The Effect of Propranolol and Midazolam on the Reconsolidation of a Morphine Place Preference in Chronically Treated Rats

A stable memory can be disrupted if amnestic treatment is applied in conjunction with memory reactivation. Recent findings in the conditioned place preference (CPP) model suggest that blocking reconsolidation attenuates the ability of environmental cues to induce craving and relapse in drug addicts, but the impact of prior physical dependence has not been described. We examined the effect of post-reactivation amnestic treatment on reconsolidation of a CPP for morphine, in animals naïve to morphine, under chronic morphine experience or abstinent. Chronic morphine experience was induced by escalating doses of morphine from 10 mg/kg/day (s.c.), and maintained on 30 mg/kg/day during the course of conditioning and reactivation procedures, or conditioning alone. Naïve and morphine-experienced animals were trained in a three-compartment apparatus by four morphine (5 mg/kg, s.c.) and four saline experiences paired with either of two large conditioning compartments. The memory was then reactivated by a CPP test, and immediately afterward animals received an injection of the beta-adrenergic antagonist propranolol (10 mg/kg, s.c.), the GABAa agonist midazolam (1 mg/kg, i.p.), or saline. Morphine-naïve rats received only a single reconsolidation-blocking treatment (Experiment 1), while chronic morphine rats were given eight reactivation sessions each followed by amnestic treatment, either before (Experiment 2) or after 10 days of withdrawal (Experiment 3). Propranolol and midazolam disrupted reconsolidation in morphine-naïve rats, but failed to disrupt the CPP when rats were trained under chronic morphine treatment, even if they were recovered from chronic opiate exposure before reactivation. In fact, propranolol increased the preference for the drug-paired context in animals trained while maintained on chronic morphine. Midazolam had little effect. Morphine experience may produce neurochemical changes which alter memory storage processes and reduce the impact of amnestic treatments on reconsolidation

Climatology of the daily temperature range annual cycle in the United States

Many researchers are presently interested in detecting long-term trends in annual or seasonal daily temperature range (DTR), and attributing these changes to anthropogenic origins. However, very little work has been done to confirm the mechanisms that are important to determining the long-term average annual cycle of the DTR. Therefore, the focus of this work is to examine the spatial and temporal difference in the DTR average annual cycle across the United States, and to associate the patterns of these cycles with potential causal variables. Three major types of DTR annual cycle exist in the United States: high sun season maximum (northern and western U.S.), low sun season maximum (south central and southeast U.S.), and transitional season maxima (middle latitude in the U.S.). The annual cycles of the DTR in the northern and western U.S. are well related to average annual cycles of cloud cover and dew point temperature; only areas to the west of the Rocky Mountains have a strong linkage between DTR and precipitation frequency annual cycles. Across the northern tier of the U.S., the loss of snow cover is important to DTR transitions during the spring season. However, the onset of snow cover in the fall does not appear to be the major factor in DTR variations, which are instead more strongly associated with cloud cover effects. As expected from their sinusoidal annual cycle, maximum and minimum temperature cycles are linearly related to the DTR in regions with a warm season or cold season DTR maximum, while non-linear relationships exist where the DTR annual cycle has maxima in the transition seasons

Dynamical Bonding Driving Mixed Valency in a Metal Boride

Samarium hexaboride is an anomaly, having many exotic and seemingly mutually incompatible properties. It was proposed to be a mixed-valent semiconductor, and later - a topological Kondo insulator, and yet has a Fermi surface despite being an insulator. We propose a new and unified understanding of SmB$_6$ centered on the hitherto unrecognized dynamical bonding effect: the coexistence of two Sm-B bonding modes within SmB$_6$, corresponding to different oxidation states of the Sm. The mixed valency arises in SmB$_6$ from thermal population of these distinct minima enabled by motion of B. Our model simultaneously explains the thermal valence fluctuations, appearance of magnetic Fermi surface, excess entropy at low temperatures, pressure-induced phase transitions, and related features in Raman spectra and their unexpected dependence on temperature and boron isotope

Submillimeter Observations of the Ultraluminous BAL Quasar APM 08279+5255

With an inferred bolometric luminosity of 5\times10^{15}{\rm \lsun}, the recently identified z=3.87, broad absorption line quasar APM 08279+5255 is apparently the most luminous object currently known. As half of its prodigious emission occurs in the infrared, APM 08279+5255 also represents the most extreme example of an Ultraluminous Infrared Galaxy. Here, we present new submillimeter observations of this phenomenal object; while indicating that a vast quantity of dust is present, these data prove to be incompatible with current models of emission mechanisms and reprocessing in ultraluminous systems. The influence of gravitational lensing upon these models is considered and we find that while the emission from the central continuum emitting region may be significantly enhanced, lensing induced magnification cannot easily reconcile the models with observations. We conclude that further modeling, including the effects of any differential magnification is required to explain the observed emission from APM 08279+5255.Comment: 12 Pages with Two figures. Accepted for publication in the Astrophysical Journal Letter

