it be ingested in adequate amounts to ensure optimal health. To compare levels of serum vitamin A concentrations from captive sea otters on daily oral vitamin A supplementation, serum samples from eight adult sea otters from three institutions were evaluated for serum vitamin A concentrations. The eight animals were fed a total of four different diets and received oral supplementation via three different methods. Multiple diet items were analyzed for vitamin A content and were found to have low to nondetectable levels of vitamin A. Oral vitamin A supplementation, as a slurry with dietary items, was shown to be effective and a mean serum concentration of approximately 170 +/- 51 microg/L was obtained for serum vitamin A concentrations in captive sea otters. Captive diets can be modified to increase vitamin A concentration and supplementation and, if accepted, can be used as a means to ensure adequate vitamin A intake.

Mothers of 627 children with autism (ages 1–17, IQs 16–146) completed the Pediatric Behavior Scale. Maternal ratings of anxiety and depression increased with age and IQ, but were unrelated to gender, parent occupation, and race. Anxiety and depression were highly correlated with each other and with autism severity, somatic complaints, mood disturbance, and social problems. Remaining correlations with behavior problems, attention deficit, hyperactivity, and sleep problems were small. The strongest combined predictors of anxiety and depression were autism severity, verbal IQ, and age, explaining 25% and 23% of the variance. Findings suggest that anxiety and depression have a direct link with autism (increasing with autism severity) and a developmental component (increasing with age and IQ). Anxiety is present in most children with autism and depression is present in about half. Therefore, all children with autism should be screened for anxiety and depression and treated if indicated. Controlled studies are needed to determine what interventions are effective in reducing anxiety and depression in autism.

Agreement between the Autism Diagnostic Interview-Revised (ADI-R) and two brief scales completed by parents was 93.1% for the Checklist for Autism Spectrum Disorder (CASD) and 89.7% for the Social Responsiveness Scale (SRS) in a sample of adolescents with suspected autism spectrum disorders. Our study is consistent with others showing that brief scales like the CASD and SRS have strong psychometric support and compare favorably with the ADI-R. The CASD and SRS are each completed and scored in 15 min, whereas the ADI-R takes over 2 h to administer and score. The CASD and SRS offer a valid and cost effective alternative to lengthy and expensive measures and, by virtue of their brevity and simplicity, could facilitate diagnosis, access to treatment, and research.

Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety. Objective: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health. Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids. Results: The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor–negative endometrial cancer), which was less than the expected population rate for these cancers. Conclusion: Daily supplementation for 2 y with 80–120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00665860","term_id":"NCT00665860"}}NCT00665860

Little is known about the validity of Gilliam Asperger's Disorder Scale (GADS), although it is widely used. This study of 199 children with high functioning autism or Asperger's Disorder, 195 with low functioning autism, and 83 with Attention Deficit Hyperactivity Disorder (ADHD) showed high classification accuracy (autism vs ADHD) for clinicians' GADS Quotients (92%), and somewhat lower accuracy (77%) for parents' Quotients. Both children with high and low functioning autism had clinicians' Quotients ( M = 99 and 101, respectively) similar to the Asperger's Disorder mean of 100 for the GADS normative sample. Children with high functioning autism scored significantly higher on the Cognitive Patterns subscale than children with low functioning autism, and the later had higher scores on the remaining subscales: Social Interaction, Restricted Patterns of Behavior, and Pragmatic Skills. Using the clinicians' Quotient and Cognitive Patterns score, 70% of children were correctly identified as having high or low functioning autism or ADHD.

Although largely unaddressed by evolutionary theory for more than a century after Darwin, over the last decade a wide range of adaptationist, byproduct, and memetic explanations have emerged for various recurrent features of religious belief and practice. One feature that has figured prominently in adaptationist accounts of religion is belief in the reality of moralizing, punishing supernatural agents. However, there is at present no unified theory of what fitness-relevant feature of the selective environment to which this cognitive predisposition is adapted. We distinguish two divergent and often conflated approaches to supernatural punishment theory which hypothesize the adaptive character of such beliefs arise from the fact that they increase cooperation or decrease the cost of incurring punishment for norm violations. We evaluate these, and group and individual selectionist versions, in view of game theoretic models, experimental studies, and ethnographic data in light of which each proposal is plausi...

We are grateful to the respondents for thoughtfully illuminating points in our analysis they view as correct and important, for graciously pointing out the ambiguous or unpersuasive, and for sugges...

