Aspects of Black Hole Quantum Mechanics and Thermodynamics in 2+1 Dimensions

We discuss the quantum mechanics and thermodynamics of the (2+1)-dimensional black hole, using both minisuperspace methods and exact results from Chern-Simons theory. In particular, we evaluate the first quantum correction to the black hole entropy. We show that the dynamical variables of the black hole arise from the possibility of a deficit angle at the (Euclidean) horizon, and briefly speculate as to how they may provide a basis for a statistical picture of black hole thermodynamics.Comment: 20 pages and 2 figures, LaTeX, IASSNS-HEP-94/34 and UCD-94-1

Hamiltonian thermodynamics of the Reissner-Nordstr\"om-anti-de Sitter black hole

We consider the Hamiltonian dynamics and thermodynamics of spherically symmetric Einstein-Maxwell spacetimes with a negative cosmological constant. We impose boundary conditions that enforce every classical solution to be an exterior region of a Reissner-Nordstr\"om-anti-de Sitter black hole with a nondegenerate Killing horizon, with the spacelike hypersurfaces extending from the horizon bifurcation two-sphere to the asymptotically anti-de Sitter infinity. The constraints are simplified by a canonical transformation, which generalizes that given by Kucha\v{r} in the spherically symmetric vacuum Einstein theory, and the theory is reduced to its true dynamical degrees of freedom. After quantization, the grand partition function of a thermodynamical grand canonical ensemble is obtained by analytically continuing the Lorentzian time evolution operator to imaginary time and taking the trace. A~similar analysis under slightly modified boundary conditions leads to the partition function of a thermodynamical canonical ensemble. The thermodynamics in each ensemble is analyzed, and the conditions that the (grand) partition function be dominated by a classical Euclidean black hole solution are found. When these conditions are satisfied, we recover in particular the Bekenstein-Hawking entropy. The limit of a vanishing cosmological constant is briefly discussed. (This paper is dedicated to Karel Kucha\v{r} on the occasion of his sixtieth birthday.)Comment: 34 pages, REVTeX v3.0. (Minor corrections and presentational revisions; added references.

Reduced phase space formalism for spherically symmetric geometry with a massive dust shell

We perform a Hamiltonian reduction of spherically symmetric Einstein gravity with a thin dust shell of positive rest mass. Three spatial topologies are considered: Euclidean (R^3), Kruskal (S^2 x R), and the spatial topology of a diametrically identified Kruskal (RP^3 - {a point at infinity}). For the Kruskal and RP^3 topologies the reduced phase space is four-dimensional, with one canonical pair associated with the shell and the other with the geometry; the latter pair disappears if one prescribes the value of the Schwarzschild mass at an asymptopia or at a throat. For the Euclidean topology the reduced phase space is necessarily two-dimensional, with only the canonical pair associated with the shell surviving. A time-reparametrization on a two-dimensional phase space is introduced and used to bring the shell Hamiltonians to a simpler (and known) form associated with the proper time of the shell. An alternative reparametrization yields a square-root Hamiltonian that generalizes the Hamiltonian of a test shell in Minkowski space with respect to Minkowski time. Quantization is briefly discussed. The discrete mass spectrum that characterizes natural minisuperspace quantizations of vacuum wormholes and RP^3-geons appears to persist as the geometrical part of the mass spectrum when the additional matter degree of freedom is added.Comment: 36 pages, REVTeX v3.1 with amsfonts. (References updated; minor typos corrected.

