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Poor communication within healthcare teams occurs commonly, contributing to inefficiency, medical errors, conflict, and other adverse outcomes. Interprofessional bedside rounds (IBR) are a promising model that brings two or more health professions together with patients and families as part of a consistent, team-based routine to share information and collaboratively arrive at a daily plan of care. The purpose of this systematic scoping review was to investigate the breadth and quality of IBR literature to identify and describe gaps and opportunities for future research. We followed an adapted Arksey and O'Malley Framework and PRISMA scoping review guidelines. PubMed, CINAHL, PsycINFO, and Embase were systematically searched for key IBR words and concepts through June 2020. Seventy-nine articles met inclusion criteria and underwent data abstraction. Study quality was assessed using the Mixed Methods Assessment Tool. Publications in this field have increased since 2014, and the majority of studies reported positive impacts of IBR implementation across an array of team, patient, and care quality/delivery outcomes. Despite the preponderance of positive findings, great heterogeneity, and a reliance on quantitative non-randomized study designs remain in the extant research. A growing number of interventions to improve safety, quality, and care experiences in hospital settings focus on redesigning daily inpatient rounds. Limited information on IBR characteristics and implementation strategies coupled with widespread variation in terminology, study quality, and design create challenges in assessing the effectiveness of models of rounds and optimal implementation strategies. This scoping review highlights the need for additional studies of rounding models, implementation strategies, and outcomes that facilitate comparative research.

BackgroundA single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent of dose. This highly protracted effect does not correlate with its ocular biodisposition or correlate with the once-daily dosing regimen for other prostanoid EP2 receptor agonists such as trapenepag or omidenepag. The underlying pharmacological mechanism for the multiday extended activity of JV-GL1 is highly intriguing. The present studies were intended to determine EP2 receptor involvement in mediating the long-term ocular hypotensive activity of JV-GL1 by using mice genetically deficient in EP2 receptors.MethodsThe protracted IOP reduction produced by JV-GL1 was investigated in C57BL/6J and EP2 receptor knock-out mice (B6.129-Ptger2tm1Brey/J; EP2KO). Both ocular normotensive and steroid-induced ocular hypertensive (SI-OHT) mice were studied. IOP was measured tonometrically under general anaesthesia. Aqueous humour outflow facility was measured ex vivo using iPerfusion in normotensive C57BL/6J mouse eyes perfused with 100 nM de-esterified JV-GL1 and in SI-OHT C57BL/6J mouse eyes that had received topical JV-GL1 (0.01%) 3 days prior.ResultsBoth the initial 1-day and the protracted multiday effects of JV-GL1 in the SI-OHT model for glaucoma were abolished by deletion of the gene encoding the EP2 receptor. Thus, JV-GL1 did not lower IOP in SI-OHT EP2KO mice, but in littermate SI-OHT EP2WT control mice, JV-GL1 statistically significantly lowered IOP for 4–6 days.ConclusionsBoth the 1-day and the long-term effects of JV-GL1 on IOP are entirely EP2 receptor dependent.

Purpose: JV-GL1 is an efficacious, potent, and long-acting antiglaucoma agent, according to studies in ocular normotensive and hypertensive monkeys. As an obligatory step in the drug development pr...

Prostaglandin (PG) E analogs are used clinically to ripen the cervix and induce labor. However, selective receptor agonists may have potential to improve induction response rates or manage unwanted uterine hypercontractility in conditions such as dysmenorrhea and preterm labor. To characterize their therapeutic value, PGE2 analogs were used to investigate the functional E-type prostanoid (EP) receptor population in isolated human uterus. Responsiveness in mouse tissues was also examined to validate its use as a preclinical model. Uterine samples were obtained from mice at dioestrus (n = 12), term gestation (n = 14), and labor (n = 12) and from the lower uterus of women undergoing hysterectomy (n = 12) or Caesarean section (n = 18). Vehicle and agonist effects were assessed using superfusion and immersion techniques. PGE2 evoked predominant excitatory responses in mouse and relaxation in human tissues. Selective EP4 agonists inhibited tissue activity in both nonpregnant species, while the EP2 mimetic CP533536 also attenuated uterine contractions throughout gestation. The uterotonic effects of the EP3/1 agonist sulprostone were more pronounced than the EP1 agonist ONO-D1-004, corresponding to abundant EP3 receptor expression in all samples. The contractile phenotype in mouse compared with human uteri may relate to regional differences as well as high expression of EP3 receptor transcripts. Similarities in nonpregnant and gestational tissues across species suggest that EP3 may represent a valuable translational drug target for preventing uterine hypercontractility by employing a selective antagonist. SIGNIFICANCE STATEMENT: This research validates the use of nonpregnant mice for preclinical drug discovery of uterine EP receptor targets. To determine the utility of novel drugs and delivery systems at term pregnancy and labor, pharmacological agents interacting with EP3 receptors have clear translational value.

