Impact of AIDS/HIV on Medical Directors.

The decade of AIDS/HIV has changed the way insurance medicine is practiced by medical directors. One director details some of these changes.

Optimizing photonic ring-resonator filters for OH-suppressed near-infrared astronomy.

Near-infrared wavelength observations are crucial for understanding numerous fields of astrophysics, such as supernova cosmology and positronium annihilation detection. However, current ground-based observations suffer from an enormous background due to OH emission in the upper atmosphere. One promising way to solve this problem is to use ring-resonator filters to suppress OH emission lines. In this work, we discuss our optimization of ring-resonator filter performance from five perspectives: resonance wavelength matching, polarization-independent operation, low insertion loss, low-loss coupling to astronomical instruments, and broadband operation. In the end, we discuss next steps needed for reliable supernova and positronium observations, thus providing a roadmap for future advances in near-infrared astronomy.

Publisher Correction: The effectiveness of plain packaging in discouraging tobacco consumption in Australia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Testing for HIV infection in the emergency departments of 2 hospitals in the Southeastern United States.

BACKGROUND: In 2006, the Centers for Disease Control and Prevention (CDC) recommended non-targeted, opt-out HIV screening in all healthcare settings, including emergency departments (EDs). Multiple HIV testing programs have been implemented in EDs across the United States with varying designs and testing platforms. We report findings from a free, non-targeted, rapid HIV testing program in 2 EDs in the Southeastern United States. METHODS: From 2008 to 2012, adults ≥18 years of age were offered free rapid HIV testing using an oral swab test (OraQuick ADVANCE Rapid HIV-1/2 antibody test) in the EDs of a large academic medical center and an affiliated community hospital in Durham, North Carolina. RESULTS: In total, 5443 ED patients were offered HIV testing. The overall acceptance rate was 66.9% (3639/5443). Younger persons were significantly more likely to accept testing (78.2% for 18-29 years old vs 67.1% for ≥30 years old; P < 0.001) as were Black participants (72.6% Black vs 66.5% White; P < 0.001). Acceptance rates improved significantly after opt-out oral consent replaced written consent (71.3% vs 63.1%; P < 0.001). Seven new HIV diagnoses were confirmed during the testing program, resulting in a seropositivity rate of 0.19% (7/3639). There were 8 false-positive rapid oral HIV tests (positive predictive value = 46.7%). CONCLUSIONS: Although the number of new HIV diagnoses was low, implementation of this rapid, non-targeted ED screening program was feasible with high acceptance rates, particularly after introducing the opt-out oral consent approach.

The effectiveness of plain packaging in discouraging tobacco consumption in Australia.

The removal of all branding and promotions from tobacco products, known as 'plain packaging', is intended to decrease tobacco consumption. Here we examine the effectiveness of Australia's plain packaging law, which coincided with a change in graphic and text health warnings, by using nationally indicative data 5 years post implementation. We measured the effect of the law on smoking prevalence, tobacco expenditure, expenditure intensity and quantity of tobacco consumed, using New Zealand as a control country in a difference-in-differences research design. We uncover a substitution effect that is robust to different specifications and control countries. In response to the policy, smokers switched from more expensive to cheaper cigarettes and reduced their overall tobacco expenditure and expenditure intensity. However, as smoking became less costly, smokers consumed more cigarettes. To discourage such substitution and to help the policy achieve its intended outcomes, policymakers should consider implementing auxiliary measures, such as taxes or price floors.

Excited state hydrogen bond dynamics: coumarin 102 in acetonitrile-water binary mixtures.