Hamiltonian thermodynamics of two-dimensional vacuum dilatonic black holes

We consider the Hamiltonian dynamics and thermodynamics of the two-dimensional vacuum dilatonic black hole in the presence of a timelike boundary with a fixed value of the dilaton field. A~canonical transformation, previously developed by Varadarajan and Lau, allows a reduction of the classical dynamics into an unconstrained Hamiltonian system with one canonical pair of degrees of freedom. The reduced theory is quantized, and a partition function of a canonical ensemble is obtained as the trace of the analytically continued time evolution operator. The partition function exists for any values of the dilaton field and the temperature at the boundary, and the heat capacity is always positive. For temperatures higher than $\beta_c^{-1} = \hbar\lambda/(2\pi)$, the partition function is dominated by a classical black hole solution, and the dominant contribution to the entropy is the two-dimensional Bekenstein-Hawking entropy. For temperatures lower than~$\beta_c^{-1}$, the partition function remains well-behaved and the heat capacity is positive in the asymptotically flat space limit, in contrast to the corresponding limit in four-dimensional spherically symmetric Einstein gravity; however, in this limit, the partition function is not dominated by a classical black hole solution.Comment: 20 pages, REVTEX. Added a discussion on the boundary action and boundary terms in Sec. IIIA. Minor changes in Acknowledgements and Reference

Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Therapy Insight: Parenteral Estrogen treatment for Prostate Cancer—a new dawn for an old therapy

Oral estrogens were the treatment of choice for carcinoma of the prostate for over four decades, but were abandoned because of an excess of cardiovascular and thromboembolic toxicity. It is now recognized that most of this toxicity is related to the first pass portal circulation, which upregulates the hepatic metabolism of hormones, lipids and coagulation proteins. Most of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration, which avoids hepatic enzyme induction. It also seems that a short-term but modest increase in cardiovascular morbidity (but not mortality) is compensated for by a long-term cardioprotective benefit, which accrues progressively as vascular remodeling develops over time. Parenteral estrogen therapy has the advantage of giving protection against the effects of andropause (similar to the female menopause), which are induced by conventional androgen suppression and include osteoporotic fracture, hot flashes, asthenia and cognitive dysfunction. In addition, parenteral estrogen therapy is significantly cheaper than contemporary endocrine therapy, with substantive economic implications for health providers

The validity of the EQ-5D-3L items: An investigation with type 2 diabetes patients from six European countries

Background: Most previous studies concerning the validity of the EQ-5D-3L items refer to applications of only a single language version of the EQ-5D-3L in only one country. Therefore, there is little information concerning the extent to which the results can be generalised across different language versions and

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

GH peak response to GHRH-arginine: relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50–90

OBJECTIVE: To assess the GH response to GHRH-arginine in apparently healthy adults in relation to cardiovascular risk factors. DESIGN: Cross-sectional. PATIENTS: Eighty-six male and female volunteers aged 50–90. MEASUREMENTS: GH peak response to GHRH-arginine and cardiovascular risk factors, including obesity, insulin resistance, low levels of high density lipoprotein (HDL) cholesterol, elevated triglycerides, and hypertension. The primary outcome measurement was GH response to GHRH-arginine. The relationship between GH peak responses and cardiovascular risk factors was determined after data collection. RESULTS: GH peaks were highly variable, ranging from 2·3 to 185 µg/l (14% with GH peaks < 9 µg/l). An increasing number of cardiovascular risk factors were associated with a lower mean GH peak (P < 0·0001). By univariate analysis, fasting glucose, insulin, body mass index (BMI), HDL cholesterol and triglycerides were significantly associated with GH peak (all P < 0·0001). Multiple regression analysis revealed that fasting glucose, fasting insulin, BMI, triglycerides and sex accounted for 54% of GH peak variability. The role of abdominal fat as it relates to GH peak was explored in a subset of 45 subjects. Trunk fat and abdominal subregion fat measured by dual energy X-ray absorptiometry (DXA) were inversely related to GH peak (P < 0·008 and 0·001, respectively). Analysis of this subgroup by multiple regression revealed that subregion abdominal fat became the significant obesity-related determinant of GH peak, but still lagged behind fasting insulin and glucose. CONCLUSIONS: GH response to secretagogues was highly variable in apparently healthy adults aged 50–90 years. Peak GH was significantly related to fasting glucose, insulin, BMI, HDL cholesterol, triglycerides, trunk fat and abdominal subregion fat, with fasting glucose ranking first by multiple regression analysis. There was a strong relationship between cardiovascular risk factors and low GH, with individual risk factors being additive. Although these data do not differentiate between low GH being a cause or an effect of these cardiovascular risk factors, they indicate that the relationship between low GH and increased cardiovascular risk may be physiologically important in the absence of pituitary disease