“Breakthrough” advanced propulsion can only take place with a correct understanding of the role of inertia in general relativity. Einstein was convinced that inertia and gravitation were the obverse and reverse of the coin. The most general statement of the principle of relativity, captured in his Equivalence Principle and the gravitational induction of inertia. His ideas and how they have fared are reprised. A rest mass fluctuation that is expected when inertia is gravitationally induced is then mentioned that can be used for propulsion. Recent work supported by National Innovative Advanced Concepts Phase 1 and 2 NASA grants to determine whether thrusters based on gravitationally induced inertia can actually be made to work is presented. A recent design innovation has dramatically increased the thrust produced by these Mach Effect Gravity Assist (MEGA) impulse engines.

Purpose: Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience and complianc...

Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

Tracking the origin of propagating wave signals in an environment with complex reflective surfaces is, in its full generality, a nearly intractable problem which has engendered multiple domain-specific literatures. We posit that, if the environment and sensor geometries are fixed, machine learning algorithms can "learn" the acoustical geometry of the environment and accurately track signal origin. In this paper, we propose the first machine-learning-based approach to identifying the source locations of semi-stationary, tonal, dolphin-whistle-like sounds in a highly reverberant space, specifically a half-cylindrical dolphin pool. Our algorithm works by supplying a learning network with an overabundance of location "clues", which are then selected under supervised training for their ability to discriminate source location in this particular environment. More specifically, we deliver estimated time-difference-of-arrivals (TDOA's) and normalized cross-correlation values computed from pairs of hydrophone signals to a random forest model for high-feature-volume classification and feature selection, and subsequently deliver the selected features into linear discriminant analysis, linear and quadratic Support Vector Machine (SVM), and Gaussian process models. Based on data from 14 sound source locations and 16 hydrophones, our classification models yielded perfect accuracy at predicting novel sound source locations. Our regression models yielded better accuracy than the established Steered-Response Power (SRP) method when all training data were used, and comparable accuracy along the pool surface when deprived of training data at testing sites; our methods additionally boast improved computation time and the potential for superior localization accuracy in all dimensions with more training data. Because of the generality of our method we argue it may be useful in a much wider variety of contexts.

Introduction In contrast to other medical specialties, trainees in Geriatrics have historically provided an increased contribution to clinical workload in General Internal Medicine and a reduced output of academic achievements. More recently, development of non-clinical skills has been recognised to have similar importance to clinical skills and the South East (SE) London Geriatrics Training Programme has thus supported trainees in applications for Out of Programme (OOP) opportunities to optimise career progression. Methods Doctors who had undertaken specialist registrar training in the SE London Geriatrics Training Programme at any time between 2011 and 2019 were sent a questionnaire to assess whether they had completed time OOP and whether they had been awarded research grants, published papers in peer-reviewed journals, had abstracts accepted for presentation at conferences, and/or published book chapters during their training programme. Chi-squared and Wilcoxon rank-sum tests were used to compare data between registrars who had completed time OOP and those who had not taken time OOP. Results 77 (24 male; 53 female) registrars completed training in the SE London Geriatrics Training Programme between 2011 and 2019. 71 registrars (92%) completed the questionnaire, of whom 31 (44%) completed time OOP. In total, registrars were awarded 15 research grants, published 86 papers in peer-reviewed journals, had abstracts accepted for 184 conference presentations and published 20 book chapters. A notably increased proportion of registrars who took time OOP had an output of research grants, papers published in peer-reviewed journals, abstracts accepted for presentation at conferences and/or book chapters respectively compared with registrars who had not taken time OOP (23% vs 5% ; 61% vs 23%; 84% vs 33%; 45% vs 5%). This equated to a combined academic output in 94% of registrars who completed time OOP compared with 48% who did not (p Conclusions A very strong association existed between registrars in Geriatrics taking time OOP and academic achievement substantiating the training programme’s aspiration to support development of non-clinical skills that may be helpful to trainees in their future careers. It would be worthwhile further work being undertaken in this area in other regions.

Since all prostanoid receptors affect intraocular pressure (IOP) and endogenous prostanoids are found in ocular tissues, the pressor effects of prostanoid antagonists were comprehensively evaluated. The absence of effects of most of these antagonists was not entirely anticipated. To ensure no false-negative results, ocular biodisposition studies were conducted.Monkeys with laser-induced ocular hypertension were used to study antagonist effects on IOP. Ocular biodisposition of each antagonist was assessed in rabbits, with LC/MS/MS analyses of tissue extracts and blood.EPThese antagonist studies provided no evidence for individual endogenous prostanoids exerting a meaningful role in regulating IOP. They do reaffirm the critical importance of studying ocular bioavailability for confirming negative data. Large differences among the antagonists in anterior segment and even ocular surface tissue biodisposition were observed in rabbits. It appears from these monkey studies, supported by rabbit ocular bioavailability data, that an absence of drug effect in the eye cannot be adequately substantiated without determination of ocular pharmacokinetics.

There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at −70 mV in vitro by optogenetic stimulation of mPFC–NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs.

Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences. Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.

Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C(max) values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule.

The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D

Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F2α-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F2α analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.—Khidhir, K. G., Woodward, D. F., Farjo, N. P., Farjo, B. K., Tang, E. S., Wang, J. W., Picksley, S. M., and Randall, V. A. The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias.