The time dependent change in the intermolecular response of solvent molecules following photoexcitation of Coumarin 102 (C102) has been measured in acetonitrile-water binary mixtures. Experiments were performed on mixtures of composition x(CH3CN) = 0.25, 0.50, 0.75, and 1.00. At low water concentrations (x(H2O) < or = 0.25) the solvent response is consistent with previous measurements probing dipolar solvation. With increasing water concentration (x(H2O) > or = 0.50) an additional response is found subsequent to dipolar solvation, exhibited as a rapid gain in the solvent's polarizability on a approximately 250 fs time scale. Monte Carlo simulations of the C102:binary mixture system were performed to quantify the number of hydrogen-bonding interactions between C102 and water. These simulations indicate that the probability of the C102 solute being hydrogen bound with two water molecules, both as donors at the carbonyl site, increases in a correlated fashion with the amplitude of the additional response in the measurements. We conclude that excitation of C102 simultaneously weakens and strengthens hydrogen bonding in complexes with two inequivalently bound waters.

Three-photon near-threshold photoionization dynamics of isooctane.

The electron survival probability following three-photon (9.3 eV total) near-threshold photoionization of neat isooctane is measured with sub-50 fs time resolution. The measured dynamics are nonexponential in time and are well described by a diffusion-controlled electron-cation recombination model. Excitation-power-dependent studies indicate that the unperturbed three-photon threshold ionization is only observed for pump irradiance below 0.5 TW cm2. At excitation fields above this level, the signal is no longer cubic in the excitation irradiance, and the observed electron survival probability dramatically changes, decaying as a single exponential in time.

Measuring the change in the intermolecular Raman spectrum during dipolar solvation.

We demonstrate a method to directly measure the change in the spectrum of intermolecular solvent fluctuations as a function of time after electronic excitation of a solute, and this method is applied to the dye Coumarin 102 (C102) in acetonitrile. The complete intermolecular response is captured following resonant excitation with time domain third-order Raman spectroscopy. In a previous report, we introduced this method and used it to probe one point in the intermolecular response as a function of time after solute excitation (Underwood, D. F., Blank, D. A. J. Phys. Chem. A 2003, 107 (7), 956). Here we extend this approach to recover the change in the entire intermolecular response as a function of time. To our knowledge the results provide the first direct measurement of the difference in the equilibrated intermolecular response after excitation of a solute and its evolution during a dipolar solvation event. Excitation of C102 results in a significant increase in the solvent-solute interaction due to a large increase in the dipole moment. The observed change in the intermolecular response is consistent with a rapid change in local solvent density, with intermolecular kinetic energy transfer changing the response on longer time scales. Evolution of the response exhibits a strong frequency dependence and suggests changes over longer distances at longer delay times. The measured change in the spectrum of solvent fluctuations represents a direct experimental confirmation of the breakdown of linear response and confirms predictions from molecular dynamics simulations.

Probing excited-state dynamics and intramolecular proton transfer in 1-acylaminoanthraquinones via the intermolecular solvent response.

The dynamics of a series of 1-acylaminoanthraquinones with varying degrees of excited-state intramolecular proton transfer are studied in acetonitrile and dichloromethane. Events are followed via changes in the third-order intermolecular Raman response as a function of time after resonant excitation of the chromophore. Compared to electronically resonant probes of the solute, measuring the ultrafast dynamics using the nonresonant solvent response offers a new and complementary perspective on the events that accompany excitation and proton transfer. Experimentally observed changes in the nuclear polarizability of the solvent follow dynamic changes in the solvent-solute interactions. Reorganization of the solvent in response to the significant changes in the intermolecular interactions upon proton transfer is found to play an important role in the reaction dynamics. With transfer of the proton taking place rapidly, the solvent controls the dynamics via the time-dependent evolution of the free energy surface, even on subpicosecond time scales. In addition, the solvent response probes the effects of intermolecular energy transfer as energy released during the reactive event is rapidly transferred to the local solvent environment and then dissipates to the bulk solvent on about a 10 ps time scale. A brief initial account of a portion of this work has appeared previously, J. Am. Chem. Soc. 2004, 126, 8620-8621.

Following the solvent directly during ultrafast excited state proton transfer.

Excited state intramolecular proton transfer in 1-chloroacetylaminoanthraquinone is investigated from the perspective of the solvent. Using a new two-dimensional nonlinear optical spectroscopy the solvent response is probed directly as the proton transfer takes place. The measurements indicate that solvent reorganization controls the proton transfer in acetonitrile by dynamically shifting the position of equilibrium in the excited state, even on subpicosecond time scales.

