A shared accretion instability for black holes and neutron stars.

Accretion disks around compact objects are expected to enter an unstable phase at high luminosity1. One instability may occur when the radiation pressure generated by accretion modifies the disk viscosity, resulting in the cyclic depletion and refilling of the inner disk on short timescales2. Such a scenario, however, has only been quantitatively verified for a single stellar-mass black hole3-5. Although there are hints of these cycles in a few isolated cases6-10, their apparent absence in the variable emission of most bright accreting neutron stars and black holes has been a continuing puzzle11. Here we report the presence of the same multiwavelength instability around an accreting neutron star. Moreover, we show that the variability across the electromagnetic spectrum-from radio to X-ray-of both black holes and neutron stars at high accretion rates can be explained consistently if the accretion disks are unstable, producing relativistic ejections during transitions that deplete or refill the inner disk. Such a new association allows us to identify the main physical components responsible for the fast multiwavelength variability of highly accreting compact objects.

X-ray quasi-periodic eruptions from two previously quiescent galaxies.

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data1,2, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole3,4. Here we report observations of QPEs in two further galaxies, obtained with a blind and systematic search of half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow that is typical of active galactic nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the QPEs reported here are inconsistent with current models that invoke radiation-pressure-driven instabilities in the accretion disk5-9. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than that of the main body10, and future X-ray observations may constrain possible changes in their period owing to orbital evolution. This model could make QPEs a viable candidate for the electromagnetic counterparts of so-called extreme-mass-ratio inspirals11-13, with considerable implications for multi-messenger astrophysics and cosmology14,15.

The corona contracts in a black-hole transient.

The geometry of the accretion flow around stellar-mass black holes can change on timescales of days to months1-3. When a black hole emerges from quiescence (that is, it 'turns on' after accreting material from its companion) it has a very hard (high-energy) X-ray spectrum produced by a hot corona4,5 positioned above its accretion disk, and then transitions to a soft (lower-energy) spectrum dominated by emission from the geometrically thin accretion disk, which extends to the innermost stable circular orbit6,7. Much debate persists over how this transition occurs and whether it is driven largely by a reduction in the truncation radius of the disk8,9 or by a reduction in the spatial extent of the corona10,11. Observations of X-ray reverberation lags in supermassive black-hole systems12,13 suggest that the corona is compact and that the disk extends nearly to the central black hole14,15. Observations of stellar-mass black holes, however, reveal equivalent (mass-scaled) reverberation lags that are much larger16, leading to the suggestion that the accretion disk in the hard-X-ray state of stellar-mass black holes is truncated at a few hundreds of gravitational radii from the black hole17,18. Here we report X-ray observations of the black-hole transient MAXI J1820+07019,20. We find that the reverberation time lags between the continuum-emitting corona and the irradiated accretion disk are 6 to 20 times shorter than previously seen. The timescale of the reverberation lags shortens by an order of magnitude over a period of weeks, whereas the shape of the broadened iron K emission line remains remarkably constant. This suggests a reduction in the spatial extent of the corona, rather than a change in the inner edge of the accretion disk.

Risk of nutritional deficiencies for dogs on a weight loss plan.

OBJECTIVES: To determine how general practice veterinarians make weight loss recommendations for dogs and if nutrients become deficient when following these recommendations. MATERIALS AND METHODS: A questionnaire of general practice veterinarians was conducted to characterise weight loss recommendations made to clients. Using this data, progressive levels of caloric restriction were applied to top-selling commercial non-therapeutic adult maintenance diets and non-therapeutic weight management diets. Nutrient intakes were compared to the National Research Council's Recommended Allowances for metabolic body weight using a theoretical current weight and ideal body weight for an obese dog. Nutrient intakes were also compared to recommendations from the Association of American Feed Control Officials using current body weight. RESULTS: Several nutrients were found at risk of deficiency, including choline, methionine, cysteine, selenium, eicosapentanoic acid, docosahexanoic acid, riboflavin, pantothenic acid and cobalamin in both non-therapeutic adult maintenance diets and non-therapeutic weight management diets. CLINICAL SIGNIFICANCE: Caution is warranted when making weight loss recommendations using commercial diets until further research on the nutrient needs of obese dogs undergoing weight loss is undertaken. Restriction of commercial diets to achieve weight loss in dogs may result in nutrient deficiencies.