Optical Spectroscopy of the Surface Population of the rho Ophiuchi Molecular Cloud: The First Wave of Star Formation

We present the results of optical spectroscopy of 139 stars obtained with the Hydra multi-object spectrograph. The objects extend over a 1.3 square degree area surrounding the main cloud of the rho Oph complex. The objects were selected from narrowband images to have H alpha in emission. Using the presence of strong H alpha emission, lithium absorption, location in the Hertzsprung-Russell diagram, or previously reported x-ray emission, we were able to identify 88 objects as young stars associated with the cloud. Strong H alpha emission was confirmed in 39 objects with line widths consistent with their origin in magnetospheric accretion columns. Two of the strongest emission-line objects are young, x-ray emitting brown dwarf candidates with M8 spectral types. Comparisons of the bolometric luminosities and effective temperatures with theoretical models suggest a medianage for this population of 2.1 Myr which is signifcantly older than the ages derived for objects in the cloud core. It appears that these stars formed contemporaneously with low mass stars in the Upper Scorpius subgroup, likely triggered by massive stars in the Upper-Centaurus subgroup.Comment: 35 pages of postscript which includes seven figures (some of which are multi-panel) and four postscript tables. Astronomical Journal (in press

Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program)

Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a)

APM 08279+5255: an ultraluminous BAL quasar at a redshift z=3.87

We report on the discovery of a highly luminous, broad absorption line quasar at a redshift of $z=3.87$ which is positionally coincident, within one arcsecond, with the IRAS FSC source F08279+5255. A chance alignment of the quasar and the IRAS source is extremely unlikely and we argue that the optical and FIR flux are different manifestations of the same object. With an R-band magnitude of 15.2, and an IRAS 60\mum flux of 0.51\jy, APM 08279+5255 is (apparently) easily the most intrinsically luminous object known, with L_{Bol}\sim5\times10^{15}L_{\odot}}. Imaging suggests that gravitational lensing may play a role in amplifying the intrinsic properties of the system. The optical spectrum of the quasar clearly reveals the presence of three potential lensing galaxies, \mg absorption systems at $z=1.18$ and $z=1.81$, and a \ly absorption system at $z=3.07$. We estimate the total amplification of the optical component to be $\approx40$, but, due to the larger scale of the emitting region, would expect the infrared amplification to be significantly less. Even making the conservative assumption that all wavelengths are amplified by a factor 40, APM 08279+5255 still possesses a phenomenal luminosity of \simgt 10^{14L_{\odot}}, indicating that it belongs to a small, but significant population of high--redshift, hyperluminous objects with copious infrared emission.Comment: 15 Pages with Four figures. Accepted for publication in the Astrophysical Journa

Considering the impact of situation-specific motivations and constraints in the design of naturally ventilated and hybrid buildings

A simple logical model of the interaction between a building and its occupants is presented based on the principle that if free to do so, people will adjust their posture, clothing or available building controls (windows, blinds, doors, fans, and thermostats) with the aim of achieving or restoring comfort and reducing discomfort. These adjustments are related to building design in two ways: first the freedom to adjust depends on the availability and ease-of-use of control options; second the use of controls affects building comfort and energy performance. Hence it is essential that these interactions are considered in the design process. The model captures occupant use of controls in response to thermal stimuli (too warm, too cold etc.) and non-thermal stimuli (e.g. desire for fresh air). The situation-specific motivations and constraints on control use are represented through trigger temperatures at which control actions occur, motivations are included as negative constraints and incorporated into a single constraint value describing the specifics of each situation. The values of constraints are quantified for a range of existing buildings in Europe and Pakistan. The integration of the model within a design flow is proposed and the impact of different levels of constraints demonstrated. It is proposed that to minimise energy use and maximise comfort in naturally ventilated and hybrid buildings the designer should take the following steps: 1. Provide unconstrained low energy adaptive control options where possible, 2. Avoid problems with indoor air quality which provide motivations for excessive ventilation rates, 3. Incorporate situation-specific adaptive behaviour of occupants in design simulations, 4. Analyse the robustness of designs against variations in patterns of use and climate, and 5. Incorporate appropriate comfort standards into the operational building controls (e.g. BEMS)