Purpose To assess the health, functional characteristics, and health care service needs of youth and young adults with special health care needs attending a comprehensive, noncategorical transition program. Methods A self-administered survey was developed from national health surveys and clinical experience to assess concepts identified as important for successful transition to adulthood. Surveys were mailed to 198 parents of youth and young adults with special health care needs attending the transition clinic. Parents were asked about the youth's health, functional status, and health care services needed. The clinical database provided demographic and patient health characteristics. Results were compared against the 2005–2006 National Survey of Children with Special Health Care Needs. Results Forty-four percent of surveys were returned. Average age of youth was 17.5 (11–22) years old and diagnoses included cerebral palsy (36%), spina bifida (10%), developmental delay or Down syndrome (17%), and autism (6%). Most youth needed assistance with personal care (69%) and routine needs (91%) and used assistive devices (59%). Compared with the 2005–2006 National Survey of Children with Special Health Care Needs, parents reported higher needs for all services except mental health care and tobacco or substance use counseling. Forty three percent reported at least one unmet health need. Few parents reported the need for counseling on substance use (1%), sexual health screening (16%), nutrition (34%), and exercise (41%). Conclusions Youth attending our transition program had more functional limitations, poorer reported health status, different diagnosis distribution, and higher levels of needed health services. Few parents identified needs for other recommended adolescent preventive services. Transition programs should assess patient health characteristics and service needs to design effective patient-centered services.

Background. Tuberculosis (TB) is difficult to diagnose in children due to lack of a gold standard, especially in resource-limited settings. Scoring systems and diagnostic criteria are often used to assist in diagnosis; however their validity, especially in areas with high HIV prevalence, remains unclear.Methods. We searched online bibliographic databases, including MEDLINE and EMBASE. We selected all studies involving scoring systems or diagnostic criteria used to aid in the diagnosis of tuberculosis in children and extracted data from these studies.Results. The search yielded 2261 titles, of which 40 met selection criteria. Eighteen studies used point-based scoring systems. Eighteen studies used diagnostic criteria. Validation of these scoring systems yielded varying sensitivities as gold standards used ranged widely. Four studies evaluated and compared multiple scoring criteria. Ten studies selected for pulmonary tuberculosis. Five studies specifically evaluated the use of scoring systems in HIV-positive children, generally finding the specificity to be lower.Conclusions. Though scoring systems and diagnostic criteria remain widely used in the diagnosis of tuberculosis in children, validation has been difficult due to lack of an established and accessible gold standard. Estimates of sensitivity and specificity vary widely, especially in populations with high HIV co-infection.

Perturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F(2α), to conventional outflow tissues alters the rate of drainage of aqueous humor through the trabecular meshwork, and into Schlemm's canal. This review summarizes recent data that characterizes endogenous bioactive lipids, their receptors and associated signaling partners in the conventional outflow tract. We also discuss the potential of targeting such signaling pathways as a strategy for the development of therapeutics to treat ocular hypertension and glaucoma.

Ocular hypotensive agents are the only approved pharmacotherapy for glaucoma. Despite significant advances during the past two decades, a large proportion of glaucoma patients require more than one drug. The most recent additions to the armamentarium of antiglaucoma drugs are fixed-combination products for the glaucoma patient who is insufficiently responsive to monotherapy. Fixed-combination products have the combined efficacy of two ocular hypotensive drugs, and the convenience of a two-drug treatment regimen in a single container, which may aid patient adherence to treatment. Available fixed-combination products consist of timolol 0.5% as an invariant with brimonidine 0.2%, dorzolamide 2%, travoprost 0.004%, latanoprost 0.005% or bimatoprost 0.03%. Research on more advanced antiglaucoma medications continues. Promising new directions appear to be the Rho-kinase inhibitors, microtubule-disrupting agents, serotonergics and cannabimimetics. Efforts continue to improve existing antiglaucoma drugs in an attempt to design second-generation cholinomimetics, adrenergics, prostaglandins and prostamides.

Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering drug that was approved in the United States in 2001 for the treatment of glaucoma and ocular hypertension. It is highly efficacious and produces greater mean reductions in IOP than other currently available antiglaucoma drugs. Conjunctival hyperemia is a common side effect of bimatoprost, but the hyperemia is typically mild and transient. No association has been found between signs of inflammation and the presence of hyperemia in bimatoprost-treated patients. Preclinical studies have elucidated the pharmacological mechanism of bimatoprost-related hyperemia and have examined the possible involvement of inflammation. Bimatoprost, as well as the free acid of latanoprost, elicited endothelium-dependent vasorelaxation in the rabbit jugular vein preparation, a quantitative in vitro model for ocular surface hyperemia (OSH). The vasorelaxant responses to either bimatoprost or latanoprost free acid were significantly inhibited by L-NAME, a nitric oxide synthase inhibitor. Similarly, the in vivo OSH responses to topically applied bimatoprost or latanoprost in dog eyes were significantly inhibited by L-NAME. As predicted, prostaglandin E(2) (PGE(2))-induced conjunctival hyperemia was not inhibited by L-NAME, since PGE(2) has a direct relaxant effect on the vascular smooth muscle. In-life observations and histopathological assessment of ocular surface tissues following bimatoprost treatment were performed for multiple-dose one month, 6 month, or 12 month safety studies in rabbits, dogs, and non-human primates. Results of these studies showed no evidence of bimatoprost-related inflammation in the ocular surface tissues. In summary, OSH related to bimatoprost treatment in laboratory animals occurs by endothelial-derived nitric oxide-mediated vasodilatation and is not associated with inflammation. These studies suggest that conjunctival hyperemia, a side effect of bimatoprost treatment, results from non-inflammatory, pharmacologically based vasodilatation.