Maternal ratings of anxiety, depression, and irritability were analyzed in 1390 children (6–16 years of age), including 233 children with high functioning autism (HFA, IQ ≥ 80), 117 children with low functioning autism (LFA, IQ

To the Editor: Sporadic epizootics of pneumonia among marine mammals have been associated with multiple animal-origin influenza A virus subtypes (1–6); seals are the only known nonhuman host for influenza B viruses (7). Recently, we reported serologic evidence of influenza A virus infection in free-ranging northern sea otters (Enhydra lutris kenyoni) captured off the coast of Washington, USA, in August 2011 (8). To investigate further which influenza A virus subtype infected these otters, we tested serum samples from these otters by ELISA for antibody-binding activity against 12 recombinant hemagglutinins (rHAs) from 7 influenza A hemagglutinin (HA) subtypes and 2 lineages of influenza B virus (Technical Appendix Table 1). Estimated ages for the otters were 2–19 years (Technical Appendix Table 2); we also tested archived serum samples from sea otters of similar ages collected from a study conducted during 2001–2002 along the Washington coast (9). Of the 30 sea otter serum samples collected during 2011, a total of 21 (70%) had detectable IgG (>200) for rHA of influenza A(H1N1)pdm09 virus (pH1N1) strain A/Texas/05/2009. Four of 7 serum samples that showed IgG ≥6,400 against pH1N1 rHA also showed low cross-reactivity (IgG 200) against rHA of A/Brisbane/59/2007, a previous seasonal influenza A(H1N1) virus (Figure, panel A; Technical Appendix Table 1). No IgG was detected in any samples for any of the other 11 rHAs tested (IgG ≤100), and the sea otter serum samples collected during 2001–2002 did not react with any of the rHAs tested, including pH1N1 (IgG ≤100; Figure, panel A). Figure Results of ELISA and hemagglutination inhibition (HI) testing for influenza viruses in serum samples from northern sea otters captured off the coast of Washington, USA, during studies conducted in August 2011 (n = 30) and 2001–2002 (n = 21). A) ... Next, we tested serum samples by using a hemagglutination inhibition (HI) assay with whole influenza virus to detect strain-specific antibodies that inhibit receptor binding. Of the 30 samples collected during 2011, a total of 22 (73%) showed HI antibody titers of ≥40 against pH1N1 virus. Titers against all other human and avian viruses tested were ≤10 for all samples by HI assay using turkey red blood cells (RBCs) (Figure, panel B; Technical Appendix Table 3). No influenza A or B virus–specific HI antibodies were detected in the samples collected during 2001–2002 (data not shown). Although nasal swab specimens were collected from sea otters in the 2011 study, all specimens were negative for influenza virus by testing in embryonated eggs and by real-time PCR for detection of influenza A viral RNA (data not shown). These results suggest that sea otters were infected with influenza A virus sometime before the August 2011 sample collection date. Although none of the 2011 samples showed HI titers to influenza A/duck/New York/96 (H1N1) virus (dk/NY/96) by testing using turkey RBCs (Technical Appendix Table 2), titers against this strain were detected when using horse RBCs, which is a more sensitive means for the detection of mammalian antibodies against some avian influenza subtypes (10). Of the 22 samples that had HI titers >40 to pH1N1 virus, 16 also had HI titers >40 against dk/NY/96 by horse RBC HI assay (Technical Appendix Table 2). However, titers against this strain were on average ≈4–8-fold lower than those for the pH1N1 virus strain, which suggests that that the titers against dk/NY/96 were the result of serologic cross-reactivity with avian- and swine-origin pH1N1 viruses. To further test for cross-reactivity, 4 sea otter serum samples were adsorbed with purified pH1N1 and dk/NY/96 virions. Adsorption with pH1N1, but not dk/NY/96, removed HI antibodies to pH1N1, whereas adsorption with either virus removed HI antibodies against dk/NY/96 (Technical Appendix Table 4). A comparison of amino acid sequences comprising the known HA antigenic sites on the pH1N1 structure confirmed high sequence identity and structural similarity with dk/NY/96 HA in Sa (12/13 aa residues) and Sb (8/12 aa residues) antigenic sites (data not shown). These results indicate that HI antibodies detected in sea otters are the result of pH1N1 virus infection but cross-react with the avian influenza A(H1N1) virus. Although we cannot exclude the possibility that sea otters were infected with classical swine influenza A(H1N1) virus, which shares high HA genetic and antigenic similarity with pH1N1 virus, our serologic evidence is consistent with isolation of pH1N1 virus from northern elephant seals (1). Therefore, we conclude that these sea otters were infected with pH1N1 virus. The origin and transmission route of pH1N1 virus infection in sea otters remain unknown. Potential contact between northern elephant seals and sea otters is one possibility; elephant seals’ summer feeding ranges and breeding areas along the Northeast Pacific coast overlap with areas where the Washington sea otter population is distributed (1). In conclusion, our results show that sea otters are susceptible to infection with influenza A virus and highlight the complex nature of interspecies transmission of influenza viruses in the marine environment. Further surveillance, especially in other sea otter populations, is required to determine virus origin, potential pathogenesis, and consequences for the marine ecosystem. Technical Appendix: Titers for influenza A and B viruses detected in serum samples from northern sea otters captured off the coast of Washington, USA, during studies conducted in August 2011. Click here to view.(52K, pdf)

