Effectiveness of Selected Air Cleaning Devices During Dental Procedures.

INTRODUCTION: The recent COVID-19 pandemic has underscored the necessity of protecting health care providers (HCPs) against the transmission of infectious agents during dental procedures. To this end, the effectiveness of several air cleaning devices (ACDs) in reducing HCPs exposure to aerosols generated during dental procedures was estimated, separately or in combination with each other. These ACDs were a chairside unit capturing aerosols at the source of generation, and four ambient ACDs: a portable ambient ACD; a negative pressure module; a custom made, fan-operated and wall-mounted air filter (WMAF); and a smaller and passive version of the latter. The last three ACDs were intended for mobile dental clinics (MDCs) only. MATERIALS AND METHODS: This assessment was performed in two different environments: in a dental clinic operatory and in a MDC. Two dental personnel, acting in the roles of dentist and dental assistant, performed on simulated patient aerosol-generating and non-aerosol-generating procedures. For each 5-minute scenario, the cumulative exposure to airborne particulate matter 10 µm in size or smaller (PM10) was determined by calculating the sum of all 1 second readings obtained with personal and ambient air monitors. The effectiveness of the ACDs in capturing PM10 was estimated based on the capability of the ACDs to keep PM10 level at or below the initial background level. RESULTS: In all conditions assessed in the dental clinic operatory, when both the chairside and portable ambient ACDs were functioning, an estimated effectiveness of 100% in capturing PM10 was achieved. In the MDC, in all conditions where the chairside ACD was used without the negative pressure module, an estimated effectiveness of 100% was also achieved. The simultaneous operation of the negative pressure module in the MDC, which led to a room negative pressure of -0.25 inch wc, reduced the chairside ACD's effectiveness in capturing aerosols. Conversely, the use of the WMAF in the MDC in combination with the chairside ACD further reduced exposure to PM10 below the initial background level. Nonetheless, in all conditions assessed in both settings (dental clinic operatory and MDC), larger visible aerosols were produced, often landing on the surrounding environment. A fair portion of these aerosols landed on the inside of the chairside ACD flange. CONCLUSIONS: This assessment suggests that the use of the tested chairside ACD, by capturing aerosols at the source of generation, had the greatest impact on reducing exposure of dental personnel to PM10 produced during dental procedures. This study also indicates that such exposure is further reduced with the addition of an ambient ACD. However, creating a negative pressure room as high as -0.25 inch wc can lead to air turbulence reducing the effectiveness of ACDs in capturing aerosols at the source. Furthermore, the presence of uncaptured droplets and spatter on the surrounding environment supports the need to complement the use of engineering controls with proper administrative controls and personal protective equipment, as recommended by governmental agencies and the scientific community for preventing the transmission of infection in health care settings.

Self-driving laboratory for accelerated discovery of thin-film materials.

Discovering and optimizing commercially viable materials for clean energy applications typically takes more than a decade. Self-driving laboratories that iteratively design, execute, and learn from materials science experiments in a fully autonomous loop present an opportunity to accelerate this research process. We report here a modular robotic platform driven by a model-based optimization algorithm capable of autonomously optimizing the optical and electronic properties of thin-film materials by modifying the film composition and processing conditions. We demonstrate the power of this platform by using it to maximize the hole mobility of organic hole transport materials commonly used in perovskite solar cells and consumer electronics. This demonstration highlights the possibilities of using autonomous laboratories to discover organic and inorganic materials relevant to materials sciences and clean energy technologies.

Pharmacological and toxicological activity of RSD921, a novel sodium channel blocker.