A helpless patient was administered 1 GBq of I to ablate thyroid remnants post-thyroidectomy. The patient was quadriplegic, doubly incontinent and unable to swallow. Published data suggest that nursing staff may receive a total effective dose of 3400 microSv when dealing with such a patient for one 8 h shift per day for 7 days post-treatment.To quantify the effective doses received by nursing staff on dealing with a helpless patient undergoing radioiodine ablation therapy.After intravenous administration of 131I, the whole-body doses received by nursing staff were measured using electronic personal dosemeters for 7 days. The nursing staff recorded the times spent in contact with the patient and the activities performed during these times.The total effective dose received by nursing staff over 7 days was 148 microSv. A nurse working alone for one 8 h shift per day for 7 days could receive an effective dose of 91 microSv. The nursing staff spent an average of 23 min (standard deviation, 15 min) per 8 h shift dealing with the patient. Nursing duties were performed at a contact distance of approximately 0.5 m from the patient.The nursing contact times required for the management of a helpless patient post-radioiodine therapy are lower than previously estimated. It is possible to successfully treat such a patient whilst keeping the effective doses to nursing staff within appropriate constraints. The measured nursing contact times provide an up-to-date summary of current nursing practice and will be a useful aid in the planning of future treatments.

Acoustic cavitation has been implicated as a cause of cell damage by lithotripter shock waves, particularly under in vitro conditions. When red blood cells were exposed to shock waves (from an electrohydraulic lithotripter) while under high hydrostatic pressure (> 80 atm), cell lysis was dramatically reduced over that seen at atmospheric pressure, which is consistent with damage due to acoustic cavitation. However, even at > 120 atm of pressure, lysis was still 97% above that of cells not exposed to shock waves, revealing significant damage that apparently was due to mechanisms other than cavitation. Hydrostatic pressure alone did not cause cell lysis, and shock-wave-dependent damage occurred when the cells were in fluid suspension, or when they were centrifuged to the end of the vial. Shock-wave damage at high pressure increased with increasing shock-wave number, and was seen at 24 and 20 kV, but not at 16 kV. This shock-wave damage at high pressure makes up a noteworthy portion of the total cell injury seen at atmospheric pressure (about 10% at 24 kV), suggesting significant noncavitational injury to cells in vitro. Because cavitation occurs far more readily in vitro than in vivo, the noncavitational damage seen in the present study could represent a substantial portion of cell injury seen in vivo with shock-wave lithotripsy.

Garreau (1981) used the Arabic term Rub 'al Khali, or Empty Quarter, to label the Intermountain West portion of the United States. In Saudi Arabia, the Empty Quarter is a large, dry, and relatively unpopulated area with a wealth of energy resources not unlike the Intermountain West. Garreau described changes in the area that were associated with changes in commerce and industry during the 20th century, particularly with respect to mining ventures and the discovery of oil and natural gas in the region. Although Garreau discussed many ways that these changes impacted the people and environment, he did not discuss the actual impact, or predicted impact on the education of children and youth in the region. The purpose of this article is to examine the impact of these changes on the functioning of schools in the Empty Quarter and to propose considerations for improving educational services in the region. The Empty Quarter of the United States includes Nevada, Utah, Colorado, Wyoming, Idaho, Montana, and Interior and Northern Coastal Alaska. Although not highlighted in Garreau's 1981 treatise on rural America, Montana exemplifies the Empty Quarter-vast open spaces, sparse population, mineral wealth, and a harsh climate in summer and winter. If superimposed over the eastern United States, Montana would stretch west to east from Chicago to Washington DC and south to north from mid-Tennessee to the upper Great Lakes. Geographically, Montana has two distinct regions-the western prairie covering the eastern two thirds of the state and the Rocky Mountain front providing a spine through the western third. Montana's economy has traditionally depended upon mining, cattle or sheep ranching, and logging. The economy has diversified to include petroleum refining, tourism, and a growing service industry. Eastern Montana is losing population as farms and ranches fail with changing federal agricultural policies and subsidies. In the spring of 2005, the Billings Gazette published a 14-part series on changes in eastern Montana's economy, education services, medical services, and land use. The series presented a dreary picture of loss in both economic and human resources, similar to what Garreau predicted for the entire region. As opportunities for employment diminish, so does the population. The loss is exacerbated as schools close, making both repopulation of a community and population retention more difficult. With over 80 one-room, one-district schools still in operation, Montana has resisted the move toward consolidation. While remote locations and unpaved county roads provide a rationale for these schools, the lack of a critical mass of students does not support an economy of scale. If two-room schools that are part of a county or town district, and the number of small, multigrade per classroom schools are considered, the number of small rural schools struggling to survive rises to nearly 130. Growth in the number of Hutterite colonies in Montana has also served to increase the number of small rural schools in the state. There are areas of growth within the state, namely south central Montana from Billings through the Yellowstone and Gallatin Valleys and northwestern Montana along the Bitterroot Range and around Flathead Lake. Demographically, adults who are forty plus years of age represent the bulk of this growth and the impact on schools is negative. The number of high school graduates is dropping because of a decreasing student population, not because of decreasing graduation rates, and this decrease impacts both public and private institutions of higher education in Montana. Economic growth could be stimulated with sales taxes that capture tourist dollars for the state infrastructure. Coal bed methane development could revitalize the east in the same manner that it has been a benefit to Wyoming. However, these avenues have not met with favorable response from a population with one of the lowest per-capita incomes in the nation and from ranchers who fear the negative effects of mineral development on scarce water resources. …