While emerging cognitive and evolutionary sciences of religion have generated important empirical findings and conceptual advances, Nathaniel Barrett is quite right to pursue integration with historical and cultural studies and to challenge the reductionism that is, if not endemic to, at least popularly ascribed to these approaches. However, we argue that in proposing an alternative paradigm, he mischaracterizes the breadth of the current research program in three ways: (1) it is not wedded to defining religion in terms of supernatural or fictive beliefs, (2) it does not construe the disposition to religious belief as "hard-wired" and context-insensitive, and (3) it does not presume an adaptationist, strongly modular account of mind. On each of these issues, the field displays a wide range of perspectives, and it is precisely the latitude of views that welcomes and indeed has spawned—from its founders to the present—interaction with cultural and historical scholars.

The extent to which freedom should prevail continues to be a lingering question in the economic discipline. The article focuses on how freedom is conceptualized. The question addressed is whose freedoms are being served through economic self-governance. The profit seeking microeconomic objective of capitalists, as addressed by Karl Marx, must lead to structural change resulting in unemployment. But unemployment has disastrous social costs. So the promotion of freedom for capitalists comes at a high cost toward society. Thus it is argued that the concept of freedom is itself a paradox. Freedom itself must be constrained to be viable.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Netrin receptors of the DCC/NEO/UNC-40/Frazzled family have well established roles in cell migration and axon guidance but can also regulate epithelial features such as adhesion, polarity and adherens junction (AJ) stability. Previously, we have shown that overexpression of Drosophila Frazzled (Fra) in the peripodial epithelium (PE) inhibits wing disc eversion and also generates cellular protrusions typical of motile cells. Here, we tested whether the molecular pathways by which Fra inhibits eversion are distinct from those driving motility. We show that in disc proper (DP) epithelial cells Fra, in addition to inducing F-Actin rich protrusions, can affect localization of AJ components and columnar cell shape. We then show that these phenotypes have different requirements for the three conserved Fra cytoplasmic P-motifs and for downstream genes. The formation of protrusions required the P3 motif of Fra, as well as integrins (mys and mew), the Rac pathway (Rac1, wave and, arpc3) and myosin regulatory light chain (Sqh). In contrast, apico-basal cell shape change, which was accompanied by increased myosin phosphorylation, was critically dependent upon the P1 motif and was promoted by RhoGef2 but inhibited by Rac1. Fra also caused a loss of AJ proteins (DE-Cad and Arm) from basolateral regions of epithelial cells. This phenotype required all 3 P-motifs, and was dependent upon the polarity factor par6. par6 was not required for protrusions or cell shape change, but was required to block eversion suggesting that control of AJ components may underlie the ability of Fra to promote epithelial stability. The results imply that multiple molecular pathways act downstream of Fra in epithelial cells., This work was supported by Australian Research Council Discovery Project DP120104443 to RS and National Health and Medical Research Council Australia Project Grant APP1107123 to MJM. SG was supported by a International Postgraduate Research Scholarship.

Justin Barrett's consideration of some challenges for religious belief raised by evolutionary and cognitive theories of religion was criticized by Howard Van Till for overstating tensions, mischaracterizing the most important epistemological issues, and proposing a solution that perpetuates war on evolution. We argue that each of these claims is untrue, and is not conducive to dialogue that constructively engages and attempts to resolve tensions between science and religion where they do exist.

