An injection and mixing element for delivery and monitoring of inhaled nitric oxide

Background Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used primarily in the critical care setting for patients concurrently supported by invasive or noninvasive positive pressure ventilation. NO delivery devices interface with ventilator breathing circuits to inject NO in proportion with the flow of air/oxygen through the circuit, in order to maintain a constant, target concentration of inhaled NO. Methods In the present article, a NO injection and mixing element is presented. The device borrows from the design of static elements to promote rapid mixing of injected NO-containing gas with breathing circuit gases. Bench experiments are reported to demonstrate the improved mixing afforded by the injection and mixing element, as compared with conventional breathing circuit adapters, for NO injection into breathing circuits. Computational fluid dynamics simulations are also presented to illustrate mixing patterns and nitrogen dioxide production within the element. Results Over the range of air flow rates and target NO concentrations investigated, mixing length, defined as the downstream distance required for NO concentration to reach within ±5 % of the target concentration, was as high as 47 cm for the conventional breathing circuit adapters, but did not exceed 7.8 cm for the injection and mixing element. Conclusion The injection and mixing element has potential to improve ease of use, compatibility and safety of inhaled NO administration with mechanical ventilators and gas delivery devices

Reversible Total Vision Loss Caused by Severe Metformin-associated Lactic Acidosis: A Case Report.

INTRODUCTION: Metformin is a biguanide used to treat diabetes mellitus (DM). Metformin-associated lactic acidosis (MALA) carries a high mortality and can occur in patients with renal failure from drug bioaccumulation. Reversible vision loss is a highly unusual, rarely reported complication of MALA. We present a case of a patient whose serum metformin concentration was unusually high and associated with vision loss. CASE REPORT: A 60-year-old woman presented to an outside hospital emergency department with acute vision loss after being found at home confused, somnolent, and hypoglycemic, having last being seen normal two days prior. She reported vomiting and diarrhea during that time and a recently treated urinary tract infection. The visual loss resolved with continuous renal replacement therapy. CONCLUSION: This novel case of a patient with Type II DM prescribed metformin and insulin who developed reversible vision loss while suffering from MALA highlights the potential for vision loss in association with MALA

Variability in uptake efficiency for pulsed versus constant concentration delivery of inhaled nitric oxide

BACKGROUND: Nitric oxide (NO) is currently administered using devices that maintain constant inspired NO concentrations. Alternatively, devices that deliver a pulse of NO during the early phase of inspiration may have use in optimizing NO dosing efficiency and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. The extent to which the amount of NO delivered for a given pulse sequence determines alveolar concentrations and uptake, and the extent to which this relationship varies with breathing pattern, physiological, and pathophysiological parameters, warrants investigation. METHODS: A mathematical model was used to analyze inhaled nitric oxide (NO) transport through the conducting airways, and to predict uptake from the alveolar region of the lung. Pulsed delivery was compared with delivery of a constant concentration of NO in the inhaled gas. RESULTS: Pulsed delivery was predicted to offer significant improvement in uptake efficiency compared with constant concentration delivery. Uptake from the alveolar region depended on pulse timing, tidal volume, respiratory rate, lung and dead space volume, and the diffusing capacity of the lung for NO (D(L)NO). It was predicted that variation in uptake efficiency with breathing pattern can be limited using a pulse time of less than 100 ms, with a delay of less than 50 ms between the onset of inhalation and pulse delivery. Nonlinear variation in uptake efficiency with D(L)NO was predicted, with uptake efficiency falling off sharply as D(L)NO decreased below ~50-60 ml/min/mm Hg. Gas mixing in the conducting airways played an important role in determining uptake, such that consideration of bulk convection alone would lead to errors in assessing efficiency of pulsed delivery systems. CONCLUSIONS: Pulsed NO delivery improves uptake efficiency compared with constant concentration delivery. Optimization of pulse timing is critical in limiting intra- and inter-subject variability in dosing

Interpreting the seasonal cycles of atmospheric oxygen and carbon dioxide concentrations at American Samoa Observatory

We present seven years of atmospheric O2/N2 ratio and CO2 concentration data measured from flask samples collected at American Samoa. These data are unusual, exhibiting higher short-term variability, and seasonal cycles not in phase with other sampling stations. The unique nature of atmospheric data from Samoa has been noted previously from measurements of CO2, methyl chloroform, and ozone. With our O2 data, we observe greater magnitude in the short-term variability, but, in contrast, no clear seasonal pattern to this variability. This we attribute to significant regional sources and sinks existing for O2 in both hemispheres, and a dependence on both the latitudinal and altitudinal origins of air masses. We also hypothesize that some samples exhibit a component of "older" air, demonstrating recirculation of air within the tropics. Our findings could be used to help constrain atmospheric transport models which are not well characterized in tropical regions

4-aminopyridine toxicity: a case report and review of the literature.