The trapeziometacarpal joint is commonly affected by degenerative arthritis, presenting with pain, stiffness, and swelling at the base of the thumb. When conservative treatment fails, surgical intervention may be warranted based on clinical and radiologic staging as well as patient demand. The concept of replacing the trapeziometacarpal joint remains attractive because of the decreased pain and stiffness, prevention of thumb shortening, and earlier recovery of strength seen with implant arthroplasty. A technique of using a cementless PyroCarbon hemiarthroplasty implant that allows excellent range of motion and decreased postoperative stiffness and pain is presented, with a focus on dorsal capsular reconstruction to prevent subluxation of the implant.

During simulated manipulation of children's forearm fractures, levels of scattered radiation from both plain radiographs and an image intensifier in different modes were measured at various sites on the surgeon, anaesthetist, radiographer, and patient both with and without recommended shielding. By using fluoroscopy in the pulsed screening mode but allowing only single pulses to occur, radiation levels could be substantially reduced to the eye, thyroid, and gonads of all those exposed. The radiographer and the anaesthetist were so far from the source and guarded by various pieces of equipment that levels were almost unrecordable. Effective dose equivalent for the surgeon using pulsed mode, based on circa six pulses per manipulation, during 100 manipulations per year, would equate to 1 microSv even in the unshielded state (< 0.1 microSv shielded), which is approximately 1/1,000 of background radiation at sea level. Because the current dose limit is 50 mSv (50,000 microSv) per year for employees, we are many orders of magnitude in the safety zone.

If you’ve watched any of a number of TV shows dealing with either “advanced propulsion” or time travel in the past several years, you’ve doubtless encountered at least the mention of wormholes. Were the topic time travel, a fairly extensive discussion of wormholes might have been involved. Maybe not a very technical discussion, but usually one accompanied by artistic renditions of what a wormhole generator might look like.

The theory underlying Mach effects – fluctuations of the restmasses of accelerating objects in which internal energy changes take place – and their use for propulsion is briefly recapitulated. Experimental apparatus based on a very sensitive thrust balance is briefly described. The experimental protocol employed to search for expected Mach effects is laid out, and the results of this experimental investigation are presented. A series of tests conducted to explore the origin of the thrust signals seen are described, and two of those tests – the most likely spurious sources of thrust signals – are considered in some detail. The thrust signals seen, if genuine Mach effects, suggest that “advanced and exotic” propulsion can be achieved with realistic resources.

Dorsal reduction (humpectomy) is a simple maneuver in principle, yet it commonly results in irregularities and general inaccuracies, along with occasional internal valve compromise. Traditionally, spreader grafts have been applied to reconstruct an internal valve disrupted during dorsal reduction. Imbricating the dissected ends of the upper lateral cartilages at their interface with the septum (spreader flaps) allows the surgeon to use this tissue, which would otherwise be discarded, to reconstruct the internal valve and design an aesthetically pleasing nasal line. The application of a spreader flap is not only an easily reproducible technique to restore middle vault structure but allows for precise incremental control when performed at the time of humpectomy. To that end, the authors provide a detailed description of their internal valve reconstruction technique, which has been honed over the past 15 years.

Owing to the variation in the results of several experiments designed to produce thrust with devices employing Mach effects, it was decided to design an experiment with the simple purpose of determining whether or not Mach effects actually exist, and if they can be produced when the “bulk” acceleration and internal energy changes required to produce them are separately supplied. In the experiment arrays of eight 500 pf high voltage capacitors are mounted on the end of a rotor and spun to and from speeds of about 60 Hz (3600 rpm) while they are excited with a 40 KHz voltage signal with amplitudes up to 6 KV. The capacitors are sandwiched between two accelerometers and any Mach effect mass fluctuation is detected as a weight fluctuation that produces signals in the accelerometers that are antiphase. Those signals are subtracted with a differential instrumentation amplifier that suppresses other signals as common mode noise. Signals with the properties sought have been found and recorded with video equipment. They suggest that Mach effects are real, and that the bulk accelerations and internal energy changes that produce them can in fact be separately supplied.

The effects of bimatoprost on aqueous humor dynamics were quantified in monkey eyes. Uveoscleral outflow was measured by the anterior chamber perfusion method, using FITC-dextran. Total outflow facility was determined by the two-level constant pressure method. Aqueous flow was measured with a scanning ocular fluorophotometer. Uveoscleral outflow was 0 . 9 6 ± 0 . 1 9 𝜇 L m i n − 1 in vehicle-treated eyes and 1 . 3 7 ± 0 . 2 7 𝜇 L m i n − 1 ( 𝑛 = 6 ; 𝑃 < . 0 5 ) in eyes that received bimatoprost 0.01% b.i.d. × 5 days. Bimatoprost had no effect on total outflow facility, which was 0 . 4 2 ± 0 . 0 5 𝜇 L m i n − 1 at baseline and 0 . 4 2 ± 0 . 0 4 𝜇 L m i n − 1 after bimatoprost treatment. Bimatoprost had no significant effect on aqueous humor flow. This study demonstrates that bimatoprost increases uveoscleral outflow but not total outflow facility or aqueous humor flow, indicating that it lowers intraocular pressure in ocular normotensive monkeys by a mechanism that exclusively involves uveoscleral outflow.