From 2002 to 2006, eight captive southern sea otters (Enhydra lutris nereis) at research and display institutions in California at risk of exposure to potentially lethal morbiliviruses were vaccinated with a commercial recombinant poxvirus vectored canine distemper (CD) vaccine. Serum-neutralizing (SN) antibody responses were followed for several years. The goal of this study was to determine whether 1) CD vaccination was a safe preventive medicine procedure for this species; 2) sea otters produce detectable SN antibodies in response to vaccination with this product; and 3) if this type of vaccination might be useful in response to a morbilivirus disease outbreak in free-ranging sea otters. Results indicate that a commercial recombinant vaccine is safe, provokes a measurable SN antibody response, and that vaccination may provide some protection from infection for free-ranging sea otters. It also resulted in the reevaluation of CD serology data that were previously published for free-ranging sea otters. Canine distemper, Enhydra lutris nereis, morbilivirus, sea otter, serology, vaccination.

Previous studies in man have shown that hyperventilation consistently enhances the amplitude of the electroretinogram (ERG) b-wave, but has little effect on the a-wave. The present study examined this phenomenon in the dog; central (centrifugal) and peripheral (sympathetic) neural effects and changes in arterial pO2 and blood pH were excluded as physiologic bases for the phenomenon. It was concluded, therefore, that the underlying mechanism must be decreased pCO2 (hypocapnia), although the specific site of action and the method by which the ERG b-wave is enhanced remain topics for future research.

Soy isoflavones have functional similarity to human estrogens and may protect against breast cancer as a result of their antiestrogenic activity or increase risk as a result of their estrogen-like properties. We examined the relation between isoflavone supplementation and mammographic density, a strong marker for breast cancer risk, among postmenopausal women. The Osteoporosis Prevention Using Soy (OPUS) study, a multi-site, randomized, double-blinded, and placebo-controlled trial assigned 406 postmenopausal women to 80 or 120 mg/d of isoflavones each or a placebo for 2 y. Percent densities were assessed in digitized mammograms using a computer-assisted method. The mammogram reader did not know the treatment status and the time of mammograms. We applied mixed models to compare breast density by treatment while considering the repeated measures. The mammographic density analysis included 358 women, 88.2% of the OPUS participants; 303 had a complete set of 3 mammograms, 49 had 2, and 6 had only 1 mammogram. At baseline, the groups were similar in age, BMI, and percent density, but mean breast density differed by study site (P = 0.02). A model with all mammograms did not show a treatment effect on any mammographic measure, but the change over time was significant; breast density decreased by 1.6%/y across groups (P < 0.001). Stratification by age and BMI did not reveal any effects in subgroups. In this randomized 2-y trial, isoflavone supplements did not modify breast density in postmenopausal women. These findings offer reassurance that isoflavones do not act like hormone replacement medication on breast density.

Costly signaling theories of religion contend that religious belief and behaviors function as costly signals of cooperative intent. Such signals are evolvable because they allow likely cooperators to find one another, while excluding potential cheats or free riders that would be unwilling (or unable) to pay the price associated with sending the signal. As a result, under the right conditions, religious costly signaling can emerge as an evolutionary stable strategy. However, reliability certifying costly signaling can evolve and stabilize only when certain necessary conditions are satisfied. In this paper we argue that current versions of the theory do not adequately demonstrate that these conditions are met.

Background Paraplegia is a devastating complication for patients undergoing repair of thoracoabdominal aortic aneurysms. A monitor to detect spinal cord ischemia is necessary if anesthesiologists are to intervene to protect the spinal cord during aortic aneurysm clamping. Methods The medical records of 60 patients who underwent thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling with evoked potential monitoring were reviewed. The authors analyzed latency and amplitude of motor evoked potentials, somatosensory evoked potentials, and H reflexes before cooling and clamping, after cooling and before clamping, during clamping, and after release of aortic cross clamp. Results Twenty minutes after the aortic cross clamp was placed, motor evoked potentials had 88% sensitivity and 65% specificity in predicting spinal cord ischemia. The negative predictive value of motor evoked potentials at 20 min after aortic cross clamping was 96%. Conclusions Rapid loss of motor evoked potentials or H reflexes after application of the aortic cross clamp identifies a subgroup of patients who are at high risk of developing spinal cord ischemia and in whom aggressive anesthetic and surgical interventions may be justified.