ELISA testing for common food antigens in four dry dog foods used in dietary elimination trials.

This study evaluated four over the counter venison dry dog foods available from one on-line retail vendor for potential contamination with common known food allergens: soy, poultry or beef. An amplified, double sandwich type enzyme linked immunosorbent assay (ELISA) test of soy, poultry and beef proteins were performed by an independent accredited food laboratory. The ELISA test for poultry protein was found to be unreliable when testing in dry dog foods because false negatives occurred. ELISA testing of control diets for both soy and beef proteins performed as expected and could be useful in antigen testing in dry dog foods. Three of the four over the counter (OTC) venison canine dry foods with no soy products named in the ingredient list were ELISA positive for soy; additionally one OTC diet tested positive for beef protein with no beef products listed as an ingredient list. One OTC venison diet was not found to be positive for soy, poultry or beef proteins. However, none of the four OTC venison diets could be considered suitable for a diagnostic elimination trial as they all contained common pet food proteins, some of which were readily identifiable on the label and some that were only detected by ELISA. Therefore, if the four OTC venison products selected in this study are representative of OTC products in general, then the use of OTC venison dry dog foods should not be used during elimination trials in suspected food allergy patients.

BMS-229724 is a tight-binding inhibitor of cytosolic phospholipase A2 that acts at the lipid/water interface and possesses anti-inflammatory activity in skin inflammation models.

Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of phospholipids and is believed to play a key cellular role in the generation of arachidonic acid. BMS-229724 (4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethyl-sulfonyl]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone) was found to be a selective inhibitor of cPLA2 (IC50 = 2.8 microM) in that it did not inhibit secreted phospholipase A2 in vitro, nor phospholipase C and phospholipase D in cells. The compound was active in inhibiting arachidonate and eicosanoid production in U937 cells, neutrophils, platelets, monocytes, and mast cells. With a synthetic covesicle substrate system, the dose-dependent inhibition could be defined by kinetic equations describing competitive inhibition at the lipid/water interface. The apparent equilibrium dissociation constant for the inhibitor bound to the enzyme at the interface (K(I)*(app)) was determined to be 1. 10(-5) mol% versus an apparent dissociation constant for the arachidonate-containing phospholipid of 0.35 mol%. The unit of concentration in the interface is mole fraction (or mol%), which is related to the surface concentration of substrate, rather than bulk concentration that has units of molarity. Thus, BMS-229724 represents a novel inhibitor of cPLA2, which partitions into the phospholipid bilayer and competes with phospholipid substrate for the active site. This potent inhibition of the enzyme translated into anti-inflammatory activity when applied topically (5%, w/v) to a phorbol ester-induced chronic inflammation model in mouse ears, inhibiting edema and neutrophil infiltration, as well as prostaglandin and leukotriene levels in the skin. In hairless guinea pigs, BMS-229724 was active orally (10 mg/kg) in a UVB-induced skin erythema model in hairless guinea pigs.

An investigation of the relationship between caloric intake and outcome in hospitalized dogs.

Malnutrition in veterinary patients is thought to increase morbidity and mortality, but this has not been statistically quantified. A study was designed to estimate the proportion of hospitalized canine patients in negative-energy balance; relate calories consumed in-hospital to appetite at home shortly after discharge; determine why these dogs were in a negative-energy balance; and assess the relationship between body condition score, physical status score (PSS), diagnosis, and caloric intake with patient outcome. Data were collected from 276 dogs over several days in one of the various referral hospitals. After eliminating partial hospital days, there were 821 dog-days for evaluation. A daily positive-energy balance (> 95% resting energy requirement) was achieved for only 27% of the 821 full dog-days. Of 226 dogs successfully followed after discharge, 83% were considered by their owners to have a normal appetite and/or food intake by the second day home. Of the 601 negative-energy-balance dog-days, 22% were due to poorly written feeding orders and 34% had orders to have feed withheld; most cases (44%) resulted from the dog refusing to eat any or all of the food offered. There were significant relationships between caloric intake and PSS, outcome and PSS, and outcome and caloric intake. In general, canine patients with lower PSSs (i.e., no or mild systemic diseases) consumed more daily calories and were more likely to be discharged whereas patients with higher PSSs (i.e., incapacitating, life-threatening systemic diseases) were less likely to meet the resting energy requirement and be discharged from the hospital.

Sulfated galactocerebrosides as potential antiinflammatory agents.