Background: Recent reports have increasingly recognized methicillin-resistant Staphylococcus aureus (MRSA) as an important etiology of pyomyositis, an uncommon disease entity. Specific virulence factors such as the Panton-Valentine leukocidin protein have been identified that may play a role in the pathophysiology of pyomyositis, especially when community-acquired MRSA is implicated. Methods: We review a case of disseminated pyomyositis and septic pulmonary emboli in an immunocompetent adult in whom a pvl+ USA300 clone was isolated. Results: The degree of dissemination in this patient suggests an emerging level of virulence for community-acquired MRSA that has not been reported previously. Conclusion: The clinical history and management of severe disseminated pyomyositis, including diagnostic modalities, antimicrobial therapy, and surgical drainage, require an aggressive approach.

Over the past several years Mach effects have been explored as a possible source of propellantless propulsion. Until June of 2006 this work was done at CSUF using a Unimeasure U‐80 position sensor fitted with a diaphragm spring, making it a thrust sensor. This work suggested that thrusts on the order of 100 μN could be produced in laboratory conditions with devices employing capacitors enclosed in coils of wire suitably energized—Mach Lorentz thrusters (MLTs). As a check on this work, two devices tested at CSUF were sent to Nembo Buldrini at the Austrian Research Center (ARC) in Seibersdorf for testing using a thrust balance designed and built there to test small thrust devices. Results obtained by Buldrini in tests in December, 2005 and February 2006 suggested that any thrusts that might be present were smaller by a factor of about 0.3 or less than those obtained at CSUF. This suggested that either the thrust signals seen at CSUF were spurious, or that the U‐80 was markedly more sensitive to very small thrusts than simple linear scaling from calibration conditions indicated should be the case. To explore these possibilities, Thomas Mahood designed and built an approximate replica of the ARC thrust balance—which he dubbed the “ARC Lite” thrust balance‐so that Buldrini's results could be checked at CSUF. Various technical problems with the balance have been addressed since the summer of 2006. Preliminary results obtained with the ARC Lite balance were reported at STAIF2007. Here, the refined version of the balance is described and results obtained with MLTs optimized for operation in special circumstances are reported. Those results suggest that MLTs may well make viable thrusters for a variety space applications. More importantly, however, if MLTs actually work, that means that the Mach effect mass fluctuation equation is essentially correct. Since that equation contains a term that is always negative—that is, that predicts an inducible transient negative mass—this technology holds out the promise of making sufficient negative mass to create practical wormholes, stargates, and warp drives.

Purpose: Determine the aqueous humour concentration of the acid hydrolysis products of bimatoprost and latanoprost after a single topical dose of bimatoprost 0.03% or latanoprost 0.005% in humans. Methods: Randomized, controlled, double-masked, prospective study. Forty-eight eyes of 48 patients scheduled for routine cataract surgery were randomized in an 8:2:2 ratio to treatment with a single 30-μL drop of bimatoprost 0.03%, latanoprost 0.005%, or placebo at 1, 3, 6, or 12 hours prior to the scheduled cataract surgery. Aqueous humour samples were withdrawn at the beginning of the surgical procedure and analyzed using HPLC-tandem mass spectrometry. Results: Bimatoprost acid (17-phenyl trinor PGF2& [alpha]) was detected in aqueous samples at a mean concentration of 5.0 nM at hour 1, 6.7 nM at hour 3, and 1.9 nM at hour 6 after bimatoprost treatment. After latanoprost treatment, the mean concentration of latanoprost acid (13,14-dihydro-17-phenyl trinor PGF2& [alpha]) in aqueous samples was 29.1 nM at hour 1, 41.3 nM at hour 3, and 2.5 nM at hour 6. Acid metabolites were below the limit of quantitation in all samples taken 12 hours after dosing and in all samples from placebo-treated patients. None of the samples from latanoprost-treated patients contained quantifiable levels of nonmetabolized latanoprost. Nonmetabolized bimatoprost was detected in aqueous samples at a mean concentration of 6.6 nM at hour 1 and 2.4 nM at hour 3 after bimatoprost treatment. Conclusions: Low levels of bimatoprost acid were detected in aqueous humour samples from cataract patients treated with a single dose of bimatoprost. Latanoprost acid concentrations in samples from patients treated with latanoprost were at least 6-fold higher. These results suggest that bimatoprost acid in the aqueous humour does not sufficiently account for the ocular hypotensive efficacy of bimatoprost.