To identify genes that modulate Rho signalling during cytokinesis we tested the effect of overexpressing a set of 2190 genes on an eye phenotype caused by defective Rho activation. The resulting 112 modifier loci fell into three main classes: cell cycle genes, signalling effectors and metabolic enzymes. We developed a further series of genetic tests to refine the interactors into those most likely to modify Rho signalling during cytokinesis. In addition to a number of genes previously implicated in the Rho pathway during cytokinesis, we identified four novel primary candidates: cdc14, Pitslre, PDK1 and thread/diap1. cdc14 orthologs have, however, been implicated in cytokinesis in other organisms, as have molecules related to Thread/Diap1. The identification of several modifiers that are genetically redundant paralogs highlights the ability of overexpression screens to identify genes that are refractory to traditional loss-of-function approaches. Overexpression screens and sensitized phenotypes, therefore, may help identify the many factors that are expected to be involved in cytokinesis but have not been discovered by previous genetic screens.

SUMMARYToxoplasma gondiiandSarcocystis neuronaare protozoan parasites with terrestrial definitive hosts, and both pathogens can cause fatal disease in a wide range of marine animals. Close monitoring of threatened southern sea otters (Enhydra lutris nereis) in California allowed for the diagnosis of dual transplacental transmission ofT. gondiiandS. neuronain a wild female otter that was chronically infected with both parasites. Congenital infection resulted in late-term abortion due to disseminated toxoplasmosis.Toxoplasma gondiiandS. neuronaDNA was amplified from placental tissue culture, as well as from fetal lung tissue. Molecular characterization ofT. gondiirevealed a Type X genotype in isolates derived from placenta and fetal brain, as well as in all tested fetal organs (brain, lung, spleen, liver and thymus). This report provides the first evidence for transplacental transmission ofT. gondiiin a chronically infected wild sea otter, and the first molecular and immunohistochemical confirmation of concurrent transplacental transmission ofT. gondiiandS. neuronain any species. Repeated fetal and/or neonatal losses in the sea otter dam also suggested thatT. gondiihas the potential to reduce fecundity in chronically infected marine mammals through parasite recrudescence and repeated fetal infection.

Seven sea otters received a single subcutaneous dose of cefovecin at 8 mg/kg body weight. Plasma samples were collected at predetermined time points and assayed for total cefovecin concentrations using ultra-performance liquid chromatography and tandem mass spectrometry. The mean (±SD) noncompartmental pharmacokinetic indices were as follows: CMax (obs) 70.6 ± 14.6 μg/mL, TMax (obs) 2.9 ± 1.5 h, elimination rate constant (kel ) 0.017 ± 0.002/h, elimination half-life (t1/2kel) 41.6 ± 4.7 h, area under the plasma concentration-vs.-time curve to last sample (AUClast) 3438.7 ± 437.7 h·μg/mL and AUC extrapolated to infinity (AUC0→∞ ) 3447.8 ± 439.0 h·μg/mL. The minimum inhibitory concentrations (MIC) for select isolates were determined and used to suggest possible dosing intervals of 10 days, 5 days, and 2.5 days for gram-positive, gram-negative, and Vibrio parahaemolyticus bacterial species, respectively. This study found a single subcutaneous dose of cefovecin sodium in sea otters to be clinically safe and a viable option for long-acting antimicrobial therapy.

Veterinarians and veterinary medicine, in general, have historically played, and continue to play, an important role in the efforts to understand sea otters and assure the conservation of free-ranging sea otter populations. There are, however, important differences between the “traditional” doctor–patient–client relationship paradigm associated with the health management of individual animals, and the manner in which health and disease are evaluated and interpreted in populations of animals. It comes as no surprise that animals in the wild die from one or combinations of a myriad of causes. Therefore, if one examines a large enough number of animals, you will find some that are, in fact, critically ill and dying. It is important to recognize that the veterinarian’s role in conservation medicine is not to “cure every sick sea otter,” but rather to provide insight into the etiopathogenesis, the epidemiology, and the implications of these diseases. This information may then be integrated into the bigger population picture involving wildlife ecology, natural history, environmental factors, and demography, all of which are critically important in the understanding, and therefore the preservation, of sea otter populations.