INTRODUCTION: 4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert-Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose. CASE REPORT: A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully. DISCUSSION: The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose

The Littlest Higgs

We present an economical theory of natural electroweak symmetry breaking, generalizing an approach based on deconstruction. This theory is the smallest extension of the Standard Model to date that stabilizes the electroweak scale with a naturally light Higgs and weakly coupled new physics at TeV energies. The Higgs is one of a set of pseudo Goldstone bosons in an $SU(5)/SO(5)$ nonlinear sigma model. The symmetry breaking scale $f$ is around a TeV, with the cutoff \Lambda \lsim 4\pi f \sim 10 TeV. A single electroweak doublet, the ``little Higgs'', is automatically much lighter than the other pseudo Goldstone bosons. The quartic self-coupling for the little Higgs is generated by the gauge and Yukawa interactions with a natural size $O(g^2,\lambda_t^2)$, while the top Yukawa coupling generates a negative mass squared triggering electroweak symmetry breaking. Beneath the TeV scale the effective theory is simply the minimal Standard Model. The new particle content at TeV energies consists of one set of spin one bosons with the same quantum numbers as the electroweak gauge bosons, an electroweak singlet quark with charge 2/3, and an electroweak triplet scalar. One loop quadratically divergent corrections to the Higgs mass are cancelled by interactions with these additional particles.Comment: 15 pages. References added. Corrected typos in the discussion of the top Yukawa couplin

Eisenstein Series of Weight One, q-Averages of the 0-Logarithm and Periods of Elliptic Curves

For any elliptic curve E over k ⊂ R with E(C) = C^×/q^Z, q = e^(2πiz),Im(z) >, we study the q-average D_(0,q), defined on E(C), of the function D_0(z) = Im(z/(1−z)). Let Ω+(E) denote the real period of E. We show that there is a rational function R ∈ Q(X_1(N)) such that for any non-cuspidal real point s ∈ X_1(N) (which defines an elliptic curve E(s) over R together with a point P(s) of order N), πD_(0,q)(P(s)) equals Ω+(E(s))R(s). In particular, if s is Q-rational point of X_1(N), a rare occurrence according to Mazur, R(s) is a rational number

The COS-Halos Survey: Physical Conditions and Baryonic Mass in the Low-Redshift Circumgalactic Medium

We analyze the physical conditions of the cool, photoionized (T $\sim 10^4$ K) circumgalactic medium (CGM) using the COS-Halos suite of gas column density measurements for 44 gaseous halos within 160 kpc of $L \sim L^*$ galaxies at $z \sim 0.2$. These data are well described by simple photoionization models, with the gas highly ionized (n$_{\rm HII}$/n$_{\rm H} \gtrsim 99\%$) by the extragalactic ultraviolet background (EUVB). Scaling by estimates for the virial radius, R$_{\rm vir}$, we show that the ionization state (tracked by the dimensionless ionization parameter, U) increases with distance from the host galaxy. The ionization parameters imply a decreasing volume density profile n$_{\rm H}$ = (10$^{-4.2 \pm 0.25}$)(R/R$_{\rm vir})^{-0.8\pm0.3}$. Our derived gas volume densities are several orders of magnitude lower than predictions from standard two-phase models with a cool medium in pressure equilibrium with a hot, coronal medium expected in virialized halos at this mass scale. Applying the ionization corrections to the HI column densities, we estimate a lower limit to the cool gas mass M$_{\rm CGM}^{\rm cool} > 6.5 \times 10^{10}$ M$_{\odot}$ for the volume within R $<$ R$_{\rm vir}$. Allowing for an additional warm-hot, OVI-traced phase, the CGM accounts for at least half of the baryons purported to be missing from dark matter halos at the 10$^{12}$ M$_{\odot}$ scale.Comment: 19 pages, 12 Figures, and a 37-page Appendix with 36 additional figures. Accepted to ApJ June 21 201

Electroweak Precision Constraints on the Littlest Higgs Model with T Parity

We compute the leading corrections to the properties of W and Z bosons induced at the one-loop level in the SU(5)/SO(5) Littlest Higgs model with T parity, and perform a global fit to precision electroweak data to determine the constraints on the model parameters. We find that a large part of the model parameter space is consistent with data. Values of the symmetry breaking scale as low as 500 GeV are allowed, indicating that no significant fine tuning in the Higgs potential is required. We identify a region within the allowed parameter space in which the lightest T-odd particle, the partner of the hypercharge gauge boson, has the correct relic abundance to play the role of dark matter. In addition, we find that a consistent fit to data can be obtained for large values of the Higgs mass, up to 800 GeV, due to the possibility of a partial cancellation between the contributions to the T parameter from Higgs loops and new physics.Comment: 23 pages, 9 figures. Minor correction