The Flight Management Computer (FMC) parallel offset is a procedure which allows a pilot to turn left or right of course in order to intercept a track which is parallel to the originally-cleared route of flight. The offset route is established by way of an input parameter to the FMC. "L5.0," for example, would establish a 5 NMI offset to the left of the original route. The aircraft may turn back to course later or simply continue on the offset path until receiving vectors in the terminal arrival area. The entire procedure is subject to Air Traffic Control (ATC) approval. At previous DASC conferences, three separate trials of the FMC offset have been described, in which: 1) the basic feasibility and pilot/controller acceptance were explored, 2) ATC handoffs across facility boundaries were exercised, and 3) potential airline benefits were calculated and pilot/controller phraseology was developed. In the most recent trial, a JetBlue flight from San Diego to New York Kennedy airport was offset soon after take-off, with the intent of staying on the parallel offset track for the entire transcontinental trip. The objective of the test was to uncover potential ATC automation issues, since a variety of situations would be encountered as the flight traversed various sectors and facility airspace.

In 1990, James F. Woodward, professor of physics at the California State University, provided a set of equations showing that it should be possible, via Mach's Principle, to change transiently the mass of a body. The major practical embodiment of these equations is a new kind of propellantless propulsion which could be directly applied to space exploration. The main goal of the experimental campaign here reported is to provide an independent test for the validity of this propulsion concept and compare it with previous experimental claims. We performed the study using a very sensitive thrust balance developed for field emission thrusters. Two devices developed and tested by Woodward have been characterized with our equipment. The results obtained to date do not seem to be in full agreement with the findings claimed by Woodward and collaborators. Nevertheless, the importance of such a discovery is sufficient to recommend going on with experimentation in order to reach a complete understanding of the phenomenon.

The treatment of glaucoma by reducing intraocular pressure has relied traditionally on inhibiting aqueous humor secretion (inflow). However, recent therapeutic approaches have targeted aqueous humor outflow. Prostanoid FP receptor agonists selectively increase uveoscleral outflow and the prostamide analog bimatoprost alters trabecular and uveoscleral outflow. An emerging therapeutic strategy is direct neuroprotection of retinal ganglion cells, which are selectively lost in glaucoma.

The results of an experiment designed to produce small amounts of “propellantless” thrust using Mach effect mass fluctuations produced by an alternating electric field in high voltage capacitors in conjunction with an externally induced alternating magnetic flux in their dielectric cores are described. Small effects of the sort expected were detected. Several tests to exclude spurious signals were performed.

Prostaglandin Flaits esters, and synthetic prostanoid FP receptor agonists causedose-related increases in ocular surface hyperemia (OSH) that may persist over the course of a day. This side effect of red eyes limited the use of PGF2aand its isopropylester (IE) for glaucoma therapy. The goal to identify a quantitative model for predictingocular OSH in humans prompted studies to correlate this effect with activity at a prostanoid receptor. Criteria for the receptor associated with OSH were that it is potently stimulated by PGF2aand linked to smooth muscle relaxation, since dilatation of theconjunctival blood vessels is a vasorelaxant response.

The Firehole River (FHR) in Yellowstone National Park (YNP) is a world-renowned recreational fishery that predominantly includes rainbow trout (RBT, Oncorhynchus mykiss) and brown trout (BNT, Salmo trutta). The trout populations apparently are closed to immigration and have been self-sustaining since 1955. Inputs from hot springs and geysers increase the temperature and mineral content of the water, including elevating the boron (B) concentrations to a maximum of approximately 1 mg B/L. Both RBT and BNT reside in warm-water reaches, except when the water is extremely warm (or = approximately 25 degrees C) during midsummer. They spawn in late fall and early winter, with documented spawning of BNT in the cold-water reach upstream from the Upper Geyser Basin and of RBT in the Lower Geyser Basin reach, where water temperatures presumably are the warmest; however, successful recruitment of RBT in waters containing approximately 1 mg B/L has not been demonstrated conclusively. Thus, we began investigating the relationships among temperature, B concentrations, other water-quality parameters, and the distribution and reproduction of trout in the FHR in spring 1997. However, atypical high water flows and concomitant lower than historical temperatures and B concentrations during summer 1997 preclude conclusions about avoidance of high B concentrations.

How well does Reference Man represent a real person when calculating radiation dose? This publication addresses this question by looking in some detail at the sources of uncertainty in the different models which make up Reference Man. A chapter is devoted to each of the models, which are: gastrointestinal tract, respiratory tract, uptake through wounds and absorption through skin, biokinetic and dosimetric. External exposure from a radioactive cloud or ground deposition is also covered. The development of models from their relatively simple ICRP30 versions to the current complex versions as typified by the ICRP60 respiratory tract model is described with helpful anatomical diagrams. Various models are compared and it seems that no factor which might affect model parameters is overlooked, e.g. the liquid gastric emptying varies according to gender, age and time of day. This is a very rigorous description, but the question the reader finds himself wanting to ask is, `Can you put a figure on the reliability of the dose estimation?' This question is dealt with in the final chapters and sadly the answer is that the more quantitative assessment methods cannot be used because generally there just is not enough data and the problem is to complex. Iodine-131 ingestion is a rare exception. The only usable method is a subjective assessment of uncertainty by experts. As an example, it is applied to a list of radionuclides commonly encountered in environmental releases from nuclear facilities. This comes as rather an anticlimax but the stated intention is not to provide comprehensive uncertainty figures but to present the strengths and weaknesses of the current models and hopefully to stimulate the necessary research. Nuclear medicine physicists should note that this commentary is primarily about environmental exposures to radioactive elements and not medical exposure to radiopharmaceuticals. In conclusion, if you enjoyed reading ICRP23 you will enjoy this publication.

