Hydrochloric Acid Infusion for the Treatment of Metabolic Alkalosis in Surgical Intensive Care Unit Patients

Background: Older reports of use of hydrochloric acid (HCl) infusions for treatment of metabolic alkalosis document variable dosing strategies and risk. Objectives: This study sought to characterize use of HCl infusions in surgical intensive care unit patients for the treatment of metabolic alkalosis. Methods: This retrospective review included patients who received a HCl infusion for \u3e8 hours. The primary end point was to evaluate the utility of common acid-base equations for predicting HCl dose requirements. Secondary end points evaluated adverse effects, efficacy, duration of therapy, and total HCl dose needed to correct metabolic alkalosis. Data on demographics, potential causes of metabolic alkalosis, fluid volume, and duration of diuretics as well as laboratory data were collected. Results: A total of 30 patients were included, and the average HCl infusion rate was 10.5 ± 3.7 mEq/h for an average of 29 ± 14.6 hours. Metabolic alkalosis was primarily diuretic-induced (n = 26). Efficacy was characterized by reduction in the median total serum CO2 from 34 to 27 mM/L (P \u3c 0.001). The change in chloride ion deficit and change in apparent strong ion difference (SIDa) were not correlated with total HCl administered. There were no documented serious adverse effects related to HCl infusions. Conclusion: HCl was effective for treating metabolic alkalosis, and no serious adverse events were seen. In this clinical setting, the baseline chloride ion deficit and SIDa were not useful for prediction of total HCl dose requirement, and serial monitoring of response is recommended

Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking

PURPOSE: This study examined the association of post-treatment changes in cognitive performance, apolipoprotein E (APOE), and smoking in breast cancer patients treated with adjuvant therapy. PARTICIPANTS AND METHODS: Breast cancer patients treated with chemotherapy (N = 55, age = 51.9 ± 7.1, education = 15.7 ± 2.6) were evaluated with a battery of neuropsychological tests prior to chemotherapy and at 1, 6, and 18 months post-chemotherapy. Matched groups of breast cancer patients not exposed to chemotherapy (N = 68, age = 56.8 ± 8.3, education = 14.8 ± 2.2) and healthy controls (N = 43, age = 53.0 ± 10.1, education = 15.2 ± 2.6) were evaluated at similar intervals. APOE epsilon 4 carrier status (APOE4+) and smoking history were also evaluated. RESULTS: The detrimental effect of APOE4+ genotype on post-treatment cognitive functioning was moderated by smoking history, that is, patients without a smoking history had significantly lower performance on measures of processing speed and working memory compared with those with a smoking history and healthy controls. Exploratory analyses revealed that APOE4+ patients without a smoking history who were exposed to chemotherapy showed a decline in performance in processing speed, compared with patients with a smoking history. A similar but less pronounced pattern was seen in the no chemotherapy group (primarily endocrine treatment). For working memory, the APOE4+ by smoking interaction was observed in the no chemotherapy group only. CONCLUSIONS: The association between APOE status, breast cancer treatment, and cognitive functioning was moderated by smoking history suggesting that both chemotherapy and endocrine therapy interact with APOE status and smoking to influence cognition. A putative mechanism is that smoking corrects a deficit in nicotinic receptor functioning and dopamine levels in APOE4+ individuals

Submillimetre line spectrum of the Seyfert galaxy NGC1068 from the Herschel-SPIRE Fourier Transform Spectrometer

The first complete submillimetre spectrum (190-670um) of the Seyfert 2 galaxy NGC1068 has been observed with the SPIRE Fourier Transform Spectrometer onboard the {\it Herschel} Space Observatory. The sequence of CO lines (Jup=4-13), lines from water, the fundamental rotational transition of HF, two o-H_2O+ lines and one line each from CH+ and OH+ have been detected, together with the two [CI] lines and the [NII]205um line. The observations in both single pointing mode with sparse image sampling and in mapping mode with full image sampling allow us to disentangle two molecular emission components, one due to the compact circum-nuclear disk (CND) and one from the extended region encompassing the star forming ring (SF-ring). Radiative transfer models show that the two CO components are characterized by density of n(H_2)=10^4.5 and 10^2.9 cm^-3 and temperature of T=100K and 127K, respectively. The comparison of the CO line intensities with photodissociation region (PDR) and X-ray dominated region (XDR) models, together with other observational constraints, such as the observed CO surface brightness and the radiation field, indicate that the best explanation for the CO excitation of the CND is an XDR with density of n(H_2) 10^4 cm^-3 and X-ray flux of 9 erg s^-1 cm^-2, consistent with illumination by the active galactic nucleus, while the CO lines in the SF-ring are better modeled by a PDR. The detected water transitions, together with those observed with the \her \sim PACS Spectrometer, can be modeled by an LVG model with low temperature (T_kin \sim 40K) and high density (n(H_2) in the range 10^6.7-10^7.9 cm^-3).Comment: Accepted for publication on the Astrophysical Journal, 30 August 201

Observations of Arp 220 using Herschel-SPIRE: An Unprecedented View of the Molecular Gas in an Extreme Star Formation Environment

We present Herschel SPIRE-FTS observations of Arp~220, a nearby ULIRG. The FTS continuously covers 190 -- 670 microns, providing a good measurement of the continuum and detection of several molecular and atomic species. We detect luminous CO (J = 4-3 to 13-12) and water ladders with comparable total luminosity; very high-J HCN absorption; OH+, H2O+, and HF in absorption; and CI and NII. Modeling of the continuum yields warm dust, with T = 66 K, and an unusually large optical depth of ~5 at 100 microns. Non-LTE modeling of the CO shows two temperature components: cold molecular gas at T ~ 50 K and warm molecular gas at T ~1350 K. The mass of the warm gas is 10% of the cold gas, but dominates the luminosity of the CO ladder. The temperature of the warm gas is in excellent agreement with H2 rotational lines. At 1350 K, H2 dominates the cooling (~20 L_sun/M_sun) in the ISM compared to CO (~0.4 L_sun/M_sun). We found that only a non-ionizing source such as the mechanical energy from supernovae and stellar winds can excite the warm gas and satisfy the energy budget of ~20 L_sun/M_sun. We detect a massive molecular outflow in Arp 220 from the analysis of strong P-Cygni line profiles observed in OH+, H2O+, and H2O. The outflow has a mass > 10^{7} M_sun and is bound to the nuclei with velocity < 250 km/s. The large column densities observed for these molecular ions strongly favor the existence of an X-ray luminous AGN (10^{44} ergs/s) in Arp 220.Comment: Accepted in ApJ on September 1, 201

Deep Underground Science and Engineering Laboratory - Preliminary Design Report

The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations

The Demise of Islet Allotransplantation in the US: A Call for an Urgent Regulatory Update The ISLETS FOR US Collaborative

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and more than minimally manipulated human cell and tissue products (HCT/Ps). Across the world, human islets are appropriately defined as minimally manipulated tissue which has led to islet transplantation becoming a standard-of-care procedure for patients with type 1 diabetes mellitus and problematic hypoglycemia. As a result of the outdated US regulations, only eleven patients underwent allo-ITx in the US between 2011-2016 and all in the setting of a clinical trial. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both, better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States