BACKGROUND: RSD921, the R,R enantiomer of the kappa (k) agonist PD117,302, lacks significant activity on opioid receptors. METHODS: The pharmacological and toxicological actions were studied with reference to cardiovascular, cardiac, antiarrhythmic, toxic and local anaesthetic activity. RESULTS: In rats, dogs and baboons, RSD921 dose-dependently reduced blood pressure and heart rate. In a manner consistent with sodium channel blockade it prolonged the PR and QRS intervals of the ECG. Furthermore, in rats and NHP, RSD921 increased the threshold currents for induction of extra-systoles and ventricular fibrillation (VFt), and prolonged effective refractory period (ERP). In rats, RSD921 was protective against arrhythmias induced by electrical stimulation and coronary artery occlusion. Application of RSD921 to voltage-clamped rat cardiac myocytes blocked sodium currents. RSD921 also blocked transient (ito) and sustained (IKsus) outward potassium currents, albeit with reduced potency relative to sodium current blockade. Sodium channel blockade due to RSD921 in myocytes and isolated hearts was enhanced under ischaemic conditions (low pH and high extracellular potassium concentration). When tested on the cardiac, neuronal and skeletal muscle forms of sodium channels expressed in Xenopus laevis oocytes, RSD921 produced equipotent tonic block of sodium currents, enhanced channel block at reduced pH (6.4) and marked use-dependent block of the cardiac isoform. RSD921 had limited but quantifiable effects in subacute toxicology studies in rats and dogs. Pharmacokinetic analyses were performed in baboons. Plasma concentrations producing cardiac actions in vivo after intravenous administration of RSD921 were similar to the concentrations effective in the in vitro assays utilized. CONCLUSIONS: RSD921 primarily blocks sodium currents, and possesses antiarrhythmic and local anaesthetic activity.

High-temperature high-pressure calorimeter for studying gram-scale heterogeneous chemical reactions.

We present an instrument for measuring pressure changes and heat flows of physical and chemical processes occurring in gram-scale solid samples under high pressures of reactive gases. Operation is demonstrated at 1232 °C under 33 bars of pure hydrogen. Calorimetric heat flow is inferred using a grey-box non-linear lumped-element heat transfer model of the instrument. Using an electrical calibration heater to deliver 900 J/1 W pulses at the sample position, we demonstrate a dynamic calorimetric power resolution of 50 mW when an 80-s moving average is applied to the signal. Integration of the power signal showed that the 900 J pulse energy could be measured with an average accuracy of 6.35% or better over the temperature range 150-1100 °C. This instrument is appropriate for the study of high-temperature metal hydride materials for thermochemical energy storage.

Acoustic buffeting by infrasound in a low vibration facility.

Measurement instruments and fabrication tools with spatial resolution on the atomic scale require facilities that mitigate the impact of vibration sources in the environment. One approach to protection from vibration in a building's foundation is to place the instrument on a massive inertia block, supported on pneumatic isolators. This opens the questions of whether or not a massive floating block is susceptible to acoustic forces, and how to mitigate the effects of any such acoustic buffeting. Here this is investigated with quantitative measurements of vibrations and sound pressure, together with finite element modeling. It is shown that a particular concern, even in a facility with multiple acoustic enclosures, is the excitation of the lowest fundamental acoustic modes of the room by infrasound in the low tens of Hz range, and the efficient coupling of the fundamental room modes to a large inertia block centered in the room.

Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline.

We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA(B) agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA(B) receptors; therefore, we hypothesized that isovaline's analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E2 in the mouse paw. Subcutaneous R-isovaline produced dose-dependent antiallodynia restricted to the injected hindlimb. This antiallodynia was blocked by co-injection with a selective group II mGluR antagonist, LY341495, but not a group III mGluR antagonist (MAP-4). The antiallodynic effect of R-isovaline was potentiated by co-administration of a group II mGluR-positive allosteric modulator, LY487379. Injection of a group II mGluR agonist (LY354740) produced an antiallodynic effect which was completely reversed by group II antagonism, but was not affected by group III or GABA(B) (CGP35348) antagonism. Similarly, group II mGluR antagonism did not alter the antiallodynia produced by the prototypical GABA(B) agonist, baclofen. Hence, there was no apparent crosstalk between group II mGluRs and GABA(B) receptors. Previous studies have demonstrated that peripheral GABA(B) receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia.

GABA(B) receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline.

Peripherally restricted analgesics are desirable to avoid central nervous system (CNS) side effects of opioids. Nonsteroidal anti-inflammatory drugs produce peripheral analgesia but have significant toxicity. GABA(B) receptors represent peripheral targets for analgesia but selective GABA(B) agonists like baclofen cross the blood-brain barrier. Recently, we found that the CNS-impermeant amino acid, isovaline, produces analgesia without apparent CNS effects. On observing that isovaline has GABA(B) activity in brain slices, we examined the hypothesis that isovaline produces peripheral analgesia mediated by GABA(B) receptors. We compared the peripheral analgesic and CNS effect profiles of isovaline, baclofen, and GABA (a CNS-impermeant, unselective GABA(B) agonist). All three amino acids attenuated allodynia induced by prostaglandin E2 injection into the mouse hindpaw and tested with von Frey filaments. The antiallodynic actions of isovaline, baclofen, and GABA were blocked by the GABA(B) antagonist, CGP52432, and potentiated by the GABA(B) modulator, CGP7930. We measured Behavioural Hyperactivity Scores and temperature change as indicators of GABAergic action in the CNS. ED(95) doses of isovaline and GABA produced no CNS effects while baclofen produced substantial sedation and hypothermia. In a mouse model of osteoarthritis, isovaline restored performance during forced exercise to baseline values. Immunohistochemical staining of cutaneous layers of the analgesic test site demonstrated co-localization of GABA(B1) and GABA(B2) receptor subunits on fine nerve endings and keratinocytes. Isovaline represents a new class of peripherally restricted analgesics without CNS effects, mediated by cutaneous GABA(B) receptors.