Charge-transfer-efficiency (CTE) is a parameter that is associated with the optical performance and radiometric accuracy of a charge-coupled device (CCD). While modern CCDs are typically quoted as having CTE > 0.99999, we show that a) this efficiency can be degraded by exposure to energetic protons and b) the measured efficiency, at least in the case of irradiated devices, is dependent on the size of the signal being transferred. A comparison of two techniques of CTE measurement is presented, with emphasis on a 55Fe x-ray charge-generation and collection technique tailored especially for use with linear CCDs. While our technique follows the same general x-ray method widely used to characterize area CCDs, its implementation, including the processing of the resulting experimental data, is somewhat novel. The x-ray technique requires no special device circuitry or equipment and, in our configuration, may be used on virtually any linear or bilinear CCD; the same general technique is used on area arrays. It is shown that the technique is appropriate for characterizing small-signal CTE with or without a high background. It is also shown that the electrical injection CTE, while requiring the injection circuitry to be designed and built-in to the CCD structure, is more appropriate for large-signal CTE measurement. Data are presented showing experimental pre- and post-irradiation CTE measured as a function of signal level and background level for a two-phase linear CCD. Additionally, it is shown that in our tests, the CTE degraded even at very small accelerated doses, but further degradation was at least partly compensated by an enhanced background due to increasing dark currents.

A simulation is describe which determines in detail the response of visible through infrared focal plane devices, used in space-based electro-optical imaging sensors, to proton irradiation from the natural space environment, as a function of the choice of orbit around the earth. The quantitative description of the natural environment (protons) is based on the NASA code AP-8 and/or the CRRES database. Simplified shielding models and other models are then used to obtain the impinging proton environment, including the proton: flux, energy distributions, and trajectories, just above the surface of the focal plane in question. The interaction of a single proton with the focal plane is modeled based on the focal plane semiconductor material, the 3D pixel geometry, and the focal plane layout. This model is then exercised in a Monte-Carlo simulation to build up the aggregate focal plane response effects due to the variety of protons encountered under appropriate orbital and shielding conditions. The output of this simulation is statistically analyzed and used to construct a database to enable system planners and architects, algorithm developers, and sensor data users to mitigate the unwanted effects of this radiation.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Recent advances in Interferometric Fiber Optic Gyroscope (IFOG) technology have enabled these devices to equal, and in some respects exceed, the performance of the floated, spinning wheel rate integrating gyroscope. However, their ability to perform in a space radiation environment has been a significant concern. Test results are presented addressing the effects of space radiation on the performance of a high precision pointing grade IFOG. Proton-induced degradation of the optical components of an IFOG is evaluated based on testing performed at the Harvard Cyclotron Laboratory (HCL). Rationale is provided for using the HCL proton accelerator as a reasonable simulation of the space environment. An analysis is presented which prioritizes the component-level dose tests based on expected radiation sensitivities. The evaluation addresses both total dose (to about 12 krad) and dose rate effects. Testing was performed at the component level as well as the system level with an expanded version of a closed-loop operational IFOG. Primary concerns include permanent attenuation and spectral transmission (wavelength) sensitivity to total dose, and angle random walk and bias stability degradation as a function of dose rate. Component level results are presented for a superfluorescent light source, integrated optics chip (IOC), coupler, and polarization maintaining fiber coils. Closed-loop transient noise results are evaluated based on dose rate testing of the IOC, coupler, and fiber coil.

The therapeutic utility of cyclooxygenase (CO) inhibitors, such as ketorolac, in reducing the inflammatory events associated with allergic conjunctivitis is not unexpected since prostanoids (PG) elicit conjunctival redness (PGD2, PGE2, PGF2 alpha), edema (PGD2, TxA2), eosinophil infiltration (PGD2, PGJ2) and mucous cell discharge (PGD2, PGJ2, TxA2). Recently, topically administered ketorolac has also been reported to alleviate the itching associated with allergic conjunctivitis. This was viewed as intriguing since CO inhibitors are not regarded as useful for treating itching dermatoses and PGs do not elicit itching when applied to the skin. In order to investigate the antipruritic activity of ketorolac, we developed a model for reproducibly measuring ocular surface itch responses. The model involves itch-scratch responses to pruritogens applied locally to the ocular surface. Painful and foreign body stimuli do not produce an itch-scratch response. Unlike reported skin studies, PGE2 was a potent itch-producing substances in the conjunctiva. PGD2 was weakly pruritogenic but PGF2 alpha and the TxA2-mimetic U-46619 were inactive. The PG precursor arachidonic acid was also a potent pruritogen and its effects were inhibited by ketorolac pretreatment. Ketorolac also dose-dependently inhibited the itching associated with experimental allergic conjunctivitis. It appears that PGs are potent itch-producing substances in the conjunctiva and the anti-itch efficacy of ketorolac in allergic conjunctivitis appears to involve inhibition of conjunctival PG biosynthesis from arachidonic acid.