J. I. Katz

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial

Background: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. Methods: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. Results: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. Conclusions: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis. GLOSSARY: ALS = amyotrophic lateral sclerosis; ALSFRS-r = revised ALS functional rating scale; AUC = area under the curve; DVT = deep venous thromboses; IGF-1 = insulin-like growth factor type I; MMT = manual muscle testing; PE = pulmonary embolisms.

LOW-FREQUENCY SPECTRA OF GAMMA-RAY BURSTS

I argue that particles heated by relativistic shocks should assume an equilibrium energy distribution. This leads to a synchrotron spectrum F(sub nu) varies as nu(sup 1/3) up to approximately the critical frequency nu(sub 0) of an electron with the mean electron energy. Application to gamma ray bursts (GRBs) implies that a burst with 10(exp -5) erg/(sq cm s) of soft gamma-rays and h(nu(sub 0)) = 300 KeV should be about 18th magnitude in visible light and a few micro-Jy at 1 GHz (less if self-absorbed).Particles with energies below the mean energy E(sub 0) in relativistic shocked plasmas should assume an equilibrium energy distribution. This leads to a synchrotron spectrum F(sub nu) proportional to nu(exp 1/3) up to approximately the critical frequency nu(sub 0) of an electron with the energy E(sub 0). Application to gamma-ray bursts (GRBs) implies that a burst with 10(exp -5) ergs/sq cm/s of soft gamma rays and h nu(sub 0) = 300 keV should simultaneously be about 18th magnitude in visible light and a few micro-J at 1 GHz (less if self-absorbed); the low-freqency intensities peak later at higher values.

Two kinds of stellar collapse

HERE I shall show that the events which produce compact objects may be divided into at least two classes on the basis of the impulse given to a binary system containing the collapsing object. This impulse may be related to the amount and symmetry of mass loss resulting from the collapse event.

A Precessing Disk in OJ 287

Sillanpaa et al. have demonstrated that the active galactic nucleus OJ 287 has intensity peaks that recur within a period of about 12 yr. I suggest that this is the result of the sweeping of a precessing relativistic beam across our line of sight. In analogy to Hercules X-1 and SS 433, precession is attributed to the torque exerted by a companion mass on an accretion disk. Secondary maxima observed 1.2 yr after two of these peaks may be evidence of nodding motion.

Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis

BACKGROUND Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. METHODS In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. FINDINGS Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. INTERPRETATION Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. FUNDING Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.

Radiation hydrodynamic calculation of super-Eddington accretion disks

The results of nonrelativistic radiation-hydrodynamic calculations of axisymmetric supercritical accretion disks around Newtonian quasi-black holes are reported. Anisotropic and isotropic constant kinematic viscosity models are used, with radiation transport described by a gray Thomson scattering opacity and flux-limited diffusion. The resulting solutions have four distinct zones: (1) centered on the disk midplane is a thick, dense region of turbulent convection; (2) above this is an accretion zone in which low angular momentum matter rapidly flows onto the black hole; (3) the accretion zone is bounded by a photocone, in which the matter becomes optically thin; (4) inside the photocone, surrounding the angular momentum axis, is a broad subrelativistic jet of expelled matter. Applications of these results to SS 433 and to extragalactic jets are discussed. 44 references.

Persistent Counterparts to Gamma-Ray Bursts

The recent discovery of persistent gamma-ray burst (GRB) counterparts at lower frequencies permits several important conclusions to be drawn. The spectrum of GRB 970508 is not consistent with an external shock origin for both the prompt GRB and the persistent emission, suggesting that at least the prompt radiation is produced by internal shocks. Comparisons among three GRBs with counterparts (or upper limits on them) establishes that GRBs are not all scaled versions of similar events. The angular size inferred from the apparent observation of self-absorption in the radio spectrum of GRB 970508 a week later implies that its expansion had slowed to semirelativistic speeds. This permits a remarkably low upper bound to be placed on its residual energy, suggesting either that radiation has been more than 99.7% efficient or that the initial outflow was strongly collimated. Observations of self-absorbed radio emission from future GRBs may permit direct measurement of their expansion and determination of their parameters and energetics. We estimate initial Lorentz factors of γ0 ~ 100 for GRB 970228 and GRB 970508, and present a solution for the evolution of a blast wave with instantaneous cooling.

Universal particle acceleration

An approximate theory, in the spirit of the mixing-length theory, of the acceleration of particles in low-density shear flows is presented. The energy required to accelerate the particles is drawn from the velocity field by means of a particle acceleration-induced viscosity. This theory is applied to a number of astrophysical flows, including accretion disks, radial accretion and convective turbulence. The most promising application is to disks, where the theory suggests a mechanism by which the bulk of the accretion power may be converted to particle acceleration.

Climate engineering responses to climate emergencies

Despite efforts to stabilize CO_2 concentrations, it is possible that the climate system could respond abruptly with catastrophic consequences. Intentional intervention in the climate system to avoid or ameliorate such consequences has been proposed as one possible response, should such a scenario arise. In a one-week study, the authors of this report conducted a technical review and evaluation of proposed climate engineering concepts that might serve as a rapid palliative response to such climate emergency scenarios. Because of their potential to induce a prompt (less than one year) global cooling, this study concentrated on Shortwave Climate Engineering (SWCE) methods for moderately reducing the amount of shortwave solar radiation reaching the Earth. The studys main objective was to outline a decade-long agenda of technical research that would maximally reduce the uncertainty surrounding the benefits and risks associated with SWCE. For rigor of technical analysis, the study focused the research agenda on one particular SWCE concept--stratospheric aerosol injection--and in doing so developed several conceptual frameworks and methods valuable for assessing any SWCE proposal.

Yet Another Model of Gamma-Ray Bursts

Sari & Piran have demonstrated that the time structure of gamma-ray bursts (GRBs) must reflect the time structure of their energy release. A model that satisfies this condition uses the electrodynamic emission of energy by the magnetized rotating ring of dense matter left by neutron star coalescence; GRBs are essentially fast, high-field, differentially rotating pulsars. The energy densities are large enough for the power to appear as an outflowing equilibrium pair plasma, which produces the burst by baryon entrainment and subsequent internal shocks. In this paper the magnetic field and the characteristic timescale for its rearrangement—which determines the observed time structure of the burst—are estimated. There may be quasi-periodic oscillations at the rotational frequencies, which are predicted to range up to 5770 Hz (in a local frame). This model is one of a general class of electrodynamic accretion models that includes the Blandford and Lovelace model of active galactic nuclei and that can also be applied to black hole X-ray sources of stellar mass. The apparent efficiency of nonthermal particle acceleration is predicted to be 10%-50%, but higher values are possible if the underlying accretion flow is super-Eddington.