During tumorigenesis, pathways that promote the epithelial-to-mesenchymal transition (EMT) can both facilitate metastasis and endow tumor cells with cancer stem cell properties. To gain a greater understanding of how these properties are interlinked in cancers we used Drosophila epithelial tumor models, which are driven by orthologues of human oncogenes (activated alleles of Ras and Notch) in cooperation with the loss of the cell polarity regulator, scribbled (scrib). Within these tumors, both invasive, mesenchymal-like cell morphology and continual tumor overgrowth, are dependent upon Jun N-terminal kinase (JNK) activity. To identify JNK-dependent changes within the tumors we used a comparative microarray analysis to define a JNK gene signature common to both Ras and Notch-driven tumors. Amongst the JNK-dependent changes was a significant enrichment for BTB-Zinc Finger (ZF) domain genes, including chronologically inappropriate morphogenesis (chinmo). chinmo was upregulated by JNK within the tumors, and overexpression of chinmo with either RasV12 or Nintra was sufficient to promote JNK-independent epithelial tumor formation in the eye/antennal disc, and, in cooperation with RasV12, promote tumor formation in the adult midgut epithelium. Chinmo primes cells for oncogene-mediated transformation through blocking differentiation in the eye disc, and promoting an escargot-expressing stem or enteroblast cell state in the adult midgut. BTB-ZF genes are also required for Ras and Notch-driven overgrowth of scrib mutant tissue, since, although loss of chinmo alone did not significantly impede tumor development, when loss of chinmo was combined with loss of a functionally related BTB-ZF gene, abrupt, tumor overgrowth was significantly reduced. abrupt is not a JNK-induced gene, however, Abrupt is present in JNK-positive tumor cells, consistent with a JNK-associated oncogenic role. As some mammalian BTB-ZF proteins are also highly oncogenic, our work suggests that EMT-promoting signals in human cancers could similarly utilize networks of these proteins to promote cancer stem cell states. Copyright

OBJECTIVES To determine the provider cost of administering intensive care unit (ICU) services, comparing 3 different staffing models for ICU coverage, and to compare the costs of using house staff vs nonphysician providers (NPPs). METHODS Data were collected on total staff composition and number of beds in ICUs from January 1, 2004, through December 31, 2004, at the 3 Mayo Clinic sites: Rochester, Minn; Jacksonville, Fla; and Scottsdale, Ariz. Institutional or national average staff salaries were used to determine total staffing costs per ICU bed per year at each site. Medicare medical education reimbursements were also taken into account. RESULTS Costs per ICU bed for physician staffing were $18,630 in Rochester, $37,515 in Jacksonville, and $38,010 in Scottsdale. When NPPs were substituted for house staff, the costs per bed were $72,466 in Rochester, $61,291 in Jacksonville, and $49,909 in Scottsdale. Incremental costs per ICU bed using NPPs were $53,836 in Rochester, $23,776 in Jacksonville, and $11,899 in Scottsdale. CONCLUSION Use of residents and fellows in ICU staffing at a major tertiary health center is more cost-efficient than use of NPPs. This finding could have implications for the cost of physician services in nonteaching community hospitals and the methods by which care is provided.

Purpose: Fumagillin and related compounds have potent antiproliferative activity through inhibition of methionine aminopeptidase-2 (MetAP-2). It has recently been reported that MetAP-2 is highly expressed in germinal center B cells and germinal center–derived non–Hodgkin's lymphomas (NHL), suggesting an important role for MetAP-2 in proliferating B cells. Therefore, we determined the importance of MetAP-2 in normal and transformed germinal center B cells by evaluating the effects of MetAP-2 inhibition on the form and function of germinal centers and germinal center–derived NHL cells. Experimental Design: To examine the activity of PPI-2458 on germinal center morphology, spleen sections from cynomolgus monkeys treated with oral PPI-2458 were analyzed. Antiproliferative activity of PPI-2458 was assessed on germinal center–derived NHL lines in culture. A MetAP-2 pharmacodynamic assay was used to determine cellular MetAP-2 inhibition following PPI-2458 treatment. Finally, inhibition of MetAP-2 and proliferation by PPI-2458 was examined in the human SR NHL line in culture and in implanted xenografts. Results: Oral PPI-2458 caused a reduction in germinal center size and number in lymphoid tissues from treated animals. PPI-2458 potently inhibited growth (GI50 = 0.2-1.9 nmol/L) of several NHL lines in a manner that correlated with MetAP-2 inhibition. Moreover, orally administered PPI-2458 significantly inhibited SR tumor growth, which correlated with inhibition of tumor MetAP-2 (>85% at 100 mg/kg) in mice. Conclusions: These results show the potent antiproliferative activity of PPI-2458 on NHL lines in vitro and oral antitumor activity in vivo and suggest the therapeutic potential of PPI-2458 as a novel agent for treatment of NHL should be evaluated in the clinical setting.