Modelling for computer controlled neuromuscular blockade.

In this paper we present data collection and methods for the selection of a model class with the goal of automated neuromuscular blockade (NMB). Neuromuscular response was measured in the presence of rocuronium in rabbits (N=5) and humans (N=14). An average response was formed and used to determine optimal ARX and Laguerre representations for a wide range of orders and parameters. A 6th order Laguerre model was selected based on its accuracy and simplicity. Models were identified for each subject. For each group, variation was measured by comparison to the average response. The standard deviation of the average impulse response static gain was 45.4 and 45.8% of the mean for the rabbit and human models, respectively. The range of static gain was 121 and 159% of the mean for the rabbit and human datasets. Frequency domain analysis showed differences in gain of 12 and 15dB, and phase of 45 and 75° for the rabbit and human models respectively. With this knowledge, design and development of appropriate controllers for NMB will proceed.

A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide vs dimethylsulfoxide with hydroxyethylstarch.

Hematopoietic stem cells intended for autologous transplantation are usually cryopreserved in solutions containing 10% dimethylsulfoxide (DMSO, v/v) or 5% DMSO in combination with 6% hydroxyethylstarch (HES, w/v). We performed a single-blinded, randomized study comparing these cryoprotectant solutions for patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. A total of 294 patients were evaluable; 148 received cells frozen with 10% DMSO and 146 received cells frozen in 5% DMSO/6% HES. Patients who received cells frozen with the combination cryoprotectant recovered their white blood cell count >or=1.0 x 10(9)/l at a median of 10 days, one day faster than those who received PBSC frozen with DMSO alone (P=0.04). Time to achieve neutrophil counts of >or=0.5 x 10(9) and >or=1.0 x 10(9)/l were similarly faster for the recipients of the cells frozen in the combination solution. This effect was more pronounced for patients who received quantities of CD34+ cells higher than the median for the population. Median time to discontinuation of antibiotic use was also one day faster for the recipients of cells cryopreserved with DMSO/HES (P=0.04). In contrast, median times to recovery of platelet count >or=20 x 10(9)/l were equivalent for each group (10 days; P=0.99) and the median numbers of red cell and platelet transfusions did not differ.

Demographic surveillance and health equity in sub-Saharan Africa.

Accurate data are always needed to inform health policy, but are especially critical in tackling health inequities. The growing number of field research stations in sub-Saharan Africa are well-placed to generate relevant data and so support health policy action. Over the past 60 years, demographic surveillance systems have been crucial research tools for the evaluation of health interventions aimed at reducing socioeconomic differentials in mortality and morbidity in sub-Saharan Africa. The bulk of such work has been carried out by field research sites, often operating in remote, resource-constrained settings. The present paper reviews what we have learned since the pioneering work carried out in the field sites of Pholela (South Africa) and Niakhar (Senegal). It then focuses on current efforts to address health equity through INDEPTH, the international network of field sites with continuous demographic evaluation of population and their health in developing countries.

Use of a cardiocerebral-protective drug cocktail prior to countershock in a porcine model of prolonged ventricular fibrillation.