Native sulfatides, as well as many sulfated glycolipids, have been shown to avidly bind to the selectin receptors. In vivo, native sulfatides significantly block activity in selectin-dependent inflammatory responses. The fact that nonsulfated galactocerebrosides did not inhibit selectin-mediated adhesion identified a critical role for the anionic sulfate residue. We therefore initiated a program to evaluate the activity of position isomers. This study showed a binding selectivity for the positions 2 and 3 of the sulfate group on the carbohydrate ring as well as enhanced activity for the disulfated analogs. Furthermore, it was discovered that the attachment of lipophilic substituents on the carbohydrate ring was tolerated, consistent with the presence of a lipophilic pocket in the binding activity. This resulted in compounds with a 6-fold increased potency.

Zinc toxicity with pancreatic acinar necrosis in piglets receiving total parenteral nutrition.

Two Hampshire-Duroc cross piglets maintained on 100% total parenteral nutrition (TPN) for 3 weeks developed pancreatic epithelial cell necrosis, diffuse acinar atrophy, and marked interstitial fibrosis. In addition, the piglets had severe villus atrophy in the small intestine as a result of TPN. Atomic absorption spectrophotometric analysis of liver samples revealed toxic hepatic zinc levels (513.5 and 491.2 ppm) in the TPN piglets (40-90 ppm in control piglets). Administering TPN bypasses homeostatic control mechanisms regulating zinc absorption at the gastrointestinal level and may reduce pancreatic secretion contributing to the accumulation of zinc in tissues. Intestinal villus atrophy, a sequela to TPN, may have also affected zinc excretion by impairing intestinal flux and desquamation. These factors should be considered in formulating TPN solutions and zinc levels administered must be reduced accordingly to avoid toxicity. Furthermore, sources and tissue levels of zinc should be investigated when necrosis, acinar atrophy, and fibrosis of the pancreas are encountered in young pigs.

Comparison of kittens fed queen's milk with those fed milk replacers.

Fifteen 2-week-old kittens were randomly assigned to 1 of 3 milk treatment groups as the sole source of nutrition for 4 weeks: queen's milk, commercially available kitten milk replacer (CMR), and an experimental milk replacer (EXP). Kittens fed queen's milk suckled ad libitum, whereas CMR- and EXP-fed kittens were tube-fed every 6 hours. Kittens were weaned at 6 weeks of age and were fed a feline growth diet ad libitum for an additional 4 weeks. Kittens were examined at 2, 4, 6, 8 and 10 weeks of age; the procedure included an ophthalmic examination and blood sample collection for CBC and serum biochemical and amino acid analyses. Kittens fed CMR and EXP diets had weight gain greater than that for queen's milk-fed kittens. The kittens fed CMR, however, had diarrhea throughout most of the milk-feeding trial and developed diffuse anterior and posterior lens opacification and vacuolation at the posterior Y-sutures. The lens opacities noticed in the kittens during the milk treatments resolved to a residual perinuclear halo, and a few incipient cortical opacities were observed by the end of the growth diet-feeding period. Serum arginine concentration was significantly (P < or = 0.05) lower in the CMR-fed kittens, but was not different during the growth diet-feeding period. We concluded that the EXP diet supported normal growth in 2- to 6-week-old kittens; CMR supported normal kitten growth rate, but resulted in diarrhea and cataract formation; and serum amino acid data indicated that low arginine concentration may have been related to the CMR-induced cataract formation.

Variance of indirect blood pressure measurements and prevalence of hypertension in clinically normal dogs.

In a series of 3 studies, indirect blood pressure measurements were obtained to define normal variance, identify hypertension, and estimate the prevalence of hypertension in apparently healthy dogs. In part 1, we measured values in 5 clinically normal dogs twice weekly for 5 weeks in a home setting. Mean +/- SD systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) was 150 +/- 16 and 86 +/- 13 mm of Hg, respectively. The DAP significantly (P less than 0.01) decreased with repeated measurements over the 5-week period. In part 2, we assessed the variation between blood pressures measured in a clinic vs those measured in the home. Within a 2-week period, measurements were obtained from 10 clinically normal dogs in a private veterinary clinic and again in their home. Significant differences were not observed between clinic and home measurements of SAP and DAP; however, heart rate was significantly (P less than 0.05) higher in the clinic. In part 3, SD about the SAP and DAP mean values were determined in 102 clinically normal dogs. Canine hypertensive status was determined, using statistical methods and data from 102 clinically normal dogs. Values of SAP greater than 202 mm of Hg and DAP greater than 116 mm of Hg were determined to be 2 SD beyond the mean and, therefore, were interpreted to be hypertensive. Approximately 10% of the 102 apparently healthy dogs measured in this study were considered hypertensive on the basis of these criteria. In addition, a border zone of suspected hypertension was estimated, using the mean + 1.282 SD. The SAP border zone was between 183 and 202 mm of Hg, whereas the DAP border zone was between 102 and 113 mm of Hg. Of the 102 dogs, 12 had values within these zones of suspected hypertension.