Cytokine activation and intestinal mucosal and renal dysfunction are reduced in endovascular AAA repair compared to surgery.

PURPOSE: To compare endovascular (EVR) to open repair (OR) of abdominal aortic aneurysm (AAA) for cytokine activation, changes in the intestinal mucosal barrier, and renal dysfunction. METHODS: In a prospective nonrandomized study, 15 patients admitted to a university hospital for elective infrarenal AAA repair (8 OR and 7 EVR) were recruited. Intestinal permeability was assessed preoperatively (PO), at day 1 (D1), and at day 3 (D3) after surgery using the lactulose/mannitol differential excretion (LMR) test. Renal damage was assessed from measurements of the urinary albumin:creatinine ratio (ACR); cytokine activation was based on the urinary concentration of tumor necrosis factor receptor p55 (TNF-Rp55) at the same time points. Serum creatinine and urea concentrations were measured preoperatively and daily for 5 days postoperatively. RESULTS: A significant increase in LMR was found in the OR group at D1 and D3 compared to PO (p<0.05). The LMR increase at D3 was significantly greater in the OR group (p<0.01). A significant difference was observed in the percentage rise in ACR on D1 in the OR group compared to the EVR group (p<0.005). The urinary TNF-Rp55 concentration was significantly elevated in the OR group at D1 (p<0.05) and D3 (p<0.05) compared to baseline; in the EVR group, it was elevated at D1 (p<0.05) compared to PO. The difference was also significant for this marker between the 2 groups at D1 (p<0.01). No significant change was observed in the serum creatinine or urea concentrations in either group perioperatively. CONCLUSIONS: Endovascular AAA repair is associated with less cytokine production and less intestinal and renal dysfunction compared to the open approach.

Nonpeptide tachykinin receptor antagonists. III. SB 235375, a low central nervous system-penetrant, potent and selective neurokinin-3 receptor antagonist, inhibits citric acid-induced cough and airways hyper-reactivity in guinea pigs.

In this report the in vitro and in vivo pharmacological and pharmacokinetic profile of (-)-(S)-N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide (SB 235375), a low central nervous system (CNS)-penetrant, human neurokinin-3 (NK-3) receptor (hNK-3R) antagonist, is described. SB 235375 inhibited (125)I-[MePhe(7)]-neurokinin B (NKB) binding to membranes of Chinese hamster ovary (CHO) cells expressing the hNK-3R (CHO-hNK-3R) with a K(i) = 2.2 nM and antagonized competitively NKB-induced Ca(2+) mobilization in human embryonic kidney (HEK) 293 cells expressing the hNK-3R (HEK 293-hNK-3R) with a K(b) = 12 nM. SB 235375 antagonized senktide (NK-3R)-induced contractions in rabbit isolated iris sphincter (pA(2) = 8.1) and guinea pig ileal circular smooth muscles (pA(2) = 8.3). SB 235375 was selective for the hNK-3R compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 209 nM), and was without effect, at 1 microM, in 68 other receptor, enzyme, and ion channel assays. Intravenous SB 235375 produced a dose-related inhibition of miosis induced by i.v. senktide in the rabbit (ED(50) of 0.56 mg/kg). Intraperitoneal SB 235375 (10-30 mg/kg) inhibited citric acid-induced cough and airways hyper-reactivity in guinea pigs. In mice oral SB 235375 (3-30 mg/kg) was without significant effect on the behavioral responses induced by intracerebral ventricular administration of senktide. Pharmacokinetic evaluation in the mouse and rat revealed that oral SB 235375 was well absorbed systemically but did not effectively cross the blood-brain barrier. The preclinical profile of SB 235375, encompassing high affinity, selectivity, oral activity, and low CNS penetration, suggests that it is an appropriate tool compound to define the pathophysiological roles of the NK-3Rs in the peripheral nervous system.