OBJECTIVES: This was the third study in a series exploring whether the use of combination pharmacotherapy with delayed countershock would produce higher rates of return of spontaneous circulation (ROSC) and one-hour survival when compared with standard advanced cardiac life support (ACLS) therapy in prolonged ventricular fibrillation (VF). METHODS: Twenty-four female, mixed-breed, domestic swine (ranging in mass from 22 to 25 kg) were used in this prospective, blinded, randomized, experimental trial. Animals were sedated (ketamine/xylazine), anesthetized (alpha-chloralose), paralyzed (pancuronium), mechanically ventilated with room air, and monitored with electrocardiography, arterial pressure, and Swan-Ganz catheters. VF was induced with a 3 s, 60 Hz, 100 mA transthoracic shock, and remained untreated for 8 min. One minute of basic life support followed (standardized by use of a mechanical device). At 9 min, animals were treated with one of three regimes: Group 1, cardiocerebral-protective cocktail (antioxidant U-74389G (3.0 mg/kg), epinephrine (0.2 mg/kg), lidocaine (1.0 mg/kg), bretylium (5.0 mg/kg), magnesium (2.0 g), and propranolol (1.0 mg)); Group 2, magnesium (2.0 g); and Group 3, standard ACLS. Groups 1 and 2 received drugs at minute nine (first countershock at minute 11), while Group 3 received first countershock at minute nine. Data were analyzed with two-tailed Fisher's exact tests. RESULTS: ROSC was achieved in Group 1, 7/7 (100%); Group 2, 3/9 (33%, P versus Group 1=0.01); and Group 3, 3/8 (38%; P versus Group 1=0.02). One-hour survival was attained in Group 1, 7/7 (100%); Group 2, 3/9 (33%; P versus Group 1=0.01), and Group 3, 1/8 (13%; P versus Group 1=0.001). CONCLUSIONS: Combination pharmacotherapy with a cardiocerebral-protective drug cocktail prior to countershock produced superior rates of ROSC and one-hour survival when compared with singular drug therapy (Group 2) and standard ACLS (Group 3) in this porcine model of prolonged VF.

Combined pre- and post-surgical bupivacaine wound infiltrations decrease opioid requirements after knee ligament reconstruction.

PURPOSE: To test the efficacy of a combination of selective pre- and post-surgical local anesthetic infiltrations of the knee, compared with standard intra-articular injection at the end of surgery alone, to reduce postoperative opioid requirements following arthroscopic cruciate ligament reconstruction (ACLR). METHODS: In a double-blind, randomized, controlled trial, we studied 23 patients (ASA I or II) scheduled for elective ACLR under general anesthesia. The treatment group (n = 12) received infiltrations with bupivacaine 0.25% with epinephrine 1:200,000 presurgically (10 ml into the portals, 10 ml at the medial tibial incision site, 10 ml at the lateral femoral incision site, and 10 ml intra-articularly) and postsurgically (5 ml at the medial tibial incision and 10 ml at the lateral femoral incision). The control group (n = 11) received infiltrations with saline 0.9% in the same manner. All patients received a standard intra-articular local anesthetic instillation of the knee (25 ml of bupivacaine 0.25% with epinephrine 1:200,000) at the completion of surgery. RESULTS: Postoperative opioid requirements were lower in the treatment group (5.8 +/- 2.9 mg morphine equivalent) than in the control group ( 13.7 +/- 5.8 mg; P = 0.008). Treatment patients were ready for discharge approximately 30 min earlier than control patients (P = 0.046). There were no adverse events in the treatment group. In the control group, 2/11 patients vomited and a third experienced transient postoperative diaphoresis, dizziness and pallor. CONCLUSION: We conclude that a combination of selective pre- and post-surgical wound infiltration with bupivacaine 0.25% provides superior analgesia compared with a standard post-surgical intra-articular injection alone.

The development and evaluation of a new aerosol irritant assay with minimal animal stress.

Current aerosol irritant assays trap animals in noxious atmospheres and put a lot of stress on them. For this reason, the Minimal Animal Stress Irritant Assay Chamber (MASIAC) was developed based on the principle of avoidance, and evaluated. The MASIAC reproducibly detected citric acid with more sensitivity than conventionally used assays. With a group of mice tested simultaneously, the responses were not significantly affected by the presence of other mice. In addition, following multiple exposures to citric acid, the mice either sensitized to the irritant, or learned to avoid it. This suggests a number of areas where the MASIAC could be applied, including behavioral and asthma research. If this new method turns out to be as good as currently used assays, it could provide investigators with an alternative, more humane method of evaluating pulmonary irritants.

Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing.

The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.

RSD1019 suppresses ischaemia-induced monophasic action potential shortening and arrhythmias in anaesthetized rabbits.