Adaptation of human oscillometric blood pressure monitors for use in dogs.

Two digital oscillometric human blood pressure measuring devices were modified and evaluated as blood pressure monitors in 12 healthy anesthetized dogs. Direct arterial pressures were measured via cannulation of the dorsal pedal artery and were correlated with indirect measurements through an inflatable cuff placed over the dorsal pedal artery below the hock joint of the contralateral limb. Direct and indirect measurements were compared for systolic, diastolic, and calculated mean arterial pressures. Blood pressure ranges between 215/145 mm of Hg and 65/30 mm of Hg were obtained, using combinations of halothane, phenylephrine, calcium, and IV administered fluids. Machine A was found to be insufficient for clinical application, on the basis of correlation coefficients between direct and indirect pressures of 0.78, 0.65, and 0.74 for systolic, diastolic, and mean arterial pressures, respectively. Higher correlation coefficients between direct and indirect pressures (0.77, 0.87, and 0.87, respectively) were obtained with machine B. The results of the study reported here suggest machine B may be an effective blood pressure monitoring device in anesthetized dogs.

Parenteral nutritional support in the small animal patient.

Malnutrition has a direct relationship to complications associated with ineffective wound and fracture healing, inadequate immune responses, decreased tolerance to cancer therapy, muscle weakness, and certain organ dysfunctions (heart and liver). Malnutrition combined with disease, injury, or stress increases the metabolic rate in patients above that of resting. These patients are undergoing an accelerated form of starvation, which is more common than presently recognized in veterinary medicine and may be responsible for the less than optimal responses to proper therapies. Diseased or injured patients unable to digest or absorb nutrients from the gastrointestinal tract require additional medical support in the form of parenteral nutrition. Advances in parenteral solutions, products, and delivery systems make parenteral nutritional support possible in veterinary medicine, although not possible in all small animal practices. Proper patient selection, well-informed clients, dedicated technicians, and knowledgeable veterinarians are all essential in the successful implementation of parenteral nutritional support.

Dietary and nutritional management of gastrointestinal diseases.

The value of proper diet in the management of the gastrointestinal patient has been demonstrated. As experience and knowledge increase, diets will become more refined to address specific diet-related abnormalities. There is an increasing awareness in veterinary medicine, and justifiably so, of the benefit of nutritional support, administered enterally or parenterally. Aggressive, early, and adequate nutritional support may be the most important factor responsible for a successful response to other aspects of therapy and recovery, and has to represent an improvement in veterinary medicine.

Nutrient digestibility of brewers single cell protein.

Six growing wethers were used in a total collection digestion trial to estimate the nutrient digestibility of brewers single cell protein (BSCP). The BSCP product was obtained by allowing microbial growth to occur aerobically on the effluent wash waters of a brewery and then harvesting the solids through a spray drying procedure. This process produced a dry powder product containing 50% crude protein. Wethers were fed a corn-based diet with BSCP replacing corn at 0, 20 and 40% of the diet in a 3 X 3 replicated Latin square design. There were no consumption or palatability problems encountered when wethers were fed BSCP-containing diets. Nutrient digestibility of BSCP was estimated by a least-squares analysis regressing apparent digestibility of each nutrient on BSCP content. Digestion coefficients of BSCP for dry matter, energy and crude protein were calculated as 66.6, 73.3 and 86.5%, respectively. The addition of BSCP to corn-based diets decreased the overall diet digestibility of dry matter, energy and carbohydrate (P less than .05). Diet crude protein digestibility was not significantly affected by the BSCP addition. Nutrient digestibilities indicate brewers single cell protein is a satisfactory source of supplemental protein, approximately equivalent to cottonseed meal on a weight basis.