A double peaked pulse profile observed in GX 1+4

The hard X-ray pulsar GX 1+4 was observed several times in the last few years with a pair of balloon-borne Xenon filled Multi-cell Proportional Counters (XMPC). In a balloon flight made on 22 March 1995, the source was detected in a bright state, the average observed source count rate being $8.0\pm0.2/s$ per detector. X-ray pulsations with a period of $121.9\pm0.1$ s were detected in the source with a broad double peak pulse feature. When observed in December 1993 with the same instrument, the pulse profile of GX 1+4 showed a single peak. This change in the pulse profile to a double pulse structure in about 15 months indicates either activation of the opposite pole of the neutron star if the magnetic field is asymmetric or possibly a change in the beam pattern, from a pencil beam to a fan beam. Assuming a fan beam configuration, the pulse profile is used to find the inclinations of the magnetic axis and the viewing axis with the spin axis. The derived angles support the GINGA observations of a dip in the pulse profile which was resolved to have a local maximum in one of the observations and was explained with resonance scattering of cyclotron line energy photons by the accretion column (Makishima et al., \markcite{maki1988}, Dotani et al., \markcite{dotani1989}.). Compared to our previous observation of the same source with the same telescope (Rao et al., \markcite{rao1994}) a period change rate of $0.72 \pm 0.40 s/yr$ is obtained which is the lowest rate of change of period for this source since its discovery. Average pulse fraction in the hard X-ray range is low (30%), consistent with its anti correlation with luminosity as reported by us earlier (Rao et al., \markcite{rao1994}) and the observed spectrum is very hard (power law photon index $1.67\pm0.12$).Comment: 10 pages, to appear in A&

Economic Comparison of Alternatives to Sulfamethazine Use in Pork Production

Sulfamethazinehas been widely used in the production of meat animals. It is effective as a product for treatment as well as prevention of animal disease leading to improved production efficiencies and lower cost meat and meat products. This was true especially in pork production. However, in recent years, use ofsulfamethazine in meat animal production has received a renewed focus. Thisstudy provides an economic analysis ofselected alternatives to the use of sulfamethazine in pork production. Alternatives evaluated were sulfathiazole, oxytetracycline, chlortetracycline, tylosin and lincomycin. Sulfathiazole isshown to be the most cost effective alternative. Production efficiency, production costs, and pork priceswere only slightly impacted when sulfathiazole was substituted for sulfamethazine. Sulfathiazole is followed by lincomycin, then the tetracyclines, and tylosi

Systems Medicine of Cancer: Bringing Together Clinical Data and Nonlinear Dynamics of Genetic Networks

Editoria

Cost-Effectiveness of Genetic Testing for All Women Diagnosed with Breast Cancer in China

Unselected multigene testing for all women with breast cancer (BC) identifies more cancer susceptibility gene (CSG) carriers who can benefit from precision prevention compared with family history (FH)/clinical-criteria-based guidelines. Very little CSG testing is undertaken in middle-income countries such as China, and its cost-effectiveness remains unaddressed. We aimed to estimate cost-effectiveness and population impact of multigene testing for all Chinese BC patients. Data from 8085 unselected BC patients recruited to a Peking University Cancer Hospital study were used for microsimulation modeling, comparing three strategies in the Chinese setting: all BC women undergo BRCA1/BRCA2/PALB2 genetic testing, only BC women fulfilling FH/clinical criteria undergo BRCA testing, and no genetic testing. Prophylactic mastectomy and salpingo-oophorectomy would be adopted where appropriate. Societal and payer perspectives with a lifetime horizon along with sensitivity analyses were presented. Incremental cost-effectiveness ratio (ICER): incremental cost per quality-adjusted life-year (QALY) gained is compared to the USD 10,260/QALY (one-times GDP per capita) willingness-to-pay threshold. BC incidence, ovarian cancer (OC) incidence, and related deaths were also estimated. FH/clinical-criteria-based BRCA testing was ruled out on the principle of extensive dominance. Compared with no genetic testing, multigene testing for all BC patients had an ICER = USD 4506/QALY (societal perspective) and USD 7266/QALY (payer perspective), well below our threshold. Probabilistic sensitivity analysis showed unselected multigene testing remained cost-effective for 94.2%/86.6% of simulations from the societal and payer perspectives. One year's unselected multigene testing could prevent 7868 BC/OC cases and 5164 BC/OC deaths in China. Therefore, unselected multigene testing is extremely cost-effective and should be offered to all Chinese women with BC

Enhanced endosomal signaling and desensitization of GLP-1R versus GIPR in pancreatic beta cells

The incretin receptors, glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), are prime therapeutic targets for the treatment of type 2 diabetes (T2D) and obesity. They are expressed in pancreatic beta cells where they potentiate insulin release in response to food intake. Despite GIP being the main incretin in healthy individuals, GLP-1R has been favored as a therapeutic target due to blunted GIPR responses in T2D patients and conflicting effects of GIPR agonists and antagonists in improving glucose tolerance and preventing weight gain. There is, however, a recently renewed interest in GIPR biology following the realization that GIPR responses can be restored after an initial period of blood glucose normalization and the recent development of dual GLP-1R/GIPR agonists with superior capacity for controlling blood glucose levels and weight. The importance of GLP-1R trafficking and subcellular signaling in the control of receptor outputs is well established, but little is known about the pattern of spatiotemporal signaling from the GIPR in beta cells. Here, we have directly compared surface expression, trafficking and signaling characteristics of both incretin receptors in pancreatic beta cells to identify potential differences that might underlie distinct pharmacological responses associated with each receptor. Our results indicate increased cell surface levels, internalization, degradation, and endosomal versus plasma membrane activity for the GLP-1R, while the GIPR is instead associated with increased plasma membrane recycling, reduced desensitization, and enhanced downstream signal amplification. These differences might have potential implications for the capacity of each incretin receptor to control beta cell function

Discovery of optical pulsations in V2116 Ophiuchi/GX 1+4

We report the detection of pulsations with $\sim 124$ s period in V2116 Oph, the optical counterpart of the low-mass X-ray binary GX 1+4. The pulsations are sinusoidal with modulation amplitude of up to 4% in blue light and were observed in ten different observing sessions during 1996 April-August using a CCD photometer at the 1.6-m and 0.6-m telescopes of Laborat\'orio Nacional de Astrof\'{\i}sica, in Brazil. The pulsations were also observed with the $UBVRI$ fast photometer. With only one exception the observed optical periods are consistent with those observed by the BATSE instrument on board the Compton Gamma Ray Observatory at the same epoch. There is a definite correlation between the observability of pulsations and the optical brightness of the system: V2116~Oph had $R$ magnitude in the range $15.3-15.5$ when the pulsed signal was detected, and $R = 16.0-17.7$ when no pulsations were present. The discovery makes GX 1+4 only the third of $\sim 35$ accretion-powered X-ray pulsars to be firmly detected as a pulsating source in the optical. The presence of flickering and pulsations in V2116 Oph adds strong evidence for an accretion disk scenario in this system. The absolute magnitude of the pulsed component on 1996 May 27 is estimated to be $M_V \sim -1.5$. The implied dimensions for the emitting region are 1.1 R_{\sun}, 3.2 R_{\sun}, and 7.0 R_{\sun}, for black-body spectral distributions with $T = 10^5$ K, $2 \times 10^4$ K, and $1 \times 10^4$ K, respectively.Comment: 9 pages, 3 figures in PostScript, latex, accepted for publication on the Astrophysical Journal Letter