The electrophysiological actions of lidocaine, tedisamil and RSD1019 were assessed on normal and ischaemic cardiac tissue using monophasic action potentials (MAPs) recorded from the epicardium of anaesthetized rabbits. Drug effects on ischaemia-induced arrhythmias were assessed simultaneously in the same rabbits. Lidocaine, infused at 2.5, 5 and 10 micromol kg(-1) min(-1) i.v., accelerated and worsened the electrophysiological derangement caused by ischaemia, had profibrillatory actions and reduced the time to the occurrence of ventricular fibrillation (VF) relative to controls. Tedisamil, infused at 0.063, 0.125 and 0.25 micromol kg(-1) min(-1) i.v., prolonged MAP duration at 90% repolarization (MAPD(90%)) before induction of ischaemia in a dose-related manner; however, this effect was not maintained 5 min after induction of ischaemia. Tedisamil had no significant antiarrhythmic actions over the dose-range tested. RSD1019, infused at 2, 4 and 8 micromol kg(-1) min(-1) i.v., produced a small increase in MAPD(90%) before induction of ischaemia and only at the highest dose tested. In contrast to tedisamil, RSD1019 suppressed ischaemia-induced MAP shortening assessed 5 min after induction of ischaemia. This effect was dose-related. RSD1019 completely prevented ischaemia-induced tachyarrhythmias at the mid and highest infusion levels tested. The results of this study illustrate a pathologically targeted approach for preventing ischaemia-induced arrhythmias. Suppression of ischaemia-induced MAP shortening, demonstrated herein for RSD1019, represents a novel antifibrillatory approach.

Effect of an administrative intervention on rates of screening for domestic violence in an urban emergency department.

OBJECTIVES: This study measured the effects of an administrative intervention on health care provider compliance with universal domestic violence screening protocols. METHODS: We used a simple, interrupted-time-series design in a stratified random sample of female emergency department patients 18 years or older (n = 1638 preintervention, n = 1617 postintervention). The intervention was a 4-tiered hospital-approved disciplinary action, and the primary outcome was screening compliance. RESULTS: Preintervention and postintervention screening rates were 29.5% and 72.8%, respectively. Before the intervention, screening was worse on the night shift (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.31, 0.68) and with psychiatric patients (OR = 0.34, 95% CI = 0.14, 0.85); after the intervention, no previous screening barriers remained significant. CONCLUSIONS: An administrative intervention significantly enhanced compliance with universal domestic violence screening.

Combination pharmacotherapy with delayed countershock vs standard advanced cardiac life support after prolonged ventricular fibrillation.

OBJECTIVE: To test the hypothesis that combination pharmacotherapy with delayed countershock would produce higher rates of return of spontaneous circulation (ROSC) and one-hour survival when compared with standard Advanced Cardiac Life Support (ACLS) therapy. METHODS: A prospective, block-randomized, blinded, laboratory experiment was conducted in an established swine model of prolonged ventricular fibrillation (VF). Fifty-six female domestic swine were anesthetized, instrumented, and shocked into VF with a bipolar pacing catheter. The VF was untreated for 8 minutes, then basic CPR was done mechanically for 1 minute. At 9 minutes of VF, the animals were randomized to treatment with one of seven therapies: group 1, combination pharmacotherapy with epinephrine (0.20 mg/kg), lidocaine (1.0 mg/kg), bretylium (5.0 mg/kg), propranolol (1.0 mg), and U-74389G (3.0 mg/kg); group 2, epinephrine (0.20 mg/kg); group 3, lidocaine (1.0 mg/kg) and bretylium (5.0 mg/kg); group 4, propranolol (1.0 mg); group 5, U-74389G (3.0 mg/kg); group 6, normal saline solution (volume equal to that for group 1); and group 7, standard ACLS (first countershock at 9 minutes of VF). Initial countershocks for groups 1-6 were given after 11 minutes of VF. Data were analyzed with two-tailed Fisher's exact test, with alpha set at 0.05. RESULTS: Return of spontaneous circulation occurred in group 1 = 8/8 (100%); group 2 = 7/8 (88%); group 3 = 3/8 (38%); group 4 = 3/8 (38%); group 5 = 5/8 (63%); group 6 = 4/8 (50%); and group 7 = 3/8 (38%). One-hour survival occurred in group 1 = 8/8 (100%); group 2 = 5/8 (63%); group 3 = 2/8 (25%); group 4 = 2/8 (25%); group 5 = 3/8 (38%); group 6 = 2/8 (25%); and group 7 = 1/8 (13%). CONCLUSIONS: Combination pharmacotherapy with delayed countershock (group 1) produced significantly higher rates of ROSC (p = 0.03) and one-hour survival (p = 0.001) when compared with standard ACLS in this porcine model of prolonged VF.